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BACKGROUND: Implementing treatments and interventions with demonstrated effectiveness is critical for improving patient health outcomes at a reduced cost. When an evidence-based intervention (EBI) is implemented with fidelity in a setting that is very similar to the setting wherein it was previously found to be effective, it is reasonable to anticipate similar benefits of that EBI. However, one goal of implementation science is to expand the use of EBIs as broadly as is feasible and appropriate in order to foster the greatest public health impact. When implementing an EBI in a novel setting, or targeting novel populations, one must consider whether there is sufficient justification that the EBI would have similar benefits to those found in earlier trials. DISCUSSION: In this paper, we introduce a new concept for implementation called scaling-out" when EBIs are adapted either to new populations or new delivery systems, or both. Using existing external validity theories and multilevel mediation modeling, we provide a logical framework for determining what new empirical evidence is required for an intervention to retain its evidence-based standard in this new context. The motivating questions are whether scale-out can reasonably be expected to produce population-level effectiveness as found in previous studies, and what additional empirical evaluations would be necessary to test for this short of an entirely new effectiveness trial. We present evaluation options for assessing whether scaling-out results in the ultimate health outcome of interest. CONCLUSION: In scaling to health or service delivery systems or population/community contexts that are different from the setting where the EBI was originally tested, there are situations where a shorter timeframe of translation is possible. We argue that implementation of an EBI in a moderately different setting or with a different population can sometimes "borrow strength" from evidence of impact in a prior effectiveness trial. The collection of additional empirical data is deemed necessary by the nature and degree of adaptations to the EBI and the context. Our argument in this paper is conceptual, and we propose formal empirical tests of mediational equivalence in a follow-up paper." | Health Plan Implementation |
Argonaute (Ago) proteins are conserved nucleic acid-guided proteins present in all domains of life. Eukaryotic Argonaute proteins (eAgos) are key players in RNA interference pathways and function as RNA-guided RNA endonucleases at physiological temperatures. Although eAgos are considered to evolve from prokaryotic Argonaute proteins (pAgos), previously studied pAgos were unable to catalyze RNA-guided RNA cleavage at physiological temperatures. Here, we describe a distinctive pAgo from mesophilic bacteria Kurthia massiliensis (KmAgo). KmAgo utilizes DNA guides to cleave single-stranded DNA (ssDNA) and RNA targets with high activity. KmAgo also utilizes RNA guides to cleave ssDNA and RNA targets at moderate temperatures. We show that KmAgo can use 5' phosphorylated DNA guides as small as 9-mers to cut ssDNA and RNA, like Clostridium butyricum Ago. Small DNA binding confers remarkable thermostability on KmAgo, and we can suppress the guide-independent plasmid processing activity of empty KmAgo by elevating the DNA guide loaded temperature. Moreover, KmAgo performs programmable cleavage of double-stranded DNA and highly structured RNA at 37 degrees C. Therefore, KmAgo can be regarded as a DNA-guided programmable omnipotent nuclease for cleaving most types of nucleic acids efficiently. This study broadens our understanding of Ago proteins and could expand the pAgo-based DNA and RNA manipulation toolbox. | Planococcaceae |
Pyrolysis of end of life tyres (ELTs) present a promising alternative to their incineration or classical product recovery using mechanical means. It can produce light hydrocarbons (HCs) and other valuable chemicals as part of the pyro-gas stream it generates. In this work, two grades of tyres namely a fresh (virgin) one and a waste disposed ELTs, were used as a feedstock to analyse their pyro-gas constituents. There wasn't much difference in the maximum conversion rate between both tyre grades where the fresh tyres had an estimated 15.17% conversion and the ELTs was 13.45% conversion (both at 800 degrees C). The difference herein was attributed to release of free radicals prior to subjecting the samples to pyrolysis due to their history. The analysis of the pyro-gas samples showed a large make of light hydrocarbon (HC) products, namely methane (CH(4)/C(1)), ethane (C(2)H(6)/C(2)), ethylene (C(2)H(4)), propane (C(3)H(8)/C(3)), propylene (C(3)H(6)), n-butane (C(4)H(10)), butadiene compounds, carbon mono and dioxide (CO,CO(2)). Light HCs mimciking natural gas were more abundant in the case of ELTs were C(1) was estimated as 14.53% at 500 degrees C and 16.73% at 800 degrees C. C(2) was also estimated higher than the fresh tyres where a 11.78% at 500 degrees C was noted and 7.67% at 800 degrees C. It can be recommended that future integration plans in oil and gas ventures, namely refinery and petrochemical complexes, are to start taking responsible measures towards the environment by substituting part of their operations with sustainable feedstock such as ELTs. | Refuse Disposal |
The diagnosis of chronic eosinophilic leukemia (CEL) is based on the evidence of an autonomous, clonal proliferation of eosinophilic precursors and the exclusion of other myeloid neoplasms with eosinophilia. Histopathological evaluations of bone marrow are rare, and reliable data on the frequency of CEL do not yet exist. A total of 100 cases characterized by eosinophilia >/=1.5x10(9)/l blood for more than 6 months were evaluated. In 87 cases, the eosinophilia turned out to be secondary and a reactive genesis was likely, but not proven in 3 further cases. Idiopathic hypereosinophilic syndrome was diagnosed in three cases. The diagnosis CEL was considered in four out of a total of seven cases with a myeloid neoplasia and all four disorders showed an abnormal karyotype. However, only one of them could be classified as CEL. We conclude that CEL is a rare disease concerning only a minority of cases with chronic eosinophilia. | Leukemia, Eosinophilic, Acute |
Bone regeneration therapy is clinically important, and targeted regulation of endoplasmic reticulum (ER) stress is important in regenerative medicine. The processing of proteins in the ER controls cell fate. The accumulation of misfolded and unfolded proteins occurs in pathological states, triggering ER stress. ER stress restores homeostasis through three main mechanisms, including protein kinase-R-like ER kinase (PERK), inositol-requiring enzyme 1a (IRE1a) and activating transcription factor 6 (ATF6), collectively known as the unfolded protein response (UPR). However, the UPR has both adaptive and apoptotic effects. Modulation of ER stress has therapeutic potential for numerous diseases. Repair of bone defects involves both angiogenesis and bone regeneration. Here, we review the effects of ER stress on osteogenesis and angiogenesis, with emphasis on ER stress under high glucose (HG) and inflammatory conditions, and the use of ER stress inducers or inhibitors to regulate osteogenesis and angiogenesis. In addition, we highlight the ability for exosomes to regulate ER stress. Recent advances in the regulation of ER stress mediated osteogenesis and angiogenesis suggest novel therapeutic options for bone defects. | eIF-2 Kinase |
BETA-LACTAMASE: The capacity to produce beta-lactamase, an enzyme which hydrolyses penicillin and cephalosporines, is the main source of bacterial resistance to beta-lactamines, thus the important contribution of beta-lactamase inhibitors (clavanulanic acid, sulbactam and tazobactam). MECHANISM OF ACTION: Beta-lactamase inhibitors inactivate these enzymes and, in association with beta-lactamines, offer wide spectrum bactericidal action (Gram negative bacilli, anaerobic germs, methicillin-sensitive staphylococci and streptococci) and can be used as first-line treatment in certain community-acquired and nosocomial infections. SIDE EFFECTS: Widespread use of these inhibitors selects intermediate or resistant strains. Toxicity is low. Undesirable effects (poor digestive tolerance for oral formulations) are dose-dependent. RIGOROUS PRESCRIPTION: Recent development of bacterial resistance emphasizes the importance of rational use of these associations and the need for a better definition of the optimal doses. Prescriptions must avoid underdosing and excessively long treatments. Treatment should be simplified if sensitivity to an antibiotic with a narrower spectrum is recognized. | Enzyme Inhibitors |
Although hypertension is highly prevalent in older adults, treatment goals require both an understanding of the various guidelines available, as well as appreciation of the unique medical, cognitive, psychosocial, and functional heterogeneity of our individual geriatric patients that may place them outside those guidelines. As a patient's clinical status changes over time, clinicians may consider deprescribing their blood pressure medications when their risks begin to outweigh their benefits. Unique clinical circumstances and incorporating the time to benefit of hypertension control help guide clinical decision-making. | Overtreatment |
Responses to changes in external salinity were examined in Halobacterium salinarum NRC-1. H. salinarum NRC-1 grows optimally at 4.3 M NaCl and is capable of growth between 2.6 and 5.1 M NaCl. Physiological changes following incubation at 2.6 M NaCl were investigated with respect to growth behavior and proteomic changes. Initial observations indicated delayed growth at low NaCl concentrations (2.6 M NaCl), and supplementation with different sugars, amino acids, or KCl to increase external osmotic pressure did not reverse these growth perturbations. To gain a more detailed insight into the adaptive responses of H. salinarum NRC-1 to changes in salinity, the proteome was characterized using iTRAQ (amine specific isobaric tagging reagents). Three hundred and nine differentially expressed proteins were shown to be associated with changes in the external sodium chloride concentration, with proteins associated with metabolism revealing the greatest response. | Halobacterium salinarum |
The sinus augmentation, or sinus lift procedure, is an internal augmentation of the maxillary sinus, which is intended to increase the vertical bony dimension in the lateral maxilla to make the placement of dental implants possible. Complication rate associated with maxillary sinus augmentation procedures in the literature is quite low. Typically, perforation of the Schneiderian membrane, hemorrhage, infection, and rhinosinusitis are more frequently encountered. Therefore, the aim of this article was to briefly review and resume the more common complications associated with sinus augmentation procedures. | Sinus Floor Augmentation |
The effects of scavenging 2, 2-diphenyl-2-picrylhydrazyl hydrate (DPPH) radicals and inhibiting low-density lipoprotein (LDL) oxidation, and phenolic quantities were used for the activity-guided separation to identify the effective components of litchi flower. The acetone extract of the flower with notable antioxidant capacities was suspended in water and sequentially partitioned with n-hexane, ethyl acetate (EA) and n-butanol. The EA partition with the highest phenolic levels and antioxidant capacities was subjected to silica gel column chromatography. Thirteen fractions (Fr. 1-13) were collected; Fr. 10-12 with higher phenolic levels and antioxidant effects were applied to Sephadex LH-20 column chromatography. Each fraction was further separated into three sub-fractions and the second ones (Fr. 10-II, 11-II, and 12-II) were the best, which two major compounds could be isolated by semi-preparative high performance liquid chromatography (HPLC). Through Mass (MS) and Nuclear Magnetic Resonance (NMR) measurements, they could be identified as (-)-epicatechin and proanthocyanidin A2. Their contents in the litchi flower were 5.52 and 11.12 mg/g of dry weight, respectively. The study was the first time to reveal the effective antioxidant components of litchi flower. | Litchi |
Neuropathological studies have shown increased cerebral spaces in alcoholics, yet, the effect of ethanol on cerebrospinal fluid (CSF) production is not known. We investigated the effects of ethanol on CSF production measured by ventriculocisternal perfusion (VCP) technique, in two groups (n=10 in each) of anesthetized, paralyzed and mechanically ventilated dogs. In group I, which served as control, VCP was performed with normal mock CSF. Ethanol (150 mg/dl of mock CSF, approximately 33 mM) was added to VCP in group II. Beginning 60 min after the start of VCP, CSF production was measured every 15 min for the next 4 h. In group I, mean (+/-S.D.) value for CSF production was 51+/-10 microliter/min initially and decreased significantly but slightly with time, to the lowest value of 44+/-11 microliter/min at the end of the experiment. In group II, values for CSF production were 41+/-8, 41+/-8, 41+/-8, 43+/-6, 43+/-8, 42+/-6, 42+/-8, 38+/-6, 37+/-6, 36+/-5, 36+/-5, microliter/min, respectively, from 15 to 165 min. These values were invariably significantly lower than their respective mean values in the control group. Furthermore, when ethanol was withdrawn at the trough of CSF production (at 165 min), production significantly increased by about 40%. We conclude that ethanol at a concentration of 150 mg/dl (far below lethal levels) is one of the most potent inhibitory drugs for decreasing CSF production. This effect is short-onset and is fully reversible within 15 min of ethanol withdrawal. | Cerebrospinal Fluid |
The detailed clinical course of coronavirus disease 2019 (COVID-19) in patients with hairy cell leukemia (HCL) is rarely reported. We report the first case of HCL diagnosed with prolonged pancytopenia after COVID-19 infection in Japan. We describe the case of a 56-year-old man who was diagnosed with COVID-19. Computed tomography revealed ground-glass opacities in the bilateral lung lobes as well as splenomegaly. Remdesivir and dexamethasone were administered for the treatment of COVID-19. Since the pancytopenia persisted, bone marrow examination was performed, and he was diagnosed with HCL. Although pancytopenia can occur with COVID-19 alone, clinicians should be alerted regarding the presence of hematologic malignancies in patients in whom pancytopenia persists after COVID-19 treatment or in those with splenomegaly. Further, the condition of all previously reported patients with COVID-19 associated with HCL was severe enough to require mechanical ventilation. This is the first case in which the disease was not severe. The interleukin-6 (IL-6) level was lower in this case than in previous cases, suggesting that racial differences in IL-6 production may have contributed to COVID-19 severity. | Leukemia, Hairy Cell |
