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Rat ventral prostate and liver were investigated for the binding in vitro to particulate fractions and for the metabolism of 5 alpha-androstane-3 beta, 17 beta-diol. Comparative investigations were carried out on the metabolism of 5 alpha-androstane-3 alpha, 17 beta-diol. Preparations of the liver were investigated in order to establish the organ specificity of the method. In the prostate, the bulk of the metabolites of 5 alpha-androstane-3 beta, 17 beta-diol was present as steroids of high polarity. Of the less polar metabolites, 17 beta-hydroxy-5 alpha-androstan-3-one, 3 beta-hydroxy-5 alpha-androstan, 17-one and 5 alpha-androstane-3 alpha, 17 beta-diol were detectable. The binding of a 5 alpha-androstane-3 beta, 17 beta-diol to mitochondria and microsomes was unspecific. In the liver, among the less polar metabolites, 3 beta-hydroxy-5 alpha-androstan-17-one was the main metabolite, and the binding was unspecific. The main metabolite in the prostate homogenate of 5 alpha-androstane-3 alpha, 17 beta-diol was 17 beta-hydroxy-5 alpha-androstan-3-one. The portion of highly polar steroids was very low. The portion of unmetabolized hormone was distributed almost equally among the different cell preparations except the nuclei, in which 17 beta-hydroxy-5 alpha-androstan-3-one was higher and 5 alpha-androstane-3 alpha, 17 beta-diol was lower than in the remaining cell fractions.
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Androstane-3,17-diol
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Gene therapy has been widely studied in colon cancer treatment. However, effective delivery of genes is a limitation for clinical applications. In the research, DOATP/mPEG-PLA-mPEG (DPLP) nanoparticles carrying the vesicular stomatitis virus matrix protein plasmid (pVSVMP) was used for colon cancer therapy, resulting in high transfection efficiency and expression efficiency in CT26 cells. Moreover, the DPLP-pVSVMP complex was provide with apoptosis induction and proliferation suppression of CT26 cells in vitro and can efficiently inhibit tumor growth in murine colon cancer model by inducing apoptosis, suppressing proliferation and angiogenesis. These results suggest that DPLP nanoparticles delivering pVSVMP might be a latent therapeutic avenue for colon cancer.
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Vesicular Stomatitis
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The retinal protein, bacteriorhodopsin (bR), has several potential bioelectronic applications and it is considered as a model for G-protein coupled receptors. Its electrical parameters, therefore, deserve particular attention. Such parameters could be determined by virtue of studying its dielectric spectrum in the low frequency range (20 Hz-1 MHz). The kinetics of dark-light adaptation of bR is reported in terms of electrical parameters of the purple membrane (PM) containing bR. The data have exhibited sudden pronounced increase in the ac-conductivity, upon illuminating the dark-adapted bR (DA-bR), which may be considered in further implications of bR for biotechnological applications. These changes turned out to be composed of, at least, two growing exponential components: one relatively fast followed by slower one. Their lifetime ratio exhibited decreases with increasing the frequency; meanwhile, their amplitude ratio displayed very exciting behavior at significant frequencies. This may correlate the kinetics of light adaptation to relaxations in PM. Moreover, the light adaptation has been observed to cause initial fast and large decreases in dc-conductivity with subsequent slower and smaller decreases. Changing the conductivity during the time of light adaptation reflects changes in the surface charge of the PM. The lifetimes of these events, therefore, help follow the kinetics of the pathway of conformational changes that might be occurring during light adaptation. The dipole moment (permanent and induced) of PM, in addition to, its size showed one exponential growth of comparable lifetime (approximately 7 min) during the light adaptation. The variation in PM size from dark to light state should be in keeping with that diffusion may influence the three-dimensional data storage in data processing based on bR.
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Purple Membrane
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African trypanosomes are well known for their ability to avoid immune elimination by switching the immunodominant variant surface glycoprotein (VSG) coat during infection. However, antigenic variation is only one of several means by which trypanosomes manipulate the immune system of their hosts. In this article, the role of parasite factors such as GPI anchor residues of the shed VSG molecule and the release of CpG DNA, in addition to host factors such as IFN-gamma, in regulating key aspects of innate and acquired immunity during infection is examined. The biological relevance of these immunoregulatory events is discussed in the context of host and parasite survival."
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Variant Surface Glycoproteins, Trypanosoma
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Which recommendations family doctors and travel health practitioners can provide to their patients, to reduce their environmental footprint when travelling? Avoiding flying is the biggest action a traveler can take to reduce their greenhouse gas emissions. Staying at eco-lodges, or carbon offsetting, may help, but one must be aware of false or exaggerated claims on their impact. Using UV light, filters, halogens or boiling water, are effective ways to disinfect water and reduce the waste created from plastic water bottles. Given the large carbon footprint of medications and laboratory exams, limiting prescription of antibiotics or antimalarials in pre-travel consultations, or limiting unnecessary laboratory exams in returning travelers by following the latest recommendations, could reduce greenhouse emissions of the medical practice.
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Carbon Footprint
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The aim of this study was to analyse homology in the telomeric region of chromosome 11 in humans and a corresponding fragment in the porcine genome using the FISH technique. The human band specific probe (HSA 11p15) was used for hybridization with pig chromosomes. The obtained results showed strong signals on human chromosome 11p15, as well as pig chromosome 2p17. Some aspects of the similarity between the human and pig chromosome segments have been discussed.
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Chromosomes, Human, Pair 11
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The creatine shuttle translocates the energy generated by oxidative phosphorylation to the cytoplasm via mitochondrial creatine kinase (MTCK) and creatine kinase B (CKB) in the cytoplasm. It is not apparent how the creatine shuttle is related to cancer. Here, we analyzed the expression and function of CKB and MTCK in colorectal cancer (CRC) and investigated the role of the creatine shuttle in CRC. Compared with normal mucosa, 184 CRC tissues had higher levels of CKB and MTCK, and these levels were associated with histological grade, tumor invasion, and distant metastasis. CK inhibitor dinitrofluorobenzene (DNFB) on CRC cell lines HT29 and CT26 inhibited cell proliferation and stemness to less than 2/3 and 1/20 of their control levels, respectively. In this treatment, the production of reactive oxygen species increased, mitochondrial respiration decreased, and mitochondrial volume and membrane potential decreased. In a syngeneic BALB/c mouse model using CT26 cells pretreated with DNFB, peritoneal metastasis was suppressed to 70%. Phosphorylation of EGFR, AKT, and ERK1/2 was inhibited in DNFB-treated tumors. High ATP concentrations prevented EGFR phosphorylation in HT29 cells following DNFB treatment, CKB or MTCK knockdown, and cyclocreatine administration. Despite not being immunoprecipitated, CKB and EGFR were brought closer together by EGF stimulation. These findings imply that blocking the creatine shuttle decreases the energy supply, suppresses oxidative phosphorylation, and blocks ATP delivery to phosphorylation signals, preventing signal transduction. These findings highlight the critical role of the creatine shuttle in cancer cells and suggest a potential new cancer treatment target."
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Creatine Kinase, Mitochondrial Form
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The Lotus japonicus symbiont Mesorhizobium loti R7A encodes two copies of nodD and here we identify striking differences in Nod factor biosynthesis gene induction by NodD1 and NodD2 both in vitro and in planta. We demonstrate that induction of Nod factor biosynthesis genes is preferentially controlled by NodD1 and NodD2 at specific stages of symbiotic infection. NodD2 is primarily responsible for induction in the rhizosphere and within nodules, while NodD1 is primarily responsible for induction within root hair infection threads. nodD1 and nodD2 mutants showed significant symbiotic phenotypes and competition studies establish that nodD1 and nodD2 mutants were severely outcompeted by wild-type R7A, indicating that both proteins are required for proficient symbiotic infection. These results suggest preferential activation of NodD1 and NodD2 by different inducing compounds produced at defined stages of symbiotic infection. We identified Lotus chalcone isomerase CHI4 as a root hair induced candidate involved in the biosynthesis of an inducer compound that may be preferentially recognized by NodD1 within root hair infection threads. We propose an alternative explanation for the function of multiple copies of nodD that provides the host plant with another level of compatibility scrutiny at the stage of infection thread development.
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Phyllobacteriaceae
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Ever since it was established that rodents serve as reservoirs of the zoonotic Lassa virus (LASV), scientists have sought to answer the questions: which populations of rodents carry the virus? How do fluctuations in LASV prevalence and rodent abundance influence Lassa fever outbreaks in humans? What does it take for the virus to adopt additional rodent hosts, proliferating what already are devastating cycles of rodent-to-human transmission? In this review, we examine key aspects of research involving the biology of rodents that affect their role as LASV reservoirs, including phylogeography, demography, virus evolution, and host switching. We discuss how this knowledge can help control Lassa fever and suggest further areas for investigation.
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Viral Zoonoses
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INTRODUCTION: Anterior and anterolaterally situated foramen magnum meningiomas are a technically complex subgroup of meningiomas. The need for an extensive exposure and bone work and their complex anatomy make them a difficult and challenging group of tumors to resect. The bone work has ranged from an extensive condylar resection to condylar preserving exposures. In this paper, we present our experience with condylar preserving or minimal condylar resection based approaches to these tumors. MATERIALS AND METHODS: All patients who underwent surgical resection of anterior and anterolaterally situated foramen magnum meningiomas were included in the analysis. The study period was more than 10 years from 2005 to 2015 at our institute; a tertiary referral centre in India. The records along with demographic profile, clinico-radiological features, surgical strategies, outcomes as well as mortality and morbidity were analysed. RESULTS: There were a total of 20 patients (9 males and 11 females) who were operated during the study period. The average age was 36.7 years. In 16 patients, gross-total or near-total resection could be achieved, four patients underwent subtotal resection. Eight patients had fresh morbidity in the form of new motor deficits, pseudomeningocele formation, worsening of the lower cranial nerve functions or post-operative adhesions leading to syrinx formation. The follow-up ranged from 6 months to 140 months. CONCLUSION: Foramen magnum meningiomas are an eminently treatable group of tumors. Condylar preservation provides a good visualization, while helping to preserve joint stability and in avoiding instrumental stabilization.
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Foramen Magnum
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PURPOSE: This systematic review examined whether diabetes self-management education (DSME) interventions for US Latino adults improve general emotional distress (eg, depression symptoms) and/or health-specific emotional distress (eg, diabetes distress). The topic is important given the high prevalence of type 2 diabetes (T2DM), concomitant distress, and worse health outcomes among Latinos and considering the barriers that distress poses for effective diabetes self-management. METHODS: Following PRISMA guidelines, a search of the online databases PsycINFO, CINAHL, PubMed, and CENTRAL was conducted from database inception through April 2018. A comprehensive search strategy identified trials testing DSME interventions for US Latinos with T2DM that reported on changes in general or health-specific emotional distress. Risk of bias was assessed using the EPHPP Quality Assessment Tool. Raw mean differences ( D) and effect sizes ( d) were computed where possible. RESULTS: Fifteen studies were included in the review. Six of 8 studies that examined depression symptoms reported significant symptom reduction. Of 10 studies that examined health-specific emotional distress, 6 reported significant symptom reduction. Effect sizes ranged from -0.20 to -3.85. Null findings were more readily found among studies with very small sample sizes (n < 30) and studies testing interventions without specific psychosocial content, with little cultural tailoring, with less frequent intervention sessions, and with support sessions lacking concurrent diabetes education. Most studies (11) received a weak rating of evidence quality. CONCLUSIONS: There is an absence of strong evidence to support that DSME programs tailored for Latino adults with T2DM are beneficial for improving emotional distress. Methodologically robust studies are needed.
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Self-Management
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Acute appendicitis and its subsequent complications continue to pose a surgical challenge. One such complication, the appendico-cutaneous fistula, represents a very rare form of enterocutaneous fistula. Very few cases have been reported thus far in the literature. The clinical presentation of this case before the final diagnosis was made makes interesting reading. The report describes a unique case that presented with the onset of cellulitis around the right lumbar/loin region, spreading down the right posterior back to the posterior gluteal area, and appearing as necrotizing fasciitis. There were no abdominal signs at all. The patient was then taken to the operating room (OR) for incision and drainage through a right flank incision, which could be extended. At drainage, there was a feculent smell with discharge that immediately raised the possibility of colonic connection with the abscess cavity. Swab sent for culture and sensitivity grew E. coli and Bacteroides. The final diagnosis proved to be a perforated appendix. Therefore, perforated appendix should always be considered in the differential diagnosis of any spreading cellulitis in the right lumbar area or right lower abdominal quadrant in the presence of limited urinary symptoms and little or no abdominal signs.
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Cecal Diseases
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This Policy Brief is the fourth in a series of reports issued by the George Washington University Center for Health Services Research and Policy that examine the design of separately-administered State Children's Health Insurance Programs (SCHIP) that is, programs that operate directly under the authority of the federal SCHIP statute rather than expansions of state Medicaid programs. These Policy Briefs also consider the implications of states' design choices for children's access to health care. The first three briefs in this series focused on three aspects of separate SCHIP programs: children's legal right to assistance under separate programs; benefit and coverage design choices under SCHIP plans; and the design and structure of freestanding managed care contracts negotiated by SCHIP agencies. This issue brief focuses on how financial eligibility for SCHIP actually is calculated, that is, the formulas that states have developed to count children's family income for purposes of measuring eligibility. This topic is of central importance to overall program administration because of the federal legal prohibition against assistance to targeted low-income children who are in fact Medicaid-eligible. This prohibition on duplication of assistance was a crucial assumption in the enactment of SCHIP. It is also key to the conservation of limited SCHIP funding for targeted low-income children who are ineligible for either Medicaid or any other form of health insurance, particularly as unemployment rises and the number of lower income children without health insurance may be poised to increase.
