Society for the Advancement of Disaster Nursing: Exploring the Path to Excellence.
Major disasters occurring within the Unites States require nursing participation as a component of a successful response. Disaster nursing includes the care of populations affected by disasters, public health emergencies, and mass casualty events, both natural and man-made. A unique knowledge base, abilities, and skills are needed to respond appropriately to health care and human service needs resulting from these events. Despite prior efforts to advance disaster nursing as a specialty, none were sustainable and a professional framework for establishing standards and guidelines remains lacking. Disaster nursing is a complex arena where the intersection of competence, scope of practice, regulation, and clinical guidelines continues to evolve. Professional credibility and our contribution to disaster response lie in our ability to articulate and advance professionalism. Disaster nursing as a specialty practice requires a similar foundational framework to nursing specialties recognized by the American Nurses Association within a model of professional practice in order to ensure population outcomes that are reflective of safe, quality, evidence-based practice. It is time to define a disaster nursing scope of practice, establish standards for care, identify best practices, and pursue the establishment of an independent professional organization within the field of disaster nursing. This will establish the necessary foundation for optimizing nursing's contribution to and support of the National Health Security Strategy. (Disaster Med Public Health Preparedness. 2017;11:641-646).


Mass vaccination against hepatitis B: the French example.
Mainland France is considered as a low endemicity area for hepatitis B, but the French Caribbean and Pacific territories are classified into areas of intermediate and high endemicity. In France vaccination programmes aimed at high-risk groups were started in 1982 (including health care workers and patients receiving blood products) and the immunization of babies born of hepatitis B virus surface antigen (HBsAg)-positive mothers was reinforced in 1992. Considering the drawbacks and limited effect of targeted vaccination policies, universal vaccination targeted particularly to the preadolescent and adolescent population was initiated in 1994. In 1995, hepatitis B virus (HBV) vaccination was included in the infant immunization schedule. However, the emotion generated by the claim that HBV vaccination could have led to the development of central nervous system demyelinating disorders resulted in a marked decline of HBV vaccine use, both in the pediatric (23.3% vaccination coverage in children less than 13 years old) and in the adult population. The current coverage rates are likely to be insufficient to bring about a significant reduction in the control of hepatitis B in France. The success of universal immunization is highly dependent on reinstating the confidence of the public and health care professionals in the safety and efficacy of hepatitis B vaccines.


Subdural haematoma and effusion in infancy.
Analysis of 116 cases of subdural haematoma and effusion in infancy showed that in 40% trauma was involved and in 5% meningitis was an aetiological factor; in the remainder there was no known antecedent disease. Apart from retinal or subhyaloid haemorrhages there were no clinical features pathognomonic of the condition, though vomiting was the commonest presenting symptom and a tense fontanelle the commonest finding on examination. Treatment by subdural pleural shunt operation, which allows the fluid to drain into the chest, where it is absorbed, was found to be effective, and there is no longer any justification for the older method of removal of the subdural membrane by craniotomy.


Concordance and Reliability of Photogrammetric Protocols for Measuring the Cervical Lordosis Angle: A Systematic Review of the Literature.
The aim of this study was to examine and interpret the concordance, accuracy, and reliability of photogrammetric protocols available in the literature for evaluating cervical lordosis in an adult population aged 18 to 59 years. A systematic search of 6 electronic databases (MEDLINE via PubMed, LILACS, CINAHL, Scopus, ScienceDirect, and Web of Science) located studies that assessed the reliability and/or concordance and/or accuracy of photogrammetric protocols for evaluating cervical lordosis, compared with radiography. Articles published through April 2016 were selected. Two independent reviewers used a critical appraisal tool (QUADAS and QAREL) to assess the quality of the selected studies. Two studies were included in the review and had high levels of reliability (intraclass correlation coefficient: 0.974-0.98). Only 1 study assessed the concordance between the methods, which was calculated using Pearson's correlation coefficient. To date, the accuracy of photogrammetry has not been investigated thoroughly. We encountered no study in the literature that investigated the accuracy of photogrammetry in diagnosing hyperlordosis of cervical spine. However, both current studies report high levels of intra- and interrater reliability. To increase the level of evidence of photogrammetry in the evaluation of cervical lordosis, it is necessary to conduct further studies using a larger sample to increase the external validity of the findings.


