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BACKGROUND: The Niemann-Pick C1-Like 1 protein, a multi-transmembrane domain molecule, is critical for intestinal cholesterol absorption, and is the entry factor for hepatitis C virus (HCV). The Chinese tree shrew (Tupaia belangeri chinensis) is closer to primates in terms of genetic evolution than rodents. Previous studies indicated that the tree shrew was suitable for HCV research; however, little is known about tree shrew NPC1L1. METHODS AND RESULTS: TsNPC1L1 cDNA was amplified by rapid amplification of cDNA ends (RACE) technology. The cDNA sequence, its encoded protein structure, and expression profile were analyzed. Results indicated that the tsNPC1L1 mRNA is 4948 bp in length and encodes a 1326 amino acid protein. TsNPC1L1 possesses 84.97% identity in homology to human NPC1L1 which is higher than both mouse (80.37%) and rat (81.80%). The protein structure was also similar to human with 13 conserved transmembrane helices, and a sterol-sensing domain (SSD). Like human NPC1L1, the tsNPC1L1 mRNA transcript is highly expressed in small intestine, but it was also well-expressed in the lung and pancreas of the tree shrew. CONCLUSION: The homology of tree shrew NPC1L1 was closer to human than that of rodent NPC1L1. The expression of tsNPC1L1 was the highest in small intestine, and was detectable in lung and pancreas. These results may be useful in the study of tsNPC1L1 function in cholesterol absorption and HCV infection. | Scandentia |
This study investigated the mechanisms which may underly the prolactin (PRL) stimulating effects of FK 33-824, a potent enkephalin analogue. FK 33-824 (1 mg) was infused in healthy volunteers before and after pretreatment with 3 mg methysergide, a serotonin receptor blocker. All subjects showed a release of PRL after FK 33-824, which was significantly diminished after pretreatment with methysergide. | Methysergide |
A new virus was detected in common fleabane (Erigeron annuus) showing virus-like symptoms including leaf yellowing, mosaic, and mottling. This virus is tentatively named fleabane yellow mosaic virus" (FbYMV). The complete genome sequence consists of two RNA segments of 7,133 nt (RNA 1) and 4,810 nt (RNA 2), excluding the poly(A) tract. Sequence analysis showed a genome organization comparable to that of members of the genus Torradovirus. The level of sequence identity between FbYMV and known members of the genus Torradovirus was below the cutoff established by the ICTV for species demarcation. Therefore, FbYMV should be classified as a new member of the genus Torradovirus." | Secoviridae |
OBJECTIVE: To analyze and to compare the recovery and the development of synkinesis in patients with idiopathic facial palsy (Bell's palsy) following treatment with two methods of rehabilitation, kinesitherapy (KT) and biofeedback/EMG (BFB/EMG). STUDY DESIGN: Retrospective cases--series review. METHODS: Seventy-four patients with Bell' palsy were clinically evaluated within 1 month from onset of palsy and at 12 months after palsy (House scale and synkinesis evaluation). Electromyography (EMG) and Electroneurography (ENG) were performed about 4 weeks after palsy to better evaluate functional abnormalities due to facial nerve lesion. The patients followed two different protocols for rehabilitation: the first 32 patients were treated with therapeutic exercises performed by therapists (KT group), the latter 42 patients were treated using BFB/EMG methods (BFB group) with inhibition of synkinetic movement as the primary goal. RESULTS: KT and BFB patients were evaluated for clinical and neurophysiological characteristics before rehabilitative treatment. BFB patients showed better clinical recovery and minor synkinesis than KT patients. CONCLUSIONS: BFB/EMG seems to be more useful than KT in Bell's palsy treatment. This could be due to the fact that BFB/EMG gives more accurate information than KT on muscle activation with better modulation in voluntary recruitment of motor unit. | Synkinesis |
The human malaria parasite, Plasmodium falciparum, ages the red blood cell during its intracellular development. During this process of erythrocyte senescence the parasitized cell becomes less dense and deformable, its biconcave disc shape becomes more spherical and is covered with microscopic protuberances (knobs); the amounts of membrane cholesterol and phospholipids are altered and phosphatidylserine (PS) is externalized. The malaria-infected cell is osmotically fragile, more permeable to a wide variety of molecules via new permeation pathways (NPP), and there is surface deposition of immunoglobulins and complement. There are declines in sialic acid, reduced glutathione, tocopherol and ATP. Hemichromes are deposited on the inner surface of the red cell membrane and there is clustering of the anion transporter, band 3 protein, as well as exposure of neoantigens which contribute to antigenic variation and adhesivity of the parasitized erythrocyte. These time-dependent changes result from oxidative assault and a combination of factors, including a decline in levels of anti-oxidants and ATP coupled with an enhanced flux of ions especially calcium. Despite these parasite-induced age effects P. falciparum is able to avoid destruction by splenic removal through microvessel sequestration in the deep tissues via PS, clustered band 3 protein and adhesive neoantigens. | Erythrocytes |
Inherited disorders of peripheral nerves represent a common group of neurologic diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B), chromosome 16 (CMT1C) and chromosome 10 (CMT1D). CMT1A is most often associated with a tandem 1.5-megabase (Mb) duplication in chromosome 17p11.2-p12. In rare patients it may result from a point mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1B is associated with point mutations in the myelin protein zero (Po or MPZ) gene. Mutations in the SIMPLE gene cause CMT1C, and CMT1D is the result of mutations in the early response 2 (ERG2 or Krox-20) gene. An X-linked form of CMT1 (CMT1X) maps to Xq13 and is associated with mutations in the connexin32 (Cx32) gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is an axonal neuropathy that maps to chromosome 1p35-p36 (CMT2A), chromosome 3q13-q22 (CMT2B), chromosome 7p14 (CMT2D), chromosome 8p21 (CMT2E), chromosome 1q22-q23 (CMT2F) or chromosome 3q13 (CMT2G). Two X-linked forms of CMT2 have been reported (CMT2XA and CMT2XB), but the genes remain unidentified. An area that has recently expanded is the identification of autosomal recessive forms of CMT type 1 and 2. Of the eight recessive forms of CMT1 that have been identified to date, only two have been fully characterized at the molecular level (CMT1 AR B 1 and CMT1 AR D). Point mutations were found in the myotubularin-related protein-2 (MTM2) gene for CMT1 AR B1. CMT1 AR D is the result of point mutations in the N-myc downstream-regulated gene 1 (NDRG1). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset demyelinating polyneuropathy syndrome that may be associated with point mutations in either the PMP22 gene, PO gene, EGR2 gene or the PRX gene (for the recessive form). It shares considerable clinical and pathological features with CMT1. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-p12 that results in reduced expression of the PMP22 gene. CMT1A and HNPP are reciprocal duplication/deletion syndromes that originate from unequal crossover during germ cell meiosis. Other rare forms of demyelinating peripheral neuropathies map to chromosome 8q, 10q and 11q." | Hereditary Sensory and Motor Neuropathy |
Lysosomal beta-galactosidase (beta-Gal) deficiency causes a group of disorders that include neuronopathic GM1 gangliosidosis and non-neuronopathic Morquio B disease. We have previously proposed the use of small molecule ligands of beta-Gal as pharmacological chaperones (PCs) for the treatment of GM1 gangliosidosis brain pathology. Although it is still under development, PC therapy has yielded promising preclinical results in several lysosomal diseases. In this study, we evaluated the effect of bicyclic 1-deoxygalactonojirimycin (DGJ) derivative of the sp(2)-iminosugar type, namely 5N,6S-(N'-butyliminomethylidene)-6-thio-1- deoxygalactonojirimycin (6S-NBI-DGJ), as a novel PC for human mutant beta-Gal. In vitro, 6S-NBI-DGJ had the ability to inhibit the activity of human beta-Gal in a competitive manner and was able to protect this enzyme from heat-induced degradation. Computational analysis supported that the rigid glycone bicyclic core of 6S-NBI-DGJ binds to the active site of the enzyme, with the aglycone N'-butyl substituent, in a precise E-orientation, located at a hydrophobic region nearby. Chaperone potential profiling indicated significant increases of enzyme activity in 24 of 88 beta-Gal mutants, including four common mutations. Finally, oral administration of 6S-NBI-DGJ ameliorated the brain pathology of GM1 gangliosidosis model mice. These results suggest that 6S-NBI-DGJ is a novel PC that may be effective on a broad range of beta-Gal mutants. | Gangliosidosis, GM1 |
Host-associated microbiota help defend against bacterial pathogens; however, the mechanisms by which pathogens overcome this defense remain largely unknown. We developed a zebrafish model and used live imaging to directly study how the human pathogen Vibrio cholerae invades the intestine. The gut microbiota of fish monocolonized by symbiotic strain Aeromonas veronii was displaced by V. cholerae expressing its type VI secretion system (T6SS), a syringe-like apparatus that deploys effector proteins into target cells. Surprisingly, displacement was independent of T6SS-mediated killing of A. veronii, driven instead by T6SS-induced enhancement of zebrafish intestinal movements that led to expulsion of the resident microbiota by the host. Deleting an actin cross-linking domain from the T6SS apparatus returned intestinal motility to normal and thwarted expulsion, without weakening V. cholerae's ability to kill A. veronii in vitro. Our finding that bacteria can manipulate host physiology to influence intermicrobial competition has implications for both pathogenesis and microbiome engineering. | Aeromonas veronii |
Teriflunomide is a once-daily oral agent that has been licensed in the EU since August 2013 for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS). More recently (September 2014), the EU summary of product characteristics (SmPC) was updated to include data from patients with a first clinical demyelinating event. This review examines the EU SmPC for teriflunomide, with reference to key clinical and safety outcomes and practical considerations for prescribing physicians. In two phase III trials (TEMSO and TOWER) in patients with relapsing forms of MS, teriflunomide 14 mg significantly reduced the annualized relapse rate and the risk of confirmed disability progression sustained for at least 12 weeks. Magnetic resonance imaging (MRI) total lesion volume, gadolinium-enhancing lesions, and unique active lesions were reduced with teriflunomide treatment in TEMSO. In the TOPIC study, in patients with a first clinical demyelinating event, teriflunomide treatment significantly reduced the time to a second clinical episode (relapse). Across the clinical studies, teriflunomide was generally well tolerated; adverse events reported in >/= 10% of teriflunomide-treated patients were diarrhea, nausea, increased alanine aminotransferase, and alopecia. Data from the clinical development program support the use of teriflunomide in a broad spectrum of patients with RRMS. | Crotonates |
Four undescribed labdane diterpenoids, 1,2-dehydro-3,7-dioxo-manoyl oxide (1), 1,2-dehydro-7 beta-hydroxy-3-oxo-manoyl oxide (2), 3,7-dioxo-manoyl oxide (3), and 3beta-hydroxy-7-oxo-manoyl oxide (4) together with three known diterpenoids (5-7) and four highly methoxylated bibenzyls (8-11) were isolated from the liverwort Frullania inouei. The absolute structures of 1-4 were established by combined analysis of NMR data, CD data coupled with TDDFT CD calculations, and single-crystal X-ray diffraction measurement. Cytotoxicity tests to human tumor KB, KB/VCR, K562 or K562/A02 cells showed bibenzyls 8-11 inhibited cell proliferation with ID(50) values ranging from 11.3 to 49.6 microM and overcame the multidrug resistance (MDR) with the reversal fold (RF) values ranging from 3.19 to 10.91 (5 microM) for vincristine-resistant KB/VCR and RF values from 4.40 to 8.26 (5 microM) for adriamycin-resistant K562/A02 cells, respectively. However, none of the diterpenoids were found to be active (ID(50)>50 microM). | Frullania |
A series of cancer vaccines have been evaluated in clinical trials with encouraging results, but the demonstration of clinical benefit in confirmatory studies has so far proven to be difficult. The development of cancer vaccines is hampered by a range of issues particular to this field of research. On 12th March 2008, the Biotherapy Development Association convened a workshop to discuss issues faced by scientists and clinicians involved in the development of cancer vaccines. This paper is a review of the field, based on discussions held at the BDA workshop, and describes biological barriers encountered in generating effective immune responses to tumours, methodological obstacles encountered in the improvement of immunological monitoring which aims to improve inter-laboratory and inter-trial comparisons, challenges in clinical trial design and problems posed by the lack of specific regulation for cancer vaccines and the impact on their development. Ultimately, a number of general solutions are posed: (1) better patient selection, (2) use of multi-modal treatments that affect several aspects of the immune system at once, (3) a requirement for the development of good biomarkers to stratify patients for selection prior to trial and as surrogates for clinical response and (4) harmonisation of SOPs for immunological monitoring of clinical trials. | Immunotherapy |