Heart failure with preserved ejection fraction (HFpEF) is a growing epidemiologic problem affecting more than half of the patients with heart failure (HF). HFpEF has a significant morbidity and mortality and so far no treatment has been clearly demonstrated to improve the outcomes in HFpEF, in contrast to the efficacy of treatment in heart failure with reduced ejection fraction (HFrEF).The failure of proven beneficial drugs in HFrEF to influence the outcome of patients with HFpEF could be related to the heterogeneity of the disease, its various phenotypes and multifactorial pathophysiology, incompletely elucidated yet. The diagnosis of HFpEF could be demanding or even inaccurate. Moreover, the therapeutic strategies were influenced by different cut-offs used to define preserved ejection fraction (EF). From this perspective, the current guidelines have classified HFpEF by an EF >/= 50%, together with a distinct entity, heart failure with mid-range ejection fraction (HFmrEF), defined by an EF ranging from 41-49%.New therapies have been developed to interfere with the mediator pathways of HFpEF at the cellular and molecular level, including mineralocorticoid receptor antagonists, soluble guanylate cyclase stimulators, or angiotensin receptor-neprilysin inhibitors. A number of antidiabetic drugs, such as sodium/glucose cotransporter 2 inhibitors and dipeptidyl peptidase-4 inhibitors are promising options, being under research in large clinical trials. Until the results of ongoing trials shed light on these therapies, guidelines recommend empirical treatment for established HFpEF, and emphasize the crucial role of addressing cardiovascular comorbidities leading to HFpEF, in particular arterial hypertension. | Stroke Volume |
PURPOSE: Postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting (PDNV) are common problems after surgery. Prophylactic combination antiemetic therapy is recommended for patients at high risk for developing PONV and PDNV. Granisetron, a serotonin antagonist, is an effective antiemetic that is devoid of sedative side effect. Although promethazine is effective, commonly used doses are associated with sedation. This study investigates the combination of low doses of granisetron and promethazine for the prevention of PONV. METHODS: Women undergoing ambulatory gynecological laparoscopy were enrolled. A standard general anesthetic regimen was prescribed. Fifteen minutes before the expected end of surgery, the patients were randomly assigned to receive granisetron 0.1 mg iv, promethazine 6.25 mg iv, or a combination of the two drugs. Prophylaxis with oral promethazine 12.5 mg, granisetron 1 mg, or both was started in the respective groups 12 hr after the end of surgery and continued every 12 hr until postoperative day 3 (a total of five oral doses). The following outcomes were recorded: total response rate (defined as no vomiting, no more than mild nausea, and no use of rescue antiemetic); incidence of nausea, vomiting, and use of rescue antiemetics; severity of nausea; patient activity level; and patient satisfaction with PONV management. RESULTS: Patients in the combination group had a higher total response rate at 6, 24, 48, and 72 hr after surgery compared with those who received promethazine alone (at 24 hr, Combination 69.6%, Promethazine 36.2%, Granisetron 53.3%; P = 0.0079). The maximum nausea scores were also lower in the combination group at 6, 24, 48, and 72 hr (Combination 1.7 +/- 2.2, Promethazine 4.0 +/- 3.6, Granisetron 3.1 +/- 3.2 at 24 hr; P < 0.05). There was no difference in the sedation scores, incidence of drowsiness, patient activity level, and satisfaction with PONV management. CONCLUSIONS: Low-dose granisetron and promethazine combination was more effective in reducing PONV and PDNV than promethazine monotherapy. The combination also reduced the severity of nausea. | Granisetron |
With high activity and specificity to conduct catalysis under mild conditions, enzymes show great promise in many fields. However, they are not acclimatized to environments in practice after leaving the familiar biological conditions. Aiming at this issue, nanobiocatalysis, a fresh area integrating nanotechnology and enzymatic catalysis, is expected to design biocatalysis based on materials science. Specifically, nano-integrated biocatalysis and bio-inspired nanocatalysis are considered as two effective nanobiocatalytic systems to meet different design needs. Notably, both systems are not entirely separated, and the combination of both further sparks more possibilities. This review summarizes the type, construction, and function of nanobiocatalytic systems, analyzing the pros and cons of different strategies. Moreover, the corresponding applications in bioassay, biotherapy, and environmental remediation are highlighted. We hope that the advent of nanobiocatalysis will help in grasping the inherence of biocatalysis and propel biocatalytic applications. | Materials Science |
PURPOSE: This study investigated the relationship between dichotic listening (DL) benefits from treatment with Auditory Rehabilitation for Interaural Asymmetry (ARIA) and the severity of DL deficits quantified prior to the onset of treatment. We hypothesized that children with more severe DL deficits would demonstrate greater benefits following ARIA. METHOD: A scale that quantifies deficit severity was applied to dichotic listening scores obtained before and after training with ARIA at multiple clinical sites (n = 92). Using multiple regression analyses, we evaluated the predictive effects of deficit severity on DL outcomes. RESULTS: Results demonstrated that deficit severity can predict benefits from ARIA, as measured by improvements in DL scores in both ears. CONCLUSION: ARIA is an adaptive training paradigm for improving binaural integration abilities in children with DL deficits. The results from this study suggest that children with more severe DL deficits achieve greater benefits from ARIA and that a severity scale may provide important clinical information for recommending intervention. | Auditory Perceptual Disorders |
Integrase (IN) is the newest validated target against AIDS and retroviral infections. The remarkable activity of raltegravir (Isentress((R))) led to its rapid approval by the FDA in 2007 as the first IN inhibitor. Several other IN strand transfer inhibitors (STIs) are in development with the primary goal to overcome resistance due to the rapid occurrence of IN mutations in raltegravir-treated patients. Thus, many scientists and drug companies are actively pursuing clinically useful IN inhibitors. The objective of this review is to provide an update on the IN inhibitors reported in the last two years, including second generation STI, recently developed hydroxylated aromatics, natural products, peptide, antibody and oligonucleotide inhibitors. Additionally, the targeting of IN cofactors such as LEDGF and Vpr will be discussed as novel strategies for the treatment of AIDS. | HIV Integrase Inhibitors |
Chelerythrine (CH) and ethoxychelerythrine (ECH) are chemical reference substances for quality control of Chinese herbal medicines, and ECH is the dihydrogen derivative of CH. In this study, their fluorescence and absorption spectra, as well as their structural changes in different protic solvents were compared. It was observed that their emission fluorescence spectra in methanol were almost the same (both emitted at 400 nm), which may be attributed to the nucleophilic and exchange reactions of CH and ECH with methanol molecules with the common product of 6-methoxy-5,6-dihydrochelerythrine (MCH). When diluted with water, MCH was converted into CH, which mainly existed in the form of positively charged CH(+) under acidic and near-neutral conditions with the fluorescence emission at 550 nm. With the increase of pH value of the aqueous solution, CH(+) converted to 6-hydroxy-5,6-dihydrochelerythrine (CHOH) with the fluorescence emission at 410 nm. The fluorescence quantum yields of MCH and CHOH were 0.13 and 0.15, respectively, and both the fluorescence intensities were much stronger than that of CH(+). It is concluded that CH and ECH can substitute each other in the same protic solvent, which was further verified by high-performance liquid chromatography. This study will help in the investigation of structural changes of benzophenanthridine alkaloids and will provide the possibility for the mutual substitution of standard substances in relevant drug testing. | Benzophenanthridines |
A high-performance liquid chromatographic method for the determination of hyaluronic acid levels in synovial fluids has been developed. The hyaluronidase sample digests, containing an internal standard (benzoic acid), were separated on a reversed-phase octadecylsilyl column eluted with 0.01 M tetrabutylammonium phosphate-acetonitrile (83:17, v/v) at pH 7.35. The determination was made on 1:10 diluted samples, by using a calibration curve from 50 to 500 micrograms/ml of human umbilical cord hyaluronic acid. For validation, the synovial fluids were simultaneously analysed by this method and a radiometric method: a high correlation was found between the two (correlation coefficient 0.94). The proposed method can be used to determine specifically the high hyaluronic acid levels of synovial fluids without interferences from other glycosaminoglycans or non-steroidal anti-inflammatory drug treatment." | Chromatography, High Pressure Liquid |
Long-term ovine fibroblast cultures contain replicative-competent lentiviruses in a latent form. This in vitro phenomenon, never described previously for lentiviruses, was clearly demonstrated by activating the expression of latent viruses with various inducing cell treatments, some of which were efficient in inducing endogenous retroviruses or latent herpesviruses. Activated lentiviruses were highly lytic in ovine fibroblasts (type I), or they established persistent infections (type II) as described previously for field isolates from sheep with progressive pneumonia (Querat et al., J. Virol. 52:671-678, 1984). | Lentiviruses, Ovine-Caprine |
Inhibitory control is the capacity to withhold or suppress a thought or action intentionally. The anterior Midcingulate Cortex (aMCC) participates in response inhibition, a proxy measure of inhibitory control. Recent research suggests that response inhibition is modulated by individual variability in the aMCC sulcal morphology. However, no study has investigated if this phenomenon is associated with neurofunctional differences during a task. In this study, 42 participants performed an Attention Network Task and a Numerical Stroop task in an MRI scanner. We investigated differences in brain activity and response inhibition efficiency between individuals with symmetric and asymmetric aMCC sulcal patterns. The results showed that aMCC morphological variability is partly associated with inhibitory control, and revealed greater activation in individuals with symmetric patterns during the Stroop task. Our findings provide novel insights into the functional correlates of the relationship between aMCC morphology and executive abilities. | Gyrus Cinguli |
PURPOSE: The purpose of this study was to determine the MR appearance of struma ovarii correlating with the pathological features. METHOD: MR findings of two patients with struma ovarii were retrospectively reviewed and compared with the pathological findings. RESULTS: Both tumors were complex masses composed of multiple cysts and solid components. The size and signal intensity of multiple cysts varied within the tumor. Hyperintense cystic areas on T1-weighted images were thought to correspond pathologically to hemorrhagic cysts and follicles containing viscous proteinaceous colloid. Solid components had as high a signal intensity as did uterine endometrium on T2-weighted images and as intermediate a signal intensity as did uterine muscle layer on T1-weighted images. After intravenous administration of gadolinium-DTPA, the solid components showed marked contrast enhancement. There was also ascitic fluid associated with adhesion and peritoneal thickening. CONCLUSION: The characteristic MR appearance of struma ovarii is thought to be a mixed mass composed of T2-hyperintense solid components with intense contrast enhancement and multiple T1-hyperintense cystic areas suggestive of hemorrhagic degeneration and viscous proteinaceous colloid. | Struma Ovarii |
We report the detection of several fungicide residues (Dichlofluanid, Benomyl, Iprodione, Procymidone and Vinclozolin) in red and white bottled wines from two Portuguese wine-producing zones. Studies were done in order to evaluate the active compound transfer percentage from grapes to the final product along fermentation process. We also investigated their effects in Saccharomyces and non-Saccharomyces yeasts as well as their influence on the physical, chemical and organoleptic wine properties. All the tested fungicides had a negative effect on in vitro yeast growth, with Dichlofluanid and Benomyl being the most toxic. Zygosaccharomyces rouxii and Saccharomyces cerevisiae were the most resistant yeasts while Rhodotorula glutinis was the most susceptible. Microvinification experiments carried out in the presence of fungicides produced wine samples with unaltered physical, chemical and organoleptic properties, though Benomyl, a slight delay in the initiation of fermentation process was observed. | Wine |
The coronary arteries have been regarded as end arteries for decades. However, there are functionally relevant anastomotic vessels, known as collateral arteries, which interconnect epicardial coronary arteries. These vessels provide an alternative source of blood supply to the myocardium in cases of occlusive coronary artery disease. The relevance of these collateral arteries is a matter of ongoing debate, but increasing evidence indicates a relevant protective role in patients with coronary artery disease. The collateral circulation can be assessed by different methods; the gold standard involves intracoronary pressure measurements. While the first clinical trials to therapeutically induce growth of collateral arteries have been unavailing, recent pilot studies using external counterpulsation or growth factors such as granulocyte colony stimulating factor (G-CSF) have shown promising results. | Collateral Circulation |
I.C.I. 50172 was used to slow the ventricular rate when conventional treatment had failed in 19 patients. All were either in congestive cardiac failure or in the immediate postoperative period following valve replacement. The ventricular rate was controlled in seven out of eight patients with atrial fibrillation, in six out of nine patients with supraventricular tachycardia, and in two patients with sinus rhythm. Important side-effects were not seen. | Sympatholytics |
Lysosomal storage diseases (LSDs) are a group of metabolism inborn errors caused by defective enzymes in the lysosome, resulting in the accumulation of undegraded substrates. Many characteristic cell features have been revealed in LSDs, including abnormal autophagy and mitochondrial dysfunction. The development of induced pluripotent stem cells (iPSCs) dramatically boosted research on LSDs, particularly regarding novel opportunities to clarify the disease etiology based on the storage of macromolecules, such as sphingolipids in lysosomes. iPSCs made from LSD patients (LSD-iPSCs) have been differentiated into neurons, endothelial cells, cardiomyocytes, hepatocytes, and macrophages, with each cell type closely resembling the primary disease phenotypes, providing new tools to probe the disease pathogenesis and to test therapeutic strategies. Abnormally accumulated substrates impaired autophagy and mitochondrial and synapse functions in LSD-iPSC-derived neurons. Reducing the accumulation with the treatment of drug candidates improved LSD-iPSC-derived neuron functions. Additionally, iPSC technology can help probe the gene expressions, proteomics, and metabolomics of LSDs. Further, gene repair and the generation of new mutations in causative genes in LSD-iPSCs can be used to understand both the specific roles of causative genes and the contributions of other genetic factors to these phenotypes. Moreover, the development of iPSC-derived organoids as disease models has bridged the gap between studies using cell lines and in vivo animal models. There are some reproducibility issues in iPSC research, however, including genetic and epigenetic abnormalities, such as chromosomal abnormalities, DNA mutations, and gene modifications via methylation. In this review, we present the disease and treatment concepts gathered using selected LSD-iPSCs, discuss iPSC research limitations, and set our future research visions. Such studies are expected to further inform and generate insights into LSDs and are important in research and clinical practice. | Lysosomal Storage Diseases |
