Varied approaches to tuberculosis control in a multihospital system.
To document the actual tuberculosis (TB) control policies and procedures in a nonoutbreak setting in a variety of hospitals. To determine if any particular practices are linked to higher rates of employee tuberculin skin-test conversion. Survey of hospital occupational health and infection control practitioners for the year 1994 regarding hospital TB policies. Review of hospital records to verify the number of patients with TB at each hospital and to verify the number of employees with positive tuberculin skin tests. Smoke-stick testing of negative-pressure ventilation rooms. A 13-hospital health system in the Midwest. Hospitals ranged in size from 40 to 1,208 beds (median 220) and employed 150 to 6,500 workers (median 875). There were seven rural and six urban centers, including four teaching hospitals. All 13 hospitals had TB control plans, and all performed annual tuberculin skin testing on employees. Annual skin-test positivity rates ranged from 0% to 1.0% (median 0.3%). Negative-pressure ventilation rooms were available in 11 hospitals. The percentage of negative-pressure rooms with effective negative pressure ranged from 44% to 100% (median 95%). Three of the 13 hospitals used high-efficiency particulate air (HEPA) masks as primary personal respiratory protection, and 8 used dust-mist or dust-mist-fume masks. We found no relation between the type of face mask used, number of functional negative-pressure rooms, or hospital TB risk category, and employee skin-test conversion rates. Considerable variation existed in the TB control policies and procedures between hospitals, but employee TB skin-test conversion rates were low in all settings.


Reduced phagocytic activity of polymorphonuclear leukocytes in alpha(1,3) fucosyltransferase VII-deficient mice.
Deficiencies in adhesion molecules or their counter-receptors in humans may have severe consequences as exemplified by leukocyte adhesion deficiency (LAD) I or II syndromes. Because such diseases occur with great rarity, animal models are valuable for studying the role of particular adhesion molecules and their natural ligands in immunity. We studied selected immune parameters and general health in mice with a defect in the sialyl-Lewis X antigen (selectin ligand) caused by disruption of the gene encoding alpha(1,3)fucosyltransferase VII (Fuc-TVII). Leukocytes from Fuc-TVII -/- and control mice were tested for adherence to cellophane membranes or polymer particles in vivo and phagocytic activity in vitro. While no difference in adherence was found, the number of neutrophil granulocytes in exudate induced by intraperitoneal injection of polymer beads was reduced in knock-out mice. Moreover, the phagocytic activity in Fuc-TVII -/- mice was significantly reduced. These animals have splenomegaly due to increased hematopoiesis and reduced weight but do not exhibit clinical signs of immunodeficiency. In conclusion, the lack of Fuc-TVII activity leads to several morphological and functional abnormalities without an impact on survival rate.


A nerve terminal anchorage protein from electric organ.
The nerve terminal and the postsynaptic receptor-containing membranes of the electric organ are both linked to the basal lamina that runs between them. We have identified an extracellular matrix protein whose physical properties suggest it anchors the nerve terminal to the basal lamina. The protein was identified because it shares an epitope with a proteoglycan component of electric organ synaptic vesicles. It too behaves like a proteoglycan. It is solubilized with difficulty from extracellular matrix fractions, elutes from DEAE Sephacel at pH 4.9 only at high ionic strength, and binds to a laminin affinity column from which it can be eluted with heparin. Under denaturing conditions it sediments rapidly and has a large excluded volume although it can be included in Sephacryl S-1000 columns. This large, highly charged extracellular matrix molecule can be readily reconstituted into liposomes consistent with the presence of a hydrophobic tail. By immunoelectron microscopy the antigen is found both in synaptic vesicles and on the plasma membrane of the nerve terminal. Since this is the first protein described that links the nerve terminal membrane to the extracellular matrix, we propose calling it terminal anchorage protein one (TAP-1).


Can intracellular signalling pathways predict developmental abnormalities?
Abstract Sensitivity of the adenylyl cyclase/c-fos protooncogene cascade to β-adrenergic agonists and glucocorticoids in foetal rat We examined whether measurements of adenylyl cyclase and its control of c-fos protooncogene mRNA expression in mid-gestation foetal rat could be used to detect developmental effects of apparently unrelated compounds: terbutaline, a β-adrenergic receptor stimulant, and dexamethasone, a glucocorticoid hormone. On gestational day 14, acute administration of terbutaline to pregnant rats resulted in sixfold induction of c-fos mRNA within 1 h; the same increase was obtained when a membrane-permeable analogue of cAMP was given. Treatment with dexamethasone on gestational days 11,12 and 13 produced the same increase in c-fos mRNA on gestational day 14 as had been seen with acute terbutaline or CAMP; no further increase could be obtained with acute CAMP treatment in the dexamethasone-pretreated animals. Adenylyl cyclase activity was evaluated on gestational day 14. Animals treated with dexamethasone showed a 50% enhancement of basal enzyme activity that reflected a parallel increase in total catalytic activity as measured with forskolin-Mn(2+). Dexamethasone also increased adenylyl cyclase activity in the presence of a β-agonist but to a lesser extent than the increase in total catalytic activity. These results indicate that cell signalling pathways mediating the expression of the genes that control cell differentiation are a likely target for structurally and mechanistically unrelated drugs and chemicals and may therefore be useful as early biomarkers of abnormal development.


Platelet binding and activity of recombinant factor VIIa.
Recombinant FVIIa was developed for the purpose of treating hemophiliacs with antibody inhibitors. It was initially assumed to act by enhancing factor X activation by a tissue factor-dependent mechanism. However, the very high levels of FVIIa required for hemostatic effect in vivo seemed inconsistent with this mechanism. After many years of debate, in now appears that platelet surface binding and activity play an important role in the efficacy of FVIIa as a bypassing agent in hemophilia. Platelet binding was initially suggested to be mediated by binding to anionic phospholipid exposed on platelet surfaces upon activation. It now appears that the glycoprotein Ib/IX/V complex also plays a role in FVIIa binding to platelets. However, the characteristics of FVIIa binding to GPIb/IX/V to not seem to fully explain platelet localization of FVIIa to platelets. Thus, there are still unanswered questions in fully understanding the mechanism of hemostatic action of recombinant FVIIa.


Changing Treatment Paradigms in Metastatic Breast Cancer: Lessons Learned.
Advances in understanding tumor biology, particularly signaling pathways, have led to the development and approval of many novel agents and have changed the landscape of therapy for patients with metastatic breast cancer. This review highlights some of the recent successes and failures in breast cancer drug development, including strategies to overcome endocrine and human epidermal growth factor 2-neu (HER2) resistance, targeting triple-negative breast cancers (which do not express the HER2, estrogen, and progesterone receptors) through novel receptors, harnessing the immune system, and new ways of targeting angiogenesis. For patients with metastatic breast cancer, expanding therapeutic options through clinical trial participation is a crucial part of modern oncology practice. As we continue to learn how to use targeted therapies in the context of genomic medicine, analysis of the tumor in real-time may become increasingly important, giving researchers the information needed to start combining therapies in a biologically informed manner.


Adolescent self-mutilation: diagnosis & treatment.
Self-mutilation is complicated and difficult to diagnose. Its incidence among adolescents has increased during the past 10 years. Most mental health professionals discover that the behavior has been part of patients' lives long before their initial visit and that patients have become very good at hiding their behavior. The literature on self-mutilation is increasing, but newer statistics, specifically about cutting and picking behaviors, need to be assessed. The disorder often co-exists with another disorder that requires psychotropic medications, the administration of which should be managed by psychiatric clinicians who specialize in children and adolescents. A multidisciplinary team is necessary to achieve the best outcomes.


Invasive squamous cell carcinoma of the conjunctiva first misdiagnosed as a pterygium: a clinicopathologic case report.
To describe the clinical findings of a patient who initially underwent surgery for a pterygium and who was finally diagnosed with invasive squamous cell carcinoma, and to determine the necessity and importance of pathologic investigation in all cases of a presumed pterygium. A case report. A 63-year-old man was referred for severe pain, redness, and purulent secretion in his right eye. A year earlier, he had undergone excision of a pterygium in his right eye by a bare sclera technique without any adjunctive antimetabolite in a private eye clinic. Furthermore, 6 months after this operation, he had undergone autologous conjunctival graft surgery because of dehiscence of the surgical site. His visual acuity was only light perception in the right eye. Slitlamp biomicroscopy showed severe nasal corneoscleral melting, purulent secretion, conjunctival hyperemia, corneal edema, hypopyon, intracamaral hemorrhage, and lid swelling. Ultrasonography showed a right hypoechoic mass invading the nasal part of the globe and a totally detached retina. Orbital magnetic resonance imaging showed a large (2 cm in diameter), irregular, lobulated mass invading the globe in the medial part of the right orbit. Results of a biopsy were consistent with squamous cell carcinoma. Because of the extensive intraocular involvement at the time of the diagnosis, subtotal orbital exenteration was performed. All pterygia should be evaluated meticulously with regard to possible underlying causes, such as carcinoma in situ or squamous cell carcinoma, and all excised lesions should also be evaluated pathologically to prevent such serious adverse outcomes that are mentioned in this case report.


Neutrophil to lymphocyte ratio as a prognostic marker in metastatic gallbladder cancer.
Neutrophil-to-lymphocyte ratio (NLR) has been used as an inflammation based prognostic marker for various malignancies. This study evaluated the association between NLR and overall survival (OS) in patients with metastatic gallbladder cancer (GBC) METHODS: An optimal cut off point for NLR was identified by plotting spline-based hazard ratio curves to identify a threshold effect and patients were divided into two groups, ≥5 or <5. Kaplan-Meier curves were plotted for NLR≥5 and NLR<5 and OS between the two groups. Of the 231 patients included, 138 (60%) had NLR <5 and 93 (40%) had NLR ≥5. There were no significant differences noted in gender, race, and administration of chemotherapy between the two groups. On univariable analysis, patients with NLR ≥5 had a significantly poor OS compared to those with NLR <5 (Median OS: 3.6 vs 8.7 months, p < 0.001). On multivariable analysis, adjusting for age, performance status, albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, platelet count and no administration of chemotherapy, NLR of ≥5 was associated with a worse OS compared to NLR <5 (HR: 1.70, 95%CI:1.20-2.39, p < 0.05). The current study demonstrates that NLR ≥5 is an independent predictor of poor prognosis in patients with metastatic GBC.