Waste management programs at the Radioactive Liquid Waste Treatment Facility (RLWTF) at the Los Alamos National Laboratory (LANL) are concerned with the levels of perchlorates due to the effects it can have on the environment and resultant regulations. The RLWTF treats industrial and radioactive wastes generated at multiple research and production facilities across the LANL. Perchloric acid is the major source of the perchlorate ion in the RLWTF used in the analytical chemistry laboratories and for metal dissolution. Perchlorate is present in the influent to the RLWTF at concentrations up to several thousands microg/l level. Ion chromatography is the method of choice to analyze the concentrations of perchlorate in the wastewater generated at the RLWTF. Perchlorate was separated by elution through a CS16/CG16 with an EG40 eluent generator. To minimize background conductivity and enhance analyte conductance, an anion self-regenerating suppressor was used. The method achieved a perchlorate method detection limit of 1 microg/l. The method is successfully being used to monitor the perchlorate levels at the RLWTF and provide data for the pilot tests to remove perchlorate from the RLWTF effluent. | Water Pollution, Radioactive |
Brain tumor typing is a major task in the daily practice of clinical neuropathologists. For more than 100 years, brain tumors have been classified on the basis of a histogenetic concept, with the definition of more than 120 brain tumor entities over time. In the past decades, biomedical research on brain tumors has led to the identification of clinically meaningful diagnostic, prognostic, and predictive molecular markers. Taking this progress into account, the 2016 update of the World Health Organization classification of tumors of the central nervous system has incorporated for the first time molecular markers for definition of brain tumor entities. This development has resulted in integrated diagnostics on the basis of histologic and molecular characteristics. This chapter summarizes essential features of brain tumors in the light of integrated diagnostics. To provide a comprehensive view on the individual tumor entities, we included crucial epidemiologic, clinical, and neuroradiologic aspects as well. In addition we illustrate neuroimaging and histologic characteristics of the various tumor types. In this way we aim to provide concise up-to-date insight into the nature and classification of brain tumors. | Brain Neoplasms |
BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is a rare, but lethal pediatric brain tumor with a median survival of less than 1 year. Existing treatment may prolong life and control symptoms, but may cause toxicity and side effects. In order to improve child- and family-centered care, we aimed to better understand the treatment decision-making experiences of parents, as studies on this topic are currently lacking. PROCEDURE: The data for this study came from 24 semistructured interviews with parents whose children were diagnosed with DIPG in two children's hospitals in Switzerland and died between 2000 and 2016. Analysis of the dataset was done using reflexive thematic analysis. RESULTS: For most parents, the decision for or against treatment was relatively straightforward given the fatality of the tumor and the absence of treatment protocols. Most of them had no regrets about their decision for or against treatment. The most distressing factor for them was observing their child's gradual loss of independence and informing them about the inescapability of death. To counter this powerlessness, many parents opted for complementary or alternative medicine in order to "do something." Many parents reported psychological problems in the aftermath of their child's death and coping strategies between mothers and fathers often differed. CONCLUSION: The challenges of DIPG are unique and explain why parental and shared decision-making is different in DIPG compared to other cancer diagnoses. Considering that treatment decisions shape parents' grief trajectory, clinicians should reassure parents by framing treatment decisions in terms of family's deeply held values and goals." | Diffuse Intrinsic Pontine Glioma |
In a multi-centre double-blind cross-over trial using the double-placebo technique, 55 patients with rheumatoid arthritis were treated for 10 days for each trial drug with ketoprofen (200 mg/day) and ibuprofen (1200 mg/day). Both drugs induced a clinically and statistically significant improvement of all the symptoms studied, except for pain at night during ibuprofen administration. Ketoprofen displayed a therapeutic efficacy significantly superior to ibuprofen in five of the eight symptoms studied. Side-effects were recorded in 10 patients receiving ketoprofen (one patient withdrew because of heartburn) and in nine patients receiving ibuprofen. | Ketoprofen |
Nine new sesquiterpenoids (1-9), five new polyacetylenes (10-14), and six known compounds were isolated from the rhizomes of Atractylodes lancea. These new chemical structures were established using NMR, MS, and ECD data. Notably, compounds 3-5, the aglycone of which possesses two stereogenic centers (C-5 and C-7), exhibited similar ECD spectra to compounds 1 and 2, the aglycone of which possesses one stereogenic center (C-7). Such a difference was supported by the experimental and calculated ECD data and single-crystallographic analyses of 3a. In addition, compound 3 inhibited lipopolysaccharide-induced NO production in BV2 cells with an IC50 value of 11.39 muM (positive control curcumin, IC50 = 4.77 muM); compound 4 showed better hepatoprotective activity against N-acetyl-p-aminophenol-induced HepG2 cell injury than the positive drug (bicyclol) at a concentration of 10 muM (p < 0.001). | Atractylodes |
This study aimed to redescribe two species of Ozolaimus, parasites of free-living green iguanas native to Marajo Island. The gastrointestinal system of four iguana specimens was evaluated for the presence of helminths. Altogether, 12,028 nematodes were found, with a prevalence of 100%, an infection range of 780 to 7,736 nematodes, an infection intensity of 3.007, and a mean abundance of 3,007. Light microscopy and scanning electron microscopy were used to determine the species of nematodes found. The cecum was the site of infection that had the highest parasitic load. Morphologically, the nematodes were compatible with the genus Ozolaimus Dujardin, 1844, with the species Ozolaimus megatyphlon (Rudolphi, 1819) Dujardin, 1845, and Ozolaimus cirratus Linstow, 1906. Scanning electron microscopy showed the presence of small structures (serrated in Ozolaimus cirratus and rounded in Ozolaimus megatyphlon) located below the esophageal leaves. We also evidenced the phasmids in both species; this is the first record of these structures in nematodes of the genus Ozolaimus. In addition, this work expands the records on the geographic distribution of these parasites. | Oxyuroidea |
The cytochrome P450 enzyme lanosterol 14alpha-demethylase (LDM) is the target of the azole antifungals used widely in medicine and agriculture as prophylaxis or treatments of infections or diseases caused by fungal pathogens. These drugs and agrochemicals contain an imidazole, triazole or tetrazole substituent, with one of the nitrogens in the azole ring coordinating as the sixth axial ligand to the LDM heme iron. Structural studies show that this membrane bound enzyme contains a relatively rigid ligand binding pocket comprised of a deeply buried heme-containing active site together with a substrate entry channel and putative product exit channel that reach to the membrane. Within the ligand binding pocket the azole antifungals have additional affinity determining interactions with hydrophobic side-chains, the polypeptide backbone and via water-mediated hydrogen bond networks. This review will describe the tools that can be used to identify and characterise the next generation of antifungals targeting LDM, with the goal of obtaining highly potent broad-spectrum fungicides that will be able to avoid target and drug efflux mediated antifungal resistance. | Steroid Synthesis Inhibitors |
OBJECTIVE: The aim of our study is to determine the general intestinal parasite prevalence in Istanbul University Istanbul Faculty of Medicine Hospital, which is located in European and Asian geographical features of Turkey. METHODS: Between January 1988 and December 2012, a total of 111,889 stool samples from patients who were admitted to the Istanbul University Istanbul Faculty of Medicine Hospital were examined microscopically by using native lugol and formalin-ether concentration technique; in addition, the cellophane tape test technique was used to examine the perianal area. RESULTS: The prevalence of intestinal parasites was found to be 5% (5486/111,889) in Istanbul. Giardia intestinalis was the leading parasite (62%), and the prevalence of the rest of the intestinal parasites was as follows: Enterobius vermicularis, Ascaris lumbricoides, and Blastocystis hominis: 16%, 7%, and 6%, respectively. Between 2000 and 2012, a highly significant reduction in general parasite prevalence was determined, compared to the 1988 and 2000 time period (p<0.001). CONCLUSION: Socio-economic conditions might be related with the both the lower prevalence of intestinal parasites in our hospital, which is located in Marmara region, and the steady decrease of the prevalence ratio in the 2000s. The results indicate the necessity of further studies to develop effective parasitic disease control measurements. | Blastocystis hominis |
The Cdc45-Mcm2-7-GINS (CMG) complex is the replication fork helicase in eukaryotes. Synthetic lethal with Dpb11-1 (Sld2) is required for the initiation of DNA replication, and the S phase cyclin-dependent kinase (S-CDK) phosphorylates Sld2 in vivo. We purified components of the replication initiation machinery and studied their interactions in vitro. We found that unphosphorylated or CDK-phosphorylated Sld2 binds to the mini chromosome maintenance (Mcm)2-7 complex with similar efficiency. Sld2 interaction with Mcm2-7 blocks the interaction between GINS and Mcm2-7. The interaction between CDK-phosphorylated Sld2 and Mcm2-7 is substantially inhibited by origin single-stranded DNA (ssDNA). Furthermore, origin ssDNA allows GINS to bind to Mcm2-7 in the presence of CDK-phosphorylated Sld2. However, unphosphorylated Sld2 blocks the interaction between GINS and Mcm2-7 even in the presence of origin ssDNA. We identified a mutant of Sld2 that does not bind to DNA. When this mutant is expressed in yeast cells, cell growth is severely inhibited with very slow progression into S phase. We propose a model wherein Sld2 blocks the interaction between GINS and Mcm2-7 in vivo. Once origin ssDNA is extruded from the Mcm2-7 ring and CDK phosphorylates Sld2, the origin ssDNA binds to CDK-phosphorylated Sld2. This event may allow the interaction between GINS and Mcm2-7 in vivo. Thus, CDK phosphorylation of Sld2 may be important to release Sld2 from Mcm2-7, thereby allowing GINS to bind Mcm2-7. Furthermore, origin ssDNA may stimulate the formation of the CMG complex by alleviating inhibitory interactions between Sld2 with Mcm2-7." | Minichromosome Maintenance Complex Component 7 |
This paper describes the preliminary biological results that novel T-type calcium channel blockers inhibit the growth of human cancer cells by blocking calcium influx into the cell, based on unknown mechanism on the cell cycle responsible for cellular proliferation. Among the selected compounds from compound library, compound 9c (KYS05041) was identified to be nearly equipotent with Cisplatin against some human cancers in the micromolar range. | Calcium Channel Blockers |
The antimicrobial effects of diethanolamine, dimethylamino-methyl-propanol, and butylethanolamine are greatly enhanced at high pH. Their antimicrobial activities are closely correlated with their uncharged forms, indicating that diffusion through cell membrane(s) is rate limiting for the antimicrobial action. Since these compounds are selectively toxic at high pH, they are appropriate antimicrobial agents for use in alkaline metalworking fluids. | Ethanolamines |
We disclosed a selective polychloromethylation and halogenation reaction of alkynes via a radical addition/spirocyclization cascade sequence, in which polyhaloalkanes were used as the precursor for polyhalomethyl and halogen radicals. Using this strategy, a series of valuable halogen-, CHCl(2)- or CCl(3)-containing spiro[5,5]trienones were synthesized in good yields with good functional group tolerance in one pot under simple and mild conditions. It is noted that an unprecedented halogenation instead of dibromomethylation was achieved when CH(2)Br(2) was used in this work. | Halogenation |