BACKGROUND: Hemoptysis, a common symptom of different lung diseases, engenders shortness of breath and increased mortality. Tranexamic acid (TXA), a commonly used antifibrinolytic agent, can control bleeding. However, the effects of its use on pulmonary hemorrhage have rarely been discussed. OBJECTIVE: We conducted this systematic review and meta-analysis of randomized controlled trials (RCTs) of TXA for hemoptysis to investigate its effectiveness in reducing hemoptysis volume and duration. METHODS: We searched the Cochrane Library, Embase, PubMed (including MEDLINE), and Scopus databases for relevant RCTs. Two of the authors individually assessed study quality by using the Cochrane risk-of-bias (RoB) 2.0 tool, and the pooled results were evaluated using RevMan 5.3. RESULTS: We obtained 617 articles, of which four RCTs met eligibility criteria. The pooled results demonstrated no significant differences in bleeding duration or hemoptysis resolution between the TXA and control groups. Nevertheless, TXA use reduced bleeding volume (mean difference [MD] = - 56.21 mL; 95% CI - 94.70 to - 17.72 mL), further intervention risk (Peto odds ratio = 0.24; 95% CI 0.08-0.67; I(2) = 0%), and length of hospital stay (MD = - 1.62 days; 95% CI - 2.93 to - 0.31; I(2) = 0%). CONCLUSION: TXA use was observed to reduce bleeding volume, further intervention risk, and length of hospital stay in patients with hemoptysis; however, our results may have low statistical power because of limited sample size. Additional large-scale RCTs are thus warranted to confirm the effectiveness and safety of TXA use. | Hemoptysis |
Extracts of stems of growing shoots of Populus deltoides and P. trichocarpa, and developing capsules of P. deltoides were analysed for gibberellins (GAs) by gas chromatography-mass spectrometry. The following known GAs were identified by comparison of their Kovats retention indices (KRIs) and mass spectra with those of standards: GA1, GA8, GA9, GA19, GA20, 16 beta,17-dihydro-17-hydroxy GA20, GA23, GA28, GA29, GA34, GA44, and GA97. Several of these have not been previously reported from Populus. In addition, two new GAs were identified as 12 beta-hydroxy GA53 (GA127) and 16 beta,17-dihydro-17-hydroxy GA53 and their structures were confirmed by partial synthesis. Evidence was found of 16,17-dihydro-16,17-dihydroxy GA9, 16,17-dihydro-16,17-dihydroxy GA12, 12-hydroxy GA14, and GA34-catabolite by comparison of mass spectra and KRIs with published data. Several putative GAs (hydroxy- and dihydroxy-GA12-like) were also found. The catabolites of active GAs or of key precursors, hydroxylated at C-2 in stems and either C-2, C-12, C-17, or C-16,17 in capsules, were the major proportion of the GAs. | Gibberellins |
This review provides a renewed look at the genus Digitalis. Emphasis will be put on those issues that attracted the most attention or even went through paradigmatic changes since the turn of the millennium. PubMed and Google Scholar were used (Digitalis" and "Foxglove" were the key words) to identify research from 2000 till 2017 containing data relevant enough to be presented here. Intriguing new results emerged from studies related to the phylogeny and taxonomy of the genus as well as to the biosynthesis and potential medicinal uses of the key active compounds, the cardiac glycosides. Several Eastern and Western Foxgloves were studied with respect to their propagation in vitro. In this context, molecular biology tools were applied and phytochemical analyses were conducted. Structure elucidation and analytical methods, which have experienced less exciting progress, will not be considered here in great detail." | Plantaginaceae |
This review summarizes properties of various naturally occurring compounds with reported calmodulin (CaM)-inhibitory properties which include about 159 natural products belonging to different structural classes. Most inhibitors are alkaloid and peptide type of compounds and have been isolated from a wide variety of natural sources, including many plant species. Among the most potent natural anti-CaM substances, however, are several animal venoms and the antibiotic polymixin. The largest number of compounds described were discovered by means of enzymatic functional assays. | Calmodulin |
Gossypol, a bis-sesquiterpene, suppresses spermatogenesis and inhibits sperm motility. The direct interaction of gossypol with human sperm was investigated. Conditions influencing the interaction of 14c-gossypol (radiolabeled on the aldehyde group with specific activity of 3.33 x 10 5 dpm per micromole) with human sperm reached saturation rapidly. Within 1 minute of exposure of motile sperm to 10 uM radiolabeled gossypol at 37 degrees Centigrade, the cincorporation of 14c-gossyol was 17 at 35% at densities of 2.5 x 106 and 8.6 x 106 per ml, respectively. Immobile sperm prepared by heating at 60 degrees Centigrade for 10 minutes incorporated the same amount of 14c-gossypol as motile sperm. Uptake of 14c-gossypol was slightly greater at 37 degrees Centigrade than at 4 degrees Centigrade, and under acidic conditions. To identify the sperm membrane components interacting with gossypol radiolabeled sperm were treated with the following 3 solutions to solubilize the membrane proteins: 0.1% Triton X-100; 1 M urea, 5 mM EDTA in 19mM Tris-HC1, pH 8.3; and 20% sodium doydecyl sulfate (SDS), 0.1M 20mercaptoethanol. The amount of radiolabeled proteins solubilized with respective media were 11, 23, and 67% with specific activities of 1.8 x 103, 2.1 x 105, and 0.3 x 103 cpm per mg protein. The radiolabeled substances solubilized with SDS, mercaptoethanol reagent were separated by gel filtration on Sephadex G-100 column. 3 peaks of radioactivities corresponding to molecular weights of approximately 100, 35, and 25 KD were eluted. The highest radioactivity was found with the 100 KD fraction. The interaction of gossypol with sperm membrane proteins is an early event, followed by inhibition of sperm motility. | Contraceptive Agents |
Hypoxia abolishes breathing movements in fetal sheep, perhaps by reducing ATP synthesis within regulatory brain cells. This possibility was examined by administering to 13 chronically catheterized fetal sheep oligomycin B, a mitochondrial ATPase inhibitor. Injections into the left external carotid artery of oligomycin B (170 +/- 19 micrograms/kg in 9 fetuses) reduced significantly (P less than 0.01) the incidence of fetal breathing movements from a control mean of 52 +/- 6.3% to 6 +/- 2.2 and 9 +/- 4.4% during the first and second hours after drug injection. Oligomycin did not decrease significantly the incidence of low voltage electrocortical activity or reduce the average duration of a cycle of low and high voltage electrocortical states. Nor did it decrease significantly the incidence of rapid eye movements. Fetal heart rate and mean arterial pressure were not significantly affected, and the arterial blood gases and pH did not significantly differ from control values. However, a large dose of the drug (700 micrograms/kg) produced an isoelectric electrocorticogram, hypertension, and bradycardia associated with a rise in arterial PO2 and a severe metabolic acidosis. In 3 fetal sheep oligomycin also inhibited continuous breathing induced by indomethacin. Injection of the vehicle (ethanol) alone did not alter the incidence of breathing movements, electrocortical activity, eye movements or blood gases. These results suggest that reduced mitochondrial production of ATP may be a mechanism by which hypoxia abolishes fetal breathing activity. | Oligomycins |
A review of the satiating effect of cholecystokinin in humans reveals that the synthetic C-terminal octapeptide of cholecystokinin (CCK-8) inhibits liquid and solid food intake in non-obese men and women, and in obese men. Side effects, such as nausea, slight stomach sickness or abdominal cramps are infrequent and transient, and they are neither necessary nor sufficient for the inhibition of intake. These results demonstrate the efficacy of the satiating effect of CCK-8 in humans. The therapeutic potential of CCK-8 cannot be estimated until further studies are performed that demonstrate the efficacy of CCK-8 for decreasing body weight and that the safety of CCK-8 when it is administered repetitively for prolonged periods is established. | Sincalide |
This study investigated long-term outcomes and factors associated with reoperations in patients who underwent surgical repair of congenital supravalvar aortic stenosis (SVAS). A total of 39 consecutive patients who underwent congenital SVAS repair from 1999 through 2018 were included. Aortic root geometry was evaluated by measuring the ratio of the sinotubular junction diameter to the aortic annulus diameter (STJ/AVA) on echocardiography and proportion of intercommissural distance (ICD) of each sinus on computed tomography. The median age and weight at the time of operation were 4.3 years and 16.9 kg, respectively. Williams syndrome was associated in 25 patients (64.1%). Modified simple sliding aortoplasty (MSSA) was mostly used (nâ¯=â¯35, 89.7%). The median follow-up duration was 9.5 years. There were no early deaths and 1 late death. Overall survival rate was 97.0% at 15 years. There were 7 reoperations during follow-up. Freedom from reoperation for left ventricular outflow tract obstruction and all-cause reoperation were 91.9% and 80.4%, respectively. Age younger than 2 years at initial repair were associated with all-cause reoperation in the univariable analysis. In 35 patients who underwent MSSA, the degree of aortic regurgitation was equal to or less than mild in all patients during follow-up. Their median STJ/AVA on postoperative echocardiography was 0.95 (0.84-1.02). SVAS repair with MSSA provided excellent long-term survival with well-preserved aortic valve competence. Age younger than 2 years at initial repair might be associated with reoperation." | Aortic Stenosis, Supravalvular |
Platelet Rich Plasma (PRP) and growth factors have had encouraging results in several surgical specialties. Their use in orthopaedics is increasing and has been trialed in fracture management, spinal fusion and tendon and ligament healing. Anterior cruciate ligament (ACL) injuries are a significant economic burden and often require surgical reconstruction. This review article used laboratory and clinical studies to evaluate the effectiveness of PRP and growth factors as an adjunct to ACL reconstruction. Overall, the results of studies to date have been disappointing especially given the success in other specialties. PRP has been relatively successful in improving vascularization within the tibial tunnel but less so in the femoral tunnels. The targeting of specific growth factors seems to show more promise than generic PRP injections with vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) showing the most significant results in graft healing. Further trials are still required before a definitive conclusion can be reached. | Anterior Cruciate Ligament |
The forecasting efficiency of two- and three-echelon menu item forecasting systems was compared. Two forecasting models were used with each system, adaptive exponential smoothing and a Box-Jenkins model. The two systems were compared in terms of forecast error costs. The two-echelon system, using adaptive exponential smoothing, was recommended. This technique resulted in the lowest forecast error costs at a majority of the lead times which probably would be used most frequently. Also, this technique was the least complicated of the four techniques which were compared. | Food Service, Hospital |
Three corn feedstocks (fibers, cobs and stover) available for sustainable second generation bioethanol production were subjected to pretreatments with the aim of preventing formation of yeast-inhibiting sugar-degradation products. After pretreatment, monosaccharides, soluble oligosaccharides and residual sugars were quantified. The size of the soluble xylans was estimated by size exclusion chromatography. The pretreatments resulted in relatively low monosaccharide release, but conditions were reached to obtain most of the xylan-structures in the soluble part. A state of the art commercial enzyme preparation, Cellic CTec2, was tested in hydrolyzing these dilute acid-pretreated feedstocks. The xylose and glucose liberated were fermented by a recombinant Saccharomyces cerevisiae strain. In the simultaneous enzymatic saccharification and fermentation system employed, a concentration of more than 5% (v/v) (0.2g per g of dry matter) of ethanol was reached. | Carbohydrate Metabolism |
We reported previously that ovariectomy alters prepubertal development of mammary myoepithelial cells (MC) by mechanisms that are not well understood. Therefore, in the present study, we analyzed expression of 2 myoepithelial differentiation markers, alpha-smooth muscle actin (SMA) and the common acute lymphoblastic leukemia antigen (CD10), in mammary parenchymal tissue from intact (INT) and ovariectomized (OVX) heifers. On d 40, Holstein heifers underwent either an ovariectomy (OVX; n=16) or a sham (INT; n=21) operation. At 55, 70, 85, 100, 130, and 160 d of age, tissues were collected, and multispectral imaging was used to quantify immunofluorescent staining for myoepithelial cell (MC) markers. Fluorescent intensity (FI) of the markers was normalized against a control sample. In the basal epithelial layer, CD10 FI was less and SMA FI was greater in OVX than INT. The ratio of SMA to CD10 FI, as a proxy indicator for MC differentiation, was greater in tissue from OVX compared with INT heifers after 55 d of age. The staining for SMA was frequently more intense along the basal aspect of cells, whereas CD10 expression was localized on the apical surface of the MC. In mammary tissue from both INT and OVX heifers, we observed basal cells that were negative for both CD10 and SMA, some of which appeared to span the distance from basement membrane to the ductal lumen. Interestingly, we also observed CD10+ cells adjacent to the ductal lumen, a situation that was more prevalent in OVX than in INT heifers. Also, ovariectomy affects MC expression of both SMA and CD10, as well as the pattern of MC development. Myoepithelial cells are known to limit parenchymal growth in other species. Involvement of MC as regulators of prepubertal bovine mammary development is worthy of further investigation. | Mammary Glands, Animal |
Directed evolution of Cp*Rh(III) -linked nitrobindin (NB), a biohybrid catalyst, was performed based on an in vitro screening approach. A key aspect of this effort was the establishment of a high-throughput screening (HTS) platform that involves an affinity purification step employing a starch-agarose resin for a maltose binding protein (MBP) tag. The HTS platform enables efficient preparation of the purified MBP-tagged biohybrid catalysts in a 96-well format and eliminates background influence of the host E. coli cells. Three rounds of directed evolution and screening of more than 4000 clones yielded a Cp*Rh(III) -linked NB(T98H/L100K/K127E) variant with a 4.9-fold enhanced activity for the cycloaddition of acetophenone oximes with alkynes. It is confirmed that this HTS platform for directed evolution provides an efficient strategy for generating highly active biohybrid catalysts incorporating a synthetic metal cofactor. | Chromatography, Agarose |
