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Kaempferia parviflora is widely used as a food supplement and a herbal medicine for vitalization. Previous study has shown that K. parviflora had CYP2E1 inducer activity. It is likely to affect the metabolism of CYP2E1 substrates such as acetaminophen which is a common household pain relief medicine. This study investigated the possible pharmacokinetic interaction between K. parviflora and acetaminophen in rats. Acetaminophen (100 mg/kg, p.o) was administered to rats for nine consecutive days. On days 4-9, K. parviflora extract (250 mg/kg, p.o) was given to the acetaminophen-treated rats. After co-administration with K. parviflora, the concentrations of acetaminophen during day 5-8 markedly decreased compared with acetaminophen-only group. At day 9, the pharmacokinetic parameters of acetaminophen in the presence of K. parviflora extract also decreased, including area under the concentration-time curve (from 1.68 +/- 0.16 to 0.34 +/- 0.04 mg.min/mL), the maximum concentration (from 19.10 +/- 1.90 to 4.48 +/- 0.56 microg/mL), and half-life (from 21.29 +/- 1.36 to 10.81 +/- 1.24 min). In addition, clearance and the elimination rate constant of acetaminophen were significantly increased (from 0.003 +/- 0.000 to 0.006 +/- 0.001 L/min and 0.03 +/- 0.00 to 0.07 +/- 0.01 min(-1), respectively) in the presence of K. parviflora extract. These findings provide the data for in vivo herb-drug interaction between K. parviflora extract and acetaminophen. Therefore, the concomitant use of K. parviflora as a food supplement and acetaminophen should occasion therapeutic and safety concerns." | Cytochrome P-450 CYP2E1 Inducers |
This review provides timely information concerning clinical, surgical, and pathologic findings of adnexal torsion (AT). AT mostly occurs in the child-bearing age group, but is not uncommon in premenarchal girls or postmenopausal women. When AT is suspected, urgent surgical intervention is indicated, and is usually performed by laparoscopy. Incidence of AT is 3.5% of all benign cystic teratomas. Despite the necrotic" appearance of the twisted ischemic ovary, detorsion is the only procedure which should be performed at surgery. Adnexectomy should be avoided as ovarian function is preserved in 88% to 100% of cases. Awareness and suspicion of the diagnosis of AT is needed in patients who present with lower abdominal pain." | Adnexal Diseases |
There is considerable interest in developing silicon-based telescopes because of their compactness and low power requirements. Three such telescopes have been flown on board the Space Shuttle to measure the linear energy transfer spectra of trapped, galactic cosmic ray, and solar energetic particles. Dosimeters based on single silicon detectors have also been flown on the Mir orbital station. A comparison of the absorbed dose and radiation quality factors calculated from these telescopes with that estimated from measurements made with a tissue equivalent proportional counter show differences which need to be fully understood if these telescopes are to be used for astronaut radiation risk assessments. Instrument performance is complicated by a variety of factors. A Monte Carlo-based technique was developed to model the behavior of both single element detectors in a proton beam, and the performance of a two-element, wide-angle telescope, in the trapped belt proton field inside the Space Shuttle. The technique is based on: (1) radiation transport intranuclear-evaporation model that takes into account the charge and angular distribution of target fragments, (2) Landau-Vavilov distribution of energy deposition allowing for electron escape, (3) true detector geometry of the telescope, (4) coincidence and discriminator settings, (5) spacecraft shielding geometry, and (6) the external space radiation environment, including albedo protons. The value of such detailed modeling and its implications in astronaut risk assessment is addressed." | Elementary Particle Interactions |
To facilitate multicentre clinical studies on targeted alpha therapy, it is necessary to develop an automated, on-site procedure for conjugating rare, short-lived, alpha-emitting radionuclides to biomolecules. Astatine-211 is one of the few alpha-emitting nuclides with appropriate chemical and physical properties for use in targeted therapies for cancer. Due to the very short range of the emitted alpha-particles, this therapy is particularly suited to treating occult, disseminated cancers. Astatine is not intrinsically tumour-specific; therefore, it requires an appropriate tumour-specific targeting vector, which can guide the radiation to the cancer cells. Consequently, an appropriate method is required for coupling the nuclide to the vector. To increase the availability of astatine-211 radiopharmaceuticals for targeted alpha therapy, their production should be automated. Here, we present a method that combines dry distillation of astatine-211 and a synthesis module for producing radiopharmaceuticals into a process platform. This platform will standardize production of astatinated radiopharmaceuticals, and hence, it will facilitate large clinical studies focused on this promising, but chemically challenging, alpha-emitting radionuclide. In this work, we describe the process platform, and we demonstrate the production of both astaine-211, for preclinical use, and astatine-211 labelled antibodies. | Astatine |
Systemic amyloid-A (AA) amyloidosis in birds occurs most frequently in waterfowl such as Pekin ducks. In chickens, AA amyloidosis is observed as amyloid arthropathy. Outbreaks of systemic amyloidosis in flocks of layers are known to be induced by repeated inflammatory stimulation, such as those resulting from multiple vaccinations with oil-emulsified bacterins. Outbreaks of fatal AA amyloidosis were observed in growing chickens in a large scale poultry farm within 3 weeks of vaccination with multiple co-administered vaccines. This study documents the histopathological changes in tissues from these birds. Amyloid deposits were also observed at a high rate in the tissues of apparently healthy chickens. Vaccination should therefore be considered as a potential risk factor for the development of AA amyloidosis in poultry. | Atadenovirus |
Amniotic band syndrome refers to the uncommon occurrence of a variety of congenital deformities, most probably due to foetal entanglement in strands ruptured from the amniotic sac. We present a rare case of an abdominal constriction band together with a short literature review. | Amniotic Band Syndrome |
Pheochromocytomas are tumors that arise from chromaffin cells of the sympathetic nervous system and act by synthesizing and releasing catecholamines. They usually occur between the fourth and fifth decade of life and have a very wide clinical presentation. They occur only in 0.1-0.2% of the hypertensive population and represent a treatable and curable cause of arterial hypertension, as well as other symptoms derived from the uncontrolled secretion of catecholamines. Peripheral arterial ischemia secondary to massive amines release by a pheochromocytoma is a very uncommon condition. Here we report a case of pheochromocytoma manifested as blue finger syndrome in a patient with palpable distal pulses and history of poor blood pressure control despite treatment with two drugs. | Blue Toe Syndrome |
There is an increasing interest by consumers for high quality food products with a specified composition. Suitable analytical techniques are needed for the quality control. Chemiluminescence (CL) detection has become quite a useful tool in the last years due to its simplicity, low cost and high sensitivity. Moreover, no external light source is needed. CL is often described as a dark-field technique: the absence of strong background light level reduces the background signal and leads to improved detection limits. Due to these advantages, CL methods have been widely applied to food analysis in recent years. Navas and Jimenez had reviewed the CL methods in food analysis in 1996. The present review covers the papers since 1996, including the CL determinations of nitrogen containing components, sugars, chemical preservatives, metals, hormonal anabolics and metabolites, and other compounds in foods. 122 references have been cited. | Pesticides |
The stamens of angiosperms are diverse in number, colour and structure. The morphological and structural changes of stamens show important evolutionary significance for improving pollination efficiency. In Clematis macropetala, the androecium consists of fertile stamens and tepaloid staminodes. However, studies on the developmental features, structures and possible functions of stamens are few. In this study, the stamen ontogeny, micromorphology and nectary structure of C. macropetala were studied by scanning electron microscopy, light microscopy and transmission electron microscopy. The results indicate that the stamens can be divided into four forms according to shape and anther size: tepaloid staminode (St(1)), spatulate staminode (St(2)), linear-spatulate fertile stamen (St(3)) and linear fertile stamen (St(4)). The characteristics of stamen development are similar in the early stage but gradually differentiate in the later stage. St(1) has delayed development and no anther differentiation. St(2) develops abnormally at the early stage of anther differentiation. St(3) and St(4) are fertile, but their anther sizes are different. Nine epidermal cell types were observed in stamens, with only 4 types in St(1) and 6-7 types in St(2), St(3) and St(4). Nectary tissue appears on the adaxial side of the filament base. The nectary is composed of only one layer of secretory epidermal cells, which have a large nucleus, dense cytoplasm and well-developed wall ingrowth. Nectar is released through micro-channels in the cuticle of the outer wall. In Ranunculaceae, the staminal nectary is often located on fertile or sterile stamens, and the position, structure and micromorphology of secretory tissues of the stamen within Ranunculales are discussed. | Clematis |
Equine herpesvirus type 1 and type 4 (EHV-1 and EHV-4) cause infections of horses worldwide. While both EHV-1 and EHV-4 cause respiratory disease, abortion and myeloencephalopathy are observed after infection with EHV-1 in the vast majority of cases. Disease control is achieved by hygiene measures that include immunization with either inactivated or modified live virus (MLV) vaccine preparations. We here compared the efficacy of commercially available vaccines, an EHV-1/EHV-4 inactivated combination and an MLV vaccine, with respect to induction of humoral responses and protection of clinical disease (abortion) in pregnant mares and foals on a large stud with a total of approximately 3500 horses. The MLV vaccine was administered twice during pregnancy (months 5 and 8 of gestation) to 383 mares (49.4%), while the inactivated vaccine was administered three times (months 5, 7, and 9) to 392 mares (50.6%). From the vaccinated mares, 192 (MLV) and 150 (inactivated) were randomly selected for serological analyses. There was no significant difference between the groups with respect to magnitude or duration of the humoral responses as assessed by serum neutralization assays (median range from 1:42 to 1:130) and probing for EHV-1-specific IgG isotypes, although neutralizing responses were higher in animals vaccinated with the MLV preparation at all time points sampled. The total number of abortions in the study population was 55/775 (7.1%), 9 of which were attributed to EHV-1. Seven of the abortions were in the inactivated and two in the MLV vaccine group (p=0.16). When foals of vaccinated mares were followed up, a dramatic drop of serum neutralizing titers (median below 1:8) was observed in all groups, indicating that the half-life of maternally derived antibody is less than 4 weeks. | Herpesvirus 4, Equid |
BACKGROUND: Since the description of Charcot-Marie-Tooth disease over a century ago. it has now been recognized that these conditions are not caused by generalized metabolic defects but rather have various discrete genetic origins. These disorders can also have variable phenotypes due to dysfunction of peripheral nerve axons or their myelin due to the genetic defects that affect the formation of specific nerve proteins. REVIEW SUMMARY: This article summarizes the clinical presentation of various phenotypes of the hereditary motor sensory neuropathies and the hereditary sensory and autonomic neuropathies, genetic mutations, and their relevant protein products. Proper identification of the genetic defects provides the opportunity for better genetic counseling and hopefully therapies in the future." | Heredodegenerative Disorders, Nervous System |
Lunasin and BBI (Bowman Birk protease inhibitor) are bioactive soy peptides that have been shown to be effective suppressors of carcinogenesis in in vitro and in vivo model systems. Since they are subject to digestion in the gastrointestinal tract, we investigated here the stabilities of lunasin and BBI to digestion in vitro by simulated intestinal fluid (SIF) and simulated gastric fluid (SGF). Samples containing lunasin and BBI of varying purities were subjected to in vitro digestion by SIF and SGF at different times and analyzed by Western blot. While the pure BBI reaction is stable after SIF and SGF digestions, the purified lunasin from soybean and synthetic lunasin are easily digested after 2 min in both in vitro digestions. In contrast, lunasin from soy protein containing BBI is comparatively stable after SIF and SGF digestions. Both lunasin and BBI are able to internalize into the cell and localize in the nucleus even after digestion, suggesting that some of the peptides are intact and bioactive. These data suggest that BBI plays a role in protecting lunasin from digestion when soy protein is consumed orally. The role of other soy protease inhibitors such as Kunitz Trypsin Inhibitor (KTI) cannot be excluded from these experiments." | Trypsin Inhibitor, Bowman-Birk Soybean |
Many genes and their regulatory relationships are involved in developmental phenomena. However, by chemical information alone, we cannot fully understand changing organ morphologies through tissue growth because deformation and growth of the organ are essentially mechanical processes. Here, we develop a mathematical model to describe the change of organ morphologies through cell proliferation. Our basic idea is that the proper specification of localized volume source (e.g., cell proliferation) is able to guide organ morphogenesis, and that the specification is given by chemical gradients. We call this idea growth-based morphogenesis." We find that this morphogenetic mechanism works if the tissue is elastic for small deformation and plastic for large deformation. To illustrate our concept, we study the development of vertebrate limb buds, in which a limb bud protrudes from a flat lateral plate and extends distally in a self-organized manner. We show how the proportion of limb bud shape depends on different parameters and also show the conditions needed for normal morphogenesis, which can explain abnormal morphology of some mutants. We believe that the ideas shown in the present paper are useful for the morphogenesis of other organs." | Limb Buds |
