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Hantaviruses are tri-segmented lipid-enveloped RNA viruses belonging to the Bunyaviridae family. Human infection corresponds to a zoonosis associated with two different clinical syndromes: hemorrhagic fever with renal syndrome that occurs in Asia and Europe and hantavirus cardiopulmonary syndrome (HCPS) that occurs in the North America, Central America and South America. The major pathogenic mechanisms in HCPS include (1) direct microvascular endothelial injury leading to increased capillary permeability and the development of noncardiogenic pulmonary edema and acute respiratory distress syndrome, and (2) exaggerated host immune response leading to secondary organ damage. The incubation period for this disease is quite long (6-39 days, median: 18 days); however, rapid progression to respiratory failure and shock can occur highlighting the importance of high index of clinical suspicion. Management revolves around high-quality supportive care. Various management and preventative strategies are currently being explored and warrant further examination to improve the overall outlook following infection with hantavirus. | Hantavirus Infections |
Six monkeys self-administered orally delivered phencyclidine (angel dust") and saccharin under concurrent fixed-ratio 16 schedules during daily three-hour sessions. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking spouts. Three saccharin concentrations (0.003%, 0.03% and 0.3%, wt/vol) were tested in a nonsystematic order. For each saccharin concentration, the following series of phencyclidine concentrations (mg/ml) was presented: 0.25, 0.5, 1, 0.25 (retest), 0.125, 0.0625, 0.0312, 0.25 (retest) and 0 (water with stimuli signaling phencyclidine). As the saccharin concentration increased, the number of drug deliveries decreased, and the peaks of the concentration-response functions were shifted to the right. The lowest saccharin concentration (0.003%, wt/vol) maintained responding in excess of phencyclidine levels in only one monkey. The two higher saccharin concentrations maintained behavior far in excess of phencyclidine, but saccharin deliveries decreased in some monkeys as phencyclidine concentration and intake (mg/kg) increased. The time course and patterns of phencyclidine-reinforced responding were also altered when saccharin was concurrently available. The results are discussed in terms of strategies to reduce drug-reinforced behavior, preference between different reinforcers, and measures of reinforcing efficacy." | Saccharin |
In this paper we examine the binding of Escherichia coli transcription termination factor rho to single-stranded RNA. Random polyribonucleotide copolymers containing low ratios of the fluorescent base 1,N6-ethenoadenosine have been synthesized using polynucleotide phosphorylase. Binding of rho to these polynucleotides elicits a significant increase in fluorescence, thus allowing either the direct monitoring of the titration of these polynucleotides with rho or measurement of the competitive displacement of the protein from these probes with other nucleic acids, even in the presence of biologically significant concentrations of ATP. By these techniques, it is shown that the binding site size (n) of rho protein to polynucleotides is 13(+/- 1) nucleotide residues per rho monomer (or 78(+/- 6) nucleotide residues per rho hexamer). Binding constants (K) and co-operativity parameters (omega) for the binding of rho to these polynucleotides have been measured as a function of nucleotide composition and of salt concentration. The results show that the affinity of rho for cytosine residues is quite strong and salt concentration independent, whilst binding to uridine residues is somewhat weaker and very salt concentration dependent. Poly(rC) and poly(dC) bind to rho competitively and with equal affinity and site size, although poly(rC) is the strongest cofactor for activating rho-dependent ATPase and poly(dC) has no ATPase cofactor activity at all. It is also shown that ATP (or ADP or ATP-gamma-S) binding does not change the binding site size of rho on RNA nor decrease its affinity for RNA binding. Circular dichroism measurements of rho binding to phage R17 RNA suggest that the affinity (K omega) of rho for RNA may be increased by ATP. The possible significance of these results for models of rho-dependent transcription termination is discussed in the companion paper. | Rho Factor |
Pancreatic ATP-sensitive K(+) channels (K(ATP)) comprise four inward rectifier subunits (Kir6.2), each associated with a sulphonylurea receptor (SUR1). ATP/ADP binding to Kir6.2 shuts K(ATP). Mg-nucleotide binding to SUR1 stimulates K(ATP). In the absence of Mg(2+), SUR1 increases the apparent affinity for nucleotide inhibition at Kir6.2 by an unknown mechanism. We simultaneously measured channel currents and nucleotide binding to Kir6.2. Fits to combined data sets suggest that K(ATP) closes with only one nucleotide molecule bound. A Kir6.2 mutation (C166S) that increases channel activity did not affect nucleotide binding, but greatly perturbed the ability of bound nucleotide to inhibit K(ATP). Mutations at position K205 in SUR1 affected both nucleotide affinity and the ability of bound nucleotide to inhibit K(ATP). This suggests a dual role for SUR1 in K(ATP) inhibition, both in directly contributing to nucleotide binding and in stabilising the nucleotide-bound closed state. | Sulfonylurea Receptors |
Desferrioxamine (DFX) remains the most effective and safe iron chelator for treatment of patients with transfusional iron overload. It is usually given by intermittent subcutaneous infusions for 8-12 h on 4-6 days weekly using a battery-driven pump. Disposable balloon infusers provide a suitable method of giving continuous subcutaneous infusions with improved patient compliance. For patients with cardiac abnormalities due to iron overload, continuous intravenous desferrioxamine is essential to eliminate toxic plasma non-transferrin bound iron and to reduce body iron stores. Deferiprone (L1, l-2 dimethyl-3hydroxy-pyrid-4-one) is a less effective iron chelator but has the advantage of being orally active. Long-term trials in which patients have taken 75 mg/kg/day have shown that deferiprone is capable of maintaining body iron stores at safe levels in a proportion of thalassaemia major patients but body iron stores, assessed by liver biopsy remain at high levels (> 15.0 mg/g dry weight) in a substantial number of patients. These concentrations have been associated with tissue damage. Trials of increased doses of deferiprone (up to 100 mg/kg/day) or of combined therapy with daily deferiprone and DFX or 1 or 2 days each week are being carried out in an attempt to achieve lower body iron burden in these patients. Preliminary results show that the drugs can be given safely together and urine iron excretion produced is additive, implying that the drugs chelate different body iron pools. Patients previously well chelated with serum ferritin levels less than 2500 micrograms/L have the fewest side-effects from deferiprone and usually may be kept at the same level of body iron for periods of at least 4 years, assessed by serum ferritin and urine iron excretion. The side-effects of deferiprone result in some patients discontinuing therapy. These side-effects, especially arthropathy, mainly occur in previously poorly chelated and so the most heavily iron-loaded patients. Nausea and other gastrointestinal symptoms, agranulocytosis or milder degrees of neutropenia account with arthropathy for nearly all the withdrawals from deferiprone therapy. Patients with cardiomyopathy due to iron overload should be given intravenous DFX rather than deferiprone. Deferiprone, licensed for pharmaceutical use in India, awaits official approval for widespread clinical use in Western Europe and North America. Meanwhile, attempts to find new orally active iron chelators and improved methods of administration of desferrioxamine are in progress. | Iron Chelating Agents |
Migraine is a highly prevalent neurological pain syndrome, and its management is limited due to side effects posed by current preventive therapies. Calcitonin gene-related peptide (CGRP) plays a crucial role in the pathogenesis of migraine. In recent years, research has been dedicated to the development of monoclonal antibodies against CGRP and CGRP receptors for the treatment of migraine. This review will focus on the first US FDA-approved CGRP-receptor monoclonal antibody developed for the prevention of migraine: erenumab. Two Phase II trials (one for episodic migraine and one for chronic migraine) and two Phase III trials for episodic migraine have been published demonstrating the efficacy and safety of erenumab in the prevention of migraine." | Receptors, Calcitonin Gene-Related Peptide |
Using a cross-sectional study, this article addresses end-of-life (EOL) care for older Iranian-American adults. The purposes are twofold: (a) to explore participants' preferences for home or hospital care in the event they face EOL conditions and (b) to learn how participants prefer to communicate these preferences. Results showed that about half of the 130 participants had communicated their EOL care preferences through written documents and/or verbal discussions. A set of factors predicted the preferences (chi(2)(9) = 17.42, p < .042) and communications (chi(2)(9) = 19.54, p = .021). Regression models indicated that higher scores of social support (p = .013) and greater numbers of cohabitants (p = .021) were associated with a preference for home care, and experience of a loved one's death was associated with participants being willing to communicate their preferences for type of care (p = .015). This study can bridge the gap between culturally diverse older adults' preferences and types of EOL care they ultimately receive. | Terminal Care |
Following the finished," euchromatic, haploid human reference genome sequence, the rapid development of novel, faster, and cheaper sequencing technologies is making possible the era of personalized human genomics. Personal diploid human genome sequences have been generated, and each has contributed to our better understanding of variation in the human genome. We have consequently begun to appreciate the vastness of individual genetic variation from single nucleotide to structural variants. Translation of genome-scale variation into medically useful information is, however, in its infancy. This review summarizes the initial steps undertaken in clinical implementation of personal genome information, and describes the application of whole-genome and exome sequencing to identify the cause of genetic diseases and to suggest adjuvant therapies. Better analysis tools and a deeper understanding of the biology of our genome are necessary in order to decipher, interpret, and optimize clinical utility of what the variation in the human genome can teach us. Personal genome sequencing may eventually become an instrument of common medical practice, providing information that assists in the formulation of a differential diagnosis. We outline herein some of the remaining challenges." | Genetic Research |
Theta-gamma network oscillations are thought to represent key reference signals for information processing in neuronal ensembles, but the underlying synaptic mechanisms remain unclear. To address this question, we performed whole-cell (WC) patch-clamp recordings from mature hippocampal granule cells (GCs) in vivo in the dentate gyrus of anesthetized and awake rats. GCs in vivo fired action potentials at low frequency, consistent with sparse coding in the dentate gyrus. GCs were exposed to barrages of fast AMPAR-mediated excitatory postsynaptic currents (EPSCs), primarily relayed from the entorhinal cortex, and inhibitory postsynaptic currents (IPSCs), presumably generated by local interneurons. EPSCs exhibited coherence with the field potential predominantly in the theta frequency band, whereas IPSCs showed coherence primarily in the gamma range. Action potentials in GCs were phase locked to network oscillations. Thus, theta-gamma-modulated synaptic currents may provide a framework for sparse temporal coding of information in the dentate gyrus." | 6-Cyano-7-nitroquinoxaline-2,3-dione |
BACKGROUND: It remains unclear to what extent the brain is affected by Maroteaux-Lamy syndrome (MPS VI), a progressive lysosomal storage disorder. While enzyme replacement therapy (ERT) elicits positive effects, the drug cannot cross the blood-brain barrier. We therefore studied cognitive development and brain abnormalities in the Dutch MPS VI patient population treated with ERT. METHODS: In a series of 11 children with MPS VI (age 2 to 20 years), we assessed cognitive functioning and brain magnetic resonance imaging prospectively at the start of ERT and at regular times thereafter up to 4.8 years. We also assessed the children's clinical characteristics, their siblings' cognitive development, and their parents' educational levels. RESULTS: The patients' intelligence scores ranged from normal to mentally delayed (range test scores 52-131). In 90%, their scores remained fairly stable during follow-up, generally lying in the same range as their siblings' test scores (median for patients = 104, median for siblings = 88) and comparing well with the parental educational levels. Native-speaking patients had higher intelligence test scores than non-native-speaking patients. Two patients, both with high baseline glycosaminoglycan levels in their urine and severe mutations in the arylsulfatase B gene, scored clearly lower than expected. Patients with pY210C performed best. Brain abnormalities were aspecific, occurring more in patients with severe symptoms. CONCLUSION: Our study shows that cognitive development in MPS VI patients is determined not only by familial and social-background factors, but, in patients with a severe form of the disease, also by the disease itself. Therefore in patients with severe disease presentation cognition should be monitored carefully." | N-Acetylgalactosamine-4-Sulfatase |
To investigate global epidemiology of Shigella sonnei, we performed multilocus variable number tandem repeat analysis of 1,672 isolates obtained since 1943 from 50 countries on 5 continents and the Pacific region. Three major clonal groups were identified; 2 were globally spread. Type 18 and its derivatives have circulated worldwide in recent decades. | Shigella sonnei |
Fibromyalgia is a common condition characterized by diffuse musculoskeletal pain and fatigue. The syndrome is defined by the presence of musculoskeletal tender points on physical examination. Additionally, persons with this syndrome have a high incidence of headaches, ocular and vestibular complaints, paresthesias, esophageal dysmotility, allergic" symptoms, irritable bowl syndrome, genitourinary symptoms and affective disorders. Recent research has revealed a number of objective biochemical, hormonal and neurotransmitter abnormalities associated with fibromyalgia, making it a clearly identifiable condition. These abnormalities may clarify our understanding of the pathogenesis and treatment of fibromyalgia." | Fibromyalgia |