INTRODUCTION: Several structures liable to compress the median nerve have been described around the elbow and proximal forearm. Signs of deficit justify surgical exploration and decompression by exoneurolysis. Better knowledge of the locations of these structures would ensure reliable and effective exploration. HYPOTHESIS: The study hypothesis was that compressive structures show precise topography, with few variations in distance along the median nerve course. MATERIAL AND METHODS: The study was performed on 36 upper-limb cadaver specimens. The measurement reference level was the humeral bi-epicondylar line. Proximal-to-distal dissection located: (1) Struthers' ligament, (2) the pronator teres bellies (PT) with their anatomic particularities of structure and insertion, (3) the lacertus fibrosus, (4) the fibrous arcade of the flexor digitorum superficialis (FDS), (5) the accessory muscles, (6) the origin of the anterior interosseous nerve (AIN), (7) and the vascular arches. RESULTS: Struthers' ligament was not located, but 1 case of medial bicipital fibrous arcade was found. The lacertus fibrosus crossed the median nerve at +1.5+/-0.6cm. PT insertion was high in 19 cases (53%). The humeral PT belly was thin in 21 cases (58%), crossing the median nerve more distally (+1.8+/-0.8cm) than the thicker muscles (+1+/-1.1cm) (p=0.016). The ulnar PT belly was fibrous in 14 cases (39%). A fibrous arcade was found between the 2 PT bellies in 23 cases (64%). The FDS arcade was located at 4.5-7cm from the bi-epicondylar line. An accessory flexor pollicis longus belly was found in 11% of cases. The AIN origin was at +4+/-1.6cm from the reference. A vascular pedicle crossed the median nerve in 3 cases. DISCUSSION: The present study inventoried and mapped 6 potentially compressive structures neighboring or crossing the median nerve. Except for the FDS arcade, they showed very precise proximal-to-distal location, with variations of 0.5 to 1.5cm. LEVEL OF EVIDENCE: IV; case series. | Median Nerve |
During the heroic age of Antarctic exploration (1895-1922) there were at least 18 expeditions to the Antarctic lasting between 18 and 30 months. This is an introduction to a series of articles about the drugs taken and used in the Antarctic at this time. Most of the information relates to the expeditions of Robert Scott and Ernest Shackleton and the main supplier of medical equipment was Burroughs Wellcome and Co. This article also describes the medical cases that were taken to the Antarctic. | Medicine Chests |
This record review of 82 children with Down Syndrome (DS) between April 2004 and March 2014 who had thyroid dysfunction, showed that majority (76, 92.6%) had subclinical hypothyroidism. Of the 60 patients who underwent radionuclide scan, 63.3% had a normal gland; the rest exhibited only impaired tracer uptake. Ultrasonograms done in 20 patients showed reduction of thyroid gland size in 3 (15%) patients only. | Thyroid Dysgenesis |
The complete amino acid sequence of porcine pepsin (EC 3.4.4.1) was constructed from the sequence of five cyanogen bromide fragments. The sequence of one of these fragments, CB2A, is reported here. The sequences of 4 other fragments are known from previous work. Porcine pepsin contains 327 residues with three structural variants. The active center aspartyl residue, which reacts with 1,2-epoxy-3-(p-nitrophenoxy)propane (Chen, K. C. S., and Tang, J. (1972) J. Biol. Chem. 247, 2566-2574), is located at residue 32. Another active site aspartyl residue, which reacts with diazo inactivators (Bayliss, R. S., Knowles, J. B., and Wybrandt, G. B. (1969) Biochem. J. 113, 377-386, IS LOCATED AT RESIDUE 215. The sequences around these 2 aspartyl residues are apparently homologous to each other. The sequences around the tryptophanyl residues at positions 39, 141, 181, and 300 are also homologous to one another. These homologous sequences could be genetic in origin. Fragment CB2A which contains 119 residues was constructed from the peptide sequences resulting from six proteolytic digestions and chemical cleavage at tryptophanyl bonds. | Pepsin A |
BACKGROUND: Despite a growing forensic psychiatry literature, no previous study has examined in detail homicidal behaviour among offenders with cluster C personality disorders - the avoidant, dependent or obsessional personality disorders. AIMS: This study aims to compare homicide offenders with cluster C personality disorders with those with other personality disorders on criminal history, offender-victim relationship and post-offence reaction variables. METHODS: The sample was drawn from all Finnish homicide cases of 1996-2004 for whom a forensic psychiatric evaluation had been conducted. Data were extracted from forensic psychiatric and crime reports. RESULTS: In a nationwide sample of 593 homicide offenders, 21 had at least one cluster C personality disorder. These offenders had significantly shorter criminal histories than the others. Offender-victim relationship did not differ between the groups, but confession to the crime and feelings of remorse were more common among people with cluster C disorders. In addition, compared with other personality disorder clusters, co-morbid depression was more common. CONCLUSIONS: Cluster C personality disorders are rare, but not nonexistent, among homicide offenders. Observed differences in their backgrounds and post-offence behaviours indicate that they may have special needs." | Dependent Personality Disorder |
The presented chest X-ray depicts the thoracic duct anatomy of a 50-year-old man who underwent heart transplantation. His postoperative course was complicated by Candida mediastinitis, treated with debridements and closure of the anterior chest wound with myocutaneous flaps. Postoperatively, he had persistent output from a right-sided chest tube. The fluid appeared milky and its triglycerides level was elevated at 254 mg/dL. The drainage persisted despite a low fat diet. The interventional radiologist identified a leak in the upper thoracic duct. It was embolised with coil and onyx. After the procedure, the chylous pleural effusions resolved. The thoracic duct has been visualised on subsequent chest X-rays (figures 1 and 2). | Thoracic Duct |
Causes of gastrointestinal bleeding and principles for their treatment are very similar in non-cirrhotic portal hypertension to those in portal hypertension due to cirrhosis. When the cause of the block responsible for portal hypertension is a thrombogenic disorder, anticoagulation must be associated. The need for anticoagulation does not modify the general rules for management but may make it more difficult. | Gastrointestinal Hemorrhage |
The repair of chromosomal double-strand breaks (DSBs) by homologous recombination is essential to maintain genome integrity. The key step in DSB repair is the RecA/Rad51-mediated process to match sequences at the broken end to homologous donor sequences that can be used as a template to repair the lesion. Here, in reviewing research about DSB repair, I consider the many factors that appear to play important roles in the successful search for homology by several homologous recombination mechanisms. See also the video abstract here: https://youtu.be/vm7-X5uIzS8. | Rec A Recombinases |
In the fields of psychology, psychiatry, and psychotherapy an understanding of manipulation can be found that often looks one-sidedly at the psychopathologies of a manipulator. Manipulation is often depicted as a deficient, egoistic form of communication that deceives and pressures the manipulated. However, in this paper, we aim to explore a more nuanced understanding of manipulation as a form of influence that can be both toxic and benevolent. To do so, we will use the arena of love as a field of experimentation, which offers opportunities to make meaningful distinctions regarding manipulation on the basis of different forms of love. We conclude that love is compatible with a benevolent manipulation. | Love |
Hairy root lines of Datura metel were established following infection of aseptic stem segments with Agrobacterium rhizogenes strain A4 and cultured in hormone-free B5 solid medium. The growth and production of hyoscyamine and scopolamine (mg/g dry wt.) of these root cultures was encouraged by using B5 liquid medium with half-strength salts. In these culture conditions, the capacity of the highest productive root line 25 to excrete scopolamine into the culture medium rose from 8.7% to 70% when the permeabilizing agent Tween 20 was added for 24 h to the medium, after 2 and 4 weeks of culture. Using an airlift bioreactor (41) with modifications in order to increase root anchorage, the Tween 20 treatment encouraged both growth and alkaloid productivity of cultured root line 25. After 4 weeks their biomass yield was 2.3 mg/l/day and 0.84 mg/l/day of scopolamine was produced (70% extracellular). The scopolamine released into the culture medium was separated with an Amberlite XAD-2 column located in the media exit. | Datura stramonium |
BACKGROUND: Many HIV research projects are plagued by the high missing rate of selfreported information during data collection. Also, due to the sensitive nature of the HIV research data, privacy protection is always a concern for data sharing in HIV studies. METHODS: This paper applies a data masking approach, called triple-matrix masking [1], to the context of HIV research for ensuring privacy protection during the process of data collection and data sharing. RESULTS: Using a set of generated HIV patient data, we show step by step how the data are randomly transformed (masked) before leaving the patients' individual data collection device (which ensures that nobody sees the actual data) and how the masked data are further transformed by a masking service provider and a data collector. We demonstrate that the masked data retain statistical utility of the original data, yielding the exactly same inference results in the planned logistic regression on the effect of age on the adherence to antiretroviral therapy and in the Cox proportional hazard model for the age effect on time to viral load suppression. CONCLUSION: Privacy-preserving data collection method may help resolve the privacy protection issue in HIV research. The individual sensitive data can be completely hidden while the same inference results can still be obtained from the masked data, with the use of common statistical analysis methods. | Data Anonymization |
Drugs that target human thymidylate synthase (hTS), a dimeric enzyme, are widely used in anticancer therapy. However, treatment with classical substrate-site-directed TS inhibitors induces over-expression of this protein and development of drug resistance. We thus pursued an alternative strategy that led us to the discovery of TS-dimer destabilizers. These compounds bind at the monomer-monomer interface and shift the dimerization equilibrium of both the recombinant and the intracellular protein toward the inactive monomers. A structural, spectroscopic, and kinetic investigation has provided evidence and quantitative information on the effects of the interaction of these small molecules with hTS. Focusing on the best among them, E7, we have shown that it inhibits hTS in cancer cells and accelerates its proteasomal degradation, thus causing a decrease in the enzyme intracellular level. E7 also showed a superior anticancer profile to fluorouracil in a mouse model of human pancreatic and ovarian cancer. Thus, over sixty years after the discovery of the first TS prodrug inhibitor, fluorouracil, E7 breaks the link between TS inhibition and enhanced expression in response, providing a strategy to fight drug-resistant cancers. | Thymidylate Synthase |
BACKGROUND: The 1,064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (Cutera, Inc., Brisbane, CA) and steroid tape (fludroxycortide tape) have been used to treat keloids and hypertrophic scars. OBJECTIVE: To evaluate the efficacy of contact-mode 1,064-nm Nd:YAG laser therapy and steroid tape for hypertrophic cesarean-section scars versus conservative therapy (steroid tape only). MATERIALS AND METHODS: A medical record review identified 40 consecutive Japanese patients who had hypertrophic scars (total Japan Scar Workshop Scar Scale [JSS] 2015 evaluation scores of 9 to 12) for more than 1 year after a vertical cesarean section and who were treated at our scar-specialist clinic from July 2015 to December 2017. All 40 patients continued treatment until the total JSS score dropped below 3. Recurrence was defined as a >/=1-point increase in the total JSW score 6 months after achieving a total JSS score <3. RESULTS: The patients had a mean age of 34.2 years. The test (n = 25) and control (n = 15) groups took on average 16.9 and 24.3 months to achieve a total JSS score <3, respectively (p < .01). In the following 6 months, none of the scars recurred. CONCLUSION: Nd:YAG laser treatment effectively decreased the total treatment time of hypertrophic cesarean-section scars. An algorithm for treating mild and severe hypertrophic cesarean-section scars is proposed. | Flurandrenolone |
The mathematics behind the quantum Hamiltonian computing (QHC) approach of designing Boolean logic gates with a quantum system are given. Using the quantum eigenvalue repulsion effect, the QHC AND, NAND, OR, NOR, XOR, and NXOR Hamiltonian Boolean matrices are constructed. This is applied to the construction of a QHC half adder Hamiltonian matrix requiring only six quantum states to fullfil a half Boolean logical truth table. The QHC design rules open a nano-architectronic way of constructing Boolean logic gates inside a single molecule or atom by atom at the surface of a passivated semi-conductor. | Quantum Theory |
