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Mycoplasma spp. are rarely recognized agents of infective endocarditis. We report a case of Mycoplasma hominis prosthetic valve endocarditis diagnosed by 16S ribosomal DNA (rDNA) PCR and culture of valves in a 74-year-old man. We reviewed the literature and found only 8 other cases reported. | Mycoplasma hominis |
Asexual sporulation is the most common reproduction mode of fungi. Most filamentous fungi have two conidiation patterns, normal conidiation and microcycle conidiation, which may be regulated by nutritional conditions. Nitrogen source can affect the fungal conidiation pattern, but the regulatory mechanism is not fully understood. In this study, we report a C2H2 zinc finger protein, MaNCP1, which has typical transcription factor characteristics and is screened from the subtractive library regulated by nitrate in the entomopathogenic fungus Metarhizium acridum. MaNCP1 and its N-terminal play critical roles in the conidiation pattern shift. Further study shows that MaNCP1 interacts with MaNmrA, which also contributes to the conidiation pattern shift and is involved in the reductive pathway of nitric oxide (NO) synthesis. Intriguingly, the conidiation pattern of the MaNCP1-disruption strain (DeltaMaNCP1) can be restored to microcycle conidiation when grown on the microcycle conidiation medium, SYA, supplemented with NO donor or overexpressing MaNmrA in DeltaMaNCP1. Here, we reveal that MaNCP1 governs the conidiation pattern shift through regulating the reductive synthesis of NO by physically targeting MaNmrA in M. acridum. This work provides new mechanistic insights into how changes in nitrogen utilization are linked to the regulation of fungal morphological changes. IMPORTANCE Fungal conidia play important roles in the response to environmental stimuli and evasion of the host immune system. The nitrogen source is one of the main factors affecting shifts in fungal conidiation patterns, but the regulatory mechanism involved is not fully understood. In this work, we report that the C2H2 zinc finger protein, MaNCP1, governs the conidiation pattern shift in M. acridum by targeting the MaNmrA gene, thereby altering the regulation of the reductive pathway for NO synthesis. This work provides further insights into how the nutritional environment can regulate the morphogenesis of filamentous fungi. | CYS2-HIS2 Zinc Fingers |
A range of treatment options are available in rosacea, which include several topical (mainly metronidazole, azelaic acid, other antibiotics, sulfur, retinoids) and oral drugs (mainly tetracyclines, metronidazole, macrolides). In some cases, the first choice is a systemic therapy because patients may have sensitive skin and topical medications can be irritant. Isotretinoin can be used in resistant cases of rosacea. Unfortunately, the majority of studies on rosacea treatments are at high or unclear risk of bias. A recent Cochrane review found that only topical metronidazole, azelaic acid, and oral doxycycline (40 mg) had some evidence to support their effectiveness in moderate to severe rosacea and concluded that further well-designed, adequately-powered randomised controlled trials are required. In our practice, we evaluate our patients for the presence of two possible triggers, Helicobacter pylori infection and small intestinal bacterial overgrowth. When they are present we use adapted antibiotic protocols. If not, we use oral metronidazole or oral tetracycline to treat papulopustolar rosacea. We also look for Demodex folliculorum infestation. When Demodex concentration is higher than 5/cm(2) we use topical crotamiton 10% or metronidazole. | Sulfacetamide |
Ethylene glycol is a common alcohol found in many household products such as household hard surface cleaner, paints, varnish, auto glass cleaner and antifreeze. While extremely toxic and often fatal on ingestion, few cases with early presentation by the patient have resulted in death; thus, rapid diagnosis is paramount to effectively treating ethylene glycol poisoning. In this study, we compare two sequential cases of ethylene glycol poisoning in a single individual, which resulted in strikingly different outcomes. | Fomepizole |
Dirithromycin is a semisynthetic derivative of erythromycin, a 14-membered ring macrolide antibiotic. The drug is converted during absorption and distribution, to an active metabolite 9-(S)-erythromycylamine, which is the predominant compound found in plasma and extravascular tissues. High tissue concentration of erythromycylamine is achieved after oral doses of dirithromycin, with slow release back into the circulation. The mechanism of action of dirithromycin is like that of erythromycin and other macrolides. These compounds inhibit RNA-dependent protein synthesis. It has recently been suggested that all macrolides stimulate dissociation of peptidyl-tRNA from ribosomes during the elongation phase, leading to inhibited protein synthesis. The antimicrobial spectrum of dirithromycin is similar to that of erythromycin, although the drug offers no significant advantage with regard to MIC values. In vitro against Gram-positive isolates, dirithromycin exhibits similar potency to that of clarithromycin, erythromycin, roxithromycin, and clindamycin. In vivo, dirithromycin is active against penicillin-susceptible Staphylococcus aureus, beta-hemolytic streptococci, and Streptococcus pneumoniae. Dirithromycin is as effective as penicillin VK against streptococcal pharyngitis and tonsilitis, and as effective as erythromycin against acute superimposed chronic bronchitis and skin and soft-tissue infections. In comparison with other newer macrolides, dirithromycin has shown similar or lesser in vitro activity. In particular, Haemophilus influenzae, Bacteroides spp., Peptococcus-Peptostreprococcus spp., Clostridium perfringens, Legionella spp., Neisseria gonorrhoeae, and Chlamydia trachomatis were all less sensitive to dirithromycin than azithromycin or clarithromycin. Once-daily oral administration of dirithromycin (500 mg) has been demonstrated to be similar in efficacy to erythromycin (250 mg, 4 times daily), each for approximately 7 days, in the treatment of acute bronchitis or acute-exacerbations of chronic bronchitis in controlled studies. Proven or presumed pathogen eradication rates were 83 and 86% for acute bronchitis patients treated with dirithromycin and erythromycin, respectively. Corresponding bacteriological response rates in acute exacerbations of chronic bronchitis were 75 to 84% with dirithromycin and 75 to 82% with erythromycin. Both agents achieved clinical cure or improvement in over 85% of the patients with either condition. The main advantage of dirithromycin over erythromycin appears to be once-daily administration. Lilly launched dirithromycin in September 1993, in Spain, received approval from FDA in August 1995, and launched it during October 1995. | Erythromycin |
We generated dose-response data for the endogenous and ultra-short-acting hallucinogen, N,N-dimethyltryptamine (DMT), in a cohort of experienced hallucinogen users, measuring multiple biological and psychological outcome measures. Subjective responses were quantified with a new rating scale, the HRS, which provided better resolution of dose effects than did the biological variables. A tolerance study then was performed, in which volunteers received four closely spaced hallucinogenic doses of DMT. Subjective responses demonstrated no tolerance, while biological measures were inconsistently reduced over the course of the sessions. Thus, DMT remains unique among classic hallucinogens in its inability to induce tolerance to its psychological effects. To assess the role of the 5-HT1A site in mediating DMT's effects, a pindolol pre-treatment study was performed. Pindolol significantly increased psychological responses to DMT, suggesting a buffering effect of 5-HT1A agonism on 5-HT2-mediated psychedelic effects. These data are opposite to those described in lower animal models of hallucinogens' mechanisms of action. | N,N-Dimethyltryptamine |
Lymphangioleiomyomatosis is a rare and complicated disorder that affects the young, almost exclusively women. It may be associated with the tuberous sclerosis complex, which includes renal angiolipoma, chylothorax and lymph node myomatosis. Its clinical pulmonary manifestations vary from simple cough to the development of recurrent pneumothoraces, hemoptysis, and even complicated pleural effusions. Progressive dyspnea develops as the disease evolves. Eventually most patients require lung transplantation. This wide array of symptoms and signs makes the differential diagnosis extensive, and the clinician must be familiar with this disorder to arrive promptly to the correct diagnosis. We report a case of a 36-year-old woman with a long history of recurrent pleuritic chest pain with associated dyspnea before being diagnosed with lymphangioleiomyomatosis. A review of the literature pertinent to this case is provided. | Lymphangiomyoma |
Transmissible spongiform encephalopathies (TSE) are characterised by a long incubation period which precedes clinical symptoms related to the degeneration of the central nervous system (CNS). The nature of their etiologic agents (TSA/prions) remains unknown, although there exists strong experimental data supporting the prion hypothesis. This hypothesis suggests a key role for the host derived protein (the prion protein, PrP) as the transmissible agent. In infected individuals, PrP accumulates proportionally to infectivity titre and resists proteinase K treatment (PrP-res). Iatrogenic Creutzfeldt-Jakob disease (CJD) cases have been described in humans after neurosurgery, treatment with pituitary derived hormones, and cornea and dura mater grafting. TSA-associated infectivity is dependent upon the nature of the organ in a given infected individual, though the CNS has the highest infectivity rate. In vitro, TSA/prions do not replicate easily: only cells of neuronal origin are susceptible, and the replication rate is very low. TSA/prions have unconventional properties; in particular, they resist to almost all the chemical and physical processes which inactivate conventional viruses. Only autoclaving at 134/136 degrees C for 1 h or treatment with either 1N NaOH or sodium hypochlorite (2% Cl) during 1 h at room temperature are considered to give inactivation that is compatible with public health criteria. In vivo, the distribution of infectivity is dependent upon strain and host, for a given inoculum injected by a given route. Although supported by numerous experimental data, the prion only hypothesis has not yet been convincingly demonstrated. | Prion Diseases |
The effects of the convulsant drug pentylenetetrazol (PTZ) were studied in neurons from isolated ganglia of the nudibranch molluscs, Archidoris montereyensis and Anisodoris nobilis, using conventional techniques of intracellular recording and constant current stimulation. PTZ was selected because it causes changes in the intracellularly recorded responses similar to the depolarization shifts recorded in mammalian epileptic neurons. When perfusate containing 120-140 mM PTZ is introduced, the intracellular recording is characterized by an initial silent period followed by small oscillations in membrane potential and irregular firing of spikes. Within 5-15 min, bursts of 2-3 spikes occurred followed by the appearance of episodic prolonged depolarizations with superimposed high-frequency spikes. In the presence of PTZ the prolonged depolarizations were evoked by intracellular stimulation and at the termination of conditioning hyperpolarizations. The prolonged depolarizations were also recorded in neurons isolated from all synpatic input by axonal ligation. Prolonged depolarizations showed threshold behavior since they can be terminated early by an intracellularly applied hyperpolarizing current. | Pentylenetetrazole |
Raising customer satisfaction in health-care organizations has been a priority for the past 5 years or more. Articles and books continue to be written on the topic and speeches and presentations are given to eager audiences of professionals who have a deep desire to improve customer satisfaction. Yet research indicates that customer satisfaction, on average, in the health-care industry barely has improved. This column will examine why some organizations, using the same best practice techniques and approaches for top customer satisfaction, achieve wonderful results as most others achieve meager results, at best. The answer to achieving top customer satisfaction lies in the leadership of the organization. When leaders change their thinking and behaviors, results will change." | Health Services Administration |
Children with autoimmune disorders are especially at risk of vaccine-preventable diseases due to their underlying disease and the immunosuppressive treatment often required for a long period. In addition, vaccine coverage remains too low in this vulnerable population. This can be explained by a fear of possible adverse effects of vaccines under immunosuppression, but also a lack of data and clear recommendations, particularly with regard to vaccination with live vaccines. In this review, the latest literature and recommendations on vaccination in immunosuppressed children are discussed in detail, with the aim to provide a set of practical guidelines on vaccination for specialists caring for children suffering from different autoimmune disorders and treated with various immunosuppressive regimens. | Vaccines, Live, Unattenuated |
Described by Chance (1948) this fracture is induced by a mechanism of flexion distraction (seat belt fracture). The injury is characterized by the following (W.S. Smith, 1969): A disruption of the vertebral body by an horizontal splitting of this formation and neural arches through the pedicles, nor, or a minimum decrease in the anterior height of the involved vertebral body, no forward or lateral displacements of the superior vertebra, location of the disruption between the first and third lumbar vertebra in the majority of cases. Four patterns of Chance's fracture are isolated in this paper: First pattern: The osseous disruption cross the posterior arches, pedicles and vertebra. The fracture is unstable. Second pattern: horizontal fracture involves both pedicles with extension anteriorly through inferior third of the vertebral body (unstable). Third pattern: Chance's fracture with anterior vertebral extension through superior third of vertebra (unstable). Fourth pattern: fracture with anterior horizontal vertebral disruption in the posterior half of the body (stable). | Spinal Injuries |
The effects of substance P, neurokinin A, physalamine, and eledoisin on the secretion of fluid and glycoproteins from the submandibular glands of various rodents were investigated. Following i.v. injection of each peptide at a dose of 20 micrograms/kg, the major glycoprotein species secreted from rats and guinea pigs were shown to be electrophoretically identical with those found in the acini. However, saliva was not elicited from the mice and hamsters. These results suggest that in both rats and guinea pigs, tachykinins act on the acinar cells of the submandibular gland only. | Eledoisin |
Lipoprotein (LP) fractions prepared from sera of normal and plasmacytoma (TEPC-183) bearing mice, were compared with respect to their effect on the in vitro anti-2,4,6-trinitrophenyl plaque forming cell response. Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions of sera from the plasmacytoma bearing mice contained immunosuppressive activity that was absent in VLDL and LDL fractions of normal serum LP fractions. The suppressive activity did not correlate with cholesterol or triglyceride content. Crossed-immunoelectrophoresis and polyacrylamide gel electrophoresis revealed components of the suppressive VLDL and LDL fractions which were not present in normal serum LP fractions, suggesting a modification of serum LPs by the plasmacytoma. | Sarcoma 37 |