OBJECTIVES: The bacterial pathogen Neisseria meningitidis is able to escape the currently available capsule-based vaccines by undergoing capsule switching. In this study, we investigated whether capsule switching has occurred in a recently emerged sequence type (ST) 7 serogroup X isolate in China, for which currently no vaccine is available. METHODS: To identify capsule switching breakpoints, the capsule locus and flanking regions of the ST-7 serogroup X isolate and three endemic ST-7 serogroup A isolates were sequenced and compared. To obtain further insight into capsule switching frequency and length of DNA fragments involved, capsule switching assays were performed using genomic DNA containing combinations of antibiotic selection markers at various locations in the capsule locus and flanking regions. RESULTS: Sequence analyses showed that capsule switching has occurred and involved a 8450 bp serogroup X DNA fragment spanning the region from galE to ctrC. Capsule switching assays indicate that capsule switching occurs at a frequency of 6.3 x 10(-6) per bacterium per mug of DNA and predominantly involved DNA fragments of about 8.1-9.6 kb in length. CONCLUSIONS: Our results show that capsule switching in N. meningitidis occurs at high frequency and involves recombination in the flanking regions of the capsule biosynthesis genes." | Neisseria meningitidis, Serogroup A |
An immunocytochemical ultrastructural study of Rhodospirillum rubrum cultured under semiaerobic conditions was conducted to correlate the localization of functional components with membrane formation. R. rubrum is a facultatively phototrophic organism. Under reduced oxygen, this bacterium forms an intracytoplasmic chromatophore membrane that is the site of the photosynthetic apparatus. Immunogold techniques were used to localize intracellular protein antigens associated with the photosynthetic apparatus. Antibody, demonstrated by immunoblotting to be specific for the reaction center and light-harvesting photochemical components, was conjugated to colloidal gold particles and used for direct immunolabeling of fixed, sectioned specimens. Membrane invaginations appeared by 4 h after transition to induction conditions, and mature chromatophore membrane was abundant by 22 h. The occurrence of chromatophore membrane was correlated with bacteriochlorophyll a content and the density of the immunolabel. In uninduced (aerobic) cells and those obtained from cultures 0.5 h posttransition, the immunogold preferentially labeled the peripheral area of the cell. In contrast, in cells obtained after 22 h of induction, the central region of the cell was preferentially immunolabeled. These findings provided immunocytochemical evidence supporting the hypothesis that the chromatophore membrane is formed by invagination of the cytoplasmic membrane. | Bacterial Chromatophores |
A three-dimensional model is presented to simulate the larynx during vocalization. The finite element method is used to calculate the airflow velocity and pressure along the larynx as well as tissue displacement. It is assumed that the larynx tissue is transversely isotropic and divided into three tissues: cover, ligament, and body. A contact-impact algorithm is incorporated to deal with the physics of the collision between both true vocal folds. The results show that the simulated larynx can reproduce the vertical and horizontal phase difference in the tissue movements and that the false vocal folds affect the pressure distribution over the larynx surfaces. The effects of exciting the larynx with different pressure drops are also investigated. | Larynx |
Antiplatelet therapy displays a critical role in the treatment and prevention of antithrombotic disorders. Many new antiplatelet agents have been developed following the emergence of various clinical limitations of classical antiplatelet drugs. This review covers mainly the recent advances in the development of P2Y(12) antagonists and GPIIb/IIIa antagonists. Meanwhile, it summarizes promising approaches to new platelet surface receptors such as prostanoid EP3 receptor, thromboxane A(2) prostanoid receptor, protease-activated receptors, GPIb-IX-V receptor and P-selectin. In addition, PI3K(beta), a critical protein at the inside signaling pathway of platelet activation is also mentioned as an important antiplatelet target. Moreover, the development of respective drug candidates is discussed in detail." | Platelet Aggregation Inhibitors |
BK viruses (BKV) comprise four subtypes that are distinguishable by serological and molecular methods with the latter indicating up to four subgroups within subtype I. In this study, the phylogeny of all BKV subtypes was analyzed. Phylogenetic analyses of the viral structural protein VP1, concatenated sequences including the T-Ag, t-Ag, VP1 and VP2 genes and the entire coding region of BKV, each employing several tree inference methods, consistently revealed seven strongly supported clades that correlate with BKV subtypes and subgroups. In general, subtype II and III viruses were found to be sister groups, the genetic distances between which were significantly lower than those between either and the other BKV subtypes. Two benchmarks of human evolution (emergence of modern humans, 200,000 years ago; out-of-Africa migration, 100,000 years ago) were assumed for the internal calibration of BKV evolution. Utilization of either calibration point resulted in the diversification of most BKV subgroups coinciding with human radiation less than 50,000 years ago. Another approach, external calibration by linking BKV divergence to the evolution of mammals, was rejected as it advances BKV divergence prior to the emergence of modern humans. | Polyomaviridae |
Aquatic viruses can spread rapidly and widely in seawater for their high infective ability. Polyinosinic-polycytidylic acid (Poly I:C), a viral dsRNA analog, is an immunostimulant that has been proved to activate various immune responses of immune cells in invertebrate. Hemolymph is a critical site that host immune response in invertebrates, and its transcriptome information obtained from Amphioctopus fangsiao stimulated by Poly I:C is crucial for understanding the antiviral molecular mechanisms of this species. In this study, we analyzed gene expression data in A. fangsiao hemolymph tissue within 24 h under Poly I:C stimulation and found 1082 and 299 differentially expressed genes (DEGs) at 6 and 24 h, respectively. Union set (1,369) DEGs were selected for subsequent analyses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were carried out for identifying DEGs related to immunity. Several significant immune-related terms and pathways, such as toll-like receptor signaling pathways term, inflammatory response term, TNF signaling pathway, and chemokine signaling pathway were identified. A protein-protein interaction (PPI) network was constructed for examining the relationships among immune-related genes. Finally, 12 hub genes, including EGFR, ACTG1, MAP2K1, and other nine hub genes, were identified based on the KEGG enrichment analysis and PPI network. The quantitative RT-PCR (qRT-PCR) was used to verify the expression profile of 12 hub genes. This research provides a reference for solving the problem of high mortality of A. fangsiao and other mollusks and provides a reference for the future production of some disease-resistant A. fangsiao. | Poly C |
This study examined and compared the importance of specific competencies for bachelor's level and master's level school health educators in Florida. A survey instrument utilizing a five-point scale was administered to 69 respondents to ascertain the importance of 135 competencies in the areas of administration, evaluation, general health knowledge, and communication. Results of the analysis of data indicate that bachelor's level health educators require competencies necessary for the direct delivery of health instruction, while master's level health educators need to possess specific competencies in administration and evaluation. | School Health Services |
Many voltage-dependent ion channels are regulated by accessory proteins. We recently reported powerful regulation of Kv1.2 potassium channels by the amino acid transporter Slc7a5. In this study, we report that Kv1.1 channels are also regulated by Slc7a5, albeit with different functional outcomes. In heterologous expression systems, Kv1.1 exhibits prominent current enhancement ('disinhibition') with holding potentials more negative than -120 mV. Knockdown of endogenous Slc7a5 leads to larger Kv1.1 currents and strongly attenuates the disinhibition effect, suggesting that Slc7a5 regulation of Kv1.1 involves channel inhibition that can be reversed by supraphysiological hyperpolarizing voltages. We investigated chimeric combinations of Kv1.1 and Kv1.2, demonstrating that exchange of the voltage-sensing domain controls the sensitivity and response to Slc7a5, and localize a specific position in S1 with prominent effects on Slc7a5 sensitivity. Overall, our study highlights multiple Slc7a5-sensitive Kv1 subunits, and identifies the voltage-sensing domain as a determinant of Slc7a5 modulation of Kv1 channels." | Large Neutral Amino Acid-Transporter 1 |
Plant peroxisomes can be isolated by Percoll density gradient centrifugation at high purity and metabolic competence as well as in relatively large quantities. According to biochemical and electrophysiological analyses, plant peroxisomes have recently been shown to differ from other cell organelles in essential structural properties. Unlike mitochondria or plastids, compartmentalization of plant peroxisomal metabolism is in major parts not caused by a boundary function of the membrane but is primarily due to the specific structure of the protein matrix. The enzymes of the photorespiratory C2 cycle of leaf peroxisomes are arranged as multienzyme complexes that allow efficient metabolic channelling with high flux rates and minimum leakage of reactive oxygen species from the organelle. Transfer of metabolites, such as carboxylates, proceeds across the peroxisomal membrane via a porin-like channel, which represents a relatively unspecific but highly efficient transport system. Because all variants of peroxisomes, which all contain only a single boundary membrane, are confronted with the task of transporting a large group of metabolites while preventing the escape of reactive intermediates, it is reasonable to speculate that the unique compartmentalization feature of leaf peroxisomes also applies to peroxisomes from fungi and mammals. | Peroxisomes |
OBJECTIVE: The main aims of this study were to identify candidates for cognitive-enhancing herbal formulae from the Korean medicine literature and to obtain preliminary data that experimental and clinical researchers could use to develop new cognitive-enhancing drugs. METHODS: The authors systematically searched for terms related to cognitive enhancement in Dongui Bogam (or Dongyi Baojian), a seminal Korean medicine book. They also reviewed the existing literature on the effects of candidates for cognitive-enhancing herbal formulae and their main constituents. RESULTS AND CONCLUSIONS: Twenty-three candidates were selected for cognitive-enhancing herbal formulae and their main constituents. For 14 herbal formulae among the 23 candidates, on average 5.6 published research papers per herbal formula describing cognitive-enhancing effects were found. In addition, some published papers were identified for 5 main constituents most frequently used to make up the 23 candidates. | Medicine, Korean Traditional |
Glucagon-like peptides (GLP-1 and GLP-2) are two proglucagon-derived intestinal hormones that mediate distinct physiological functions through two related receptors (GLP-1R and GLP-2R) which are important drug targets for metabolic disorders and Crohn's disease, respectively. Despite great progress in GLP-1R structure determination, our understanding on the differences of peptide binding and signal transduction between these two receptors remains elusive. Here we report the electron microscopy structure of the human GLP-2R in complex with GLP-2 and a G(s) heterotrimer. To accommodate GLP-2 rather than GLP-1, GLP-2R fine-tunes the conformations of the extracellular parts of transmembrane helices (TMs) 1, 5, 7 and extracellular loop 1 (ECL1). In contrast to GLP-1, the N-terminal histidine of GLP-2 penetrates into the receptor core with a unique orientation. The middle region of GLP-2 engages with TM1 and TM7 more extensively than with ECL2, and the GLP-2 C-terminus closely attaches to ECL1, which is the most protruded among 9 class B G protein-coupled receptors (GPCRs). Functional studies revealed that the above three segments of GLP-2 are essential for GLP-2 recognition and receptor activation, especially the middle region. These results provide new insights into the molecular basis of ligand specificity in class B GPCRs and may facilitate the development of more specific therapeutics." | Glucagon-Like Peptide Receptors |
Glomus tumors of the fingers. Glomus tumors of the fingers are benign lesions. The main symptom is a paroxysmal pain with particular hypersensiti notvity to temperature changes. They are rare in their census, but there is very probably a very high rate of misdiagnosis, due to the very ignorance of their existence by the medical corpus. Their diagnosis is based on a typical clinical exami notnation and characteristic imaging. The only treatment is their complete surgical resection, which is essential for recovery. Different surgical techniques have been described in the medical literature to achieve a painless finger without nail deformity after tumor resection, while limiting recurrences."" | Nail Diseases |
This report describes the case of a woman in her early 20s who presented with a 3-day history of mobile foreign bodies and watering from her right eye. She had recently returned from vacation on a Greek island and presented to an ophthalmology unit in London, UK. A sample taken demonstrated Oestrus ovis infestation and confirmed the diagnosis of ophthalmomyiasis externa. She was treated with prophylactic topical antibiotics and subsequently made a full recovery. This was only the sixth presentation of O. ovis ophthalmomyiasis externa documented within the UK and the only case documented within the last 20 years. This is the fifth documented case found to have been transmitted within Greece. | Eye Infections, Parasitic |