Three active components were isolated from treated dry-fruits of Brucea javanica (L.) Merr by chromatographic methods, and they were identified as Brusatol (I), Bruceine D (II), Bruceosidae A (III) by means of UV, IR, 1H-NMR, 13C-NMR spectroscopic analysis methods. | Brucea |
BACKGROUND: Hydrocephalus is managed by surgically implanting flow-diversion technologies such as differential pressure valves and antisiphoning devices; however, such hardware is prone to failure. Extensive research has tested them in flow-controlled settings using saline or de-aerated water, yet little has been done to validate their performance in a setting recreating physiologically relevant parameters, including intracranial pressures, cerebrospinal fluid (CSF) protein content, and body position. OBJECTIVE: To more accurately chart the episodic drainage characteristics of flow-diversion technology. A gravity-driven benchtop model of flow was designed and tested continuously during weeks-long trials. METHODS: Using a hydrostatic pressure gradient as the sole driving force, interval flow rates of 6 valves were examined in parallel with various fluids. Daily trials in the upright and supine positions were run with fluid output collected from distal catheters placed at alternating heights for extended intervals. RESULTS: Significant variability in flow rates was observed, both within specific individual valves across different trials and among multiple valves of the same type. These intervalve and intravalve variabilities were greatest during supine trials and with increased protein. None of the valves showed evidence of overt obstruction during 30 d of exposure to CSF containing 5 g/L protein. CONCLUSION: Day-to-day variability of ball-in-cone differential pressure shunt valves may increase overdrainage risk. Narrow-lumen high-resistance flow control devices as tested here under similar conditions appear to achieve more consistent flow rates, suggesting their use may be advantageous, and did not demonstrate any blockage or trend of decreasing flow over the 3 wk of chronic use. | Cerebrospinal Fluid Pressure |
Ability to recognize and differentiate between predators and non-predators is a crucial component of successful anti-predator behavior. While there is evidence that both genetic and experiential mechanisms mediate anti-predator behaviors in various animal species, it is unknown to what extent each of these two mechanisms are utilized by the green monkey (Chlorocebus sabaeus). Green monkeys on the West Indies island of Barbados offer a unique opportunity to investigate the underpinnings of anti-predator behaviors in a species that has been isolated from ancestral predators for over 350 years. In the first experiment, monkeys in two free-ranging troops were presented with photographs of an ancestral predator (leopard, Panthera pardus) and a non-predator (African Buffalo, Syncerus caffer). Relative to non-predator stimuli, images of a leopard elicited less approach, more alarm calls, and more escape responses. Subsequent experiments were conducted to determine whether the monkeys were responding to a leopard-specific feature (spotted fur) or a general predator feature (forward facing eyes). The monkeys showed similar approach to images of an unfamiliar non-predator regardless of whether the image had forward facing predator eyes or side facing non-predator eyes. However, once near the images, the monkeys were less likely to reach for peanuts near the predator eyes than the non-predator eyes. The monkeys avoided an image of spotted leopard fur but approached the same image of fur when the dark spots had been removed. Taken together, the results suggest that green monkey anti-predator behavior is at least partially mediated by genetic factors. | Chlorocebus aethiops |
Strong temperature dependent low angle X-ray scattering by trifluoroethanol- and hexafluoro-2-propanol-water mixtures was observed in conditions commonly used in NMR work on peptides. At least two types of molecular effects may contribute to the observed scattering: formation of clathrate hydrate-like aggregates of alcohol with water as have been proposed for the similar system tert-butanol-water (Iwasaki, K. and Fujiyama, T. (1976) J. Phys. Chem. 81, 1908-1912) and a further heterogeneity of the solution resulting from immiscibility of the two components. | 1-Propanol |
Aortic valve sparing surgery offers a unique opportunity to save the normal aortic valve in patients who require surgery for aortic root disease such as aneurysms, annuloaortic ectasia or aortic dissection. The surgical anatomy of the aortic root and the basic concepts of aortic valve sparing surgery are reviewed to provide surgeons and cardiologists a better understanding of when such operations might be suitable. | Aortic Diseases |
BACKGROUND: Compliance with hand hygiene by healthcare workers is a vital aspect of the quality and safety in healthcare. The current method of monitoring compliance, known as direct observation, has been questioned as have the various electronic measures proposed as alternatives. In our earlier work we established the capacity of video-based monitoring systems (VMS) to collect data with increased efficacy, efficiency and accuracy. However, the spectre of the approach being seen as an unacceptable invasion of patient privacy, was raised as a barrier to implementation by healthcare workers. METHODS: In depth, semi structured interviews were conducted with 8 patients in order to explore their beliefs and options regarding the proposed approach. Interviews were transcribed and then thematic and content analysis was conducted in order to uncover themes from the data. RESULTS: Despite healthcare worker predictions, patients were generally accepting of the use of video-based monitoring systems for the auditing of hand hygiene compliance. However, this acceptance was conditional. Four interconnected themes emerged from the interview data; quality and safety of care versus privacy, consumer Involvement-knowledge, understanding and consent, technical features of the system, and rules of operation. CONCLUSION: The use of within zone VMS approaches to hand hygiene auditing has the potential to improve the efficacy, efficiency and accuracy of hand hygiene auditing and hence the safety and quality of healthcare. By combining a suite of technical and operational specifications with high level consumer engagement and information the acceptability of the approach for patients may be significantly enhanced. | Hand Disinfection |
Two adult-size endoscopes (Olympus GIF-K2 and ACMI TX-8) were compared for extent of duodenal intubation by the endoscopist's estimate of location and x-ray position in 55 patients. The endoscopes were not different in duodenal position when separately analyzed for the endoscopist's estimate or x-ray location. Combining the results for both endoscopes showed the endoscopist's estimate to differ significantly from x-ray location in 47% of patients (p = 0.02). When incorrect, the endoscopist overestimated 62% of the time and underestimated 38% of the time. X-ray evaluation of insertion depth confirmed that the second portion of the duodenum was reached in 96%, third portion in 51%, and fourth portion or beyond in 38% of patients. We conclude that fluoroscopic confirmation may be necessary when endoscopically assessing distal duodenal segments for pathology. | Duodenoscopy |
An animal model was used to study tumor blood flow by the Doppler CW technique. The objective was to determine when neovascularity could be detected as a function of tumor size and time since transplantation. A Walker 256 carcinosarcoma tumor was inoculated into the flank of 17 Sprague-Dawley rats. Doppler examinations, using a 9 MHz CW probe, were performed daily from day 0 to day 7. The contralateral flank was used as a control. No signals were detected from the control side nor from the inoculated side until day 3. By day 3, Doppler signals could be easily detected in all tumor implants with a minimum weight of only 50 mg. These signals showed a mean systolic frequency shift of 3.3 +/- 0.47 kHz at 3 days and 3.46 +/- 0.58 kHz at 7 days. The diastolic Doppler shifted frequency was 1.78 +/- 0.31 kHz at 3 days and 1.88 +/- 0.23 kHz at 7 days giving a Pourcelot index of 0.47 +/- 0.1 at 3 days and 0.46 +/- 0.09 at day 7. These figures indicate the presence of low impedance vessels with high velocity flow such as has been reported in many human tumors. The vascular morphology was further evaluated by digital angiography which demonstrated coincidence between the site of the high velocity Doppler signals and the presence of arteriovenous anastomoses manifested by simultaneous arterial and venous filling. Further infusion techniques using India ink or Microfil showed the chaotic arrangement of tumor vessels located around the growing edge of the tumor implant. The development of such vascularity is a well-recognized prerequisite for tumor growth and invasion.(ABSTRACT TRUNCATED AT 250 WORDS) | Carcinoma 256, Walker |
Bedbugs have experienced an extraordinary upsurge in the recent past across the world. This cross-sectional study aimed to explore the community perception of the pest outbreaks, the population dynamics, and dispersal patterns under different habitat systems. A survey was conducted within communities in nine counties in Kenya, where geographical coordinates of the sites of bedbug presence were recorded and maximum entropy distribution modelling (MaxEnt) was used to map and predict the potentially suitable habitat, while system thinking and system dynamics approach with Vensim PLE 8.0.9 software was applied to implement bedbug infestation dynamics. Our results indicated that majority of the respondents had ample knowledge on bedbugs and were concerned about the physico-psychologic and socio-economic health effects. Spatial distribution analysis showed regions in Kenya with optimal to suitable for bedbug occurrence in the whole country, and similar results were found at continental level across Africa. Furthermore, infestation dynamics results showed a rapid mobility of bedbug from one house to another. In terms of management strategies, the models showed that the combination of chemical with other control methods was considerably much more effective compared to the use of chemical approach only, appointing integrated pest management strategy as a better intervention approach in controlling the pest. | Cimicidae |
Intra-epidermal electrical stimulation (IEES) has been shown to activate selectively Adelta fibers subserving spinothalamic-mediated sensations. Owing to electrically induced highly synchronous afferent volleys, IEES induces Adelta-mediated evoked potentials at nonpainful intensities, contrasting with thermo-nociceptive laser pulses which entail painful pricking sensations. Here, we recorded intracortical responses from sensory and limbic-cognitive regions of human subjects in response to IEE and laser stimuli, in order to test the hypothesis that IEES could dissociate the sensory from nonsensory networks of nociceptive processing. Intracortical evoked potentials were obtained in 11 epileptic patients with stereotactically implanted electrodes in sensory regions receiving spinothalamic afferents (posterior insula), limbic regions receiving spino-parabrachial input (amygdalar nucleus), and high-order affective-cognitive regions (anteromedial frontal cortex, including perigenual anterior cingulate and rostromedial prefrontal areas). Responses in the sensory posterior insula were of similar amplitude and latency to IEE and laser stimuli (after accounting for heat-transduction time of laser), and consistent in both cases with spinothalamic activation. However, responses to IEES in the amygdala and the anteromedial frontal regions were inconsistent and significantly smaller compared to those evoked to the laser stimulation. Thus, IEES can effectively activate the spinothalamic-sensory system with little recruitment of affective-motivational networks, including those triggered by spino-parabrachio-amygdalar projections. The fact that identical sensory responses were associated to either painful or nonpainful percepts underscores that subjective pain perception is not solely dependent on the sensory recruitment, but rather on the combined activation of sensory, limbic and cognitive areas with precise spatiotemporal relations. | Periamygdaloid Cortex |
We have isolated the avian ortholog for CBFbeta, the common non-DNA binding subunit of the core binding factor (CBF) that has important regulatory roles in major developmental pathways. CBFbeta forms heterodimers with the DNA-binding Runx proteins and increases their affinity for DNA and their protein stability. Here, we describe the Cbfbeta expression pattern during the first 4 days of chick embryo development, with a special interest in the developing hematopoietic system. We have compared its expression pattern to that of Runx1, which is crucial for the generation of definitive hematopoietic cells, and to other hematopoietic- or endothelial-specific markers (c-Myb, Pu.1, CD45, c-Ets-1 and VE-Cadherin). Initially, Cbfbeta is widely expressed in the early mesoderm in both the yolk sac and the embryo proper, but later its expression becomes restricted to specific organs or cell types. We have found that Cbfbeta expression overlaps with Runx1 in the hematopoietic system and neural tube. The somitic and mesonephric structures, however, express Cbfbeta in the absence of detectable Runx1. Finally, Cbfbeta and Runx1 display multiple combinatorial patterns in the endoderm and in specific nerves or ganglia. Taken together, we show that Cbfbeta exhibits a dynamic expression pattern that varies according to the organ, cell type or developmental stage. By revealing multiple combinatorial patterns between Cbfbeta and Runx1, these data provide new insights into the role of CBF during early development." | Core Binding Factor beta Subunit |