OBJECTIVES: The relationships of Paired Like Homeodomain 2 (PITX2), Ninjurin 2 (NINJ2), TWIST-Related Protein 1 (TWIST1), Ras Interacting Protein 1 (Rasip1), Solute Carrier Family 17 Member 3 (SLC17A3), Methylmalonyl Co-A Mutase (MUT) and Fer3 Like BHLH Transcription Factor (FERD3L) polymorphisms and gene expression with ischemic stroke have yet to be determined in Malaysia. Hence, this study aimed to explore the associations of single nucleotide polymorphisms (SNPs) and gene expression with ischemic stroke risk among population who resided at the Northern region of Malaysia. MATERIALS AND METHODS: Study subjects including 216 ischemic stroke patients and 203 healthy controls were recruited upon obtaining ethical clearance. SNP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism assays. Gene expression levels were quantified by real-time polymerase chain reaction assays. Statistical and genetic analyses were conducted with SPSS version 22.2, PLINK version 1.07 and multifactor dimensionality reduction software. RESULTS: Study subjects with G allele, CG or GG genotypes of SLC17A3 rs9379800 demonstrated increased risk of ischemic stroke with the odds ratios ranging from 1.76-fold to 3.14-fold (p<0.05). When stratified study subjects according to the ethnicity, SLC17A3 rs9379800 G allele and CG genotype contributed to 2.14- and 2.96-fold of ischemic stroke risk among Malay population significantly, in the multivariate analysis (p<0.05). However, no significant associations were observed for PITX2, NINJ2, TWIST1, Rasip1, and MUT polymorphisms with ischemic stroke risk in the multivariate analysis for the pooled cases and controls as well as when stratified them according to the ethnicity. Lower mRNA expression levels of Rasip1, SLC17A3, MUT and FERD3L were observed among cases (p<0.05). After FDR adjustment, the mRNA level of SLC17A3 remained significantly associated with ischemic stroke among Malay population (q=0.034). CONCLUSION: In conclusion, this study suggests that SLC17A3 rs9379800 polymorphism and its gene expression contribute to significant ischemic stroke risk among Malaysian population, particularly the Malay who resided at the Northern Region of the country. Our findings can provide useful information for the future diagnosis, management and treatment of ischemic stroke patients." | Sodium-Phosphate Cotransporter Proteins, Type I |
From the earliest recorded history, people with disabilities have been ostracized, rejected, and discriminated against in society. Although social work has a history rich in advocacy for oppressed people, the profession has been hesitant to become involved with people with disabilities. This article addresses historical and contemporary issues concerning disability. Recent developments in the disability movement, including independent living, are discussed and compared to social work's approaches to disability. Finally, a plea is made to the social work profession and the disability movement to combine efforts to enhance the lives of people with disabilities. | Social Work |
Cancer metabolism is rewired to support cell survival in response to intrinsic and environmental stressors. Identification of strategies to target these adaptions is an area of active research. We previously described a cytosolic aspartate aminotransaminase (GOT1)-driven pathway in pancreatic cancer used to maintain redox balance. Here, we sought to identify metabolic dependencies following GOT1 inhibition to exploit this feature of pancreatic cancer and to provide additional insight into regulation of redox metabolism. Using pharmacological methods, we identify cysteine, glutathione, and lipid antioxidant function as metabolic vulnerabilities following GOT1 withdrawal. We demonstrate that targeting any of these pathways triggers ferroptosis, an oxidative, iron-dependent form of cell death, in GOT1 knockdown cells. Mechanistically, we reveal that GOT1 inhibition represses mitochondrial metabolism and promotes a catabolic state. Consequently, we find that this enhances labile iron availability through autophagy, which potentiates the activity of ferroptotic stimuli. Overall, our study identifies a biochemical connection between GOT1, iron regulation, and ferroptosis." | Aspartate Aminotransferase, Cytoplasmic |
The effect of ethyl alcohol ingestion on erythromycin kinetics was studied. Nine healthy volunteers, four males and five females, participated in the study. They received, in two separate occasions, 500 mg of erythromycin ethylsuccinate ester given with water or with an alcoholic beverage. The antibiotic was assayed in plasma, using a microbiological method. Absorption and disposition parameters were calculated according to classical pharmacokinetic techniques. A longer lag time and a decrease in AUC were observed when the antibiotic was given with alcohol. The differences were statistically significant. It is likely that the effect of alcohol on gastric emptying could be responsible for the delayed absorption of the antibiotic. | Erythromycin Ethylsuccinate |
The accumulation of fluoride in tea leaves from various cultivars exhibits significant differences. However, the molecular basis and mechanism remain largely unknown. Here, we reported that two genes of CsFEX (fluoride export genes in Camellia sinensis), CsFEX1 and CsFEX2, transport fluoride out of cells, alleviate the cellular fluoride toxin, and rescue the yeast mutant (FEX1DeltaFEX2Delta) and Arabidopsis mutant (fex), as their efflux activities are coupled with proton gradients. Further analysis found that CsFEX1 and CsFEX2 localize to the plasma membrane both in yeast and Arabidopsis cells. CsFEX2 is more effective to reduce fluoride toxicity in yeast and Arabidopsis compared with CsFEX1 even at low pH. CsFEX2 induced by fluoride treatment is around tenfold higher in a low-fluoride cultivar (Yunkang 10) than that in a high-fluoride cultivar (Pingyang Tezaocha), suggesting that CsFEX2 possibly plays a critical role in reducing fluoride accumulation in tea leaves. | Theaceae |
Von Willebrand disease (VWD) is the most common inherited bleeding disorder. Most patients with mild and moderate VWD can be treated effectively with desmopressin. The management of severe VWD patients, mostly affected by type 2 and type 3 disease, can be challenging. In this article we review the current diagnosis and treatment of severe VWD patients. We will also discuss the management of severe VWD patients in specific situations, such as pregnancy, delivery, patients developing alloantibodies against von Willebrand factor and VWD patients with recurrent gastrointestinal bleeding. Moreover, we review emerging treatments that may be applied in future management of patients with severe VWD." | von Willebrand Disease, Type 2 |
The glycosylation of asparagine residues is the predominant protein modification in all three domains of life. An oligosaccharide chain is preassembled on a lipid-phospho carrier and transferred onto asparagine residues by the action of a membrane-bound enzyme, oligosaccharyltransferase. The oligosaccharide donor for the oligosaccharyl transfer reaction is dolichol-diphosphate-oligosaccharide in Eukaryota and polyprenol-diphosphate-oligosaccharide in Eubacteria. The donor in some archaeal species was reportedly dolichol-monophosphate-oligosaccharide. Thus, the difference in the number of phosphate groups aroused interest in whether the use of the dolichol-monophosphate type donors is widespread in the domain Archaea. Currently, all of the archaeal species with identified oligosaccharide donors have belonged to the phylum Euryarchaeota. Here, we analyzed the donor structures of two species belonging to the phylum Crenarchaeota, Pyrobaculum calidifontis and Sulfolobus solfataricus, in addition to two species from the Euryarchaeota, Pyrococcus furiosus and Archaeoglobus fulgidus The electrospray ionization tandem mass spectrometry analyses confirmed that the two euryarchaeal oligosaccharide donors were the dolichol-monophosphate type and newly revealed that the two crenarchaeal oligosaccharide donors were the dolichol-diphosphate type. This novel finding is consistent with the hypothesis that the ancestor of Eukaryota is rooted within the TACK (Thaum-, Aig-, Cren-, and Korarchaeota) superphylum, which includes Crenarchaea. Our comprehensive study also revealed that one archaeal species could contain two distinct oligosaccharide donors for the oligosaccharyl transfer reaction. The A. fulgidus cells contained two oligosaccharide donors bearing oligosaccharide moieties with different backbone structures, and the S. solfataricus cells contained two oligosaccharide donors bearing stereochemically different dolichol chains." | Polyisoprenyl Phosphate Oligosaccharides |
Occipital condyle fractures (OCFs) are uncommon and potentially fatal lesions. After the advent of CT, prompt diagnosis can be readily made and consequently better prognosis of these patients is expected. Early recognition of some types of OCF is imperative to avoid fatal results. We analyzed 121 cases of OCF (116 from the literature and five of our own). Rarely patients with a deficit of the lower cranial nerves make a complete recovery. However, quoad vitam prognosis of patients with pure OCFs" remains good. Immobilization provides good recovery of most OCFs, but delay of treatment can lead to serious morbidity. We want to emphasize that not only an OCF with instability of O-C1-C2 can be a fatal injury unless prompt surgical intervention, but a displacement and migration of the fractured condylar fragment can also result in a fatal outcome. A high level of suspicion is fundamental for the early diagnosis of these fractures, so that when a posterior basal cranial or occipital squama fracture occurs, a CT study of the occipital condyles becomes imperative." | Skull Fractures |
Homeobox transcription factors of the vertebrate CRX/OTX family play critical roles in photoreceptor neurons, the rostral brain and circadian processes. In mouse, the three related proteins, CRX, OTX1, and OTX2, fulfill these functions. In Drosophila, the single founding member of this gene family, called orthodenticle (otd), is required during embryonic brain and photoreceptor neuron development. We have used global gene expression analysis in late pupal heads to better characterize the post-embryonic functions of Otd in Drosophila. We have identified 61 genes that are differentially expressed between wild type and a viable eye-specific otd mutant allele. Among them, about one-third represent potentially direct targets of Otd based on their association with evolutionarily conserved Otd-binding sequences. The spectrum of biological functions associated with these gene targets establishes Otd as a critical regulator of photoreceptor morphology and phototransduction, as well as suggests its involvement in circadian processes. Together with the well-documented role of otd in embryonic patterning, this evidence shows that vertebrate and fly genes contribute to analogous biological processes, notwithstanding the significant divergence of the underlying genetic pathways. Our findings underscore the common evolutionary history of photoperception-based functions in vertebrates and invertebrates and support the view that a complex nervous system was already present in the last common ancestor of all bilateria. | Otx Transcription Factors |
NADP-dependent malate dehydrogenase was rapidly inactivated in the presence of mercurous chloride. Titration of malate dehydrogenase by 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) in a solution of 8 M urea revealed 18 SH groups per molecule of the enzyme. Eight sulphydryl groups reacted with DTNB in native malate dehydrogenase and their modification was not accompanied by a loss of the enzyme activity. The interaction of p-chloromercury benzoate (PCMB) with malate dehydrogenase resulted in a 70% decrease in the enzyme activity. The binding of the thiol reagents by the malate dehydrogenase molecule appreciably increased the Michaelis constant value for the substrate. In the presence of magnesium ions, NADP and malate did not affect the process of malate dehydrogenase modification by DTNB and did not protect the enzyme from the inactivation by PCMB. It is suggested from the data obtained that the sulphyryl groups are involved in maintaining the active conformation of the enzyme. | Malate Dehydrogenase (NADP+) |
Lysimachia foenum-graecum Hance (Primulaceae) is a medicinal plant used for cold, pain, ascariasis, etc., in China. Triterpenoid saponins have been found to be the main components of this genus. In this work, a pair of oleanane-type triterpenoid saponins with an unprecedented 4/5/6 fused tricyclic skeleton, foegraecumoside O (1) and foegraecumoside P (2) were isolated from the butanol fraction of the aerial parts of L. foenum-graecum. Their structures were determined using chemical methods and extensive spectroscopic analyses, along with quantum chemical calculations. Compound 2 displayed moderate cytotoxicity against HepG2, MGC-803, T24, NCI-H460, A549, and A549/CDDP (drug-resistant lung-cancer cell line) with IC(50) at 12.4-19.2 muM in an MTT assay, comparing with the positive control doxorubicin, which had IC(50) at 0.53-4.92 muM, but was inactive for A549/CDDP. Furthermore, a possible biosynthetic pathway for forming compounds 1 and 2 was proposed. | Lysimachia |
BACKGROUND: Several case control studies have reported an increased risk of cardiovascular events following discontinuation of antiplatelet agents in high-risk patients. We therefore sought to investigate the risk of recurrent stroke and cardiovascular events following discontinuation of antiplatelet study medication in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial, a large randomized secondary stroke prevention study. METHODS: The recurrent stroke and cardiovascular event rates following discontinuation of aspirin plus extended-release dipyridamole (ASA + ERDP) or clopidogrel were compared to the event rates in the on-treatment populations (patients who had discontinued their antiplatelet medication due to an outcome event were kept in the on-treatment population in order not to underestimate the on-treatment stroke rate). RESULTS: In 7,212 treated ASA + ERDP patients, the stroke incidence rate for the on-treatment group was 729 strokes with an average exposure of 17,048 person-years (0.12 per 1,000 person-days). For 7,864 treated clopidogrel patients, the stroke incidence rate for the on-treatment group was 737 strokes with an average exposure of 18,715 person-years (0.11 per 1,000 person-days). ASA + ERDP was discontinued in 2,843 patients (in 57.7% due to an adverse event, 28.2% noncompliance, 1.4% loss to follow-up, 4.5% withdrawal of consent and 8.1% other/nonspecified reasons) and clopidogrel was permanently discontinued in 2,176 patients (49.0% due to an adverse event, 34.2% noncompliance, 1.8% loss to follow-up, 5.3% withdrawal of consent and 9.7% other/nonspecified reasons). Within 30 days, a recurrent stroke occurred in 31 patients (0.37 per 1,000 person-days) after discontinuation of ASA + ERDP and in 15 patients (0.24 per 1,000 person-days) after discontinuation of clopidogrel. This corresponds to an absolute excess risk of 0.77% within 30 days after discontinuation of ASA + ERDP and 0.40% within 30 days after discontinuation of clopidogrel compared with the on-treatment study populations. A combined vascular endpoint (stroke, myocardial infarction, vascular death) occurred in 68 patients (0.82 per 1,000 person-days) within 30 days after discontinuation of ASA + ERDP and in 47 patients (0.75 per 1,000 person-days) within 30 days after discontinuation of clopidogrel. This corresponds to an absolute excess risk of 2.02% within 30 days after discontinuation of ASA + ERDP and 1.83% within 30 days after discontinuation of clopidogrel compared with the on-treatment study populations. CONCLUSION: Discontinuation of antiplatelet medication after ischemic stroke should be advocated only when the risk and severity of bleeding clearly outweigh the risk of cardiovascular events." | Aspirin, Dipyridamole Drug Combination |