The B-fragment of diphtheria toxin binds to cell surface receptors and facilitates entry of the enzymatically active A-fragment into the cytosol. The roles of the amino- and carboxyl-terminal regions of the B-fragment in interactions with the cell membrane were studied by measuring specific binding, insertion into membranes at low pH, and formation of cation-selective channels, as well as by toxicity measurements after association with active A-fragment. Deletion of the amino-terminal 12 amino acids of the B-fragment did not affect its ability to bind to receptors and to form ion channels at low pH, whereas both abilities were strongly impaired when one more amino acid (Trp206) was removed. Replacement of the amino-terminal 31 residues with an amphipathic sequence from human apolipoprotein A1 restored receptor binding but not ion channel formation. The binding to cells was virtually abolished when 9 residues were deleted from the carboxyl terminus. Deletion of only 4 residues or extension by 12 residues did not prevent specific binding, but reduced insertion, channel formation, and toxicity. Those deletions that reduced receptor binding ability increased the trypsin sensitivity of the B-fragment. The results indicate that the amino- and carboxyl-terminal regions of diphtheria toxin B-fragment are important for receptor binding, possibly because they contribute to keep the B-fragment in a binding-competent conformation. Small alterations in the carboxyl-terminal end reduced insertion, channel formation, and toxicity more than the ability of the B-fragment to bind to cells. | Diphtheria Toxin |
Although the central role of ameloblasts in synthesis and resorption of enamel matrix proteins during amelogenesis is well documented, the Ca(2+)-transport/extrusion mechanism remains to be fully elucidated. To clarify Ca(2+)-transport in rat ameloblasts, we investigated expression and localization of Na(+)-Ca(2+) exchanger (NCX) isoforms and the functional characteristics of their ion transporting/pharmacological properties. RT-PCR and immunohistochemical analyses revealed expression of NCX1 and NCX3 in ameloblasts, localized in the apical membrane. In patch-clamp recordings, Ca(2+) efflux by Na(+)-Ca(2+) exchange showed dependence on external Na(+). Ca(2+) influx by Na(+)-Ca(2+) exchange, measured by fura-2 fluorescence, showed dependence on extracellular Ca(2+) concentration, and it was blocked by NCX inhibitors KB-R7943, SEA0400, and SN-6. These results showed significant expression of NCX1 and NCX3 in ameloblasts, indicating their involvement in the directional Ca(2+) extrusion pathway from cells to the enamel mineralizing front. | Sodium-Calcium Exchanger |
Target size effect on the sensory signaling intensity of polydiacetylene (PDA) liposome microarrays was systematically investigated. Influenza A virus M1 peptide and M1 antibody were selected as a probe-target pair. While red fluorescence from the PDA liposome microarrays was observed when the larger M1 antibody was used as a target, when the same M1 antibody was used as a probe to detect the smaller M1 peptide sensory signal did not appear. The results reveal that the intensity of the PDA sensory signal is mainly related to the steric repulsion between probe-target complexes not the strength of the probe-target binding force. Based on this finding, we devised a PDA sensory system that directly detects influenza A whole virus as a larger target, and confirmed the target size effect on the signaling efficiency of PDA. | Polyacetylene Polymer |
Tomato spotted wilt virus (TSWV) is a devastating disease to peanut growers in the South-eastern region of the United States. Newly released peanut cultivars in recent years are crucial as they have some levels of resistance to TSWV. One mapping population of recombinant inbred line (RIL) used in this study was derived from peanut lines of SunOleic 97R and NC94022. A whole genome re-sequencing approach was used to sequence these two parents and 140 RILs. A recombination bin-based genetic map was constructed, with 5,816 bins and 20 linkage groups covering a total length of 2004 cM. Using this map, we identified three QTLs which were colocalized on chromosome A01. One QTL had the largest effect of 36.51% to the phenotypic variation and encompassed 89.5 Kb genomic region. This genome region had a cluster of genes, which code for chitinases, strictosidine synthase-like, and NBS-LRR proteins. SNPs linked to this QTL were used to develop Kompetitive allele specific PCR (KASP) markers, and the validated KASP markers showed expected segregation of alleles coming from resistant and susceptible parents within the population. Therefore, this bin-map and QTL associated with TSWV resistance made it possible for functional gene mapping, map-based cloning, and marker-assisted breeding. This study identified the highest number of SNP makers and demonstrated recombination bin-based map for QTL identification in peanut. The chitinase gene clusters and NBS-LRR disease resistance genes in this region suggest the possible involvement in peanut resistance to TSWV. | Arachis |
Great progress has been made in in vivo imaging for cancer metastasis. Eisenblaetter et al. developed an innovative S100A8/A9-specific single photon emission computed tomography (SPECT) probe for imaging and succeeded in detecting the metastatic organ favored by the cancer before the cancer arrival. By utilizing this advanced method, researchers have also found that cancer-derived monocytes are the main source of the abundant production of S100A8/A9 in the pre-metastatic area. The CCL2-CCR2 axis is associated with S100A8/A9 production. Clinical establishment of this technique is expected to enable accurate prediction and monitoring of cancer metastasis during therapy. | Calgranulin A |
Running pacing has become a focus of interest over recent years due to its relationship with performance, however, it is still unknown the consistency of each race in different editions. The aim of this study is to analyze the consistency of pacing profile in three consecutive editions of three marathon races. A database of 282,808 runners, compiled from three different races (Chicago, London, and Tokyo Marathon) and three editions (2017, 2018, and 2019) was analyzed. Participants were categorized according to their time performance in the marathon, every 30 min from 2:30 h to sub-6 h. The relative speed of each section for each runner was calculated as a percentage of the average speed for the entire race. The intraclass correlation coefficients (ICC) of relative speed at the different pacing section, taking into account the runner time categories, was excellent over the three marathon editions (ICC > 0.93). The artificial intelligence model showed an accuracy of 86.8% to classify the runners' data in three marathons, suggesting a consistency between editions with identifiable differences between races. In conclusion, although some differences have been observed between editions in certain sections and marathon runner categories, excellent consistency of the pacing profile was observed. The study of pacing profile in a specific marathon can, therefore, be helpful for runners, coaches and marathon organizers for planning the race and improving its organization. | Cities |
A new alkaloid glycoside named fordianoside (1), together with three known compounds arabinothalictoside (2), 6-O-p-coumaroyl-beta-fructofuranosyl-(2 --> 1)-alpha-d-glucopyranoside (3) and 4-[formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl] butanoic acid (4), was isolated from the rhizomes of Aristolochia fordiana. The structure of 1 was established as (1S)-1,2,3,4-tetrahydro-7-hydroxy-1-[(4-hydroxybenzyl) methyl]-2,2-dimethyl-8-O-isoquinolinyl beta-d-glucopyranoside by using chemical and spectroscopic methods including HR-ESI-MS, 1D and 2D NMR. | Aristolochiaceae |
Cisplatin is a highly effective chemotherapeutic agent against many tumors; however, it is also a potent nephrotoxicant. Given that there have been no significant advances in our ability to clinically manage acute renal failure since the advent of dialysis, the development of novel strategies to ablate nephrotoxicity would represent a significant development. In this study, we investigated the ability of an inhibitor of soluble epoxide hydrolase (sEH), n-butyl ester of 12-(3-adamantan-1-yl-ureiido)-dodecanoic acid (nbAUDA), to attenuate cisplatin-induced nephrotoxicity. nbAUDA is quickly converted to AUDA and results in maintenance of high AUDA levels in vivo. Subcutaneous administration of 40 mg/kg of nbAUDA to C3H mice every 24 h resulted in elevated blood levels of AUDA; this protocol was also associated with attenuation of nephrotoxicity induced by cisplatin (intraperitoneal injection) as assessed by BUN levels and histological evaluation of kidneys. This is the first report of the use of sEH inhibitors to protect against acute nephrotoxicity and suggests a therapeutic potential of these compounds. | Lauric Acids |
Ketosteroid isomerase (Delta(5)-3-keto steroid isomerase or steroid Delta-isomerase) is a highly efficient enzyme at the centre of current debates on enzyme catalysis. We have modelled the reaction mechanism of the isomerization of 3-oxo-Delta(5)-steroids into their Delta(4)-conjugated isomers using high-level combined quantum mechanics/molecular mechanics (QM/MM) methods, and semi-empirical QM/MM molecular dynamics simulations. Energy profiles were obtained at various levels of QM theory (AM1, B3LYP and SCS-MP2). The high-level QM/MM profile is consistent with experimental data. QM/MM dynamics simulations indicate that active site closure and desolvation of the catalytic Asp38 occur before or during formation of dienolate intermediates. These changes have a significant effect on the reaction barrier. A low barrier to reaction is found only when the active site is closed, poising it for catalysis. This conformational change is thus integral to the whole process. The effects on the barrier are apparently largely due to changes in solvation. The combination of high-level QM/MM energy profiles and QM/MM dynamics simulation shows that the reaction involves active site closure, desolvation of the catalytic base, efficient isomerization and re-opening of the active site. These changes highlight the transition between the ligand binding/releasing form and the catalytic form of the enzyme. The results demonstrate that electrostatic interactions (as a consequence of pre-organization of the active site) are crucial for stabilization during the chemical reaction step, but closure of the active site is essential for efficient catalysis to occur." | Carbon-Carbon Double Bond Isomerases |
Ciliary neurotrophic factor (CNTF) is a cytokine supporting the differentiation and survival of various cell types in the peripheral and central nervous systems. Its receptor complex consists of a non-signaling alpha chain, CNTFR, and two signaling beta chains, gp130 and the leukemia inhibitory factor receptor (LIFR). Striking phenotypic differences between CNTF- and CNTFR-deficient mice suggest that CNTFR serves as a receptor for a second, developmentally important ligand. We have identified this factor as a stable secreted complex of cardiotrophin-like cytokine (CLC) and the soluble receptor cytokine-like factor-1 (CLF). CLF expression was required for CLC secretion, and the complex acted only on cells expressing functional CNTF receptors. The CLF/CLC complex activated gp130, LIFR and signal transducer and activator of transcription 3 (STAT3) and supported motor neuron survival. Our results indicate that the CLF/CLC complex is a second ligand for CNTFR with potentially important implications in nervous system development." | Receptor, Ciliary Neurotrophic Factor |
Whereas research into the effects of the gonadal hormones on learning and memory has primarily focused on estrogen in females, recent evidence suggests that testosterone can also modulate learning in males through an interaction with the cholinergic system. In the present study, the interactive effects of testosterone and scopolamine (0.1- 0.32 mg/kg), a muscarinic receptor antagonist, on complex behavioral processes were investigated in male rats trained to respond under a multiple schedule of repeated acquisition and performance. In the acquisition component, subjects acquired a different 3-response sequence each session, whereas in the performance component, they responded on the same 3-response sequence each session. Although gonadectomy did not disrupt responding in either component, gonadectomized rats were less sensitive to the disruptive effects of scopolamine on both response rate and accuracy. In contrast, after receiving exogenous testosterone replacement, these gonadectomized males were more sensitive to the behavioral disruptions produced by scopolamine (i.e., the effects of scopolamine were similar to those obtained in gonadally intact males). These results suggest that testosterone replacement can enhance scopolamine-induced behavioral effects in gonadectomized male rats responding under a multiple schedule of repeated acquisition and performance, a finding that is in contrast to those previously found for certain spatial tasks. Furthermore, the present findings suggest that testosterone may decrease the activity of the cholinergic system during nonspatial tasks and thereby work in concert with the antagonism produced by scopolamine. | Testosterone Propionate |
This minireview highlights the recent advances in the therapeutic agents that aim to provide synergistic enhancements of focused ultrasound treatment of tumors. Even though focused ultrasound therapy itself can bring therapeutic effects in cancers, many biochemical agents have been reported in the literature to enhance the treatment efficacy significantly. Until now, many mechanisms have been researched to advance the therapy, such as sonodynamic-plus-chemo-therapy, microbubble-aided therapy, localized release or delivery of nanomaterials, and multimodal image-guided therapy. Here, the novel materials adopted in each mechanism are briefly reviewed to provide a trend in the field and encourage future research towards the successful deployment of focused ultrasound therapy in real clinical environments. | Microbubbles |
A fraction of third-trimester small fetuses does not achieve their endowed growth potential mainly due to placental insufficiency, usually not evident in terms of impaired umbilical artery Doppler, but severe enough to increase the risk of perinatal adverse outcomes and long-term complications. The identification of those fetuses at higher-risk helps to optimize their follow-up and to decrease the risk of intrauterine demise. Several parameters can help in the identification of those fetuses at higher risk, defined as fetal growth restricted (FGR) fetuses. Severe smallness and the cerebroplacental ratio are the most consistent parameters; regarding uterine artery Doppler, although some evidence in favour has been published, there is currently no consensus about its use. Thirty-two weeks of gestation is the accepted cut-off to define late FGR. The differentiation with early FGR is necessary as these two entities have different clinical maternal manifestations, and different associated short-term and long-term neonatal outcomes. The use of angiogenic factors is promising but more research is needed on this field. | Placental Insufficiency |