Patients undergoing endoscopy are at risk of infection from the use of contaminated equipment. Dangers arise from the transmission of organisms from one patient to another and from the introduction of opportunist organisms which colonize endoscopic equipment on storage and can lead to sepsis and death in those who are immunocompromised and at ERCP. Staff are in danger from needle-stick injury and sensitivity to aldehyde disinfectants. These risks can be eliminated by careful attention to disinfection techniques. The most important part of endoscope disinfection is thorough mechanical cleaning first, followed by 5-10 min total immersion of the instrument and all channels in 2% glutaraldehyde (or the equivalent). At the end of the endoscopy list, following the disinfection protocol, all equipment should be dried internally and externally prior to storage. Staff must be fully aware of the risks of infection in endoscopy, be protected from hepatitis B by vaccination, and be fully trained in disinfection techniques. Glutaraldehyde should be used only in closed systems or in well-ventilated areas with the operator protected from direct contact from splashing and fumes. Institutions should designate an individual to be responsible for preparing, monitoring and overseeing disinfection procedures within the endoscopy room and for ensuring that regular microbiological testing of equipment (including automatic disinfecting machines) is undertaken. | Disinfection |
Archaeal integrases facilitate the formation of two distinctive types of integrated element within archaeal chromosomes: the SSV type and pNOB8 type. The former carries a smaller N-terminal and a larger C-terminal integrase gene fragment, and the latter an intact integrase gene. All integrated elements overlap tRNA genes that were target sites for integration. It has been demonstrated that SSV (Sulfolobus spindle virus) viruses, carrying an SSV-type integrase gene, and conjugative plasmids, carrying a pNOB8-type integrase, are integrative elements. Two mechanisms have been proposed for stably maintaining an integrated element within archaeal chromosomes. There is also evidence for changes having occurred in the captured integrated elements present in archaeal genomes. Thus we infer that site-specific integration constitutes an important mechanism for horizontal gene transfer and genome evolution. | Chromosomes, Archaeal |
OBJECTIVE: To review current understanding of the epidemiology, pathophysiology, diagnosis, and management of celiac disease. QUALITY OF EVIDENCE: Few recent randomized controlled trials (level I evidence) have studied treatments for celiac disease. There are recent comparative studies (level II evidence) and there is well established consensus (level III evidence) on diagnosis and treatment of celiac disease. MAIN MESSAGE: Celiac disease is an immune-mediated small bowel enteropathy caused by exposure to wheat gluten protein. The disease can be insidious and often presents with only subtle extraintestinal manifestations in a variety of organ systems. Recent epidemiologic surveys suggest celiac disease is much more common in North America than previously thought. Advances in immunology and screening have made diagnosis more reliable than in the past. Removing gluten from the diet is effective in most cases. CONCLUSION: Celiac disease manifests subtly and is an easy diagnosis to miss. Good laboratory screening tests and effective treatment are available. Family practitioners should consider celiac disease in patients who present with confounding symptoms. | Celiac Disease |
Gram-negative bacteria of the genus Xenorhabdus exhibit a mutualistic association with steinernematid entomopathogenic nematodes and a pathogenic relationship with insects. Here we describe two isolates of the entomopathogenic nematode Steinernema aciari collected from China and Japan. 16S rRNA gene sequence similarity and phylogenetic analysis indicated that the isolates obtained from S. aciari belonged to the genus Xenorhabdus. Multilocus sequence analysis based on five universal protein-coding gene sequences revealed that the isolates were closely related to Xenorhabdus ehlersii DSM 16337(T) and Xenorhabdus griffiniae ID10(T) but that they exhibited <97 % sequence similarity with these reference strains, which indicated that the isolates were distinct from previously described species. Based on these genetic differences and several differential phenotypic traits, we propose that the isolates represent a novel species of the genus Xenorhabdus, for which we propose the name Xenorhabdus ishibashii sp. nov. The type strain is GDh7(T) ( = DSM 22670(T) = CGMCC 1.9166(T)). | Xenorhabdus |
The involvement of afferent neuronal systems in the maintenance of basal and prolactin-stimulated tuberoinfundibular dopaminergic (TIDA) neuronal activity was examined in female and male rats. The synthesis and turnover of dopamine (DA) was measured in the median eminence, the terminal region of the TIDA neurons, to estimate the activity of these neurons. Complete and retrochiasmatic deafferentations of the mediobasal hypothalamus were made 7 days prior to experimentation to either completely isolate the TIDA neurons from the rest of the brain or to interrupt neuronal connections from rostral brain regions to the TIDA neurons, respectively. Both complete and retrochiasmatic deafferentations decreased the basal rate of DA synthesis and turnover in the median eminence of female, but not of male rats. These results suggest that neuronal afferents originating rostral to the mediobasal hypothalamus stimulate TIDA neurons in the female but not in the male rat. Intracerebroventricular administration of rat prolactin increased DA synthesis in the median eminence of both sham and retrochiasmatic deafferentiated female and male rats showing that the stimulatory action of prolactin is not blocked by retrochiasmatic deafferentation. Ovariectomy reduced the rate of DA synthesis in the median eminence but retrochiasmatic deafferentation did not cause a further decrease in ovariectomized rats. These results suggest that retrochiasmatic deafferentation and ovariectomy may remove a stimulatory input to the TIDA neurons which is mediated through a common afferent neuronal pathway. These afferent influences do not appear to be operational in the adult male rat since retrochiasmatic deafferentation did not reverse the castration-induced increase in the rate of DA synthesis in the median eminence of male rats. | Tuber Cinereum |
Tilapiine fishes of the genus Oreochromis vary in their euryhaline capabilities, therefore inhabiting aquatic environments of different salinities across the African continent. We analyzed the differential gene expression in the gills before and after 6 weeks salinity challenge between the highly tolerant Mozambique tilapia (Oreochromis mossambicus) and the less tolerant Nile tilapia (O. niloticus). The pathways triggered by salinity in both tilapia species reveal immune and cell stress responses as well as turnover of ionocytes. Nevertheless, the actual differential expressed genes vary between these two species, pointing at differential transcriptomic architecture, which likely contribute to the species osmoregulation capabilities in elevated salinities. | Tilapia |
Purpose: To evaluate the efficacy and safety of mycophenolate mofetil (MMF) in the treatment of recalcitrant intermediate uveitis in a tertiary referral eye-care center over a 1-year period. Methods: Patients with at least three recurrences of intermediate uveitis per year, defined as relapse of disease after quiescent phase for >3 months after discontinuing all treatments and those with a minimum follow-up of 1 year, were analyzed retrospectively. MMF was initiated with oral steroids and the Standardization of Uveitis Nomenclature guidelines were used to evaluate patients at every visit. Response to treatment, worsening of uveitis, visual benefit, steroid withdrawal rates, and side-effect due to MMF were monitored. Results: Data from 30 eyes of 19 patients were analyzed, of which 10 were men and 11 has bilateral disease. The mean age of presentation was 32.6 +/- 15.4 years and the commonest presenting complaints were floaters (26 eyes). The mean vitreous haze was 3+ at presentation and reduced to 0 at last follow-up (24 eyes). Out of the 30 eyes, 80% had complete resolution of vitreous haze at the end of one year. Worsening intermediate uveitis was seen in six eyes (15.78%). Steroid withdrawal was successful in 85% of eyes. Vision improved in 56% of eyes. None of the patient developed serious systemic complications warranting withdrawal of MMF. Conclusion: MMF in our series was a safe and effective drug in controlling disease and preventing worsening in majority eyes with the most severe forms of intermediate uveitis. Larger studies are required before MMF is widely adopted for the management of recalcitrant intermediate uveitis. | Uveitis, Intermediate |
Essential thrombocythemia (ET) is a clonal disorder of the myeloid stem cell that causes pathologic expansion of the megakaryocytic elements in the bone marrow, with a persistent increase in the platelet count. In order to avoid the mutagenic effects of radioactive phosphorous and alkylating agents, various European clinicians use pipobroman rather than hydroxyurea as single chemotherapeutic treatment, since it is simple and well tolerated and does not lead to hematological complications or the risk of visceral cancer. Here we describe a 63-year-old ET patient who showed myelodysplastic transformation (RAEB-t) of the primary disease after about eight years of therapy with pipobroman at variable dosages. | Pipobroman |
Hyperpolarized metabolites offer a tremendous sensitivity advantage (>10(4) fold) when measuring flux and enzyme activity in living tissues by magnetic resonance methods. These sensitivity gains can also be applied to mechanistic studies that impose time and metabolite concentration limitations. Here we explore the use of hyperpolarization by dissolution dynamic nuclear polarization (DNP) in mechanistic studies of alanine transaminase (ALT), a well-established biomarker of liver disease and cancer that converts pyruvate to alanine using glutamate as a nitrogen donor. A specific deuterated, (13)C-enriched analog of pyruvic acid, (13)C3D(3)-pyruvic acid, is demonstrated to have advantages in terms of detection by both direct (13)C observation and indirect observation through methyl protons introduced by ALT-catalyzed H-D exchange. Exchange on injecting hyperpolarized (13)C3D(3)-pyruvate into ALT dissolved in buffered (1)H(2)O, combined with an experimental approach to measure proton incorporation, provided information on mechanistic details of transaminase action on a 1.5s timescale. ALT introduced, on average, 0.8 new protons into the methyl group of the alanine produced, indicating the presence of an off-pathway enamine intermediate. The opportunities for exploiting mechanism-dependent molecular signatures as well as indirect detection of hyperpolarized (13)C3-pyruvate and products in imaging applications are discussed. | Alanine Transaminase |
As part of the National Institutes of Health Human BioMolecular Atlas Program to develop a global platform to map the 37 trillion cells in the adult human body, we are generating a comprehensive molecular characterization of the female reproductive system. Data gathered from multiple single-cell/single-nucleus and spatial molecular assays will be used to build a 3D molecular atlas. Herein, we describe our multistep protocol, beginning with an optimized organ procurement workflow that maintains functional characteristics of the uterus, ovaries, and fallopian tubes by perfusing these organs with preservation solution. We have also developed a structured tissue sampling procedure that retains information on individual-level anatomic, physiologic, and individual diversity of the female reproductive system, toward full exploration of the function and structure of female reproductive cells. (c) 2023 Wiley Periodicals LLC. Basic Protocol 1: Preparation and preservation of the female reproductive system (ovaries, fallopian tubes, and uterus) prior to procurement Basic Protocol 2: Removal of the female reproductive system en bloc Basic Protocol 3: Postsurgical dissection of ovaries Basic Protocol 4: Postsurgical dissection of fallopian tubes Basic Protocol 5: Postsurgical dissection of cervix Basic Protocol 6: Postsurgical dissection of uterine body Support Protocol 1: OCT-embedded tissue protocol Support Protocol 2: Tissue fixation protocol Support Protocol 3: Snap-frozen tissue protocol Basic Protocol 7: Tissue slice preparation for Visium analysis Support Protocol 4: Hematoxylin and eosin staining for 10X Visium imaging Basic Protocol 8: Manual tissue dissociation for Multiome analysis Basic Protocol 9: Tissue dissociation for Multiome analysis using S2 Singulator. | Urogenital System |
Porcine diarrhea and gastroenteritis are major causes of piglet mortality that result in devastating economic losses to the industry. A plethora of pathogens can cause these diseases, with the transmissible gastroenteritis virus (TGEV) and enterotoxigenic Escherichia coli K88 (ETEC) being two of the most salient. In the December 2017 issue of Proteomics Clinical Aplications, Xia and colleagues used comparative proteomics to shed light on how these microbes interact to cause severe disease . The authors discovered that TGEV induces an epithelial-mesenchymal transition-like phenotype that augments cell adhesion proteins mediating the attachment of ETEC to intestinal epithelial cells. Moreover, coinfection was found to modulate several host proteins that could bolster pathogen persistence. Importantly, the authors observed that ETEC suppresses the production of inflammatory cytokines induced by TGEV, which may in turn promote the long-term survival of both microbes. | Alphacoronavirus |
Glaucoma is an optic neuropathy that results in the progressive loss of retinal ganglion cells (RGCs), which are known to exhibit functional changes prior to cell loss. The electroretinogram (ERG) is a method that enables an objective assessment of retinal function, and the photopic negative response (PhNR) has conventionally been used to provide a measure of RGC function. This study sought to examine if additional parameters from the ERG (amplitudes of the a-, b-, i-wave, as well the trough between the b- and i-wave), a multivariate adaptive regression splines (MARS; a non-linear) model and achromatic stimuli could better predict glaucoma severity in 103 eyes of 55 individuals with glaucoma. Glaucoma severity was determined using standard automated perimetry and optical coherence tomography imaging. ERGs targeting the PhNR were recorded with a chromatic (red-on-blue) and achromatic (white-on-white) stimulus with the same luminance. Linear and MARS models were fitted to predict glaucoma severity using the PhNR only or all ERG markers, derived from chromatic and achromatic stimuli. Use of all ERG markers predicted glaucoma severity significantly better than the PhNR alone (P </= 0.02), and the MARS performed better than linear models when using all markers (P = 0.01), but there was no significant difference between the achromatic and chromatic stimulus models. This study shows that there is more information present in the photopic ERG beyond the conventional PhNR measure in characterizing RGC function. | Electroretinography |
Shelled acanthors (= eggs) of two isolates of Moniliformis moniliformis (Acanthocephala) were tested for their capacity to respond to a hatching stimulus in vitro and for their retention of infectivity to a natural intermediate host (Periplaneta americana). The shelled acanthors were stored for more than 120 weeks (Australian isolate) and for 104 weeks (Texan isolate) together with rat faeces in an incubator maintained at 22.2 +/- 0.1 degrees C. In both cases, infectivity to P. americana was shown to have been retained. In vitro tests of the hatching response were carried out on many occasions during this period of faecal storage. Shelled acanthors continued to respond and no differences were detected either between isolates or within an isolate through time. | Moniliformis |