Herein, a new method was demonstrated for effective immobilization of the antibacterial peptide nisin on Grifola frondosa hydrophobin (HGFI), without the need of any additional complex reaction. Hydrophobin can self-assemble as a monolayer to form continuous negative-charged surfaces with enhanced wettability and biocompatibility. Adding nisin solution to such hydrophobin surface created antibacterial surfaces. The quantification analysis revealed that more nisin could be adsorbed on the HGFI-coated than to control polystyrene surfaces at different pH values. This suggested that electronic attraction and wettability may play important roles in this process. The transmission electron microscopy, atomic force microscopy and fourier transform infrared (FTIR) analysis indicated the adsorption mode of nisin on the HGFI film, i.e., hydrophobins served as an adhesive layer for binding charged peptides to interfaces. The antibacterial activity of the treated surface was investigated via counting, a nucleic acid release test, scanning electron microscopy, and biofilm detection. These results indicated the excellent antibacterial activity of nisin adsorbed on the HGFI-coated surfaces. The activity retention of adsorbed nisin was demonstrated by immersing the modified substrates in a flowed liquid condition. | Grifola |
Functional residual capacity (FRC) of the lung was measured by the closed-circuit helium equilibration method before and for five days after upper abdominal operations in 28 patients (25 had cholecystectomies). Measurements in many were made with the patient both sitting in bed and sitting in a chair. Vital capacity (VC), residual volume (RV), and forced expiratory volume in one second (FEV1), as well as FRC, all decreased after operation, with the maximum decrease on days 1 and 2 and a gradual return toward preoperative values by day 5. Patients with 40% or less decrease in FRC after operation did not develop pulmonary complications. Change in position from bed to chair increased FRC 14.2% preoperatively and 17% postoperatively. The use of intermittent positive pressure breathing had no measurable effect on FRC. Similar changes in FEV1, VC, and RV also occurred, with maximum decreases on day 1. | Functional Residual Capacity |
Ocean acidification (OA) and warming currently threaten coastal ecosystems across the globe. However, it is possible that the former process could actually benefit marine plants, such as seagrasses. The purpose of this study was to examine whether the effects of the seagrass Thalassia hemprichii can increase the resilience of OA-challenged coral reef mesocosms whose temperatures were gradually elevated. It was found that seagrass shoot density, photosynthetic efficiency, and leaf growth rate actually increased with rising temperatures under OA. Macroalgal growth rates were higher in the seagrass-free mesocosms, but the calcification rate of the model reef coral Pocillopora damicornis was higher in coral reef mesocosms featuring seagrasses under OA at 25 and 28⯠degrees C. Both the macroalgal growth rate and the coral calcification rate decreased in all mesocosms when the temperature was raised to 31⯠degrees C under OA. However, the variation in gross primary production, ecosystem respiration, and net ecosystem production in the seagrass mesocosms was lower than in seagrass-free controls, suggesting that the presence of seagrass in the mesocosms helped to stabilize the metabolism of the system in response to simulated climate change. | Hydrocharitaceae |
Port-wine stain (PWS) birthmarks are one class of benign congenital vascular malformation. Laser therapy is the most successful treatment modality of PWS. Unfortunately, this approach has limited efficacy, with only 10% of patients experiencing complete blanching of the PWS. To address this problem, several research groups have developed technologies and methods designed to study treatment outcome and improve treatment efficacy. This article reviews seven optical imaging techniques currently in use or under development to assess treatment efficacy, focusing on: reflectance spectrophotometers/tristimulus colorimeters; laser Doppler flowmetry and laser Doppler imaging; cross-polarized diffuse reflectance colour imaging system; reflectance confocal microscopy; optical coherence tomography; spatial frequency domain imaging; and laser speckle imaging. | Port-Wine Stain |
Cytogenetic studies were performed on a fibrosarcoma of a newborn. Only numerical chromosome changes (+8, +11, +20) were identified in this rare but distinct soft tissue sarcoma that occurs in children less than 5 years old. | Fibrosarcoma |
The systematic review and meta-analysis evaluated the effect of aerobic, resistance and combined exercise on RMR (kCal.day(-1)) and performed a methodological assessment of indirect calorimetry protocols within the included studies. Subgroup analyses included energy/diet restriction and body composition changes. Randomized control trials (RCTs), quasi - RCTs and cohort trials featuring a physical activity intervention of any form and duration excluding single exercise bouts were included. Participant exclusions included medical conditions impacting upon RMR, the elderly (>/=65 years of age) or pregnant, lactating or post-menopausal women. The review was registered in the International Prospective Register of Systematic Reviews (CRD 42,017,058,503). 1669 articles were identified; 22 were included in the qualitative analysis and 18 were meta-analysed. Exercise interventions (aerobic and resistance exercise combined) did not increase resting metabolic rate (mean difference (MD): 74.6 kCal.day(-1)[95% CI: -13.01, 161.33], P = 0.10). While there was no effect of aerobic exercise on RMR (MD: 81.65 kCal.day(-1)[95% CI: -57.81, 221.10], P = 0.25), resistance exercise increased RMR compared to controls (MD: 96.17 kCal.day(-1)[95% CI: 45.17, 147.16], P = 0.0002). This systematic review effectively synthesises the effect of exercise interventions on RMR in comparison to controls; despite heterogenous methodologies and high risk of bias within included studies. | Basal Metabolism |
The branched DNA (bDNA) assay is a reliable method for quantifying the RNA of human immunodeficiency virus type 1 (HIV-1). The positive controls and standards for this assay for the detection of HIV-1 consist of naked RNA, which is susceptible to degradation by RNase. Armored RNA is a good candidate for an RNase-resistant positive control or standard. However, its use has been limited by the maximal length of the exogenous RNA packaged into virus-like particles by routine armored RNA technology. In the present study, we produced armored long RNA (armored L-RNA) controls or standards (AR-HIV-pol-3034b) for a bDNA assay of HIV-1 by increasing the amount and affinity of the pac sites (the pac site is a specific 19-nucleotide stem-loop region located at the 5' terminus of the MS2 bacteriophage replicase gene) by a one-plasmid double-expression system. AR-HIV-pol-3034b was completely resistant to DNase and RNase, was stable in normal human EDTA-preserved plasma at 4 degrees C for at least 6 months, and produced reproducible, linear results in the Versant HIV-1 RNA 3.0 assay. In conclusion, AR-HIV-pol-3034b could act as a positive control or standard in a bDNA assay for the detection of HIV-1. In addition, the one-plasmid double-expression system can be used as a better platform than the one-plasmid expression system and the two-plasmid coexpression system for expressing armored L-RNA." | Branched DNA Signal Amplification Assay |
Two new coffee relatives (tribe Coffeeae, Rubiaceae), discovered during botanical expeditions to Cameroon, are examined for generic placement, and the placement of three previously known species (Argocoffeopsis fosimondi, A. spathulata and Calycosiphonia pentamera) is reinvestigated using plastid sequence (accD-psa1, rpl16, trnL-F) and morphological data. Seed biochemistry of the new species and pollen micromorphology (only one of the two species) are also studied. Based on the plastid sequence data, the new taxa are nested in a well-supported monophyletic group that includes Argocoffeopsis and Calycosiphonia. Within this clade, three well-supported subclades are recovered that are morphologically easy to diagnose: (1) Calycosiphonia (excluding C. pentamera), (2) Argocoffeopsis (excluding A. fosimondi and A. spathulata), and (3) a clade including the above excluded species, in addition to the new species. Based on the results, Kupeantha, a new genus of five species, is described, including two new Critically Endangered taxa from the Highlands of Cameroon: Kupeantha ebo and K. kupensis. Phytochemical analysis of Kupeantha seeds reveals compounds assigned as hydroxycinnamic acid derivatives, amino acids and ent-kaurane diterpenoids; caffeine was not detected. Kupeantha is the first new genus described in tribe Coffeeae in 40 years. | Rubiaceae |
AIM: Adaptive mechanisms in spinal circuits are likely involved in homeostatic responses to maintain motor output in amyotrophic lateral sclerosis. Given the role of Renshaw cells in regulating the motoneuron input/output gain, we investigated the modulation of heteronymous recurrent inhibition. METHODS: Electrical stimulations were used to activate recurrent collaterals resulting in the Hoffmann reflex depression. Inhibitions from soleus motor axons to quadriceps motoneurons, and vice versa, were tested in 38 patients and matched group of 42 controls. RESULTS: Compared with controls, the mean depression of quadriceps reflex was larger in patients, while that of soleus was smaller, suggesting that heteronymous recurrent inhibition was enhanced in quadriceps but reduced in soleus. The modulation of recurrent inhibition was linked to the size of maximal direct motor response and lower limb dysfunctions, suggesting a significant relationship with the integrity of the target motoneuron pool and functional abilities. No significant link was found between the integrity of motor axons activating Renshaw cells and the level of inhibition. Enhanced inhibition was particularly observed in patients within the first year after symptom onset and with slow progression of lower limb dysfunctions. Normal or reduced inhibitions were mainly observed in patients with motor weakness first in lower limbs and greater dysfunctions in lower limbs. CONCLUSION: We provide the first evidence for enhanced recurrent inhibition and speculate that Renshaw cells might have transient protective role on motoneuron by counteracting hyperexcitability at early stages. Several mechanisms likely participate including cortical influence on Renshaw cell and reinnervation by slow motoneurons. | Renshaw Cells |
An acetone extract from the aerial parts of Euphorbia bungei afforded three new (2, 3 and 5) and one known (4) macrocyclic diterpenoids. Several cycloartane triterpenoids were also obtained, two of which (6a and 6b) were assayed for antiviral effects. The structures of all new compounds were elucidated using modern spectroscopic methods including 2D NMR and HRMS. | Euphorbia |
BACKGROUND: In spite of the availability of single nucleotide polymorphism (SNP) array data, differentiation between observed homozygosity and that caused by mating between relatives (autozygosity) introduces major difficulties. Homozygosity estimators show large variation due to different causes, namely, Mendelian sampling, population structure, and differences among chromosomes. Therefore, the ascertainment of how inbreeding is reflected in the genome is still an issue. The aim of this research was to study the usefulness of genomic information for the assessment of genetic diversity in the highly endangered Gochu Asturcelta pig breed. Pedigree depth varied from 0 (founders) to 4 equivalent discrete generations (t). Four homozygosity parameters (runs of homozygosity, F(ROH); heterozygosity-rich regions, F(HRR); Li and Horvitz's, F(LH); and Yang and colleague's F(YAN)) were computed for each individual, adjusted for the variability in the base population (BP; six individuals) and further jackknifed over autosomes. Individual increases in homozygosity (depending on t) and increases in pairwise homozygosity (i.e., increase in the parents' mean) were computed for each individual in the pedigree, and effective population size (N(e)) was computed for five subpopulations (cohorts). Genealogical parameters (individual inbreeding, individual increase in inbreeding, and N(e)) were used for comparisons. RESULTS: The mean F was 0.120 +/- 0.074 and the mean BP-adjusted homozygosity ranged from 0.099 +/- 0.081 (F(LH)) to 0.152 +/- 0.075 (F(YAN)). After jackknifing, the mean values were slightly lower. The increase in pairwise homozygosity tended to be twofold higher than the corresponding individual increase in homozygosity values. When compared with genealogical estimates, estimates of N(e) obtained using F(YAN) tended to have low root-mean-squared errors. However, N(e) estimates based on increases in pairwise homozygosity using both F(ROH) and F(HRR) estimates of genomic inbreeding had lower root-mean-squared errors. CONCLUSIONS: Parameters characterizing homozygosity may not accurately depict losses of variability in small populations in which breeding policy prohibits matings between close relatives. After BP adjustment, the performance of F(ROH) and F(HRR) was highly consistent. Assuming that an increase in homozygosity depends only on pedigree depth can lead to underestimating it in populations with shallow pedigrees. An increase in pairwise homozygosity computed from either F(ROH) or F(HRR) is a promising approach for characterizing autozygosity. | Homozygote |
BACKGROUND: The pathogenesis of inflammatory bowel diseases (IBD) involves complex interactions between the microbiome and the immune system. We evaluated the association between the gut microbiota and disease activity in IBD patients. METHODS: Systematic review of clinical studies based on a published protocol. Included patients had ulcerative colitis (UC) or Crohn's disease (CD) classified as active or in remission. We selected bacteria assessed in at least three studies identified through electronic and manual searches (November 2015). Bias control was evaluated with the Newcastle Ottawa scale (NOS). Results of random-effects meta-analyses were presented as mean differences (MD). RESULTS: Three prospective and seven cross-sectional studies (NOS score 6-8) were included. Five studies included patients with CD (231 patients) and eight included patients with UC (392 patients). Compared to patients in remission, patients with active IBD had lower abundance of Clostridium coccoides (MD = -0.49, 95% CI: -0.79 to -0.19), Clostridium leptum (MD = -0.44, 95% CI: -0.74 to -0.14), Faecalibacterium prausnitzii (MD = -0.81, 95% CI: -1.23 to -0.39) and Bifidobacterium (MD = -0.37, 95% CI: -0.56 to -0.17). Subgroup analyses showed a difference in all four bacteria between patients with UC classified as active or in remission. Patients with active CD had fewer C. leptum, F. prausnitzii and Bifidobacterium, but not C. coccoides. CONCLUSION: This systematic review suggests that dysbiosis may be involved in the activity of IBD and that there may be differences between patients with CD and UC. | Faecalibacterium |