Previous studies have reported that test anxiety is closely related to unreasonable cognitive patterns and maladaptive emotional responses. However, its underlying brain structural and functional basis has not been thoroughly studied. This study aimed to evaluate the potential difference in local gyration index (LGI) and corresponding resting-state functional connectivity (RSFC) in individuals with high test anxiety (HTA) compared with low test anxiety (LTA). Twenty-six individuals with HTA and 28 individuals with LTA underwent T1-weighted structural and resting-state functional magnetic resonance imaging scans. Using FreeSurfer software, we contrasted the LGI between the HTA and LTA groups using a surface-based general linear model to map group contrasts on a vertex-by-vertex basis. By selecting the cortical regions with significant differences in the LGI analysis as the regions of interest, the seed-based RSFC analysis was further carried out using the Resting-State fMRI Data Analysis Toolkit to examine the differences in the functional connectivity of these cortical regions with the whole brain between the two groups. The results showed that the LGI in several cortical regions of the executive control network (ECN) and the right lateral occipital gyrus was lower in the HTA group than in the LTA group. Furthermore, compared with the LTA group, the HTA group exhibited abnormal RSFC within the ECN, between the ECN and the visual network, and between the ECN and the sensorimotor network. Our findings might provide preliminary evidence for brain morphology and functional alterations in individuals with HTA and contribute to a better understanding of the pathophysiology of TA. | Performance Anxiety |
Bleeding and thrombosis represent common complications in myeloproliferative neoplasms (MPN) and significantly contribute to morbidity and mortality. Molecular markers, including CALR mutations, were considered not only as diagnostic markers, but also as risk factors for bleeding and thrombosis associated with MPN, especially for patients in remote primary hospitals. We sought to develop an easy-to-use assay for the rapid detection of CALR type 1 (CALR-1) and type 2 (CALR-2) mutations in Philadelphia chromosome-negative MPN patients. Peptide nucleic acid-locked nucleic acid (PNA-LNA) clamping loop-mediated isothermal amplification (LAMP) assays were established, which were integrated into a centrifugal compact disc (CD) microfluidic platform. A total of 158 clinical blood samples were tested simultaneously by this microfluidic platform and an in-house real time PCR assay. The detection performance of the LAMP arrays was validated and conflicting results were identified by Sanger sequencing. The results suggested that the LAMP methods we developed exhibited good sensitivity, specificity, and precision. By real time fluorescence assay the detection limit for CALR-1 and CALR-2 mutations could reach as low as 1% and 0.5% respectively, and 10% and 5% respectively by visual method. There were no nonspecific background amplifications among different detection systems. For the CALR-1 and CALR-2 LAMP detection systems, intra-batch CV values of 1% mutated plasmid were 10.56% and 10.51% respectively, and the inter-batch CV values were 19.55% and 18.39%, respectively. The products were all analyzed by melting curve analysis and electrophoresis followed by Sanger sequencing analysis, which were consistent with the database sequences. The microfluidic platform could complete rapid detection of CALR-1/2 mutations within 60â¯min. The results of clinical samples detected by our CD-like microfluidic chipLAMP assay and rtPCR assay suggested that 133 samples were CALR wild type, 15 were CALR-1 mutation type, and 9 were CALR-2 mutation type. The correlation coefficient value (Kendall's tau_b) of the two assays was 0.99. Interestingly, by the newly established detection platform, we were surprised to find that one patient of Chinese origin harbored both CALR-1 and CALR-2 mutations. This result was verified by Sanger sequencing analysis. The LAMP detection systems developed herein displayed good sensitivity, specificity, and stability. Additionally, the detection results could be directly judged by color changes of the reaction systems without any auxiliary equipment. Thus, the platform we developed has the potential of being widely used in remote and economically undeveloped areas in the future." | Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative |
Although digital technology is commonly used in various forms of dental treatment, its application to fabrication of removable dentures is still associated with limitations or challenges, such as the recording of occlusal vertical dimensions and determination of the occlusal plane. Here, a simple and inexpensive technique for fabrication of removable complete dentures, partly aided by digital technology, is proposed. | Dental Occlusion, Centric |
BACKGROUND: Increasing evidence is becoming available on the aetiology and management of fevers in Asia; the importance of these fevers has increased with the decline in the incidence of malaria. AIMS: To conduct a narrative review of the epidemiology and management of fevers in South and South-East Asia and to highlight gaps in our knowledge that impair evidence-based health policy decisions. SOURCES: A narrative review of papers published since 2012 on developments in fever epidemiology, diagnosis and treatment in South and South-East Asia. The papers that the authors felt were pivotal, from their personal perspectives, are discussed. CONTENT: We identified 100 studies. Among the 30 studies (30%)-including both children and adults-that investigated three or more pathogens, the most frequently reported fever aetiology was dengue (reported by 15, 50%), followed by leptospirosis (eight, 27%), scrub typhus (seven, 23%) and Salmonella serovar Typhi (six, 20%). Among four studies investigating three or more pathogens in children, dengue and Staphylococcus aureus were the most frequent, followed by non-typhoidal Salmonella spp, Streptococcus pneumoniae, Salmonella serovar Typhi, and Orientia tsutsugamushi. Increased awareness is needed that rickettsial pathogens are common but do not respond to cephalosporins, and that alternative therapies, such as tetracyclines, are required. IMPLICATIONS: Many key gaps remain, and consensus guidelines for study design are needed to aid comparative understanding of the epidemiology of fevers. More investment in developing accurate and affordable diagnostic tests for rural Asia and independent evaluation of those already on the market are needed. Treatment algorithms, including simple biomarker assays, appropriate for empirical therapy of fevers in different areas of rural Asia should be a major aim of fever research. Enhanced antimicrobial resistance (AMR) surveillance and openly accessible databases of geography-specific AMR data would inform policy on empirical and specific therapy. More investment in innovative strategies facilitating infectious disease surveillance in remote rural communities would be an important component of poverty reduction and improving public health. | Fever |
Genetic manipulation of multidrug-resistant bacteria is often difficult and hinders progress in understanding their physiology and pathogenesis. This book chapter highlights advances in genetic manipulation of Burkholderia cenocepacia, which are also applicable to other members of the Burkholderia cepacia complex and multidrug-resistant gram-negative bacteria of other genera. The method detailed here is based on the I-SceI homing endonuclease system, which can be efficiently used for chromosomal integration, deletion, and genetic replacement. This system creates markerless mutations and insertions without leaving a genetic scar and thus can be reused successively to generate multiple modifications in the same strain. | Burkholderia cenocepacia |
To evaluate the overall treatment benefits of premature ejaculation desensitisation therapy combined with 30 mg dapoxetine hydrochloride treatment on patients with primary premature ejaculation (PPE). Ninety-nine PPE patients were randomly divided into two groups at the ratio of 2:1. Sixty-six PPE patients received premature ejaculation desensitisation therapy accomplished by Weili Automatic Semen Collection-Penis Erection Detection and Analysis workstation (WLJY-2008) combined with 30 mg dapoxetine hydrochloride treatment (DTCD group), and another 33 patients received 30 mg dapoxetine hydrochloride-only treatment (DO group). Intravaginal ejaculation latency time (IELT) and premature ejaculation profile (PEP) were recorded before and during the treatment, and clinical global impression of change (CGIC) in PPE was recorded at the fourth week and the end of the treatment and the items. In both groups were significantly improved (p < 0.0001) in IELT, PEP and CGIC for premature ejaculation compared with baseline, and DTCD treatment showed a more significant improvement on PPE patients in the items compared with DO treatment (p < 0.05). Thus, premature ejaculation desensitisation combined with dapoxetine therapy may be a better choice for improving premature ejaculation with PPE. | Premature Ejaculation |
The oncogene (v-abl) of A-MuLV is a fragment of a normal mouse gene. Only 1.2 kb on the 5'-end of the v-abl is sufficient to encode a tyrosine-specific protein kinase whose activity is important in transformation. This A-MuLV protein kinase can be active in E. coli and it phosphorylates bacterial proteins. The lack of discrimination in its selection for substrates is puzzling. Because of the demonstration of such promiscuity, the identification of physiologically-relevant phosphorylation events must rely on evidence of functional modification rather than physical modification of proteins. | Abelson murine leukemia virus |
PURPOSE: Interleukin 4 (IL4), interleukin 4 receptor (IL4R) and interleukin 13 (IL13) play a key role in the pathogenesis of allergy and asthma development. IL4 and IL13 strongly influence bronchial hyperreactivity in response to allergen, airway remodeling, airway inflammation and airway smooth muscle proliferation. Both IL4 and IL13 exert biologic effect via interleukin 4 receptor. The aim of this study was to evaluate the impact of the polymorphisms within interleukin 4 (rs2243250, rs2227284), interleukin 4 receptor alpha chain (rs1805010, rs1805011) and interleukin 13 (rs20541) genes on the incidence of allergic phenotype in Polish pediatric population. MATERIAL/METHODS: We compared 177 asthmatic pediatric patients with 194 healthy children. Five polymorphisms within IL4, IL13 and IL4Ralpha genes were analyzed. Genotypes of four polymorphisms (rs2243250, rs2227284, rs1805011, rs20541) were assigned by TaqMan SNP Genotyping Assays (Applied Biosystems), whereas rs18050100 polymorphism was established using PCR-RFLP method. RESULTS: We observed an association of rs1805011 polymorphism of IL4Ralpha gene with allergy (p=0.021), mild asthma (p=0.00005) and atopic dermatitis (p=0.0056). Significant correlation was found between rs20541 in IL-13 gene and the positive skin prick test results (p=0.029), along with rs2243250 polymorphism with clinical atopy (p=0.033) and rs2227284 with total IgE levels (p=0.00047). No associations were found for rs1805010. CONCLUSIONS: Our results indicate that rs1805011 polymorphism of IL4Ralpha gene seems to influence allergy risk, especially mild asthma and atopic dermatitis predisposition in Polish children. Subgroup analysis of three other SNPs revealed possible influence on allergy development." | Receptors, Interleukin-4, Type II |
Although adeno-associated virus type 2 (AAV) has gained attention as a potentially useful alternative to the more commonly used retrovirus- and adenovirus-based vectors for human gene therapy, efficient gene transfer and transgene expression by AAV vectors require that the following two obstacles be overcome. First, the target cell must express the receptor and the coreceptor for AAV infection, and second, the cell must allow for viral second-strand DNA synthesis. We now describe a third obstacle, impaired intracellular trafficking of AAV to the nucleus, which results in the lack of transgene expression in murine fibroblasts which do express the AAV receptor and the coreceptor and which are permissive for viral second-strand DNA synthesis. We document that AAV vectors bind efficiently and gain entry successfully into NIH 3T3 cells, but trafficking into the nucleus is significantly impaired in these cells. In contrast, viral trafficking to the nucleus in cells known to be efficiently transduced by AAV vectors is both rapid and efficient. The demonstration of yet another obstacle in AAV-mediated gene transfer has implications for the optimal use of these vectors in human gene therapy. | Tyrphostins |
Low-density lipoprotein (LDL) transport while incorporating the thickening of the arterial wall and cholesterol lipid accumulation is analyzed. A multi-layered model is adopted to represent the heterogeneity using the Darcy-Brinkman and Staverman filtration equations to describe transport within the porous layers of the wall. The fiber matrix model is utilized to represent the cholesterol lipid accumulation and the resulting variable properties. The impact of atherosclerotic wall thickening is shown to be negligible in the axial direction, but is found to be considerable in the radial direction within intima. The reference values of intima's porosity and effective fiber radius are obtained through the fiber matrix model, which characterizes the microstructure within the intima. Transport through dysfunctional endothelium and fibrous cap, and the impact on hydraulic and molecular transport properties by LDL accumulation in a thickened arterial wall is analyzed. The effect of variable properties on plasma and LDL molecular transport is also discussed. | Plaque, Atherosclerotic |
Fascial plane blocks (FPBs) are increasingly numerous and are often touted as effective solutions to many perioperative challenges facing anesthesiologists. As 'new' FPBs are being described, questions regarding their effectiveness remain unanswered as appropriate studies are lacking and publications are often limited to case discussions or technical reports. It is often unclear if newly named FPBs truly represent a novel intervention with new indications, or if these new publications describe mere ultrasound facilitated modifications of existing techniques. Here, we present broad concepts and potential mechanisms of FPB. In addition, we discuss major FPBs of (1) the extremities (2) the posterior torso and (3) the anterior torso. The characteristics, indications and a brief summary of the literature on these blocks is included. Finally, we provide an estimate of the overall level of evidence currently supporting individual approaches as FPBs continue to rapidly evolve. | Fascia |
BACKGROUND: Reducing the gaps in health inequality at a regional level and improving health equity have been emphasized in Korea, it is essential to accurately measure the burden of disease by region. This study aimed to estimate years of life lost (YLLs) in 17 Si and Do of Korea from 1997 to 2015 and determine the trends of regional differences in health status and disease structure. METHODS: YLL was calculated by subtracting the age at death from the life expectancy. Data on the region, gender, and age-stratified cause-specific death were obtained from the Korean Statistical Information Service of Statistics Korea. RESULTS: Age-standardized YLLs per 100,000 population decreased by year in all regions from 1997 to 2015 by 27.4% (27.5% for men; 27.2% for women). Despite the decline in YLLs, the regions with the highest and lowest YLLs did not change between 1997 and 2015. The diseases showing regional differences were caused by injury, often classified as avoidable mortality. We also confirmed that YLLs were higher in the regions with a higher deprivation index. CONCLUSION: The present study identified that YLLs differed by regions in Korea with specific causes. The findings of this study can be used by decision-makers to prioritize the reduction of regional gaps in premature deaths. | Population Health |