Infectious bursal disease virus (IBDV) serotype 1 is the causative agent of a highly contagious immunosuppressive disease of young chickens. In the past, a number of antigenic, as well as pathogenic, subtypes have been described. The determination of the antigenic makeup of circulating strains is of vital interest to the poultry industry because changes in the antigenicity of circulating field strains have an impact on the use of vaccines. To obtain a more comprehensive overview of the relationship between the nucleotide and amino acid sequence and the antigenic makeup of field isolates, a system based on reverse genetics of IBDV was established. Using this approach, a database for field isolates from three different states in the United States (Georgia, Alabama, and Louisiana), consisting of nucleotide sequence, amino acid sequence, and a reaction pattern based on a panel of monoclonal antibodies, was established. The obtained results showed that phylogenic analysis, which is based on the similarity of sequences, would lead to false conclusions regarding a possible antigenic makeup of the particular isolate. Sequences of field samples were divided into three groups: 1) those that grouped with variant strain E/Del sequences but were antigenically different, 2) those that did not group with sequences of E/Del but were similar in their antigenic makeup, and 3) those that did not group with E/Del sequences and were antigenically different. In addition, using the reverse-genetics approach, a number of field isolates showed no reactivity with any of the used monoclonal antibodies, indicating that an unknown, antigenic subtype of IBDV serotype 1 is circulating in the field." | Infectious bursal disease virus |
BACKGROUND: Peptic ulcers recur, suggesting that ulcer healing may leave tissue predisposed to subsequent damage. In mice, we have identified that the regenerated epithelium found after ulcer healing will remain abnormal for months after healing. AIM: To determine whether healed gastric mucosa has altered epithelial function, as measured by electrophysiologic parameters. METHOD: Ulcers were induced in mouse gastric corpus by serosal local application of acetic acid. Thirty days or 8 months after ulcer induction, tissue was mounted in an Ussing chamber. Transepithelial electrophysiologic parameters (short-circuit current, I(sc). resistance, R) were compared between the regenerated healed ulcer region and the non-ulcerated contralateral region, in response to luminal hyperosmolar NaCl challenge (0.5 M). RESULTS: In unperturbed stomach, luminal application of hyperosmolar NaCl transiently dropped I(sc) followed by gradual recovery over 2 h. Compared to the starting baseline I(sc), percent I(sc) recovery was reduced in 30-day healing mucosa, but not at 8 months. Prior to NaCl challenge, a lower baseline I(sc) was observed in trefoil factor 2 (TFF2) knockout (KO) versus wild type (WT), with no I(sc) recovery in either non-ulcerated or healing mucosa of KO. Inhibiting Na/H exchanger (NHE) transport in WT mucosa inhibited I(sc) recovery in response to luminal challenge. NHE2-KO baseline I(sc) was reduced versus NHE2-WT. In murine gastric organoids, NHE inhibition slowed recovery of intracellular pH and delayed the repair of photic induced damage. CONCLUSION: Healing gastric mucosa has deficient electrophysiological recovery in response to hypertonic NaCl. TFF2 and NHE2 contribute to I(sc) regulation, and the recovery and healing of transepithelial function. | Trefoil Factor-2 |
Nanophthalmic uveal effusion syndrome (UES) is an extremely rare idiopathic disease characterized by a short axial length of the eye, extremely thick sclera and choroid. These structural changes can lead to spontaneous serous detachment of the retina and peripheral choroid. There are many other causes of UES such as trauma, inflammation, cataract surgery, glaucoma, or retinal detachment. UES is classified into three types. All are characterized by a relapsing-remitting clinical course. The loss of visual acuity ranges from mild to very severe, depending on macular involvement. Changes of the retinal pigment epithelium develop secondary after long-standing choroidal effusion and retinal detachment. Subretinal exudates could be seen and mistakenly diagnosed as chorioretinitis. UES can be very difficult to treat. The most commonly used treatment is surgery involving the creation of surgical sclerostomies (scleral window surgery) or partial thickness sclerectomies to support transscleral drainage. In our case, we present a bilateral nanophthalmic UES, which was misdiagnosed as bilateral ocular Vogt-Koyanagi-Harada disease. We documented the course of the disease and the results of the different surgical approaches in both eyes. A pars plana vitrectomy was performed in the right eye and a sclerectomy with sclerostomies in the left eye. In the left eye, even long lasting loss of visual acuity due to a serous retinal detachment was partially reversed. | Uveal Effusion Syndrome |
This article discusses relevant literature on group sex events--defined as events at which some people have sex with more than one partner--as risk environments, with a particular focus on group sex events where people who take drugs by non-injection routes of administration participate and where the event is not primarily LGBT-identified, at a classic" crack house, nor in a brothel. It also briefly presents some findings from a small ethnography of such events. Group sex participation by people who take drugs by non-injection routes of administration seems to be widespread. It involves both behavioural and network risk for HIV and STI infection, including documented high-risk behaviour and sexual mixing of STI- and HIV-infected people with those who are uninfected. Indeed several HIV and STI outbreaks have been documented as based on such group sex events. Further, group sex events often serve as potential bridge environments that may allow infections to pass from members of one high-risk-behavioural category to another, and to branch out through these people's sexual and/or injection networks to other members of the local community. The ethnographic data presented here suggest a serious possibility of "third party transmission" of infectious agents between people who do not have sex with each other. This can occur even when condoms are consistently used since condoms and sex toys are sometimes used with different people without being removed or cleaned, and since fingers and mouths come into contact with mucosal surfaces of other members of the same or opposite sex. In addition to being risk environments, many of these group sex events are venues where risk-reducing norms, activities and roles are present--which lays the basis for harm reduction interventions. Research in more geographical locations is needed so we can better understand risks associated with group sex events in which drug users participate--and, in particular, how both participants and others can intervene effectively to reduce the risks posed to participants and non-participants by these group sex events. Such interventions are needed and should be developed." | Contraceptive Devices, Male |
Contractile activation in striated muscles requires a Ca(2+) reservoir of large capacity inside the sarcoplasmic reticulum (SR), presumably the protein calsequestrin. The buffering power of calsequestrin in vitro has a paradoxical dependence on [Ca(2+)] that should be valuable for function. Here, we demonstrate that this dependence is present in living cells. Ca(2+) signals elicited by membrane depolarization under voltage clamp were compared in single skeletal fibers of wild-type (WT) and double (d) Casq-null mice, which lack both calsequestrin isoforms. In nulls, Ca(2+) release started normally, but the store depleted much more rapidly than in the WT. This deficit was reflected in the evolution of SR evacuability, E, which is directly proportional to SR Ca(2+) permeability and inversely to its Ca(2+) buffering power, B. In WT mice E starts low and increases progressively as the SR is depleted. In dCasq-nulls, E started high and decreased upon Ca(2+) depletion. An elevated E in nulls is consistent with the decrease in B expected upon deletion of calsequestrin. The different value and time course of E in cells without calsequestrin indicate that the normal evolution of E reflects loss of B upon SR Ca(2+) depletion. Decrement of B upon SR depletion was supported further. When SR calcium was reduced by exposure to low extracellular [Ca(2+)], release kinetics in the WT became similar to that in the dCasq-null. E became much higher, similar to that of null cells. These results indicate that calsequestrin not only stores Ca(2+), but also varies its affinity in ways that progressively increase the ability of the store to deliver Ca(2+) as it becomes depleted, a novel feedback mechanism of potentially valuable functional implications. The study revealed a surprisingly modest loss of Ca(2+) storage capacity in null cells, which may reflect concurrent changes, rather than detract from the physiological importance of calsequestrin. | Calsequestrin |
Membrane rafts (MRs) are specialized microdomains in the cell membrane with an altered lipid composition. Upon various stimulations, MRs can be clustered to aggregate or recruit NADPH oxidase sub-units and related proteins to form MR redox signalosomes in the membrane of cells like vascular endothelial cells (ECs). Multiple protein complexes, like MR redox signalosomes, are now considered to play a crucial role in the regulation of cell function and in the development of different cell dysfunctions. To form such redox signalosomes, ceramide will be generated from the hydrolysis of sphingomyelin by lysosomal acid sphingomyelinase that has been translocated via lysosome fusion to the MR area. In this brief review, current information is provided to help understand the occurrence and function of MR redox signalosomes. This may increase enthusiasm of the scientific community for further studies on the molecular mechanisms and the functional significance of forming such MR redox signalosomes. | Endothelial Cells |
Biocompatible and proteolysis-resistant poly-beta-peptides have broad applications and are dominantly synthesized via the harsh and water-sensitive ring-opening polymerization of beta-lactams in a glovebox or using a Schlenk line, catalyzed by the strong base LiN(SiMe(3) )(2) . We have developed a controllable and water-insensitive ring-opening polymerization of beta-amino acid N-thiocarboxyanhydrides (beta-NTAs) that can be operated in open vessels to prepare poly-beta-peptides in high yields, with diverse functional groups, variable chain length, narrow dispersity and defined architecture. These merits imply wide applications of beta-NTA polymerization and resulting poly-beta-peptides, which is validated by the finding of a HDP-mimicking poly-beta-peptide with potent antimicrobial activities. The living beta-NTA polymerization enables the controllable synthesis of random, block copolymers and easy tuning of both terminal groups of polypeptides, which facilitated the unravelling of the antibacterial mechanism using the fluorophore-labelled poly-beta-peptide. | Anhydrides |
Antibody reactivities to hepatitis C virus (HCV) antigens and to synthetic peptides derived from different parts of the HCV genome (core, NS4, and NS5) were evaluated in HCV-infected hemodialysis patients. In the RIBA 3 assay, NS5 was significantly less recognizable by sera of hemodialysis patients compared to other HCV-infected subjects. Among hemodialysis patients, those coinfected with hepatitis B virus (HBV) (positive for hepatitis B surface antigen [HBsAg+]) showed a reduction in reactivity to C33 and C100. Sera of only 23% of the hemodialysis patients (37 of 161) reacted with more than three of eight peptides tested, significantly fewer than the 60% (12 of 20) of the sera of other HCV-infected patients tested (P = 0.001). This immunosuppression was also manifested by a reduced frequency of recognition of additional peptides on follow-up. An even more reduced reactivity was observed among the HBV-coinfected patients (HBsAg+). The low-responder hemodialysis patients were not infected with any particular genotype of HCV, and the same HCV genotypes observed in the whole group of hemodialysis patients (1a, 1b, 2a, and 3a) were found circulating in the low-responder group. Even in this low-responder population, the good performance of two peptides (peptide 716, corresponding to a portion of the core, and peptide 59, corresponding to a portion of NS4) corroborates the immunodominance of the conserved epitopes within these peptides. | Hepatitis C Antigens |
Members of the Immunoglobulin Superfamily (Ig) present in the surface of rodent mast cells include the high affinity IgE receptor (Fc epsilon RI), the low affinity receptors for the Fc portion of IgG, the Fc gamma RII family and Fc gamma RIII as well as the recently cloned gp49 family that includes three members gp49A, gp49B1 and gp49B2. Fc epsilon RI and Fc gamma RIII are members of the multi-chain immune recognition receptor (MIRR) family since they possess a multimeric structure in which the signal transducing chains (gamma chains) contain six acids that conform the Antigen Homology Receptor 1 Motif (ARH1M), also present in the T cell receptor (TCR) transducing chains. gp49B1, gp49B2 and the FC gamma R family are monomeric chains that also contain the partial of full AHR1M motif in their cytoplasmic domain indicating the capability for signal transduction through tyrosine phosphorylation and the possibility of cell activation with mediator (s) or cytokine (s) release. Distribution of the Fc gamma R receptors and gp49 family members varies in the different stages of mast cell differentiation and maturation. | Receptors, IgG |
Dehydroepiandrosterone (DHEA) and its sulphated metabolite (DHEA-S) are endogenous steroid hormones, synthesized by the adrenal cortex, gonads and CNS. The secretion profile changes with age and depends on the sex. Human DHEA and DHEA-S levels decline linearly and systematically with age and suggest the potential importance of that parameter as a biomarker of ageing. The counteraction of DHEA against atherosclerotic disease, cancer growth, diabetes mellitus, insulin resistance, obesity and the influence on immunological functions are observed in researches. DHEA influences the condition of mind, cognition functions, memory and well-being. DHEA hormonal replacement therapy is expected to lengthen human life by the stoppage of physiological degeneration changes and prevention of age-related clinical disorders. | Dehydroepiandrosterone |
Vascular cognitive impairment, the second most common cause of dementia, profoundly affects hippocampal-dependent functions. However, while the growing literature covers complex neuronal interactions, little is known about the sustaining hippocampal microcirculation. Here we examined vasoconstriction to physiological pressures of hippocampal arterioles, a fundamental feature of small arteries, in a genetic mouse model of CADASIL, an archetypal cerebral small vessel disease. Using diameter and membrane potential recordings on isolated arterioles, we observed both blunted pressure-induced vasoconstriction and smooth muscle cell depolarization in CADASIL. This impairment was abolished in the presence of voltage-gated potassium (K(V)1) channel blocker 4-aminopyridine, or by application of heparin-binding EGF-like growth factor (HB-EGF), which promotes K(V)1 channel down-regulations. Interestingly, we observed that HB-EGF induced a depolarization of the myocyte plasma membrane within the arteriolar wall in CADASIL, but not wild-type, arterioles. Collectively, our results indicate that hippocampal arterioles in CADASIL mice display a blunted contractile response to luminal pressure, similar to the defect we previously reported in cortical arterioles and pial arteries, that is rescued by HB-EGF. Hippocampal vascular dysfunction in CADASIL could then contribute to the decreased vascular reserve associated with decreased cognitive performance, and its correction may provide a therapeutic option for treating vascular cognitive impairment." | Heparin-binding EGF-like Growth Factor |