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Eligibility Determination
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CSF from the subarachnoid space moves rapidly into the brain along paravascular routes surrounding penetrating cerebral arteries, exchanging with brain interstitial fluid (ISF) and facilitating the clearance of interstitial solutes, such as amyloid beta, in a pathway that we have termed the glymphatic" system. Prior reports have suggested that paravascular bulk flow of CSF or ISF may be driven by arterial pulsation. However, cerebral arterial pulsation could not be directly assessed. In the present study, we use in vivo two-photon microscopy in mice to visualize vascular wall pulsatility in penetrating intracortical arteries. We observed that unilateral ligation of the internal carotid artery significantly reduced arterial pulsatility by ~50%, while systemic administration of the adrenergic agonist dobutamine increased pulsatility of penetrating arteries by ~60%. When paravascular CSF-ISF exchange was evaluated in real time using in vivo two-photon and ex vivo fluorescence imaging, we observed that internal carotid artery ligation slowed the rate of paravascular CSF-ISF exchange, while dobutamine increased the rate of paravascular CSF-ISF exchange. These findings demonstrate that cerebral arterial pulsatility is a key driver of paravascular CSF influx into and through the brain parenchyma, and suggest that changes in arterial pulsatility may contribute to accumulation and deposition of toxic solutes, including amyloid beta, in the aging brain."
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Extracellular Fluid
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The usual pigmentation pattern in mammalian skin consists of fixed melanocytes in the basal layer of the epidermis, supplying keratinocytes with melanosomes. We observed that the glabrous skin (rhinaria and footpads) of dogs deviates from this pattern. In dogs, melanocytes are found in both the dermis and epidermis. The epidermal melanocytes are situated in the intercellular spaces of the basal and spinous layers. They are characterized by a quantity of cytoplasm containing a centriole, also developing melanosomes, and in some cases annulate lamellae. There is a high frequency of closely apposed melanocytes in the epidermis. Melanosomes in different stages of formation are also abundant. The morphology of the glabrous skin of dogs suggests transport of melanocytes from the dermis into the epidermis and formation of melanosomes in the epidermis. A distributed and intense pigment formation may be necessary to achieve the black noses of many dog breeds and wild canids, as well as dark footpads despite heavy abrasion and rapid skin renewal.
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Melanosomes
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Ca(2+)/calmodulin-dependent protein kinase II (CAMK2) is a key player in synaptic plasticity and memory formation. Mutations in Camk2a or Camk2b cause intellectual disability in humans, and severe plasticity and learning deficits in mice, indicating unique functions for each isoform. However, considering the high homology between CAMK2A and CAMK2B, it is conceivable that for critical functions, one isoform compensates for the absence of the other, and that the full functional spectrum of neuronal CAMK2 remains to be revealed.Here we show that germline as well as adult deletion of both CAMK2 isoforms in male or female mice is lethal. Moreover, Ca(2+)-dependent activity as well as autonomous activity of CAMK2 is essential for survival. Loss of both CAMK2 isoforms abolished LTP, whereas synaptic transmission remained intact. The double-mutants showed no gross morphological changes of the brain, and in contrast to the long-considered role for CAMK2 in the structural organization of the postsynaptic density (PSD), deletion of both CAMK2 isoforms did not affect the biochemical composition of the PSD. Together, these results reveal an essential role for CAMK2 signaling in early postnatal development as well as the mature brain, and indicate that the full spectrum of CAMK2 requirements cannot be revealed in the single mutants because of partial overlapping functions of CAMK2A and CAMK2B.SIGNIFICANCE STATEMENT CAMK2A and CAMK2B have been studied for over 30 years for their role in neuronal functioning. However, most studies were performed using single knock-out mice. Because the two isoforms show high homology with respect to structure and function, it is likely that some redundancy exists between the two isoforms, meaning that for critical functions CAMK2B compensates for the absence of CAMK2A and vice versa, leaving these functions to uncover. In this study, we generated Camk2a/Camk2b double-mutant mice, and observed that loss of CAMK2, as well as the loss of Ca(2+)-dependent and Ca(2+)-independent activity of CAMK2 is lethal. These results indicate that despite 30 years of research the full spectrum of CAMK2 functioning in neurons remains to be unraveled."
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Non-ribosomal peptides are built from both proteinogenic and non-proteinogenic amino acids. The latter resemble amino acids but contain modifications not found in proteins. The recent characterization of a non-heme Fe(2+) and alpha-ketoglutarate-dependent oxygenase that stereospecifically generates beta-hydroxyasparagine, an unnatural amino acid building block for the biosynthesis of calcium-dependent antibiotic, a lipopeptide antibiotic. This work improves our understanding of how these non-proteinogenic amino acids are synthesized.
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Asparagine
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(230)U and its daughter nuclide (226)Th are novel therapeutic nuclides for application in targeted alpha-therapy of cancer. We have investigated the feasibility of producing (230)U/(226)Th via proton irradiation of (231)Pa according to the reaction (231)Pa(p,2n)(230)U. The experimental excitation function for this reaction is reported for the first time. Cross sections were measured using thin targets of (231)Pa prepared by electrodeposition and (230)U yields were analyzed using alpha-spectrometry. Beam parameters (energy and intensity) were determined both by calculation using a mathematical model based on measured beam orbits and beam current integrator and by parallel monitor reactions on copper foils using high-resolution gamma-spectrometry and IAEA recommended cross-section data. The measured cross sections are in good agreement with model calculations using the EMPIRE-II code and are sufficiently high for the production of (230)U/(226)Th in clinically relevant amounts. A highly effective separation process was developed to isolate clinical grade (230)U from irradiated protactinium oxide targets. Product purity was assessed using alpha- and gamma-spectrometry as well as ICPMS.
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Protactinium
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Histamine H2-receptor antagonists must be used with caution to define the pharmacology of histamine effects on lymphocyte mitogenesis induced by PHA, because they can enhance and/or suppress in their own right, because these effects are similar to those of histamine itself, because mitogenic doses of PHA can release significant amounts of histamine from supposedly pure mononuclear cell preparations.
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Burimamide
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Computation plays an important role in functional genomics. THEMATICS is a computational method that predicts chemical and electrostatic properties of residues in enzymes and utilizes information contained in those predictions to identify active sites. The only input required is the three-dimensional structure of the query protein. The identification of residues involved in catalysis and in recognition is discussed. The two serine proteases Kex2 from Saccharomyces cerevisiae and subtilisin from Bacillus subtilis are used as examples to illustrate how the method finds the catalytic residues for both enzymes. In addition, Kex2 is specific for dibasic sites and THEMATICS finds the recognition residues for both the S1 and S2 sites of Kex2. In contrast, no such recognition sites are found for the non-specific enzyme subtilisin. The ability to identify sites that govern recognition opens the door to better understanding of specificity and to the design of highly specific inhibitors.
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Subtilisins
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OBJECTIVES: To study the role of monocyte chemoattractant protein-4 (MCP-4)/CCL13 in the pathogenesis of rheumatoid arthritis (RA), we analysed the expression of MCP-4/CCL13 in chondrocytes, synovial fluid and serum from patients with RA and investigated the effect of MCP-4/CCL13 on the proliferation of synovial cells. METHODS: Human articular cartilage specimens were obtained from joints from RA and osteoarthritis (OA) patients and normal joints (controls). Transcript levels of MCP-4 in cartilage were determined by real-time polymerase chain reaction. Protein levels were measured by enzyme-linked immunoassay. Cultured fibroblast-like synoviocytes (FLS) were treated with various concentrations of recombinant MCP-4/CCL13 protein, and cell proliferation was evaluated with a viability assay. RESULTS: The gene expression of MCP-4 was significantly higher in cartilage from RA patients than in that from OA patients (P = 0.00902) and in normal cartilage (P = 0.00902). The concentration of MCP-4/CCL13 protein in serum from RA patients (mean 94.7 +/- 37.6 pg/ml) was significantly higher than in serum from OA patients (mean 49.2 +/- 31.2 pg/ml, P = 0.0051) and controls (mean 32.6 +/- 23.9 pg/ml, P = 0.0001). The concentration of MCP-4/CCL13 protein in synovial fluid from RA patients (mean 247.2 +/- 161.2 pg/ml) was also significantly higher than in that from OA patients (mean 29.6 +/- 50.5 pg/ml, P = 0.000019). Moreover, MCP-4/CCL13 enhanced the proliferation of FLS in a dose-dependent manner. CONCLUSIONS: MCP-4/CCL13 is highly expressed in RA joints at the mRNA and protein levels. Our results suggest that MCP-4/CCL13 is secreted from chondrocytes and activates the proliferation of rheumatoid synovial cells, thereby leading to joint destruction in RA."
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Monocyte Chemoattractant Proteins
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Peroxidase-proximity protein labeling was performed using a hemin-parallel G-quadruplex (G4) complex. A tyrosine labeling reaction using an N-methyl luminol derivative was accelerated in close proximity to the hemin with enhanced peroxidase activity by binding to parallel G4. The TERRA-hemin complex activated the labeling of many RNA-binding proteins, including heterogeneous nuclear ribonucleoproteins, in a HeLa cell lysate."
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Heterogeneous-Nuclear Ribonucleoprotein Group A-B
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Due to the rising life expectancy, bone diseases (e.g. osteoporosis, osteoarthritis) and trauma (e.g. fracture) have become an important socio-economic burden. Accurate visualization and quantification of the bone microstructure in vivo is seen as an important step to enhance diagnosis and treatment. Micro-computed tomography (microCT) has become the gold standard in three-dimensional (3D) imaging of trabecular bone structure. Yet, usage is limited to ex vivo analyses, hence, it cannot be used to evaluate bone and bone adaptive responses in a patient. High-resolution peripheral computed tomography (HR-pQCT) is considered the best technique to measure the bone microarchitecture in vivo. By design HR-pQCT is limited to scanning extremities, such as the distal radius and distal tibia with a limited field of view and long scanning time (~2â¯a 3â¯min. for a stack of 0.9â¯cm). Cone-beam computed tomography (CBCT) is a promising alternative with a much larger field of view. Yet, CBCT is challenged by artefacts that reduce image contrast, such that it is currently being used for qualitative evaluation only. Therefore, the aims of this work were first to enhance image contrast and second to determine the accuracy of high-resolution CBCT for bone microarchitectural assessment. Trapezia of nineteen female arthritic patients were scanned twice ex vivo; once using CBCT (NewTom 5G, Cefla, Verona, Italy) at a nominal voxel size of 75 mum and once using microCT (SkyScan 1172, Bruker, Kontich, Belgium) at a voxel size of 19.84 mum. The CBCT-scans were reconstructed following 2 protocols: (1) using the commercial software delivered with the scanner and (2) using in-house developed software. After reconstruction and image processing, the images were segmented using adaptive thresholding. Bone morphometric parameters including bone volume (BV), total tissue volume (TV), bone volume fraction (BV/TV), bone surface density (BS/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp) and trabecular number (Tb.N) were calculated. Statistical evaluations were made at a significance level of 5%. Significant correlations were found between the CBCT-based bone parameters and the microCT-based parameters with R(2)â¯>â¯0.68 The in-house reconstructed software outperformed the commercial software. Smaller bias (overestimation of Tb.Th decreased from 114.24% to 59.96%) as well as higher correlations were observed for the in-house processed images. Still, a significant overestimation was observed for BV/TV and Tb. Th and an underestimation for Tb.N. We conclude that our CBCT image reconstruction improved image contrast which allowed for an accurate quantification of trabecular bone microarchitecture.
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Trapezium Bone
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Rothmund-Thomson syndrome (RTS) is an autosomal recessive disorder characterized by skin abnormalities that appear in infancy, skeletal abnormalities, juvenile cataracts and other manifestations of premature aging, and a predisposition to malignancy. The diagnosis is made on clinical grounds as no consistent laboratory test has been identified. Chromosome studies have been reported for only three patients with RTS and in two of these three, trisomy 8 mosaicism was found. We performed a variety of cytogenetic and molecular genetic studies on two siblings with RTS and on their phenotypically normal parents. Two chromosomally abnormal clones involving either trisomy 8 or i(8q) were found in both patients with RTS. These clones were present in vivo, as they were seen in interphase buccal smears and lymphocytes from unstimulated preparations using both conventional cytogenetic studies and fluorescence in situ hybridization (FISH) with a centromere probe for chromosome 8. These results suggest that RTS is associated with in vivo clonal chromosomal rearrangements causing an acquired somatic mosaicism.