The idea of establishing the amyloid-like fibrillation tendency of pro- and antisurvival proteins of human apoptotic pathways is relevant for delineating the conditions that lead to aberrant differentiation, development, and tissue homeostasis. As the first step in this direction, we report here that the caspase recruitment domain (CARD) of recombinant human apoptotic protease activating factor-1 (Apaf-1) can be induced to undergo amyloid-like fibrillation. The study was initiated with a set of biophysical investigations into the possibility and in vitro conditions for fibril growth. By scanning the pH-induced conformational transitions, protein stability, and stopped-flow folding-unfolding kinetics, we detected a molten globule (MG) transition of the CARD at pH <4. In a bid to reduce the surface-accessible hydrophobic patches in the MG state, the CARD monomer undergoes self-association to produce soluble oligomers that serve as precursor aggregates for protofibril formation. The monomer-to-oligomer self-association process is akin to the well-known homophilic CARD-CARD interaction by which CARDs of the same or different apoptotic proteins associate to transduce and regulate the apoptotic signal. The fibrillation reaction of the Apaf-1 CARD was conducted at pH 2.1 and 60 degrees C, because reduction of exposed hydrophobic surfaces in the MG state is more favored under the moderated solution condition. The Gaussian distributions of diameters of the fibril population suggest values of 2.1 and 2.7 nm for the mean diameter of precursor aggregates and protofibrils or elongated fibrils, respectively." | CARD Signaling Adaptor Proteins |
Complementary and alternative medicine (CAM) is increasingly being used in Western countries despite the lack of conclusive research studies. Several CAM modalities have only shown variable therapeutic efficacy in infectious disease management. Clinicians should be familiar with these therapies in order to advise patients about alternative therapeutic options when treating infections. | Materia Medica |
This study aimed to analyze the scientific production about audit in nursing, published in national papers, between 1998 and 2008. A systematic review of the literature was conducted, with articles being searched in the databases LILACS and SciELO, from the key words: audit, nursing, quality health care and nursing supervision. The sample consisted of ten works. The analyzed publications describe the main distortions and non-conformities found in nursing records, relating them mainly with the quality of nursing care and with the financial damage to the institutions. The publications also include the administrative role of the nurse, especially her/his leadership role in the team of nursing; and nursing audit as an educational process. | Nursing Audit |
Sialic acids are a group of nine-carbon alpha-keto acids. Sialic acid exists in more than 50 forms, with the natural types discovered as N-acetylneuraminic acid (Neu5Ac), deaminoneuraminic acid (2-keto-3-deoxy-nonulononic acid or Kdn), and N-glycolylneuraminic acid (Neu5Gc). Sialic acid level varies depending on the source, where edible bird's nest (EBN), predominantly Neu5Ac, is among the major sources of sialic acid. Due to its high nutritive value and complexity, sialic acid has been studied extensively through acid, aqueous, and enzymatic extraction. Although detection by chromatographic methods or mass spectrometry is common, the isolation and recovery work remained limited. Sialic acid is well-recognised for its bioactivities, including brain and cognition development, immune-enhancing, anti-hypertensive, anticancer, and skin whitening properties. Therefore, sialic acid can be used as a functional ingredient in the various industries. This paper reviews the current trend in the biochemistry, sources, extraction, and functions of sialic acids with special reference to EBN. | Sugar Acids |
The diagnosis of cardiac amyloidosis (CA) often necessitates invasive myocardial biopsy. We sought to evaluate whether late gadolinium enhancement (LGE) of the atrial myocardium by cardiac magnetic resonance imaging was associated with impaired left atrial (LA) function and whether the extent of LA LGE may enhance diagnostic differentiation of CA from other cardiomyopathies. Twenty-two patients with biopsy-proven CA, 37 with systemic hypertension (SH), and 22 with nonischemic dilated cardiomyopathy (NIDC) underwent cardiac magnetic resonance imaging and echocardiographic evaluation. Patients with CA had greater minimal LA volume (57 +/- 53 vs 24 +/- 18 in SH and 19 +/- 25% in NIDC, p = 0.003), and significantly lower total LA emptying function (19 +/- 14 vs 40 +/- 14 in SH and 33 +/- 20% in NIDC, p = 0.0006). The mean proportion of atrial enhancement (LGELA%) was significantly greater in patients with CA than with SH and NIDC (59 +/- 36% vs 7.4 +/- 2.1 and 2.9 +/- 9.0%, p <0.0001, respectively). There was also a strong inverse correlation between both active and total atrial emptying (r = -0.69, p = 0.001; r = -0.67, p = 0.01, respectively) with LGELA% for patients with CA. In multivariate regression analysis, LGELA% was the strongest adjusted predictor for CA diagnosis. Using receiver operating characteristic analysis, LGELA% >/=33% produced the greatest diagnostic utility for CA (sensitivity 76%, specificity 94%). Patients with CA may have extensive LGE of the LA myocardium, which is associated with marked reduction in LA emptying function. The extent of LA LGE was highly predictive for the diagnosis of CA. | Atrial Function, Left |
The binding properties of seven mouse monoclonal antibodies (McAbs) raised against cowpea mosaic virus (CPMV) were characterized by conventional and inhibition enzyme-linked immunosorbent assay (ELISA) technique. McAb binding to CPMV on electron microscope (EM) grids was also assayed with gold-labeled anti-mouse antibodies. Two of the seven McAbs (5B2 and 10B7) were found to bind tighter to CPMV than the others in the inhibition ELISA and the EM assay. F(ab) fragments from both of these McAbs were prepared and complexed with CPMV in solution. Electron micrographs of flash frozen (vitrified) samples of native CPMV and CPMV complexed with F(ab) fragments from McAbs 5B2 and 10B7 as well as IgGs from 5B2 were recorded and reconstructions were computed at 23 A resolution for the CPMV/F(ab) complexes and 30 A resolution for the CPMV/IgG complex. Structures of all three complexes clearly displayed the F(ab) fragments distributed with icosahedral symmetry on the surface of CPMV. The IgG bound in a monodentate fashion with only one F(ab) attached to the virus surface. F(ab) fragments from 5B2 and 10B7 bound to nearly identical positions. The refined 2.8 A X-ray structure of CPMV was used to identify the roughly 30 amino acids covered by the F(ab) fragments. The footprint" spans a subunit interface and appears spatially similar to antigenic site 3B on poliovirus. In a previous, preliminary report of the CPMV/F(ab) 5B2 complex (Wang et al., 1992, Nature 355, 275-278) the wrong enantiomorph of the reconstruction was chosen. This was corrected and, since the F(ab) binds close to a mirror plane, the change in the footprint was minor." | Comovirus |
Several short-lived, high-energy beta emitters are being proposed as the radionuclide components for molecular- targeted potential cancer therapeutic agents. The laboratory mice used to determine the efficacy of these new agents have organs that are relatively small compared to the ranges of these high-energy particles. The dosimetry model developed by Hui et al. was extended to provide realistic beta-dose estimates for organs in mice that received therapeutic radiopharmaceuticals containing (90)Y, (188)Re, (166)Ho, (149)Pm, (64)Cu, and (177)Lu. Major organs in this model included the liver, spleen, kidneys, lungs, heart, stomach, small and large bowel, thyroid, pancreas, bone, marrow, carcass, and a 0.025-g tumor. The study as reported in this paper verifies their results for (90)Y and extends them by using their organ geometry factors combined with newly calculated organ self-absorbed fractions from PEREGRINE and MCNP. PEREGRINE and MCNP agree to within 8% for the worst-case organ with average differences (averaged over all organs) decreasing from 5% for (90)Y to 1% for (177)Lu. When used with typical biodistribution data, the three different models predict doses that are in agreement to within 5% for the worst-case organ. The beta-absorbed fractions and cross-organ-deposited energy provided in this paper can be used by researchers to predict mouse-organ doses and should contribute to an improved understanding of the relationship between dose and radiation toxicity in mouse models where use of these isotopes is favorable. | Promethium |
The ability to regenerate extensive portions of the body is widespread among the phylum Annelida and this group includes some of the most highly regenerative animals known. Knowledge of the cellular and molecular basis of regeneration in this group is thus important for understanding how regenerative processes have evolved both within the group and across animal phyla. Here, the cellular basis of annelid regeneration is reviewed, with a focus on the earliest steps of regeneration, namely wound-healing and formation of the blastema. Information from a wide range of annelids is compiled in order to identify common and variable elements. There is a large body of valuable older literature on the cellular basis of regeneration in annelids and an effort is made to review this literature in addition to more recent studies. Annelids typically seal the wound through muscular contraction and undergo some autolysis of tissue at the site of the wound. Bodily injury elicits extensive cell migration toward the wound, involving several different types of cells. Some migrating cells form a tissue-clot and phagocytize damaged tissues, whereas others are inferred to contribute to regenerated tissue, specifically mesodermal tissue. In one annelid subgroup, the clitellates, a group of mesodermal cells, sometimes referred to as neoblasts, is inferred to migrate over considerable distances, with cells moving to the wound from several segments away. Epidermis and gut epithelia severed upon amputation typically heal by fusing with like tissue, although not always. After amputation, cellular contacts with the extracellular matrix are disrupted and major changes in cell morphology and adhesion occur within tissues near the wound. Interactions of tissues at the wound appear key for initiating a blastema, with a particularly important role suggested for the ventral nerve cord, although species are variable in this regard; longer-distance effects mediated by the brain are also reported. The anterior-posterior polarity of the blastema can be mis-assigned, leading most commonly to double-headed worms, and the dorsal-ventral polarity of the blastema appears to be induced by the ventral nerve cord. The blastema is thought to arise from contributions of all three tissue layers, with each layer replacing itself in a tissue-specific manner. Blastemal cells originate mostly locally, although some long-distance migration of source-cells is suggested in clitellates. A number of important questions remain about the cellular basis of regeneration in annelids and addressing many of these would be greatly aided by developing approaches to identify and isolate specific cell types and techniques to image and trace cells in vivo. | Annelida |
BACKGROUND & AIMS: Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare lethal autosomal recessive liver disorder caused by loss-of-function variations of the ABCB4 gene, encoding a phosphatidylcholine transporter (ABCB4/MDR3). Currently, no effective treatment exists for PFIC3 outside of liver transplantation. METHODS: We have produced and screened chemically and genetically modified mRNA variants encoding human ABCB4 (hABCB4 mRNA) encapsulated in lipid nanoparticles (LNPs). We examined their pharmacological effects in a cell-based model and in a new in vivo mouse model resembling human PFIC3 as a result of homozygous disruption of the Abcb4 gene in fibrosis-susceptible BALB/c.Abcb4(-/-) mice. RESULTS: We show that treatment with liver-targeted hABCB4 mRNA resulted in de novo expression of functional hABCB4 protein and restored phospholipid transport in cultured cells and in PFIC3 mouse livers. Importantly, repeated injections of the hABCB4 mRNA effectively rescued the severe disease phenotype in young Abcb4(-/-) mice, with rapid and dramatic normalisation of all clinically relevant parameters such as inflammation, ductular reaction, and liver fibrosis. Synthetic mRNA therapy also promoted favourable hepatocyte-driven liver regeneration to restore normal homeostasis, including liver weight, body weight, liver enzymes, and portal vein blood pressure. CONCLUSIONS: Our data provide strong preclinical proof-of-concept for hABCB4 mRNA therapy as a potential treatment option for patients with PFIC3. LAY SUMMARY: This report describes the development of an innovative mRNA therapy as a potential treatment for PFIC3, a devastating rare paediatric liver disease with no treatment options except liver transplantation. We show that administration of our mRNA construct completely rescues severe liver disease in a genetic model of PFIC3 in mice." | ATP Binding Cassette Transporter, Subfamily B |
Divergent natural selection, adaptive divergence and gene flow may interact in a number of ways. Recent studies have focused on the balance between selection and gene flow in natural populations, and empirical work has shown that gene flow can constrain adaptive divergence, and that divergent selection can constrain gene flow. A caveat is that phenotypic diversification may be under the direct influence of environmental factors (i.e. it may be due to phenotypic plasticity), in addition to partial genetic influence. In this case, phenotypic divergence may occur between populations despite high gene flow that imposes a constraint on genetic divergence. Plasticity may dampen the effects of natural selection by allowing individuals to rapidly adapt phenotypically to new conditions, thus slowing adaptive genetic divergence. On the other hand, plasticity may promote future adaptive divergence by allowing populations to persist in novel environments. Plasticity may promote gene flow between selective regimes by allowing dispersers to adapt to alternate conditions, or high gene flow may result in the selection for increased plasticity. Here I expand frameworks for understanding relationships among selection, adaptation and gene flow to include the effects of phenotypic plasticity in natural populations, and highlight its importance in evolutionary diversification. | Gene Flow |
Sterol regulatory element-binding protein (SREBP)-1a is a unique membrane-bound transcription factor highly expressed in actively growing cells and involved in the biosynthesis of cholesterol, fatty acids, and phospholipids. Because mammalian cells need to synthesize membrane lipids for cell replication, the functional relevance of SREBP-1a in cell proliferation has been considered a biological adaptation. However, the effect of this potent lipid-synthesis activator on cell growth has never been explored. Here, we show that induction of nuclear SREBP-1a, but not SREBP-2, completely inhibited cell growth in inducible Chinese hamster ovary (CHO) cell lines. Growth inhibition occurred through G(1) cell-cycle arrest, which is observed in various cell types with transient expression of nuclear SREBP-1a. SREBP-1a caused the accumulation of cyclin-dependent kinase (cdk) inhibitors such as p27, p21, and p16, leading to reduced cdk2 and cdk4 activities and hypophosphorylation of Rb protein. In contrast to transactivation of p21, SREBP-1a activated p27 by enhancing stabilization of the protein through inhibition of SKP2 and KPC1. In vivo, SREBP-1a-expressing livers of transgenic mice exhibited impaired regeneration after partial hepatectomy. SREBP-1-null mouse embryonic fibroblasts had a higher cell proliferation rate than wild-type cells. The unexpected cell growth-inhibitory role of SREBP-1a provides a new paradigm to link lipid synthesis and cell growth." | Sterol Regulatory Element Binding Protein 1 |