Posterior Reversible Encephalopathy Syndrome (PRES) is an acute neurological syndrome clinically characterized by seizures, altered mental status, headache, and visual disturbances. It is caused by a variety of abnormalities in the endothelial function that ultimately result in vasogenic edema in the circulation of the central nervous system. This is reflected by the neuroimaging findings, that most often show reversible parieto-occipital edema. An important proportion of patients with PRES present with Systemic Lupus Erythematosus (SLE), and its complications, as their sole risk factors. This review describes the relationship between these two clinical entities and explains the pathophysiological models that have been proposed to describe the development of PRES. We explain how SLE can cause alterations in every pathway implicated in the development of PRES. Given the relatively high frequency and the distinct clinical course, PRES in the setting of SLE might be best described as a distinct neuropsychiatric syndrome associated with SLE. | Hypertensive Encephalopathy |
Unlike other classical protein tyrosine phosphatases (PTPs), PTPRQ (PTP receptor type Q) has dephosphorylating activity towards phosphatidylinositide (PI) substrates. Here, the structure of the catalytic domain of PTPRQ was solved at 1.56 A resolution. Overall, PTPRQ adopts a tertiary fold typical of other classical PTPs. However, the disordered M6 loop of PTPRQ surrounding the catalytic core and the concomitant absence of interactions of this loop with residues in the PTP loop results in a flat active-site pocket. On the basis of structural and biochemical analyses, it is proposed that this structural feature might facilitate the accommodation of large substrates, making it suitable for the dephosphorylation of PI substrates. Moreover, subsequent kinetic experiments showed that PTPRQ has a strong preferences for PI(3,4,5)P3 over other PI substrates, suggesting that its regulation of cell survival and proliferation reflects downregulation of Akt signalling." | Receptor-Like Protein Tyrosine Phosphatases, Class 3 |
A 69-year-old man with hypogonadism was found to have a 47,XYY karyotype. Clinical and laboratory data revealed acute nonlymphocytic leukemia (ANLL) of the M2 type. The association between the XYY and ANLL-M2 is most likely accidental coincidence. | Sex Chromosome Aberrations |
BACKGROUND: Preterm infants often have long hospital stays and frequent blood tests; they often develop anemia requiring multiple blood transfusions. Placental transfusion via delayed cord clamping (DCC) or umbilical cord milking (UCM) helps increase blood volume. We hypothesized umbilical cord milking (UCM), together with DCC, would be superior in reducing blood transfusions. OBJECTIVES: To compare the effects of DCC and DCC combined with UCM on hematologic outcomes among preterm infants. METHODS: One hundred twenty singleton preterm infants born at 280/7- 336/7 weeks of gestation at Thammasat University Hospital were enrolled in an open-label, randomized, controlled trial. They were placed into three groups (1:1:1) by a block-of-three randomization: DCC for 45 s, DCC with UCM performed before clamping (DCM-B), and DCC with UCM performed after clamping (DCM-A). The primary outcomes were hematocrit levels and number of infants receiving blood transfusions during the first 28 days of life. Intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC) were secondary outcomes. Analyses were performed with an intent-to-treat approach. RESULTS: One hundred twenty preterm infants were randomized. There was no statistically significant difference in neonatal outcomes; hematocrit on admission 54.0 +/- 5.5, 53.3 +/- 6.0, and 54.3 +/- 5.8 (p = 0.88), receiving blood transfusions 25%, 20%, and 12.5% (p = 0.24), incidence of NEC 7.5, 0 and 10% (p = 0.78) in the DCC, DCM-B and DCM-A groups, respectively. There were no preterm infants with severe IVH, polycythemia, maternal or neonatal death. CONCLUSION: The placental transfusion techniques utilized, DCC and DCC combined with UCM, provided the same benefits for preterm infants born at GA 28 and 33 weeks in terms of reducing the need for RBC transfusions, severities of IVH and incidence of NEC without increasing comorbidity. TRIAL REGISTRATION: TCTR20190131002 . Registered 31 January 2019-Retrospectively registered. | Umbilical Cord Clamping |
One of the identifying characteristics of tetrapods (limbed vertebrates) is the presence of fingers and toes. Whereas the proximal part of the tetrapod limb skeleton can easily be homologized with the paired fin skeletons of sarcopterygian (lobe-finned) fish, there has been much debate about the origin of digits. Early hypotheses interpreted digits as derivatives of fin radials, but during the 1990s the idea gained acceptance that digits are evolutionary novelties without direct equivalents in fish fin skeletons. This was partly based on developmental genetic data, but also substantially on the pectoral fin skeleton of the elpistostegid (transitional fish/tetrapod) Panderichthys, which appeared to lack distal digit-like radials. Here we present a CT scan study of an undisturbed pectoral fin of Panderichthys demonstrating that the plate-like 'ulnare' of previous reconstructions is an artefact and that distal radials are in fact present. This distal portion is more tetrapod-like than that found in Tiktaalik and, in combination with new data about fin development in basal actinopterygians, sharks and lungfish, makes a strong case for fingers not being a novelty of tetrapods but derived from pre-existing distal radials present in all sarcopterygian fish. | Fishes |
A new type of fluorogenic and fluorochromic probe based on the reduction of weakly fluorescent 4-azido-6-(4-cyanophenyl)cinnoline to the corresponding fluorescent cinnoline-4-amine was developed. We found that the fluorescence of 6-(4-cyanophenyl)cinnoline-4-amine is strongly affected by the nature of the solvent. The fluorogenic effect for the amine was detected in polar solvents with the strongest fluorescence increase in water. The environment-sensitive fluorogenic properties of cinnoline-4-amine in water were explained as a combination of two types of fluorescence mechanisms: aggregation-induced emission (AIE) and excited state intermolecular proton transfer (ESPT). The suitability of an azide-amine pair as a fluorogenic probe was tested using a HepG2 hepatic cancer cell line with detection by fluorescent microscopy, flow cytometry, and HPLC analysis of cells lysates. The results obtained confirm the possibility of the transformation of the azide to amine in cells and the potential applicability of the discovered fluorogenic and fluorochromic probe for different analytical and biological applications in aqueous medium. | Indicators and Reagents |
Polyvinyl alcohol (PVA) micelles were firstly synthesized by using hemin molecules as novel crosslinked bridges (PVA-H crosslinked micelles). On one hand, the crosslinked micelles can allow high stability against extensive dilution (1800-fold) to reduce side-effects; On the other hand, the bridges not only can destruct by means of laser irradiation (405nm, 200mw), but also can induce the production of singlet oxygen ((1)O(2)) and the release of 5-fluorouracil (5FU) (i.e. 46% release in 360min). But above all, that 5FU-loaded PVA-H crosslinked micelles irradiating by laser is more efficient than PVA-H crosslinked micelles and free 5FU in killing tumor cells, suggest the effective synergistic antitumor effect about chemotherapy and photodynamic therapy (PDT). | Polyvinyls |
Coagulopathy has recently been recognized as a recurring complication of COVID-19, most typically associated with critical illness. There are epidemiological, mechanistic and transcriptomic evidence that link Selenium with SARS-CoV-2's intracellular latency. Taking into consideration the vital role of selenoproteins in maintaining an adequate immune response, endothelial homeostasis and a non-prothrombotic platelet activation status, we propose that impairment in selenocysteine synthesis, via perturbations in the aforementioned physiological functions, potentially constitutes a mechanism of coagulopathy in COVID 19 patients other than those developed in critical illness. | Selenocysteine |
Formation of enveloped viruses involves assembly and budding at cellular membranes. In this study, we elucidated the morphogenesis of hepadnaviruses on the ultrastructural and biochemical level using duck hepatitis B virus (DHBV) as a model system. Formation of virus progeny initiates at the endoplasmic reticulum (ER) and is conserved both in vitro and in vivo. The morphogenesis proceeds via membrane-surrounded vesicles containing both virions and subviral particles, indicating a common morphogenetic pathway. The virus particle-containing vesicles (VCVs) are generated and maintained by reorganization of endomembranes accompanied by a striking disorganization of the rough ER (rER). VCVs are novel organelles with unique identity and properties of ER, intermediate compartment, endosomes, and multivesicular bodies. VCVs are dynamic structures whose size and shape are regulated by both membrane fusion and fission. CONCLUSION: Our data indicate a strong reorganization of endomembranes during DHBV infection, resulting in the biogenesis of novel organelles serving as multifunctional platforms for assembly and budding of virus progeny. | Avihepadnavirus |
AIMS: To investigate the natural history and genotype-phenotype correlation of pantothenate kinase-associated neurodegeneration. METHODS: We collected data of patients with PKAN by searching from available publications in English and Chinese. Patients diagnosed in our center (Peking University First Hospital) were also included. The difference in natural history and genotype between early-onset (<10 year of age at onset) and late-onset patients (>/=10 year of age at onset) with PKAN was compared. RESULTS: A total of 248 patients were included. The median age at onset was 3.0 years in the early-onset group and 18.0 years in the late-onset group. Dystonia in lower limbs was the most common initial symptom in both groups. In the early-onset group, the median interval between the disease onset and occurrence of oromandibular dystonia, generalized dystonia, loss of independent ambulance was 6.0 years, 5.0 years, and 5.0 years. The corresponding values in late-onset group were 1.0 year, 4.0 years, and 6.0 years. About 20.0% died at median age of 12.5 years and 9.5 years after the onset in early-onset group. About 2.0% of the late-onset patients died during the follow-up. A total of 176 mutations were identified. Patients carrying two null alleles in PANK2 showed significantly earlier age of disease onset and progressed more rapidly to loss of independent ambulance. CONCLUSIONS: This study provided a comprehensive review on the natural history and genotype of 248 patients with PKAN. The results will serve as a historical control data for future clinical trial on PKAN. | Neuroaxonal Dystrophies |
Social deprivation in mice switches the role of astrocytes from supporting to inhibiting cognition. | Social Isolation |
Natural compounds have always represented an important source for new drugs. Although fungi represent one such viable source, to date, no fungal metabolite has been marketed as an anticancer drug. Based on our work with phytotoxins as potential chemical scaffolds and our recent findings involving three phytopathogenic fungi, i.e., Cochliobolus australiensis, Kalmusia variispora and Hymenoscyphus fraxineus, herein, we evaluate the in vitro anti-cancer activity of the metabolites of these fungi by MTT assays on three cancer cell models harboring various resistance levels to chemotherapeutic drugs. Radicinin, a phytotoxic dihydropyranopyran-4,5-dione produced by Cochliobolus australiensis, with great potential for the biocontrol of the invasive weed buffelgrass (Cenchrus ciliaris), showed significant anticancer activity in the micromolar range. Furthermore, a SAR study was carried out using radicinin, some natural analogues and hemisynthetic derivatives prepared by synthetic methods developed as part of work aimed at the potential application of these molecules as bioherbicides. This investigation opens new avenues for the design and synthesis of novel radicinin analogues as potential anticancer agents. | Cenchrus |
The automatic control of grammage (basis weight) in paper and board production is based upon on-line grammage measurement. Furthermore, the automatic control of other quality variables such as moisture, ash content and coat weight, may rely on the grammage measurement. The integrity of Kr-85 based on-line grammage measurement systems was studied, by performing basic calibrations with traceably calibrated plastic reference standards. The calibrations were performed according to the EN ISO/IEC 17025 standard, which is a requirement for calibration laboratories. The observed relative measurement errors were 3.3% in the first time calibrations at the 95% confidence level. With the traceable basic calibration method, however, these errors can be reduced to under 0.5%, thus improving the integrity of on-line grammage measurements. Also a standardised algorithm, based on the experience from the performed calibrations, is proposed to ease the adjustment of the different grammage measurement systems. The calibration technique can basically be applied to all beta-radiation based grammage measurements. | Weights and Measures |
The purpose of this study is to examine whether benzyl alcohol affects N-methyl-D-aspartate (NMDA) receptor in cortical cells. Benzyl alcohol (0.5-2 mM) inhibited NMDA-induced cytotoxicity. The protective effect of benzyl alcohol on NMDA-induced toxicity disappeared by washing cells with buffer to remove benzyl alcohol. Benzyl alcohol reduced NMDA receptor-mediated calcium accumulation, indicating that benzyl alcohol inhibits NMDA receptor activity. | Benzyl Alcohol |
Five patients with avulsed scalps were treated with replantation between 1992 and 1998. All patients were women age 20 to 36 years. The percentage of the avulsed scalp ranged from 50% to 100% of the whole scalp. The vessels chosen for anastomosis were the superficial temporal artery, occipital artery, and superficial temporal vein. A vein graft harvested from the cephalic vein of the forearm was performed on the venous and arterial sides in 1 patient. Two patients experienced complete survival of the replanted scalp. Three patients showed 40%, 50%, and 80% survival areas, with the remaining defects resurfaced as split-thickness skin grafts. Six months later, the scar areas in the last 3 patients were reconstructed with an expansion of the normal or replanted scalp. The follow-up period ranged from 1 to 7 years. In 4 patients a partial return of sensation in the replanted scalp and motor function of the frontalis muscle were observed. All patients were satisfied with the aesthetic results of their surgery. | Scalp |
Increasing evidence has linked the humoral immune response with the development of various cancers. Therefore, there is growing interest in investigating the predictive value of antibodies to assess overall and tissue site-specific cancer risk. Given the large amount of antibody types and the broad scope of the search (i.e. cancer risk), the primary aim of this systematic review was to present an overview of the most researched antibodies (i.e. immunoglobulin (Ig) isotypes (IgG, IgM, IgA, and IgE), tumour and self-antigen-reactive antibodies, infection-related antibodies) in relation to overall and site-specific cancer risk. We identified various antibody types that have been associated with the risk of cancer. While no significant associations were found for IgM serum levels, studies found an inconsistent association among IgE, IgA, and IgG serum levels in relation to cancer risk. When evaluating antibodies against infectious agents, most studies reported a positive link with specific cancers known to be associated with the specific agent recognized by serum antibodies (i.e. helicobacter pylori and gastric cancer, hepatitis B virus and hepatocellular carcinoma, and human papillomavirus and cervical cancer). Several reports identified autoantibodies, as single biomarkers (e.g. anti-p53, anti-MUC1, and anti-CA125) but especially in panels of multiple autoantibodies, to have potential as diagnostic biomarkers for specific cancer types. Overall, there is emerging evidence associating certain antibodies to cancer risk, especially immunoglobulin isotypes, tumour-associated antigen-specific, and self-reactive antibodies. Further experimental studies are necessary to assess the efficacy of specific antibodies as markers for the early diagnosis of cancer. | Serum Globulins |