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Rothmund-Thomson Syndrome
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An important challenge in brain research is to make out the relation between the features of olfactory stimuli and the electroencephalogram (EEG) signal. Yet, no one has discovered any relation between the structures of olfactory stimuli and the EEG signal. This study investigates the relation between the structures of EEG signal and the olfactory stimulus (odorant). We show that the complexity of the EEG signal is coupled with the molecular complexity of the odorant, where more structurally complex odorant causes less fractal EEG signal. Also, odorant having higher entropy causes the EEG signal to have lower approximate entropy. The method discussed here can be applied and investigated in case of patients with brain diseases as the rehabilitation purpose.
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Olfactory Cortex
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Recent years have seen unprecedented investment in research and development for countermeasures for high-threat pathogens, including specific and ambitious objectives for development of diagnostics, therapeutics, and vaccines. The inadequate availability of biological reference materials for these pathogens poses a genuine obstacle in pursuit of these objectives, and the lack of a comprehensive and equitable framework for developing reference materials is a weakness. We outline the need for internationally standardized biological materials for high-threat pathogens as a core element of global health security. We also outline the key components of a framework for addressing this deficiency.
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Communicable Diseases
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PURPOSE: The chosen treatment and long-term evaluation of hindfoot blast injuries are not well-represented in the literature. The first objective of this retrospective study was to evaluate functional outcomes in French service personnel who had sustained such injuries caused by improvised explosive devices. The second objective was to compare the results for patients who had amputations with those who did not. The hypothesis was that amputee recovered better function. METHODS: Long-term functional evaluations were carried out using the American Orthopaedic Foot and Ankle Society scale (AOFAS), the Foot and Ankle Ability Measure (FAAM), and the Short Form 12 health survey (SF-12). RESULTS: Eight servicemen with ten hindfoot blast injuries were reviewed at a mean follow-up time of seven years. Primary management was always conservative although half of the patients required late amputation for chronic pain. The patients who underwent amputation reported significantly lower levels of pain than those who did not have an amputation, with higher FAAM and SF-12 scores. CONCLUSION: In this series, long-term functional results appear better in the amputated group.
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Blast Injuries
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Safety deals with the surveillance and detection of possible threats that can arise against a patient. It might not be an obvious one, like an anaphylactic shock, but a bizarre syndrome of late onset preceded by vague signs or symptoms. To be able to conclude about a possible causal relationship between a drug and such a state with as short a delay in time as possible, the collection and analysis of adverse events during the total clinical trial program of a drug is mandatory. To ask investigators for adverse drug reactions instead is to produce an effective filter, which may help in keeping the incidence figures down in the international data sheet but which also may prove to be hazardous for the pharmaceutical industry in the long run.
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Practolol
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We assessed two aspects of numerical cognition in a group of nine captive spider monkeys (Ateles geoffroyi). Petri dishes with varying amounts of food were used to assess relative quantity discrimination, and boxes fitted with dotted cards were used to assess discrete number discrimination with equally-sized dots and various-sized dots, respectively. We found that all animals succeeded in all three tasks and, as a group, reached the learning criterion of 70% correct responses within 110 trials in the quantity discrimination task, 160 trials in the numerosity task with equally-sized dots, and 30 trials in the numerosity task with various-sized dots. In all three tasks, the animals displayed a significant correlation between performance in terms of success rate and task difficulty in terms of numerical similarity of the stimuli and thus a ratio effect. The spider monkeys performed clearly better compared to strepsirrhine, catarrhine, and other platyrrhine primates tested previously on both types of numerical cognition tasks and at the same level as chimpanzees, bonobos, and orangutans. Our results support the notion that ecological traits such as a high degree of frugivory and/or social traits such as a high degree of fission-fusion dynamics may underlie between-species differences in cognitive abilities.
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Ateles geoffroyi
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BACKGROUND: The pioneer transcription factor (TF) GATA4 (GATA Binding Protein 4) is expressed in multiple cardiovascular lineages and is essential for heart development. GATA4 lineage-specific occupancy in the developing heart underlies its lineage specific activities. Here, we characterized GATA4 chromatin occupancy in cardiomyocyte and endocardial lineages, dissected mechanisms that control lineage specific occupancy, and analyzed GATA4 regulation of endocardial gene expression. METHODS: We mapped GATA4 chromatin occupancy in cardiomyocyte and endocardial cells of embryonic day 12.5 (E12.5) mouse heart using lineage specific, Cre-activated biotinylation of GATA4. Regulation of GATA4 pioneering activity was studied in cell lines stably overexpressing GATA4. GATA4 regulation of endocardial gene expression was analyzed using single cell RNA sequencing and luciferase reporter assays. RESULTS: Cardiomyocyte-selective and endothelial-selective GATA4 occupied genomic regions had features of lineage specific enhancers. Footprints within cardiomyocyte- and endothelial-selective GATA4 regions were enriched for NKX2-5 (NK2 homeobox 5) and ETS1 (ETS Proto-Oncogene 1) motifs, respectively, and both of these TFs interacted with GATA4 in co-immunoprecipitation assays. In stable NIH3T3 cell lines expressing GATA4 with or without NKX2-5 or ETS1, the partner TFs re-directed GATA4 pioneer binding and augmented its ability to open previously inaccessible regions, with ETS1 displaying greater potency as a pioneer partner than NKX2-5. Single-cell RNA sequencing of embryonic hearts with endothelial cell-specific Gata4 inactivation identified Gata4-regulated endocardial genes, which were adjacent to GATA4-bound, endothelial regions enriched for both GATA4 and ETS1 motifs. In reporter assays, GATA4 and ETS1 cooperatively stimulated endothelial cell enhancer activity. CONCLUSIONS: Lineage selective non-pioneer TFs NKX2-5 and ETS1 guide the activity of pioneer TF GATA4 to bind and open chromatin and create active enhancers and mechanistically link ETS1 interaction to GATA4 regulation of endocardial development."
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Proto-Oncogene Protein c-ets-1
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BACKGROUND: Returning to a healthy level of physical activity is among the most commonly discussed clinical goals for patients recovering from anterior cruciate ligament reconstruction (ACLR). However, physical activity has not been objectively measured in this population. PURPOSE: To investigate differences in the mean time (min/d) spent in moderate-to-vigorous physical activity (MVPA) as well as the daily step count (steps/d) between patients who underwent ACLR and matched controls. A second purpose was to investigate relationships between MVPA and objective assessments of the daily step count and Tegner and Marx activity scales. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Physical activity was assessed using ActiGraph accelerometers in 33 participants with a history of primary unilateral or bilateral ACLR (mean time from surgery, 27.8 +/- 17.5 months; range, 6-67 months) as well as in 33 healthy controls (matched on age, sex, and activity level). Participants wore the accelerometer for 7 days and completed the International Knee Documentation Committee subjective form and the Tegner and Marx activity scales. Independent t tests were used to determine differences in each dependent variable per group. RESULTS: Patients who underwent ACLR spent less time in MVPA (ACLR: 79.37 +/- 23.95 min/d; control: 93.12 +/- 23.94 min/d; P = .02) and had a lower daily step count (ACLR: 8158 +/- 2780 steps/d; control: 9769 +/- 2785 steps/d; P = .02) compared with healthy matched controls. However, the Marx (ACLR median: 11.0 [interquartile range (IQR), 7-14]; control median: 12.0 [IQR, 8-13]; P = .85) and Tegner (ACLR median: 6.0 [IQR, 5-8]; control median: 7.0 [IQR, 6-8]; P = .12) scores did not differ between the groups, and no relationships were observed between objectively measured physical activity and scale measures ( P > .05), except for a moderate relationship between the Tegner score and daily step count in the ACLR group ( r = 0.36, P = .04). Only 24% of patients who underwent ACLR met the guideline of 10,000 steps per day compared with 42% of controls. CONCLUSION: Patients who underwent ACLR spent less time in MVPA and had a lower daily step count compared with highly matched controls (age, sex, and activity level) with no history of knee injuries. This was true despite being similar in activity levels, which brings into question the utility of the Tegner and Marx activity scales.
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Lysholm Knee Score
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BACKGROUND: To clarify the differences in diaphragm thickness between male and female participants in healthy young adults with ultrasonography using the mean intima media thickness (IMT) method and to investigate the relationship between diaphragm thickness and respiratory pressure. METHODS: Twenty-nine healthy individuals (16 females and 13 males) participated in the study. Diaphragm thickness was measured at total lung capacity (TLC) and at functional residual capacity (FRC) in each participant. We measured the diaphragm thickness using a method for mean intima media thickness. Moreover, change ratio of diaphragm thickness was calculated with the diaphragm thickness at TLC and FRC. RESULTS: Mean diaphragm thicknesses at FRC in males were significantly narrower than those in females (p < 0.001). The change ratio of diaphragm thickness was significantly augmented in males compared with that in females (p < 0.001). There was a positive correlation between the change ratio of diaphragm thickness and pulmonary function data and respiratory muscle strength in healthy young adults. CONCLUSIONS: The change ratio of diaphragm thickness using the IMT method can be accurately performed with a high degree of reproducibility by clinical laboratory technicians and may be a useful indicator for evaluating diaphragm muscle strength.
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Abdominal Core
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During cell aging, proteins accumulate damages, which affect their structure and activity. The protein l-isoaspartyl methyltransferase (PIMT) is involved in the repair of proteins containing abnormal L-isoaspartyl residues. Although its mechanism of action is well defined, little is known about the pathways involved in the regulation of PIMT expression. In this study, we demonstrated that glycogen synthase kinase-3 (GSK-3) and beta-catenin are involved in the regulation of PIMT expression. Treatment of astrocytoma cells (U-87) with direct pharmacological GSK-3 inhibitors such as lithium, SB-216763 and SB-415286 stimulated PIMT expression ( approximately twofold). As expected, GSK-3 inhibition led to an increase of phosphorylated GSK-3beta (Ser9) and to beta-catenin accumulation. PIMT induction by lithium was dependent on increased protein synthesis. In addition, RT-PCR analysis showed higher level of PIMT mRNA following GSK-3 inhibition, which was abolished by the transcriptional inhibitor actinomycin D. These results demonstrated regulation of PIMT expression by lithium at both the transcriptional and the translational levels. Additionally, inhibition by siRNA of GSK-3 and beta-catenin modulated the expression of the PIMT in accordance with GSK-3 pharmacological inhibition. Valproic acid, an antiepileptic drug with mood-stabilizing properties, up-regulated phospho-GSK-3beta (Ser9), beta-catenin and PIMT levels similarly to lithium. This study reports that PIMT expression is up-regulated by GSK-3 inhibition and beta-catenin stabilization upon treatments with lithium and valproic acid. These findings suggest a possible therapeutic role for PIMT in certain brain diseases including epilepsy.
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Protein O-Methyltransferase
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Evaluation of the skin irritancy and corrosivity potential of an ingredient is a necessity in the safety assessment of cosmetic ingredients. To date, there are two formally validated alternatives to the rabbit Draize test for skin corrosivity in place, namely the rat skin transcutaneous electrical resistance (TER) assay and the Human Skin Model Test using EpiSkin, EpiDerm and SkinEthic reconstructed human epidermal equivalents. For skin irritation, EpiSkin, EpiDerm and SkinEthic are validated as stand-alone test replacements for the rabbit Draize test. Data from these tests are rarely considered in isolation and are evaluated in combination with other factors to establish the overall irritating or corrosive potential of an ingredient. In light of the deadlines established in the Cosmetics Directive for cessation of animal testing for cosmetic ingredients, a COLIPA scientific meeting was held in Brussels on 30th January, 2008 to review the use of alternative approaches and to set up a decision tree approach for their integration into tiered testing strategies for hazard and safety assessment of cosmetic ingredients and their use in products. In conclusion, the safety assessments for skin irritation/corrosion of new chemicals for use in cosmetics can be confidently accomplished using exclusively alternative methods.
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Skin Irritancy Tests
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Protein immobilization has gained high interest in recent years for its valuable applications in life sciences involving drug delivery and protein arrays. Herein, we combine sortase-mediated protein immobilization with the versatility of magnetic nanoparticles and a sensitive GFP-based quantification system. Using this method, we successfully immobilized and quantified the amount of coupled enzymes by fluorescence spectroscopy and assessed their activity by kinetic measurements. We show that sortase-mediated coupling of enzymes enables preparation of biological samples with a high demand of purity as demonstrated by single-molecule FRET. Here, we report that sortase-mediated protein ligation allows both N- and C-terminal site-specific protein immobilization. Additionally, we demonstrate that sortase-mediated protein immobilization is suitable for direct protein immobilization from complex lysates. Direct immobilization from lysate allows study of enzyme functionality without the need of time-consuming enzyme purification, while magnetic nanoparticles permit easy addition and removal of coupled enzymes to and from a reaction mixture.
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Aminoacyltransferases
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Many subliminal priming experiments are thought to demonstrate unconscious access to semantics. However, most of them can be reinterpreted in a non-semantic framework that supposes only that subjects learn to map non-semantic visual features of the subliminal stimuli onto motor responses. In order to clarify this issue, we engaged subjects in a number comparison task in which the target number was preceded by another invisible masked number. We show that unconscious semantic priming occurs even for prime stimuli that are never presented as target stimuli, and for which no stimulus-response learning could conceivably occur. We also report analyses of the impact of the numerical relation between prime and target, and of the impact of learning on priming, all of which confirm that unconscious utilization of semantic information is indeed possible.