Pain in the tongue or oral tissues described as burning" has been referred to by many terms including burning mouth syndrome. When a burning sensation in the mouth is caused by local or systemic factors, it is called secondary burning mouth syndrome and when these factors are treated the pain will resolve. When burning mouth syndrome occurs in the absence of identified risk indicators, the term primary burning mouth syndrome is utilized. This article focuses on descriptions, etiologic theories, and management of primary burning mouth syndrome, a condition for which underlying causative agents have been ruled out." | Burning Mouth Syndrome |
Ten patients with laryngoscleromatous subglottic stenosis have been treated by local two per cent acriflavine solution by a newly designed technique. Two patients with the fibrotic form of this disease were not cured, but the other eight patients (with the granulomatous form) gained a reasonable airway which enabled them to discard their tracheostomy tubes two months after the start of therapy. Up to the present time, for as long as five months after detubation, no single patient has needed a revision tracheostomy. The overall results of this work encourage a trial of local two per cent acriflavine in cases with granulomatous laryngoscleroma. | Aminoacridines |
Glucose is the most abundant monosaccharide, and an essential source of energy for most living cells. Glucose transport across the cell membrane is mediated by two types of transporters: facilitative glucose transporters (gene name: solute carrier 2A) and sodium-glucose cotransporters (SGLTs; gene name: solute carrier 5A). Each transporter has its own substrate specificity, distribution, and regulatory mechanisms. Recently, SGLT1 and SGLT2 have attracted much attention as therapeutic targets for various diseases. This review addresses the basal and functional properties of glucose transporters and SGLTs, and describes the pharmaceutical potential of SGLT1 and SGLT2. | Sodium-Glucose Transporter 1 |
A 26-year-old woman with no significant medical history was referred for 5 months of dry cough, dyspnea, presyncope and chest pressure, and nausea with exertion. The family history was notable for thromboembolic disease in the setting of malignancy and autoimmune disease. She was not on any medications. She is a never smoker and did not use recreational drugs. She had no work-related exposures. Her BP was 95/67 mm Hg; her heart rate was 93 beats per minute, and oxygen saturation was 98% on room air. Lung fields were clear to auscultation. She had a prominent P2 heart sound. There was no jugular venous distension or edema. There was no clubbing, rash, or synovitis. | Dyspnea |
Embryo quality related to its developmental potential is now one of the most important issues in modern embryology. It has been demonstrated that some in vitro produced blastocysts fail to hatch and implant after transfer despite a normal morphology. Although embryos are able to adjust to sub-optimal culture conditions, significant changes in expression profiles of developmentally important genes have been noticed. Timing of the first zygotic cleavage is considered a non-invasive marker of embryo developmental potential and has been successfully used in human IVF programs for identifying embryos of superior quality. Early-cleaving zygotes are more likely to develop to the blastocyst stage than their late-cleaving counterparts. The timing of the first zygotic cleavage has been associated with several parameters that may affect developmental potential of the resulting embryos. The mechanism causing variation in the timing of the first zygotic cleavage has not been identified. It may be related to culture environment or to some intrinsic factors within the oocyte, the sperm or both. In this paper we discuss some of the important aspects related to the timing of the first zygotic cleavage and its influence on the developmental competence of resulting embryos. | Cleavage Stage, Ovum |
The current study describes a straightforward, biologically and environmentally friendly method for creating magnetic iron oxide (gamma-Fe(2)O(3)) nanoparticles. We report here that the Bacillus subtilis SE05 strain, isolated from offshore formation water near Zaafarana, the Red Sea, Hurghada, Egypt, can produce highly magnetic iron oxide nanoparticles of the maghemite type (gamma-Fe(2)O(3)). To the best of our knowledge, the ability of this bacterium to reduce Fe(2)O(3) has yet to be demonstrated. As a result, this study reports on the fabrication of enzyme-NPs and the biological immobilization of alpha-amylase on a solid support. The identified strain was deposited in GenBank with accession number MT422787. The bacterial cells used for the synthesis of magnetic nanoparticles produced about 15.2 g of dry weight, which is considered a high quantity compared to the previous studies. The XRD pattern revealed the crystalline cubic spinel structure of gamma-Fe(2)O(3). TEM micrographs showed the spherically shaped IONPs had an average size of 7.68 nm. Further, the importance of protein-SPION interaction and the successful synthesis of stabilized SPIONs in the amylase enzyme hybrid system are also mentioned. The system showed the applicability of these nanomaterials in biofuel production, which demonstrated significant production (54%) compared to the free amylase enzyme (22%). Thus, it is predicted that these nanoparticles can be used in energy fields. | Amylases |
The discriminative stimulus properties of l-alpha-acetylmethadol (LAAM), its metabolities 1-alpha-acetyl-N-normethadol (NorLaam) and l-alpha-acetyl-N,N-dinormethadol (DiNorLAAM), and methadone were evaluated in rats trained to discriminate between saline and morphine in a two-choice discrete-trial avoidance paradigm. All four compounds produced dose-related increases in the number of trials completed on the morphine-appropriate choice lever after either SC or oral administration indicating that the discriminative stimulus properties of the four compounds and morphine are qualitatively similar. LAAM and DiNorLAAM had a slow onset and long duration of action, and an oral: parenteral potency ratio of 1:3. NorLaam had a more rapid onset and shorter duration of action and was more potent following SC administration than either LAAM or DiNorLAAM; its oral: parenteral potency ratio was 1:10. These results are consistent with evidence from other studies that the pharmacologic activity of LAAM is dependent upon the conversion of LAAM to an active metabolite, probably NorLAAM. The similarities between DiNorLAAM and LAAM suggest that the discriminative stimulus effects of the former compound are also attributable to a metabolite. | Methadyl Acetate |
Scientists have studied organs and their development for centuries and, along that path, described models and mechanisms explaining the developmental principles of organogenesis. In particular, with respect to the heart, new fundamental discoveries are reported continuously that keep changing the way we think about early cardiac development. These discoveries are driven by the need to answer long-standing questions regarding the origin of the earliest cells specified to the cardiac lineage, the differentiation potential of distinct cardiac progenitor cells, and, very importantly, the molecular mechanisms underlying these specification events. As evidenced by numerous examples, the wealth of developmental knowledge collected over the years has had an invaluable impact on establishing efficient strategies to generate cardiovascular cell types ex vivo, from either pluripotent stem cells or via direct reprogramming approaches. The ability to generate functional cardiovascular cells in an efficient and reliable manner will contribute to therapeutic strategies aimed at alleviating the increasing burden of cardiovascular disease and morbidity. Here we will discuss the recent discoveries in the field of cardiac progenitor biology and their translation to the pluripotent stem cell model to illustrate how developmental concepts have instructed regenerative model systems in the past and promise to do so in the future. Developmental Dynamics 245:1130-1144, 2016. (c) 2016 Wiley Periodicals, Inc. | Myocardium |
Interleukin-21 (IL-21) is a new member of the interleukin-2 family. It is mainly synthesized and secreted by the activated of CD4(+) T cells and natural killer T cells. IL-21 receptor (IL-21R) is mainly expressed in T cells, B cells, and natural killer (NK) cells. After binding to its receptor, IL-21 can regulate the activation and proliferation of T cells, B cells, and NK cells through activating JAKs-STATs signaling pathways. As a new immunoregulatory factor, IL-21 and its receptor play important roles in the development and progression of various autoimmune diseases. Regulation of the expression levels of IL-21 and IL-21R and blocking of their signal transduction pathways with blockers may be new treatment options for autoimmune diseases. | Receptors, Interleukin-21 |
After an initial acute infection with cell killing, chicken or duck embryo fibroblasts infected in culture with reticuloendotheliosis viruses set up a chronic infection with no cell killing or morphological transformation. Essentially all of the chronically infected cells produced virus. The virus production was not sensitive to cytosine arabinoside or mitomycin C as was virus production in an acute infection. The chronically infected cells had a strong group-specific resistancto the c.p.e. of superinfecting reticuloendotheliosis viruses. However, they were sensitive to vesicular stomatitis virus and avian leukosis-sarcoma viruses. After double infection, single cells produced reticuloendotheliosis virus and avian leukosis-sarcoma virus." | Reticuloendotheliosis Viruses, Avian |
Germ granules are cytoplasmic assemblies of RNA-binding proteins (RBPs) required for germ cell development and fertility. During the first four cell divisions of the Caenorhabditis elegans zygote, regulated assembly of germ (P) granules leads to their selective segregation to the future germ cell. Here we investigate the role of DLC-1, a hub protein implicated in stabilization and function of diverse protein complexes, in maintaining P granule integrity. We find that DLC-1 directly interacts with several core P granule proteins, predominantly during embryogenesis. The loss of dlc-1 disrupts assembly of P granule components into phase-separated organelles in the embryos, regardless of whether or not DLC-1 directly interacts with these proteins. Finally, we infer that P granule dispersal in the absence of dlc-1 is likely independent of DLC-1's function as a subunit of the dynein motor and does not result from a loss of cell polarity." | Germ Cell Ribonucleoprotein Granules |
BACKGROUND: Recurrent pregnancy loss negatively affects the reproductive outcomes of natural conception. Preimplantation genetic testing for aneuploidies has been the focus of interventions in women with recurrent pregnancy loss. However, the risk of no embryos being available, high costs, and uncertainties surrounding its effectiveness limit its use. Factors beyond euploidy, such as an appropriate intrauterine environment, are also important for improving the reproductive outcomes in women with recurrent pregnancy loss. It remains unknown whether a history of recurrent pregnancy loss can affect reproductive outcomes after fertility treatment. OBJECTIVE: This study aimed to investigate the impact of history of recurrent pregnancy loss on the reproductive outcomes of women undergoing fertility treatment. STUDY DESIGN: This was a retrospective cohort study of women who underwent their first frozen embryo transfer cycle or intrauterine insemination cycle between January 2014 and July 2020 in Shanghai, China. We excluded couples with known karyotypic abnormalities (eg, balanced translocation) or uterine malformation. We performed multivariate binary logistic regressions for biochemical pregnancy, miscarriage, and live birth rates to investigate the associations between recurrent pregnancy loss history and reproductive outcomes. RESULTS: A total of 29,825 women who underwent frozen embryo transfer cycles and 5476 women who underwent intrauterine insemination cycles were included in this study. In those who underwent frozen embryo transfer, history of recurrent pregnancy loss was not significantly associated with biochemical pregnancy (adjusted odds ratio, 1.19; 95% confidence interval, 0.87-1.63), miscarriage (adjusted odds ratio, 0.99; 95% confidence interval, 0.78-1.26), or live birth rates (adjusted odds ratio, 0.91; 95% confidence interval, 0.79-1.06). Similarly, in frozen embryo transfer cycles that led to clinical pregnancy, recurrent pregnancy loss history was not significantly associated with live birth (adjusted odds ratio, 0.99; 95% confidence interval, 0.76-1.28) or miscarriage rates (adjusted odds ratio, 1.04; 95% confidence interval, 0.81-1.35). In women with intrauterine insemination, history of recurrent pregnancy loss showed no significant associations with fertility outcomes in all cycles ([adjusted odds ratio, 1.36; 95% confidence interval, 0.88-2.10] for live birth rate and [adjusted odds ratio, 1.74; 95% confidence interval, 0.75-4.01], for miscarriage rate) and in cycles that led to clinical pregnancy ([adjusted odds ratio, 0.70; 95% confidence interval, 0.31-1.63] for live birth rate and [adjusted odds ratio, 1.45; 95% confidence interval, 0.58-3.63] for miscarriage rate). CONCLUSION: In women without obvious chromosome abnormality and uterine malformation who undergo fertility treatment, recurrent pregnancy loss history was not significantly associated with miscarriage and live birth rates, suggesting that it has little or no prognostic value in predicting the reproductive outcomes of frozen embryo transfer or intrauterine insemination cycles. | Live Birth |