Eight ankles from fresh cadavera were tested under simulated clinical conditions to determine the effect of increasing the size of the posterior malleolar fracture on the contact area of the ankle joint and on the distribution of joint pressure. The surface area of contact decreased with increased size of the posterior malleolar fragment. However, the documented changes were smaller than expected on the basis of the findings of Ramsey and Hamilton; they reported a 42 per cent reduction in contact area with only a one-millimeter lateral shift of the talus, which clinically would be associated with a similar one-millimeter shift of the distal tibial fragment. In addition, clinical experience has shown a high rate of post-traumatic degenerative arthritis associated with an inadequately reduced one-half-size posterior fragment. There were considerable changes in the load-distribution patterns, with increased confluence and concentration of loads as the size of the fragment was increased. In plantar flexion, many specimens had three separate areas of contact between the tibia and the talus. With increased size of the posterior fragment, the three areas of contact always joined to become one. Similarly, for all positions of the ankle, increased size of the posterior fragment caused decreases in the contact area. The maximum loss of contact area was 35 per cent for specimens with one-half-size fractures that were tested in the neutral position. | Ankle Joint |
OBJECTIVE: The purpose of our study was to prospectively compare the cost, effectiveness, and patient tolerance of milk and VoLumen, a 0.1% barium suspension, in patients undergoing abdominal and pelvic CT with oral and i.v. contrast media. SUBJECTS AND METHODS: Two hundred fifteen consecutive outpatients were randomly assigned to receive either whole milk (n = 115) or VoLumen (n = 100). Results were independently reviewed by two radiologists who were blinded to the oral contrast agent used. Degree of bowel distention was qualitatively scored on a 4-point scale, and bowel wall visibility was graded qualitatively on a yes-or-no basis. A questionnaire regarding oral contrast tolerability was provided to each patient. Cost comparison of the two agents was performed. RESULTS: No statistically significant differences were seen between whole milk and VoLumen with respect to degree of bowel distention and mural visualization for all segments of bowel studied (p > 0.05 for both reviewers). Significantly more patients ranked milk as pleasant in taste compared with VoLumen (p < 0.0001). More patients preferred milk compared with VoLumen (p < 0.0001). Milk was better tolerated than VoLumen, with fewer abdominal side effects, including abdominal discomfort (p = 0.019), cramping (p = 0.019), nausea (p = 0.016), and diarrhea (p = 0.0002). The cost per patient for VoLumen is $18 compared with $1.48 for milk. CONCLUSION: Whole milk is comparable to VoLumen with respect to bowel distention and bowel wall visualization and has a lower cost, better patient acceptance, and fewer adverse symptoms. Milk is a cost-effective alternative to VoLumen as a low-attenuation oral contrast agent. | Barium Sulfate |
Complaints of sexual impropriety against healthcare practitioners are escalating. Professionalism in the practitioner-patient relationship and the role-based trust in health care do not allow crossing of sexual boundaries. Communication with patients is key to prevent erroneous allegations of sexual misconduct. The intimate examination is difficult to define. A chaperone present during an intimate examination protects the patient and practitioner and should be considered a risk reduction strategy in practice. | Medical Chaperones |
Clinical and histological characteristics of non polypoid colorectal cancers with an hereditary predisposition are presented. The various known genetic syndromes (hereditary non polyposis colorectal cancers, Lynch syndrome type I and type II, Torre-Muir's syndrome, hereditary flat adenoma syndrome) are discussed to find a possible correlation between this nosological classification and their molecular substratum. The main problem today, is to correctly define the population of hereditary predisposed patients to colon cancer, in order to seek and identify the major responsible gene. Any physician, specialist or not, should be encouraged to give the details of the cancer familial context of his patients, in order to aid the oncologist geneticist in his task. | Genes, APC |
Applications of virtual reality (VR) and augmented reality (AR) assist both health care providers and patients in cardiovascular education, complementing traditional learning methods. Interventionalists have successfully used VR to plan difficult procedures and AR to facilitate complex interventions. VR/AR has already been used to treat patients, during interventions in rehabilitation programs and in immobilized intensive care patients. There are numerous additional potential applications in the catheterization laboratory. By using AR, interventionalists could combine visual fluoroscopy information projected and registered on the patient body with data derived from preprocedural imaging and live fusion of different imaging modalities such as fluoroscopy with echocardiography. Persistent technical challenges to overcome include the integration of different imaging modalities into VR/AR and the harmonization of data flow and interfaces. Cybersickness might exclude some patients and users from the potential benefits of VR/AR. Critical ethical considerations arise in the application of VR/AR in vulnerable patients. In addition, digital applications must not distract physicians from the patient. It is our duty as physicians to participate in the development of these innovations to ensure a virtual health reality benefit for our patients in a real-world setting. The purpose of this review is to summarize the current and future role of VR and AR in different fields within cardiology, its challenges, and perspectives. | Predictive Value of Tests |
Autochthonous outbreaks of chikungunya have occurred in the European Union (EU) after virus introduction by infected travelers. We reviewed the surveillance data of travel-related cases reported in the EU during 2012-2018 to document factors associated with increased infection rates among travelers and to assess how surveillance data could support preparedness against secondary transmission and timely control of outbreaks. Thirteen EU countries reported 2,616 travel-related chikungunya cases. We observed 3 successive epidemiologic periods; the highest number of cases (75%) occurred during 2014-2015, when most cases were associated with the Caribbean and South America. The highest infection rates among travelers were observed during the same phase. Although surveillance of travel-related cases is relevant for estimating the infection risk for travelers, we could not identify a relationship between the number of infected travelers and a higher likelihood of secondary transmission in the EU. | Travel-Related Illness |
A 17-year-old patient with pre-existing grade II spondylolisthesis of L5/S1 sustained a partial disruption of the left sacroiliac joint with haematoma of the iliac muscle after a fall. The haematoma probably led to occlusion of the left ureter, resulting in a urinary tract infection. After initial conservative treatment the patient developed fever and radicular pain of the left leg. Magnetic resonance imaging (MRI) revealed a left-sided epidural abscess at L5/S1, which had probably spread from the infected iliac haematoma along the injured sacroiliac joint. Prompt surgical drainage and antibiotic coverage with cefuroxime and flucloxacillin led to rapid clinical improvement. Staphylococcus aureus was identified as the pathogen. At follow-up 6 months postoperatively all symptoms had resolved, while MRI still revealed residual osseous oedema of the sacroiliac joint. The haematoma of the iliac muscle resolved without surgical intervention. | Perimeningeal Infections |
Human papillomaviruses (HPVs) cause persistent infections in stratified cutaneous and mucosal epithelia. In these infections, the viral DNA replicates as low-copy-number, extrachromosomal, double-stranded-DNA circular plasmids in the nucleus of the dividing basal cells. When the infected cells begin the process of differentiation, the viral DNA amplifies to a high copy number and virions are assembled in the superficial cells. To study HPV DNA replication, our laboratory generates primary keratinocyte cell lines that contain replicating extrachromosomal HPV genomes. Here, we describe protocols to culture human keratinocytes, to transfect viral DNA into cells using electroporation, to determine the efficiency of genome establishment in cells with a colony-forming assay, and to measure the copy number and extrachromosomal status of viral genomes using Southern blotting. These methods can be used to study DNA replication of different oncogenic Alphapapillomavirus HPV types. Published 2021. This article is a U.S. Government work and is in the public domain in the USA. Basic Protocol 1: Electroporation to transfect keratinocytes with recircularized HPV genomes Alternate Protocol: Use of HPV replicon containing selection marker in keratinocyte transfection Support Protocol 1: Rheinwald-Green method of co-culture of irradiated J2 3T3 feeders and human keratinocytes Support Protocol 2: Recircularization of HPV genomes Basic Protocol 2: Quantitative colony formation assay to measure the efficiency of HPV genome establishment Basic Protocol 3: Southern blot analysis of extrachromosomal viral DNA Support Protocol 3: Hirt extraction of low-molecular-weight DNA Support Protocol 4: Qiagen DNeasy Blood & Tissue DNA extraction Support Protocol 5: Generation of a (32) P-labeled HPV DNA probe. | DNA Tumor Viruses |
The physiological tuning and pathophysiological alterations of renal proximal reabsorption of inorganic phosphate can be ascribed to the net amount of the Na/Pi-cotransporter NaPi-IIa localized in the brush border membrane. The net amount of NaPi-IIa appears to be the result of an endocytotic rate regulated by a complex network of different protein kinases. New approaches demonstrated that NaPi-IIa is part of heteromeric protein complexes, organized by PDZ (postsynaptic protein PSD95, Drosophila junction protein Disc-large, tight junction protein ZO-1) proteins. Such complexes are thought to play important roles in the apical positioning and regulated endocytosis of NaPi-IIa and therefore such interactions have to be considered when explaining proximal phosphate ion reabsorption." | Sodium-Phosphate Cotransporter Proteins, Type IIa |
The study was undertaken to evaluate macrophage-derived chemokine (CCL22) levels in the peritoneal fluid (PF) and plasma of patients with ovarian cancer (n = 93) in relation to regulatory T cells (Tregs; n = 75). The peritoneal fluid CCL22 concentrations were significantly higher in epithelial ovarian cancer (EOC) patients than in patients with benign tumors-serous cystadenoma (n = 32). There was no difference in plasma levels of CCL22 in EOC patients compared with the non-cancer and healthy volunteers (n = 10). There were no significant differences in the plasma and PF CCL22 levels based on tumor grade. However, women with stage IV FIGO (International Federation of Gynecologists and Obstetricians) had significantly higher plasma CCL22 levels than patients with stages I and III. Women with stage I FIGO had significantly higher PF CCL22 levels than patients with stages II and III. Women with endometrioid cystadenocarcinoma had higher PF CCL22 levels than women with undifferentiated carcinoma. The percentage of tumor-infiltrating Tregs (11.06 %) was significantly higher compared to PF (3.05 %) and peripheral blood (PB) (2.01 %). Moreover, the percentage of Tregs was higher in the PF than in the PB of EOC patients. There were no significant differences in the PB, PF, and tumor-infiltrating Tregs percentage based on tumor stage, grade, or histology. Elevated levels of CCL22 found in the ascites could create a chemokine gradient aiding in Treg cells migration. Increased Tregs percentage in the local microenvironment of ovarian cancer might be an important mechanism of immunosuppression. | Chemokine CCL22 |
In a phase I study, a monthly regimen of dianhydrogalactitol 60 mg/m2 X 1 day, VP-16-213 60 mg/m2 X 3 days, and cis-platinum 20 mg/m2 X 3 days produced clinically acceptable toxicity. The program is suitable for outpatient administration and may have a role in the management of selected patients with advanced cancer. | Dianhydrogalactitol |
The ever-increasing presence of contaminants in environmental waters is an alarming issue, not only because of their harmful effects in the environment but also because of their risk to human health. Pharmaceuticals and pesticides, among other compounds of daily use, such as personal care products or plasticisers, are being released into water bodies. This release mainly occurs through wastewater since the treatments applied in many wastewater treatment plants are not able to completely remove these substances. Therefore, the analysis of these contaminants is essential but this is difficult due to the great variety of contaminating substances. Facing this analytical challenge, electrochemical sensing based on molecularly imprinted polymers (MIPs) has become an interesting field for environmental monitoring. Benefiting from their superior chemical and physical stability, low-cost production, high selectivity and rapid response, MIPs combined with miniaturized electrochemical transducers offer the possibility to detect target analytes in-situ. In most reports, the construction of these sensors include nanomaterials to improve their analytical characteristics, especially their sensitivity. Moreover, these sensors have been successfully applied in real water samples without the need of laborious pre-treatment steps. This review provides a general overview of electrochemical MIP-based sensors that have been reported for the detection of pharmaceuticals, pesticides, heavy metals and other contaminants in water samples in the past decade. Special attention is given to the construction of the sensors, including different functional monomers, sensing platforms and materials employed to achieve the best sensitivity. Additionally, several parameters, such as the limit of detection, the linear concentration range and the type of water samples that were analysed are compiled." | Molecularly Imprinted Polymers |