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Perceptual Masking
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Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome with exceptionally high lifetime cancer risks, caused primarily by germline TP53 variants. Early-onset breast cancer is the most common cancer in women with LFS. Associations between female reproductive factors and breast cancer risk have been widely studied in the general population and BRCA1/2 mutation carriers but not in LFS. We evaluated whether reproductive factors are associated with breast cancer in LFS. Questionnaire data were collected for 152 women with confirmed germline TP53 variants enrolled in the National Cancer Institute's LFS study (NCT01443468); of which, 85 had breast cancer, confirmed by pathology/medical reports. Fisher's exact test and Cox proportional hazards were used to calculate the effect of reproductive factors on breast cancer risk. Lifetime breastfeeding for at least 7 months was associated with lower breast cancer risk (hazard ratio [HR] 0.57, p = 0.05). Parity did not independently change breast cancer risk (HR 1.08, p = 0.8) but suggested an increased risk with older age at first live birth (HR 2.14, p = 0.05). Age at menarche (HR 1.09, p = 0.24) and use of oral contraceptives (HR 0.88; p = 0.7) did not significantly affect breast cancer risk. In this first study of reproductive factors and breast cancer in women with LFS, breastfeeding was observed to be protective against breast cancer risk, especially with at least 7 months of lifetime breastfeeding. Older age at first live birth was suggested to slightly increase breast cancer risk. Larger prospective studies of reproductive factors are warranted in women with LFS before making definitive clinical recommendations.
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Li-Fraumeni Syndrome
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The structure of circulating chromogranin A (CgA) of phaeochromocytoma patients was characterised and compared with that of CgA extracted from tumours. Size exclusion chromatography experiments provided evidence that CgA is present in the blood of different patients, as well as in tumour extracts, as multiple forms having different hydrodynamic sizes of 600 kDa (CgA-I), 100 kDa (CgA-II) and 55 kDA (CgA-III). The amount of each CgA form as a proportion of the total antigenic material was different in different patients. Western blot analysis of chromatographic fractions indicated that these forms are made up by polypeptides of similar molecular weight (about 60-70 kDa). All CgA forms express the epitopes recognised by two monoclonal antibodies (A11 and B4E11), directed against residues 68-70 and 81-90 of human CgA. However, their relative immunoreactivity was markedly different. No evidence for the presence of multimeric complexes in the CgA-I fraction was obtained by various immunological and biochemical methods. These results suggest that circulating CgA in phaeochromocytoma patients consists of at least three forms that appear to be made up by polypeptides with similar molecular weight and different hydrodynamic properties and immunoreactivity. We hypothesise that different conformations and shapes contribute to the heterogeneity of circulating CgA.
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Chromogranins
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Temperature-sensitive shibire mutants of Drosophila melanogaster become rapidly paralyzed upon a shift to the restrictive temperature, which is due to a block in synaptic vesicle endocytosis. The shibire gene encodes the GTPase dynamin. Recent studies have shown that dynamin forms rings at the neck of invaginated clathrin-coated pits, and have suggested that a conformational change in the ring, which correlates with GTP hydrolysis, plays an essential role in vesicle fission.
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GTP Phosphohydrolases
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Paleontologists are urged to take a stand against a market that may provide cover for continued poaching.
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Afrotheria
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After growth in the absence of nitrogenous oxides under anaerobic phototrophic conditions, several strains of Rhodopseudomonas capsulata were shown to possess a nitrous oxide reductase activity. The enzyme responsible for this activity had a periplasmic location and resembled a nitrous oxide reductase purified from Pseudomonas perfectomarinus. Electron flow to nitrous oxide reductase was coupled to generation of a membrane potential and inhibited by rotenone but not antimycin. It is suggested that electron flow to nitrous oxide reductase branches at the level of ubiquinone from the previously characterized electron transfer components of R. capsulata. This pathway of electron transport could include cytochrome c', a component hitherto without a recognized function. R. capsulata grew under dark anaerobic conditions in the presence of malate as carbon source and nitrous oxide as electron acceptor. This confirms that nitrous oxide respiration is linked to ATP synthesis. Phototrophically and anaerobically grown cultures of nondenitrifying strains of Rhodopseudomonas sphaeroides, Rhodopseudomonas palustris, and Rhodospirillum rubrum also possessed nitrous oxide reductase activity.
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Rhodospirillum
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CONSTRICTIVE PERICARDITIS is characterized by progressive inflammation and fibrosis of the pericardium. It manifests with symptoms of heart failure. The only effective treatment is surgical pericardiectomy. The assessment and diagnosis of constrictive pericarditis with echocardiography is well described with spontaneous ventilation. However, there are limited data on constrictive pericarditis assessment with transesophageal echocardiography with positive pressure ventilation. Also, intraoperative hepatic venous Doppler flow mostly is used intraoperatively to assess the severity of tricuspid regurgitation by focusing on the flow reversal during systole. In this e-challenge, the authors focus on the hepatic vein Doppler tracing as a means to show improvement in diastolic function during positive pressure ventilation in a patient undergoing pericardiectomy. This case demonstrates a severely blunted diastolic flow pattern in the hepatic vein that is reversed after successful pericardiectomy. Also, it shows blunted flow during systole compared to diastole post-pericardiectomy, indicating high right atrial pressure.
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Hepatic Veins
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Insertion, management, and withdrawal of chest tubes is part of the routine activity of thoracic surgeons. The selection of the chest tube and the strategy for each of these steps is usually built on knowledge, practice, experience, and judgment. The indication to insert a chest tube into the pleural cavity is the presence of air or fluid within it. Various types and sizes of chest tubes are now commercially available.
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Chest Tubes
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The use of mindfulness in psychotherapy has garnered the attention of both researchers and therapists over recent years. Based on established research, use of mindfulness with clients is recommended to improve awareness during sessions, reduce ruminative thinking patterns, and increase self-compassion regardless of theoretical orientation. In this article, de-identified clinical material is used to illustrate both informal and formal mindfulness training in session. Further, we provide illustrations of presession and within-session therapist mindfulness, recommending that therapists develop their own mindfulness practice, as research has demonstrated that it is related to important clinical skills including attentiveness, nonjudgment, and improved client perceptions.
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Psychotherapy
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This study compared and contrasted the manifestation of neuropathic pain behaviors in several strains of rats. These included ACI, Brown-Norway, Fischer 344, Lewis, Long-Evans, Sprague-Dawley, and Wistar-Furth, all obtained from Harlan Sprague-Dawley Inc. Comparison was also made between two substrains of Sprague-Dawley rats: one from Harlan and the other from Sasco. Neuropathic injury was produced by tightly ligating the left L5 and L6 spinal nerves with the animals under halothane anesthesia. Tests were conducted for 2 weeks to examine behavioral signs representing mechanical allodynia, cold allodynia, and spontaneous pain. There was no difference between strains in any of the tested behaviors before surgery. After neuropathic injury, rats in most groups developed high levels of behavioral signs of various components of neuropathic pain; however, some strains of rats showed weak behavioral signs of neuropathic pain. When a comparison was made between two substrains of Sprague-Dawley rats from two different sources, the ones from Sasco showed weaker behavioral signs than those from Harlan. When comparisons were made between different strains of rats from the same source (Harlan), Brown-Norway and Long-Evans rats showed the smallest magnitude of neuropathic pain behaviors. The data indicate that different strains and substrains of rats display different degrees of pain behaviors, suggesting that strains and substrains are important variables in the development of neuropathic pain after peripheral nerve injury.
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Rats
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Accuracy of taxonomic identifications is crucial to data quality in online repositories of species occurrence data, such as the Global Biodiversity Information Facility (GBIF), which have accumulated several hundred million records over the past 15 years. These data serve as basis for large scale analyses of macroecological and biogeographic patterns and to document environmental changes over time. However, taxonomic identifications are often unreliable, especially for non-vascular plants and fungi including lichens, which may lack critical revisions of voucher specimens. Due to the scale of the problem, restudy of millions of collections is unrealistic and other strategies are needed. Here we propose to use verified, georeferenced occurrence data of a given species to apply predictive niche modeling that can then be used to evaluate unverified occurrences of that species. Selecting the charismatic lichen fungus, Usnea longissima, as a case study, we used georeferenced occurrence records based on sequenced specimens to model its predicted niche. Our results suggest that the target species is largely restricted to a narrow range of boreal and temperate forest in the Northern Hemisphere and that occurrence records in GBIF from tropical regions and the Southern Hemisphere do not represent this taxon, a prediction tested by comparison with taxonomic revisions of Usnea for these regions. As a novel approach, we employed Principal Component Analysis on the environmental grid data used for predictive modeling to visualize potential ecogeographical barriers for the target species; we found that tropical regions conform a strong barrier, explaining why potential niches in the Southern Hemisphere were not colonized by Usnea longissima and instead by morphologically similar species. This approach is an example of how data from two of the most important biodiversity repositories, GenBank and GBIF, can be effectively combined to remotely address the problem of inaccuracy of taxonomic identifications in occurrence data repositories and to provide a filtering mechanism which can considerably reduce the number of voucher specimens that need critical revision, in this case from 4,672 to about 100.
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Usnea
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Bronchiolitis obliterans after lung transplantation is the major factor which limits the long term survival. It affects 35-68% of those patients who survive longer than 3 months. Nowadays, the results of treatment and evaluation of bronchiolitis obliterans risk factors are not very encouraging. Although several risk factors of the development of bronchiolitis obliterans have already been identified, their role and importance have not been clearly defined yet. The objective of this article is to give an overview of the current international knowledge in treatment strategies and analyse to international trends in the research of risk factors of the development of this complication together with available results. Special attention is given to donor and recipient risk factors. (Tab. 2, Fig. 1, Ref. 32.)
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Bronchiolitis Obliterans
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Breast cancer is a major cause of cancer-related morbidity and mortality in women. Estrogen receptor-positive breast cancer accounts for roughly 70%-80% of breast tumors, and estrogen receptor alpha (ERalpha) has been considered as a key driver in promoting breast cancer progression. In the present study, we identified USP37 as a novel modulator in modulating ERalpha ubiquitination and stability. The expression of USP37 was upregulated in ERalpha-positive breast cancer and correlated with ERalpha protein level. High expression of USP37 was associated with unfavorable prognosis. USP37 depletion resulted in significantly decreased ERalpha protein level, ERalpha target genes expression as well as the estrogen response element activity in breast cancer cells. Further mechanistic study revealed the interaction between USP37 and ERalpha: USP37 regulated ERalpha signaling through modulating protein stability instead of gene expression, in which it stabilized ERalpha protein via inhibiting the K48-specific polyubiquitination process. Additionally, USP37 depletion led to growth inhibition and cell cycle arrest of ERalpha-positive breast cancer cells, which could be further rescued by ERalpha overexpression. Overall, our study proposed a novel post-translational mechanism of ERalpha in promoting breast cancer progression. Targeting USP37 may be proved to be a promising strategy for patients with ERalpha-positive breast cancer.
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Estrogen Receptor alpha
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The idea of constructing a taxonomy of rehabilitation interventions has been around for quite some time, but other than small and mostly ad hoc efforts, not much progress has been made, in spite of articulate pleas by some well-respected clinician scholars. In this article, treatment taxonomies used in health care, and in rehabilitation specifically, are selectively reviewed, with a focus on the need to base a rehabilitation treatment taxonomy (RTT) on the active ingredients" of treatments and their link to patient/client deficits/problems that are targeted in therapy. This is followed by a description of what we see as a fruitful approach to the development of an RTT that crosses disciplines, settings, and patient diagnoses, and a discussion of the potential uses in and benefits of a well-developed RTT for clinical service, research, education, and service administration."
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Physical Therapy Specialty
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When an integrated delivery system (IDS) determines it must divest itself of a previously acquired physician practice, it must manage the transaction with care. The IDS most likely will want to maintain a positive ongoing relationship with the physician practice, while avoiding concessions to the practice that could be construed as violations of state and Federal laws. Before proceeding, the IDS should evaluate the reasons for divesting the practice, assess legal issues involved in terminating contracts with the practice, decide how to deal with the practice's assets and office facilities, consider whether covenants not to compete should be enforced, ensure continued access to essential medical records, consider whether to incorporate a "non-disparagement" clause in the termination agreement, and determine what mutual general releases may be necessary."
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Practice Valuation and Purchase
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Acetogenic bacteria are imperative to environmental carbon cycling and diverse biotechnological applications, but their extensive physiological and taxonomical diversity is an impediment to systematic taxonomic studies. Acetogens are chemolithoautotrophic bacteria that perform reductive carbon fixation under anaerobic conditions through the Wood-Ljungdahl pathway (WLP)/acetyl-coenzyme A pathway. The gene-encoding formyltetrahydrofolate synthetase (FTHFS), a key enzyme of this pathway, is highly conserved and can be used as a molecular marker to probe acetogenic communities. However, there is a lack of systematic collection of FTHFS sequence data at nucleotide and protein levels. In an attempt to streamline investigations on acetogens, we developed AcetoBase - a repository and database for systematically collecting and organizing information related to FTHFS sequences. AcetoBase also provides an opportunity to submit data and obtain accession numbers, perform homology searches for sequence identification and access a customized blast database of submitted sequences. AcetoBase provides the prospect to identify potential acetogenic bacteria, based on metadata information related to genome content and the WLP, supplemented with FTHFS sequence accessions, and can be an important tool in the study of acetogenic communities. AcetoBase can be publicly accessed at https://acetobase.molbio.slu.se."