In response to an increase in osmolarity or a decrease in plasma volume, surgical patients often experience thirst during the perioperative period. Thirst causes intense discomfort for patients, but perioperative nurses and health care providers have received minimal direction on how to address this concern. This article presents evidence related to the advances in the management of patients' thirst and discusses clinical strategies that perioperative personnel can safely implement for their patients during the preoperative and postoperative periods. The Thirst Study and Research Group at Londrina State University, Brazil, developed the Thirst Management Model to provide a standardized method for perioperative personnel. Four pillars comprise this model: identification of thirst, measurement of thirst, safety assessment for the management of thirst, and application of relief strategies. This evidence-based model should assist perioperative nurses with translating knowledge and scientific evidence into clinical practice to provide safe patient care. | Drive |
Retrofitting a crown to an existing partial removable dental prosthesis (PRDP) is difficult, labor intensive, and time consuming. This article presents an alternative technique for fabricating a crown under an existing PRDP by using an intraoral digital scanner and computer-assisted design and computer-aided manufacturing (CAD/CAM) technology. This technique involves less human error and provides a well-fitting restoration. | Technology, Dental |
The present checklist contains 22 species belonging to 14 genera of six families of leeches known to date from Iran. Five species including Dina punctata punctata Johannson, 1927, Erpobdella monostriata (Lindenfeld & Pietruszynski, 1890), E. vilnensis (Liskiewicz, 1925), Trocheta haskonis Grosser, 2000 and Glossiphonia concolor (Apathty, 1888) are new records for the country. | Leeches |
We retrospectively evaluated the effect of the Loma Prieta earthquake on calls to 2 designated regional poison control centers (San Francisco and Santa Clara) in the area. In the immediate 12 hours after the earthquake, there was an initial drop (31%) in call volume, related to telephone system overload and other technical problems. Calls from Bay Area counties outside of San Francisco and Santa Clara decreased more dramatically than those from within the host counties where the poison control centers are located. In the next 2 days, each poison control center then handled a 27% increase in call volume. Requests for information regarding safety of water supplies and other environmental concerns were significantly increased. The number of cases of actual poisoning exposure decreased, particularly poison and drug ingestions in children. Most calls directly related to the earthquake included spills and leaks of hazardous materials and questions about water and food safety. Regional poison control centers play an essential role in the emergency medical response to major disasters and are critically dependent on an operational telephone system. | Poison Control Centers |
Development of nanomaterials has drawn interest on silver nanoparticles (AgNPs), which are being incorporated in several biomedical and environmental applications, especially anti-bacterial properties of AgNPs has intense excitement for their commercial use. However, the impact of AgNPs on cell membranes, such as phospholipid membrane properties, is not clearly understood yet. By applying curcumin as a probe molecule, this work was done for the first time to investigate the effect of AgNPs on membrane properties, such as permeability and phase transition temperature using 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes as a model for phospholipid membranes. We concluded that AgNPs at low concentration decrease the partition of curcumin into DMPC liposomes by approximately 4-fold. In the presence of AgNPs, curcumin was found to be located close to the stern layer of DMPC liposomes by using a hydrophobic quencher, cetylpyridinium bromide (CPB). In addition, AgNPs broadened the phase transition temperature of DMPC liposomes, which ranged from 20 degrees C to 35 degrees C. | Cetylpyridinium |
External cervical resorption (ECR) is the loss of dental hard tissue as a result of odontoclastic action; it usually begins on the cervical region of the root surface of the teeth. The etiology, predisposing factors, diagnosis, and management of ECR are reviewed. Effective management and appropriate treatment can only be carried out if the true nature and exact location of the ECR lesion are known. The role of cone beam computed tomography as a diagnostic adjunct for the management of ECR is also reviewed. | Tooth Cervix |
Wolbachia strain wMelPop reduces the longevity of its Drosophila melanogaster host and, when introduced into the mosquito Aedes aegypti, halves its life span. We show that wMelPop induces up-regulation of the mosquito's innate immune system and that its presence inhibits the development of filarial nematodes in the mosquito. These data suggest that wMelPop could be used in the global effort to eliminate lymphatic filariasis and possibly for the control of other mosquito-borne parasites where immune preactivation inhibits their development. The cost of constitutive immune up-regulation may contribute to the life-shortening phenotype. | Brugia pahangi |
The biomarker analysis of benzene, toluene, ethylbenzene and xylene (BTEXs) in biological samples is the primary technique for evaluating these compounds in occupational and environmental exposures. The BTEX biomarkers are widely used to study the BTEX distribution in the environment and workplaces. Liquid-liquid extraction and solid-phase liquid extraction are among the most commonly used conventional methods to analyze biological indices of BTEXs. New methods have been proposed to analyze BTEX biomarkers using novel adsorbents such as sol-gel composite nanotubes, molecularly imprinted polymers and metal-organic frameworks, which are based on the application of needle trap devices, microextraction by packed sorbent, and solid-phase microextraction techniques. This paper provides an overview of new methods since 2015 regarding applying microextraction methods based on new adsorbents and analyzing BTEX biomarker compounds for occupational and environmental exposures. The results were compared with the liquid-phase microextraction methods recommended for urinary BTEX biomarkers. | Benzene Derivatives |
Methylmercury (MeHg) is well known as a neurotoxic chemical. However, little is mentioned about its neurotoxic mechanism or molecular target in human neuronal cells in particular. We show in this study that exposure of human neuronal cell line, SH-SY5Y, to MeHg dose- and time-dependently impairs viability and mRNA expression of selenoprotein W (SeW) with a significant difference, unlike other selenoenzymes such as, SeP, GPX4, 5DI, and 5'DI. Using real-time RT PCR, the influence of selenium (Se) and glutathione (GSH) on SeW expression was also investigated. While Se depletion caused a weakly reduced SeW mRNA levels, additional Se caused an increase of SeW mRNA levels. Although 2 mM GSH had induced a weak shift on SeW level, the expression of SeW mRNA was down-regulated in SH-SY5Y cells treated with 25 microM BSO, an inhibitor of GSH synthesis. To understand the relationship between a decrease of SeW expression and intracellular GSH and ROS, we measured the concentration of intracellular GSH and ROS in cells treated to 1.4 microM MeHg using fluorescence based assays. A positive correlation was found between SeW mRNA level and intracellular GSH but no significant correlation was observed between intracellular ROS and SeW mRNA level or intracellular GSH contents. Therefore, we suggest that SeW is the novel molecular target of MeHg in human neuronal cells and down-regulation of this selenoenzyme by MeHg is dependent not on generation of ROS but on depletion of GSH. | Selenoprotein W |
Pancreatic stellate cells (PSCs) are crucial for metabolism and disease progression in pancreatic ductal adenocarcinoma (PDAC). However, detailed mechanisms of PSCs in glutamine (Gln) metabolism and tumor-stromal metabolic interactions have not been well clarified. Here we showed that tumor tissues displayed Gln deficiency in orthotopic PDAC models. Single-cell RNA sequencing analysis revealed metabolic heterogeneity in PDAC, with significantly higher expression of Gln catabolism pathway in stromal cells. Significantly higher glutamine synthetase (GS) protein expression was further validated in human tissues and cells. Elevated GS levels in tumor and stroma were independently prognostic of poorer prognosis in PDAC patients. Gln secreted by PSCs increased basal oxygen consumption rate in PCCs. Depletion of GS in PSCs significantly decreased PCCs proliferation in vitro and in vivo. Mechanistically, activation of Wnt signaling induced directly binding of beta-catenin/TCF7 complex to GS promoter region and upregulated GS expression. Rescue experiments testified that GS overexpression recovered beta-catenin knockdown-mediated function on Gln synthesis and tumor-promoting ability of PSCs. Overall, these findings identify the Wnt/beta-catenin/TCF7/GS-mediated growth-promoting effect of PSCs and provide new insights into stromal Gln metabolism, which may offer novel therapeutic strategies for PDAC. | Pancreatic Stellate Cells |
PURPOSE: Although the receipt of peer sexual harassment in schools has been linked to deliberate self-injury, the direction of association over time has not been tested. Two longitudinal studies examined whether receipt of peer sexual harassment within schools predicts engagement in deliberate self-injury or vice versa. Differences between boys and girls were also tested. METHODS: Surveys were conducted in two countries, Canada and Sweden. Measures of sexual harassment and deliberate self-injury were administered yearly in classrooms. Two waves of data were collected in the Canadian study (N = 161, 59.6% girls, mean age = 13.82 years); three waves of data were collected in Sweden (N = 513, 47% girls, mean age = 13.23 years). RESULTS: In the Canadian study, deliberate self-injury predicted subsequent peer sexual harassment; the converse relationship was not significant. No significant gender differences were found. Across the three waves of the Swedish study, peer sexual harassment predicted self-injury from T1 to T2, and self-injury predicted peer sexual harassment from T2 to T3. However, self-injury did not mediate peer sexual harassment at T1 and T3. Tests of gender differences revealed self-injury predicted sexual harassment from T2 to T3 among Swedish girls but not boys. CONCLUSIONS: Adolescents who deliberately self-injure may be vulnerable to sexual harassment by peers at school. Cultural norms may have a role in whether this process applies primarily to girls or to both genders. Sexual harassment by peers may also increase self-injury, but this is not subsequently linked to increases in receipt of sexual harassment. | Sexual Harassment |
The purpose of this article is to outline a clinical approach to patients with failure to thrive in old age. The article starts with a hypothetical clinical case presentation epitomizing the problem seen in an outpatient clinic by geriatricians. This case is then used as a basis to discuss salient features of failure to thrive which may be different from patient to patient. The focus is on using standard outpatient evaluation methods to identify common problems causing failure to thrive. | Failure to Thrive |
A previously unreported side effect--serosanguineous bullae--was found in one patient receiving minoxidil. The eruption disappeared with cessation of the drug and reappeared on rechallenge. The question arises whether continuation of minoxidil treatment could have led to vasculitis. | Minoxidil |