Gene transfer and gene mapping in mammalian cells in culture.
The ability to transfer mammalian genes parasexually has opened new possibilities for gene mapping and fine structure mapping and offers great potential for contributing to several aspects of mammalian biology, including gene expression and genetic engineering. The DNA transferred has ranged from whole genomes to single genes and smaller segments of DNA. The transfer of whole genomes by cell fusion forms cell hybrids, which has promoted the extensive mapping of human and mouse genes. Transfer, by cell fusion, of rearranged chromosomes has contributed significantly to determining close linkage and the assignment of genes to specific chromosomal regions. Transfer of single chromosomes has been achieved utilizing microcells fused to recipient cells. Metaphase chromosomes have been isolated and used to transfer single-to-multigenic DNA segments. DNA-mediated gene transfer, simulating bacterial transformation, has achieved transfer of single-copy genes. By utilizing DNA cleaved with restriction endonucleases, gene transfer is being empolyed as a bioassay for the purification of genes. Gene mapping and the fate of transferred genes can be examined now at the molecular level using sequence-specific probles. Recently, single genes have been cloned into eucaryotic and procaryotic vectors for transfer into mammalian cells. Moreover, recombinant libraries in which entire mammalian genomes are represented collectively are a rich new source of transferable genes. Methodology for transferring mammalian genetic information and applications for mapping mammalian genes is presented and prospects for the future discussed.


Autologous hematopoietic stem cell transplantation in refractory rheumatoid arthritis: sustained response in two of four patients.
To investigate the safety and efficacy of immune ablation with subsequent autologous hematopoietic stem cell transplantation (HSCT) in severe rheumatoid arthritis (RA). Four patients with refractory RA and poor prognostic indicators were treated. Stem cells were collected and lymphocytes were depleted by 2.3-4.0 logs. The conditioning regimen included cyclophosphamide (200 mg/kg), antithymocyte globulin (90 mg/kg), and, for 1 patient, total body irradiation (TBI) with 400 cGy. Improvement was evaluated according to the American College of Rheumatology (ACR) preliminary definition of improvement in RA (ACR 20), and also according to the ACR 50 and ACR 70 criteria. HSCT was well tolerated. Three patients fulfilled the ACR 70 criteria at 1 month and 3 months post-HSCT. One patient did not fulfill the ACR 20 criteria because of persistent joint tenderness, despite improvement of the joint swelling. At 6 months post-HSCT, 1 patient fulfilled the ACR 70 criteria and 1 fulfilled the ACR 50 criteria, and these 2 patients fulfilled the ACR 70 criteria at 9 months post-HSCT. The other 2 patients (including the patient who received TBI) did not meet the ACR 20 criteria at 6 months and 9 months post-HSCT. The only patient with followup of >9 months fulfilled the ACR 70 criteria at 20 months post-HSCT. In this series, autologous HSCT was safe and effective in inducing major clinical response and maintained significant benefit for 2 patients at 9 months and 20 months posttreatment, respectively. Sustained response did not occur for 2 of 4 patients. A regimen dose-response effect may exist, but the addition of TBI did not prevent disease relapse for 1 of the patients. More aggressive T cell depletion of the autograft, use of a myeloablative regimen, or use of an allograft may be necessary to decrease relapse rates.


Language development and brain reorganization in a child born without the left hemisphere.
We present a case of a 14-year-old girl born without the left hemisphere due to prenatal left internal carotid occlusion. We combined longitudinal language and cognitive assessments with functional and structural neuroimaging data to situate the case within age-matched, typically developing children. Despite having had a delay in getting language off the ground during the preschool years, our case performed within the normal range on a variety of standardized language tests, and exceptionally well on phonology and word reading, during the elementary and middle school years. Moreover, her spatial, number, and reasoning skills also fell in the average to above-average range based on assessments during these time periods. Functional MRI data revealed activation in right fronto-temporal areas when listening to short stories, resembling the bilateral activation patterns in age-matched typically developing children. Diffusion MRI data showed significantly larger dorsal white matter association tracts (the direct and anterior segments of the arcuate fasciculus) connecting areas active during language processing in her remaining right hemisphere, compared to either hemisphere in control children. We hypothesize that these changes in functional and structural brain organization are the result of compensatory brain plasticity, manifesting in unusually large right dorsal tracts, and exceptional performance in phonology, speech repetition, and decoding. More specifically, we posit that our case's large white matter connections might have played a compensatory role by providing fast and reliable transfer of information between cortical areas for language in the right hemisphere.


India's foreign medical graduates: an opportunity to correct India's physician shortage.
India's current estimated doctor-population ratio of 1:1700 against targeted ratio of 1: 1000 shows a clear shortage. A mismatch in number of medical aspirants and available seats, intense competition and unaffordable costs of medical education prompt many Indian students to pursue training opportunities abroad. Many later return to India, and these foreign medical graduates (FMGs) must pass a qualification test which is a required to practice medicine in India. This review undertakes a situational analysis of FMGs in India and suggests a roadmap to better utilize this resource pool of physicians. A thorough literature search was carried out using Google Scholar, PubMed and websites of the Central Board of Secondary Education and Medical Council of India. Foreign Medical Graduate Examination (FMGE) data was obtained from India's National Board of Examinations. From 2002 to 2014, growth was seen in the number of FMGs who took the FMGE, with more having trained in China than any other country. However, typically only 25% of FMGs pass the FMGE. In 2013, 9,700 FMGs were unable to pass the FMGE to enter practice in India. At least 7,500 FMG physicians are unable to become licensed each year for failure to pass the FMGE, including those who retake and again fail the exam. There are possible solutions. Additional training and hands-on apprenticeships can be introduced to help FMGs build their skills to then be able to pass the FMGE. FMGs can now learn by participating as observers in the established programs. Opportunities also exist for FMGs to work outside of clinical care, including in research, hospital administration and public health. As of now, FMGs are an untapped resource and lost opportunity to a country with shortages of physicians.


Prescription medication by physiotherapists: a Brazilian view of the United Kingdom, Canada, Australia and New Zealand.
Many health systems (HS) have adopted novel models of care which have included non-medical prescription (NMP) by physiotherapists. The aim of this study was to verify in the literature the existence of this practice and its possible benefits. A literature review was carried out through search on Science Direct, PubMed, SciELO, Lilacs and Google Scholar, and in the World Confederation for Physical Therapy and Chartered Society of Physiotherapy websites. In recent decades the United Kingdom adopted the NMP for health professionals, followed by Canada. In Australia and New Zealand physiotherapists have acted in the prescription and administration of medications under medical orders, which is the first step into independent prescription. Brazilian physiotherapists cannot prescribe any medication, despite of high demands from patients in the Brazilian HS, shortage of physicians in many regions and bureaucracy in accessing health services. The adoption of NMP by physiotherapists may play an important role in the HS, and it seems to be an inevitable achievement in the next years in Australia and New Zealand. The main benefits include decreasing bureaucracy for assistance, population demands for medication as well as major professional refinement.


Osmolar changes in haemorrhage: the effects of an altered nutritional status.
Fed and 24-30 hour starved rats were submitted to haemorrhagic hypotension, 70 mmHg, with a modified Wigger's system. Neuroleptanalgesia was used to ensure a normal degree of stress reactivity. Despite fed animals losing 53% of their original blood volume (BV) and starved animals 47% (BV = 6% prestarved body weight), blood gas data and creatinine levels confirmed a well intact and compensated status in both groups. Fed animals compensated for the greater haemorrhage with a haematocrit reduction which was double that in starved animals. When the alterations in osmole skeletons were compared, evidence for an intracellular fluid (ICF) shift to the interstitium was obtained in fed rats. Their NaCl space increased by 5.5%. Glucose increased its osmolar effect by 224% among fed animals and was reduced in those which had been starved. Glucose was identified as the solute causing an acute mobilisation of ICF to the interstitium.


Enantioselective Brønsted Acid Catalysis as a Tool for the Synthesis of Natural Products and Pharmaceuticals.
Synthesis of biologically active molecules (whether at laboratory or industrial scale) remains a highly appealing area of modern organic chemistry. Nowadays, the need to access original bioactive scaffolds goes together with the desire to improve synthetic efficiency, while reducing the environmental footprint of chemical activities. Long neglected in the field of total synthesis, enantioselective organocatalysis has recently emerged as an environmentally friendly and indispensable tool for the construction of relevant bioactive molecules. Notably, enantioselective Brønsted acid catalysis has offered new opportunities in terms of both retrosynthetic disconnections and controlling stereoselectivity. The present report attempts to provide an overview of enantioselective total or formal syntheses designed around Brønsted acid-catalyzed transformations. To demonstrate the versatility of the reactions promoted and the diversity of the accessible motifs, this Minireview draws a systematic parallel between methods and retrosynthetic analysis. The manuscript is organized according to the main reaction types and the nature of newly-formed bonds.


In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target.
Immunotherapy with PD-1 checkpoint blockade is effective in only a minority of patients with cancer, suggesting that additional treatment strategies are needed. Here we use a pooled in vivo genetic screening approach using CRISPR-Cas9 genome editing in transplantable tumours in mice treated with immunotherapy to discover previously undescribed immunotherapy targets. We tested 2,368 genes expressed by melanoma cells to identify those that synergize with or cause resistance to checkpoint blockade. We recovered the known immune evasion molecules PD-L1 and CD47, and confirmed that defects in interferon-γ signalling caused resistance to immunotherapy. Tumours were sensitized to immunotherapy by deletion of genes involved in several diverse pathways, including NF-κB signalling, antigen presentation and the unfolded protein response. In addition, deletion of the protein tyrosine phosphatase PTPN2 in tumour cells increased the efficacy of immunotherapy by enhancing interferon-γ-mediated effects on antigen presentation and growth suppression. In vivo genetic screens in tumour models can identify new immunotherapy targets in unanticipated pathways.


Large cell neuroendocrine carcinoma of the uterine cervix.
We report a case of large cell neuroendocrine carcinoma of the uterine cervix. A 33-year-old woman presented with a 4-month history of irregular vaginal bleeding and suspicious cervix. Transvaginal ultrasound showed a 3×3.8 cm cervical mass with a marked increase in the blood flow. MRI pelvis showed an exophytic tumour with left external iliac lymph node metastasis. Immunohistochemistry of the tumour cells showed strong positivity for the neuroendocrine markers synaptophysin and a very high Ki67 proliferation index. A diagnosis of high-grade large cell neuroendocrine carcinoma of the uterine cervix was made with FIGO stage IIA2. She was treated with chemotherapy and palliative radiotherapy but died 21 months after presenting. Neuroendocrine tumour of the uterine cervix is an extremely aggressive cancer with the late presentation-the need for a more rigorous treatment protocol as well as potential screening methods could improve outcomes for these patients.