Three cases of spirit possession were studied to determine common underlying psychodynamic factors. The spirits were believed to represent culture bound defense mechanisms, and attempts at problem solving in individuals suffering from unresolved conflicts. These being anomic anxiety, dependency, sexual identity and aggression. The symptoms, therefore, were considered to be attempts at conflict resolution. Furthermore the psychodynamic process is described as a transition phase in psychic development between externalization and internalization of intrapsychic distress or collective versus individual ego solutions to life stress. As such, therapy will be facilitated by knowledge of myths and customs and culturally significant methods of healing. | Anomie |
The notion of role morality suggests individuals may adopt a different morality depending on the roles they undertake. Investigating role morality is important, since the mentality of role morality may allow agents to believe they can abdicate moral responsibility when acting in a role. This is particularly significant in the literature dealing with professional morality where professionals, because of their special status, may find themselves at odds with their best moral judgments. Here I tell four stories and draw out some distinctions. I conclude that role morality is a genuine and useful distinction. However, I suggest that the purported distinction between role morality and professional morality is over-determined. Therefore, alleged conflicts between the demands of role and profession (such as the different pressures on Pinto designers as employees and as engineers) are not conflicts between different kinds of demands, but rather conflicts arising from divergent roles that most workers will encounter regularly. Another analytical perspective is to look at moral choices at work in terms of power and the ability to bring about change. Finally, I draw the implication that we should stress moral awareness at a fairly abstract level for all employees and reinforce the moral primacy of individual choice. | Complicity |
Infection of macrophages by bacterial pathogens can trigger Toll-like receptor (TLR) activation as well as Nod-like receptors (NLRs) leading to inflammasome formation and cell death dependent on caspase-1 (pyroptosis). Complicating the study of inflammasome activation is priming. Here, we develop a priming-free NLRC4 inflammasome activation system to address the necessity and role of priming in pyroptotic cell death and damage-associated molecular pattern (DAMP) release. We find pyroptosis is not dependent on priming and when priming is re-introduced pyroptosis is unaffected. Cells undergoing unprimed pyroptosis appear to be independent of mitochondrial involvement and do not produce inflammatory cytokines, nitrous oxide (NO), or reactive oxygen species (ROS). Nevertheless, they undergo an explosive cell death releasing a chemotactic isoform of the DAMP high mobility group protein box 1 (HMGB1). Importantly, priming through surface TLRs but not endosomal TLRs during pyroptosis leads to the release of a new TLR4-agonist cysteine redox isoform of HMGB1. These results show that pyroptosis is dominant to priming signals and indicates that metabolic changes triggered by priming can affect how cell death is perceived by the immune system." | Neuronal Apoptosis-Inhibitory Protein |
The objective of this research was to generate the evidence on the private sector's contribution to overall immunization coverage for selected pediatric vaccines in India. Using IMS Health's (now IQVIA) vaccine sales audit data and innovative methodological approach we estimated private-sector vaccine share in the total immunization coverage across selected pediatric vaccines in India. Our estimates suggest that private sector remains an important contributor to immunization services in India not only for Universal Immunization Program vaccines (Bacillus Calmette-Guerin [19.23%], HiB pentavalent [11.09%], hepatitis B [5.75%], oral poliovirus vaccine [5.48%], Diphtheria-Pertussis-Tetanus [2.66%], and measles [2.17%]) but also for newer vaccines (hepatitis A [4.2%], rotavirus [3.4%], typhoid [3.3%], and pneumococcal conjugate vaccine [2.5%]). As the private sector continues to remain an important access point for immunization services in the country, avenues for potential synergy between public and private sectors should be explored to improve the coverage and quality of immunization services. | Private Sector |
PADAM stands for partial androgen deficiency in the aging male, and it is currently diagnosed with a testosterone level below 3 ng/ml (300 ng/dl or 12 nmol/l), and with symptoms varying according to the individual. The symptoms are a reduction or even loss of libido, a decline in muscle mass and strength, enhancement of visceral fatty tissue-padding, dryness of the skin, apathy, tiredness and distortion of mood right up to depression, and ostalgia due to osteoporosis. Before starting any form of hormonal substitution, which is only indicated if clinical symptoms and testosterone deficiency correlate, it is absolutely essential to exclude prostate cancer by using clinical evaluation and PSA values. Close PSA monitoring is necessary during testosterone substitution. In more than 95% of all patients with erectile dysfunction, the cause is not testosterone deficiency. Even a decreased level of dehydroepiandrosterone (DHEA) in an elderly male needs no replacement. There is also no indication for estradiol therapy in men--except in the rare case of aromatase deficiency. | Libido |
The microsporidium Glugea gasterostei from the three-spined stickleback Gasterosteus aculeatus was described as an independent species basing upon morphological and ecological traits of the parasite (Voronin, 1974), further supported by ultrastructural characters of its spores (Voronin, 1983). During the revision of microsporidia of the genus Glugea (Canning, Lom, 1986; Lom, 2002), the validity of this species was doubted and it was synonymized with G. anomala. Nevertheless, the molecular phylogenetic analysis performed in the present study showed the unique molecular haplotype of small subunit rRNA gene of G. gasterostei (Genbank accession number KM977990) and its close relatedness to G. anomala, G. atherinae and G. hertwigi (sequence similarity of 99.7 %). One of typical characters of G. gasterostei, as opposed to G. anomala, is the formation of xenomas on inner tissues and not on the surface of infected fishes. This feature is retained even after the infection of different host species. Taken together, these data confirm the validity of G. gasterostei as a separate species among closely related taxa that had diverged comparatively recently. | Glugea |
Cercarial dermatitis (swimmer's itch) is caused by the penetration of human skin by cercariae of schistosome parasites that develop in and are released from snail hosts. Cercarial dermatitis is frequently acquired in freshwater habitats, and less commonly in marine or estuarine waters. To investigate reports of a dermatitis outbreak in San Francisco Bay, California, we surveyed local snails for schistosome infections during 2005-2008. We found schistosomes only in Haminoea japonica, an Asian snail first reported in San Francisco Bay in 1999. Genetic markers place this schistosome within a large clade of avian schistosomes, but do not match any species for which there are genetic data. It is the second known schistosome species to cause dermatitis in western North American coastal waters; these species are transmitted by exotic snails. Introduction of exotic hosts can support unexpected emergence of an unknown parasite with serious medical or veterinary implications. | Cercaria |
Recent mass spectrometric studies of species and processes relevant to the chemistry of atmospheres are reported. New species have been detected, including HO(3); a stratospheric reservoir of OH radicals; the [H(2)O(+)O(2)(-)] charge transfer complex, central to the atmospheric photonucleation theory; and the OSOSO oxide and its cation, likely present in the Io's atmosphere. As to ionic processes, a new route to tropospheric N(2)O in air ionized by lightning and coronas is reported, as well as the complex chemistry promoted by ionization of ozone/freon and ozone/carbonyl sulfide mixtures and the formation of O(5)(+), relevant to the problem of (18)O excess in stratospheric ozone. | Air Ionization |
The objective of this study is to report operative time and associated complications of six types of implants and to determine if surgeons are adequately compensated. Hardware removals were analyzed from 2014-2019. Implants were flexible nails, intramedullary rigid nails, long plates, screw(s), single guided-growth plates, and multiple guided-growth plates. Patient demographics, operative time, blood loss, complications, and relative value units (RVU)/min were collected. RVU/min was used to maximize rate. In total, 392 patients were analyzed. Long plate removals took significantly longer than screw removal, therefore RVU/min was significantly lower (p < 0.001). Long plate removals also took significantly longer, and RVU/min was significantly lower compared to guided-growth plate removal (p < 0.001). Intramedullary nails took significantly longer compared to flexible nails, nearly double the RVU/min (p = 0.02). The results from this study indicate that the RVU/ minute for these six different types of implant removals are not equal. Surgeons can use this data to set up their schedule to ensure maximum utilization. (Journal of Surgical Orthopaedic Advances 30(1):020-023, 2021). | Surgical Equipment |
OBJECTIVE: To determine the reasons for the elimination of student sperm donors after semen analysis, physical examination, and laboratory tests in the Hubei Provincial Human Sperm Bank. Understanding the status of student sperm donors can provide a valid reference for the screening work of sperm banks. STUDY DESIGN: The screening data from 3,564 student sperm donors in Hubei Provincial Human Sperm Bank from January 1, 2010-April 30, 2013, were retrospectively analyzed. RESULTS: A total of 733 students (20.57%) qualified for semen analysis in the human sperm bank, whereas 602 students (16.89%) completed the sperm donation procedure. The main reasons for elimination were as follows: unqualified semen parameters (2,748 cases), failed semen extraction (83 cases), sexually transmitted diseases (44 cases), hereditary or chromosomal disorders (44 cases), and hepatitis B infection (25 cases). Education level and temperature/climate possibly affect semen quality. CONCLUSION: Unqualified semen parameters were the main reason for elimination among student sperm donors. Human sperm banks should promote reproductive health knowledge and information on improving semen quality among students when promoting sperm donation. | Sperm Banks |
The history of glutaryl-CoA dehydrogenase deficiency is determined by acute encephalopathic crises that are precipitated by common febrile diseases, vaccinations or surgical interventions during infancy and early childhood. Such crises result in an irreversible destruction of the basal ganglia (in particular of the putamina), and consequently dystonia, dyskinesia and choreoathetosis. Secondary complications include feeding and speech problems, failure to thrive, recurrent aspiration, immobilization, severe motor deficits and early death. It is generally accepted that maintenance treatment based on dietary lysine or protein restriction and supplementation with carnitine (and riboflavin) is insufficient to prevent acute crises during intercurrent illnesses or conditions that enhance catabolic state. Consequently, outpatient and inpatient emergency therapies have been implemented. The present review describes a recommended approach to emergency therapy for this disease. | Glutaryl-CoA Dehydrogenase |
A 22-month-old girl with a history of a congenital occipital cutaneous cyst was brought to the paediatric emergency department for lethargy and occipital headache. She had been discharged 5 days before for acute meningitis without bacterial isolates. At physical observation, she presented with irritability and neck hyperextension, with negative meningeal signs. CT scan revealed a vermian cyst and hydrocephalus. She was submitted to neurosurgery with removal of an infected midline dermoid cyst with a fistulous track to the skin. Surgery was successful and without complications. During follow-up, the child was asymptomatic with normal psychomotor development. | Lethargy |
OBJECTIVE: To assess the adequacy of the iodine supply in the Netherlands and to study possible ways of increasing the iodine intake. DESIGN, SETTINGS AND SUBJECTS: Goitre and nutrition surveillance studies (intake and urinary excretion of iodine) among population groups (age: 12-85 y, n=57-1704) in the Netherlands in the period 1981-1993. Simulation studies, based on the Dutch Nutrition Food Consumption Surveys (n=6000), calculating iodine intake among population groups after fictively iodizing different food groups. RESULTS: Mean intake of iodine, measured with different food consumption methods in the period 1984-1993, met the recommended amount of 150-300 microg per day in males, but not in females. Median urinary iodine excretion levels were in the range for mild Iodine Deficiency Disorders in both sexes. According to dietary methods reflecting habitual intake and urinary iodine excretion per kg body weight or per mmol creatinin the prevalence of low iodine supply among adults is between 4 and 20% for women and between 5 and 15% for men. Iodization of different products would increase mean iodine intakes by up to 45% and would give a reduction of roughly 65% in the prevalence of low iodine intakes. CONCLUSION: The present goitre prophylaxis in the Netherlands is not optimally effective. The iodine supply is below cut-off points in 4-20% of the adult population. It is possible to decrease the prevalence of low iodine intakes without a clear risk of exceeding the maximum acceptable daily iodine intake by increasing the iodine content of baker's salt and/or by adding iodine to other foods. | Iodine |
Epithelial polarity is controlled by a polarity machinery that includes Rho GTPase CDC42 and Scribble/PAR. By using intestinal stem cell (ISC)-specific deletion of CDC42 in olfactomedin-4 (Olfm4)-internal ribosome entry site (IRES)-EGFP/CreERT2;CDC42(flox/flox) mice, we find that CDC42 loss initiated in the ISCs causes a drastic hyperproliferation of transit amplifying (TA) cells and disrupts epithelial polarity. CDC42-null crypts display expanded TA cell and diminished ISC populations, accompanied by elevated Hippo signaling via YAP/TAZ-Ereg (yes-associated protein/WW domain-containing transcription regulator protein 1-epiregulin) and mechanistic target of rapamycin (mTOR) activation, independent from canonical Wnt signaling. YAP/TAZ conditional knockout (KO) restores the balance of ISC/TA cell populations and crypt proliferation but does not rescue the polarity in CDC42-null small intestine. mTOR or epidermal growth factor receptor (EGFR) inhibitor treatment of CDC42 KO mice exhibits similar rescuing effects without affecting YAP/TAZ signaling. Inducible ablation of Scribble in intestinal epithelial cells mimics that of CDC42 KO defects, including crypt hyperplasia and Hippo signaling activation. Mammalian epithelial polarity regulates ISC/TA cell fate and proliferation via a Hippo-Ereg-mTOR cascade. | cdc42 GTP-Binding Protein |