Cryopreservation of lactic acid bacteria may lead to undesirable cell death and functionality losses. The membrane is the first target for cell injury and plays a key role in bacterial cryotolerance. This work aimed at investigating at a subcellular resolution the membrane fluidity of two populations of Lactobacillus delbrueckii subsp. bulgaricus when subjected to cold and osmotic stresses associated to freezing. Cells were cultivated at 42 degrees C in mild whey medium, and they were exposed to sucrose solutions of different osmolarities (300 and 1800 mOsm L(-1)) after harvest. Synchrotron fluorescence microscopy was used to measure membrane fluidity of cells labeled with the cytoplasmic membrane probe 1-[4 (trimethylamino) phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH). Images were acquired at 25 and 0 degrees C, and more than a thousand cells were individually analyzed. Results revealed that a bacterial population characterized by high membrane fluidity and a homogeneous distribution of fluidity values appeared to be positively related to freeze-thaw resistance. Furthermore, rigid domains with different anisotropy values were observed and the occurrence of these domains was more important in the freeze-sensitive bacterial population. The freeze-sensitive cells exhibited a broadening of existing highly rigid lipid domains with osmotic stress. The enlargement of domains might be ascribed to the interaction of sucrose with membrane phospholipids, leading to membrane disorganization and cell degradation. | Lactobacillus delbrueckii |
The plant enzyme horseradish peroxidase (HRP) is used in several important industrial and medical applications, of which especially biosensors and diagnostic kits describe an emerging field. Although there is an increasing demand for high amounts of pure enzyme preparations, HRP is still isolated from the plant as a mixture of different isoenzymes with different biochemical properties. Based on a recent next generation sequencing approach of the horseradish transcriptome, we produced 19 individual HRP isoenzymes recombinantly in the yeast Pichia pastoris. After optimizing a previously reported 2-step purification strategy for the recombinant isoenzyme HRP C1A by substituting an unfavorable size exclusion chromatography step with an anion exchange step using a monolithic column, we purified the 19 HRP isoenzymes with varying success. Subsequent basic biochemical characterization revealed differences in catalytic activity, substrate specificity and thermal stability of the purified HRP preparations. The preparations of the isoenzymes HRP A2A and HRP A2B were found to be highly interesting candidates for future applications in diagnostic kits with increased sensitivity. | Horseradish Peroxidase |
In order to reduce maternal mortality due to cephalopelvic disproportion (CPD), it is important to screen women for short stature, especially in rural areas of developing countries. We measured the height of 1733 women as they left the maternity services in Ouagadougou and recorded the type of delivery. Women less than 155 cm tall were 4.9 times more likely to have a cesarean section delivery. We propose simplified screening criteria for use by traditional birth attendants. | Obstetric Labor Complications |
Two Medicaid programs offer personal care services: (1) the Title XIX Personal Care Services (PCS) optional State plan benefit; and (2) the 1915(c) home and community-based services (HCBS) waivers. By 1998-1999, 26 States offered the PCS optional State plan benefit; 45 offered personal care services via a waiver(s). Nationwide, the former program was larger. The latter was the more popular administrative mechanism, possibly because it more reliably controls growth. States vary dramatically in terms of Medicaid personal care. Medicaid personal care participants per 1,000 State population ranged from 7.33 to 0.04. Per capita expenditures ranged from $91.21 to $0.02. | Personal Health Services |
A rare patient with infantile spasms, hypsarrhythmia, cytochrome c oxidase deficiency and Leigh syndrome is reported. Although rare, infantile spasms and Leigh syndrome may occur simultaneously. Leigh syndrome should be included in the differential diagnosis of infantile spasms." | Cytochrome-c Oxidase Deficiency |
Symphysiotomy is an alternative operative procedure where a deliberate division of symphysis pubis is carried out to facilitate delivery in cases of cephalopelvic disproportion, so as to permit the birth of baby by natural passages. Symphysiotomy results in a permanent increase in pelvic diameter (up to 1 cm) by surgically dividing the ligaments of the symphysis under local or general anaesthesia. Symphysiotomy should only be done in a established case of obstructed labour but not in anticipation of obstructed labour. This operation was reviewed in 21 cases of established obstructed labour in Silchar Medical College with little modifications of original operations. All the cases were done by subcutaneous method which is cosmetic and simple. The operation was carried out by dividing upper ligament completely and anterior arcuate ligament partially under local anaesthesia. The posterior arcuate ligament was not touched at all. None of the cases required forceps or vaccum extraction. It resulted in almost negligible complications in comparison to morbidity and mortality in primary caesarean section. Considering the usefulness of the operation it can even be started in rural hospitals by the gynaecologist if they are properly trained to do it in a justified manner in properly selected cases. | Symphysiotomy |
This article deals with the morphological and molecular assessments of 3 species of mosquitoes collected in Yunnan Province, China, i.e Anopheles monticola Somboon, Namgay & Harbach, the only species of the Baileyi Complex identified, Culex sasai Kano, Nitahara & Awaya, and Lutzia vorax Edwards. Interestingly, some adult specimens of An. monticola exhibited a variant form in having pale fringe spots, as found in An. simlensis James, another species of the Baileyi Complex. Culex sasai was recorded for the first time in Yunnan and mainland China. The prevalence of Lt. vorax was confirmed, and previous records of Lt. halifaxii in China are regarded as misidentifications of Lt. vorax. | Culicomorpha |
Cyclic GMP-AMP synthase (cGAS) functions as a key sensor for microbial invasion and cellular damage by detecting emerging cytosolic DNA. Here, we report that GTPase-activating protein-(SH3 domain)-binding protein 1 (G3BP1) primes cGAS for its prompt activation by engaging cGAS in a primary liquid-phase condensation state. Using high-resolution microscopy, we show that in resting cells, cGAS exhibits particle-like morphological characteristics, which are markedly weakened when G3BP1 is deleted. Upon DNA challenge, the pre-condensed cGAS undergoes liquid-liquid phase separation (LLPS) more efficiently. Importantly, G3BP1 deficiency or its inhibition dramatically diminishes DNA-induced LLPS and the subsequent activation of cGAS. Interestingly, RNA, previously reported to form condensates with cGAS, does not activate cGAS. Accordingly, we find that DNA - but not RNA - treatment leads to the dissociation of G3BP1 from cGAS. Taken together, our study shows that the primary condensation state of cGAS is critical for its rapid response to DNA." | Cytoplasmic Ribonucleoprotein Granules |
The aim of this study is to determine the location of MB2 in maxillary first molars in relation to the MB1 using the cone-beam computed tomography (CBCT) imaging. In this retrospective study, electronic health records' system was utilised to identify patients who acquired CBCT for the maxillary first molar as an imaging adjunct to their endodontic treatment. Data were evaluated, and statistical analysis was performed. For the initial treatment cases, the distance from MB1 to MB2 was 2.06 +/- 0.52 mm. This did not change significantly for cases that were being retreated. Statistically significant differences were observed between the distances from MB1 to MB2 in males vs. female teeth with males demonstrating longer distances as compared to females. Variations in anatomy exist between patients but this study established some guidelines for clinicians to locate the MB2 canal orifices. This could potentially help with treating these teeth with minimal failure rates." | Spiral Cone-Beam Computed Tomography |
Liposarcoma is the single most common soft tissue sarcoma accounting for up to 35 % of sarcomas. It represents a histologically diverse group of soft tissue tumors that demonstrate a wide range of imaging appearances with varied behavior patterns. Correspondingly, more aggressive histological subtypes often require management that includes a combination of surgery, chemotherapy, and radiation therapy. Distinguishing among liposarcoma subtypes has important therapeutic and prognostic implications. In this manuscript, we review the liposarcoma subtypes and their histologic and MRI findings, prognostic implications, and differential diagnostic considerations. | Liposarcoma |
The catecholamine dopamine plays an important role as a neurotransmitter or neurohormone in the brain and pituitary gland. Dopamine exerts its effects through activation of two types of receptors called D-1 and D-2. These receptors are distinguished by their different pharmacological characteristics and signal transduction mechanism(s). Release of dopamine inhibits the activity of dopaminergic neurons through activation of so-called dopamine autoreceptors which are of the D-2 type. In general, these receptors occur both in the soma-dendritic region of the dopaminergic neuron, where they are involved in the inhibition of the firing rate and on the dopaminergic terminals where they mediate the inhibition of dopamine synthesis and release. D-2 receptors occur also on the target cells of dopaminergic neurons both in the brain (postsynaptic D-2 receptors) and pituitary gland. On the basis of data gathered from in vivo (behavioral- as well as electrophysiological) studies it has been concluded that D-2 agonists are much more potent at dopamine autoreceptors as compared to postsynaptic D-2 receptors, indicating the possibility of a pharmacological distinction between these differentially located D-2 receptors. This concept led to the introduction of a whole group of drugs allegedly displaying a selective agonist profile at the dopamine autoreceptor. In contrast, biochemical (in vitro) studies with brain tissue as well as the pituitary gland, did not reveal any significant difference between the pharmacological profiles of autoreceptors and postsynaptic D-2 receptors. In the present minireview a balanced discussion is presented of these in vivo and in vitro findings and it is concluded that both autoreceptors as well as postsynaptic D-2 receptors are similar if not identical entities. | Receptors, Dopamine |
By using metabolically altered mutants and acrylate, novel putative intermediates of alpha-pinene metabolism by Pseudomonas putida PIN11 were detected. They were characterized as 3-isopropylbut-3-enoic acid and (zeta)-2-methyl-5-isopropylhexa-2,5-dienoic acid. | Pseudomonas |
The stability of four pesticides (desethylatrazine, fenamiphos, fenitrothion and fonofos) was examined under different storage conditions after preconcentration in disposable solid-phase extraction (SPE) cartridges containing new polymer sorbent materials (Hysphere-1, IST EnviroLut and LiChrolut). Complete recovery for all the compounds was observed in precolumns kept at -20 degrees C for 1 month when preconcentrating 26 ml of ground water sample spiked at 10 micrograms/l. Degradation of fenamiphos and fenitrothion occurred in precolumns stored at 4 degrees C and at room temperature after 1 month. Fonofos was stable when compared to their storage in C18 precolumns. Problems in the quantification of the analytes after storage at 4 degrees C and at room temperature were encountered due to the presence of many interfering peaks in the chromatograms. Analysis of blanks with C18 precolumns was carried out, to determine the interferences. The stability of the pesticides was also examined in acidifed and non-acidified ground water in order to compare it to the stability of pesticides stored on SPE cartridges. Significant losses of fenamiphos and fenitrothion were achieved and were related to the pH of the water sample and their chemical structure. Finally, the new polymeric sorbent Hysphere-I was evaluated in terms of breakthroughs and compared with those of C18, obtaining higher recoveries for desethylatrazine. | Fonofos |
BACKGROUND: The proliferation of non-Langerhans cell histiocytes is a poorly understood process of unknown cause. Variation in the clinical features and/or histopathology of histiocytic proliferation has led to subclassification of the general category of non-Langerhans cell histiocytes. Although the current classification may provide some useful generalizations in regard to the anticipated clinical course, wide variability in presentation and outcome make this classification less than optimal when dealing with individual patients. The objectives of the study were to present four cases of generalized non-Langerhans cell histiocytosis. MATERIALS AND METHODS: Medical records and slides of four patients diagnosed with non-Langerhans cell histiocytosis at the Cleveland Clinic are reviewed. RESULTS: The patients exhibit features of more than one subtype of non-Langerhans cell histiocytosis. CONCLUSION: The overlap among the clinical and histologic features of the generalized cutaneous non-Langerhans cell histiocytic disorders suggests that they represent one disease entity with a wide spectrum of presentations rather than many distinct disorders." | Histiocytosis, Non-Langerhans-Cell |
Theists often receive the benefit of being stereotyped as trustworthy and moral, whereas atheists are viewed as untrustworthy and immoral. The extreme divergence between the stereotypes of theists and atheists suggests that mental images of the two groups may also diverge. We investigated whether people have biased mental images of theists and atheists. The results suggest that mental images of theists are associated with more positive attributes than images of atheists (Study 1), and these mental images influence who is believed to behave morally and immorally (Study 2). Together the findings suggest that mental images may represent a subtle mechanism reinforcing group-based prejudices. (PsycINFO Database Record | Imagination |