Tough and strong porous bioactive glass-PLA composites for structural bone repair.
Bioactive glass scaffolds have been used to heal small contained bone defects but their application to repairing structural bone is limited by concerns about their mechanical reliability. In the present study, the addition of an adherent polymer layer to the external surface of strong porous bioactive glass (13-93) scaffolds was investigated to improve their toughness. Finite element modeling (FEM) of the flexural mechanical response of beams composed of a porous glass and an adherent polymer layer predicted a reduction in the tensile stress in the glass with increasing thickness and elastic modulus of the polymer layer. Mechanical testing of composites with structures similar to the models, formed from 13-93 glass and polylactic acid (PLA), showed trends predicted by the FEM simulations but the observed effects were considerably more dramatic. A PLA layer of thickness -400 µm, equal to -12.5% of the scaffold thickness, increased the load-bearing capacity of the scaffold in four-point bending by ~50%. The work of fracture increased by more than 10,000%, resulting in a non-brittle mechanical response. These bioactive glass-PLA composites, combining bioactivity, high strength, high work of fracture and an internal architecture shown to be conducive to bone infiltration, could provide optimal implants for healing structural bone defects.


CDA Templates - Utilizing the MediCUBE.
The specification and customization of clinical document types are tasks that need a strong collaboration between domain experts and IT specialists. However, these collaborators are often faced with difficulties due to different interpretation of domain knowledge. Therefore, an adequate method for sharing domain knowledge about documents is necessary. Even though there are some tools that help to define medical document types, there is a lack of approaches that focus on the understandability of the specification for the domain experts. This paper proposes a modeling approach based on the Clinical Document Architecture to address this gap.


Preventive and Therapeutic Role of Functional Ingredients of Barley Grass for Chronic Diseases in Human Beings.
Barley grass powder is the best functional food that provides nutrition and eliminates toxins from cells in human beings; however, its functional ingredients have played an important role as health benefit. In order to better cognize the preventive and therapeutic role of barley grass for chronic diseases, we carried out the systematic strategies for functional ingredients of barley grass, based on the comprehensive databases, especially the PubMed, Baidu, ISI Web of Science, and CNKI, between 2008 and 2017. Barley grass is rich in functional ingredients, such as gamma-aminobutyric acid (GABA), flavonoids, saponarin, lutonarin, superoxide dismutase (SOD), K, Ca, Se, tryptophan, chlorophyll, vitamins (A, B1, C, and E), dietary fiber, polysaccharide, alkaloid, metallothioneins, and polyphenols. Barley grass promotes sleep; has antidiabetic effect; regulates blood pressure; enhances immunity; protects liver; has anti-acne/detoxifying and antidepressant effects; improves gastrointestinal function; has anticancer, anti-inflammatory, antioxidant, hypolipidemic, and antigout effects; reduces hyperuricemia; prevents hypoxia, cardiovascular diseases, fatigue, and constipation; alleviates atopic dermatitis; is a calcium supplement; improves cognition; and so on. These results support that barley grass may be one of the best functional foods for preventive chronic diseases and the best raw material of modern diet structure in promoting the development of large health industry and further reveal that GABA, flavonoids, SOD, K-Ca, vitamins, and tryptophan mechanism of barley grass have preventive and therapeutic role for chronic diseases. This paper can be used as a scientific evidence for developing functional foods and novel drugs for barley grass for preventive chronic diseases.


Differential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams.
Proton therapy allows to avoid excess radiation dose on normal tissues. However, there are some limitations. Indeed, passive delivery of proton beams results in an increase in the lateral dose upstream of the tumor and active scanning leads to strong differences in dose delivery. This study aims to assess possible differences in the transcriptomic response of skin in C57BL/6 mice after TBI irradiation by active or passive proton beams at the dose of 6 Gy compared to unirradiated mice. In that purpose, total RNA was extracted from skin samples 3 months after irradiation and RNA-Seq was performed. Results showed that active and passive delivery lead to completely different transcription profiles. Indeed, 140 and 167 genes were differentially expressed after active and passive scanning compared to unirradiated, respectively, with only one common gene corresponding to RIKEN cDNA 9930021J03. Moreover, protein-protein interactions performed by STRING analysis showed that 31 and 25 genes are functionally related after active and passive delivery, respectively, with no common gene between both types of proton delivery. Analysis showed that active scanning led to the regulation of genes involved in skin development which was not the case with passive delivery. Moreover, 14 ncRNA were differentially regulated after active scanning against none for passive delivery. Active scanning led to 49 potential mRNA-ncRNA pairs with one ncRNA mainly involved, Gm44383 which is a miRNA. The 43 genes potentially regulated by the miRNA Gm44393 confirmed an important role of active scanning on skin keratin pathway. Our results demonstrated that there are differences in skin gene expression still 3 months after proton irradiation versus unirradiated mouse skin. And strong differences do exist in late skin gene expression between scattered or scanned proton beams. Further investigations are strongly needed to understand this discrepancy and to improve treatments by proton therapy.


MicroRNA‑3666 inhibits breast cancer cell proliferation by targeting sirtuin 7.
The abnormal expression of microRNAs (miRNAs) is associated with cancer initiation and progression. miRNAs functioning as oncogenes or tumor suppressors represent novel biomarkers for cancer diagnosis, prognosis, and serve as therapeutic tools. MiR‑3666 has been reported as a tumor suppressor in various types of cancer; however, its role in breast cancer remains unknown. In the current study, the aim was to investigate the potential role of miR‑3666 in breast cancer. It was identified that miR‑3666 was decreased in breast cancer cell lines and that the overexpression of miR‑3666 inhibited breast cancer cell proliferation. Furthermore, miR‑3666 promotes cell apoptosis of breast cancer cells. Bioinformatics analysis and dual‑luciferase reporter assay demonstrated that miR‑3666 targeted the 3'‑untranslated region of sirtuin 7 (SIRT7) which was recognized as an oncogene. Overexpression of miR‑3666 decreased SIRT7 expression levels, and knockdown of SIRT7 suppressed proliferation and promoted apoptosis of breast cancer cells. A rescue assay demonstrated that the restoration of SIRT7 expression markedly reversed the miR‑3666‑induced anti‑tumor effects. Thus, the current study indicates that miR‑3666 suppresses breast cancer cell proliferation by targeting SIRT7, and propose miR‑3666 as a potential candidate for breast cancer therapy.


Detection and characterization of optical inhomogeneities with diffuse photon density waves: a signal-to-noise analysis.
Diffusing photons provide information about the optical properties of turbid media. In biological tissues these optical properties may be correlated to physiological parameters, enabling one to probe effectively the physiological states of tissue for abnormalities such as tumors and hemorrhages. We show that positional uncertainty in the source and detector lead to significant random errors that degrade the optical information available from diffusing photons. We investigate the limits for the detection, localization, and characterization of optical inhomogeneities by using diffusing photons as a probe. Although detection is sufficient for tumor screening, full characterization of the optical properties is desirable for specification of the tumor. Our findings in model breast systems with realistic signal-to-noise ratios indicate that tumors as small as 0.3 cm in diameter can be unambiguously detected; however, simultaneous determination of tumor size and optical properties is possible only if its diameter is of the order of 1.0 cm or larger. On the other hand, if a priori information about the size (optical properties) is available, then the optical properties (size) of tumors as small as 0.3 cm in diameter can be determined.


Identification and characterization of a heterotrimeric archaeal DNA polymerase holoenzyme.
Since their initial characterization over 30 years ago, it has been believed that the archaeal B-family DNA polymerases are single-subunit enzymes. This contrasts with the multi-subunit B-family replicative polymerases of eukaryotes. Here we reveal that the highly studied PolB1 from Sulfolobus solfataricus exists as a heterotrimeric complex in cell extracts. Two small subunits, PBP1 and PBP2, associate with distinct surfaces of the larger catalytic subunit and influence the enzymatic properties of the DNA polymerase. Thus, multi-subunit replicative DNA polymerase holoenzymes are present in all three domains of life. We reveal the architecture of the assembly by a combination of cross-linking coupled with mass spectrometry, X-ray crystallography and single-particle electron microscopy. The small subunits stabilize the holoenzyme assembly and the acidic tail of one small subunit mitigates the ability of the enzyme to perform strand-displacement synthesis, with important implications for lagging strand DNA synthesis.


Intravascular targeting of a new anticoagulant heparin compound.
Since most thrombotic reactions occur on the vessel wall, interaction of anticoagulants with vascular components is critical. Heparin (H) is the primary drug for treatment and prevention of thrombosis. To improve H's efficacy and bioavailability, a covalent complex of H and its biological target, antithrombin (AT), was developed. While H has a short, variable intravenous half-life leading to unpredictable anticoagulation, clearance of covalent ATH complex is slower. H's variable anticoagulant effect arises from interactions with plasma and vessel wall proteins. ATH has increased bioavailability due to lower plasma protein and endothelial binding relative to H. Pharmacodynamic studies demonstrate that the AT moiety can regulate ATH binding to target tissues. For example, blood vessel binding is enhanced using ATH containing recombinant AT with oligomannose structures that can interact with endothelial mannose receptor lectins. Furthermore, recent work has shown that inhibition of factor VIIa/tissue factor complex by ATH is significantly faster than AT + H. Similarly, thrombin bound to endothelial thrombomodulin is inhibited more efficiently by ATH than by AT + H, which might improve regulation of thrombin generation. Overall, linking H to AT may prevent unwanted protein interactions and allow vessel wall sites to be targeted. This review examines ATH biodistribution.