OBJECTIVES: Mikulicz's disease (MD) was considered to be a subtype of Sjogren's syndrome (SS), based on histopathological similarities. However, recent studies have indicated that patients with MD show high serum IgG4 concentration, and suggested that MD is one of IgG4-related disease" and distinguishable from SS. Therefore, we clinically and histopathologically examined the disease states of MD and SS in detail. MATERIALS AND METHODS: Twenty patients with Mikulicz's disease and 18 with SS were comparatively studied to determine clinical characteristics in MD patients. RESULTS: Sialography in MD patients did not show the "apple-tree sign" typically seen in SS. Serologically, high serum IgG4 levels but not anti-SS-A or anti-SS-B antibodies were observed in MD. SS showed lymphocytic infiltration of various subsets with atrophy or severe destruction of the acini, while MD showed selective infiltration of IgG4+ plasma cells with hyperplastic germinal centers and mild acini destruction. Corticosteroid treatment of MD reduced IgG and IgG4 levels and improved salivary function. A negative correlation between disease duration and increasing rate of salivary flow was observed in MD. CONCLUSIONS: These results suggested that the pathogenesis of MD might be different from those of SS. CLINICAL RELEVANCE: early diagnosis and treatment of MD is important for the improvement of salivary function." | Mikulicz' Disease |
Experiments were designed to determine the influence of the endothelium on the relaxing potency of the nitrovasodilator SIN-1. Rings of coronary arteries were suspended for isometric-tension recording in organ chambers filled with modified Krebs-Ringer bicarbonate solution, aerated with 95% O2-5% CO2 and warmed to 37 degrees C. The experiments were performed in the presence of indomethacin and propranolol in order to inhibit cyclooxygenase and beta-adrenoceptors, respectively. In rings contracted with prostaglandin F2 alpha, SIN-1 caused concentration-dependent relaxations that were increased following endothelium removal. In rings denuded of endothelium, the relaxations evoked by SIN-1 were not affected by NG-monomethyl-L-arginine (L-NMMA, which inhibits the production of endothelium-derived relaxing factor), or by superoxide dismutase and catalase (scavengers of oxygen-derived free radicals), or by L-NMMA plus superoxide dismutase and catalase. In rings with endothelium, relaxations evoked by SIN-1 were increased significantly by L-NMMA or by superoxide dismutase and catalase, and were increased further by the combination of L-NMMA plus superoxide dismutase and catalase. The difference in potency of SIN-1 between arterial rings with and without endothelium was reduced by either L-NMMA or by superoxide dismutase and catalase, and was abolished by the combination of L-NMMA plus superoxide dismutase and catalase. Therefore, the inhibitory interaction between SIN-1 and the endothelium may result from an endothelium-dependent production of oxygen-derived free radicals that may inactivate the nitric oxide generated by SIN-1, and from an inhibitory interaction between SIN-1 and endothelium-derived relaxing factor, released under basal conditions. | Molsidomine |
Confirmation experiments on colony formation of M. leprae on the M-Y 14b agar medium developed by Murohashi and Yoshida were carried out for two years independently by individual members of an organized research group, according to the method described by Murohashi and Yoshida. The results obtained can be summarized as follows: a) No colony production by M. leprae on M-Y 14b agar medium was seen. b) No increase in the number of cells of M. leprae on M-Y 14b agar medium during cultivation was seen. c) Light and electron microscopic observation indicated that there was an increase in the number of non-solid bacterial cells and ghost cells with time of cultivation. d) It was found by mouse foot pad inoculation that four of six samples of M. leprae used as inocula were definitely viable. e) By means of mouse foot pad inoculation, it was shown that viability of M. leprae inoculated onto M-Y 14b agar medium was lost within approximately seven weeks of cultivation. From these results, can be definitely concluded that there is no evidence indicating that multiplication of M. leprae took place on M-Y 14b agar medium. | Mycobacterium leprae |
INTRODUCTION: The complications of the open-wedge osteotomy technique (slope, hypo- and hypercorrection and fractures) are related to difficulties in the control of the open-wedge angle during surgery. MATERIALS AND METHODS: In this cadaveric study, we evaluated the safety and precision of a novel system, the Realignment High Control System (RHC), in the correction of knee mechanical axis and slope. The RHC has a fixation plate coupled to a dynamic device that opens the osteotomy continuously, allowing plate fixation before osteotomy wedge opening. RESULTS: All procedures were easily performed, with no fractures. The openings equaled the indicated by the navigation system for 7.5 degrees and 10 degrees , and for 5 degrees , there was a statistically, although not clinically significant, difference of 0.6 degrees . The slope shown by the RHC setting and in the navigation system was significantly different for the 10 degrees setting only, with a mean difference of 0.563 degrees . CONCLUSIONS: RHC facilitates the surgical technique of high tibial osteotomy, with gradual wedge opening, precise correction of the mechanical axis, and appropriate control of the tibial slope, even with larger openings. | Osteotomy |
It has been found that damage to a tissue of a rabbit or a rat, such as results from a skin incision or an incision through the skin and muscles into the abdominal cavity, is followed 24 hr later by a significant increase in the concentration of leucogenenol in the animal's serum. Likewise, loss of approximately one-quarter to one-half of the blood in the circulation of rabbits or rats causes an increase 24 hr later in the animals' serum leucogenenol concentration. | Leucogenenol |
Leg injuries on dairy cows are a common and highly visible welfare concern on commercial dairy farms. With greater attention being placed on food animal welfare and limited research being conducted on tiestall farms, this study aimed to identify prevalence and risk factors for hock and knee injuries on dairy cows housed in tiestall barns in Ontario (n=40) and Quebec (n=60). A sample of 40 cows was purposively selected per farm and several animal- and farm-based measures were taken. Both hocks and both knees on each cow were scored as injured (presence of lesions or swelling) or not injured (no alterations or hair loss), and the highest score of each of the 2 knees and the 2 hocks was considered the cow's hock or knee score. Possible animal- and farm-based risk factors were incorporated into 2 separate multivariable logistic models for hock injuries and knee injuries respectively at the cow level. Mean (+/-SD) percentage of cow with hock injuries per farm was found to be 56+/-18% and mean percentage of knee injuries per farm was found to be 43+/-23%. Animal-based factors found to be associated with a greater odds of hock injuries at the cow level were increased days in milk (DIM), lower body condition score (BCS), lameness, higher parity, higher cow width, median lying bout duration, and median number of lying bouts. Environmental factors found to be associated with hock injuries at the cow level were province, stall width, tie rail position, stall base, chain length, and age of stall base. Animal-based factors found to be associated with knee injuries at the cow level were DIM, BCS, and median lying time. Environmental factors found to be associated with knee injuries at the cow level were stall width, chain length, province, stall base, and bed length. Quadratic and interaction terms were also identified between these variables in both the hock and knee models. This study demonstrates that hock and knee injuries are still a common problem on tiestall dairy farms in Canada. Several animal- and housing-based factors contribute to their presence. Further research to confirm causal relationships between these factors would help identify the cause of knee and hock injuries and determine how to best reduce the incidence of injuries in cows on commercial tiestall dairy farms in Canada. | Tarsus, Animal |
Prediction of primary stability is a major challenge in the surgical planning of dental and orthopedic implants. Computational methods become attractive to estimate primary stability from clinical CT images, but implicit finite element analysis of implant press-fit faces convergence issues due to contact and highly distorted elements. This study aims to develop and validate an explicit finite element method to simulate the insertion and primary stability of a rigid implant in a deformable bone while accounting for damage occurring at the bone-implant interface. Accordingly, a press-fit experiment of a conical implant into predrilled bovine trabecular bone was designed and realized for six samples. A displacement-driven cyclic protocol was used to quantify the reaction force and stiffness of the bone-implant system. Homogenized finite element analyses of the experiments were performed by modeling contact with friction and converting an existing constitutive model with elasto-plasticity and damage of bone tissue to be applicable to an explicit time integration scheme where highly distorted elements get deleted. The computed reaction forces and unloading stiffnesses showed high correlations (R(2) = 0.95 and R(2) = 0.94) with the experiment. Friction between bone and implant exhibited a strong influence on both reaction force and stiffness. In conclusion, the developed explicit finite element approach with frictional contact and element deletion accounts properly for bone damage during press-fit and will help optimizing dental or orthopedic implant design towards maximal primary stability. | Bone-Implant Interface |
In vitro binding of zinc to proteins of the human ejaculate and of the various male accessory gland secretions was evaluated. The proteins were separated by sodium dodecyl sulfate gel electrophoresis and transferred to nitrocellulose filters that were subsequently incubated with 65ZnCl2. High levels of zinc binding were observed to approximately 20 protein bands (14 to 70 kDa) of the coagulated seminal plasma. There was only low binding to proteins of the spermatozoa and virtually no binding to any protein of the epididymal and prostatic fluids. When sperm liquefaction was allowed to occur, 65ZnCl2 binding to high-molecular weight proteins decreased rapidly, and after 15 min only the binding to proteins of molecular weights less than 25 kDa remained. In addition, zinc concentration was determined both in the centrifugate and in the supernatant after centrifugation of the coagulum. Zinc concentrations in the centrifugate and the supernatant were, respectively, 147 +/- 72 micrograms/g and 31 +/- 22 micrograms/g. The whole supernatant contained only 12% +/- 4% of total sperm zinc. Finally, in highly viscous sperm samples the concentration of zinc was not significantly different from that in normally liquefying sperm (167 +/- 87 micrograms/ml compared to 188 +/- 107 micrograms/ml). The main extracellular targets of prostatic zinc in humans are the secreted seminal vesicle proteins. The role of this binding remains unknown, however, because no direct relationship could be established between the concentrations of this metal and the phenomena of coagulation and liquefaction. | Seminal Proteins |
A hot spring is a distinctive aquatic environment that provides an excellent system to investigate microorganisms and their function in elemental cycling processes. Previous studies of terrestrial hot springs have been mostly focused on the microbial community, one special phylum or category, or genes involved in a particular metabolic step, while little is known about the overall functional metabolic profiles of microorganisms inhabiting the terrestrial hot springs. Here, we analyzed the microbial community structure and their functional genes based on metagenomic sequencing of six selected hot springs with different temperature and pH conditions. We sequenced a total of 11 samples from six hot springs and constructed 162 metagenome-assembled genomes (MAGs) with completeness above 70% and contamination lower than 10%. Crenarchaeota, Euryarchaeota and Aquificae were found to be the dominant phyla. Functional annotation revealed that bacteria encode versatile carbohydrate-active enzymes (CAZYmes) for the degradation of complex polysaccharides, while archaea tend to assimilate C1 compounds through carbon fixation. Under nitrogen-deficient conditions, there were correspondingly fewer genes involved in nitrogen metabolism, while abundant and diverse set of genes participating in sulfur metabolism, particularly those associated with sulfide oxidation and thiosulfate disproportionation. In summary, archaea and bacteria residing in the hot springs display distinct carbon metabolism fate, while sharing the common energy preference through sulfur metabolism. Overall, this research contributes to a better comprehension of biogeochemistry of terrestrial hot springs. | Hot Springs |
Temperature is a fundamental thermodynamic property that can serve as a probe of biochemical reactions. Extracellular thermometry has previously been used to probe cancer metabolism and thermoregulation, with measured temperature changes of ~1-2 K in tissues, consistent with theoretical predictions. In contrast, previous intracellular thermometry studies remain disputed due to reports of >1 K intracellular temperature rises over 5 min or more that are inconsistent with theory. Thus, the origins of such anomalous temperature rises remain unclear. An improved quantitative understanding of intracellular thermometry is necessary to provide a clearer perspective for future measurements. Here, we develop a generalizable framework for modeling cellular heat diffusion over a range of subcellular-to-tissue length scales. Our model shows that local intracellular temperature changes reach measurable limits (>0.1 K) only when exogenously stimulated. On the other hand, extracellular temperatures can be measurable (>0.1 K) in tissues even from endogenous biochemical pathways. Using these insights, we provide a comprehensive approach to choosing an appropriate cellular thermometry technique by analyzing thermogenic reactions of different heat rates and time constants across length scales ranging from subcellular to tissues. Our work provides clarity on cellular heat diffusion modeling and on the required thermometry approach for probing thermogenic biochemical pathways. | Thermometry |
This work sought correlates of pitch perception, defined by neural activity above the lower limit of pitch (LLP), in auditory cortical neural ensembles, and examined their topographical distribution. Local field potentials (LFPs) were recorded in eight patients undergoing invasive recordings for pharmaco-resistant epilepsy. Stimuli consisted of bursts of broadband noise followed by regular interval noise (RIN). RIN was presented at rates below and above the LLP to distinguish responses related to the regularity of the stimulus and the presence of pitch itself. LFPs were recorded from human cortical homologues of auditory core, belt, and parabelt regions using multicontact depth electrodes implanted in Heschl's gyrus (HG) and Planum Temporale (PT), and subdural grid electrodes implanted over lateral superior temporal gyrus (STG). Evoked responses corresponding to the temporal regularity of the stimulus were assessed using autocorrelation of the evoked responses, and occurred for stimuli below and above the LLP. Induced responses throughout the high gamma range (60-200â¯Hz) were present for pitch values above the LLP, with onset latencies of approximately 70â¯ms. Mapping of the induced responses onto a common brain space demonstrated variability in the topographical distribution of high gamma responses across subjects. Induced responses were present throughout the length of HG and on PT, which is consistent with previous functional neuroimaging studies. Moreover, in each subject, a region within lateral STG showed robust induced responses at pitch-evoking stimulus rates. This work suggests a distributed representation of pitch processing in neural ensembles in human homologues of core and non-core auditory cortex. | Electrocorticography |