Early initiation of rational and effective combination therapy consisting of antihypertensive drugs with two different and complementary mechanisms of actions is increasingly becoming accepted in clinical practice and by guidelines as a first-line approach to control blood pressure (BP) and prevent cardiovascular outcomes in patients with hypertension. Once-daily combination therapy provides more rapid control of BP, which is important for preventing cardiovascular events, with similar or improved tolerability compared with the component monotherapies, and improved adherence because of regimen simplification. Combination therapy with a calcium channel antagonist (calcium channel blocker [CCB]) and an inhibitor of the renin-angiotensin-aldosterone system (RAAS) is a rational approach to achieve BP goals and provide protection against renal and cardiovascular morbidity and mortality. A number of CCB/RAAS inhibitor combinations, including CCB/angiotensin-converting enzyme (ACE) inhibitor and CCB/ angiotensin II type 1 receptor antagonist (angiotensin receptor blocker [ARB]) combinations are available as fixed-dose formulations. There is substantial evidence for the BP-lowering efficacy of CCB/RAAS inhibitor combinations in diverse patient populations, and their use in combination is associated with favourable tolerability and fewer adverse metabolic effects than some other combination therapies. Recent evidence from large outcome trials supports the use of CCB/RAAS inhibitor combinations for reducing the risk of cardiovascular and renal events, particularly in high-risk patients, together with evidence that the benefits of CCB/RAAS inhibitor combinations may extend beyond their efficacy in lowering BP in terms of protecting against fatal and nonfatal stroke, myocardial infarction and cardiovascular-related deaths. The efficacy of the CCB amlodipine and the ARB valsartan in lowering BP and protecting against cardiovascular events and stroke across a range of hypertensive patient populations has been established over many years. Fixed-dose amlodipine/valsartan combinations are available in many countries and have shown greater BP reductions and better BP control than the respective monotherapies in diverse patient populations, together with a favourable tolerability profile. Once-daily amlodipine/valsartan is a rational and convenient treatment option for the effective management of patients with hypertension, improving adherence to antihypertensive medication and protecting against cardiovascular and renal morbidity and mortality." | Amlodipine, Valsartan Drug Combination |
Most previously described immunohistochemical markers of cervical high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma may help to improve diagnostic accuracy but have a minimal prognostic value. The goals of the current study were to identify and validate novel candidate biomarkers that could potentially improve diagnostic and prognostic accuracy for cervical HSIL and squamous cell carcinoma. Microdissected tissue sections from formalin-fixed paraffin-embedded normal ectocervical squamous mucosa, low-grade squamous intraepithelial lesion (LSIL), HSIL and squamous cell carcinoma sections were analyzed by mass spectrometry-based shotgun proteomics for biomarker discovery. The diagnostic specificity of candidate biomarkers was subsequently evaluated by immunohistochemical analysis of tissue microarrays. Among 1750 proteins identified by proteomic analyses, keratin 4 (KRT4) and keratin 17 (KRT17) showed reciprocal patterns of expression in the spectrum of cases ranging from normal ectocervical squamous mucosa to squamous cell carcinoma. Immunohistochemical studies confirmed that KRT4 expression was significantly decreased in squamous cell carcinoma compared with the other diagnostic categories. By contrast, KRT17 expression was significantly increased in HSIL and squamous cell carcinoma compared with normal ectocervical squamous mucosa and LSIL. KRT17 was also highly expressed in immature squamous metaplasia and in endocervical reserve cells but was generally not detected in mature squamous metaplasia. Furthermore, high levels of KRT17 expression were significantly associated with poor survival of squamous cell carcinoma patients (Hazard ratio=14.76, P=0.01). In summary, both KRT4 and KRT17 expressions are related to the histopathology of the cervical squamous mucosa; KRT17 is highly overexpressed in immature squamous metaplasia, in HSIL, and in squamous cell carcinoma and the level of KRT17 in squamous cell carcinoma may help to identify patients who are at greatest risk for cervical cancer mortality. | Keratin-4 |
Apoptosis is a fundamental feature in the development of many organisms and tissue systems. It is also a mechanism of host defense against environmental stress factors or pathogens by contributing to the elimination of infected cells. Hemocytes play a key role in defense mechanisms in invertebrates and previous studies have shown that physical or chemical stress can increase apoptosis in hemocytes in mollusks. However this phenomenon has rarely been investigated in bivalves especially in the flat oyster Ostrea edulis. The apoptotic response of hemocytes from flat oysters, O. edulis, was investigated after exposure to UV and dexamethasone, two agents known to induce apoptosis in vertebrates. Flow cytometry and microscopy were combined to demonstrate that apoptosis occurs in flat oyster hemocytes. Investigated parameters like intracytoplasmic calcium activity, mitochondrial membrane potential and phosphatidyl-serine externalization were significantly modulated in cells exposed to UV whereas dexamethasone only induced an increase of DNA fragmentation. Morphological changes were also observed on UV-treated cells using fluorescence microscopy and transmission electron microscopy. Our results confirm the apoptotic effect of UV on hemocytes of O. edulis and suggest that apoptosis is an important mechanism developed by the flat oyster against stress factors. | Ostrea |
We have isolated Azospirillum (Spirullum lipoferum) from roots of grasses of several genera collected from a number of tropical and subtropical-temperate locations. Pure cultures were obtained from a small percentage of samples; no higher percentage was secured from tropical than from other grasses. Acetylene reduction and distinctive growth in N-free soft agar deeps were inadequate to identify this genus, although helpful in initial screening. Fluorescent antibody tests with antiserum against characterized strains were helpful. There is some evidence that this genus of bacteria may be favored in the rhizoplane. | Spirillaceae |
Broca's region, corresponding roughly to cytoarchitectonic areas 44 and 45 in the inferior frontal cortex, holds a multifunctional role in language processing, as shown, e.g., by functional imaging data. Neuro-navigated transcranial magnetic stimulation (TMS) enables complementary non-invasive mapping of cortical functions with high spatial resolution. Here, we report on detailed TMS language mapping of Broca's region in 12 healthy participants. The test protocol with an object naming task was adapted for high-resolution and semi-quantitative mapping of TMS-induced effects on speech and language performance. Hierarchical cluster analysis of normalized ratings of error frequency and severity revealed a clear focus of TMS impact at dorso-posterior target sites, close to the inferior frontal junction. Adjacent clusters of moderate and slightly affected stimulation sites yielded a posterosuperior-to-anteroinferior gradient of TMS susceptibility. Our findings indicate that the part of Broca's region most susceptible to TMS-induced language inhibition in object naming is located in the dorsal area 44. | Broca Area |
Characterization and counting of the different immune cell subpopulations are largely used in order to predict the quality of vaccination or the progression of diseases. As such, flow cytometry is a valuable technology to perform an exact cartography of the immune cell subsets. In the context of B-cell responses, specialized structures emerge in B-follicles of second lymphoid organs where B-cells undergo maturation processes under the guidance of specific T-cells, follicular helper T-cells, and follicular regulatory T-cells. Thus, tracking these cell types is of high interest, especially in the context of protein vaccination. In this purpose, we describe here, how we can track antigen-specific follicular helper T-cells and follicular regulatory T-cells by flow cytometry after protein vaccination in nonmodified wild-type mice, which ultimately provides a comprehensive way to better understand the function of these particular cells in vivo." | Leukocytes |
Fourteen tissue sites from the bovine reticulo-rumen were examined by scanning electron microscopy to determine the distribution patterns of bacterial populations adhering to the epithelium. Although diet variations did not appear to influence the total number of tissue-adherent bacteria present in adult Herefords, diet affected their distribution. It appeared that the distribution of the bacterial populations may be directly affected by the physical state of the digesta. The digesta may be mechanically removing adherent bacteria from the tissue surface by abrasive action. The total adherent population consisted of subpopulations with separate distribution patterns, and macropopulations of morphologically similar bacteria were occasionally observed at specific sites on the epithelial surface. Ureolytic organisms on the epithelium followed a distribution pattern considerably different from the general bacterial distribution. | Reticulum |
ShcA (Src homologous- collagen homologue), family of adapter proteins, consists of three isoforms which integrate and transduce external stimuli to different signaling networks. ShcA family consists of p46Shc, p52Shc and p66Shc isoforms, characterized by having multiple protein-lipid and protein-protein interaction domains implying their functional diversity. Among the three isoforms p66Shc is structurally different containing an additional CH2 domain which attributes to its dual functionality in cell growth, mediating both cell proliferation and apoptosis. Besides, p66Shc is also involved in different biological processes including reactive oxygen species (ROS) production, cell migration, ageing, cytoskeletal reorganization and cell adhesion. Moreover, the interplay between p66Shc and ROS is implicated in the pathology of various dreadful diseases. Accordingly, here we discuss the recent structural aspects of all ShcA adaptor proteins but are highlighting the case of p66Shc as model isoform. Furthermore, this review insights the role of p66Shc in progression of chronic age-related diseases like neuro diseases, metabolic disorders (non-alcoholic fatty liver, obesity, diabetes, cardiovascular diseases, vascular endothelial dysfunction) and cancer in relation to ROS. We finally conclude that p66Shc might act as a valuable biomarker for the prognosis of these diseases and could be used as a potential therapeutic target." | Src Homology 2 Domain-Containing, Transforming Protein 1 |
BACKGROUND: Lidocaine and epinephrine could potentially decrease adipocyte viability, but these effects have not been substantiated. The phosphorylation status of perilipin in adipocytes may be predictive of cell viability. Perilipin coats lipid droplets and restricts access of lipases; phospho-perilipin lacks this protective function. OBJECTIVES: The authors investigated the effects of tumescent solution containing lidocaine and epinephrine on the phosphorylation status of perilipin in adipocytes. METHODS: In this in vitro study, lipoaspirates were collected before and after tumescence from 15 women who underwent abdominoplasty. Fat samples were fixed, sectioned, and stained for histologic and immunohistochemical analyses. Relative phosphorylation of perilipin was inferred from pixel intensities of immunostained adipocytes observed with confocal microscopy. RESULTS: For adipocytes collected before tumescent infiltration, 10.08% of total perilipin was phosphorylated. In contrast, 30.62% of total perilipin was phosphorylated for adipocytes collected from tumescent tissue (P < .01). CONCLUSIONS: The tumescent technique increases the relative phosphorylation of perilipin in adipocytes, making these cells more vulnerable to lipolysis. Tumescent solution applied for analgesia or hemostasis of the donor site should contain the lowest possible concentrations of lidocaine and epinephrine. LEVEL OF EVIDENCE 5. | Perilipin-1 |
The measurement of low levels of bacterial lipopolysaccharides (endotoxins) in protein samples can be a challenge due to potential interference from the inherent properties of the protein, its formulation or other substances that may be present. Other factors include the expression system which may have endotoxin species distinct from the standard, as well as different purification bioprocesses. The endotoxin measurement assays also have a number of variables. Those studied include differences between laboratories, reagents and standards, and detection modalities. A variety of protein samples from a range of expression systems was included in the evaluation. Endotoxin levels are relatively stable when samples are stored frozen with test variations between 1 and 38% among different aliquots. Test variation between labs was not significantly different when the same procedure was followed (intermediate precision) by trained analysts. Most testing modalities gave results within a 50-100% variation, a difference generally regarded as within assay variability. However, about 25% of the samples showed significant differences between testing modalities and/or reagents. The sources of these differences were further examined by traditional as well as novel sample treatments. These findings demonstrate that for some samples, endotoxin may be over- or under-estimated and a more thorough pre-treatment or testing modality may be required. | Limulus Test |
INTRODUCTION: The cell wall beta-1,3-glucan of fungal pathogen Candida albicans is an attractive antifungal target. beta-1,3-Glucan is the skeletal structure in the cell wall and the major scaffold for cell wall proteins. In previous studies using Saccharomyces cerevisiae, strong emulsification was detected by mixing cell wall proteins with oil. To date, there have been no reports of applying an emulsification phenomenon to assessing beta-1,3-glucan synthesis inhibition. OBJECTIVE: The aim of this study was to clarify that emulsification is useful as an indicator for evaluating beta-1,3-glucan synthesis inhibition in C. albicans. METHODS: At first, whether cell wall proteins released from cells by beta-1,3-glucanase treatment worked as an effective emulsifier in C. albicans was examined. Next, whether emulsification occurred even in the culture supernatant brought about by treating with bioactive compounds, including beta-1,3-glucan synthesis inhibitors, under osmotic protection was investigated. In addition, the release of cell wall proteins into the culture medium by treating with those compounds was examined. Finally, a simpler evaluation method using emulsion formation was examined for application to screening of inhibitors. RESULTS: Emulsification occurred by cell wall proteins obtained by treating with beta-1,3-glucanase in C. albicans. In addition, cell wall proteins were released into the culture medium by treating with beta-1,3-glucan synthesis inhibitors, resulting in emulsification. However, such phenomena were not observed in the case of other bioactive compounds. Furthermore, emulsification could be detected in the culture broth obtained by static culture on a small scale. CONCLUSIONS: The obtained results strongly implied that emulsification results from decreased beta-1,3-glucan levels in the cell wall. As emulsification can be simply evaluated by mixing the culture broth with oil, in the future application to the initial assessment and screening of beta-1,3-glucan synthesis inhibitors is expected. | Glucan 1,3-beta-Glucosidase |