The claims about (1) the lack of empirical support for a model of strong reciprocation and (2) the irrelevant empirical role of costly punishment to support cooperation in the field need qualifications. The interpretation of field evidence is not straightforward, and other-regarding preferences are also likely to play a role in the field. | Punishment |
Experiments on rats were made to study the content of ascorbic (AA), Dehydroascorbic (DAA) and diketogulonic (DKGA) acids in the blood serum, daily urine, liver, adrenal, kidney, spleen and lung tissues under varying body supply with vitamin K. The rats with vitamin K deficiency manifested the decreased content of AA, DAA and the elevated content of DKGA in the blood serum, daily urine and test tissues. The percentage of AA absorption by blood proteins was found to be increased upon vitamin K deficiency in the body. The changes in AA metabolism correlated with the reduced capillary resistance. Administration of AA to rats with vitamin K deficiency led to an increase in the content of AA, DAA and to a lowering of DKGA in the blood serum and tissues promoting the normalization of capillary resistance. The data obtained attest to the dependence of AA metabolism on the body supply with vitamin K, pointing to the necessity of exercising the control over AA metabolism in different forms of vitamin K deficiency. | Ethyl Biscoumacetate |
BACKGROUND: Cannulation of children is often required for administration of intravenous fluids and medications, but can cause pain and anxiety. Amethocaine and a eutectic mixture of local anaesthetics (EMLA) cream are two of the most commonly used local anaesthetic creams. OBJECTIVE: To examine the evidence for the superiority of Amethocaine cream compared with EMLA cream in facilitating successful first-time cannulation in children. METHOD: A systematic search was undertaken in MEDLINE and EMBASE in June 2014. Studies examining cannulation, undertaken with children and providing data about first-time cannulation success rates were considered for inclusion. Three randomised controlled trials met the inclusion criteria and were included in the meta-analysis. Data extraction was undertaken independently by the two authors using predefined data fields. RESULTS: Pooled analysis was based on a random effects model. Low statistical heterogeneity was observed. Amethocaine cream increased the likelihood of successful first-time cannulation (RR 1.046, CI 0.975 to 1.122), although this did not reach statistical significance (p=0.211). CONCLUSIONS: Amethocaine cream does not appear to significantly facilitate successful first-time cannulation. Lack of precision and design weaknesses of the included studies hinder the formation of a strong recommendation for either cream. IMPLICATIONS: Based on the evidence reviewed here and considering analgesic properties and cost-savings associated with both creams, a weak recommendation can be issued in favour of Amethocaine cream for cannulation in children based on high-quality evidence but where the treatment choice will depend on other factors including cost and provider preference." | Lidocaine, Prilocaine Drug Combination |
Tamai, Kenzo (Kanazawa University, Kanazawa, Japan), and Shoki Nishida. Taxonomy of Clostridium bifermentans and Clostridium sordellii. II. Toxigenic and sporulating potencies in substrains of a Clostridium sordellii strain. J. Bacteriol. 88:1647-1651. 1964.-The existence of six biological criteria for distinction of Clostridium bifermentans and C. sordellii was confirmed. The difference in the six criteria gradually disappeared as the sporulating potency of the substrains of C. sordellii 4708 was strengthened. The substrains which could resist heating at 90 C for 10, 20, or 30 min were found to have lost all six criteria for distinction and were biologically in agreement with C. bifermentans. We further demonstrated that all newly isolated strains of C. bifermentans examined possessed extremely strong sporulating potency. | Clostridium bifermentans |
Medulloblastoma (MB) is the most common malignant brain tumor in children and is highly invasive and metastatic. Despite recent advances, most MB patients suffer significant therapy-related morbidity, and the survival rate for patients with metastatic MB remains unsatisfactory. Altered expression of FOXM1 has been detected in many types of cancers, and the inhibition of FOXM1 has been studied as a cancer therapy. In the present study, we evaluated the impact of the inhibition of FOXM1 by thiostrepton in Daoy MB cells. Cells were treated with different concentrations of thiostrepton alone or in combination with cisplatin. Cell viability was measured with CCK-8 assays, and cell cycle distribution and apoptosis were assessed by flow cytometric analysis. Changes in protein expression were examined by western blotting. RNAi experiments were performed using siRNA oligonucleotides. The invasion and migration studies were performed using 8-microm Transwell plates. Inhibition of FOXM1 by thiostrepton significantly decreased MB cell proliferation. Cell arrest at the G2/M phase and apoptosis were significantly increased in MB cell lines that were treated with thiostrepton or transfected with siRNA. Thiostrepton decreased the IC50 value of cisplatin for MB treatment by enhancing cisplatin-induced apoptosis. Thiostrepton also decreased cell invasion and migration, which are crucial steps for tumor progression. Our data suggest that targeting FOXM1 with small-molecule inhibitors results in potent antitumor activity and chemosensitizing effects in human medulloblastoma cells. | Thiostrepton |
PURPOSE: The classic model for the effects of NaHCO3 on myocardial function predicts transient myocardial depression after an intravenous bolus of sodium bicarbonate in association with myocardial acidosis. METHODS: Five anesthetized, paralyzed, and ventilated dogs underwent midline sternotomy. Myocardial global function was assessed by cardiac output, left ventricular (LV) dp/dt, LV end-systolic, and LV end-diastolic pressures. Regional myocardial function assessed by measuring the LV regional end-systolic, LV end-diastolic lengths, and LAD coronary blood flow. Coronary sinus, intramyocardial and arterial pH were measured as was free serum Ca++. Animals were made acidemia by infusion of 0.3 N HCl and then given a bolus of sodium bicarbonate. This produced transient depression followed by recovery of myocardial function. RESULTS: During the depression phase there was no significant decrease in interstitial pH or an increase in A-VCO2 difference as predicted by the current model. However, there was a significant decrease in the serum free Ca++ that coincided with myocardial depression. CONCLUSION: We could not confirm the predictions of the classic model and hypothesize that myocardial depression may be caused by decreased availability of free Ca++ of decreased Ca++ flux rather than intracellular acidosis. | Sodium Bicarbonate |
For young children with autism spectrum disorders, one of the choice interventions is Early Intensive Behavioral Intervention. Over the past ten years, its effectiveness has been abundantly evaluated based on various parameters, including the intensity and duration of the intervention. Despite major advances in effectiveness evaluation, data concerning the implementation of the intervention are often described briefly, and the active ingredients of the intervention are but rarely linked to the documented effects. OBJECTIVES: This study aims at reviewing with a systematic method, the studies pertaining to EIBI provided to children with autism spectrum disorders over the past ten years (2005-2015) and at documenting the program implementation components described in the studies, based on Dane and Schneider's (1998) model in accordance with PRISMA guidelines. RESULTS: The results show that, although the variables related to intervention dosage and protocol are relatively well described, the authors do not always consider them in the effects analysis. Furthermore, the majority of the studies did not report information on intervention participation, differentiation or quality. CONCLUSIONS: Data concerning the implementation of the intervention are partially described in the articles retained. In this regard, a better description of the intervention provided and a more systematic evaluation of its implementation seem necessary to detect the subtle differences in the effects of the intervention. | Early Medical Intervention |
Military children often present with psychological health concerns related to their experience of deployments, reintegration, and frequent moves common in military life. MilitaryKidsConnect is a Department of Defense (DoD) Web site designed to enhance the coping of military children in the context of their military life experience. The purpose of this paper is to describe the development of the Web site as a resource that provides psychoeducation, coping strategies, and peer support to military children." | United States Department of Defense |
Bone marrow failure syndromes (BMFS) are a group of disorders with complex pathophysiology characterized by a common phenotype of peripheral cytopenia and/or hypoplastic bone marrow. Understanding genetic factors contributing to the pathophysiology of BMFS has enabled the identification of causative genes and development of diagnostic tests. To date more than 40 mutations in genes involved in maintenance of genomic stability, DNA repair, ribosome and telomere biology have been identified. In addition, pathophysiological studies have provided insights into several biological pathways leading to the characterization of genotype/phenotype correlations as well as the development of diagnostic approaches and management strategies. Recent developments in bone marrow transplant techniques and the choice of conditioning regimens have helped improve transplant outcomes. However, current morbidity and mortality remain unacceptable underlining the need for further research in this area. Studies in mice have largely been unable to mimic disease phenotype in humans due to difficulties in fully replicating the human mutations and the differences between mouse and human cells with regard to telomere length regulation, processing of reactive oxygen species and lifespan. Recent advances in induced pluripotency have provided novel insights into disease pathogenesis and have generated excellent platforms for identifying signaling pathways and functional mapping of haplo-insufficient genes involved in large-scale chromosomal deletions-associated disorders. In this review, we have summarized the current state of knowledge in the field of BMFS with specific focus on modeling the inherited forms and how to best utilize these models for the development of targeted therapies. Stem Cells 2017;35:284-298. | Bone Marrow Diseases |
Bacterial recovery by a portable Reuter centrifugal air sampler and a standard Mattson-Garvin slit-to-agar air sampler was compared in a series of experiments. Microbial air quality was monitored in seven typical laboratory locations. Tests showed that the Reuter centrifugal air sampler yielded significantly higher recoveries than did the slit-to-agar unit. | Centrifugation |
OBJECTIVE: Rural areas in the Southern United States are characterized by certain cultural values that may delay or prevent mental health service utilization. The present study examined a four-stage chain of serial mediation where higher levels of general self-reliance would be related to greater levels of public stigma, which would in turn be related to higher levels of self-stigma, followed by greater self-reliance about managing mental health problems, and finally, more negative attitudes toward seeking help from psychologists. METHOD: Community members who lived in rural counties in the Southern United States (N = 783) completed measures of these constructs online. RESULTS: Mediation analyses supported a direct association between general self-reliance and attitudes toward help-seeking that was explained in serial by higher levels of public stigma, self-stigma, and mental health self-reliance. CONCLUSIONS: Clinical implications for rural practitioners are suggested including instilling policy changes, increasing provider visibility, and addressing barriers in therapy. | Mediation Analysis |
Dyspnea is defined as a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity. It is a common symptom among patients with respiratory diseases that reduces daily activities, induces deconditioning, and is self-perpetuating. Although clinical interventions are needed to reduce dyspnea, its underlying mechanism is poorly understood depending on the intertwined peripheral and central neural mechanisms as well as emotional factors. Nonetheless, experimental and clinical observations suggest that dyspnea results from dissociation or a mismatch between the intended respiratory motor output set caused by the respiratory neuronal network in the lower brainstem and the ventilatory output accomplished. The brain regions responsible for detecting the mismatch between the two are not established. The mechanism underlying the transmission of neural signals for dyspnea to higher sensory brain centers is not known. Further, information from central and peripheral chemoreceptors that control the milieu of body fluids is summated at higher brain centers, which modify dyspneic sensations. The mental status also affects the sensitivity to and the threshold of dyspnea perception. The currently used methods for relieving dyspnea are not necessarily fully effective. The search for more effective therapy requires further insights into the pathophysiology of dyspnea." | Signs and Symptoms, Respiratory |
Even in the 21st century, studies aimed at characterizing the pathological paradigms associated with the development and progression of central nervous system diseases are primarily performed in laboratory animals. However, limited translational significance, high cost, and labor to develop the appropriate model (e.g., transgenic or inbred strains) have favored parallel in vitro approaches. In vitro models are of particular interest for cerebrovascular studies of the blood-brain barrier (BBB), which plays a critical role in maintaining the brain homeostasis and neuronal functions. Because the BBB dynamically responds to many events associated with rheological and systemic impairments (e.g., hypoperfusion), including the exposure of potentially harmful xenobiotics, the development of more sophisticated artificial systems capable of replicating the vascular properties of the brain microcapillaries are becoming a major focus in basic, translational, and pharmaceutical research. In vitro BBB models are valuable and easy to use supporting tools that can precede and complement animal and human studies. In this article, we provide a detailed review and analysis of currently available in vitro BBB models ranging from static culture systems to the most advanced flow-based and three-dimensional coculture apparatus. We also discuss recent and perspective developments in this ever expanding research field. | Blood-Brain Barrier |