High-Volume Transanal Surgery with CPH34 HV for the Treatment of III-IV Degree Haemorrhoids: Final Short-Term Results of an Italian Multicenter Clinical Study.
The clinical chart of 621 patients with III-IV haemorrhoids undergoing Stapled Hemorrhoidopexy (SH) with CPH34 HV in 2012-2014 was consecutively reviewed to assess its safety and efficacy after at least 12 months of follow-up. Mean volume of prolapsectomy was significantly higher (13.0 mL; SD, 1.4) in larger prolapse (9.3 mL; SD, 1.2) (p < 0.001). Residual or recurrent haemorrhoids occurred in 11 of 621 patients (1.8%) and in 12 of 581 patients (1.9%), respectively. Relapse was correlated with higher preoperative Constipation Scoring System (CSS) (p = 0.000), Pescatori's degree (p = 0.000), Goligher's grade (p = 0.003), prolapse exceeding half of the length of the Circular Anal Dilator (CAD) (p = 0.000), and higher volume of prolapsectomy (p = 0.000). At regression analysis, only the preoperative CSS, Pescatori's degree, Goligher's grade, and volume of resection were significantly predictive of relapse. A high level of satisfaction (VAS = 8.6; SD, 1.0) coupled with a reduction of 12-month CSS (Δ preoperative CSS/12 mo CSS = 3.4, SD, 2.0; p < 0.001) was observed. The wider prolapsectomy achievable with CPH34 HV determined an overall 3.7% relapse rate in patients with high prevalence of large internal rectal prolapse, coupled with high satisfaction index, significant reduction of CSS, and very low complication rates.


Alginate/aminopropyl-silicate/alginate membrane immunoisolatability and insulin secretion of encapsulated islets.
We utilized the sol-gel reaction to prepare an immunoisolatable membrane for a microcapsule-shaped bioartificial pancreas. The membrane, derived from two precursors, 3-(aminopropyl)trimethoxysilane (APTrMOS) and tetramethoxysilane (TMOS), was formed onto calcium-alginate gel beads via electrostatic interaction. The molecular weight cutoff point of less than 150 000 required for immunoisolation was achieved at molar ratios ([APTrMOS]/[TMOS]) ranging from 0.60 to 2.40 with the amount of APTrMOS fixed at 3.40 mmol/(10 mL of calcium-alginate). When encapsulated in a membrane prepared at the molar ratio of 0.60, the islets contracted in volume and showed no response to stimulation by a high glucose concentration. However, islets in a membrane prepared at the molar ratio of 2.40 showed no contraction and responded to the glucose stimulation at almost the same level as free islets. These results demonstrated that the molar ratio of the precursors was a dominant factor affecting membrane permeability and the insulin secretion activity of the encapsulated islets.


[Changes in the lipid composition of the lymphocyte membranes and in the reactions of the lymphocytic Fc receptors in obesity].
The paper is concerned with a study of a response of lymphocytic Fc receptors (FcR) to modulators regulating their expression (prostaglandins E2 and F2, 2 X 10(-9) M, isoproterenol 10(-5), 10(-6) M) as compared to changes in the lymphocyte membrane lipid composition of patients with obesity of II-III degree with a high blood cholesterol level up to 9-10 nmol/l. Two groups were distinguished among obese patients: "areactive" in which lymphocytic FcR did not respond to modulators, and "reactive" in which FcR responded at least to one of 4 utilized modulators. Research into the lipid spectrum of lymphocytic membranes revealed a significant decrease in the concentration of nonesterified fatty acids in membranes of "areactive" lymphocytes to 4 +/- 0.6% (against the normal level of 8.9 +/- 0.7%). In order to make up completely for immunodeficiency in obesity, lipotropic agents and food rich in polyunsaturated fatty acids could be recommended.


Social risk or genetic liability for psychosis? A study of children born in Sweden and reared by adoptive parents.
Recent studies suggest a role for social factors during childhood in the later development of schizophrenia. Since social conditions in childhood are closely related to parental psychiatric illness, there is a need to disentangle how genes and social environmental factors interact. A total of 13,163 children born in Sweden between 1955 and 1984 and reared in Swedish adoptive families were linked to the National Patient Register until 2006 regarding admissions for non-affective psychoses, including schizophrenia. Hazard ratios for nonaffective psychoses were estimated in relation to three indicators of socioeconomic position in childhood (household data of the rearing family obtained via linkage to the National Censuses of 1960-1985) and in relation to indicator of genetic liability (biological parental inpatient care for psychosis). In addition, the total Swedish-born population was investigated. Increased risks for nonaffective psychosis were found among adoptees (without biological parental history of psychosis) reared in families with disadvantaged socioeconomic position, which consisted of adoptive parental unemployment (hazard ratio=2.0), single-parent household (hazard ratio=1.2), and living in apartments (hazard ratio=1.3). The risk was also increased among persons with genetic liability for psychosis alone (hazard ratio=4.7). Among those exposed to both genetic liability and a disadvantaged socioeconomic situation in childhood, the risk was considerably higher (hazard ratio=15.0, 10.3, and 5.7 for parental unemployment, single-parent household, and apartment living, respectively). Analyses in the larger population supported these results. The results indicate that children reared in families with a disadvantaged socioeconomic position have an increased risk for psychosis. There was also some support for an interaction effect, suggesting that social disadvantage increases this risk more in children with genetic liability for psychosis.


Comorbidities of diabetes and hypertension: mechanisms and approach to target organ protection.
Up to 75% of adults with diabetes also have hypertension, and patients with hypertension alone often show evidence of insulin resistance. Thus, hypertension and diabetes are common, intertwined conditions that share a significant overlap in underlying risk factors (including ethnicity, familial, dyslipidemia, and lifestyle determinants) and complications. These complications include microvascular and macrovascular disorders. The macrovascular complications, which are well recognized in patients with longstanding diabetes or hypertension, include coronary artery disease, myocardial infarction, stroke, congestive heart failure, and peripheral vascular disease. Although microvascular complications (retinopathy, nephropathy, and neuropathy) are conventionally linked to hyperglycemia, studies have shown that hypertension constitutes an important risk factor, especially for nephropathy. The familial predisposition to diabetes and hypertension appears to be polygenic in origin, which militates against the feasibility of a "gene therapy" approach to the control or prevention of these conditions. On the other hand, the shared lifestyle factors in the etiology of hypertension and diabetes provide ample opportunity for nonpharmacologic intervention. Thus, the initial approach to the management of both diabetes and hypertension must emphasize weight control, physical activity, and dietary modification. Interestingly, lifestyle intervention is remarkably effective in the primary prevention of diabetes and hypertension. These principles also are pertinent to the prevention of downstream macrovascular complications of the two disorders. In addition to lifestyle modification, most patients will require specific medications to achieve national treatment goals for hypertension and diabetes. Management of hyperglycemia, hypertension, dyslipidemia, and the underlying hypercoagulable and proinflammatory states requires the use of multiple medications in combination.


Unilateral ptosis associated with paramedian thalamiic infarction.
The paramedian artery arises from P1 segment of posterior cerebral artery and supplies a variable extent of thalamus but usually the dorsomedian, median, internal medullary lamina and the intralaminar nuclei. The typical clinical picture of unilateral paramedian thalamic infarctions consist of arousal and memory disorders, language or visuospatial disorders depending on the side of the lesion accompanied with gaze palsies and sensory-motor deficits. Ipsilateral ptosis associated with paramedian thalamic infarctions has been rarely reported. We report a 31 years old patient presenting with unilateral ptosis and right sided facial numbness associated with right paramedian thalamic infarction.


The present situation of human taeniases and cysticercosis in Asia.
Three human Taenia species, Taenia solium, Taenia saginata, and Taenia asiatica, are endemic in rural regions of Asia, with these species sympatrically distributed in parts of Thailand and China. The pork tapeworm, T. solium, is the most pathogenic to humans, causing cysticercosis and neurocysticercosis (NCC). Due to its public health impact, T. solium taeniasis/cysticercosis is one of 17 neglected tropical diseases (NTDs) prioritized by the World Health Organization. In this review, the current status of taeniasis and NCC in several Asian countries will be presented as will possible prevention and control strategies. Among the known T. solium endemic areas in Asia, Bali, Indonesia is of high importance due to the risk of tourists becoming infected. Therefore, special attention will be given to ongoing control initiatives in Bali.


Androgen-dependent regulation of medium and long chain fatty acids uptake in prostate cancer.
Epidemiological and experimental studies suggest that both fatty acids and androgens have a role in the development and progression of prostate cancer (PC). Plasma membrane fatty acid binding protein (FABP(pm)) is a transporter of medium and long chain fatty acids (MCFA and LCFA) across the plasma membrane, and is identical to the mitochondrial protein aspartate aminotransferase (mAAT) that is regulated by testosterone only in prostate epithelial cells, a site where PC initially develops. We therefore hypothesized that FABP(pm) is also regulated by androgens. We examined the effect of a synthetic androgen, R1881, and that of androgen receptor (AR) blocker, bicalutamide, on the expression of FABP(pm) and mAAT and on the uptake of fatty acids in the androgen-sensitive LNCaP, androgen responsive 22rv1 and androgen-independent CL1 human PC cells. This was done using immunofluorescence and confocal microscopy, Western blot, flow cytometry, and (3)H-oleate uptake studies. Androgen supplementation increased the cellular and surface expression of FABP(pm) and mAAT and increased the uptake of fluorescently labeled MCFA and LCFA and that of (3)H-oleate only in PC cells that express the AR. Bicalutamide inhibited this phenomenon. The uptake of MCFA and LCFA into PC cells is androgen regulated as well as the expression of FABP(pm) and mAAT.


Better Mobility Is Associated With Higher Incomes and Longer Working Years Among Older Adults.
Robust physical mobility is the key to healthy independent aging. Although the association between socioeconomic status and health is well documented, it is unclear whether there is a relationship between mobility and income, because income data are not readily available. (1) Do individuals with better mobility have higher incomes? (2) Does maintaining mobility over time allow individuals to keep working? (3) Is exercise associated with higher mobility over time? We obtained longitudinal income and health data from the nationally representative Health and Retirement Study. Three cohorts were used. First, we studied the relationship between household income and mobility (on a 6-point index of walking impairment) in 19,430 adults who were assessed in 2016 (representing 93% of the 20,805-person total cohort). We measured the association of mobility and household income in a multivariate linear regression analysis of age, gender, health conditions, and education. We then identified a second group of 1094 individuals with unrestricted mobility in the year 2000 and compared differences in income and working rates between those who maintained mobility and those who lost mobility after 10 years. Finally, we identified a third group of 7063 individuals who were 60 to 80 years old in 2012, divided the group by how often they engaged in exercise, and observed differences in mobility after 4 years. After adjusting for covariates, a drop of one level of mobility was associated with a USD 3410 reduction in annual household income (95% CI USD 2890 to USD 3920; p < 0.001). After 10 years, individuals who maintained their mobility had incomes that were USD 6500 higher than that of individuals who were not working (95% CI USD 2300 to USD 10,300; p < 0.001) and were more likely to be working (40% versus 34.5%; p < 0.001). Exercising at least once per week was associated with better mobility 4 years later (mobility score 4.46 ± 0.08 versus 3.66 ± 0.08; p < 0.001). Better mobility was associated with more than USD 3000 in annual income. Regular exercise and other interventions that improve mobility may have meaningful returns on investment. Because greater mobility is strongly associated with higher income, orthopaedic interventions may be undervalued.