The V(D)J recombination machinery assembles antigen receptor genes from germline V, D and J segments duringlymphocyte development. In alphabetaT cells, this leads to the production of the T-cell receptor (TCR) alpha and beta chains. Notably, V(D)J recombination at the Tcrb locus is tightly controlled at various levels, including cell-type and stage specificities, intralocus ordering and allelic exclusion. Although many of these controls are partly mediated at the level of genomic accessibility to the V(D)J recombinase, recent studies have uncovered novel mechanisms that are also likely to contribute to the developmental regulation of Tcrb gene rearrangement events. In this chapter, we summarize our current knowledge and highlight unanswered questions regarding the regulation of V(D)J recombination at the Tcrb locus, placing emphasis on mouse transgenesis and gene-targeting approaches." | Gene Rearrangement, beta-Chain T-Cell Antigen Receptor |
Extracellular RNA has been proposed to mediate communication between cells and organisms however relatively little is understood regarding how specific sequences are selected for export. Here, we describe a specific Argonaute protein (exWAGO) that is secreted in extracellular vesicles (EVs) released by the gastrointestinal nematode Heligmosomoides bakeri, at multiple copies per EV. Phylogenetic and gene expression analyses demonstrate exWAGO orthologues are highly conserved and abundantly expressed in related parasites but highly diverged in free-living genus Caenorhabditis. We show that the most abundant small RNAs released from the nematode parasite are not microRNAs as previously thought, but rather secondary small interfering RNAs (siRNAs) that are produced by RNA-dependent RNA Polymerases. The siRNAs that are released in EVs have distinct evolutionary properties compared to those resident in free-living or parasitic nematodes. Immunoprecipitation of exWAGO demonstrates that it specifically associates with siRNAs from transposons and newly evolved repetitive elements that are packaged in EVs and released into the host environment. Together this work demonstrates molecular and evolutionary selectivity in the small RNA sequences that are released in EVs into the host environment and identifies a novel Argonaute protein as the mediator of this. | Heligmosomatoidea |
A facile total synthesis of hainanensine (1), a structurally unique Cephalotaxus alkaloid, via an effective acid-mediated rearrangement/Friedel-Crafts annulation cascade (7a/7b --> 8a/8b), is described. | Harringtonines |
The neurobiological processes that underlie initial use of drugs of abuse and the transition to drug abuse, addiction, and dependence are poorly understood. Intrinsic and drug-related alterations in complex brain functions such as motivation, learning, memory, reward, attention, and arousal seemingly underlie the process of drug abuse and addiction. This discussion focuses on the use of functional brain imaging techniques such as positron emission tomography and functional magnetic resonance imaging to define the roles of the amygdala in the sequence of behavioral processes that span initial drug use to addiction and its consequences. The functional images of the human amygdala demonstrate or implicate this limbic structure in the processes of reward learning and memory, conditioned reward and emotion dysregulation related to drug use, and the transition to addiction. While these roles of the amygdala reflect its involvement in the actions of large-scale neural systems comprising cortical and subcortical structures, its important roles as a neural substrate mediating or modulating behaviors related to initial drug use to addiction, and its personal and social consequences, are increasingly defined by functional brain imaging studies. | Amygdala |
Histone tails harbor a plethora of post-translational modifications that direct the function of chromatin regulators, which recognize them through effector domains. Effector domain/histone interactions have been broadly studied, but largely using peptide fragments of histone tails. Here, we extend these studies into the nucleosome context and find that the conformation adopted by the histone H3 tails is inhibitory to BPTF PHD finger binding. Using NMR spectroscopy and MD simulations, we show that the H3 tails interact robustly but dynamically with nucleosomal DNA, substantially reducing PHD finger association. Altering the electrostatics of the H3 tail via modification or mutation increases accessibility to the PHD finger, indicating that PTM crosstalk can regulate effector domain binding by altering nucleosome conformation. Together, our results demonstrate that the nucleosome context has a dramatic impact on signaling events at the histone tails, and highlights the importance of studying histone binding in the context of the nucleosome. | PHD Zinc Fingers |
Herein, we report, for the first time, the screening of several ligands in terms of their ability to bind and stabilize G-quadruplexes (G4) found in seven human Papillomavirus (HPV) genomes. Using a variety of biophysical assays, HPV G-quadruplexes were shown to possess a high degree of structural polymorphism upon ligand binding, which may have an impact on transcription, replication, and viral protein production. A sequence found in high-risk HPV16 genotype folds into multiple non-canonical DNA structures; it was converted into a major G4 conformation upon interaction with a well-characterized highly selective G4 ligand, PhenDC3, which may have an impact on the viral infection. Likewise, HPV57 and 58, which fold into multiple G4 structures, were found to form single stable complexes in the presence of two other G4 ligands, C(8) and pyridostatin, respectively. In addition, one of the selected compounds, the acridine derivative C(8), demonstrated a significant antiviral effect in HPV18-infected organotypic raft cultures. Altogether, these results indicate that targeting HPV G4s may be an alternative route for the development of novel antiviral therapies. | Human papillomavirus 16 |
A fast, reliable, and sensitive (< 20 pmol) method for the quantification of 4-hydroxyproline is described. It ensures good separation of imino acid peaks, eliminates interference by primary amino acids, and guarantees full (96-105%) recovery of hydroxyproline (HYP). Interfering primary amino acids are derivatized by o-phthaldialdehyde and removed from the sample by use of a discardable C18 column. HYP is measured photometrically at 254 nm after a second derivatization with phenylisothiocyanate and isocratic separation on a reversed-phase HPLC column. | Hydroxyproline |
Virtual reality has become a popular means to study human behavior in a wide range of settings, including the role of pedestrians in traffic research. To understand distance perception in virtual environments is thereby crucial to the interpretation of results, as reactions to complex and dynamic traffic scenarios depend on perceptual processes allowing for the correct anticipation of future events. A number of approaches have been suggested to quantify perceived distances. While previous studies imply that the selected method influences the estimates' accuracy, it is unclear how the respective estimates depend on depth information provided by different perceptual modalities. In the present study, six methodological approaches were compared in a virtual city scenery. The respective influence of visual and non-visual cues was investigated by manipulating the ratio between visually perceived and physically walked distances. In a repeated measures design with 30 participants, significant differences between methods were observed, with the smallest error occurring for visually guided walking and verbal estimates. A linear relation emerged between the visual-to-physical ratio and the extent of underestimation, indicating that non-visual cues during walking affected distance estimates. This relationship was mainly evident for methods building on actual or imagined walking movements and verbal estimates. | Distance Perception |
PURPOSE: To assess the specificity of simulation-based virtual reality ophthalmic cataract surgery training on the Eyesi ophthalmic virtual reality surgical simulator, and test the hypothesis that microsurgical motor learning is highly specific. METHODS: Retrospective educational interventional case series. The rates of vitreous loss and retained lens material, and vitreous loss and retained lens material associated with an errant continuous curvilinear capsulorhexis (CCC) were assessed among 1037 consecutive cataract surgeries performed during four consecutive academic years at a teaching hospital. The data were grouped by Eyesi use and capsulorhexis intensive training curriculum (CITC) completion. The main intervention was the completion of the CITC on the Eyesi. RESULTS: In the Eyesi simulator experience-based stratification, the vitreous loss rate was similar in each group (chi square p=0.95) and was not preceded by an errant CCC in 86.2% for CITC done at least once", 57.1% for "CITC not done, but some Eyesi use", and 48.9% for "none" training groups (p=4x10-5). Retained lens material overall and occurring among the errant CCC cases was similar among training groups (p=0.82 and p=0.71, respectively). CONCLUSIONS: Eyesi capsulorhexis training was not associated with lower vitreous loss rates overall. However, non-errant CCC associated vitreous loss was higher among those who underwent Eyesi capsulorhexis training. Training focused on the CCC portion of cataract surgery may not reduce vitreous loss unassociated with an errant CCC. It is likely that surgical training is highly specific to the task being trained. Residents may need to be trained for all surgical steps with adequate intensity to minimize overall complication rates." | Capsulorhexis |
Mistranslation is toxic to bacterial and mammalian cells and can lead to neurodegeneration in the mouse. Mistranslation is caused by the attachment of the wrong amino acid to a specific tRNA. Many aminoacyl-tRNA synthetases have an editing activity that deacylates the mischarged amino acid before capture by the elongation factor and transport to the ribosome. For class I tRNA synthetases, the editing activity is encoded by the CP1 domain, which is distinct from the active site for aminoacylation. What is not clear is whether the enzymes also have an editing activity that is separable from CP1. A point mutation in CP1 of class I leucyl-tRNA synthetase inactivates deacylase activity and produces misacylated tRNA. In contrast, although deletion of the entire CP1 domain also disabled the deacylase activity, the deletion-bearing enzyme produced no mischarged tRNA. Further investigation showed that a second tRNA-dependent activity prevented misacylation and is intrinsic to the active site for aminoacylation. | Leucine-tRNA Ligase |
The circadian system is a key integrator of behavior and metabolism that synchronizes physiological processes with the rotation of the Earth on its axis. In mammals, the clock is present not only within the central pacemaker neurons of the hypothalamus, but also within extra-suprachiasmatic nucleus (SCN) regions of brain and nearly all peripheral tissues. Recent evidence suggests that the complex feedback networks that encompass both the circadian and metabolic systems are intimately intertwined and that disruption of either system leads to reciprocal disturbances in the other. We anticipate that improved understanding of the interconnections between the circadian and metabolic networks will open new windows on the treatment of sleep and metabolic disorders, including diabetes mellitus and obesity." | Circadian Rhythm Signaling Peptides and Proteins |
The ongoing rapid expansion of point-of-care ultrasound (POCUS) and its corresponding supporting literature leaves the frontline clinician in a difficult position when trying to keep abreast of the latest developments. Our group of POCUS experts has selected ten influential POCUS-related papers from the past twelve months and provided a short summary of each. Our aim is to give to emergency physicians, intensivists, and other acute care providers key information, helping them to keep up to date on rapidly evolving POCUS literature. | Point-of-Care Testing |
PURPOSE: To present the 1-year follow-up of a novel surgical technique that allows for suture fixation of a posteriorly dislocated lens-bag complex without the need for conjunctival incision. METHODS: A retrospective chart review of 19 patients who underwent posterior chamber intraocular lens rescue using the novel surgical technique was performed. Data were collected 1 year after surgery for all patients. RESULTS: Average preoperative vision was 20/500, whereas 3 months and 12 months postoperatively, the vision was 20/65 and 20/54, respectively. Three of 15 eyes had decentration of the sutured intraocular lens, 2 of which required additional surgical repair. CONCLUSION: Outcome data at 1 year support this novel technique as a viable option for the surgical repair of a dislocated lens-capsular bag complex." | Artificial Lens Implant Migration |
PURPOSE: To determine the efficiency of transferring human zygotes as opposed to human day 2 or 3 embryos. METHODS: A prospective, randomized, Multicenter trial. Patients were randomized into zygote or embryo transfer. Patients were prepared for oocyte retrieval using standardized protocols. Oocyte retrieval was performed under general anesthesia. Oocytes and spermatozoa were treated using standard laboratory techniques. All protocols were coordinated by the coordinating center. RESULTS: A total of 386 patients were included in the trial. Pregnancy rates were 36.5% after zygote transfer and 42% after embryo transfer. Implantation rates were equivalent (17%) in both groups. CONCLUSIONS: No general difference was observed for zygote or embryo transfer. The results suggest that zygote transfer is a valid alternative to embryo transfer." | Zygote Intrafallopian Transfer |
Globally, people are struggling with obesity. Many effective, nonconventional methods of weight reduction, such as herbal and natural dietary supplements, are increasingly being sought. Fat burners are believed to raise metabolism, burn more calories and hasten fat loss. Despite patient perceptions that herbal remedies are free of adverse effects, some supplements are associated with severe hepatotoxicity. The present report describes a young healthy woman who presented with fulminant hepatic failure requiring emergent liver transplantation caused by a dietary supplement and fat burner containing usnic acid, green tea and guggul tree extracts. Thorough investigation, including histopathological examination, revealed no other cause of hepatotoxicity. The present case adds to the increasing number of reports of hepatotoxicity associated with dietary supplements containing usnic acid, and highlights that herbal extracts from green tea or guggul tree may not be free of adverse effects. Until these products are more closely regulated and their advertising better scrutinized, physicians and patients should become more familiar with herbal products that are commonly used as weight loss supplements and recognize those that are potentially harmful. | Commiphora |
OBJECTIVE: The aim of this study is to conduct a systematic review of the published research to examine the extent, nature, and risk factors of mortality due to physical restraint use. METHOD: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement, this review examined all peer-reviewed studies published in English describing mortality due to physical restraint in nursing home residents. RESULTS: The combined searches yielded 2,016 records of which eight articles were eligible for inclusion. There were 174 deaths due to physical restraint in nursing home residents across the eight studies. Neck compression ( n = 8) was the most common mechanism of harm resulting in death due to mechanical asphyxia. CONCLUSIONS: Physical restraint is associated with deaths in nursing home residents. Further research is needed to investigate alternative interventions to restraint use. | Restraint, Physical |