Particles suspended in non-Newtonian liquids flowing in channels may migrate transversally to the main flow direction as a result of normal stress gradients. Viscoelasticity-induced migration has proven to be an efficient mechanism to promote 3D flow-focusing in cylindrical microchannels, avoiding the need for complex and expensive apparati. In this work, we demonstrate the existence of a single dimensionless number (Theta) that governs the migration dynamics of particles in viscoelastic liquids flowing in micropipes at low Deborah numbers (Deborah number is the ratio of fluid and flow characteristic times). The definition of Theta in terms of the relevant fluid, flow and geometrical quantities is obtained by generalizing the particle migration velocity expression given in previous asymptotic analytical theories through numerical simulations. An extensive experimental investigation quantitatively confirms the novel predictions: the experimental particle distributions along the channel axial direction collapse on a single curve when rescaled in terms of the proposed dimensionless number. The results reported in this work give a simple and general way to define the flow-focusing conditions promoted by viscoelastic effects. | Povidone |
In a study of the HL-A system in 56 selected asbestos workers referred to the Pneumoconiosis Medical Panel with definite or suspected asbestosis, the W 27 antigen was found more often than among a control population. Six of the 10 asbestos workers with the W 27 antigen had definite radiographic evidence of asbestosis compared to 13 out of 46 without the W 27 antigen. These observations, if confirmed, suggest that the W 27 antigen may provide a useful marker of an enhanced susceptibility to the tissue-damaging effects of asbestos dust. | Asbestosis |
A ribozyme based gene control element enabled the spatio-temporal regulation of gene function in mammalian cell culture with light. | Toyocamycin |
The 5-lipoxygenase pathway is responsible for the production of leukotrienes--inflammatory lipid mediators that have a role in innate immunity, but that can also have pathological effects in inflammatory diseases. Recently, a potential link between leukotriene production and atherosclerosis has been proposed. The expression of leukotriene biosynthetic enzymes and leukotriene receptors has been identified in coronary and carotid atherosclerotic plaques, and the levels of biosynthetic enzymes have been correlated with the clinical symptoms of unstable plaques. Genetic variants in 5-lipoxygenase pathway genes have also been associated with a relative risk of developing myocardial infarction and stroke. On the basis of these discoveries, antileukotriene compounds are now being evaluated for the treatment of cardiovascular disease. Several tool compounds have been shown to limit the progression of lesion development in preclinical models of atherosclerosis, and three compounds, including two drugs previously developed for asthma, are undergoing clinical trials in patients with acute coronary syndromes. | Lipoxygenase Inhibitors |
The first derivation of human embryonic stem cells brought with it a clear understanding that animal models of human disease might be replaced by an unlimited supply of human cells for research, drug discovery, and drug development. With the advent of clinical trials using human pluripotent stem cell-based therapies, it is both timely and relevant to reflect on factors that will facilitate future translation of this technology. Human pluripotent cells are increasingly being used to investigate the molecular mechanisms that underpin normal and pathological human development. Their differentiated progeny are also being used to identify novel pharmaceuticals, to screen for toxic effects of known chemicals, and to investigate cell or tissue transplantation strategies. The intrinsic assumption of these research efforts is that the information gained from these studies will be more accurate, and therefore of greater relevance, than traditional investigations based on animal models of human disease and injury. This review will therefore evaluate how animals and animal-derived products are used for human pluripotent stem cell research, and will indicate how efforts to further reduce or remove animals and animal products from this research will increase the clinical translation of human pluripotent stem cell technologies through drug discovery, toxicology screening, and cell replacement therapies. | Pluripotent Stem Cells |
OBJECTIVES: This study aimed (a) to determine the views of pediatric nurses regarding their roles and responsibilities in the implementation of child rights in healthcare services and children's right to participate in implementations related to their treatment and care, and (b) to examine the relation between these views and sociodemographic features. METHOD: This cross-sectional study included 335 pediatric nurses recruited in public hospitals in a province located in the Eastern Black Sea Region of Turkey. The data were collected using a digital questionnaire that included variables to determine the sociodemographic features of the participants and their views on the implementation of child rights in healthcare services and children's right to participate in decision-making about their health and care. The final number of the participants in this study was 321 nurses (96% of the population). RESULTS: Most of the participants stated that they agreed with the implementation of child rights in healthcare services adopted by UNICEF. However, the participants' views on the implementation of child rights in healthcare services were affected by variables such as age, gender, marital status, level of education, the state of having children, and the number of years in the profession. Overall, 87.9% of the participants stated that children had the right to participate in the decision-making about their own health and care at an early age. the variables of marital status, educational level, the state of having children, and number of years in the profession affected the participants' views about children's right to actively participate in their health care. CONCLUSION: The majority of pediatric nurses agreed with the implementation of child rights in healthcare services. Moreover, the variables of age, gender, marital status, educational level, the state of having children, and the number of years in the profession were significantly relevant to the views of pediatric nurses regarding child rights. | Right to Health |
BACKGROUND: The use of non-surgical treatment for childhood obstructive sleep apnea (OSA) is gaining popularity, especially in children with mild disease. OBJECTIVE: To test the hypothesis that intranasal corticosteroids reduce disease severity in children with mild OSA. STUDY DESIGN: A randomized, double-blinded, placebo-controlled trial of intranasal mometasone furoate (MF) versus placebo in children aged 6 to 18 years with mild OSA. The primary outcome was the change from baseline obstructive apnea hypopnea index (OAHI), as documented by overnight polysomnography, after four months of treatment. RESULTS: Sixty-two children were recruited but 12 dropped out. This left 24 and 26 children for final analysis in the MF and placebo group, respectively. The OAHI and oxygen desaturation index (ODI) improved significantly in the MF group only. The OAHI decreased from 2.7 +/- 0.2 to 1.7 +/- 0.3 in the MF group, but increased from 2.5 +/- 0.2 to 2.9 +/- 0.6 in the placebo group (p = 0.039). The mean changes in ODI in the MF group and placebo group were -0.6 +/- 0.5 and +0.7 +/- 0.4, respectively (p = 0.037). CONCLUSION: Four months of treatment with intranasal mometasone furoate effectively reduces the severity of mild OSA in children. | Mometasone Furoate |
Cardiac development is comprised of a series of morphological events tightly controlled both spatially and temporally. The molecular pathways controlling early cardiac differentiation are poorly understood, but Wnt signaling is emerging as a critical pathway for multiple aspects of early cardiovascular development. The Wnt pathway plays multiple roles in regulating cellular behavior including proliferation, differentiation, cell migration, and cell polarity. Recent data have demonstrated that Wnt activity is important for early precardiac mesoderm differentiation but must be inhibited in subsequent steps for cardiomyocyte differentiation to proceed. Given the important role that Wnt signaling plays in both the differentiation of cardiomyocytes from pluripotential stem cells and tissue regeneration in general, an increased understanding of this pathway is likely to enhance our knowledge about both cardiovascular development and reparative mechanisms. | Wnt2 Protein |
Forty-one pregnant sheep showing positive immune responses to Brucella melitensis in serological or allergic tests were selected from naturally infected flocks and kept in an isolated pen for lambing. The resulting 62 lambs were maintained in the same pen with their dams during lactation. When the lambs were weaned, the dams were slaughtered for bacteriological study and the lambs were reared in a clean pen. Fourteen ewes excreted B melitensis during lactation and 17 were found to be infected postmortem, B melitensis was not isolated from seven lambs (three born to infected dams) which died after birth or from eight seronegative lambs (four born to infected dams) which were slaughtered between two and seven months after weaning. However, one permanently seropositive lamb born to a culture-negative dam was found to be infected when necropsied five months after weaning. The remaining 46 lambs were reared until adulthood and slaughtered at intervals for bacteriological study. Four ewe lambs (two born to culture-negative dams) were found to be infected postmortem, but were negative in immunological tests for B melitensis. | Brucella melitensis |
BACKGROUND: The internal mammary artery is used widely as a conduit for coronary artery bypass grafting. Most practicing cardiac surgeons are unaware of an aberrant side branch, the lateral costal artery (LCA), that arises proximally. Unligated, this side branch has been held responsible for early recurrence of angina in a small number of patients in the literature. In this study we identified the incidence and length of the LCA. METHODS: We studied 103 patients who had coronary artery bypass grafting with bilateral internal mammary arteries. The presence or absence of an LCA was noted, and a record was made of the number of intercostal spaces traversed. RESULTS: Thirty-one of 103 patients had an LCA on one or the other side. Twenty-five patients had bilateral LCAs in which length was equal on both sides in 18. Median length was two intercostal spaces (range, one to six). The LCA extended to the fifth space or beyond in 5 patients. CONCLUSIONS: The LCA was present in one third of patients who had coronary artery bypass grafting. A few patients had vessels sizable enough to raise concerns about recurrence of angina. It is prudent to exclude the presence of an LCA in all patients who have cardiac operations. | Mammary Arteries |
Misdiagnosis may result from biopsy site selection, technique, or choice of transport media. Important potential sources of error include false-negative direct immunofluorescence results based on poor site selection, uninformative biopsy specimens based on both site selection and technique, and spurious interpretations of pigmented lesions and nonmelanoma skin cancer based on biopsy technique. Part I of this 2-part continuing medical education article addresses common pitfalls involving site selection and biopsy technique in the diagnosis of bullous diseases, vasculitis, panniculitis, connective tissue diseases, drug eruptions, graft-versus-host disease, staphylococcal scalded skin syndrome, hair disorders, and neoplastic disorders. Understanding these potential pitfalls can result in improved diagnostic yield and patient outcomes." | Staphylococcal Scalded Skin Syndrome |
BACKGROUND: Oxygen is essential for life, and investigation of the skin's oxygen environment and identification of its effects on the skin may lead to the discovery of new antiaging targets. To understand individual skin differences and age-related changes, we developed a noninvasive method using near infrared spectroscopy (NIRS) to measure the regional saturation of oxygen (rSO(2) ) of human skin. MATERIALS AND METHODS: To construct an NIRS sensor probe specialized for skin measurement, the distance between the sensor transmitter and receiver was optimized based on data for the thickness of the facial skin to the subcutaneous fat layer. To analyze the relationship between skin oxygen saturation and body oxygen saturation, rSO(2) was measured by NIRS, oxygen saturation of peripheral artery (SpO(2) ) was measured by pulse oximeter, and physical conditions were considered, such as body mass index (BMI) and muscle mass, in Japanese women (age 20s-60s). RESULTS: Both skin rSO(2) and SpO(2) varied among individuals and decreased with age. Only SpO(2) showed a relationship with BMI and muscle mass, whereas rSO(2) showed no relationship with these physical conditions. No relationship between rSO2 and SpO(2) was observed. CONCLUSION: Individual and age-related differences in skin by rSO(2) values were found by NIRS optimized for local skin; however, the factors affecting rSO(2) differed from those affecting SpO(2) , and further study is needed. | Oxygen Saturation |
Elucidating the mechanisms that modulate calcium channels via opioid receptor activation is fundamental to our understanding of both pain perception and how opioids modulate pain. Neuronal voltage-gated N-type calcium channels (Cav2.2) are inhibited by activation of G protein-coupled opioid receptors (ORs). However, inhibition of R-type (Cav2.3) channels by mu- or kappa-ORs is poorly defined and has not been reported for delta-ORs. To investigate such interactions, we coexpressed human mu-, delta-, or kappa-ORs with human Cav2.3 or Cav2.2 in human embryonic kidney 293 cells and measured depolarization-activated Ba(2+) currents (IBa). Selective agonists of mu-, delta-, and kappa-ORs inhibited IBa through Cav2.3 channels by 35%. Cav2.2 channels were inhibited to a similar extent by kappa-ORs, but more potently (60%) via mu- and delta-ORs. Antagonists of delta- and kappa-ORs potentiated IBa amplitude mediated by Cav2.3 and Cav2.2 channels. Consistent with G protein betagamma (Gbetagamma) interaction, modulation of Cav2.2 was primarily voltage-dependent and transiently relieved by depolarizing prepulses. In contrast, Cav2.3 modulation was voltage-independent and unaffected by depolarizing prepulses. However, Cav2.3 inhibition was sensitive to pertussis toxin and to intracellular application of guanosine 5'-[beta-thio]diphosphate trilithium salt and guanosine 5'-[gamma-thio]triphosphate tetralithium salt. Coexpression of Gbetagamma-specific scavengers-namely, the carboxyl terminus of the G protein-coupled receptor kinase 2 or membrane-targeted myristoylated-phosducin-attenuated or abolished Cav2.3 modulation. Our study reveals the diversity of OR-mediated signaling at Cav2 channels and identifies neuronal Cav2.3 channels as potential targets for opioid analgesics. Their novel modulation is dependent on pre-existing OR activity and mediated by membrane-delimited Gbetagamma subunits in a voltage-independent manner. | Calcium Channels, R-Type |