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Formate-Tetrahydrofolate Ligase
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BACKGROUND: The use of single RAS-blockade is currently the recommended first-line treatment for proteinuric diabetic or non-diabetic nephropathy, as these agents were repeatedly shown in studies with hard renal outcomes to retard the progression of renal injury. However, CKD will continue to progress on optimum single RAS-blockade, and other options to ameliorate renal injury were explored. Dual RAS-blockade was associated with an increased risk of adverse-events with no apparent benefits and, therefore, is currently abandoned. Based on the phenomenon of aldosterone escape and the well-documented harmful effects of aldosterone on renal tissue, several randomized trials have studied the effects of a MRA in diabetic and non-diabetic nephropathy. METHOD: This is a review of the literature in relevance to data evaluating the effect of MRA on renal outcomes. RESULTS: Studies with spironolactone and eplerenone added to single RAS-blockade showed that these agents are associated with greater reductions in urine albumin or protein excretion compared to either placebo or dual RASblockade. However, studies with these agents on hard renal outcomes are currently missing and the reasonable skepticism of physicians on the real-world incidence of hyperkalemia in CKD patients are limiting their use. A non-steroidal MRA, finerenone, has also great potency in decreasing albuminuria in diabetic nephropathy with possibly lower rates of hyperkalemia. Two multi-center clinical trials examining the effect of finerenone on hard cardiovascular and renal outcomes are currently ongoing. CONCLUSION: MRAs are able to reduce albuminuria and proteinuria on top of single RAS-blockade in patients with proteinuric CKD. Ongoing clinical trials are expected to clarify whether such an effect is accompanied by delay in CKD progression."
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Mineralocorticoid Receptor Antagonists
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Studies were performed on phagocytosis and on bactericidal capacity of human neutrophils (HN), isolated from healthy volunteers. Effects of indomethacin, PGE2, and TFX-Thymomodulin on function of the cells were examined. Only in a proportion of cases indomethacin was significantly reducing bactericidal activity of HN indicating that the activity might require the presence of endogenous prostaglandin. On the other hand, exogenous PGE2, inhibited bacterial killing in all cases and the suppression was abolished by TFX-Thymomodulin. The results might indicate antagonistic action on target cells of PGE2 on the one hand and of TFX-Thymomodulin on the other, which could point to the presence of receptors for thymic factors on HN.
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Thymus Extracts
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BACKGROUND: With the rapid development of long-read sequencing technologies, it is possible to reveal the full spectrum of genetic structural variation (SV). However, the expensive cost, finite read length and high sequencing error for long-read data greatly limit the widespread adoption of SV calling. Therefore, it is urgent to establish guidance concerning sequencing coverage, read length, and error rate to maintain high SV yields and to achieve the lowest cost simultaneously. RESULTS: In this study, we generated a full range of simulated error-prone long-read datasets containing various sequencing settings and comprehensively evaluated the performance of SV calling with state-of-the-art long-read SV detection methods. The benchmark results demonstrate that almost all SV callers perform better when the long-read data reach 20x coverage, 20 kbp average read length, and approximately 10-7.5% or below 1% error rates. Furthermore, high sequencing coverage is the most influential factor in promoting SV calling, while it also directly determines the expensive costs. CONCLUSIONS: Based on the comprehensive evaluation results, we provide important guidelines for selecting long-read sequencing settings for efficient SV calling. We believe these recommended settings of long-read sequencing will have extraordinary guiding significance in cutting-edge genomic studies and clinical practices.
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Genomic Structural Variation
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A sequence of technically reproducible procedures is mandatory to guarantee a proper preservation of tissues and to build up the basis for sound diagnoses. However, while the goal of these procedures was, until recently, to assure only structural (histological and cytological) preservation, an appropriate preservation of antigenic properties and of nucleic acid integrity is now additionally requested, in order to permit pathologists to provide the biological information necessary for the adoption of personalized therapies. The present review analyses the sequence of technical steps open to critical variations. Passages such as dehydration, paraffin embedding, sectioning and staining are relatively well standardized and allow adoption of dedicated (automatic) apparatuses, while other pre-analytical steps, i.e. time and modalities of transfer of surgical specimens from the surgical theatre to the pathology laboratory (s.c. ischemia time") and the type and length of fixation are not standardized and are a potential cause of discrepancies in diagnostic results. Our group is involved in European-funded projects tackling these problems with the concrete objective of implementing a model of effective tumors investigations by high performance genetic and molecular methodologies. The problem of the discrepant quality level of histopathological and cytological preparations involved five European countries and exploiting the potential of "virtual slide technology". Concrete issues, techniques and pitfalls, as well as proposed guidelines for processing the tissues are shown in this presentation."
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Preservation, Biological
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Angiography is presently felt to be the most accurate means of evaluating the carotid artery bifurcation, and is required preoperatively by most vascular surgeons. Arterial digital subtraction angiography (DSA) is the method commonly used. Angiography, however, is expensive and invasive, with significant morbidity and mortality. Duplex scanning (DS) has gained acceptance as a screening technique and has recently been advocated as the sole preoperative study in several centers because it is non-invasive and has an accuracy that is equal to or better than angiography. This study preoperatively evaluated 41 carotid arteries in 38 patients by arterial digital subtraction angiography and duplex scanning, and the results were compared to the surgical specimen. One artery was excluded because of an inadequate duplex scan, leaving 40 arteries studied by both techniques. Forty arteries (100%) studied by duplex scans corresponded with the surgical specimen, whereas only 31 arteries (77.5%) studied by DSA corresponded with the surgical specimen. Nine arteries (22.5%) studied by DSA had stenosis at the time of surgery significantly greater than predicted by DSA. Three arteries (7%) were felt to be normal by DSA, but had approximately 80 per cent stenosis by DS and at surgery. Our findings indicate that duplex scanning at our institution is more accurate than arterial DSA in determining percent diameter stenosis and plaque morphology of carotid arteries.
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Carotid Artery, Common
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Since African swine fever (ASF) was re-introduced into Eastern Europe in April 2007, the disease has spread through five countries, drastically changing the European ASF situation. This re-introduction has significant implications for the affected countries, and it puts the European Union (EU) at serious risk of ASF introduction. Numerous factors are complicating the control of ASF in the Russian Federation and neighboring areas, particularly the absence of a coordinated control program, the abundance of backyard pig units with low or no biosecurity and the traditional use of swill feeding. All these risk factors are driven in turn by socio-economic, political and cultural factors. Moreover, the lack of clear information regarding the current situation of ASF in the Trans-Caucasus countries such as Armenia and Georgia may be increasing the risk of ASF spread into neighboring areas. The ASF situation in Eastern Europe poses a constant risk of ASF entry into the EU, especially via routes that are difficult to control, such as wild boar movements, illegal movement of animals and animal products and movements of contaminated vehicles or other fomites. This paper reviews and discusses current ASF epidemiology in Eastern Europe, the factors that may contribute to disease endemicity in the area, the current challenges for disease control, and the risk of introduction into the EU.
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Asfarviridae
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OBJECTIVE: Leptin, a hormone present in breast milk, is involved in energy regulation and metabolism. The purpose of this investigation was to determine whether leptin is present in either preterm breast milk (PBM) or preterm formula (PF). The effects of delivery methods and pasteurization on leptin levels also were evaluated. METHODS: PBM samples were obtained from 29 mothers who delivered infants at between 23 and 34 weeks' gestation. Leptin levels were measured in PBM and PF with the use of a radioimmunoassay specific for human and bovine leptin, respectively. Milk samples were pasteurized by fast- and slow-heating methods. PBM and PF spiked with human leptin were delivered through catheters by bolus and continuous administration to determine the effects of delivery method on recoverable leptin levels. RESULTS: Median PBM leptin concentration was 5.28 ng/mL (intraquartile range: 24.79). Birth gestational age, birth weight, and gender of the infant did not significantly influence PBM leptin levels. Neither bolus nor continuous feeding practices affected leptin levels in PBM or spiked PF. However, pasteurization significantly reduced the amount of detectable leptin in PBM. CONCLUSIONS: PBM leptin levels were highly variable and similar to levels reported for term breast milk. There was no effect of postnatal age on PBM leptin concentrations. Sterilization decreased detectable leptin levels, whereas feeding practices had no adverse effect on the quantity of leptin delivered. Although no infant formula contained leptin, leptin could be added to formula and delivered through various feeding methods without loss.
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Leptin
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Newly synthesized proteins constitute an important subset of the proteome involved in every cellular process, yet existing chemical tools used to study them have major shortcomings. Herein we report a suite of cell-permeable puromycin analogues capable of being metabolically incorporated into newly synthesized proteins in different mammalian cells, including neuronal cells. Subsequent labeling with suitable bioorthogonal reporters, in both fixed and live cells, enabled direct imaging and enrichment of these proteins. By taking advantage of the mutually orthogonal reactivity of these analogues, we showed multiplexed labeling of different protein populations, as well as quantitative measurements of protein dynamics by fluorescence correlation spectroscopy, could be achieved in live-cell environments.
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Puromycin
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Eighty Italian adults (53 females, 18-69 years, and 27 males, 18-60 years) underwent double-blind tests involving the intake of increasing amounts (125, 250, 500, 1000 ml/d) of four types of milk with normal or low lactose and/or fat content. The tests were completed satisfactorily by 71 subjects. Forty were lactose malabsorbers (LMs) and 31 were absorbers (LAs), according to a standard oral lactose tolerance test. Each subject reported on a questionnaire whether he/she experienced symptoms during the 24 h after milk intake, and the intensity of the symptoms, adopting a score of 0 to 12, according to an already tested procedure. The aim of the study was to investigate the relationship between lactose malabsorption or absorption and intolerance to milk in Italian adults, relative to lactose and fat contents, dose of milk and individual sensitivity. LMs reported symptoms overall more frequently and with greater intensity than LAs (P less than 0.001). The amount of milk ingested was positively associated with the frequency of symptoms both in LMs and LAs. Contrary to earlier findings, fat seemed to contribute to milk intolerance in LMs rather than to reduce it. According to analysis of variance individual differences accounted for 40 per cent of total variation in symptom frequency.
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Lactose Tolerance Test
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In the present study, we describe intraperitoneal development of the FR3 strain of Brugia malayi in Mongolian jirds (Meriones unguiculatus). The third molt for male worms occurred between 4 and 7 days postinfection (dpi) and between 4 and 8 dpi for females. The fourth and final molt occurred between days 21 and 29 for males and 25 and 34 for females, considerably earlier than the times reported for subcutaneous infection models using cats and jirds. The timing of the third molt coincided largely with reports for subcutaneous Brugia pahangi infections of cats and jirds, but the final molt occurred considerably later and lasted longer than those reported for subcutaneous B. pahangi models. Spermatogenesis occurred by at least 50 dpi in adult males, and insemination of females likely occurred between 50 and 60 dpi. Microfilariae were observed in the uteri and ovejectors of adult females at 65 dpi.
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Brugia
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A woman presented at age 18 years with partial myelitis and diplopia and experienced multiple subsequent relapses. Her MRI demonstrated T2 abnormalities characteristic of multiple sclerosis (MS) (white matter ovoid lesions and Dawson fingers), and CSF demonstrated an elevated IgG index and oligoclonal bands restricted to the CSF. Diagnosed with clinically definite relapsing-remitting MS, she was treated with various MS disease-modifying therapies and eventually began experiencing secondary progression. At age 57 years, she developed an acute longitudinally extensive transverse myelitis and was found to have AQP4 antibodies by cell-based assay. Our analysis of the clinical course, radiographic findings, molecular diagnostic methods, and treatment response characteristics support the hypothesis that our patient most likely had 2 CNS inflammatory disorders: MS, which manifested as a teenager, and neuromyelitis optica spectrum disorder, which evolved in her sixth decade of life. This case emphasizes a key principle in neurology practice, which is to reconsider whether the original working diagnosis remains tenable, especially when confronted with evidence (clinical and/or paraclinical) that raises the possibility of a distinctively different disorder.
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Myelitis, Transverse
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A Gram-stain-negative bacterial strain, JBTF-M27T, was isolated from a tidal flat from Yellow Sea, Republic of Korea. Neighbor-joining phylogenetic tree of 16S rRNA gene sequences showed that strain JBTF-M27T fell within the clade comprising the type strains of Sulfitobacter species. Strain JBTF-M27T exhibited the highest 16S rRNA gene sequence similarity (98.8%) to the type strain of S. porphyrae. Genomic ANI and dDDH values of strain JBTF-M27T between the type strains of Sulfitobacter species were less than 76.1 and 19.2%, respectively. Mean DNA-DNA relatedness value between strain JBTF-M27T and the type strain of S. porphyrae was 21%. DNA G + C content of strain JBTF-M27T from genome sequence was 57.8% (genomic analysis). Strain JBTF-M27T contained Q-10 as the predominant ubiquinone and C18:1omega7c as the major fatty acid. The major polar lipids of strain JBTF-M27T were phosphatidylcholine, phosphatidylglycerol and one unidentified aminolipid. Distinguished phenotypic properties, along with the phylogenetic and genetic distinctiveness, revealed that strain JBTF-M27T is separated from recognized Sulfitobacter species. On the basis of the data presented, strain JBTF-M27T ( = KACC 21648T = NBRC 114356T) is considered to represent a novel species of the genus Sulfitobacter, for which the name Sulfitobacter sediminilitoris sp. nov. is proposed.