BACKGROUND: There have been conflicting results regarding clinical dexamethasone-sugammadex interactions in adults and pediatric patients under general anesthesia. METHODS: This study used a systematic review with meta-analysis of randomized controlled trials and non-randomized studies based on the Cochrane Review Methods. A comprehensive literature search was conducted to identify clinical trials that investigated the effect of dexamethasone on sugammadex reversal of rocuronium-induced neuromuscular blockade in surgical patients undergoing general anesthesia. RESULTS: Among the 314 patients in the 6 studies, 147 received intravenous dexamethasone (dexamethasone group), and 167 received intravenous saline or other antiemetics (control group). The primary outcome, the time to recovery after sugammadex administration (the time to recovery of the train-of-four ratio to 0.9 after sugammadex administration; s) was comparable between the 2 groups, the weighted mean difference (95% confidence interval [CI]) being -2.93 (-36.19, 30.33) (I2 = 94%). The time to extubation after sugammadex administration (s) and incidence of postoperative nausea and vomiting was not different between the 2 groups, the weighted mean difference (95% CI) being 23.31 (-2.26, 48.88) (I2 = 86%) and the pooled risk ratio (95% CI) being 0.25 (0.03, 2.11), respectively. The time to recovery after sugammadex administration might be different according to the study design or study region. CONCLUSION: This meta-analysis showed that use of dexamethasone in the perioperative period neither delayed nor facilitated the reversal of rocuronium-induced neuromuscular blockade with sugammadex in patients undergoing elective surgery with general anesthesia. However, given that the results showed high heterogeneity, further randomized controlled trials are needed to confirm these findings. | Sugammadex |
Asymmetrical flow field-flow fractionation (AF4) hyphenated with inductively coupled plasma-mass spectrometry (ICP-MS) has been widely used to characterize metal containing particles. This study demonstrates the advantages of coupling AF4 with ICP-time-of-flight mass spectrometry (ICP-TOFMS) in standard and single particle modes to determine size distribution, elemental composition, and number concentration of composite particles. The coupled system was used to characterize two complex particle mixtures. The first mixture consisted of particles extracted from micro-alloyed steels with two size populations of different elemental composition. The second mixture consisted of particles extracted from soil spiked with various engineered nanoparticles (ENPs). The equivalent hydrodynamic sizes of individual micro-alloyed steel particles were up to 6 times larger than the sizes determined by single particle (sp)-ICP-TOFMS. The larger AF4 sizes were attributed to the presence of a surface coating, which is not reflected in the core size determined by sp-ICP-TOFMS. Two particle populations could not be separated by AF4 due to their broad size distributions but were resolved by sp-ICP-TOFMS using their unique elemental signatures. Multi-angle light scattering and ICP-TOFMS signals of soil suspensions increased with the spiked ENP concentrations. However, only after conducting full element screening and single particle fingerprinting by ICP-TOFMS could this increase be attributed to enhanced extraction efficiency of natural particles and the risk for false conclusions be eliminated. In this study, we describe how AF4 coupled to ICP-TOFMS can be applied to study complex samples of inorganic particles which contain organic compounds. | Fractionation, Field Flow |
Loiasis is a chronic cutaneous disease caused by a filarial nematode for whom humans are the only definitive host: Loa loa, an African eyeworm transmitted by Chrysops flies. The parasite is seen on blood smears, in the skin, or during its ocular migration, but rarely on a bone marrow smear. We report the case of a 57-year-old Gabonese woman whose bone marrow aspiration during a work-up for T-cell leukemia fortuitously found Loa loa filariae." | Leukemia, Prolymphocytic, T-Cell |
This study describes our experience with using a virtual reality simulator, CricSim, to enhance the training of combat medics to perform a cricothyroidotomy (surgical airway) while in Iraq. Over a six month period, 65 medics used the simulator as part of a Combat Medic Advanced Skills Training class while in Iraq and were asked to evaluate it. Students self-assessed comfort level with the procedure improved dramatically from baseline (p<5.6 x 10(-17)). The CricSim was rated highly on realism but only moderately on ease of use. The use of this simulator in a far forward setting was feasible, enhanced training, and provided necessary end-user feedback for future development of this training platform. | Tracheotomy |
Cucumber mosaic virus (CMV) is a very serious hazard to vegetable production worldwide. This study is focused on evaluation of resistance stimulated by the plant growth-promoting fungus, Phoma sp. GS8-3, or nanosilica against CMV under pot and field conditions. The specific aim was to illustrate the mechanism of resistance stimulated by GS8-3 against CMV using microarray technology. Treatments with GS8-3 as well as nanosilica significantly decreased CMV severity and titer in tobacco and cucumber under pot and field conditions, respectively. Growth characters of tobacco and cucumber were significantly increased due to GS8-3 inoculation followed by nanosilica compared with control and BTH treatments. Microarray results showed highly upregulation of defense-related genes expression specially those related to heat shock proteins. Therefore, GS8-3 as well as nanosilica is suitable to serve as effective inducers against CMV in cucumber plants. | Cucumovirus |
BACKGROUND: Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) can manifest with a wide range of neurological and psychiatric symptoms. CASE PRESENTATION: A previously healthy man in his late twenties was admitted several times over the course of half a year. He had acute episodes of reduced consciousness, involuntary movements and psychotic symptoms (e.g. hallucinations and delusions). Initial examinations were normal except for a positive urine drug screen (tetrahydrocannabinol), and the patient was diagnosed with cannabinoid intoxication. During the next admission cerebrospinal fluid analysis showed mild pleocytosis. Screening for anti-neuronal antibodies was negative, but anti-thyroid peroxidase antibodies were detected in serum and cerebrospinal fluid. He was successfully given steroid treatment on a tentative diagnosis of SREAT, but relapsed when the steroids were discontinued. After receiving a prolonged steroid treatment with gradual dose reduction over a year, he remains symptom-free 18 months after treatment discontinuation. INTERPRETATION: The diagnostic delay might have been mitigated with an earlier inclusion of neuroimmunological disorders in the differential diagnosis. Unexplained pleocytosis in the cerebrospinal fluid in the presence of paroxysmal neuropsychiatric symptoms should trigger an investigation that includes autoimmune encephalopathies. | Thyroiditis, Autoimmune |
A case of idiopathic autoimmune hemolytic anemia occurring during the third trimester of pregnancy is presented. The hemolytic process was quite severe in the mother but responded to steroid therapy. A healthy baby without evidence of hemolysis was delivered uneventfully through the vagina. We postulate the mechanism of the discuss the clinical picture, management of the disease and the possible effect on the fetus." | Pregnancy Complications, Hematologic |
In the past, Medical Economics has conducted an annual survey of fees charged by office based physicians in general practice, family and internal medicine, obstetrics-gynecology and pediatrics, and general surgery. This year, the data-base was expanded to include six other specialties. The article provides a series of tables exhibiting the fees charged by physicians for first office visits, return visits, history and physical exams, and other general procedures specific to particular specialties. It is pointed out that the fee for return office visits has doubled in eight years. The increase in costs of routine services accounts for much of the 9.6% increase in physicians' fees during the last year. Primary care doctors have initiated the highest fee hikes for 1978. This is attributed to young physicians entering the field and charging more than their older colleagues. Surgical fees have doubled in cost in the last ten years. For the past three years, physicians' fees have increased at the average rate of 9.5%, usually exceeding the Consumer Price Index. Physician services only account for 20% of the entire health care bill, but due to their visibility, they are subject to criticism and careful review. Since the pressure is on for health care cost containment, the author advises physicians to think again before raising their fees in the near future. | Economics, Medical |
Neuroimaging techniques that can sensitivity characterize healthy brain aging and detect subtle neuropathologies have enormous potential to assist in the early detection of neurodegenerative conditions such as Alzheimer's disease. Magnetic resonance elastography (MRE) has recently emerged as a reliable, high-resolution, and especially sensitive technique that can noninvasively characterize tissue biomechanical properties (i.e., viscoelasticity) in vivo in the living human brain. Brain tissue viscoelasticity provides a unique biophysical signature of neuroanatomy that are representative of the composition and organization of the complex tissue microstructure. In this article, we detail how progress in brain MRE technology has provided unique insights into healthy brain aging, neurodegeneration, and structure-function relationships. We further discuss additional promising technical innovations that will enhance the specificity and sensitivity for brain MRE to reveal considerably more about brain aging as well as its potentially valuable role as an imaging biomarker of neurodegeneration. MRE sensitivity may be particularly useful for assessing the efficacy of rehabilitation strategies, assisting in differentiating between dementia subtypes, and in understanding the causal mechanisms of disease which may lead to eventual pharmacotherapeutic development. | Elasticity Imaging Techniques |
Our aim was to compare Corpus luteum (CL) development and blood plasma concentration of progesterone ([P4]) in thoroughbred mares after spontaneous ( CONTROL: C) or human chorionic gonadotrophin (hCG)-induced ovulation. Lactating mares (C=12; hCG=21) were daily teased and mated during second oestrus post-partum. Treated mares received 2500 IU hCG i.v. at first day of behavioural oestrus when dominant follicular size was >35, <or=42 mm and mated 12-24 h after. CONTROL mares in oestrus were mated with dominant follicular size>or=45 mm. Dominant follicle before ovulation, CL and gestational sac were measured by ultrasound and [P4] by radioimmunoassay (RIA). Blood sampling and ultrasound CL exams were done at days 1, 2, 3, 4, 8, 12, 16, 20, 25, 30, 35, 40, 45, 60 and 90 after ovulation and gestational sac from day 12 after ovulation in pregnant (P) mares; non-pregnant (NP) were followed until oestrus returned. Data analyses considered four subgroups: hCG-P, hCG-NP, C-P and C-NP. Preovulatory follicular size was smaller in hCG mares than in C: 39.2+/-2.7 mm vs 51.0+/-1.8 mm (p<0.0001). All hCG mares ovulated 24-48 h after treatment and presented similar oestrus duration as controls. C. luteum size in P mares showed the same pattern of development through days 4-35, presenting erratic differences during initial establishment. Thus, on days 1 and 3, CL was smaller in hCG-P (p<0.05); while in hCG-NP, CL size was greater than in C-NP on day three (p=0.03). Corpus luteum size remained stable until day 90 in hCG-P mares, while in C-P a transient and apparently not functional increase was detected on days 40 and 45 (p<0.05) and the decrease from day 60 onwards, made this difference to disappear. No differences were observed in [P4] pattern between P, or between NP subgroups, respectively. So, hCG-induced ovulation does not affect CL development, neither [P4] during early pregnancy. One cycle pregnancy rate tended to be lower in hCG mares while season pregnancy rates were similar to controls. | Ovulation |
The text book of Pediatric Advanced Life Support of the American Heart Association recommends that a reservoir is used with a self inflating bag valve device. The figure in the book suggests that if such a device is connected to an oxygen supply, the oxygen will fill the bag first and then go on to fill the reservoir. However the valve structure of the self-inflating device does not permit active entry of oxygen into the bag, unless the bag is deflated and allowed to reinflate, drawing oxygen from the reservoir. We did this study to test the concentration of oxygen delivered in the first few breaths with the help of a Miniox-III oxygen monitor probe (MSA Medical Products, Pittsburgh, PA 15230) inserted into a self inflating bag (AMBU). Twenty-one percent oxygen is delivered with first breath and it rose to 42 and 58% with the second and third inflations, respectively. Eighty percent oxygen was achieved after eight reinflation cycles. We developed a formula to calculate the concentration of oxygen in the bag after each inflation effort, assuming that there was no passive diffusion of oxygen. We suggest that compressing the bag 8-12 times prior to putting the mask to the face of the patient will allow 80% oxygen to be delivered with first breath. | Oxygen |
A divided nevus of the penis is a rare embryological occurrence. The appearance of a congenital melanocytic nevus can be difficult to distinguish from penile melanosis. This article presents the successful excision and histopathologic evaluation of one such nevus. | Nevus, Intradermal |
Copper phthalate coordination polymers incorporating the kinked and hydrogen-bonding-capable imines 4,4'-dipyridylketone (dpk) and 4,4'-dipyridylamine (dpa) have been prepared and structurally characterized by single-crystal X-ray diffraction. [Cu(pht)(dpk)].0.33CH(3)OH(n) (1; pht = phthalate) possesses helical subunits built from the fusion of [Cu(dpk)](n) 3-fold double helices and [Cu(pht)](n) 3-fold helices with opposite handedness. The resulting achiral [Cu(pht)(dpk)](n) helices are conjoined by bridging phthalate carboxylate oxygen atoms to construct Cu(2)O(2) dimeric units, which serve as 8-connected nodes for a three-dimensional (3D) coordination polymer lattice with an unprecedented 3(6)4(12)5(8)6(2) topology, evocative of a 3D Kagome lattice. [Cu(2)(pht)(2)(dpa)].H(2)O(n) (2) manifests homochiral septuple left-handed [Cu(2)O(2)(dpa)](n) helices formed by copper ions, phthalate oxygen atoms, and dpa ligands. The septuple helices are bracketed by pht anions to construct chiral one-dimensional nanobarrels with solvent-free star-shaped" channels. Compounds 1 and 2 display antiferromagnetic [J = -9.85(5) cm(-1)] and ferromagnetic [J = +1.36(3) cm(-1)] coupling across their Cu(2)O(2) dimeric units, respectively." | 2,2'-Dipyridyl |
Ichthyosis prematurity syndrome (IPS) is an autosomal-recessive disorder characterized by premature birth and neonatal asphyxia, followed by a lifelong nonscaly ichthyosis with atopic manifestations. Here we show that the gene encoding the fatty acid transport protein 4 (FATP4) is mutated in individuals with IPS. Fibroblasts derived from a patient with IPS show reduced activity of very long-chain fatty acids (VLCFA)-CoA synthetase and a specific reduction in the incorporation of VLCFA into cellular lipids. The human phenotype is consistent with Fatp4 deficiency in mice that is characterized by a severe skin phenotype, a defective permeability barrier function, and perturbed VLCFA metabolism. Our results further emphasize the importance of fatty acid metabolism for normal epidermal barrier function illustrated by deficiency of a member in the FATP family of proteins. | Fatty Acid Transport Proteins |