Single-nucleotide polymorphisms (SNPs) in the human ether-a-go-go-related gene 1, hERG1, are associated with cardiac arrhythmias. The Kv11.1 channels encoded by hERG1 are also essential for rhythmic excitability of the pituitary, where they are regulated by thyroid hormone through a signal transduction cascade involving the phosphatidylinositol 3-kinase (PI3K) and the Ser/Thr-directed protein phosphatase, PP5. Here, we show that the hERG1 polymorphism at codon 897, which is read as a Thr instead of a Lys, creates a phosphorylation site for the Akt protein kinase on the Kv11.1 channel protein. Consequently, hormonal signaling through the PI3K signaling cascade, which normally stimulates K897 channels through PP5-mediated dephosphorylation, inhibits T897 channels through Akt-mediated phosphorylation. Thus, hormonal regulation of Kv11.1 in humans with the T897 polymorphism is predicted to prolong the QT interval of cardiac myocytes. A systematic bioinformatics search for SNPs in human ion channel genes identified 15 additional candidates for such "phosphorylopathies," which are predicted to create or destroy putative phosphorylation sites. Changes in protein phosphorylation might represent a general mechanism for the interaction of genetic variation and environment on human health." | Ether-A-Go-Go Potassium Channels |
The vasoreactivity of the intracranial segment of the internal carotid artery to transmitters, present in the perivascular sympathetic, parasympathetic and sensory nerves, as well as to other vasoactive agents of relevance for headache, was tested in man and monkey. The total arterial segment from both species is equipped with contractile receptors for noradrenaline, serotonin, prostaglandin F2 alpha, ergotamine and sumatriptan. Further, the total arterial segment dilated upon exposure to calcitonin gene-related peptide in both species. Other vascoactive transmitters, acetylcholine, substance P and neurokinin A, caused only weak dilatation, restricted to the proximal extracavernous segment in the monkey. The findings are discussed in relation to the pathogenesis and treatment of cluster headache. | Vasomotor System |
The use of non-destructive forensic methods for cocaine identification is of outstanding importance, given the amount of samples seized. Techniques such as ATR-FTIR, Raman, and NIR spectroscopy have become alternatives to circumvent this problem, as they allow fast, cheap analysis, and enable the reanalysis of samples. When combined with chemometrics, these spectroscopic methods can be used to determine and quantify cocaine samples, meaning that the limitations of existing techniques can be overcome. This review article covers spectroscopic techniques for identifying cocaine in different forms and matrices, such as food and textiles, which are materials used for smuggling. The chemometric identification of cocaine in oral fluid and water is also discussed. In addition, vibrational spectroscopy techniques using portable equipment are described. This work seeks to evaluate the main chemometric applications of spectroscopic data and to find new perspectives on the identification of cocaine using chemometrics. | Chemometrics |
Endothelin receptor antagonists (ETRAs) are approved for the treatment of pulmonary hypertension and scleroderma-related digital ulcers. The efforts to approve this class of drugs for renal indications, however, failed so far. Preclinical studies were promising. Transgenic overexpression of ET-1 or ET-2 in rodents causes chronic renal failure. Blocking the ET system was effective in the treatment of renal failure in rodent models. However, various animal studies indicate that blocking the renal tubular ETAR and ETBR causes water and salt retention partially mediated via the epithelial sodium transporter in tubular cells. ETRAs were successfully tested clinically in renal indications in phase 2 trials for the treatment of diabetic nephropathy. They showed efficacy in terms of reducing albumin excretion on top of guideline based background therapy (RAS blockade). However, these promising results could not be translated to successful phase III trials so far. The spectrum of serious adverse events was similar to other phase III trials using ETRAs. Potential underlying reasons for these failures and options to solve these issues are discussed. In addition preclinical and clinical studies suggest caution when addressing renal patient populations such as patients with hepatorenal syndrome, patients with any type of cystic kidney disease and patients at risk of contrast media induced nephropathy. The lessons learned in renal indications are also important for other potential promising indications of ETRAs like cancer and heart failure." | Endothelin Receptor Antagonists |
The authors report three observations of rather extensive aggressive chondroblastoma and draw attention to difficulties of histological diagnosis, which result out of a less typical histological picture, in which signs of differentiation into cartilaginous tissue may be missing. Differential diagnosis may be facilitated by proper recognition of the cytologic character of chondroblasts by the positivity of S-100 protein, and by proving characteristic properties of chondroblasts in electronmicroscopic examination. In treating this type of tumors an increased risk of local recurrence (in one of our patients) and aggressive behaviour to surrounding tissues should be considered, exceptionally pulmonary metastases may develop, as was the case in one of our presented patients. | Femoral Neoplasms |
BACKGROUND: The purpose of this study was to evaluate the effectiveness of tap water iontophoresis as a treatment for plantar hyperhidrosis. METHODS: Thirty participants living with idiopathic plantar hyperhidrosis and consented to undergo treatment using iontophoresis were recruited. The Hyperhidrosis Disease Severity Score was used to evaluate the severity of the condition before and after treatment. RESULTS: Tap water iontophoresis was found to be effective in the treatment of plantar hyperhidrosis in the study group (P = .005). CONCLUSIONS: Treatment with iontophoresis led to the reduction of disease severity and improvement of quality of life, and it is a safe, easy-to-use method with minimal side effects. This technique should be considered before the use of systemic or aggressive surgical interventions, which could have potentially more severe side effects. | Iontophoresis |
The widely favored hypothesis that ovarian epithelial tumors arise from the mesothelial cell layer lining the ovarian surface fails to explain the resemblance of these tumors to those arising in organs that are embryologically derived from the Mullerian ducts such as fallopian tubes, endometrium, and endocervix. In addition, this theory cannot account for the fact that tumors that are morphologically identical to ovarian carcinomas can sometimes be found outside the ovary. A suggestion is made that components of the secondary Mullerian system, which include paraovarian/paratubal cysts, rete ovarii, endosalpingiosis, endometriosis, and endomucinosis, merit some consideration as to their possible role in ovarian tumorigenesis. | Mullerian Ducts |
OBJECTIVE: Glucose-dependent insulinotropic polypeptide is an intestinally derived hormone that is essential for normal metabolic regulation. Loss of the GIP receptor (GIPR) through genetic elimination or pharmacological antagonism reduces body weight and adiposity in the context of nutrient excess. Interrupting GIPR signaling also enhances the sensitivity of the receptor for the other incretin peptide, glucagon-like peptide 1 (GLP-1). The role of GLP-1 compensation in loss of GIPR signaling to protect against obesity has not been directly tested. METHODS: We blocked the GIPR and GLP-1R with specific antibodies, alone and in combination, in healthy and diet-induced obese (DIO) mice. The primary outcome measure of these interventions was the effect on body weight and composition. RESULTS: Antagonism of either the GIPR or GLP-1R system reduced food intake and weight gain during high-fat feeding and enhanced sensitivity to the alternative incretin signaling system. Combined antagonism of both GIPR and GLP-1R produced additive effects to mitigate DIO. Acute pharmacological studies using GIPR and GLP-1R agonists demonstrated both peptides reduced food intake, which was prevented by co-administration of the respective antagonists. CONCLUSIONS: Disruption of either axis of the incretin system protects against diet-induced obesity in mice. However, combined antagonism of both GIPR and GLP-1R produced additional protection against diet-induced obesity, suggesting additional factors beyond compensation by the complementary incretin axis. While antagonizing the GLP-1 system decreases weight gain, GLP-1R agonists are used clinically to target obesity. Hence, the phenotype arising from loss of function of GLP-1R does not implicate GLP-1 as an obesogenic hormone. By extension, caution is warranted in labeling GIP as an obesogenic hormone based on loss-of-function studies. | Incretins |
Citrus essential oils are routinely adulterated because of the lack of regulations or reliable authentication methods. Unfortunately, the relatively simple chemical makeup and the tremendous price variations among Citrus varieties encouraged the interspecies adulteration of citrus oils. In this study, a sensitive UPLC-MS/MS method for the quantitation of 14 coumarins and furanocoumarins is developed and validated. This method was applied to screen the essential oils of 12 different Citrus species. This study, to our knowledge, represents the most comprehensive investigation of coumarin and furanocoumarin profiles across commercial-scale Citrus oils to date. Results show that the lowest amount was detected in calamansi oil. Expressed oil of Italian bergamot showed the highest furanocoumarin content and the highest level of any individual furanocoumarin (bergamottin). Notable differences were observed in the coumarin and furanocoumarin levels among oils of different crop varieties and origins within the same species. Potential correlations were observed between bergapten and xanthotoxin which matches with known biosynthetic pathways. We found patterns in furanocoumarin profiles that line up with known variations among the Citrus ancestral taxa. However, contrary to the literature, we also detected xanthotoxin in sweet orange and members of the mandarin taxon. Using multivariate analysis, we were able to divide the Citrus oils into 5 main groups and correlate them to the coumarin compositions. | 5-Methoxypsoralen |
Variable lymphocyte receptors (VLRs) rather than antibodies play the primary role in recognition of antigens in the adaptive immune system of jawless vertebrates. Combinatorial assembly of leucine-rich repeat (LRR) gene segments achieves the required repertoire for antigen recognition. We have determined a crystal structure for a VLR-antigen complex, VLR RBC36 in complex with the H-antigen trisaccharide from human blood type O erythrocytes, at 1.67 angstrom resolution. RBC36 binds the H-trisaccharide on the concave surface of the LRR modules of the solenoid structure where three key hydrophilic residues, multiple van der Waals interactions, and the highly variable insert of the carboxyl-terminal LRR module determine antigen recognition and specificity. The concave surface assembled from the most highly variable regions of the LRRs, along with diversity in the sequence and length of the highly variable insert, can account for the recognition of diverse antigens by VLRs. | Receptors, Antigen |
The average general orthopaedic surgeon examines and treats a considerable number of acute lateral ankle ligament sprains in a busy office practice. A cursory review of recent articles published on this subject will present a confusing picture regarding diagnosis and treatment of Grade III injuries. An air of controversy surrounds the interpretation of diagnostic x-rays, and the management of these common ankle problems. This review article is presented to summarize current thoughts on the anatomy, biomechanics, diagnosis, and treatment of acute lateral ankle ligament sprains. | Ligaments, Articular |
There is an increasing burden of responsibility for intensivists to optimize donation potential after the declaration of brain death in patients with catastrophic brain injury. Best practice for donor management, if present, has been formed on low quality and mainly observational studies or consensus. In particular, research into the use of corticosteroids has shown varied benefit. The specific and limited results of the CORTICOME study are less important than the systematic methodology and the development of rigour in the study of deceased organ donation. Donor management would benefit from continued systematic analysis of current literature, understanding of the physiologic basis for therapy, and further prospective controlled trials. Worldwide collaboration partnerships and funding are needed to optimize the management of deceased organ donation. | Nordefrin |
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