High-throughput RNA sequencing (RNA-seq) analysis of samples from Mallotus japonicus, a traditional medicinal plant, yielded two novel RNA viruses tentatively named Mallotus japonicus virus A (MjVA) and Mallotus japonicus virus B (MjVB). The MjVA and MjVB genomes encode proteins showing amino acid sequence similarities to those of poleroviruses (the genus Polerovirus, the family Solemoviridae) and amalgaviruses (the genus Amalgavirus, the family Amalgaviridae), respectively. The MjVA genome contains seven highly overlapping open reading frames, which are translated to seven proteins through various translational mechanisms, including -1 programmed ribosomal frameshifting (PRF) at the slippery motif GGGAAAC, non-AUG translational initiation, and stop codon readthrough. The MjVB genome encodes two proteins; one of which is translated by +1 PRF mechanism at the slippery motif UUUCGN. The abundance analysis of virus-derived RNA fragments revealed that MjVA is highly concentrated in plant parts with well-developed phloem tissues as previously demonstrated in other poleroviruses, which are transmitted by phloem feeders, such as aphids. MjVB, an amalgavirus generally transmitted by seeds, is distributed in all samples at low concentrations. Thus, this study demonstrates the effectiveness and usefulness of RNA-seq analysis of plant samples for the identification of novel RNA viruses and analysis of their tissue distribution. Keywords: Polerovirus; Amalgavirus; Mallotus japonicus; RNA virus; viral genome; programmed ribosomal frameshifting. | Mallotus Plant |
Plants that perform the Crassulacean acid metabolism (CAM), which obtain CO(2) overnight and convert it mainly in malic acid, successfully grow in environments with water and nutrient shortages, that is partly associated with their higher water- and nitrogen-use efficiencies. Water and nutrient limitations can impair photosynthesis through the reduction of RuBisCO and increment of photorespiration, disturbing the plant carbon balance. In this context, we conducted a controlled experiment with the epiphytic C(3)-CAM bromeliad Guzmania monostachia to investigate how the combined water and nutritional deficits affect the activity of RuBisCO and its activation state (RAS), and to evaluate the efficiency of photosynthesis during the transition from C(3) to CAM. Apart from an increase in CAM activity, bromeliads submitted to both water and nutritional deficits showed higher RAS values and unaltered RuBisCO activity compared to C(3) bromeliads and, surprisingly, the maximum quantum efficiency of photosynthesis increased. Glucose, fructose and starch levels were maintained, while sucrose concentrations increased over time. These results, combined with the high RAS values, suggest an increased efficiency of RuBisCO functioning. Our results reinforce the ability of epiphytic bromeliads to deal with stressful habitats by a higher efficiency of RuBisCO during the transition to CAM, another feature that may allow their evolution in the epiphytic environment. | Bromeliaceae |
The exceptionally high prevalence of diastrophic dysplasia in Finland has enabled us to analyse the foot deformities of 102 patients at their first orthopaedic evaluation and classify 204 feet into five categories. The most common finding (43%) was a foot with tarsal valgus deformity and metatarsus adductus; 37% showed either equinovarus adductus (29%) or equinus (8%) deformities. At the first examination 13% showed metatarsus adductus deformity alone, and 7% were clinically normal. The expression 'club foot', generally used for the foot deformity in diastrophic dysplasia is a misnomer. There is a wide spectrum of deformities, some of them specific for the condition. | Foot Deformities, Congenital |
STUDY DESIGN: Prospective evaluation of a new suspension test to determine curve flexibility in adolescent idiopathic scoliosis (AIS) in comparison with erect side-bending. OBJECTIVE: To verify whether the suspension is a better method than side-bending to estimate curve reducibility and to assess spine flexibility. SUMMARY OF BACKGROUND DATA: Spinal flexibility is a decisive biomechanical parameter for the planning of AIS surgery. Side-bending is often referred as the gold standard, but it has a low reproducibility and there is no agreement amongst surgeons about the most advantageous method to use. Even more, every technique evaluates reducibility instead of flexibility since the forces involved in the change in shape of the spine are not considered. METHODS: Eighteen patients scheduled for AIS surgery were studied. Preoperative radiological evaluation consisted of 4 radiographs: standing posteroanterior, left and right erect side-bending, and suspension. The side-bending and the suspension tests were compared on the basis of the apical vertebrae derotation and the scoliosis curve reduction. Frontal and axial flexibility indices, expressed as the ratio between the moment induced by the body weight and the reduction, were calculated from the suspension data. RESULTS: The average scoliosis curve reduction and apical vertebra derotation were 21 degrees (37%) and 3 degrees (12%), respectively for erect side-bending and 26 degrees (39%) and 7 degrees (28%), respectively for suspension. The erect side-bending test generated a larger curve reduction (P = 0.05) when considering the moderate curves only and the suspension test (P = 0.02) when considering the severe curves. The suspension test produced a larger axial derotation (P = 0.007) when considering all the curves. The average traction force during suspension was 306 N (187 N-377 N). The average estimation for the frontal flexibility index was 1.64 degrees/Nm (0.84-2.82) and 0.51 degrees/Nm (0.01-1.39) for the axial flexibility index. CONCLUSION: Results of this study demonstrate the feasibility to really evaluate the spine flexibility with the suspension test. The estimated flexibility values are realistic and similar to those reported in vitro. Suspension should be used in the future for spine flexibility assessment. | Arthrography |
This report is the first published case of cerebral melioidosis in the western hemisphere. In this paper the authors review the literature on neurological melioidosis and its presentation and treatment in endemic areas, describe the clinical course of this unique case of a presentation of the disease with cranial abscess in the US, review the pathological and radiological findings associated with this seminal case, and put forth recommendations for recognizing and treating possible future instances of the disease within the western hemisphere. | Melioidosis |
Evolution has endowed all humans with a continuum of innate, hard-wired, automatically activated defense behaviors, termed the defense cascade. Arousal is the first step in activating the defense cascade; flight or fight is an active defense response for dealing with threat; freezing is a flight-or-fight response put on hold; tonic immobility and collapsed immobility are responses of last resort to inescapable threat, when active defense responses have failed; and quiescent immobility is a state of quiescence that promotes rest and healing. Each of these defense reactions has a distinctive neural pattern mediated by a common neural pathway: activation and inhibition of particular functional components in the amygdala, hypothalamus, periaqueductal gray, and sympathetic and vagal nuclei. Unlike animals, which generally are able to restore their standard mode of functioning once the danger is past, humans often are not, and they may find themselves locked into the same, recurring pattern of response tied in with the original danger or trauma. Understanding the signature patterns of these innate responses--the particular components that combine to yield the given pattern of defense-is important for developing treatment interventions. Effective interventions aim to activate or deactivate one or more components of the signature neural pattern, thereby producing a shift in the neural pattern and, with it, in mind-body state. The process of shifting the neural pattern is the necessary first step in unlocking the patient's trauma response, in breaking the cycle of suffering, and in helping the patient to adapt to, and overcome, past trauma. | Perceptual Defense |
Membranous nephropathy is a major cause of nephrotic syndrome of non-diabetic origin in adults. It is the second or third leading cause of end-stage renal disease in patients with primary glomerulonephritis, and is the leading glomerulopathy that recurs after kidney transplantation (occurring in about 40% of patients). Treatment with costly and potentially toxic drugs remains controversial and challenging, partly because of insufficient insight into the pathogenesis of the disease and absence of sensitive biomarkers of disease activity. The disease is caused by the formation of immune deposits on the outer aspect of the glomerular basement membrane, which contain podocyte or planted antigens and circulating antibodies specific to those antigens, resulting in complement activation. In 2002, podocyte neutral endopeptidase was identified as an antigenic target of circulating antibodies in alloimmune neonatal nephropathy, and in 2009, podocyte phospholipase A2 receptor (PLA2R) was reported as an antigenic target in autoimmune adult membranous nephropathy. These major breakthroughs were translated to clinical practice very quickly. Measurement of anti-PLA2R antibodies in serum and detection of PLA2R antigen in glomerular deposits can now be done routinely. Anti-PLA2R antibodies have high specificity (close to 100%), sensitivity (70-80%), and predictive value. PLA2R detection in immune deposits allows for retrospective diagnosis of PLA2R-related membranous nephropathy in archival kidney biopsies. These tests already have a major effect on diagnosis and monitoring of treatment, including after transplantation. | Receptors, Phospholipase A2 |
The clinical immunology laboratory is primarily concerned with tests for diagnosing disease and monitoring the therapy and course of diseases mediated by immune mechanisms. In the future, the immunology laboratory will provide test services on a disease-oriented basis and will utilize assays of humoral and cellular immunity, as well as other assays based on molecular techniques. The laboratory scientist will work closely with clinicians and provide interactive consultation. The major factors that will influence future laboratory tests are: (a) governmental regulations, (b) healthcare economics, (c) advances in technology, and (d) advances in development and use of therapeutic agents. Here I discuss the interplay of these factors and their likely effect on the future role of the immunology laboratory. | Chemistry, Clinical |
Systemic lupus erythematosus (SLE) is a chronic disease caused by an aberrant autoimmune response, with a large spectrum of clinical manifestations. It strikingly affects women. Recent papers reveal that the men with Klinefelter syndrome (47, XXY) have a higher incidence of lupus than the men in the general population, similar with that of genotypic females. On the other hand, there is a great lack of information regarding the association of SLE with Turner syndrome, but it seems to be a lower risk for females with Turner to develop SLE. We present a rare association of a Turner syndrome with SLE, with negative immunology for SLE and with diagnosis made on renal biopsy. These data suggest that the presence of two X chromosomes may predispose to SLE, the ligand (CD40 ligand) for one of the genes that contributes to the pathogenesis of SLE being located on the X chromosome." | Methylprednisolone Hemisuccinate |
Lewy body dementia (LBD) is the second most common dementia after Alzheimer's disease (AD). LBD is characterized clinically by visual hallucinations, extrapyramidal symptoms, cognitive fluctuations and neuroleptic sensitivity. LBD and AD share many common features in pathology, genetics and biochemical alterations; however, correct clinical distinction between these disorders has prognostic and therapeutic implications. There are currently no definitive radiological or biological markers for LBD, but studies suggest that premorbid differences in cognitive domains and personality traits, differences in clinical presentation, and alterations in autonomic function and sleep may improve diagnosis. Cholinergic dysfunction plays a major role in both AD and LBD; however, dysfunction is greater in LBD. This may account for the more prominent hallucinations, and offers the possibility of a greater response to cholinesterase inhibitors in LBD. The treatment of LBD is symptomatic and is based on a limited number of clinical trials and extension of results from trials in AD. Current research is focused on the role of synuclein aggregation with possible roles for synuclein-derived peptides as aggregation inhibitors. Other approaches target amyloid, neuroinflammation, oxidative injury, proteolysis, lipid peroxidation and immunotherapies with variable results. Improved understanding of disease mechanisms may open new therapeutic avenues for LBD in the future. | Lewy Body Disease |
CONTEXT: Both short and long interpregnancy intervals (IPIs) have recently been associated with increased risk of autism spectrum disorder (ASD). However, this association has not been systematically evaluated. OBJECTIVE: To examine the relationship between birth spacing and the risk of ASD and other neurodevelopmental disabilities. DATA SOURCES: Electronic databases from their inception to December 2015, bibliographies, and conference proceedings. STUDY SELECTION: Observational studies with results adjusted for potential confounding factors that reported on the association between IPIs or birth intervals and neurodevelopmental disabilities. DATA EXTRACTION: Two reviewers independently extracted data on study characteristics, IPIs/birth intervals, and outcome measures. RESULTS: Seven studies (1 140 210 children) reported an association between short IPIs and increased risk of ASD, mainly the former subtype autistic disorder. Compared with children born to women with IPIs of >/=36 months, children born to women with IPIs of <12 months had a significantly increased risk of any ASD (pooled adjusted odds ratio [OR] 1.90, 95% confidence interval [CI] 1.16-3.09). This association was stronger for autistic disorder (pooled adjusted OR 2.62, 95% CI 1.53-4.50). Three of these studies also reported a significant association between long IPIs and increased risk of ASD. Short intervals were associated with a significantly increased risk of developmental delay (3 studies; 174 940 children) and cerebral palsy (2 studies; 19 419 children). LIMITATIONS: Substantial heterogeneity, and few studies assessing neurodevelopmental disabilities other than ASD. CONCLUSIONS: Short IPIs are associated with a significantly increased risk of ASD. Long IPIs also appear to increase the risk of ASD. | Birth Intervals |
Seventy-three patients were asked to fill in a questionnaire to determine whether a laryngectomee can be rehabilitated better with the oesophageal voice or with the vibrator voice. This evaluation showed no significant difference between these two methods of voice rehabilitation. Patients rehabilitated with the vibrator learn oesophageal voice in addition without undue difficulties. Therefore, we recommend voice rehabilitation of the laryngectomee by both the above methods. | Speech, Alaryngeal |