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Rhodobacteraceae
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The beta protein from group B Streptococcus (GBS) is a approximately 132-kDa, cell-surface exposed molecule that binds to multiple host-derived ligands, including complement factor H (FH). Many details regarding this interaction and its significance to immune evasion by GBS remain unclear. In this study, we identified a three-helix bundle domain within the C-terminal half of the B75KN region of beta as the major FH-binding determinant and determined its crystal structure at 2.5 A resolution. Analysis of this structure suggested a role in FH binding for a loop region connecting helices alpha1 and alpha2, which we confirmed by mutagenesis and direct binding studies. Using a combination of protein cross-linking and mass spectrometry, we observed that B75KN bound to complement control protein (CCP)3 and CCP4 domains of FH. Although this binding site lies within a complement regulatory region of FH, we determined that FH bound by beta retained its decay acceleration and cofactor activities. Heterologous expression of beta by Lactococcus lactis resulted in recruitment of FH to the bacterial surface and a significant reduction of C3b deposition following exposure to human serum. Surprisingly, we found that FH binding by beta was not required for bacterial resistance to phagocytosis by neutrophils or killing of bacteria by whole human blood. However, loss of the B75KN region significantly diminished bacterial survival in both assays. Although our results show that FH recruited to the bacterial surface through a high-affinity interaction maintains key complement-regulatory functions, they raise questions about the importance of FH binding to immune evasion by GBS as a whole.
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Opsonization
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Hemangiopericytoma is an uncommon vascular tumor with variable malignant potential. The origin, structure and function of pericytes remains controversial. Intra-abdominal hemangiopericytomas are highly aggressive soft tissue tumors with a great propensity for malignant transformation. We report on a case of hemangiopericytoma of the pancreas in a 53-year-old female presenting with abdominal pain. Ultrasonography and CT scan revealed a cystic tumor of the head of the pancreas. The patient underwent successful pancreaticoduodenal resection and is alive with no signs of recurrence 25 months following surgery. Ultrastructural studies are necessary to differentiate hemangiopericytomas from other sarcomas. Malignancy may be ascertained only in the presence of metastases or local recurrence. Routine surveillance is advocated.
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Hemangiopericytoma
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Leptin receptors (LepRs) expressed in the midbrain contribute to the action of leptin on feeding regulation. The midbrain neurons release a variety of neurotransmitters including dopamine (DA), glutamate and GABA. However, which neurotransmitter mediates midbrain leptin action on feeding remains unclear. Here, we showed that midbrain LepR neurons overlap with a subset of dopaminergic, GABAergic and glutamatergic neurons. Specific removal of vesicular monoamine transporter 2 (VMAT2) in midbrain LepR neurons (KO mice) disrupted DA accumulation in vesicles, but failed to cause a significant change in the evoked release of either glutamate or GABA to downstream neurons. While KO mice showed no differences on chow, they presented a reduced high-fat diet (HFD) intake and resisted to HFD-induced obesity. Specific activation of midbrain LepR neurons promoted VMAT2-dependent feeding on chow and HFD. When tested with an intermittent access to HFD where first 2.5-h HFD eating (binge-like) and 24-h HFD feeding were measured, KO mice exhibited more binge-like, but less 24-h HFD feeding. Interestingly, leptin inhibited 24-h HFD feeding in controls but not in KO mice. Thus, VMAT2-mediated neurotransmission from midbrain LepR neurons contributes to both binge-like eating and HFD feeding regulation."
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Vesicular Monoamine Transport Proteins
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Osteoarthritis (OA) is a degenerative disease of the joints which is associated with an impaired production of the cartilage matrix by the chondrocytes. Here, we investigated the role of Lysine-Specific Demethylase-1 (LSD1), a chromatin remodeling enzyme whose role in articular chondrocytes was previously associated with a catabolic activity and which is potentially involved during OA. Following a loss of function strategy and RNA sequencing analysis, we detail the genes which are targeted by LSD1 in human articular chondrocytes and identify COL9A1, a gene encoding the alpha1 chain of the cartilage-specific type IX collagen, as negatively regulated by LSD1. We show that LSD1 interacts with the transcription factor SOX9 and is recruited to the promoter of COL9A1. Interestingly, we observe that OA cartilage displays stronger LSD1 immunostaining compared with normal, and we demonstrate that the depletion of LSD1 in OA chondrocytes prevents the decrease in COL9A1 following Il-1beta treatment. These results suggest LSD1 is a new regulator of the anabolic activity of articular chondrocytes potentially destabilizing the cartilage matrix, since it negatively regulates COL9A1, a gene encoding a crucial anchoring collagen molecule. This newly identified role played by LSD1 may thus participate in the alteration of the cartilage matrix during OA.
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Fibril-Associated Collagens
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Prolactin injected into pseudopregnant rabbits led to a parallel enhancement of casein synthesis and casein mRNA concentration. When this stimulation was followed by a withdrawal of prolactin obtained by injections of bromocriptine, the rate of casein synthesis progressively diminished. In the presence of endogenous prolactin after the initial stimulation, the decline of casein synthesis was delayed. Hydrocortisone acetate injected with bromocriptine after the initial stimulation by prolactin was able to maintain a high rate of casein synthesis. Measurements of casein mRNA concentration by hybridization with casein cDNA indicated that in all cases the amount of casein mRNA was correlated with the magnitude of casein synthesis. This suggests that the lactogenic hormones, prolactin and glucocorticoids, which were previously demonstrated to be responsible for the enhancement of casein mRNA concentration are involved in their stabilization.
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Lactose Synthase
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This paper presents an overview of current methods for determining nurse staffing requirements. A range of methods is described and the strengths and drawbacks of each are discussed. There follows an examination of some of the wider issues raised by the use of particular methods for determining nurse staffing. The paper concludes that since a perfect workload measurement system is unlikely ever to exist, such systems can be used to facilitate, but not to dictate, decisions about nurse staffing."
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Personnel Staffing and Scheduling
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The polyene antibiotic candicidin produces a rapid efflux of K(+) ions from a suspension of Candida albicans. Onset of K(+) leakage depends on the culture age, stationary-phase yeasts leaking K(+) more slowly than exponential-phase yeasts. The time taken for potassium leakage to begin represents the time taken by the antibiotic to cross the cell wall and produce membrane damage. It was shown that there were factors in the cell wall of C. albicans that increased their total binding capacity and their affinity for candicidin during growth. An attempt was made to relate changes in the lipid content of the yeast cell with the increased time taken to produce membrane damage.
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Candicidin
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1. Ketanserin or slow-release nifedipine were added to the treatment of 24 patients with hypertension uncontrolled by a thiazide diuretic plus beta-adrenoceptor antagonist in an observer-blind, randomised parallel-group study of 6 months duration. 2. At 6 months the mean falls in supine blood pressure were for ketanserin (mean daily dose 77 mg) 7/5 mm Hg and for nifedipine (mean daily dose 62 mg) 27/10 mm Hg. The difference between the treatments was significant for systolic blood pressure (P less than 0.02) and mean arterial pressure (P less than 0.05). Six nifedipine-treated patients reached target blood pressure, compared with one patient with ketanserin (P less than 0.02). 3. One patient taking nifedipine, and none taking ketanserin withdrew because of side-effects. The tolerability of the two drugs was broadly similar. 4. Ketanserin treatment was associated with significant changes in supine pulse rate (-8 beats min-1, P less than 0.05) and corrected QT interval (+27 ms, P less than 0.05). Nifedipine treatment had no effect on these variables. The change in pulse rate was significantly different between the groups. 5. In patients treated with a diuretic and beta-adrenoceptor blocker who required additional treatment ketanserin was significantly inferior to nifedipine.
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Ketanserin
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Arterial hypoxia was produced in 10 conscious, chronically instrumented, tracheostomized dogs by allowing them to breathe 7.5% O2 in N2 for 10 min. Hypoxia (Pao2 = 28 +/- 0.7 (SE) Torr) caused significant increases in coronary blood flow (+196%), left ventricular dP/dt max (+60%), aortic blood flow (+48%), heart rate (+50%), and left ventricular systolic (+12%) and aortic (+10%) pressures. Left ventricular end-diastolic pressure and stroke volume were unchanged, while systemic (-30%) and coronary diastolic (-66%) vascular resistances declined significantly. When equivalent levels of arterial hypoxia were produced in four of these dogs after chronic sinoaortic denervation, the coronary, cardiac, and systemic hemodynamic responses were not significantly different, with the exception that the small arterial pressure response was abolished. Thus the peripheral chemoreflexes are not essential for the normal coronary vasodilator and cardiac adjustments to occur during hypoxia in the conscious dog. The data support the hypothesis that a large part of the cardiac adjustments to hypoxia is initiated outside the sinoaortic reflexogenic zones, probably within the central nervous system.
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Paraganglia, Nonchromaffin
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BACKGROUND: Traumatic acute subdural haematoma is a debilitating condition. Laterality intuitively influences management and outcome. However, in contrast to stroke, this research area is rarely studied. The aim is to investigate whether the hemisphere location of the ASDH influences patient outcome. METHODS: For this multicentre observational retrospective cohort study, patients were considered eligible when they were treated by a neurosurgeon for traumatic brain injury between 2008 and 2012, were > 16 years of age, had sustained brain injury with direct presentation to the emergency room and showed a hyperdense, crescent shaped lesion on the computed tomography scan. Patients were followed for a duration of 3-9 months post-trauma for functional outcome and 2-6 years for health-related quality of life. Main outcomes and measures included mortality, Glasgow Outcome Scale and the Quality of Life after Brain Injury score. The hypothesis was formulated after data collection. RESULTS: Of the 187 patients included, 90 had a left-sided ASDH and 97 had a right-sided haematoma. Both groups were comparable at baseline and with respect to the executed treatment. Furthermore, both groups showed no significant difference in mortality and Glasgow Outcome Scale score. Health-related quality of life, assessed 59 months (IQR 43-66) post-injury, was higher for patients with a right-sided haematoma (Quality of Life after Brain Injury score: 80 vs 61, P = 0.07). CONCLUSIONS: This study suggests patients with a right-sided acute subdural haematoma have a better long-term health-related quality of life compared to patients with a left-sided acute subdural haematoma.
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Hematoma, Subdural, Acute
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We describe a previously healthy 15-month-old girl who developed ecthyma gangrenosum (EG)-like lesions secondary to methicillin-sensitive Staphylococcus aureus (MSSA). Her systemic symptoms and negative blood cultures suggested MSSA toxin-mediated effects. When toxin-mediated systemic symptoms accompany such lesions, pathogens other than Pseudomonas aeruginosa should be considered."
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Staphylococcal Skin Infections
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Two-hundred and thirty-four Italian patients with a clinical diagnosis of macular, cone and cone-rod dystrophies (MD, CD, and CRD) were examined using next-generation sequencing (NGS) and gene sequencing panels targeting a specific set of genes, Sanger sequencing and-when necessary-multiplex ligation-dependent probe amplification (MLPA) to diagnose the molecular cause of the aforementioned diseases. When possible, segregation analysis was performed in order to confirm unsolved cases. Each patient's retinal phenotypic characteristics were determined using focal and full-field ERGs, perimetry, spectral domain optical coherence tomography and fundus autofluorescence. We identified 236 potentially causative variants in 136 patients representing the 58.1% of the total cohort, 43 of which were unpublished. After stratifying the patients according to their clinical suspicion, the diagnostic yield was 62.5% and 53.8% for patients with MD and for those with CD/CRD, respectively. The mode of inheritance of all cases confirmed by genetic analysis was 70% autosomal recessive, 26% dominant, and 4% X-linked. The main cause (59%) of both MD and CD/CRD cases was the presence of variants in the ABCA4 gene, followed by variants in PRPH2 (9%) and BEST1 (6%). A careful morpho-functional evaluation of the phenotype, together with genetic counselling, resulted in an acceptable diagnostic yield in a large cohort of Italian patients. Our study emphasizes the role of targeted NGS to diagnose MDs, CDs, and CRDs, as well as the clinical usefulness of segregation analysis for patients with unsolved diagnosis.
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Cone-Rod Dystrophies
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LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Identify the key social media platforms to use. 2. Recall the primary components of the code of conduct when using social media. 3. Recognize how to build a social media presence and brand. 4. Summarize the primary applications of social media in plastic surgery. SUMMARY: Social media are a growing new tool that has emerged in recent years, with numerous applications that have allowed for an effective means to rapidly disseminate information. Plastic surgeons must gain an understanding of the technology to both grow their practices and the specialty as a whole in an ethical and responsible way. The different platforms available; code of conduct; how to build a social media presence; and the main applications of advertising, education, and research, as based on evidence-based recommendations, are presented.