Botulinum neurotoxins (BoNTs) produced by Clostridia species are the most potent identified natural toxins. Classically, the toxic neurological syndrome is characterized by an (afebrile) acute symmetric descending flaccid paralysis. The most know typical clinical syndrome of botulism refers to the foodborne form. All different forms are characterized by the same symptoms, caused by toxin-induced neuromuscular paralysis. The diagnosis of botulism is essentially clinical, as well as the decision to apply the specific antidotal treatment. The role of the laboratory is mandatory to confirm the clinical suspicion in relation to regulatory agencies, to identify the BoNTs involved and the source of intoxication. The laboratory diagnosis of foodborne botulism is based on the detection of BoNTs in clinical specimens/food samples and the isolation of BoNT from stools. Foodborne botulism intoxication is often underdiagnosed; the initial symptoms can be confused with more common clinical conditions (i.e., stroke, myasthenia gravis, Guillain-Barre syndrome-Miller-Fisher variant, Eaton-Lambert syndrome, tick paralysis and shellfish or tetrodotoxin poisoning). The treatment includes procedures for decontamination, antidote administration and, when required, support of respiratory function; few differences are related to the different way of exposure. | Botulism |
We present a review of the literature on clinical presentations, diagnosis, treatment and prevention of neuroendocrine dysfunctions (NED) in patients with mental disorders during psychopharmacological treatment. Prolactinemia syndrome, metabolic syndrome and dysthyreosis are considered. Risk factors for NED and practical recommendations on diagnostic and therapeutic approaches to NED minimization are presented. | Hyperprolactinemia |
Mucosal mast-cell hyperplasia is frequently observed in intestinal nematode infections and it has been suggested that mast-cell responses to parasite antigens are involved in worm expulsion (self cure). To evaluate the importance of this mechanism, the course of infection and expulsion of Nippostrongylus brasiliensis was compared in mast-cell deficient W/WV and normal (+/+) mice. Initial infectivity rates were similar, but the subsequent kinetics of expulsion of adult worms differed principally in that the onset of expulsion in mast-cell deficient mice appeared to occur 24-36 h later than that in normal mice. Expulsion was complete by the 14th day post infection in both W/WV and normal mice. Worm fertility (as estimated by faecal egg output) also differed in W/WV and normal mice, with maximal egg output in W/WV mice occurring 24 h later than that in normal mice. Although a few mast cells were present in the intestinal mucosa and tongue of W/WV mice, their numbers did not change during the course of infection with N. brasiliensis. In contrast, worm expulsion in normal mice was associated with a moderate increase in numbers of intestinal mast cells, commencing at the onset of expulsion and peaking several days after expulsion was completed. | Nippostrongylus |
Urinary tract and prostatic infections are common in men, and most are treated by primary providers. Acute bacterial prostatitis is caused by uropathogens, presents with a tender prostate gland, and responds promptly to antibiotic therapy. Chronic bacterial prostatitis is a subacute infection, may present with a variety of pelvic pain and voiding symptoms, and is characterized by recurrent urinary tract infections. Effective treatment may be difficult and requires prolonged antibiotic therapy. Nonbacterial prostatitis and chronic pelvic pain syndrome are more common than bacterial prostatitis, and their etiologies are largely unknown. Treatment for both nonbacterial disorders is primarily symptomatic. An underlying anatomic or functional condition usually complicates urinary tract infections in men, but uncomplicated infections occur, often related to sexual activity. Gram-negative bacilli cause most urinary tract and prostate infections. Therapy for prostatic infections requires an agent that penetrates prostatic tissue and secretions, such as trimethoprim-sulfamethoxazole or, preferably, a fluoroquinolone. Duration of antibiotic therapy is typically 1 to 2 weeks for cystitis, 4 weeks for acute bacterial prostatitis, and 6 to 12 weeks for chronic bacterial prostatitis. Long-term suppressive antibiotic therapy and nonspecific measures aimed at palliation may be useful in selected patients with recurrent bacteriuria or persistent symptoms of chronic bacterial prostatitis. | Prostatitis |
Current knowledge of leptospirosis in farmed deer in New Zealand is reviewed. Over the past 25 years, leptospirosis has been reported to occur in individual cases as well as in herd outbreaks in farmed deer and in human cases linked to farmed deer. Serological studies and evidence from bacterial culture suggest infection is widespread. Mixing of young stock from several sources appears to be a significant risk factor for outbreaks. The culture of Leptospira interrogans serovars Hardjobovis, Pomona and Copenhageni has been reported. Infection with serovar Hardjobovis had the highest prevalence, either individually or mixed with serovar Pomona. Infection with serovar Copenhageni appears uncommon and its pathogenicity in deer is unproven. Titres to serovars Australis, Ballum, Balcanica and Tarassovi have been reported. Deer appear to be maintenance hosts for serovar Hardjobovis, incidental or accidental hosts and probably a maintenance population for serovar Pomona, since some infections persist for several months, and accidental hosts for serovar Copenhageni. Serovar Pomona appears to produce clinical and probably subclinical disease, whereas serovar Hardjobovis appears to cause only subclinical disease, although the relative risk of disease causation has not been determined. Clinical disease is usually manifested by haemolysis, jaundice, renal lesions, haemoglobinuria and often by sudden death. Renal lesions are commonly observed at slaughter and many are associated with leptospiral infections. Occupationally, slaughterhouse workers appear to be at greatest risk of contracting the disease from deer. Vaccination produces serological responses, but its effectiveness in protecting against disease, and prevention or reduction of shedding in urine, has not yet been confirmed in deer. More robust knowledge of the epidemiology of leptospiral infections in deer, and the effectiveness of vaccines and vaccination regimes, is needed to assist the deer industry to develop a strategy to manage this disease." | Leptospira interrogans serovar pomona |
INTRODUCTION: Extant literature lack studies on behavioural training or pharmacotherapy in Indian preschool children. With adverse long term outcomes, effective, safe and affordable early interventions for ADHD are a priority. Aim of this prospective study is to report on short term outcome of preschool ADHD with specific focus on safety and tolerability of medications. METHODS: Children with ADHD aged 2.5-6 years were assessed for severity and adverse events at baseline and follow-up using Conner's abbreviated rating scale and Clinical Global Impression-Severity scale. Children with Autism spectrum disorder and those with social quotient less than 50 were excluded. Statistical Analysis included descriptive statistics and Repeated measures ANOVA. RESULTS: Of 56 children recruited, 33.93 %(N = 19) were on behavioural interventions alone, 66.07 %(N = 37) were on a combination of medication and behavioural intervention. All children received treatment according to standard care. The most prescribed drug was clonidine (44.64%), then risperidone (28.7%), methylphenidate (10.7%) and atomoxetine (10.7%). Medication choice was determined by affordability, availability and comorbidity profile. Sedation occurred in 24 % of children on clonidine. Atomoxetine was not well tolerated in 2 children. Methylphenidate was well tolerated. Irrespective of medication choice, all children showed significant improvement at 12 weeks (p < 0.001). CONCLUSIONS: Choice of interventions is largely determined by availability and affordability. There is a need for structured parent behavioural training program deliverable in low resource setting. Anti-ADHD medications should be made available under the NMHP, RBSK program and all government settings in India, to address over-prescription of antipsychotics in preschool ADHD. | Drug Prescriptions |
Infantile hemangioma (IH) is the most common benign vascular tumor of infancy, occurring predominantly in the head and neck. It is characterized by specific endothelial expression of glucose transporter-1 (GLUT-1) and involution with time, spontaneous or on beta-blockers treatment. Although some predisposing factors are known, the exact pathogenesis remains unclear. We report a case of pulmonary IH GLUT-1 positive, initially suspected as a cystic pulmonary airway malformation, in a child presenting with both cardiac and renal malformations. The clinical, radiological, pathological, and genetics findings are discussed with a review of the literature. Although pulmonary IH is a rare lesion, it should be suspected when facing a pulmonary cystic mass in a child. | Single Umbilical Artery |
PURPOSE: Although invasive intracranial devices (IIDs) are the gold standard for intracranial pressure (ICP) measurement, ultrasonography of the optic nerve sheath diameter (ONSD) has been suggested as a potential non-invasive ICP estimator. We performed a meta-analysis to evaluate the diagnostic accuracy of sonographic ONSD measurement for assessment of intracranial hypertension (IH) in adult patients. METHODS: We searched on electronic databases (MEDLINE/PubMed((R)), Scopus((R)), Web of Science((R)), ScienceDirect((R)), Cochrane Library((R))) until 31 May 2018 for comparative studies that evaluated the efficacy of sonographic ONSD vs. ICP measurement with IID. Data were extracted independently by two authors. We used the QUADAS-2 tool for assessing the risk of bias (RB) of each study. A diagnostic meta-analysis following the bivariate approach and random-effects model was performed. RESULTS: Seven prospective studies (320 patients) were evaluated for IH detection (assumed with ICP > 20 mmHg or > 25 cmH(2)O). The accuracy of included studies ranged from 0.811 (95% CI 0.678âÂÂ0.847) to 0.954 (95% CI 0.853âÂÂ0.983). Three studies were at high RB. No significant heterogeneity was found for the diagnostic odds ratio (DOR), positive likelihood ratio (PLR) and negative likelihood ratio (NLR), with I(2) < 50% for each parameter. The pooled DOR, PLR and NLR were 67.5 (95% CI 29âÂÂ135), 5.35 (95% CI 3.76âÂÂ7.53) and 0.088 (95% CI 0.046âÂÂ0.152), respectively. The area under the hierarchical summary receiver-operating characteristic curve (AUHSROC) was 0.938. In the subset of five studies (275 patients) with IH defined for ICP > 20 mmHg, the pooled DOR, PLR and NLR were 68.10 (95% CI 26.8âÂÂ144), 5.18 (95% CI 3.59âÂÂ7.37) and 0.087 (95% CI 0.041âÂÂ0.158), respectively, while the AUHSROC was 0.932. CONCLUSIONS: Although the wide 95% CI in our pooled DOR suggests caution, ultrasonographic ONSD may be a potentially useful approach for assessing IH when IIDs are not indicated or available (CRD42018089137, PROSPERO). | Optic Nerve |
The author has reviewed in this paper the difficulties in developing a more generally accepted test of criminal responsibility. Such difficulties are more clearly seen when studying the applicability of the criminal responsibility test in Canadian law, Section 16, which the author describes as a disguised M'Naghten rule. Finally it is agrued that, because of the strictures encountered in the application of M'Naghten, some alternative routes have been developed at the courtroom level, notably Section 215 of the Criminal Code which deals with provocation. Section 215 gives legal footing to emotional conditions, producing an impairment in an accused's ability to form intent. | Insanity Defense |
The emission rate ((S)) of fibers released from asbestos-cement plates due to mechanical impact was determined experimentally. The emission rate has been defined as a number of fibers (F) emitted from a unit area (m(2)) due to the unit impact energy (J). For fiber longer than 5 microm the obtained surface emission factor for asbestos-cement slabs slightly increased with deteriorating surface, changing from 2.7 x 10(3) F/(m(2)J) for samples with a very good surface to 6.9 x 10(3) F/(m(2)J) for the sample with worn surface (in the SI system the emission rate unit should be (m(-2)J(-1))). The emission rate for short fibers (L < or = 5 microm) was little higher compared with emission of long fibers for all studied asbestos materials. The averaged emission rate for all studied samples was about 5000 and 6000 of long and short fibers, respectively, emitted per square meter (because of the impact energy equal to 1J). The dominating population of emitted fibers ranged from 2 to around 8 microm in length. The second part of this work constitutes the report on the concentration of airborne respirable fibers, and their length distribution in two different groups of homes in Upper Silesia, Poland. Mean concentration level of the respirable fibers, longer than 5 microm, was found to be 850 F/m(3) (according to the SI system the fiber concentration unit is (m(-3))) in the buildings covered with asbestos-cement sheets and 280 F/m(3) in the homes without asbestos-containing facades, located away from other asbestos sources. Although the laboratory and field measurements have been made by using the MIE Laser Fiber Monitor FM-7400 only, the obtained results indicate that the outdoor asbestos-cement building facades are significant sources of airborne fibers inside the dwellings in Upper Silesian towns. | Asbestos |
The energetic properties of N-phenyl-1,2-naphthylamine have been determined using a series of theoretical calculations and their geometries have been optimized using Hartree-Fock (HF) and Density Functional Theory (DFT). The structures have been examined to predict lower-lying energy structure of the title molecule within the considered potential conformations. Structural parameters and energetics, such as total energies with Zero-Point energy corrections, highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energies, have been analyzed and compared between the structural isomers. 1-NPN is the most commonly used molecule for many purposes, mainly as the fluorescent probe in binding assays. When compared the two structures, we showed that 2-NPN isomers are energetically more stable than 1-NPN isomers. It is possible that 2-NPN may be favored in many applications with respect to 1-NPN, and thus its function may be understood in the light of its molecular and structural properties. | 2-Naphthylamine |