Mapping of host range restriction of the rakkyo strain of tobacco mosaic virus in Nicotiana tabacum cv. bright yellow.
The rakkyo strain (TMV-R) and the common strain (TMV-U1) of tobacco mosaic virus exhibit distinct host range differences. TMV-R infects rakkyo plants, a monocot host that TMV-U1 is unable to infect. However, TMV-R causes only latent infection in Nicotiana tabacum cv. Bright Yellow (BY) in inoculated leaves, whereas TMV-U1 infects BY systemically and induces mosaic symptoms. Complete nucleotide sequencing of the TMV-R genomic RNA revealed amino acid changes in the 130K/ 180K replicase proteins, the 30K protein, and the coat protein and nucleotide changes in the 5' and 3' noncoding regions compared to TMV-U1. To identify viral components involved in determination of differences in host range, we have mapped determinants for the differential infection phenotype in BY plants by constructing chimeric viruses between the two strains in the present study. Examination of the infection phenotypes of the 14 constructed chimeric viruses in BY showed that determinants defining the differential infection phenotype in BY reside in the 130K/180K replicase proteins and the 3' noncoding region. Cognate combination of the 130K/180K replicase proteins and the 3' noncoding region of TMV-U1 origin is required to produce systemic infection in BY plants.


Molecular basis of semaphorin-mediated axon guidance.
The semaphorin family of proteins constitute one of the major cues for axonal guidance. The prototypic member of this family is Sema3A, previously designated semD/III or collapsin-1. Sema3A acts as a diffusible, repulsive guidance cue in vivo for the peripheral projections of embryonic dorsal root ganglion neurons. Sema3A binds with high affinity to neuropilin-1 on growth cone filopodial tips. Although neuropilin-1 is required for Sema3A action, it is incapable of transmitting a Sema3A signal to the growth cone interior. Instead, the Sema3A/neuropilin-1 complex interacts with another transmembrane protein, plexin, on the surface of growth cones. Certain semaphorins, other than Sema3A, can bind directly to plexins. The intracellular domain of plexin is responsible for initiating the signal transduction cascade leading to growth cone collapse, axon repulsion, or growth cone turning. This intracellular cascade involves the monomeric G-protein, Rac1, and a family of neuronal proteins, the CRMPs. Rac1 is likely to be involved in semaphorin-induced rearrangements of the actin cytoskeleton, but how plexin controls Rac1 activity is not known. Vertebrate CRMPs are homologous to the Caenorhabditis elegans unc-33 protein, which is required for proper axon morphology in worms. CRMPs are essential for Sema3A-induced, neuropilin-plexin-mediated growth cone collapse, but the molecular interactions of growth cone CRMPs are not well defined. Mechanistic aspects of plexin-based signaling for semaphorin guidance cues may have implications for other axon guidance events and for the basis of growth cone motility.


Deep Learning on Construction Sites: A Case Study of Sparse Data Learning Techniques for Rebar Segmentation.
Recent advances in deep learning models for image interpretation finally made it possible to automate construction site monitoring processes that rely on remote sensing. However, the major drawback of these models is their dependency on large datasets of training images labeled at pixel level, which must be produced manually by skilled personnel. To reduce the need for training data, this study evaluates weakly and semi-supervised semantic segmentation models for construction site imagery to efficiently automate monitoring tasks. As a case study, we compare fully, weakly and semi-supervised methods for the detection of rebar covers, which are useful for quality control. In the experiments, recent models, i.e., IRNet, DeepLabv3+ and the cross-consistency training model are compared for their ability to segment rebar covers from construction site imagery with minimal manual input. The results show that weakly and semi-supervised models can indeed rival with the performance of fully supervised models with the majority of the target objects being properly found. This study provides construction site stakeholders with detailed information on how to leverage deep learning for efficient construction site monitoring and weigh preprocessing, training, and testing efforts against each other in order to decide between fully, weakly and semi-supervised training.


Rhizosphere protists are key determinants of plant health.
Plant health is intimately influenced by the rhizosphere microbiome, a complex assembly of organisms that changes markedly across plant growth. However, most rhizosphere microbiome research has focused on fractions of this microbiome, particularly bacteria and fungi. It remains unknown how other microbial components, especially key microbiome predators-protists-are linked to plant health. Here, we investigated the holistic rhizosphere microbiome including bacteria, microbial eukaryotes (fungi and protists), as well as functional microbial metabolism genes. We investigated these communities and functional genes throughout the growth of tomato plants that either developed disease symptoms or remained healthy under field conditions. We found that pathogen dynamics across plant growth is best predicted by protists. More specifically, communities of microbial-feeding phagotrophic protists differed between later healthy and diseased plants at plant establishment. The relative abundance of these phagotrophs negatively correlated with pathogen abundance across plant growth, suggesting that predator-prey interactions influence pathogen performance. Furthermore, phagotrophic protists likely shifted bacterial functioning by enhancing pathogen-suppressing secondary metabolite genes involved in mitigating pathogen success. We illustrate the importance of protists as top-down controllers of microbiome functioning linked to plant health. We propose that a holistic microbiome perspective, including bacteria and protists, provides the optimal next step in predicting plant performance. Video Abstract.


L1 cell adhesion molecule as a potential therapeutic target in murine models of endometriosis using a monoclonal antibody approach.
The neural cell adhesion molecule L1CAM is a transmembrane glycoprotein abnormally expressed in tumors and previously associated with cell proliferation, adhesion and invasion, as well as neurite outgrowth in endometriosis. Being an attractive target molecule for antibody-based therapy, the present study assessed the ability of the monoclonal anti-L1 antibody (anti-L1 mAb) to impair the development of endometriotic lesions in vivo and endometriosis-associated nerve fiber growth. Endometriosis was experimentally induced in sexually mature B6C3F1 (n=34) and CD-1 nude (n=21) mice by autologous and heterologous transplantation, respectively, of endometrial fragments into the peritoneal cavity. Transplantation was confirmed four weeks post-surgery by in vivo magnetic resonance imaging and laparotomy, respectively. Mice were then intraperitoneally injected with anti-L1 mAb or an IgG isotype control antibody twice weekly, over a period of four weeks. Upon treatment completion, mice were sacrificed and endometrial implants were excised, measured and fixed. Endometriosis was histologically confirmed and L1CAM was detected by immunohistochemistry. Endometriotic lesion size was significantly reduced in anti-L1-treated B6C3F1 and CD-1 nude mice compared to mice treated with control antibody (P<0.05). Accordingly, a decreased number of PCNA positive epithelial and stromal cells was detected in autologously and heterologously induced endometriotic lesions exposed to anti-L1 mAb treatment. Anti-L1-treated mice also presented a diminished number of intraperitoneal adhesions at implantation sites compared with controls. Furthermore, a double-blind counting of anti-neurofilament L stained nerves revealed significantly reduced nerve density within peritoneal lesions in anti-L1 treated B6C3F1 mice (P=0.0039). Local anti-L1 mAb treatment suppressed endometriosis growth in B6C3F1 and CD-1 nude mice and exerted a potent anti-neurogenic effect on induced endometriotic lesions in vivo. The findings of this preliminary study in mice provide a strong basis for further testing in in vivo models.


M6 membrane protein plays an essential role in Drosophila oogenesis.
We had previously shown that the transmembrane glycoprotein M6a, a member of the proteolipid protein (PLP) family, regulates neurite/filopodium outgrowth, hence, M6a might be involved in neuronal remodeling and differentiation. In this work we focused on M6, the only PLP family member present in Drosophila, and ortholog to M6a. Unexpectedly, we found that decreased expression of M6 leads to female sterility. M6 is expressed in the membrane of the follicular epithelium in ovarioles throughout oogenesis. Phenotypes triggered by M6 downregulation in hypomorphic mutants included egg collapse and egg permeability, thus suggesting M6 involvement in eggshell biosynthesis. In addition, RNAi-mediated M6 knockdown targeted specifically to follicle cells induced an arrest of egg chamber development, revealing that M6 is essential in oogenesis. Interestingly, M6-associated phenotypes evidenced abnormal changes of the follicle cell shape and disrupted follicular epithelium in mid- and late-stage egg chambers. Therefore, we propose that M6 plays a role in follicular epithelium maintenance involving membrane cell remodeling during oogenesis in Drosophila.


Effect of interleukin-1 and dexamethasone on interleukin-6 production and growth in human meningiomas.
Interleukin-6 (IL-6) has been shown to be released by cultured human meningioma cells and may be a positive or negative regulator of tumour growth. IL-6 protein and mRNA levels have been examined in a series of meningiomas. In 14 cases, the results are compared with the effects of IL-6 and dexamethasone on growth and IL-6 secretion in vitro. Tumours with the highest in vivo IL-6 mRNA expression also showed maximum induction of IL-6 and increased cellular proliferation on IL-1 stimulation in vitro. Dexamethasone decreased the IL-1-stimulated IL-6 release in all cases. Meningiomas which had little or no IL-6 message were refractory to IL-1 control of IL-6. Remarkably, these formed the group of meningiomas that increased their growth rate in response to dexamethasone.