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Surgery, Plastic
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Aims Irish haemodialysis (HD) units operate the electronic Kidney Disease Clinical Patient Management System (KDCPMS). KDCMPS is not always used as the primary electronic patient record. At this study setting, KDCPMS information accuracy has not been examined to date. This study aims to identify, characterise and quantify medication discrepancies within KDCPMS records of HD outpatients. Methods Prospective, observational study conducted on the HD unit of Tallaght University Hospital. Medicine reconciliation was conducted to identify KDCPMS discrepancies with medication review to document Drug Related Problems (DRPs). Clinical pharmacists issued recommendations to resolve DRPs. Results All KDCPMS records examined contained intentional and unintentional discrepancies (n=36). Unintentional discrepancies corresponding to 8.8 discrepancies per patient (5.13SD) was observed. One-hundred-and-forty-three DRPs were identified in 34 patients (94.4%). Sixty-five per cent (65%) of pharmacist recommendations were accepted (n=93), 22.4% rejected (n=32), 8.4% (n=12) referred to the renal multidisciplinary team (MDT) and 4.2% not actioned (n=6). Conclusion KDCPMS contains inaccuracies potentially leading to systemic error. Robust clinical governance supported by national policy is required to support KDCPMS as the primary platform for renal patients. Enhanced pharmaceutical care by specialist clinical pharmacists should be supported within national models of care for chronic disease management to improve patient outcomes.
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Medication Reconciliation
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This 2-week randomized, double-blind, placebo-controlled fixed-dose study (NCT02919501) explored the potential of accelerating onset of antidepressant efficacy and plasma exposure with single-dose intravenous vortioxetine at oral vortioxetine treatment initiation. Outpatients (ages 18-65 years) with major depressive disorder and a current depressive episode (Montgomery Asberg Depression Rating Scale total score >/=30) were randomized to an initial single dose of either intravenous vortioxetine 17 mg (n = 27) or intravenous placebo (n = 28), both treatments followed by 2 weeks of oral vortioxetine (10 mg/day). From baseline to day 7, both groups exhibited fast and substantial improvements by approximately 14 Montgomery Asberg Depression Rating Scale points, with no statistically significant treatment difference for this primary endpoint. Improvements were substantial already within 24 hours, with numerical treatment differences of 1.3 and 1.6 points at days 1 and 3, respectively, in favour of intravenous vortioxetine + oral vortioxetine. Pharmacokinetic data confirmed that intravenous vortioxetine facilitated reaching steady-state plasma concentration within 24 hours. Intravenous vortioxetine + oral vortioxetine was safe and well-tolerated, with nausea as the most common adverse event. This study supported intravenous vortioxetine as a means of rapidly reaching therapeutic vortioxetine blood levels.
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Vortioxetine
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The putative primase gene and other genes associated with the Sfi21-prototype genome replication module are highly conserved in Streptococcus thermophilus bacteriophages. Expression of antisense RNAs complementary to the putative primase gene (pri3.1) from S. thermophilus phage kappa 3 provided significant protection from kappa 3 and two other Sfi21-type phages. Expression of pri3.10-AS, an antisense RNA that covered the entire primase gene, reduced the efficiency of plaquing (EOP) of kappa 3 to 3 x 10(-3) and reduced its burst size by 20%. Mutant phages capable of overcoming antisense inhibition were not recovered. Thirteen primase-specific antisense cassettes of different lengths (478 to 1,512 bp) were systematically designed to target various regions of the gene. Each cassette conferred some effect, reducing the EOP to between 0.8 and 3 x 10(-3). The largest antisense RNAs (1.5 kb) were generally found to confer the greatest reductions in EOP, but shorter (0.5 kb) antisense RNAs were also effective, especially when directed to the 5' region of the gene. The impacts of primase-targeted antisense RNAs on phage development were examined. The expression of pri3.10-AS resulted in reductions in target RNA abundance and the number of phage genomes synthesized. Targeting a key genome replication function with antisense RNA provided effective phage protection in S. thermophilus.
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Streptococcus Phages
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We report on 2 cases of kerions in children: one of them was located on the pubis, an exceptional location; the second one was located on the scalp and presented like multiple abscess of the scalp, for which surgical drainage was performed. In both cases, Trichophyton mentagrophytes was involved. This dermatophyte is zoophilic, contrary to the dermatophytes usually involved in tinea capitis, which could explain the poor adaptation of the dermatophyte to the human host, who would therefore react by generating a severe inflammatory reaction. Antifungal drugs are recommended for the treatment of kerions, especially griseofuline for 6 to 8 weeks. The value of oral steroids and surgery continues to be debated.
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Tinea Favosa
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Inflammatory responses have been implicated in the elaboration of several forms of central nervous system injury, including cerebral vasospasm after subarachnoid hemorrhage (SAH). A critical event participating in such responses is the recruitment of circulating leukocytes into the inflammatory site. CD34 is a key adhesion molecule responsible for recruitment of monocytes/macrophages and the attachment of leukocytes to endothelial cells. However, it has not been investigated whether, and to what degree, CD34 is induced by SAH and also the role of CD34 in the pathogenesis of cerebral vasospasm following SAH remains unknown. Experiment 1 aimed to investigate the timecourse of the CD34 expression in the basilar artery after SAH. In experiment 2, we chose the maximum time point of vasospasm (day 3) and assessed the effect of monoclonal antibody against CD34 on regulation of cerebral vasospasm. As a result, the elevated expression of CD34 was detected in the basilar artery after SAH and peaked on day 3. After intracisternal administration of CD34 monoclonal antibody, the vasospasm was markedly attenuated after blood injection on day 3. Our results suggest that CD34 is increasingly expressed in a parallel time course to the development of cerebral vasospasm in a rat experimental model of SAH and administration of the specific CD34 antibody could prevent or reduce cerebral vasospasm caused by SAH.
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Antigens, CD34
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We designed a single unit type controlled release tablet containing nateglinide to decrease both postprandial blood glucose level (PBG) and fasting blood glucose level (FBG) in normal beagle dogs. The tablet contains 60 mg of nateglinide in an immediate release portion, and 90 mg of nateglinide in a controlled release portion. Compressionable enteric coated granules were selected as the controlled release portion to primarily decrease FBG, and they were prepared by an aqueous coating with Eudragit. Three types of nateglinide controlled release tablets were obtained, and their weights were 418.1-425.1 mg/tablet containing the above compressionable enteric coated granules. Even after tableting, the dissolution behavior of enteric coated granules was maintained approximately. In vivo single oral administration studies using normal male beagle dogs demonstrated that these tablets were able to decrease both PBG and FBG. The relative bioavailability values of the obtained tablets containing enteric coated granules having a dissolution pH of 6.0 and 6.8 were estimated at about 57.2 and 60.8% respectively against nateglinide immediate release tablets. In an in vivo repeated administration study with the tablets containing enteric coated granules having a dissolution pH of 6.8 (an interval: 8 h), decreases in both PBG and FBG were observed continuously twice. On the basis of the above results, it is expected to enable control of both PBG and FBG for moderate and severe diabetes patients with a controlled release formulation containing a short-acting type oral blood glucose regulator, not only nateglinide but also meglitinides (repaglinide, mitiglinide, etc.).
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Nateglinide
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Almost all suicidal persons who consult physicians wish to live. Generally they fall into one of two groups. Interpersonal suiciders manifest frequent threats and attempts, are emotionally labile, have ill-defined suicide plans, and clear ideas as to how their crises might be resolved. Intrapersonal suiciders are less open in manifestations of suicidal drive, withdrawn rather than emotional, often have clearly-formulated suicide plans and do not have ideas (other than suicide) as to how their crises might end. The suicidal situation results from two factors: (1) the loss of some valuable person or commodity, and (2) the loss of self-esteem. What ensues is temporary character disorganization-crisis. Treatment is based on restoration or replacement of lost objects and building up of self-esteem.
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Suicide Prevention
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Isolated systolic hypertension is associated with higher risk of cardiovascular disease and all-cause mortality. Despite being the most common form of hypertension in the elderly, it is also detectable among young and middle-aged subjects. Dietary salt (sodium chloride) intake is an important determinant of blood pressure, and high salt intake is associated with greater risk of hypertension and cardiovascular events. In most countries, habitual salt intake at all age categories largely exceeds the international recommendations. Excess salt intake, often interacting with overweight and insulin resistance, may contribute to the development and maintenance of isolated systolic hypertension in young individuals by causing endothelial dysfunction and promoting arterial stiffness through a number of mechanisms, namely increase in the renin-angiotensin-aldosterone system activity, sympathetic tone and salt-sensitivity. This short review focused on the epidemiological and clinical evidence, the mechanistic pathways and the cluster of pathophysiological factors whereby excess salt intake may favor the development and maintenance of isolated systolic hypertension in young people."
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Isolated Systolic Hypertension
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PURPOSE: To integrate the available data published on squamous odontogenic tumors (SOT) and squamous odontogenic tumor-like proliferations in odontogenic cysts (SOT-LPOC) into a comprehensive analysis of their clinical/radiologic features. MATERIALS AND METHODS: An electronic search was undertaken in January 2017. Eligibility criteria included publications having enough clinical/radiological/histological information to confirm a definite diagnosis. RESULTS: A total of 74 publications reporting 110 SOTs (102 central, 8 peripheral) and 60 SOT-LPOC were included. Compared to SOT-LPOC, SOT showed lower mean age, no preference regarding maxilla or mandible localization, significant association with cortical bone perforation, multilocular radiographic appearance, and mobility of the tooth/teeth associated with the lesion. While 5 recurrent SOT were reported after enucleation, no recurrent SOT-LPOC was found. CONCLUSIONS: SOT shows a more aggressive biologic behavior than SOT-LPOC, which supports the hypothesis that the two lesions are distinct clinicopathological conditions.
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Odontogenic Tumor, Squamous
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Hematopoiesis has long served as a paradigm of stem cell biology and tissue homeostasis. In the past decade, the genomics revolution has ushered in powerful new methods for investigating the hematopoietic system that have provided transformative insights into its biology. As part of the advances in genomics, increasingly accurate deep sequencing and novel methods of cell tracking have revealed hematopoiesis to be more of a continuous and less of a discrete and punctuated process than originally envisioned. In part, this continuous nature of hematopoiesis is made possible by the emergent outcomes of vast, interconnected regulatory networks that influence cell fates and lineage commitment. It is also becoming clear how these mechanisms are modulated by genetic variation present throughout the population. This review describes how these recently uncovered complexities are reshaping our concept of tissue development and homeostasis while opening up a more comprehensive future understanding of hematopoiesis.
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Cell Lineage
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Chronic urticaria (CU) is a skin disorder characterized by transient, pruritic wheals persisting for longer than 6 weeks. According to the European Academy of Allergy and Clinical Immunology (EAACI) guidelines, CU can be categorized into two main types: chronic spontaneous urticaria (CSU), in which the wheals appear spontaneously, and inducible urticaria, that is triggered by physical agents. CSU may be due to triggering factors such as food allergens or infections, but in at least 40% of cases it is autoimmune in origin, caused by circulating autoantibodies anti-FcepsilonR1 or anti-IgE, or autoreactive. In the present paper, re-evaluating the EAACI guidelines, we have developed a document containing some practical indications which are useful for diagnosis and management of CSU in the context of the Italian situation. Concerning CSU treatment, second generation antihistamines are the first-line treatment; these drugs can be used, as second-line treatment, at a higher than licensed dose in patients who do not respond adequately at licensed doses. The third-line treatment includes leukotriene receptor antagonists which, however, do not have a specific indication for the treatment of CSU, cyclosporine, whose use in this disease is still off-label, and omalizumab. The latter is a recombinant monoclonal IgG antibody that binds free IgE, down regulates mast cell function and induces eosinophil apoptosis. Recently, it has emerged as an effective and safe treatment for antihistamine-unresponsive CSU of both autoimmune/autoreactive and non-autoimmune/non-autoreactive, and has been officially approved for use against this disease.
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Urticaria
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Tendon cells respond to mechanical loads. The character (anabolic or catabolic) and sensitivity of this response is determined by the mechanostat set point of the cell, which is governed by the cytoskeleton and its interaction with the extracellular matrix. To determine if loss of cytoskeletal tension following stress deprivation decreases the mechanoresponsiveness of tendon cells, we cultured rat tail tendons under stress-deprived conditions for 48 hours and then cyclically loaded them for 24 hours at 1%, 3%, or 6% strain at 0.17 Hz. Stress deprivation upregulated MMP-13 mRNA expression and caused progressive loss of cell-matrix contact compared to fresh controls. The application of 1% strain to fresh tendons for 24 hours inhibited MMP-13 mRNA expression compared to stress-deprived tendons over the same period. However, when tendons were stress-deprived for 48 hours and then subjected to the same loading regime, the inhibition of MMP-13 mRNA expression was decreased. In stress-deprived tendons, it was necessary to increase the strain magnitude to 3% to achieve the same level of MMP-13 mRNA inhibition seen in fresh tendons exercised at 1% strain. The data suggest loss of cytoskeletal tension alters the mechanostat set point and decreases the mechanoresponsiveness of tendon cells.