In order to assign appropriate baseline estimation algorithms to different fetal heart rate tracing, a method to evaluate the fetal heart rate (FHR) baseline combining with the fetal movement information was proposed. Fetal actography and tocography were used to extract the fetal movement information. The results showed that the combined method, where the fetal movement detection result was the union of results of actography and tocography, achieved a better performance with the highest sensitivity and an acceptable positive predictive value (PPV). Furthermore, the mean absolute errors (MAEs) of basal FHR values between the two algorithms and the expert were calculated with respect to the duration coefficient of fetal movement. The results showed that the algorithm using empirical mode decomposition (EMD) and Kohonen neural network (KNN) had lower MAEs than a traditional linear baseline estimation algorithm as the duration coefficient increased. However, if the duration coefficient is below 0.2, the errors may be tolerant for the FHR baseline estimation by a linear baseline estimation algorithm, which indicates that different algorithms may be selected for FHR baseline estimation based on different duration coefficients of fetal movement. | Uterine Monitoring |
Traditional bioanalytical measurements determine concentrations of drug and metabolites in plasma; however, most drugs exert their effects in defined target tissues. As there is no clear relation between concentrations in plasma and those in tissue, alternative methods must be employed to study the absorption, distribution, metabolism and excretion properties of new therapeutic agents. Quantitative whole-body autoradiography is used in the drug development process to determine the distribution and concentrations of radiolabeled test compounds in laboratory animals. Quantitative whole-body autoradiography can provide information on tissue PKs, penetration, accumulation and retention. Although the technique is considered the industry standard for performing preclinical tissue distribution studies, it is perhaps timely, 60 years after the first reported use of the method, to re-assess the technique against modern alternatives. | Autoradiography |
PURPOSE: To describe a series of patients with acquired epiblepharon secondary to thyroid-related orbitopathy. METHODS: Retrospective case series of 9 patients with thyroid-related orbitopathy who had epiblepharon. RESULTS: Seven patients had epiblepharon in both lower eyelids and 2 patients had it in one lower eyelid. Six of the 9 patients were Asian. Each patient had punctate keratopathy. Epiblepharon resolved in all but one patient after treating coexisting manifestations of thyroid-related orbitopathy. One patient required epiblepharon repair. CONCLUSIONS: We describe a new finding of acquired epiblepharon in the setting of thyroid-related orbitopathy. The majority of patients have spontaneous resolution of the epiblepharon after other surgical procedures for thyroid-related orbitopathy. | Graves Disease |
The article aimed to update scientific literature information about respiratory health effects caused by sugarcane burning, considering the expansion of sugarcane plantations in Brazil and in the state of Sao Paulo. Articles published between 1996 and 2006, which deal with the health effects of sugarcane burning and/or air pollutants originating from this burning, were discussed. These studies suggest that part of the population--especially the elderly, children and asthmatics--suffers health effects of sugarcane burning. As a result, these people require health care, thus affecting health services and their families. | Incineration |
Endothelin-1 produced a phasic contraction in the longitudinal muscle preparation isolated from the rat gastric body, but produced a sustained contraction in the circular muscle preparation. Indomethacin, a cyclo-oxygenase inhibitor, decreased the endothelin-1-induced contraction of the longitudinal preparation, but did not affect the endothelin-1-induced contractions of the circular muscle. In the absence of indomethacin, the maximal contractile tension (Emax) and the concentration producing a half-maximal contraction (EC50) induced by endothelin-3 in the longitudinal muscle preparations were smaller than those for endothelin-1, whereas in the circular muscle preparations there were no significant differences between the values (EC50, Emax) for endothelin-1 and endothelin-3. In the presence of indomethacin, endothelin-3-induced contraction of the longitudinal muscle preparation is more potent than that of endothelin-1. SC-19220, a prostaglandin E2 receptor antagonist, significantly decreased endothelin-1-induced contraction of the longitudinal preparation, prostaglandin E2 produced a concentration-dependent contraction in the longitudinal preparation, but had no effects in the circular muscle preparation. Endothelin-1 (10(-8) M) significantly increased the release of immunoassayable prostaglandin E2 from rat gastric smooth muscle. These results point to the existence of distinct endothelin receptor subtypes in the smooth muscle of rat gastric body, and a potential role of endothelin-1 in regulating gastric motility. Moreover, one of the endothelin receptor subtypes is related to the production of prostaglandin E2." | Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide |
Monoclonal antibodies were produced following immunization of rats with delta sleep-including peptide (DSIP). The spleen cells of the rats were fused with the myeloma cell line SP2/0. The supernatants of hybridomas were screened on a solid-phase immunoassay using dot-immunobinding of DSIP and some DSIP fragments. The supernatants of six stable producer clones were found to react with DSIP. From this procedure it was also deduced that all these monoclonal antibodies recognized epitope(s) of the penta carboxy-terminal region of DSIP (DSIP5-9). Application of these monoclonal antibodies to rat median eminence sections gave a strong immunolabelling of a large population of fibres and terminal-like structures, mainly localized through the lateral areas. Elution-restaining experiments using a monoclonal antibody to DSIP and a polyclonal antiserum to luteinizing hormone-releasing hormone (LHRH) showed that the patterns of immunoreactivity respectively visualized overlap almost completely. Although numerous LHRH-immunoreactive neuronal elements were also easily demonstrated in the median eminence of the mouse, the hamster and the gerbil species, incubation of sections with monoclonal antibodies to DSIP failed to give any immunoreaction. Taken together these data argue for the independence of the DSIP/LHRH immunolabelling systems. Furthermore, it was demonstrated that DSIP5-9-related epitopes detected in the rat median eminence have no counterpart in the three other rodent species investigated. These species differences may reflect the fact that the carboxy-terminal sequence of the nonapeptide DSIP originally discovered in the rabbit is not conserved in all rodent species. | Delta Sleep-Inducing Peptide |
Host defense against Staphylococcus aureus greatly depends on bacterial clearance by phagocytic cells. LukGH (or LukAB) is the most potent staphylococcal leukocidin towards human phagocytes in vitro, but its role in pathogenesis is obscured by the lack of suitable small animal models because LukGH has limited or no cytotoxicity towards rodent and rabbit compared with human polymorphonuclear cells (PMNs) likely due to an impaired interaction with its cellular receptor, CD11b. We aimed at adapting LukGH for the rabbit host by improving binding to the rabbit homolog of CD11b, specifically its I-domain (CD11b-I). Targeted amino acid substitutions were introduced into the LukH polypeptide to map its receptor interaction site(s). We found that the binding affinity of LukGH variants to the human and rabbit CD11b-I correlated well with their PMN cytotoxicity. Importantly, we identified LukGH variants with significantly improved cytotoxicity towards rabbit PMNs, when expressed recombinantly (10-15-fold) or by engineered S. aureus strains. These findings support the development of small animal models of S. aureus infection with the potential for demonstrating the importance of LukGH in pathogenesis. | Leukocidins |
PURPOSE: The aim of this study is to determine whether short-term exposure to fine particulate matter (PM(2.5)) is associated with emergency ambulance dispatches for cardiovascular diseases in Japan. METHODS: The nationwide data on emergency dispatches of ambulance for cardiovascular diseases classified as I00-I99 by International Classification of Diseases-10th revision in 30 Japanese prefectures between April 1 and December 31, in 2010 were analyzed. Data on weather variability including PM(2.5), temperature and relative humidity were acquired from ambient air pollution monitoring stations. Conditional Poisson regression models were used to estimate the prefecture-specific effects of PM(2.5) on morbidity, and adjust for confounding factors. A meta-analysis was then applied to pool estimates at the 30-prefecture level. RESULTS: A total of 160,566 emergency ambulance dispatches for cardiovascular diseases were reported during the study period. The risk of emergency ambulance dispatch for cardiovascular diseases significantly increased with an increase in the exposure to PM(2.5) in Fukuoka and Iwate Prefectures. However, we found no statistically significant associations between PM(2.5) and emergency ambulance dispatches in the pooled analysis (odds ratio 1.00, 95 % confidence interval 0.99-1.00). Heterogeneity was not observed between prefectures (Cochran Q test, p = 0.187, I (2) = 18.4 %). CONCLUSIONS: Exposure to PM(2.5) is not associated with overall emergency ambulance dispatches for cardiovascular diseases in Japan. | Emergency Medical Dispatch |
Beyond improvement of glucose control, thiazolidinediones exert pleiotropic effects, which may contribute to some cardiovascular protection. PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events") has provided valuable, although controversial, information on the impact of pioglitazone on cardiovascular outcomes in a high-risk population of patients with type 2 diabetes and established macrovascular disease. Since 2005, there has been much debate on the relative value of the statistically non-significant 10% reduction in the quite challenging primary composite endpoint (combining cardiovascular disease-driven and procedural events in all vascular beds) versus the statistically significant 16% decrease in the more robust and conventional main secondary endpoint (all-cause mortality, myocardial infarction, and stroke) observed with pioglitazone. Revisiting PROactive deserves much interest following the report of inconclusive results on cardiovascular efficacy and safety of rosiglitazone in RECORD, the withdrawal (limitation) of rosiglitazone because of cardiovascular safety concern, the recent publication of a statement positioning pioglitazone in type 2 diabetes and the near availability of cheaper generics of pioglitazone. Although subanalyses may have more limited value from a statistical viewpoint, they nonetheless can provide valuable information on the drug efficacy/safety profile and clinical insights into which patients might benefit most (in terms of cardiovascular outcomes) from pioglitazone therapy." | Thiazolidinediones |
BACKGROUND: The incidence of invasive fungal infections has increased globally as a result of several factors. Conventional amphotericin B (sodium deoxycholate) has been used as standard therapy for the treatment of invasive fungal infections; however, it is associated with adverse drug reactions, including acute kidney injury (AKI). New formulations of amphotericin B have aimed to improve the safety profile of the conventional formulation. OBJECTIVES: This review aimed to assess the effects of amphotericin B deoxycholate versus liposomal amphotericin B on kidney function. SEARCH METHODS: We searched Cochrane Kidney and Transplant's Specialised Register to 10 March 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared amphotericin B sodium deoxycholate with liposomal amphotericin B. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for eligibility and conducted risk of bias evaluation. MAIN RESULTS: We included 12 studies (2298 participants) in this review. Of these, 10 were meta-analysed (2172 participants). Liposomal amphotericin B was found to be significantly safer than conventional amphotericin B in terms of serum creatinine increase (RR 0.49, 95% CI 0.40 to 0.59). There was significant decrease in all infusion-related reactions in the liposomal group compared with the conventional group: fever (4 studies, 1092 participants): RR 0.39, 95% CI 0.28 to 0.55; I(2) = 32%); chills and/or rigours (5 studies, 1081 participants): RR 0.27, 95% CI 0.15 to 0.48; I(2) = 75%); fever and/or rigours (2 studies, 720 participants): RR 0.68, 95% CI 0.52 to 0.90; I(2) = 58%); nausea (6 studies, 1187 participants): RR 0.50, 95% CI 0.35 to 0.72; I(2) = 0%); and vomiting (3 studies, 1019 participants): RR 0.51, 95% CI 0.27 to 0.95; I(2) = 61%). Overall, risk of bias in included studies was low or unclear for most domains. However, blinding of participants and personnel, blinding of outcome assessment and other bias (funding) tended to have a high risk of bias. The sensitivity analysis performed did not change the significance of difference in favour of the liposomal formulation. Assessment for publication bias found that review results were robust. AUTHORS' CONCLUSIONS: Current evidence suggests that liposomal amphotericin B is less nephrotoxic than conventional amphotericin B (when the effect on kidney function is measured as an increase in serum creatinine level equal to or greater than two-fold from the baseline level). We also found that there were fewer infusion-related reactions associated with the liposomal formulation. | Chills |
Methanogenic archaea are genotypically and phenotypically diverse organisms that are integral to carbon cycling in anaerobic environments. Owing to their genetic tractability and ability to be readily cultivated, Methanosarcina spp. have become a powerful model system for understanding methanogen biology at the cellular systems level. However, relatively little is known of how genotypic and phenotypic variation is partitioned in Methanosarcina populations inhabiting natural environments and the possible ecological and evolutionary implications of such variation. Here, we have identified how genomic and phenotypic diversity is partitioned within and between Methanosarcina mazei populations obtained from two different sediment environments in the Columbia River Estuary (Oregon, USA). Population genomic analysis of 56 M. mazei isolates averaging <1% nucleotide divergence revealed two distinct clades, which we refer to as 'mazei-T' and 'mazei-WC'. Genomic analyses showed that these clades differed in gene content and fixation of allelic variants, which point to potential differences in primary metabolism and also interactions with foreign genetic elements. This hypothesis of niche partitioning was supported by laboratory growth experiments that revealed significant differences in trimethylamine utilization. These findings improve our understanding of the ecologically relevant scales of genomic variation in natural systems and demonstrate interactions between genetic and ecological diversity in these easily cultivable and genetically tractable model methanogens. | Methanosarcina |