The signaling petri net-based simulator: a non-parametric strategy for characterizing the dynamics of cell-specific signaling networks.
Reconstructing cellular signaling networks and understanding how they work are major endeavors in cell biology. The scale and complexity of these networks, however, render their analysis using experimental biology approaches alone very challenging. As a result, computational methods have been developed and combined with experimental biology approaches, producing powerful tools for the analysis of these networks. These computational methods mostly fall on either end of a spectrum of model parameterization. On one end is a class of structural network analysis methods; these typically use the network connectivity alone to generate hypotheses about global properties. On the other end is a class of dynamic network analysis methods; these use, in addition to the connectivity, kinetic parameters of the biochemical reactions to predict the network's dynamic behavior. These predictions provide detailed insights into the properties that determine aspects of the network's structure and behavior. However, the difficulty of obtaining numerical values of kinetic parameters is widely recognized to limit the applicability of this latter class of methods. Several researchers have observed that the connectivity of a network alone can provide significant insights into its dynamics. Motivated by this fundamental observation, we present the signaling Petri net, a non-parametric model of cellular signaling networks, and the signaling Petri net-based simulator, a Petri net execution strategy for characterizing the dynamics of signal flow through a signaling network using token distribution and sampling. The result is a very fast method, which can analyze large-scale networks, and provide insights into the trends of molecules' activity-levels in response to an external stimulus, based solely on the network's connectivity. We have implemented the signaling Petri net-based simulator in the PathwayOracle toolkit, which is publicly available at http://bioinfo.cs.rice.edu/pathwayoracle. Using this method, we studied a MAPK1,2 and AKT signaling network downstream from EGFR in two breast tumor cell lines. We analyzed, both experimentally and computationally, the activity level of several molecules in response to a targeted manipulation of TSC2 and mTOR-Raptor. The results from our method agreed with experimental results in greater than 90% of the cases considered, and in those where they did not agree, our approach provided valuable insights into discrepancies between known network connectivities and experimental observations.


El'gygytgyn impact crater, Chukotka, Arctic Russia: Impact cratering aspects of the 2009 ICDP drilling project.
The El'gygytgyn impact structure in Chukutka, Arctic Russia, is the only impact crater currently known on Earth that was formed in mostly acid volcanic rocks (mainly of rhyolitic, with some andesitic and dacitic, compositions). In addition, because of its depth, it has provided an excellent sediment trap that records paleoclimatic information for the 3.6 Myr since its formation. For these two main reasons, because of the importance for impact and paleoclimate research, El'gygytgyn was the subject of an International Continental Scientific Drilling Program (ICDP) drilling project in 2009. During this project, which, due to its logistical and financial challenges, took almost a decade to come to fruition, a total of 642.3 m of drill core was recovered at two sites, from four holes. The obtained material included sedimentary and impactite rocks. In terms of impactites, which were recovered from 316.08 to 517.30 m depth below lake bottom (mblb), three main parts of that core segment were identified: from 316 to 390 mblb polymict lithic impact breccia, mostly suevite, with volcanic and impact melt clasts that locally contain shocked minerals, in a fine-grained clastic matrix; from 385 to 423 mblb, a brecciated sequence of volcanic rocks including both felsic and mafic (basalt) members; and from 423 to 517 mblb, a greenish rhyodacitic ignimbrite (mostly monomict breccia). The uppermost impactite (316-328 mblb) contains lacustrine sediment mixed with impact-affected components. Over the whole length of the impactite core, the abundance of shock features decreases rapidly from the top to the bottom of the studied core section. The distinction between original volcanic melt fragments and those that formed later as the result of the impact event posed major problems in the study of these rocks. The sequence that contains fairly unambiguous evidence of impact melt (which is not very abundant anyway, usually less than a few volume%) is only about 75 m thick. The reason for this rather thin fallback impactite sequence may be the location of the drill core on an elevated part of the central uplift. A general lack of large coherent melt bodies is evident, similar to that found at the similarly sized Bosumtwi impact crater in Ghana that, however, was formed in a target composed of a thin layer of sediment above crystalline rocks.


Prospects of plant-derived exosome-like nanocarriers in oncology and tissue engineering.
Almost all cell types, either in vivo or in vitro, create extracellular vesicles (EVs). Among them are exosomes (EXOs), i.e., tiny nanovesicles containing a lipid bilayer, proteins, and RNAs that are actively involved in cellular communication, indicating that they may be exploited as both diagnostics and therapeutics for conditions like cancer. These nanoparticles can also be used as nanocarriers in many types of research to carry agents such as drugs. Plant-derived exosome-like nanoparticles (PENs) are currently under investigation as a substitute for EXOs formed from mammalian cells, allowing researchers to get beyond the technical constraints of mammalian vesicles. Because of their physiological, chemical, and biological properties, PENs have a lot of promise for use as nanocarriers in drug delivery systems that can deliver various dosages, especially when it comes to large-scale repeatability. The present study has looked at the origins and isolation techniques of PENs, their anticancer properties, their usage as nanocarriers in the treatment of different illnesses, and their antioxidant properties. These nanoparticles can aid in the achievement of therapeutic objectives, as they have benign, non-immunogenic side effects and can pass biological barriers. Time-consuming and perhaps damaging PEN separation techniques is used. For the current PEN separation techniques to be used in commercial and therapeutic settings, they must be altered. In this regard, the concurrent application of biological sciences can be beneficial for improving PEN separation techniques. PENs' innate metabolic properties provide them a great deal of promise for application in drug delivery systems. However, there could be a risk to both the loaded medications and the intrinsic bioactive components if these particles are heavily armed with drugs. Therefore, to prevent these side effects, more studies are needed to devise sophisticated drug-loading procedures and to learn more about the physiology of PENs.


Extending PTR based breath analysis to real-time monitoring of reactive volatile organic compounds.
Reactive exhaled volatile organic compounds (VOCs) such as nitrogen- and sulfur-containing substances may be related to diseases, metabolic processes and bacterial activity. As these compounds may interact with any surface of the analytical system, time-resolved monitoring and reliable quantification is difficult. We describe a proton transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS) based analytical method for direct breath-resolved monitoring of reactive compounds. Aliphatic amines were used as test substances. Matrix adapted gas standards were generated by means of a liquid calibration unit. Calibration conditions were adapted in terms of materials, temperature and equilibration time. PTR-ToF-MS conditions were optimized in terms of inlet materials, transfer line and drift tube temperature and drift tube reduced electric field (E/N). Optimized PTR conditions in combination with inert materials and high temperatures considerably reduced the interactions of compounds with the surfaces of the analytical system. Good linearity (R2 > 0.99, RSDs < 5%) with LODs between 0.15 ppbV and 1.23 ppbV and LOQs between 0.24 ppbV and 1.94 ppbV could be achieved. The method was then applied to breath-resolved monitoring of reactive compounds in 17 healthy subjects after high and low oral protein challenge. Exhaled concentrations of trimethylamine, indole, methanethiol, dimethylsulfide, acetone, 2-propanol, 2-butanone and phenol showed significant changes after protein intake. Methanethiol concentrations increased 6-fold within minutes after the protein intake. Optimization of methods and instrument design enabled reliable breath-resolved PTR-MS based analysis of exhaled reactive VOCs in the sub-ppbV range. Continuous in vivo monitoring of exhaled amines and sulphur containing compounds may provide novel non-invasive insight into endogenous and gut bacteria driven protein metabolism.


Invasive pneumococcal disease (IPD) in HIV infected patients in Israel since the introduction of pneumococcal conjugated vaccines (PCV): Analysis of a nationwide surveillance study, 2009-2014.
to assess the incidence, risk factors and outcome of invasive pneumococcal disease (IPD) among the Israeli HIV population. A matched case-control study nested in a nationwide, prospective, population-based, cohort of adult IPD was performed. In addition, the HIV-IPD patients were compared to the general adult HIV population in Israel. from the introduction of PCV into the national immunization program (NIP) in July 2009 to June 2014. Each HIV patient within the IPD cohort was matched to 4 non-HIV controls. Serotyping was performed by a central laboratory using the Quellung reaction. Thirty-five IPD episodes in 33 HIV patients were identified, with a median annual incidence of 128/100,000 HIV+ persons compared to 5.1/100,000 in the age-matched, non-HIV population. Compared to the general HIV population, HIV-IPD patients practiced intravenous drug use more frequently and originated from a country with generalized epidemic (OGE), mainly non-citizens lacking medical insurance. The proportion of men who have sex with men (MSM) was lower than in the general HIV population. Pneumonia was the most common clinical presentation (81%), while meningitis occurred in only one patient. Outcomes were similar to those of the IPD non-HIV population. Nineteen serotypes were identified, of which only 42% were covered by PCV13 vaccine. By 2014, none of the HIV-IPD cases belonged to serotypes covered by PCV13. In conclusion, most HIV IPD cases were from marginalized populations with poor access to health services. A decrease in IPD cases covered by PCV 13 was observed.


Comparative proteomic analysis of BTH and BABA-induced resistance in pea (Pisum sativum) toward infection with pea rust (Uromyces pisi).
Systemic acquired resistance (SAR) to Uromyces pisi in pea was studied by using a proteomic approach. Two-dimensional electrophoresis (2-DE) was used in order to compare the leaf proteome of two pea genotypes displaying different phenotypes (susceptible and partial resistance to the fungus), and in response to parasite infection under the effect of two inducers of SAR, BTH and BABA. Multivariate statistical analysis identified 126 differential protein spots under the experimental conditions (genotypes/treatments). All of these 126 protein spots were subjected to MALDI-TOF/TOF mass spectrometry to deduce their possible functions. A total of 50 proteins were identified using a combination of peptide mass fingerprinting (PMF) and MSMS fragmentation. Most of the identified proteins corresponded to enzymes belonging to photosynthesis, metabolism, biosynthesis, binding and defense response, whose behavior pattern was different in relation to susceptibility/resistance of the genotypes studied and to the BTH/BABA induction to pathogen response. Results obtained in this work suggested that plants could reduce their photosynthesis and other energy metabolism and enhance the production of defense-related proteins to cope the stress. On the other side, we postulated that resistance induced by the chemicals operates via different mechanisms: BABA inducer could act via phenolic biosynthesis pathway, whereas resistance provided by BTH inducer seems to be mediated by defense and stress-related proteins. The results are discussed in terms of response to rust under the effect of inducers.