This study was undertaken to identify the role of scavenger receptors in the catabolism of lipopolysaccharide (LPS) and lipoteichoic acid (LTA). LPS is mainly cleared from the blood by the liver. The Kupffer cells are primarily responsible for this clearance. Although several binding sites have been described for LPS and LTA, only CD14 is involved in LPS signalling. Scavenger receptor type A (SR-A) is expressed in the liver on endothelial cells and Kupffer cells, and macrosialin (class D scavenger receptor) is expressed on Kupffer cells. Fucoidin and poly-I are both good inhibitors of scavenger receptors. Fucoidin significantly reduced the serum clearance of [125I]-LPS and decreased liver uptake of [125I]-LPS by approximately 40%. Poly-I inhibited the binding of [125I]-LPS to isolated Kupffer and endothelial cells by 75%, while poly-A, a polyanionic substrate that does not block scavenger receptors, had no effect. LPS significantly inhibited the binding of acetylated LDL and oxidized LDL (two well-described scavenger receptor ligands) to isolated Kupffer and liver endothelial cells. OxLDL and acLDL did not affect the binding of LPS to these cells. We conclude that on both endothelial cells and Kupffer cells, LPS mainly binds to scavenger receptors, but SR-A and macrosialin contribute to a limited extent to the binding of LPS. Injection of LTA into C57Bl6 mice resulted in a maximal liver uptake of 20% of the injected dose. In the liver, 50% was bound by the Kupffer cells, 20% by parenchymal cells and 30% by liver endothelial cells. The contribution of SR-A to the plasma clearance of LTA was limited. A main component in the catabolism of LTA is the interaction of LTA with plasma lipoproteins, which limit the uptake of LTA by tissues and extend the plasma half-life of LTA. | Scavenger Receptors, Class D |
The ability of the rat brain to activate the phosphorothionate insecticide parathion to its potent anticholinesterase metabolite paraoxon in situ was observed by ligating the posterior portion of the circulatory system and thus removing the liver from the circulation. Under these conditions no acetylcholinesterase inhibition was observed in 15 min at a dosage of parathion (nominally 2.4 mg/kg) which yielded 95% inhibition when the liver was in the circulation. However, at a higher dose (nominally 48 mg/kg) there was substantial (about 70%) inhibition of brain acetylcholinesterase after 15 min, suggesting that the brain does have the ability to activate parathion in the intact situation. | Parathion |
Endometriosis, a condition in which uterine tissue grows outside the uterus, is a debilitating disease, affecting millions of women and costing the United States approximately $78 billion annually in pain- related disability. It is also the leading cause of chronic pelvic pain (CPP), which is often unresponsive to existing treatments. Adolescent women with the disease are at particular risk as there are often significant diagnostic delays, which in turn can exacerbate pain. Research and treatment guidelines for adolescents with endometriosis are largely based on studies for adult women due to the limited number of studies focusing on adolescents. The current paper critically reviews the literature as it pertains to endometriosis pathophysiology, mechanisms contributing to CPP, and treatment implications and recommendations with a focus on gaps related to adolescents. | Pelvic Pain |
beta-escin is a mixture of triterpene saponins isolated from the horse chestnut seeds (Aesculus hippocastanum L.). The anti-edematous, anti-inflammatory and venotonic properties of beta-escin have been the most extensively clinically investigated effects of this plant-based drug and randomized controlled trials have proved the efficacy of beta-escin for the treatment of chronic venous insufficiency. However, despite the clinical recognition of the drug its pharmacological mechanism of action still remains largely elusive. To determine the cellular and molecular basis for the therapeutic effectiveness of beta-escin we performed discovery and targeted proteomic analyses and in vitro evaluation of cellular and molecular responses in human endothelial cells under inflammatory conditions. Our results demonstrate that in endothelial cells beta-escin potently induces cholesterol synthesis which is rapidly followed with marked fall in actin cytoskeleton integrity. The concomitant changes in cell functioning result in a significantly diminished responses to TNF-alpha stimulation. These include reduced migration, alleviated endothelial monolayer permeability, and inhibition of NFkappaB signal transduction leading to down-expression of TNF-alpha-induced effector proteins. Moreover, the study provides evidence for novel therapeutic potential of beta-escin beyond the current vascular indications. | Escin |
Mutations in the interdomain linker of the gene for the AraC regulatory protein of Escherichia coli that severely interfere with the protein's ability either to repress or to activate transcription have been found. These mutations have relatively small effects on the dimerization domain's ability to bind arabinose or to dimerize the protein or on the DNA-binding domain's affinity for a single DNA half-site. The linker mutations, however, dramatically change the affinity of AraC for binding to two direct-repeat DNA half-sites. Less dramatically, the induction-deficient linker variants also display altered DNA sequence selectivity. These results show that changing the sequence of the interdomain linker can profoundly affect the dimerization domain-DNA-binding domain interactions in AraC. The smaller effects on the functions of the individual domains could be the direct result of the linker alterations but more likely are the indirect result of the altered dimerization domain-DNA-binding domain interactions. In summary, the linker does not simply function as a passive and flexible connector between the domains of AraC but, instead, is more directly involved in the protein's dimerization domain-DNA-binding domain interactions. | AraC Transcription Factor |
OBJECTIVE: We hypothesized that academic adult cardiac surgeons (CSs) and general thoracic surgeons (GTSs) would have distinct practice patterns of, not just case-mix, but also time devoted to outpatient care, involvement in critical care, and work relative value unit (wRVU) generation for the procedures they perform. METHODS: We queried the University Health System Consortium-Association of American Medical Colleges Faculty Practice Solution Center database for fiscal years 2007-2008, 2008-2009, and 2009-2010 for the frequency of inpatient and outpatient current procedural terminology coding and wRVU data of academic GTSs and CSs. The Faculty Practice Solution Center database is a compilation of productivity and payer data from 86 academic institutions. RESULTS: The greatest wRVU generating current procedural terminology codes for CSs were, in order, coronary artery bypass grafting, aortic valve replacement, and mitral valve replacement. In contrast, open lobectomy, video-assisted thoracic surgery wedge, and video-assisted thoracic surgery lobectomy were greatest for GTSs. The 10 greatest wRVU-generating procedures for CSs generated more wRVUs than those for GTSs (P<.001). Although CSs generated significantly more hospital inpatient evaluation and management (E & M) wRVUs than did GTSs (P<.001), only 2.5% of the total wRVUs generated by CSs were from E & M codes versus 18.8% for GTSs. Critical care codes were 1.5% of total evaluation and management billing for both CSs and GTSs. CONCLUSIONS: Academic CSs and GTSs have distinct practice patterns. CSs receive greater reimbursement for services because of the greater wRVUs of the procedures performed compared with GTSs, and evaluation and management coding is a more important wRVU generator for GTSs. The results of our study could guide academic CS and GTS practice structure and time prioritization. | Thoracic Surgical Procedures |
BACKGROUND: Preterm birth (PTB) remains a significant cause of neonatal morbidity and mortality. Women with a prior PTB are at risk for recurrent PTB. Treatment with 17-alpha hydroxyprogesterone caproate (17OHP-C) has become standard of care for women with prior PTB to help reduce this risk. Factors that affect a woman's decision to use this medication are largely unknown. OBJECTIVE: The objective of our study was to investigate patient-level barriers to 17OHP-C. We studied a cohort of women eligible for 17OHP-C with the hypothesis that 17OHP-C is underutilized and certain patient characteristics, such as obstetrical history, influence its use. STUDY DESIGN: A cross-sectional study of all women seen at a specialty prematurity clinic from 2009 through 2013 was performed. Women with a singleton pregnancy were included if they had a prior spontaneous PTB (sPTB). The chi(2) tests were performed for univariate analyses. Multivariable logistic regression was used to control for confounders. RESULTS: In all, 243 women had 17OHP-C recommended to them based on obstetrical history. There were 218 women with a pregnancy during our study period that were included in our analysis. A total of 163 (74.7%) had documented 17OHP-C use. Women were more likely to accept 17OHP-C if they had a history of a second-trimester loss only (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.17-4.58) or received recommendation for cerclage due to a short cervical length (OR, 4.12; 95% CI, 1.55-10.99). Women with a prior full-term birth were less likely to accept 17OHP-C (OR, 0.48; 95% CI, 0.26-0.89), especially when the prior full-term birth was subsequent rather than prior to the PTB (OR, 0.19; 95% CI, 0.08-0.47). Race, obesity, and insurance status did not impact 17OHP-C use. There was no difference in the rate of sPTB between those who used and did not use 17OHP-C (37.2 vs 34.0%, P = .7). CONCLUSION: Obstetric history impacted 17OHP-C use. This study identifies biases regarding 17OHP-C at the patient level and can be used to develop strategies to increase its use. However, the similarity in the sPTB rate between users and nonusers highlights the importance of identifying specific populations where 17OHP-C is and is not effective in preventing PTB. | 17-alpha-Hydroxyprogesterone |
Nerve sheath tumors of the upper extremity are among the common neoplastic pathologies encountered by hand surgeons. A majority of these tumors are benign schwannomas or neurofibromas and may be associated with neurofibromatosis. Clinical signs of malignant transformation include new onset of pain and rapid growth. Imaging characteristics, such as standardized uptake value greater than 4.0 on PET scan, may aid in the diagnosis of a malignant tumor. Surgical excision, often with intrafascicular dissection with nerve preservation, is recommended treatment of benign lesions. Wide surgical excision is recommended for malignant lesions. | Neoplasms, Nerve Tissue |
[18F]-5-fluorocytosine-arabinoside (2) and [18F]-5-fluorocyclocytidine (4) were prepared by reaction of [18F]-acetylhypofluorite with cytosine-arabinoside (1) or cyclocytidine (3) in acetic acid and were isolated in an overall radiochemical yield of 20% and 9%, respectively. The biodistribution of both radiopharmaceuticals was determined in melanoma bearing Syrian golden hamsters. It was found that 2 is a good tumour-localizing agent for pigmented and non-pigmented Greene melanoma. | Ancitabine |
The clinical importance of a reliable human serum vitamin B12 assay to aid the diagnosis of pernicious anemia (PA) cannot be overemphasized. Our review of the literature indicates that a reference method for the quantitation of serum vitamin B12 (serum B12) with the required accuracy, precision and rapidity has not been reported to-date. Controversies, debates and criticisms over human serum B12 assays (especially commercial kits) have been common-place. Various methods of quantitation of B12 reviewed in this communication include: microbiological, radioisotopic, high-performance liquid chromatography (HPLC) and the most recent radioimmunoassay (RIA) techniques. This review attempts to provide awareness of the limitations of these methods and establishes the base for eventual development of a B12 reference method in our laboratory. | Intrinsic Factor |
Loomis' mountain mint, Pycnanthemum loomisii Nuttall, is a species of mint native to the American Southeast. In the present study, 38 odorants were identified employing aroma extract dilution analysis (AEDA) performed on a distillate prepared by solvent extraction and solvent-assisted flavor evaporation (SAFE) distillation of dried P. loomisii. Seven odorants with flavor dilution (FD) factors >/=16 were quantitated using stable isotope dilution assays (SIDA), and their odor activity values (OAV) were calculated. In addition, the stereochemical composition of chiral odorants was also determined by chiral chromatography. Odor simulation experiments demonstrated that when 1,8-cineole (eucalyptus; OAV 6400), linalool (floral, citrus; OAV 120), beta-ionone (floral, violet; OAV 86), borneol (earthy; OAV 56), and eugenol (clove; OAV 2.5) were combined in their natural concentrations, the model successfully mimicked the plant's aroma. The results of this investigation provide a foundation for additional investigations into the natural variation in aroma chemistry of different selections of P. loomisii and other members of the Pycnanthemum genus. | Olfactometry |
Advances in blepharoplasty have resulted in an improved understanding of preoperative risk factors, intraoperative hemostasis, and wound closure. This has reduced the risk of severe adverse events. The aim of this review is to determine the current evidence base for routine postblepharoplasty management. A literature review was performed using MEDLINE, PUBMED, and EMBASE databases. Expanded search criterion bleph*" was combined with individual terms assessing postoperative management. Articles were assessed and qualified as per Oxford Centre of Evidence-Based Medicine levels 1 to 5 (1 = highest level of evidence). A total of 47 unique articles matched our search strategy. Most articles were a description of individual expert opinion, surveys of practice, or case series (level 4-5 evidence). Few randomized controlled trials were performed (level 2). Many articles describe the clinical experience of senior facial plastic surgeons. Our review found some evidence for postoperative cooling and preincision antisepsis to be effective. This review highlights the need for higher-quality studies to improve the evidence base for routine postoperative management." | Postoperative Period |
Proteins from the BCL-2 family control cell survival and apoptosis in health and disease, and regulate apoptosis-unrelated cellular processes. BCL-Gonad (BCL-G, also known as BCL2-like 14) is a non-typical protein of the family as its long isoform (BCL-G(L)) consists of BH2 and BH3 domains without the BH1 motif. BCL-G is predominantly expressed in normal testes and different organs of the gastrointestinal tract. The complexity of regulatory mechanisms of BCL-G expression and post-translational modifications suggests that BCL-G may play distinct roles in different types of cells and disorders. While several genetic alterations of BCL2L14 have been reported, gene deletions and amplifications prevail, which is also confirmed by the analysis of sequencing data for different types of cancer. Although the studies validating the phenotypic consequences of genetic manipulations of BCL-G are limited, the role of BCL-G in apoptosis has been undermined. Recent studies using gene-perturbation approaches have revealed apoptosis-unrelated functions of BCL-G in intracellular trafficking, immunomodulation, and regulation of the mucin scaffolding network. These studies were, however, limited mainly to the role of BCL-G in the gastrointestinal tract. Therefore, further efforts using state-of-the-art methods and various types of cells are required to find out more about BCL-G activities. Deciphering the isoform-specific functions of BCL-G and the BCL-G interactome may result in the designing of novel therapeutic approaches, in which BCL-G activity will be either imitated using small-molecule BH3 mimetics or inhibited to counteract BCL-G upregulation. This review summarizes two decades of research on BCL-G. | Apoptosis Regulatory Proteins |