BACKGROUND: Various methods of tissue processing have been used to treat melanoma with Mohs micrographic surgery (MMS). OBJECTIVE: We describe a method of treating melanoma with MMS that combines breadloaf frozen sectioning of the central debulking excision with complete peripheral and deep microscopic margin evaluation, allowing detection of upstaging and comprehensive pathologic margin assessment before reconstruction. METHODS: We conducted a retrospective cohort study evaluating for local recurrence and upstaging in 614 invasive or in situ melanomas in 577 patients treated with this MMS tissue processing methodology using frozen sections with melanoma antigen recognized by T cells 1 (MART-1) immunostaining. Follow-up was available in 597 melanomas in 563 patients. RESULTS: Local recurrence was identified in 0.34% (2/597) lesions with a mean follow-up time of 1026 days (2.8 years). Upstaging occurred in 34 of 614 lesions (5.5%), of which 97% (33/34) were detected by the Mohs surgeon before reconstruction. LIMITATIONS: Limitations include retrospective study, intermediate follow-up time, and that the recurrence status of 39.6% of patients was self-reported. CONCLUSION: Treating melanoma with MMS that combines breadloaf sectioning of the central debulking excision with complete peripheral and deep microscopic margin evaluation permits identification of upstaging and consideration of sentinel lymph node biopsy before definitive reconstruction and achieves low local recurrence rates compared with conventional excision. | MART-1 Antigen |
In historical cases, missing persons' identification, mass disasters, and ancient DNA investigations, bone and teeth samples are often the only, and almost always the best, biological material available for DNA typing. This is because of the physical and chemical barrier that the protein:mineral matrix of bone poses to environmental deterioration and biological attack. Most bone extraction protocols utilized in the forensic community involve an incubation period of bone powder in extraction buffer for proteinase digestion, followed by the collection of the supernatant, and the disposal of large quantities of undissolved bone powder. Here we present an extremely efficient protocol for recovery of DNA by complete demineralization, resulting in full physical dissolution of the bone sample. This is performed in a manner that retains and concentrates all the reagent volume, for complete DNA recovery. For our study, we selected 14 challenging bone samples. The bones were extracted side-by-side with our new demineralization protocol and the standard extraction protocol in use at AFDIL. A real-time quantification assay based on the amplification of a 143 bp mtDNA fragment showed that this new demineralization protocol significantly enhances the quantity of DNA that can be extracted and amplified from degraded skeletal remains. We have used this technique to successfully recover authentic DNA sequences from extremely challenging samples that failed repeatedly using the standard protocol." | Bone Demineralization Technique |
Arrhythmogenic right ventricular (RV) dysplasia/cardiomyopathy (ARVD/C) is a heart muscle disease characterized by peculiar RV involvement and electrical instability that precipitates ventricular arrhythmias and sudden death. The purpose of the present consensus report of the Study Group on ARVD/C of the Working Groups on Myocardial and Pericardial Disease and Arrhythmias of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the World Heart Federation is to review the considerable progress in our understanding of the etiopathogenesis, morbid anatomy, and clinical presentation of ARVD/C since it first was described in 1977. The present article focuses on important but still unanswered issues, mostly regarding risk stratification, clinical outcome, and management of affected patients. Because ARVD/C is relatively uncommon and any one center may have experience with only a few patients, an international registry is being established to accumulate information and enhance the numbers of patients that can be analyzed and thus answer pending questions. The registry also will facilitate pathological, molecular, and genetics research on the causes and pathogenesis of the ARVD/C. Furthermore, availability of an international database will enhance awareness of this largely unrecognized condition among the medical community. Physicians are encouraged to enroll patients in the International Registry of ARVD/C." | Arrhythmogenic Right Ventricular Dysplasia |
Loss of intercellular adhesion and increased cell motility synergistically facilitate tumor cell invasion. We studied these factors in 90 patients with gastric cancers by using an immunohistochemical technique to detect strong or weak expression of E-cadherin (ECD) and autocrine motility factor receptor (AMFR). Normal gastric mucosa (control) reacted strongly for ECD and weakly for AMFR. In study cases, ECD was weak in 47 cases, and AMFR was strong in 39 cases. Weak ECD and strong AMFR expression were associated with tumor dedifferentiation. AMFR expression correlated positively with depth of invasion but not with lymph node metastasis. ECD expression correlated negatively with lymph node metastasis but not with depth of invasion. A strong inverse correlation was found between ECD and AMFR expression. Tumors with weak ECD and strong AMFR expression displayed a more aggressive phenotype than tumors with strong ECD and weak AMFR expression. The postoperative survival of patients with tumors with weak ECD and strong AMFR expression was significantly shorter than that of other groups. Since they are involved in the pathway to development of tumors with a more aggressive phenotype, ECD and AMFR should be examined to evaluate the biologic potential of gastric cancers." | Receptors, Autocrine Motility Factor |
A patient with Waldenstr]om's macroglobulinemia whose serum demonstrated properties of both pyroglobulin and cryoglobulin was studied. A monoclonal (M) protein in the serum of the patient was identified by immunoelectrophoresis (IEP) and immunofixation electrophoresis (IFE) as IgM-lambda. The M-protein was separated by gel permeation high-performance liquid chromatography (HPLC). Cryoglobulin in the serum was isolated by the method of cold precipitation. The cryoglobulin was identified as IgM-lambda type by IEP and was the same M-protein as that which occurred in this patient's serum. The purified cryoglobulin also had the properties of a pyroglobulin. Neither property disappeared following pretreatment with 2-mercaptoethanol (2-ME), urea, and Triton X-100 detergent, and deglycosylation with N-glycanase (E.C. 3.5.1.52). We suggest that these abnormal properties were caused by the molecular abnormality of the IgM-lambda M-protein. | Pyroglobulins |
Hyperimmune antirickettsial serum was shown to prevent the attachment/penetration stage of Rickettsia tsutsugamushi infection of suspended chicken cells. The extent of the inhibition depended on the serum concentration but not on the presence of complement. The neutralizing activity was reduced by prior adsorption of immune serum with staphylococcal protein A or with intact rickettsiae but was not affected by adsorption with target cells. In the neutralization tests, there was no cross-reactivity between the Karp and Gilliam strains of R. tsutsugamushi. Incubation of rickettsiae with immune serum did not alter their capacity to metabolize glutamate nor grossly damage the permeability barrier function of their cytoplasmic membranes. Although the assay method had the capacity to detect some aggregated infectious organisms, none were found in immune serum-treated suspensions. It was concluded that immune serum may inhibit rickettsial infection by blocking a surface component(s) whose function is necessary for attachment to and/or penetration of target cells. | Orientia tsutsugamushi |
Many non-steroidal anti-inflammatory drugs (NSAIDs) (including sulphasalazine, sulindac, indomethacin, naproxen, salicylic acid, ibuprofen, piroxicam and mefenamic acid) were found to be competitive inhibitors (with respect to folate) of avian liver phosphoribosylaminoimidazolecarboxamide formyltransferase (AICAR transformylase, EC 2.1.2.3) and bovine liver dihydrofolate reductase (EC 1.5.1.3). In contrast, aspirin and the antipyretic-analgesic drugs acetaminophen and antipyrine were weak inhibitors of these enzymes. Structure-activity correlation suggests that an aromatic ring with a side chain containing a carboxylic acid is a requirement for competitive inhibition of the transformylase. The above-listed NSAIDs also inhibited the folate-coenzyme-mediated biosynthesis of serine from glycine and formate (i.e., the C1 index) by human blood mononuclear cells (BMCs) in experiments where the drug was added to a culture of BMCs. Acetaminophen had a weak inhibitory effect on the C1 index. Consistent with the results obtained in vitro is the observation that the C1 index of BMCs from rheumatoid-arthritis patients treated with drugs which possess little antifolate activity (e.g. acetaminophen) is higher than the C1 index of BMCs from rheumatoid-arthritis patients treated with NSAIDs possessing more potent antifolate activity (e.g. sulindac, sulphasalazine, naproxen and ibuprofen). The mean activity of the transformylase in BMCs taken from healthy humans was 1.98 nmol of product/h per 10(6) cells and the activity was positively correlated with BMC folate levels. These results are consistent with the hypothesis that (1) the antifolate activity of NSAIDs, and hence cytostatic consequences, are important factors in producing anti-inflammatory activity and (2) aspirin exerts its anti-inflammatory effects after its conversion into salicylic acid, which possesses greater antifolate activity than its parent compound." | Phosphoribosylaminoimidazolecarboxamide Formyltransferase |
Aldehydes are ubiquitous contaminants in the human environment. Intracellular aldehydes are mainly derived from the metabolism of polyunsaturated fatty acids and from lipid peroxidation, which is significantly elevated under oxidative stress conditions. Oxidative stress has long been suspected to be involved in many disease processes, including carcinogenesis, neurodegeneration and aging, but its mechanisms are largely unknown. Aldehydes are reactive not only toward nucleic acids but also to many amino acids, and these aldehyde-protein interactions have been suspected of affecting many cellular functions, including DNA repair. To test this possibility we determined the effect of malondialdehyde (MDA), one of the most abundant intracellular aldehyde, on ultraviolet (UV) light- and benzo(a)pyrene diol epoxide (BPDE)-induced cytotoxicity and mutagenesis in human cells. We found that MDA treatment greatly sensitized cells to both UV- and BPDE-induced cell killing and that, MDA pre-treatment significantly enhanced UV-induced mutagenesis. Using in vitro DNA repair synthesis and host cell reactivation assays we found that MDA treatment of cells greatly inhibited nucleotide excision repair for both and UV light- and BPDE-induced DNA damage. Further experiments raise the possibility that the inhibitory effect on nucleotide excision repair is mainly caused by the direct interaction of MDA with cellular repair proteins. Together these results strongly suggest that intracellular aldehydes play an important role in oxidative stress-related mutagenesis and carcinogenesis through their inhibitory effect on DNA repair mechanisms as well as on induction of DNA damage. | Malondialdehyde |
This study compared the efficacy of 4 different hamstring-stretching techniques. Flexibility can be achieved by a variety of stretching techniques, yet little research has been performed on the most effective method. The 2 basic types include active stretching, in which range of motion is increased through voluntary contraction, and passive stretching, in which range of motion is increased through external assistance. The 2 types of active stretching include neuromobilization and proprioceptive neuromuscular facilitation (PNF). Our study aims to determine which type of stretching technique is most effective in improving hamstring length. One hundred subjects between the ages of 21 and 57 were enrolled in the study. Intrarater reliability of hamstring length measurement was performed using 10 subjects. All 100 subjects were included in a randomized controlled trial of 5 different groups comparing different hamstring-stretching techniques. Outcome measures, including hamstring length and perceived level of hamstring tightness, were recorded on all subjects initially, at 4 weeks, and at 8 weeks. After 4 weeks of stretching, there was a statistically significant improvement in hamstring length (p < 0.05) using active stretches as compared with passive stretches. From weeks 4 through 8, hamstring length for the active stretching groups decreased. After 8 weeks of stretching, the straight leg raise (SLR) passive stretch group had the greatest improvement in hamstring length. There was no correlation between hamstring flexibility and age, initial tightness, or frequency of exercise per week. Improvement in hamstring flexibility was greatest for the SLR passive stretch. Also, using PNF in the 90/90 active stretch provided better knee range-of-motion improvements than the 90/90 passive methods did. | Muscle Stretching Exercises |
OBJECTIVES: To determine whether there is an association between overprescription of proton pump inhibitors (PPIs) and multimorbidities in older patients. DESIGN: Multicenter prospective study. SETTING: Acute geriatric medicine at the University Hospital of Nantes and the Hospital of Saint-Nazaire. PARTICIPANTS: Older patients aged 75 and over hospitalized in acute geriatric medicine. MEASUREMENTS: Older patients in acute geriatric medicine who received proton pump inhibitors. Variables studied were individual multimorbidities, the burden of multimorbidity evaluated by the Cumulative Illness Rating Scale, age, sex, type of residence (living in nursing home or not), functional abilities (Lawton and Katz scales), nutritional status (Body Mass Index), and the type of concomitant medications (antiaggregant, corticosteroids', or anticoagulants). RESULTS: Overprescription of proton pump inhibitors was found in 73.9% older patients. In the full model, cardiac diseases (odds ratio [OR] = 4.17, p = 0.010), metabolic diseases (OR = 2.14, p = 0.042) and corticosteroids (OR = 5.39, p = 0.028) were significantly associated with overprescription of proton pump inhibitors. Esogastric diseases (OR = 0.49, p = 0.033) were negatively associated with overprescription of proton pump inhibitors. CONCLUSION: Cardiac diseases and metabolic diseases were significantly associated with overprescription of proton pump inhibitors. | Prescription Drug Overuse |
Keratinase is an important enzyme that is used to degrade feather wastes produced by poultry industries and slaughterhouses that accumulate rapidly over time. The search for keratinase-producing microorganisms is important to potentially substitute physicochemical treatments of feather waste. In this study, the genome of Bacillus cereus HD1 and its keratinolytic prowess was investigated. The whole-genome shotgun size is 5,668,864 bp consisting of 6083 genes, 69 tRNAs, and 10 rRNAs. The genomic analyses revealed 15 potential keratinase genes and other enzymes that might assist keratin degradation, such as disulfide reductase and cysteine dioxygenase. The optimal conditions for feather degradation and keratinase production by B. cereus HD1 such as incubation time, pH, temperature, yeast extract, and glycerol concentrations were determined to be 5 days, pH 8, 37 degrees C, 0.05% (w/v), and 0.1% (v/v), respectively. Under optimized conditions, B. cereus HD1 exhibited feather degradation of 65%, with bacterial growth and maximum keratinase activity of 1.3 x 10(11) CFU/mL and 41 U/mL, respectively, after 5 days of incubation in a feather basal medium. The findings obtained from this study may facilitate further research into utilizing B. cereus HD1 as a prominent keratinolytic enzymes production host and warrant potential biotechnological applications. | Bacillus cereus |