Susceptibility to alcohol-related liver injury.
Alcohol affects the liver through metabolic disturbances associated with its oxidation. Redox changes produced by the hepatic alcohol dehydrogenase pathway affect lipid, carbohydrate and protein metabolism. Ethanol is also oxidized in liver microsomes by the ethanol-inducible cytochrome P4502E1, resulting in ethanol tolerance and selective hepatic perivenular damage. Furthermore, P4502E1 activates various xenobiotics, explaining the increased susceptibility of the heavy drinker to the toxicity of anesthetics, commonly used medications (i.e. isoniazid), analgesics (i.e. acetaminophen), and chemical carcinogens. Induction of microsomal enzymes also contributes to vitamin A depletion, enhances its hepatotoxicity and results in increased acetaldehyde generation from ethanol, with formation of protein adducts, glutathione depletion, free-radical-mediated toxicity, and lipid peroxidation. Chronic ethanol consumption strikingly enhances the number of hepatic collagen-producing activated lipocytes. Both in vivo (in our baboon model of alcoholic cirrhosis) and in vitro (in cultured myofibroblasts and activated lipocytes) ethanol and/or its metabolite acetaldehyde increase collagen accumulation and mRNA for collagen. Gender differences are related, in part, to lower gastric ADH activity (with consequent reduction of first pass ethanol metabolism) in young women, decreased hepatic fatty acid binding protein and increased free-fatty acid levels as well as lesser omega-hydroxylation, all of which result in increased vulnerability to ethanol. Elucidation of the biochemical effects of ethanol are now resulting in improved therapy: in baboons, S-adenosyl-L-methionine attenuates the ethanol-induced glutathione depletion and associated mitochondrial lesions, and polyenylphosphatidylcholine opposes the ethanol-induced hepatic phospholipid depletion, the decrease in phosphatidylethanolamine methyltransferase activity and the activation of hepatic lipocytes, with full prevention of ethanol-induced septal fibrosis and cirrhosis; its dilinoleoyl species also increases collagenase activity in lipocytes. The efficacy of this compound in man is now being studied in randomized multicenter clinical trials.


Intergranular Strain Evolution During Biaxial Loading: A Multiscale FE-FFT Approach.
Predicting the macroscopic and microscopic mechanical response of metals and alloys subjected to complex loading conditions necessarily requires a synergistic combination of multiscale material models and characterization techniques. This article focuses on the use of a multiscale approach to study the difference between intergranular lattice strain evolution for various grain families measured during in situ neutron diffraction on dog bone and cruciform 316L samples. At the macroscale, finite element simulations capture the complex coupling between applied forces and gauge stresses in cruciform geometries. The predicted gauge stresses are used as macroscopic boundary conditions to drive a mesoscale full-field elasto-viscoplastic fast Fourier transform crystal plasticity model. The results highlight the role of grain neighborhood on the intergranular strain evolution under uniaxial and equibiaxial loading.


Local RNA translation at the synapse and in disease.
Local regulation of protein synthesis in neurons has emerged as a leading research focus because of its importance in synaptic plasticity and neurological diseases. The complexity of neuronal subcellular domains and their distance from the soma demand local spatial and temporal control of protein synthesis. Synthesis of many synaptic proteins, such as GluR and PSD-95, is under local control. mRNA binding proteins (RBPs), such as FMRP, function as key regulators of local RNA translation, and the mTORC1 pathway acts as a primary signaling cascade for regulation of these proteins. Much of the regulation occurs through structures termed RNA granules, which are based on reversible aggregation of the RBPs, some of which have aggregation prone domains with sequence features similar to yeast prion proteins. Mutations in many of these RBPs are associated with neurological diseases, including FMRP in fragile X syndrome; TDP-43, FUS (fused in sarcoma), angiogenin, and ataxin-2 in amyotrophic lateral sclerosis; ataxin-2 in spinocerebellar ataxia; and SMN (survival of motor neuron protein) in spinal muscular atrophy.


Therapies for treatment of osteoporosis in US women: cost-effectiveness and budget impact considerations.
To evaluate the cost-effectiveness of osteoporosis treatments for women at high fracture risk and estimate the population-level impact of providing bisphosphonate therapy to all eligible high-risk US women. Fractures, healthcare costs, and quality-adjusted life-years (QALYs) were estimated over 10 years using a Markov model. No therapy, risedronate, alendronate, ibandronate, and teriperatide (PTH) were compared among 4 risk groups. Sensitivity analyses examined the robustness of model results for 65-year-old women with low bone density and previous vertebral fracture. Women treated with a bisphosphonate experienced fewer fractures and more QALYs compared with no therapy or PTH. Total costs were lowest for the untreated cohort, followed by risedronate, alendronate, ibandronate, and PTH in all risk groups except women aged 75 years with previous fracture. The incremental cost-effectiveness of risedronate compared with no therapy ranged from cost saving for the base case to $66,722 per QALY for women aged 65 years with no previous fracture. Ibandronate and PTH were dominated in all risk groups. (A dominated treatment has a higher cost and poorer outcome.) Treating all eligible women with a bisphosphonate would cost an estimated additional $5563 million (21% total increase) and would result in 390,049 fewer fractures (35% decrease). In the highest risk group, the additional cost of therapy was offset by other healthcare cost savings. Osteoporosis treatment of high-risk women is cost-effective, with bisphosphonates providing the most benefit at lowest cost. For highest risk women, costs are offset by savings from fracture prevention.


The fable of "The Doctor and the Goose," by Charles Chauvin Boisclair Deléry, D.M.P.
Charles Chauvin Boisclair Deléry, D.M.P. - doctor of medicine of Paris, was perhaps the prototypical representative of Creole physicians, practising medicine in Louisiana in the 1800s, who were regarded as being equally proficient with pen, pills or pistols. This paper presents accounts of Deléry's yellow fever debate with Jean-Charles Faget, D.M.P., and their near duel, and his famous duel with Joseph Rouanet. Because of the personal and professional need to maintain honor, Rouanet may have challenged Deléry to a duel, not only because of vociferous disagreements between them over blood transfusion safety and efficacy, but due to Deléry's humiliation of Rouanet in his fable, "the Doctor and the Goose." We recovered the poem, transcribed and translated it, and discuss it as a device of witty rhetorical persuasion-a technique of the time used to belittle one's learned opponents. Fortunately, Deléry was not as equally proficient with pens and pistols, as both he and Rouanet survived the duel.


Treponema isoptericolens sp. nov., a novel spirochaete from the hindgut of the termite Incisitermes tabogae.
A novel spirochaete, Treponema sp. strain SPIT5T, was isolated from hindgut contents of the drywood termite Incisitermes tabogae (Snyder). The cells of strain SPIT5T were motile, helical in shape, 0.4-0.5 microm in diameter and generally 12-20 microm long. The strain is obligately anaerobic and ferments different mono-, di- and oligosaccharides by forming ethanol as the main liquid fermentation end product. Furthermore, strain SPIT5T was able to grow anaerobically with yeast extract as sole carbon and energy source. Fastest growth was obtained at 30 degrees C, the temperature at which the termites were also grown. The optimum pH for growth was 7.2, with a range of pH 6.5-8.0. The cells possessed various enzyme activities that are involved in the degradation of lignocellulose in the termite hindgut, such as beta-d-glucosidase, alpha-l-arabinosidase and beta-d-xylosidase. The G+C content of the DNA was 47.7 mol%. Based on 16S rRNA gene sequence analysis, strain SPIT5T was shown to belong to the so-called 'termite cluster I' of the genus Treponema. The closest relative of strain SPIT5T was Treponema primitia ZAS-2T, with 92.3 % sequence similarity. On the basis of its phenotypic and genotypic properties, strain SPIT5T can be distinguished from other described species of the genus Treponema. Therefore, strain SPIT5T represents a novel species of Treponema, for which the name Treponema isoptericolens sp. nov. is proposed. The type strain is strain SPIT5T (=DSM 18056T =JCM 13955T).


A case of vitiligo after COVID-19 vaccination: a possible role of thymic dysfunction.
During the coronavirus disease 2019 (COVID-19) pandemic, vaccines help control the spread of infection. To date, 47 vaccines have been approved, with another 227 candidates in various stages of development. In the short period of time since the beginning of their use, evidence has begun to emerge of complications following vaccination in the form of the development or exacerbation of a number of pathological conditions (Block et al., 2022; Haseeb et al., 2022). For example, a population-based study in France identified 1612 cases of myocarditis and 1613 cases of pericarditis requiring hospital treatment within five months of vaccination (le Vu et al., 2022).


Adrenal relapse of primary central nervous system diffuse large B-cell lymphoma: A case report.
Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma with a dismal outcome. Most patients relapse in intracranial sites and <5% of patients relapse in extracranial sites. Here, we present the first case of PCNSL with an adrenal relapse. A 72-year-old woman, first presented 7 years ago with complaints of headache and dizziness. Enhanced magnetic resonance imaging revealed the mass within the splenium of the corpus callosum. On histological examination, there was a diffuse growth pattern of neoplastic cells in the brain biopsy. Immunohistochemistry and flow cytometric analysis demonstrated that the neoplastic cells were of B-cell lineage. The patient underwent methotrexate-based chemotherapy and whole-brain radiotherapy after the initial diagnosis of primary central nervous system-large B-cell lymphoma (CNS-DLBCL). After 4 years of clinical remission, the patient was diagnosed with endometrial cancer. Interestingly, a radiological study following the treatment of endometrial cancer demonstrated a right adrenal mass, which was suspicious for malignancy. Morphologic examination and immunohistochemistry studies confirmed the diagnosis of diffuse large B-cell lymphoma. A fluorescent in situ hybridization panel for lymphoma showed rearrangement of Immunoglobulin heavy chain (IGH) and B-cell lymphoma 6 (BCL6), respectively, suggesting fusion of BCL6/IGH. Immunoglobulin kappa analysis demonstrated a common origin for the brain and adrenal lesions, which led to the final diagnosis of an adrenal relapse of CNS-DLBCL. PCNSL is a highly infiltrative neoplasm, particularly at relapse. To the best of our knowledge, this is the first case of CNS-DLBCL with adrenal relapse. Considering the poor outcome of CNS-DLBCL, molecular genetic studies should be done to identify a common origin for the primary and secondary lesion.


Spleen ultrasound elastography: state of the art and future directions - a systematic review.
An early and accurate diagnosis of clinically significant portal hypertension is mandatory for a correct prediction and management of the complications usually observed in patients affected by chronic liver disease (CLD). Spleen stiffness measurement is arising as a promising non-invasive technique, giving a reliable measure of haemodynamic changes occurring during cirrhosis progression, but contrasting data are available to date. A systematic review was performed including the several studies dealing with the spleen stiffness measurement in the evaluation of portal hypertension in adult patients affected by hepatic or extra-hepatic portal hypertension (PH). Results were organized in technical classification from the first one-dimensional device (TE) to the latest ultrasound elastographic techniques (pSWE and 2D-SWE). We evaluated a total of nearly twenty studies dealing with all available elastographic techniques that were usually compared with HVPG, which is the gold standard for diagnosing the presence of PH. Spleen stiffness showed overall a good diagnostic accuracy to diagnose clinically significant PH in CLD, in some cases even with reliable cut-off values for severe PH. Spleen ultrasound elastography could be an accurate non-invasive tool for assessing the presence of portal hypertension. However, the different techniques available to date and the various cut-off values suggested might still limit the impact on clinical practice.