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Matrix Metalloproteinase 13
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Platycodon grandiflorum (PG) is a traditional Chinese medicine with a long history, but its active compounds have not been reported. In this study, novel carbon dots (CDs), PG-based CDs (PGC-CDs), were discovered and prepared from PG via calcinations and characterized by transmission electron microscopy; high-resolution transmission electron microscopy; X-ray diffraction, fluorescence, ultraviolet-visible, and Fourier-transform infrared spectrometers; X-ray photoelectron spectroscopy; and high-performance liquid chromatography. In addition, the safety and antioxidant activity of PGC-CDs was evaluated by RAW264.7 cells and LO2 cells. The therapeutic effects of PGC-CDs on hyperbilirubinemia and liver protection were evaluated in a bilirubin-induced hyperbilirubinemia mice model. The experiment confirmed that the diameter range of PGC-CDs was from 1.2 to 3.6 nm. PGC-CDs had no toxicity to RAW264.7 cells and LO2 cells at a concentration of 3.91 to 1000 microg/mL and could reduce the oxidative damage of cells caused by H(2)O(2). PGC-CDs could inhibit the increase levels of bilirubin and inflammation factors and increase the levels of antioxidants and survival rate, demonstrating that PGC-CDs possessed anti-inflammatory and anti-oxidation activity. PGC-CDs may reduce the content of bilirubin, so as to reduce a series of pathological lesions caused by bilirubin, which has potential in treating hyperbilirubinemia and preventing liver damage induced by hyperbilirubinemia.
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Platycodon
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A first compilation of georeferenced tick locations in Austria and South Tyrol, Italy, is presented here. This allows the tick fauna to be examined in the various climatic regions of the European Alps. The dataset comprises 424 tick locations of Austria and 48 tick locations of South Tyrol, which were digitized from literature and visualized in the form of geographical maps. The tick fauna of Austria includes two species of Argasidae in the genera Argas and Carios and 15 species of Ixodidae in the genera Dermacentor, Haemaphysalis, and Ixodes, altogether 17 tick species. In addition, two species of Ixodidae in the genera Hyalomma (each spring imported by migratory birds) and Rhipicephalus (occasionally imported by dogs returning from abroad with their owners) are included in the tick atlas. Of these, the georeferenced locations of 18 tick species are depicted in maps. The occurrence of the one remaining tick species, Ixodes inopinatus, is given at the level of the federal states. The first Austrian distribution map of the long-legged bat tick Ixodes vespertilionis, which was reported from 21 caves, deserves special mention. The most common and widespread tick species is Ixodes ricinus, with records in all nine federal states of Austria, followed by Ixodes canisuga, Ixodes hexagonus, and I. vespertilionis in six federal states each. Haemaphysalis concinna and Dermacentor reticulatus are only endemic in the eastern plains, while Dermacentor marginatus only occurs in the west, in the Tyrolean Alpine valleys. Eight tick species were reported from South Tyrol, Italy. There, the most frequently flagged tick from the vegetation is also I. ricinus, while D. marginatus and Haemaphysalis punctata are often collected from sheep. The locations are shown together with those from North and East Tyrol on a separate Tyrol map. The tick atlas in Austria and South Tyrol as well as the underlying digital dataset in the supplement contribute to the closing of data gaps in global distribution maps of ticks and improve the data basis for new species distribution models.
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Ticks
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Peptide drugs have the advantages of target specificity and good drugability and have become one of the most increasingly important hotspots in new drug research in biomedical sciences. However, peptide drugs generally have low bioavailability and metabolic stability, and therefore, the modification of existing peptide drugs for the purpose of improving stability and retaining activity is of viable importance. It is known that glucagon is an effective therapy for treating severe hypoglycemia, but its short half-life prevents its wide therapeutic use. Herein, we report that combined unnatural residues and long fatty acid conjugation afford potent alpha/sulfono-gamma-AApeptide hybrid analogues of Glucagon with enhanced stability and prolonged in vivo activity. This strategy could be adopted to develop stabilized analogues of other short-acting bioactive peptides.
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Glucagon
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Idiopathic priapism is rarely seen in children. Two children with idiopathic priapism are presented, followed by a detailed discussion of priapism. Particular attention is paid to idiopathic priapism. Additionally, an algorithm for diagnosing and managing children presenting with priapism is presented.
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Penile Diseases
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During 1978 I carried out a clinical trial in my pediatric practice with the new corticoid dermaticum Alfason, which contains the active substance hydrocortisone-17 abutyrate--an ester of hydrocortisone not previously used therapeutically. To begin with Alfason was given in an open trial to 100 children and later, because of the favourable results obtained, it was employed in another group of 100 children in a double-blind trial against a fluorinated corticoid, a substance which up to then I had most often prescribed. The results showed a good to very good effect in over 90% of the cases treated with either drug, there was no substance related statistical difference. According to the literature the ratio of success regarding side effects is particularly favourable for Alfason so that its use in the treatment of corticoid-requiring dermatoses in childhood can be recommended.
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Algestone Acetophenide
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The results of 131I treatment in combination with pre- and post-treatment with carbimazole (n = 122) were compared to the results of 131I used as the only antithyroid treatment (n = 203). The two groups of patients were fully comparable in regard to age, size of goitre and time of observation, and the same diagnostic criteria and dosage regimen of 131I were used. The incidence of early myxoedema in patients with diffuse goitre was significantly reduced after combination therapy, 5 per cent, compared to 16 per cent after 131I as the only antithyroid therapy (P less than 0.05). The incidence of late myxoedema was 6 per cent in both groups 3 years after the last treatment, and fully compensated myxoedema was found in 13 and 22 per cent (n.s.). No severe acute side effects were observed after 131I therapy in any of the two groups. It is concluded that--in diffuse toxic goitre--a lower early incidence of myxoedema was obtained on the combined regimen because of either a possibly lower absorbed radiation dose or a more fractionate therapy. A major advantage of the combination therapy is also, that the patients are rendered euthyroid shortly after the diagnosis and remain so during the prolonged period of treatment. 131I treatment in combination with carbimazole is advocated in all patients with diffuse and nodular toxic goitre if the patient is above fertile age and thyroidectomy is not indicated.
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Goiter
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The essential oil of perilla (Perilla frutescens) contains volatile low molecular weight compounds such as monoterpenes and phenylpropenes. The composition of the essential oil is classified into about ten chemotypes. The biosynthesis of these constituents is strictly controlled genetically. Among the compounds contained in perilla essential oil, the bioconversion of pure compounds such as perillaldehyde, limonene, and citral has been reported, but that of many other components has not. In addition, changes in the volatile components of raw plant material during brewing have also been investigated for wine and beer. In this study, we examined the bioconversion of perilla essential oil components by Saccharomyces cerevisiae during the brewing of liquor with perilla leaves. S. cerevisiae was added to the ethanol-water extract of dried leaves of P. frutescens and P. citriodora for seven essential oil types: perillaldehyde type, piperitenone type, perillene type, perillaketone type, elsholtziaketone type, citral type, and phenylpropanoid type. Volatile compounds in the reaction mixtures were analyzed by solid-phase microextraction (SPME)-GC-MS, revealing bioconversion of perillaldehyde, isoegomaketone, neral, and geranial by S. cerevisiae. Analysis of the conversion products suggests that they were formed by the reduction of C=C bonds and aldehydes, as well as by esterification and dehydration reactions.
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Perilla
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The main form of folate in human plasma is 5-methyltetrahydrofolate (5MTHF). The observation that folate in human serum is photosensitive supports the hypothesis that humans developed dark skin in high ultraviolet fluences areas in order to protect folate in the blood from UV radiation. However, folates alone are quite photostable. Therefore, in this study, we examined for the first time the photodegradation of 5MTHF in the presence of the endogenous photosensitizer uroporphyrin (Uro), which is sometimes present in low concentration in human serum, under UV and near-UV light exposure. We found strong indications that while 5MTHF alone is rather photostable, it is degraded quickly in the presence of Uro. Using deuterium oxide (D(2)O) as an enhancer of the lifetime of singlet oxygen and the singlet oxygen sensor green reagent (SOSG) as a scavenger of singlet oxygen, we have found that the photodegradation most likely proceeds via a type II photosensitization. Our results show that singlet oxygen is likely to be the main intermediate in the photodegradation of 5MTHF mediated by Uro. Our findings may be useful for further studies the evolution of human skin colours.
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Uroporphyrins
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PURPOSE: To report a very late recurrence of choroidal neovascularization (CNV) in elderly patients with noninfectious multifocal choroiditis (MFC). METHODS: Retrospective case series of patients with MFC with confirmed recurrence of CNV. Choroidal neovascularization was diagnosed with multimodal imaging, including optical coherence tomography angiography. Multifocal choroiditis-associated CNV eyes were treated with intravitreal injections of anti-vascular endothelial growth factor medication. RESULTS: Four eyes of three patients were included in our study, with a mean (range) age of 73 years (67-78). The period between the original CNV and the recurrence was 53 years, with a range of 48-60 years. The mean number (range) of injections given after the late recurrence per eye was 7 (5-11). The mean duration (range) of follow-up post-treatment initiation was 93 (40-122) weeks. All eyes improved to 20/30 visual acuity or better at 6 months after initial treatment. CONCLUSION: Patients with MFC are never exempt from recurrent CNV, warranting follow-up in perpetuity. Age-related factors are important to consider which may increase the susceptibility for activating MFC-associated CNV in elderly people. Macular neovascularization could respond to a standard approach to management, in these patients with MFC, by a judicious use of intravitreal injections of anti-vascular endothelial growth factor therapy.
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Multifocal Choroiditis
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Vitamin B12 is an essential nutrient acquired via dietary intake. Receptor-mediated endocytosis is a key mechanism in vitamin B12 absorption, cellular uptake, and reabsorption. CD320 is a type I transmembrane protein responsible for cellular uptake of vitamin B12 in peripheral tissues. In this study, we examined segmental distribution and cellular expression of CD320 in mouse kidneys and intestines. We show that CD320 is expressed on the luminal surface in the small intestine and in proximal tubules in the kidney, suggesting that, in addition to its role in vitamin B12 uptake in peripheral tissues, CD320 may participate in vitamin B12 absorption in the small intestine and reabsorption in the kidney. Moreover, we show that an amino acid motif, DSSDE, in the second low-density lipoprotein receptor class A domain of CD320 is a key apical membrane targeting signal in both renal and intestinal epithelial cells. Mutations or deletion of this motif abolish the specific apical membrane expression of CD320 in polarized Madin-Darby canine kidney cells and human colon cancer-derived Caco-2 cells. In short-hairpin RNA-based gene knockdown experiments, we show that the apical membrane targeting of CD320 is mediated by a Rab11a-dependent mechanism. These results extend our knowledge regarding the cell biology of CD320 and its role in vitamin B12 metabolism."
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Madin Darby Canine Kidney Cells
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Cluster headache (CH) is characterized by attacks of severe, strictly unilateral pain that is orbital, supraorbital, temporal, or any combination of these, lasts 15-180 min, and occurs from once every other day to eight times a day. The pain is associated with ipsilateral conjunctival injection, lacrimation, nasal congestion, rhinorrhea, forehead and facial sweating, miosis, ptosis and/or eyelid edema, and/or with restlessness or agitation. The understanding of the pathophysiological mechanisms behind CH is far from complete, but CH is considered to be a neurovascular and chronobiologic headache disorder, with a pivotal role played by the central brain mechanisms. The diagnosis of CH is based on a careful history that elicits the clinical features of attacks, ipsilateral autonomic phenomena, and the cyclical nature of the bouts in which the attacks occur. Additional diagnostic interventions are needed to rule out secondary causes of CH. The main focus of therapy is to abort attacks once they have begun and to prevent future attacks. Alternative interventions in patients with CH who have not experienced any meaningful benefit from preventive drugs are well defined. Although there have been advances in the diagnosis and therapy of CH, a significant number of CH patients experience misdiagnoses and diagnostic delay, which stalls the possibility of the timely application of adequate abortive and preventive therapy.
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Cluster Headache
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Hemorrhagic cystitis is a well known complication of allogeneic bone marrow transplantation (BMT) and is normally attributed to the use of high-dose cyclophosphamide in the preparative regimen. Hemorrhagic cystitis occurring late after BMT is unlikely to be due to the effects of this conditioning, and probably has an infective etiology. Three patients undergoing BMT for chronic granulocytic leukemia (CGL) developed terminal dysuria and hematuria at 38, 56, and 149 days post-BMT. Electron microscopy (EM) of urine voided at these times revealed large numbers of papovavirions, which were subsequently identified as BK virus. Urine samples inoculated onto human embryonic lung fibroblasts induced infection of the cells and replication of the virus as detected by EM of tissue culture fluid. Urine from one of these patients was examined by standard cytological techniques, and EM of urothelial cells showed nuclear inclusions consisting of nonencapsulated virus particles of diameter 40 nm, consistent with papovavirus. Five further patients were found to be excreting BK virus without symptoms of cystitis, although one of these patients did experience abnormalities of liver function that were otherwise unexplained. BK virus has already been implicated in hepatic dysfunction posttransplant, and in cystitis in nonimmunosuppressed children. We postulate that it may also be involved in the etiology of late hemorrhagic cystitis after BMT.
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Polyomavirus
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