BACKGROUNDS: Studies have reported that non-motor symptoms are an important component of primary dystonia. However, evidence supporting cognitive impairment in primary dystonia is limited and contradictory. METHODS: We applied the Chinese version of the Addenbrooke's Cognitive Examination-Revised and the Mini-Mental State Examination (MMSE) to screen for cognitive impairment in patients with primary blepharospasm. In addition, we investigated the relationship between performance on the Addenbrooke's Cognitive Examination-Revised and quality of life as measured by the Medical Outcomes Study 36-item Short-Form (SF36). RESULTS: The study included 68 primary blepharospasm patients and 68 controls matched by age, sex and education. The prevalence of cognitive deficits was 22.0% and 32.3% in primary blepharospasm patients group, as measured by the MMSE and the Addenbrooke's Cognitive Examination-Revised, respectively. Primary blepharospasm patents had a broad range of cognitive deficits, with the most frequently affected domains being visuospatial function (30.9%) and language (30.9%), followed by memory (27.9%), orientation/attention (26.4%) and verbal fluency (22.0%). Patients with cognitive deficits had lower total SF36 scores, especially in the subdomains of physical functioning, role-physical and social functioning, compared to those without cognitive deficits. Scores on the Addenbrooke's Cognitive Examination-Revised were significantly correlated with both the SF36 scores and the scores on the subdomains of physical functioning and social functioning. CONCLUSIONS: Some patients with primary blepharospasm have cognitive deficits. Poor performance on the Addenbrooke's Cognitive Examination-Revised is related to poorer quality of life. | Blepharospasm |
BACKGROUND: In this paper we attempt to describe the clinical features, visual outcomes, and surgical results of patients with acute retinal necrosis (ARN) syndrome and elucidate the risk factors for a poor prognosis. We also review the methods of treatment. METHODS: This was a retrospective, noncomparative, observational study of patients diagnosed with ARN syndrome. Nine patients (11 eyes) in Chang Gung Memorial Hospital, Kaohsiung from January 1990 to December of 2002 were enrolled. Blood sera and vitreous specimens were analyzed. Necrosis locations and surgical results are described. RESULTS: Bilateral involvement occurred in 2 of our 9 patients (2/9, 22.2%). There was no specific relationship between age and level of the serum virus antibody. All of our polymerase chain reaction data for herpes simplex virus were negative. All 6 eyes of 6 patients who underwent surgery for retinal detachment had partial retinal reattachment postoperatively. Overall, anatomic success was achieved in 8 eyes (8/11, 72.7%). The percentage of eyes with ambulatory visual acuity was 36.3% (4/11), and visual acuity was preserved in 27.3% (3/11) at the last visit. CONCLUSIONS: We found that retinal necrosis which extended rapidly to the posterior pole was associated with a poor visual outcome. Eyes with less than grade II necrosis extension are good candidates for prophylactic peripheral retinal photocoagulation. Early detection and prompt treatment with acyclovir seems to improve the final visual outcome." | Retinal Necrosis Syndrome, Acute |
BACKGROUND: High sound pressure levels may be harmful to the maturing newborn. Current guidelines suggest that the sound pressure levels within a neonatal intensive care unit should not exceed 45 dB(A). It is likely that environmental noise as well as the noise generated by the incubator fan and respiratory equipment may contribute to the total sound pressure levels. Knowledge of the contribution of each component and source is important to develop effective strategies to reduce noise within the incubator. AIMS: The objectives of this study were to determine the sound levels, sound spectra, and major sources of sound within a modern neonatal incubator (Giraffe Omnibed; GE Healthcare, Helsinki, Finland) using a sound simulation study to replicate the conditions of a preterm infant undergoing high-frequency jet ventilation (Life Pulse, Bunnell, UT). METHODS: Using advanced sound data acquisition and signal processing equipment, we measured and analyzed the sound level at a dummy infant's ear and at the head level outside the enclosure. The sound data time histories were digitally acquired and processed using a digital Fast Fourier Transform algorithm to provide spectra of the sound and cumulative sound pressure levels (dBA). The simulation was done with the incubator cooling fan and ventilator switched on or off. In addition, tests were carried out with the enclosure sides closed and hood down and then with the enclosure sides open and the hood up to determine the importance of interior incubator reverberance on the interior sound levels RESULTS: With all the equipment off and the hood down, the sound pressure levels were 53 dB(A) inside the incubator. The sound pressure levels increased to 68 dB(A) with all equipment switched on (approximately 10 times louder than recommended). The sound intensity was 6.0 x 10(-8) watts/m(2); this sound level is roughly comparable with that generated by a kitchen exhaust fan on high. Turning the ventilator off reduced the overall sound pressure levels to 64 dB(A) and the sound pressure levels in the low-frequency band of 0 to 100 Hz were reduced by 10 dB(A). The incubator fan generated tones at 200, 400, and 600 Hz that raised the sound level by approximately 2 dB(A)-3 dB(A). Opening the enclosure (with all equipment turned on) reduced the sound levels above 50 Hz by reducing the revereberance within the enclosure. CONCLUSION: The sound levels, especially at low frequencies, within a modern incubator may reach levels that are likely to be harmful to the developing newborn. Much of the noise is at low frequencies and thus difficult to reduce by conventional means. Therefore, advanced forms of noise control are needed to address this issue. | Incubators, Infant |
Unlike vertebrate skeletal muscle, smooth muscle myosin heavy chain isoforms are encoded by a single gene. Alternative splicing of the primary transcript from a single gene generates four smooth muscle myosin heavy chain isoforms. These isoforms differ both at the carboxyl terminus (SM1 and SM2 isoforms) and at the amino terminus (SM-A and SM-B isoforms). The smooth muscle myosin heavy chain isoforms are differentially expressed during smooth muscle development and in different smooth muscle cell types. The mechanical properties of smooth muscle may be correlated with the myosin heavy chain content/isoform expression. However, the precise function of each smooth muscle myosin heavy chain isoform to muscle contraction remains to be determined. This review mainly focuses on the molecular basis of smooth muscle myosin heavy chain isoform diversity, its expression during development and disease, and its role in muscle physiology. | Myosin Heavy Chains |
This work describes the preparation, characterization and antimicrobial activity of four palladium(II) complexes, namely, [Pd(meg)(1,10-phen)] 1, [Pd(meg)(PPh(3))(2)] 2, [Pd(og)(1,10-phen)] 3 and [Pd(og)(PPh(3))(2)] 4, where meg = methyl gallate, og = octyl gallate, 1,10-phen = 1,10-phenanthroline and PPh(3) = triphenylphosphine. As to the chemical structures, spectral and physicochemical studies of 1-4 indicated that methyl or octyl gallate coordinates a palladium(II) ion through two oxygen atoms upon deprotonation. A chelating bidentate phenanthroline or two triphenylphosphine molecules complete the coordination sphere of palladium(II) ion, depending on the complex. The metal complexes were tested against the Mycobacterium tuberculosis H37Rv strain and 2 exhibited high activity (MIC = 3.28 mug/mL). As to the tests with Campylobacter jejuni, complex 1 showed a significant effect in reducing bacterial population (greater than 7 log CFU) in planktonic forms, as well as in the biomass intensity (IBF: 0.87) when compared to peracetic acid (IBF: 1.11) at a concentration of 400 mug/mL. The effect provided by these complexes has specificity according to the target microorganism and represent a promising alternative for the control of microorganisms of public health importance. | Palladium |
INTRODUCTION: Abdominal aortic aneurysms (AAA) more commonly affect men than women and are estimated to affect 4% to 8% of men older that age 60 years. Mortality because of a ruptured AAA is high, but elective repair is an effective and relatively safe intervention. CASE PRESENTATION: A 79-year-old man came to the Emergency Department because of worsening back pain. Workup revealed a previously unknown, 10-cm aneurysm that had ruptured. Unfortunately, the patient died during emergency surgery. DISCUSSION: A literature review of proper screening, referral timeframe, the most common surgical techniques, potential complications, and postoperative surveillance was conducted. Early detection, referral to vascular surgery, and possible open or endovascular repair are key to limiting the morbidity and mortality associated with AAA. | Aortic Aneurysm, Abdominal |
OBJECTIVE: To determine the effects on maternal satisfaction of the use of the birthing ball as a method of pain relief compared to the subcutaneous administration of pethidine (50mg) and haloperidol (2.5mg), during the latent phase of labour. METHOD: Randomised, unicentric, parallel and controlled clinical trial. PARTICIPANTS: Low-risk pregnant women hospitalised in a pathological pregnancy ward at the Gregorio Maranon University General Hospital (Madrid) due to prolonged pregnancy, premature rupture of membranes, or labour prodromes. INTERVENTION: once the patient's labour had become painful, a series of pre-established movements were implemented with a birthing ball in the intervention group, or pethidine and haloperidol were administered at the same dose subcutaneously. After the intervention and on the post-natal ward, satisfaction was measured with the Mackey Satisfaction Childbirth scale, validated in Spanish in 2016, in the first 48-72hours after delivery. ANALYSIS: group comparisons: Student's t for continuous variables and Chi-squared for categorical variables. Significance at p<0.05. RESULTS: The maternal satisfaction was significantly higher in the experimental group than in the comparison group, in all the domains of the scale: obstetrician (4.24/3.87), dilatation (4.02/3.35), second stage (4.27/3.67), newborn (4.72/4.43), accompaniment and comfort (4.78/4.44). There were, however, no statistically significant differences in the midwife subscale, although the scores were equally high (4.65/4.45). CONCLUSION: Using birthing balls during the latent phase of labour increases women's satisfaction with their labour process more than administering pethidine and haloperidol during this period. | Analgesia, Obstetrical |
PURPOSE: Latissimus dorsi flap is a widely used technique in breast reconstruction. Here we describe a modified method, the partial latissimus dorsi muscle flap with vertical incision for immediate implant-based breast reconstruction which has been used at our institution since 2014. Our primary objective is to determine the safety, prognostic benefit, and cosmetic outcome of this surgical procedure. METHODS: The study included a cohort of 31 breast cancer patients who underwent unilateral breast reconstruction with detailed follow-up information at Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2014 to March 2015. All procedures were performed by the same surgical team at the department of breast surgery. The data for selecting the appropriate implant and evaluating the surgical outcome were collected. The cosmetic outcome was evaluated by the BREAST-Q 1 y after surgery. RESULTS: After a median follow-up of 69 mo, none of the patients showed local recurrence (although two patients had distant metastasis). The 5-y distant metastasis-free survival was 93.5%. The median duration of surgical procedure was 2 h and 24 min with few surgical and functional complications. Based on BREAST-Q, the outcome of Satisfaction with Breasts was excellent" or "good" in 96.7% of the patients. CONCLUSIONS: Partial latissimus dorsi muscle flap with the vertical incision is a safe, effective, time-saving, and feasible alternative to the whole latissimus dorsi flap which has superior cosmetic outcome and reduces recovery time. It is, therefore, worth advocating for application in clinical practice." | Superficial Back Muscles |
Background and Objectives: We have recently reported that stains have calcium channel blocking activity in isolated jejunal preparations. In this study, we examined the effects of atorvastatin and fluvastatin on blood vessels for a possible vasorelaxant effect. We also studied the possible additional vasorelaxant effect of atorvastatin and fluvastatin, in the presence of amlodipine, to quantify its effects on the systolic blood pressure of experimental animals. Materials and Methods: Atorvastatin and fluvastatin were tested in isolated rabbits' aortic strip preparations using 80mM Potassium Chloride (KCl) induced contractions and 1 micro molar Norepinephrine (NE) induced contractions. A positive relaxing effect on 80 mM KCl induced contractions were further confirmed in the absence and presence of atorvastatin and fluvastatin by constructing calcium concentration response curves (CCRCs) while using verapamil as a standard calcium channel blocker. In another series of experiments, hypertension was induced in Wistar rats and different test concentrations of atorvastatin and fluvastatin were administered in their respective EC(50) values to the test animals. A fall in their systolic blood pressure was noted using amlodipine as a standard vasorelaxant drug. Results: The results show that fluvastatin is more potent than amlodipine as it relaxed NE induced contractions where the amplitude reached 10% of its control in denuded aortae. Atorvastatin relaxed KCL induced contractions with an amplitude reaching 34.4% of control response as compared to the amlodipine response, i.e., 39.1%. A right shift in the EC(50) (Log Ca++ M) of Calcium Concentration Response Curves (CCRCs) implies that statins have calcium channel blocking activity. A right shift in the EC(50) of fluvastatin with relatively less EC(50) value (-2.8 Log Ca++ M) in the presence of test concentration (1.2 x 10(-7) M) of fluvastatin implies that fluvastatin is more potent than atorvastatin. The shift in EC(50) resembles the shift of Verapamil, a standard calcium channel blocker (-1.41 Log Ca++ M). Conclusions: Atorvastatin and fluvastatin relax the aortic strip preparations predominantly through the inhibition of voltage gated calcium channels in high molar KCL induced contractions. These statins also inhibit the effects of NE induced contractions. The study also confirms that atorvastatin and fluvastatin potentiate blood pressure lowering effects in hypertensive rats. | Fluvastatin |
There are more CRH-like immunoreactive neurons in the preoptic nucleus and nucleus lateralis tuberis in the brain of feral brown trout, Salmo trutta, living in cadmium- and zinc-contaminated regions of the Eagle River than in fish from an uncontaminated control site. Histological analyses revealed that interrenal cells are more stimulated (exhibiting both hypertrophy and hyperplasia) in fish living in contaminated sites than interrenal cells of fish at the control site. These results suggest that the hypothalamo-pituitary-interrenal (HPI) axis of fish living in the metal-contaminated water shows evidence of chronic stimulation. We suggest that assessment of these parameters of the HPI axis may be useful indices of chronic environmental stress in trout. | Interrenal Gland |
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