The indications for total shoulder replacement and the radiologic evaluation prior to the operation are discussed in depth in this article. Different approaches to clinical problems are also discussed and illustrated, as are normal findings. This is followed by a discussion of the complications of shoulder reconstruction, including infection, fractures, and heterotopic bone formation. A review of the results is also given followed by a brief mention of a number of other orthopedic shoulder devices and plates. | Shoulder Joint |
This review emphasizes aspects of biology that can be understood through repeated applications of simple causal rules. The selected topics include perspectives on gene regulation, phage lambda development, epigenetics, microbial ecology, as well as model approaches to diversity and to punctuated equilibrium in evolution. Two outstanding features are repeatedly described. One is the minimal number of rules to sustain specific states of complex systems for a long time. The other is the collapse of such states and the subsequent dynamical cycle of situations that restitute the system to a potentially new metastable state. | Siphoviridae |
Secondary and tertiary hyperparathyroidism is an important problem of chronic kidney disease. Brown tumor is a benign, unusual, reactive lesion as a result of disturbed bone remodeling, from long-standing increase in parathyroid hormone level. Brown tumors may cause morbidity due to pressure symptoms on neural structures and spontaneous bone fractures. Herein, we presented a peritoneal dialysis patient with tertiary hyperparathyroidism under calcand calcitriol treatment for 4 years due to refusing of the parathyroidectomy operation. She admitted to hospital for sudden onset back pain with difficulty in gait and walking, and imaging studies showed an expansile mass lesion in the thoracic spine. She was operated for mass and diagnosed with brown tumor. After operation, she lost the ability of walking than become paraplegic and she underwent rehabilitation program. Preventive measures including calcitriol and cinacalcet may cause a modest decrease in parathyroid hormone levels but it should be remembered for the development of bone complications such as brown tumor formation in patients with moderate elevated PTH levels, especially those with tertiary hyperparathyroidism. Parathyroidectomy should be performed without delay in these cases. | Osteitis Fibrosa Cystica |
Heterozygous mutations in HNF1B in humans result in a multisystem disorder, including pancreatic hypoplasia and diabetes mellitus. Here we used a well-controlled human induced pluripotent stem cell pancreatic differentiation model to elucidate the molecular mechanisms underlying HNF1B-associated diabetes. Our results show that lack of HNF1B blocks specification of pancreatic fate from the foregut progenitor (FP) stage, but HNF1B haploinsufficiency allows differentiation of multipotent pancreatic progenitor cells (MPCs) and insulin-secreting beta-like cells. We show that HNF1B haploinsufficiency impairs cell proliferation in FPs and MPCs. This could be attributed to impaired induction of key pancreatic developmental genes, including SOX11, ROBO2, and additional TEAD1 target genes whose function is associated with MPC self-renewal. In this work we uncover an exhaustive list of potential HNF1B gene targets during human pancreas organogenesis whose downregulation might underlie HNF1B-associated diabetes onset in humans, thus providing an important resource to understand the pathogenesis of this disease." | Hepatocyte Nuclear Factor 1-beta |
Since cloning of the dopamine receptor D4 (DRD4), its role in the brain has remained unclear. It has been reported that polymorphism of the DRD4 gene in humans is associated with reactivity to cues related to tobacco smoking. However, the role of DRD4 in animal models of nicotine addiction has seldom been explored. In our study, male Long-Evans rats learned to intravenously self-administer nicotine under a fixed-ratio (FR) schedule of reinforcement. Effects of the selective DRD4 antagonist L-745,870 were evaluated on nicotine self-administration behavior and on reinstatement of extinguished nicotine-seeking behavior induced by nicotine-associated cues or by priming injections of nicotine. L-745,870 was also tested on reinstatement of extinguished food-seeking behavior as a control. In addition, the selective DRD4 agonist PD 168,077 was tested for its ability to reinstate extinguished nicotine-seeking behavior. Finally, L-745,870 was tested in Sprague Dawley rats trained to discriminate administration of 0.4 mg/kg nicotine from vehicle under an FR schedule of food delivery. L-745,870 significantly attenuated reinstatement of nicotine-seeking induced by both nicotine-associated cues and nicotine priming. In contrast, L-745,870 did not affect established nicotine self-administration behavior or reinstatement of food-seeking behavior induced by food cues or food priming. L-745,870 did not produce nicotine-like discriminative-stimulus effects and did not alter discriminative-stimulus effects of nicotine. PD 168,077 did not reinstate extinguished nicotine-seeking behavior. As DRD4 blockade by L-745,870 selectively attenuated both cue- and nicotine-induced reinstatement of nicotine-seeking behavior, without affecting cue- or food-induced reinstatement of food-seeking behavior, DRD4 antagonists are potential therapeutic agents against tobacco smoking relapse. | Receptors, Dopamine D4 |
Intimate partner violence (IPV) negatively affects children. Although IPV-related reports frequently come to the attention of child protective services (CPS), there is neither a unified standard for how CPS systems should respond, nor sufficient research documenting that reaction. The current study used population-based administrative records from California to assess how CPS responds to reported allegations of IPV, with and without physical abuse and/or neglect allegations. We used multinomial regression to model the likelihood of investigation outcomes. Results indicate that 20.7% of CPS reports had IPV alleged during hotline screening, and of those, just 3.2% were screened out compared to 20.2% for reports where IPV was not alleged. Almost half (45.5%) of IPV-alleged reports came from law enforcement, in contrast to 15.2% of reports that did not allege IPV. IPV-alleged reports were more likely to have allegations substantiated without a case opened for services, but less likely to result in foster care placements. Several statistically significant differences were identified by the type of alleged maltreatment co-reported with IPV. This study contributes to an understanding of how CPS responds to IPV-alleged reports. | Child Protective Services |
The approximately 20,000 cells of the suprachiasmatic nucleus (SCN), the master circadian clock of the mammalian brain, coordinate subordinate cellular clocks across the organism, driving adaptive daily rhythms of physiology and behavior. The canonical model for SCN timekeeping pivots around transcriptional/translational feedback loops (TTFL) whereby PERIOD (PER) and CRYPTOCHROME (CRY) clock proteins associate and translocate to the nucleus to inhibit their own expression. The fundamental individual and interactive behaviors of PER and CRY in the SCN cellular environment and the mechanisms that regulate them are poorly understood. We therefore used confocal imaging to explore the behavior of endogenous PER2 in the SCN of PER2::Venus reporter mice, transduced with viral vectors expressing various forms of CRY1 and CRY2. In contrast to nuclear localization in wild-type SCN, in the absence of CRY proteins, PER2 was predominantly cytoplasmic and more mobile, as measured by fluorescence recovery after photobleaching. Virally expressed CRY1 or CRY2 relocalized PER2 to the nucleus, initiated SCN circadian rhythms, and determined their period. We used translational switching to control CRY1 cellular abundance and found that low levels of CRY1 resulted in minimal relocalization of PER2, but yet, remarkably, were sufficient to initiate and maintain circadian rhythmicity. Importantly, the C-terminal tail was necessary for CRY1 to localize PER2 to the nucleus and to initiate SCN rhythms. In CRY1-null SCN, CRY1Deltatail opposed PER2 nuclear localization and correspondingly shortened SCN period. Through manipulation of CRY proteins, we have obtained insights into the spatiotemporal behaviors of PER and CRY sitting at the heart of the TTFL molecular mechanism." | Suprachiasmatic Nucleus Neurons |
P6 a retrospective study outcome in patients with Argentine haemorrhagic fever was associated with the amount of neutralising antibodies against Junin virus present in the transfused units of immune plasma. Low doses of neutralising antibodies were associated with higher mortality. A prospective study gave comparable results. A dose of no less than 3000 therapeutic units of neutralising antibodies per kg body weight is recommended. It is also suggested that the lack of effectiveness of immune plasma in the treatment of other viral haemorrhagic fevers, such as Lassa fever and Crimean-Congo haemorrhagic fever, may be due to a low dose of the specific neutralising antibodies. | Hemorrhagic Fever, American |
Jeune syndrome is a rare autosomal-recessive skeletal disorder. Anesthetic management of these patients is often difficult because of thoracic and lung hypoplasia. A 5-month-old boy with Jeune syndrome was scheduled to undergo a tracheotomy. Despite 5-minute preoxygenation with continuous positive airway pressure, the patient's oxygen saturation rapidly dropped during the induction of anesthesia. The continuous positive airway pressure should have been titrated to effective tidal volume during preoxygenation to recruit the patient's functional residual capacity and to prevent desaturation. During tracheotomy, volume-controlled ventilation with a high respiratory rate and sufficient inspiratory time effectively improved the patient's respiratory status. | Ellis-Van Creveld Syndrome |
INTRODUCTION: Previous studies have shown the potentials of anti-angiogenesis inhibitors in extensive-stage small-cell lung cancer (SCLC). This single-institutional phase 1b study aimed to determine the recommended dose of ramucirumab (anti-vascular endothelial growth factor receptor-2 antibody) in combination with irinotecan plus cisplatin for extensive-stage SCLC. METHODS: Chemo-naive patients with extensive-stage SCLC were enrolled and received ramucirumab (day 1 and 15) with irinotecan (60 mg/m(2), day 1, 8, and 15) plus cisplatin (60 mg/m(2), day 1) every 4 weeks for four cycles, followed by biweekly maintenance ramucirumab. The recommended ramucirumab dose (10 or 8 mg/kg) was determined using a traditional 3 + 3 design, and the number of patients treated at the recommended dose was set at 10 to evaluate drug efficacy and tolerability (UMIN000032671). RESULTS: The first 3 patients that received irinotecan plus cisplatin with ramucirumab 10 mg/kg did not experience dose-limiting toxicities. Thus, the recommended dose of ramucirumab was set at 10 mg/kg, and 10 patients received this dose. The objective response rate was 100% (95% CI, 69-100%), with a median progression-free survival of 7.2 months (95% CI, 5.3-9.0) and median overall survival of 22.4 months (95% CI, 12.1-not reached). Grade 3 neutropenia and hypertension were observed in 4 and 2 patients, respectively. No ramucirumab-related deaths were noted; hypertension and bleeding events were observed in 5 and 6 patients, respectively. CONCLUSIONS: This study showed the satisfactory tolerability and efficacy of ramucirumab at 10 mg/kg in combination with irinotecan plus cisplatin in chemo-naive patients with extensive-stage SCLC. | Irinotecan |
SCOPE: To examine the association between milk and dairy products intake and the prevalence of cognitive decline among Spanish individuals at high cardiovascular risk. METHODS AND RESULTS: Cross-sectional analyses are performed on baseline data from 6744 adults (aged 55-75 years old). Intake of milk and dairy products is estimated using a food frequency questionnaire grouped into quartiles. The risk of developing cognitive impairment is based on the Mini-Mental State Examination (MMSE). A higher prevalence of cognitive decline was found in subjects who consumed more grams. Patients with worse MMSE score (10-24) consumed a mean of 395.14 +/- 12.21 g, while patients with better MMSE score (27-30) consumed a mean of 341.23 +/- 2.73 g (p < 0.05). Those subjects with the lower milk consumption (<220 g/day) had a higher MMSE score (28.35 +/- 0.045). Higher intake of fermented dairy products was observed in participants with a lower MMSE score (OR 1.340, p = 0.003). A positive correlation was found between the consumption of whole milk and the MMSE score (r = 0.066, p < 0.001). CONCLUSIONS: These findings suggest that greater consumption of milk and dairy products could be associated with greater cognitive decline according to MMSE. Conversely, consumption of whole-fat milk could be linked with less cognitive impairment in the cross-sectional study. | Dairy Products |
The tumor microenvironment (TME), comprising cancer cells and stroma, plays a significant role in determining clinical outcomes, which makes targeting cancer cells in the TME an important area of research. One way in which cancer cells in the TME can be specifically targeted is by coating drug-encapsulated nanoparticles (NPs) with homotypic cancer cell membranes. However, incomplete targeting is inevitable for biomimetic nanoformulations coated with only cancer cell membranes because of the inherent heterogeneity of the TME. After observing the structural connection between glioma-associated stromal cells (GASCs) and glioma cells from a clinic, we designed a novel drug delivery system that targets the TME by coating polylactic-co-glycolic acid (PLGA) NPs with GASC-glioma cell fusion cell (SG cell) membranes. The resulting SGNPs inherited membrane proteins from both the glioma membrane and GASC membrane, significantly enhancing the tumor targeting efficiency compared to nanoformulations coated with cancer cell membranes alone. We further demonstrated that encapsulation of temozolomide (TMZ) improved the therapeutic efficacy of TMZ in both heterotopic and orthotopic glioma mouse models. Owing to its significant efficacy, our TME-targeting nanoplatform has potential for clinical applications in the treatment of various cancers. | Temozolomide |
Frontotemporal dementia is a new name for clinical Pick's disease; the eponymic term PiD has been increasingly restricted to the pathologic variant with Pick bodies. This article describes the clinical picture, pathology, and genetic mechanisms of frontal lobe dementia. Frontotemporal dementia is still under-diagnosed and underestimated, partly because the individual components of the complex are considered separately or are considered heterogeneous," a somewhat misleading adjective used in many descriptions. This article emphasizes the considerable overlap among the different varieties of frontotemporal dementia, as well as the distinctive features of each." | Pick Disease of the Brain |
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