Functional interaction of clock genes and pituitary hormones was investigated by focusing on bone morphogenetic protein (BMP)-4 and melatonin actions in anterior pituitary cells. A significant correlation between the mRNA expression of proopiomelanocortin (POMC) and Per2 was revealed in serial cultures of corticotrope AtT20 cells. Knockdown of Per2 expression by siRNA in AtT20 cells resulted in a significant reduction of POMC mRNA level with or without corticotropin-releasing hormone (CRH) stimulation. Treatments with BMP-4 and melatonin, both of which suppress POMC expression, reduced Per2 mRNA as well as protein levels in AtT20 cells. On the other hand, in lactosomatotrope GH3 cells, an expressional correlation was found between prolactin (PRL) and Clock mRNA levels, which was attenuated in the presence of forskolin treatment. The siRNA-mediated knockdown of Clock expression, but not that of Bmal1, significantly reduced PRL mRNA levels in GH3 cells. Interestingly, Clock mRNA and protein levels did not fluctuate with melatonin, BMP-4 or forskolin treatment, although Bmal1 expression was significantly increased by forskolin treatment. Collectively, a significant correlation between the expression of POMC and Per2 and that between PRL and Clock were uncovered in corticotrope and lactosomatotrope cells, respectively. Per2 expression was inhibited by POMC modulators including melatonin and BMP-4, while Clock expression was steadily maintained. Thus, the effects of melatonin and BMP-4 on clock gene expression may imply differential stability of circadian rhythms of adrenocorticotropin (ACTH) and PRL secreted from the anterior pituitary. | Corticotrophs |
Perineal trauma (PT) may be considered as a very common injury during the childbirth. The incidence of PT was estimated in 30% to 85%, with 60% to 70% requiring suture. The present study was a prospective, single-blinded, randomised, clinical trial carried out from January 2015 to January 2016. For this study, 49 secundigravida women diagnosed with gestational oedema were recruited and randomly divided into two groups (A and B). Group A (n = 30) received the conventional treatment plus perineal massage and group B (n = 19) the conventional treatment plus manual lymphatic drainage (MLD). Visual analogue scale (VAS) and King Health's Questionnaire (KHQ) were performed to assess pain intensity and quality of life-related with urinary incontinence (UI). Pain intensity measurements showed statistically significant differences for a decrease after 30-weeks (P = .037), after 36-weeks (P = .000), and at the end of puerperium (P = .014) for MLD with respect to perineal massage group. Moreover, inter-groups repeated measures ANOVA for the values related statistically significant differences to the interaction of each applied treatment (perineal massage and MLD group, separately) over the pain intensity variable. MLD treatment reduced pain intensity with respect to perineal massage in secundigravida women with gestational oedema from 25-weeks of gestation to the end of puerperium. | Manual Lymphatic Drainage |
Monoclonal antibodies are being widely used for the treatment of various diseases. Microparticle formation in high-concentration protein solutions is a major problem during the manufacture of therapeutic monoclonal antibodies, because aggregation leads to fouling of aseptic filters and may lead to an immunogenic reaction in patients. We found that stirring using a traditional bottom-magnetic type stirrer results in extensive and sustained formation of 500-nm diameter protein microparticles arising from shear stress on protein molecules. The antibody solution stirred for only 5 min using this type of stirrer exhibited significant fouling of aseptic filter membranes. In contrast, a top-entering type stirrer did not lead to the formation of microparticles, and the solution did not exhibit membrane fouling even after 30 min of stirring. We conclude that a top-entering type stirrer is more suited for the manufacture of concentrated therapeutic monoclonal antibody solutions. | Chemistry, Pharmaceutical |
The cane toad (Bufo marinus) is one of the most notorious animal pests encountered in Australia. Members of the genus Bufo historically have been regarded as having genotypic sex determination with male homogamety/female heterogamety. Nevertheless, as with many toads, karyotypic analyses of the cane toad have so far failed to identify heteromorphics sex chromosomes. In this study, we used comparative genomic hybridization, reverse fluorescence staining, C-banding, and morphometric analyses of chromosomes to characterize sex chromosome dimorphism in B. marinus. We found that females consistently had a length dimorphism associated with a nucleolus organizer region (NOR) on one of the chromosome 7 pair. A strong signal over the longer NOR in females, and the absence of a signal in males indicated sex-specific DNA sequences. All females were heterozygous and all males homozygous, indicating a ZZ/ZW sex chromosomal system. Our study confirms the existence of sex chromosomes in this species. The ability to reliably identify genotypic sex of cane toads will be of value in monitoring and control efforts in Australia and abroad. | Bufo marinus |
Radiation-induced oral mucositis is a common and dose-limiting complication of head and neck radiotherapy with no effective treatment. Previous studies revealed that sildenafil, a phosphodiesterase 5 inhibitor, has anti-inflammatory and anti-cancer effects. In this study, we investigated the effect of sildenafil on radiation-induced mucositis in rats. Two doses of radiation (8 and 26 Gy X-ray) were used to induce low-grade and high-grade oral mucositis, separately. A control group and three groups of sildenafil citrate-treated rats (5, 10, and 40 mg/kg/day) were used for each dose of radiation. Radiation increased MDA and activated NF-kappaB, ERK and JNK signalling pathways. Sildenafil significantly decreased MDA level, nitric oxide (NO) level, IL1beta, IL6 and TNF-alpha. The most effective dose of sildenafil was 40 mg/kg/day in this study. Sildenafil also significantly inhibited NF-kappaB, ERK and JNK signalling pathways and increased bcl2/bax ratio. In addition, high-dose radiation severely destructed the mucosal layer in histopathology and led to mucosal cell apoptosis in the TUNEL assay. Sildenafil significantly improved mucosal structure and decreased inflammatory cell infiltration after exposure to high-dose radiation and reduced apoptosis in the TUNEL assay. These findings show that sildenafil can improve radiation-induced oral mucositis and decrease the apoptosis of mucosal cells via attenuation of inflammation and oxidative stress. | Sildenafil Citrate |
BACKGROUND AND OBJECTIVES: Imagery rescripting (ImRs) is a promising therapeutic technique used in treatment for a variety of psychiatric disorders. During an ImRs session, an aversive disorder-related memory, is activated in imagination and rescripted to a more positive outcome. It has been shown to successfully weaken the negative cognitive meaning, so-called encapsulated beliefs of the targeted aversive memory. In many studies, ImRs is preceded by a cognitive restructuring (CR) technique focused on the encapsulated belief of the target memory. It is not clear whether adding such a CR technique is necessary or that ImRs as standalone technique can achieve comparable effects. METHODS: Students with mild psychological distress (N = 53) were randomized over one session of cognitive restructuring plus imagery rescripting (CR + ImRs), a therapist attention placebo plus imagery rescripting (PLA + ImRs) and a double therapist attention placebo (PLA + PLA). Believability of the idiosyncratic encapsulated belief (primary outcome) and quality (vividness, distress and emotional connotation: secondary outcome) of the target memory were assessed at pre, post and at 1-week follow-up. RESULTS: Results indicate that both, CR + ImRs and PLA + ImRs, reduced the believability of the encapsulated beliefs in greater extent than PLA + PLA. No differences appeared between the two ImRs conditions. For the secondary outcomes no differences between the three conditions were found. LIMITATIONS: This study should be seen as a pilot study, moreover a non-clinical sample was used. CONCLUSION: Findings suggest that a CR technique preceding ImRs is redundant. However, this study needs replication in a larger sample. | Cognitive Restructuring |
The influence of glutamic acid (E)-alanine (A) dimorphism at position 74 of the DR4 beta chain on cytotoxic T cell recognition of an antigenic rubella virus peptide, E1(273-284), was studied using a panel of B cell lines and B cell transfectants expressing different HLA-DRB1 alleles as antigen-presenting cells and targets in 51Cr-release assays. Only B cell lines expressing the DRB1*0403, DRB1*0406 or DRB1*0407 subtypes which shared a residue, E, at position 74 in the DR4 beta chain when sensitized with E1(273-284) elicited strong cytotoxic T lymphocyte responses. However, in direct binding and antibody inhibition assays, it was shown that biotinylated E1(272-285) could bind to DR molecules with residues other than E at position 74, including DRB1*0401, DRB1*0404 and DRB1*1101 expressed on transfectants. E1(272-285) bound with similar affinity to the transfectant with DRB1*0403, which has E at position 74, as well as the transfectant with DRB1*0404, which does not. When T-B cell engagement rates were compared in cell conjugate assays, the percentage of T-B conjugates was higher when peptide-pulsed transfectants with DRB1*0403 were used than with transfectants expressing DRB1*0404. Hence, the HLA DR beta 1 polymorphism at position 74, while not critical for the binding affinity of E1(272-285) to the HLA molecule, appears to be a primary determinant of restricted recognition and subsequent activation of the peptide-specific T cells. | HLA-DR4 Antigen |
Suturing a gingival graft is often the most time-consuming stage of the grafting procedure, especially in regions of difficult access. Previously, it has been suggested that a combination of adhesive cellophane and cyanoacrylate may be used to immobilize the graft without suturing. The technique presented here attempts to simplify further sutureless grafting with the following modifications: - Bandage tape is used instead of adhesive cellophane. - The tape is not placed on the teeth but on the attached gingiva on either side of the graft site. - The use of cyanoacrylate is discarded. The success of the procedure depends on complete haemostasis as any moisture will prevent the tape from adhering to the gingiva. Inherent advantages of sutureless grafting accomplished with the use of bandage tape are: - The graft lies flat on the recipient site and is kept under slight pressure by the tape. - Minimal blood clot is present between the graft and the recipient site. - The wick" effect of the sutures is eliminated. - The chairside time is greatly reduced. - A shorter appointment and no sutures to remove imply less discomfort for the patient. The technique is contraindicated should the patient present an allergic background to bandage tape." | Gingivoplasty |
INTRODUCTION: Chronic spontaneous urticaria (CSU) refers to urticaria (wheals) or angioedema, which occur for a period of six weeks or longer without an apparent cause. The condition may impair the patient's quality of life. AREAS COVERED: Treatment for CSU is mainly symptomatic. Both AAAAI/ACAAI practice parameters and EAACI/GA2LEN/EDF/WAO guidelines suggest CSU management in a stepwise manner. First-line therapy is with second-generation H(1)-antihistamines. Treatment should be stepped up along the algorithm if symptoms are not adequately controlled. Increasing the dosage of second-generation H(1)-antihistamines, with the addition of first-generation H(1)-antihistamines, H(2) antagonist, omalizumab, ciclosporin A, or short-term corticosteroid may be necessary. New medications are being developed to treat refractory CSU. They include spleen tyrosine kinase inhibitor, Bruton tyrosine kinase inhibitor, prostaglandin D(2) receptor inhibitor, H(4)-antihistamine, and other agents. The authors discuss these treatments and provide expert perspectives on the management of CSU. EXPERT OPINION: Second-generation H(1)-antihistamines remain the first-line therapeutic options for the management of CSU. For patients not responding to higher-dose H(1)-antihistamines, international guidelines recommend the addition of omalizumab. Efficacy and safety data for newer agents are still pending. Large-scale, well-designed, randomized, double-blind, placebo-controlled trials will further provide evidence on the safety profile and efficacy of these agents in patients with CSU. | Chronic Urticaria |
The interior lumen of acidic organelles (e.g., endosomes, secretory granules, lysosomes and plant vacuoles) is an important platform for modification, transport and degradation of biomolecules as well as signal transduction, which remains challenging to investigate using conventional fluorescent proteins (FPs). Due to the highly acidic luminal environment (pH ~ 4.5(-)6.0), most FPs and related sensors are apt to lose their fluorescence. To address the need to image in acidic environments, several research groups have developed acid-tolerant FPs in a wide color range. Furthermore, the engineering of pH insensitive sensors, and their concomitant use with pH sensitive sensors for the purpose of pH-calibration has enabled characterization of the role of luminal ions. In this short review, we summarize the recent development of acid-tolerant FPs and related functional sensors and discuss the future prospects for this field. | Green Fluorescent Proteins |
The three-dimensional ultrastructure of multinucleate giant cells in subcutaneous granulomas was compared with those of peritoneal macrophages using a quick-freezing and deep-etching method. Subcutaneous granulomas were induced by implanting plastic coverslips in the dorsal subcutaneous tissue of rats. The quick-freezing and deep-etching replicas were prepared from the cells attached to the coverslips. Dense networks of actin filaments were distributed along all peripheral aspects (beneath the plasma membrane, and on free and coverslip-attached surfaces) of the multinucleate giant cells. On the coverslip-attached surface, numerous clathrin-coated pits and vesicles occurred between the actin filaments. In these cells, intermediate filaments, but not actin filaments, were the predominant cytoskeletal components in perinuclear regions and were attached to the cell nucleus, mitochondria and other vesicular cell organelles. A similar distribution of cytoskeletal components was observed in the mononuclear macrophages of the granulomas and the peritoneal macrophages. These results show that the cytoskeletal organization varies in different regions of the cytoplasm of multinucleate giant cells, while the characteristic cytoskeletal arrangement, resembling that of mononuclear macrophages, is maintained." | Shadowing Technique, Histology |
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