Newly installed MHA Chairman Edward B. McRee, president of Ingham Medical Center in Lansing, addressed MHA members and guests during the association's 1991 Annual Corporate Membership Meeting on Mackinac Island this summer, saying the key to success for the association, and for the health care industry in general, lies in our cohesiveness. Following is the text of his remarks to the group. | Public Relations |
BACKGROUND/AIMS: IL-4 is a multifunctional cytokine that is related with the pathological conditions of periodontal disease. However, it is uncertain whether IL-4 could control T cells migration in periodontal lesions. The aim of this study was to examine the effects of IL-4 on CCL11, which is a Th2-type chemokine, and CCL20, which is related with Th17 cells migration, productions from human periodontal ligament cells (HPDLCs). METHODS: CCL20 and CCL11 productions from HPDLCs were monitored by ELISA. Western blot analysis was performed to detect phosphorylations of signal transduction molecules in HPDLCs. RESULTS: IL-1beta could induce both CCL11 and CCL20 productions in HPDLCs. IL-4 enhanced CCL11 productions from IL-1beta-stimulated HPDLCs, though IL-4 inhibited CCL20 production. Western blot analysis showed that protein kinase B (Akt) and signal transducer and activator of transcription (STAT)6 pathways were highly activated in IL-4/IL-1beta-stimulated HPDLCs. Akt and STAT6 inhibitors decreased CCL11 production, but enhanced CCL20 production in HPDLCs stimulated with IL-4 and IL-1beta. CONCLUSIONS: These results mean that IL-4 enhanced Th2 cells migration in periodontal lesion to induce CCL11 production from HPDLCs. On the other hand, IL-4 inhibits Th17 cells accumulation in periodontally diseased tissues to inhibit CCL20 production. Therefore, IL-4 is positively related with the pathogenesis of periodontal disease to control chemokine productions in periodontal lesions. | Chemokine CCL11 |
Malignancies can compromise innate immunity, but the mechanisms of this are largely unknown. Here we found that, via tumor-derived exosomes (TEXs), cancers were able to transfer activated epidermal growth factor receptor (EGFR) to host macrophages and thereby suppress innate antiviral immunity. Screening of the human kinome identified the kinase MEKK2 in macrophages as an effector of TEX-delivered EGFR that negatively regulated the antiviral immune response. In the context of experimental tumor implantation, MEKK2-deficient mice were more resistant to viral infection than were wild-type mice. Injection of TEXs into mice reduced innate immunity, increased viral load and increased morbidity in an EGFR- and MEKK2-dependent manner. MEKK2 phosphorylated IRF3, a transcription factor crucial for the production of type I interferons; this triggered poly-ubiquitination of IRF3 and blocked its dimerization, translocation to the nucleus and transcriptional activity after viral infection. These findings identify a mechanism by which cancer cells can dampen host innate immunity and potentially cause patients with cancer to become immunocompromised. | MAP Kinase Kinase Kinase 2 |
PAP80-2a, purified from Pholiota adiposa mycelia, is a polysaccharide exhibiting prominent antitumor effects. However, the yield of PAP80-2a was low and its structure has not been characterized, impeding the exploration of its structure-function relationship, thus influencing the development of oral drugs for antitumor therapy and immunomodulation. In order to improve the yield of PAP80-2a, response surface methodology along with Box-Behnken design was applied to optimize the ultrasonic-assisted extraction conditions for polysaccharides. Then, the structure of PAP80-2a exhibiting antitumor activity was determined from different angles. The results showed that the extraction yield of P. adiposa polysaccharides increased by 11.5% under optimized ultrasonic extraction conditions. Structural analysis showed that PAP80-2a was mainly composed of glucose, rhamnose, xylose, and galactose in a ratio of 10.00: 2.09: 4.09: 1.13. The total amino acid content in the sugar chain was 69.92 mug/mL. The sugar chain structure was [alpha-Rha (1 --> 3)-]n, and rhamnose was located at the non-reducing end of the sugar chain, while glucose was located at the non-reducing end or in the sugar chain in 1,2,6- and 1,3,6-linked forms. Our study clearly illuminates the primary structure of PAP80-2a, but 3D structure of PAP80-2a and its structure-function relationship is a future challenge. | Pholiota |
INTRODUCTION: Recently, promising results concerning uptake in vivo in tumors of D-amino acids have been published. Therefore, we decided to evaluate the tumor uptake of the D-analogue of [(123)I]-2-iodo-L-tyrosine, a tracer recently introduced by our group into clinical trials. The uptake of 2-amino-3-(4-hydroxy-2-[(123/125)I]iodophenyl)-D-propanoic acid (2-iodo-D-tyrosine) was studied in vitro in LAT1-expressing R1M rat rhabdomyosarcoma cells and in vivo in R1M tumor-bearing Wag/Rij rats. METHODS: The uptake of [(125)I]-2-iodo-L-tyrosine and [(125)I]-2-iodo-D-tyrosine into R1M cells was determined in appropriate buffers, allowing the study of the involved transport systems. In vivo, the biodistribution in R1M-bearing rats of [(123)I]-2-iodo-L-tyrosine and [(123)I]-2-iodo-D-tyrosine was performed by both dynamic and static planar imaging with a gamma camera. RESULTS: In in vitro conditions, the uptake of both [(125)I]-2-iodo-L-tyrosine and [(125)I]-2-iodo-D-tyrosine in the HEPES buffer was 25% higher in the presence of Na(+) ions. In the absence of Na(+) ions, [(125)I]-2-iodo-D-tyrosine was taken up reversibly in the R1M cells, with an apparent accumulation, probably for the larger part by the LAT1 system. Dynamic planar imaging showed that the uptake in the tumors of [(123)I]-2-iodo-D-tyrosine was somewhat lower than that of [(123)I]-2-iodo-L-tyrosine. At 30 min postinjection, the mean differential uptake ratio values of the L- and D-enantiomers are 2.5+/-0.7 and 1.7+/-0.6, respectively. Although the uptake of the D-isomer is lower, probably due to a faster clearance from the blood, the tumor-background ratio is the same as that of the l-analogue. CONCLUSION: A large part (75%) of [(125)I]-2-iodo-D-tyrosine in vitro and [(123)I]-2-iodo-D-tyrosine in vivo is reversibly highly taken up in R1M tumor cells by Na(+)-independent LAT transport systems, more likely by the LAT1. The clearance from the blood of [(123)I]-2-iodo-D-tyrosine in the rats is faster than that of the L-analogue, resulting in a slightly lower tumor uptake but with the same tumor-background ratio. | Monoiodotyrosine |
Following the complete sequencing of the Escherichia coli genome, it has been shown that the proposed second citrate synthase of this organism, recently described by the authors, is in fact a 2-methylcitrate synthase that possesses citrate synthase activity as a minor component. Whereas the hexameric citrate synthase is constitutively produced, the 2-methylcitrate synthase is induced during growth on propionate, and the catabolism of propionate to succinate and pyruvate via 2-methylcitrate is proposed. The citrate synthases of the psychrotolerant eubacterium DS2-3R, and of the thermophilic archaea Thermoplasma acidophilum and Pyrococcus furiosus, are approximately 40% identical in sequence to the Escherichia coli 2-methylcitrate synthase and also possess 2-methylcitrate synthase activity. The data are discussed with respect to the structure, function and evolution of citrate synthase and 2-methylcitrate synthase. | Oxo-Acid-Lyases |
A new lignan, named (8S, 8'S)-2,2',3,3'-tetramethoxy-4'-hydroxy-epoxylignan-4-O-beta-D-glucoside (1), together with eight known compounds (2-9), was isolated from the leaves of P. tectorius. Their structures were elucidated on the basis of spectral characteristics and comparison with the data of literatures. Besides, the absolute configuration of 1 was established by using ECD calculations. The cytotoxicity of 1 in vitro against three selected tumor cell lines (A549, HeLa and MCF-7) was evaluated by MTT assay. The results showed that compound 1 exhibited moderate cytotoxicity against HeLa cell with IC(50) value of 19.30 +/- 4.46 muM. | Pandanaceae |
Although a decline in the all-cause and cardiac mortality rates following myocardial infarction (MI) during the past 3 decades has been reported, MI is a major cause of death and disability worldwide. From a pathological point of view MI consists in a particular myocardial cell death due to prolonged ischemia. After the onset of myocardial ischemia, cell death is not immediate, but takes a finite period of time to develop. Once complete myocytes' necrosis has occurred, a process leading to a healed infarction takes place. In fact, MI is a dynamic process that begins with the transition from reversible to irreversible ischemic injury and culminates in the replacement of dead myocardium by a fibrous scar. The pathobiological mechanisms underlying this process are very complex, involving an inflammatory response by several pathways, and pose a major challenge to ability to improve our knowledge. An improved understanding of the pathobiology of cardiac repair after MI and further studies of its underlying mechanisms provide avenues for the development of future strategies directed toward the identification of novel therapies. The chronologic dating of MI is of great importance both to clinical and forensic investigation, that is, the ability to create a theoretical timeline upon which either clinicians or forensic pathologists may increase their ability to estimate the time of MI. Aging of MI has very important practical implications in clinical practice since, based on the chronological dating of MI, attractive alternatives to solve therapeutic strategies in the various phases of MI are developing. | Ventricular Remodeling |
PURPOSE OF REVIEW: Rapid and effective airway management is priority for trauma patients. Trauma patients are often at an increased risk of experiencing hypoxia, and thus at increased risk of morbidity and mortality. Apneic oxygenation has been widely debated but has been reported to provide benefit in terms of increased peri-intubation oxygen saturation and decreased rates of desaturation. This review aims to evaluate the current literature on the efficacy of apneic oxygenation in the setting of rapid sequence intubation (RSI) in trauma patients. RECENT FINDINGS: Two prospective studies published this year, demonstrated that apneic oxygenation was effective in reducing hypoxic events and hypoxic duration during RSI. SUMMARY: The use of apneic oxygenation can play an important role in preventing hypoxic events in trauma patients undergoing RSI. The use of apneic oxygenation is cheap, and should be considered to reduce hypoxemic events. Additional studies are required to see the effects of apneic oxygenation on outcomes in trauma patients undergoing RSI, specifically desaturation and hypoxemic events and duration, and early onset mortality." | Rapid Sequence Induction and Intubation |
BACKGROUND: Recent studies demonstrate substantial effects of deceptive placebo on experimentally induced sadness, even on autonomic activity. Whether deception is necessary, remains to be elucidated. We investigated the effect of an open-label placebo (OLP) treatment, i.e. an openly administered placebo delivered with a convincing rationale for its sadness-protecting effect. METHODS: Eighty-four healthy females were randomized to an OLP group or a no-treatment control group. All participants received the same detailed information about the OLP effect, only the OLP group received an OLP nasal spray. Before and after the OLP intervention, participants underwent a sad mood induction procedure combining self-deprecating statements (Velten's method) and sad music. Sadness was assessed by the Positive and Negative Affect Schedule (PANAS-X). Autonomic activity was measured continuously. RESULTS: Participants in the OLP group reported a significantly attenuated increase in sadness upon mood induction and less sadness after induction compared to the control group (d = 0.79). Regardless of intervention, heart rate decreased during mood inductions with a more pronounced deceleration in the second mood induction. LIMITATIONS: Generalizability is limited due to the selective sample and the reliance on an experimentally controlled mood induction. CONCLUSION: OLP treatment had a beneficial effect on perceived sadness, at least at the subjective level. Hence, deception may not necessarily be required for placebos to modulate experienced sad mood. Investigating the beneficial effects of OLP in (sub-)clinical samples would seem a promising and required next step towards a clinical use of placebo-associated positive treatment expectations. | Sadness |
Nanoporous electrified surfaces create a unique nonfaradaic electrochemical behavior that is sensitively influenced by pore size, morphology, ionic strength, and electric field modulation. Here, we report the contributions of ion concentration and applied ac frequency to the electrode impedance through an electrical double layer overlap and ion transport along the nanopores. Nanoporous Pt with uniform pore size and geometry (L2-ePt) responded more sensitively to conductivity changes in aqueous solutions than Pt black with poor uniformity despite similar real surface areas and enabled the previously difficult quantitative conductometry measurements at high electrolyte concentrations. The nanopores of L2-ePt were more effective in reducing the electrode impedance and exhibited superior linear responses to not only flat Pt but also Pt black, leading to successful conductometric detection in ion chromatography without ion suppressors and at high ionic strengths. | Electrolytes |
Prohibitive voice behaviors are employees' expressions of concern about practices, incidents, or behaviors that may potentially harm the organization. In this study, we examined a potential biological correlate of prohibitive voice: prenatal exposure to testosterone. In a sample of bankers, we used 2D:4D (i.e., the ratio of the length of the index finger to the length of the ring finger) as a marker for prenatal exposure to testosterone (lower 2D:4D suggests higher prenatal exposure to testosterone). We used a self-report scale to measure prohibitive voice. For low-ranked employees, lower 2D:4D was related to using less voice. No such relation was found for high-ranked employees. Conclusions should be drawn with caution, because the findings only applied to voice regarding the organization as a whole (and not to voice regarding the own team), and because of methodological limitations. However, the findings are consistent with the ideas that (a) people low in 2D:4D tend to strive to attain and maintain social status and that (b) remaining silent about perceived problems in the organization is-at least for low-ranked employees-a means to achieve this goal. | Whistleblowing |
A new method of drying and sterilizing the amnion extends the life of the product to more than nine months and enables it to be stored at room temperature. The bovine amnion is unique and the first of its kind, there being no comparable series in the literature, to our knowledge. Bovine amnion has a large surface area and can provide bulk supplies. The membrane as prepared has been tested in 12 rabbits experimentally and in 70 patients of different ages with a variety of surgical lesions, mainly burns. More than 150 applications of the dried amnion have been made as the sole dressing for these patients. The results indicate that amnion, both human and bovine, is quite safe and effective as a biological dressing. The dried material retains all the physical and biological characteristics of the fresh membrane. | Amnion |
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