The Meshless Analysis of Scale-Dependent Problems for Coupled Fields.
The meshless local Petrov-Galerkin (MLPG) method was developed to analyze 2D problems for flexoelectricity and higher-grade thermoelectricity. Both problems were multiphysical and scale-dependent. The size effect was considered by the strain and electric field gradients in the flexoelectricity, and higher-grade heat flux in the thermoelectricity. The variational principle was applied to derive the governing equations within the higher-grade theory of considered continuous media. The order of derivatives in the governing equations was higher than in their counterparts in classical theory. In the numerical treatment, the coupled governing partial differential equations (PDE) were satisfied in a local weak-form on small fictitious subdomains with a simple test function. Physical fields were approximated by the moving least-squares (MLS) scheme. Applying the spatial approximations in local integral equations and to boundary conditions, a system of algebraic equations was obtained for the nodal unknowns.


Transport of glucose by Bifidobacterium animalis subsp. lactis occurs via facilitated diffusion.
Two strains of Bifidobacterium animalis subsp. lactis were indistinguishable by several nucleic acid-based techniques; however, the type strain DSMZ 10140 was glucose utilization positive, while RB 4825, an industrially employed strain, was unable to grow rapidly on glucose as the principal carbon source. This difference was attributed to the presence of a low-affinity facilitated-diffusion glucose transporter identified in DSMZ 10140 but lacking in RB 4825. Uptake of D-[U-(14)C]glucose in DSMZ 10140 was stimulated by monovalent cations (ammonium, sodium, potassium, and lithium) and inhibited by divalent cations (calcium and magnesium). When competitor carbohydrates were included in the uptake assays, stereospecific inhibition was exhibited, with greater competition by methyl-beta-glucoside than methyl-alpha-glucoside. Significant inhibition (>30%) was observed with phloretin, an inhibitor of facilitated diffusion of glucose, whereas there was no inhibition by sodium fluoride, iodoacetate, sodium arsenate, sodium azide, 2,4-dinitrophenol, monensin, or valinomycin, which typically reduce energy-driven transport. Based on kinetic analyses, the mean values for K(t) and V(max) were 14.8 +/- 3.4 mM D-glucose and 0.13 +/- 0.03 micromol glucose/min/mg cell protein, respectively. Glucose uptake by several glucose-utilizing commercial strains of B. animalis subsp. lactis was also inhibited by phloretin, indicating the presence of facilitated diffusion glucose transporters in those strains. Since DSMZ 10140 has been previously reported to lack a functional glucose phosphoenolpyruvate phosphotransferase system, the glucose transporter identified here is responsible for much of the organism's glucose uptake.


New signs characteristic of myocardial bridging demonstrated by intracoronary ultrasound and Doppler.
Large discrepancies exist concerning the incidence of myocardial bridging. This has been reported to be 0.5%-2.5% following coronary angiography but 15%-85% following autopsy. The purpose of the study was to use intravascular ultrasound and intracoronary Doppler to study the morphology and flow characteristics of myocardial bridging in order to find feasible parameters of this syndrome. Intravascular ultrasound was performed in 62/69 patients in whom typical angiographic 'milking effects' were present. In 48 patients, intracoronary Doppler was performed. A specific, echolucent 'half moon' phenomenon surrounding the myocardial bridge was found in all the patients. The thickness of the half moon area was 0.47 +/- 0.19 mm in diastole and 0.52 +/- 0.23 mm in systole. There was systolic compression of the myocardial bridge with a lumen reduction during systole of 36.4 +/- 8.8%. Using intracoronary Doppler, a characteristic early diastolic 'finger tip' phenomenon was observed in 42 (87%) of the patients. All patients showed no or reduced antegrade systolic flow. Coronary flow velocity reserve was 2.03 +/- 0. 54. After intracoronary nitroglycerin injection, retrograde systolic flow occurred in 37 (77%) of the 48 patients, with a velocity of -22. 2 +/- 13.2 cm. s(-1). Intravascular ultrasound revealed atherosclerotic involvement of the proximal segment in 61 (88%) of the 69 patients, with an area stenosis of 42 +/- 13%. No plaques were found in the bridge or distal segments in the 62 patients in whom it was possible to introduce the ultrasound catheter throughout the bridging segment. Myocardial bridging is characterized by the following morphological and functional signs: a specific, echolucent half moon phenomenon over the bridge segment, which exists throughout the cardiac cycle; systolic compression of the bridge segment of the coronary artery; accelerated flow velocity at early diastole (finger-tip phenomenon); no or reduced systolic antegrade flow; decreased diastolic/systolic velocity ratio; retrograde flow in the proximal segment, which is provoked and enhanced by nitroglycerin injection.


[Laser-assisted tonsillotomy in children with obstructive sleep apnea and adenotonsillary hyperplasia--experiences as an outpatient procedure].
The adenotonsillar hyperplasia is the most relevant cause for the obstructive sleep apnea in children. Since several years laser-assisted tonsillotomy becomes more common as an alternative treatment especially in children having no tonsillitis history. The therapeutical effect of laser-assisted tonsillotomy in combination with the traditional adenotomy treating the obstructive sleep apnea in children has not yet been researched. In addition literature indicates less pain and fast recovery of the children compared to conventional tonsillectomy. Starting May 2000 until May 2004 laser-assisted tonsillotomy and adenotomy have been performed in 50 outpatient children, mean age of 5.3 +/- 1.7 years, with adenotonsillar hyperplasia and possible sleep apnea. Postoperatively the parents of the patients were questioned with an anonymous questionnaire. Pre- and postoperative symptoms and Brouillette score, the degree of pain and the post-surgical time of recovery have been investigated. 36 questionnaires have been evaluated. The follow-up time was between 4 weeks and 4 years (mean = 1.3 years). With regard to the symptoms snoring, difficulty breathing during sleep and apnea 32 of the children (89%) were symptom-free after laser-assisted tonsillotomy with adenotomy. The Brouillette-score improved significantly (p = 0.001), snoring was reduced in 91%, difficulty breathing in 93% and apnea in 100% of the children. The pain of the surgical intervention has been valued by the patient's parents as mild to moderate. Postoperatively 91.6% of the children recovered within 6 days (mean = 4.7 days), no bleeding occurred. Outpatient laser-assisted tonsillotomy with adenotomy can be recommended in children with adenotonsillar hyperplasia and possible obstructive sleep apnea. The surgical intervention is less painful, the children recover more quickly and the results on snoring, difficulty breathing and apnea are equal in comparison to conventional tonsillectomy with adenotomy. In addition the recommended procedure shows less post-operative complications.


Cholesterol, triglycerides, and the Five-Factor Model of personality.
Unhealthy lipid levels are among the leading controllable risk factors for coronary heart disease. To identify the psychological factors associated with dyslipidemia, this study investigates the personality correlates of cholesterol (total, LDL, and HDL) and triglycerides. A community-based sample (N=5532) from Sardinia, Italy, had their cholesterol and triglyceride levels assessed and completed a comprehensive personality questionnaire, the NEO-PI-R. All analyses controlled for age, sex, BMI, smoking, drinking, hypertension, and diabetes. Low Conscientiousness and traits related to impulsivity were associated with lower HDL cholesterol and higher triglycerides. Compared to the lowest 10%, those who scored in top 10% on Impulsivity had a 2.5 times greater risk of exceeding the clinical threshold for elevated triglycerides (OR=2.51, CI=1.56-4.07). In addition, sex moderated the association between trait depression (a component of Neuroticism) and HDL cholesterol, such that trait depression was associated with lower levels of HDL cholesterol in women but not men. When considering the connection between personality and health, unhealthy lipid profiles may be one intermediate biomarker between personality and morbidity and mortality.


The psychosocial impact of natural disasters among adult survivors: an integrative review.
The aim of this review was to identify the psychosocial impact of natural disasters on adult (over the age of 18 years) survivors. Databases searched included PsycInfo, CINAHL, Proquest, Ovid SP, Scopus, and Science Direct. The search was limited to articles written in English and published between 2002 and 2012. A total of 1,642 abstracts and articles were obtained during the first search; 39 articles were retained. The results indicate that PTSD is the most-studied psychosocial impact after a disaster. Mental health nurses have a significant role to play in supporting survivors and can assist with the development of resilience in community members.


[Exoprotease biosynthesis by an Actinomyces spheroides culture on a medium with limited carbon, nitrogen and sulfur sources].
The biosynthesis of exoproteases by Actinomyces spheroides 35 was studied in the conditions of limitation of the growth medium with the source of carbon, nitrogen and sulfur. The absence of these sources from the medium was found to induce the synthesis of exoproteases by the washed mycelium of Actinomyces spheroides. The enzymes were synthesized at a highest rate in the absence of nitrogen and sulfur sources. Protein as a sole source of carbon, nitrogen or sulfur in the medium suppressed rather than induced the biosynthesis of exoproteases by the culture.


Efficacy of ultrasound-guided core-needle biopsy in the diagnosis of hepatic alveolar echinococcosis: a retrospective analysis.
This study retrospectively analyzed the clinical data, laboratory results, imaging findings, and histopathological features of 28 patients who underwent ultrasound-guided core-needle biopsy from a hepatic lesion and were diagnosed with alveolar echinococcosis. Among 28 patients included in the study, 16 were females and 12 were males. The mean age of the studied population was 53 ± 16 years, and the age range was 18-79 years. The most common presenting symptom was abdominal pain, which was observed in 14 patients. A total of 36 lesions were detected in the patients' livers, out of which 7 had a cystic appearance. Hepatic vascular involvement, bile duct involvement, and other organ involvement were depicted in 14, 5, and 7 patients, respectively. The average number of cores taken from the lesions was 2.7, ranging between 2 and 5. In histopathological evaluation, PAS+ parasitic membrane structures were visualized on a necrotic background in all cases. Regarding seven patients, who were operated, the pathological findings of preoperative percutaneous biopsies were in perfect agreement with the pathological examinations after surgical resections. None of the patients developed major complications after biopsy. Ultrasound-guided core-needle biopsy is a minimally invasive, reliable, and effective diagnostic tool for the definitive diagnosis of hepatic alveolar echinococcosis.