Pleiotropic effects of sphingosine-1-phosphate signaling to control human chorionic mesenchymal stem cell physiology.
Chorionic stem cells represent a promising opportunity for regenerative medicine. A deeper understanding of the stimuli that regulate their physiology, could lead to innovative clinical approaches. We revealed the presence of multiple sphingosine-1-phosphate (S1P) receptor isoforms in chorion-derived mesenchymal stem cells (CMSCs). Their activation simultaneously propagated from the plasma membrane through Gi and other heterotrimeric G proteins and further diverged toward extracellular-signal-regulated kinase 1/2 (ERK1/2), p38 and protein kinase D 1. At a functional level, S1P signaling inhibited CMSC migration, while promoting proliferation. Instead, a reduction of cell density was obtained when S1P was combined to treatments that increased cAMP intracellular concentration. Such surprising reduction of cell viability was relatively specific as it was not observed with stromal stem cells from bone marrow. Neither it was observed by activating analogous G proteins with bradykinin nor by inducing cell death via a cAMP-independent pathway. S1P could thus reveal novel keys to improve CMSC differentiation programs acting on cAMP concentration. Furthermore, S1P receptor agonists/antagonists could become instrumental in favoring CMSC engraftment by controlling cell motility.


Evidence for the chylomicron origin of lipids accumulating in diabetic eruptive xanthomas: a correlative lipid biochemical, histochemical, and electron microscopic study.
Plasma lipoprotein alterations in nine insulin-dependent diabetics with hyperlipemia have been related to the lipid accumulating in eruptive xanthomas evolving in these patients. Histochemical and electron microscopic examination of xanthomas have been correlated with the lipid analyses in order to obtain additional evidence regarding the lipoprotein origin of lipids accumulating in the lesions. Both analytical and morphologic evidence suggested that circulating chylomicrons significantly contribute to the xanthoma lipids. All the patients had large quantities of circulating triglyceriderich chylomicrons which carried approximately 70% of the triglyceride found in the plasma. The fatty acid pattern of chylomicron and xanthoma triglycerides were similar. Triglyceride constituted the major lipid found in the xanthomas when they were sampled during their eruption. These findings, take in conjunction with histochemical and electron microscopic evidence of chylomicron particles in the dermal capillary walls, support the theory that blood lipoproteins, and particularly chylomicrons, permeated the vascular walls and the triglycerides carried by these lipoproteins apparently accumulated in tissue macrophages and perithelial cells which evolved into foam cells. Initiation of appropriate therapy resulted in clearance of the chylomicronemia and a concomitant resolution of the xanthomas as reflected by a decrease in total xanthoma lipid. Sequential studies of resolving xanthomas in five patients revealed that xanthoma triglyceride was mobilized more rapidly than cholesterol, resulting in a redistribution of the xanthoma lipids, so that the resolving lesions were cholesterol rich. Consistent with this change in lipid composition, correlative electron microscopy revealed loss of amorphous material from many of the foam cell vacuoles.


Influence of Religiousness and Spirituality on Remission Rate, Mental Health, and Quality of Life of Patients With Active Crohn's Disease: A Longitudinal 2-Year Follow-up Study.
Studies on inflammatory bowel disease [IBD] have shown that religiousness and spirituality [R/S] were associated with better mental health and quality of life [QOL]. However, longitudinal studies assessing the impact of R/S on long-term clinical outcomes of Crohn's disease [CD] are scarce. The aim of this study was to assess the influence of R/S on the course of CD after a 2-year follow-up and to determine whether these R/S beliefs were associated with mental health and QOL. A longitudinal 2-year follow-up study was conducted at a referral centre for IBD, including patients with moderately to severely active CD. Clinical data, disease activity [Harvey-Bradshaw Index], QOL [Inflammatory Bowel Disease Questionnaire-IBDQ], depression and anxiety [Hospital Anxiety and Depression Scale-HADS], and R/S [Duke Religion Index-DUREL, Spirituality Self-Rating Scale-SSRS, and Spiritual/Religious Coping-SRCOPE scale] were assessed at baseline and at the end of the 2-year follow-up. Linear and logistic regression models were employed. A total of 90 patients [88.2%] were followed up for 2 years. On logistic regression, baseline levels of spirituality (odds ratio [OR] = 1.309; 95% confidence interval [CI]= 1.104-1.552, p = 0.002) and intrinsic religiousness [OR = 1.682; 95% CI = 1.221-2.317, p = 0.001] were predictors of remission at 2 years. On linear regression, the different dimensions of R/S did not significantly predict IBDQ or anxiety and depression scores after 2 years. R/S predicted remission of CD patients after a 2-year follow-up. However, these beliefs failed to predict mental health or QOL. Health professionals who treat CD should be aware of the religious and spiritual beliefs of their patients, given these beliefs may impact on the disease course.


Molecular mechanisms of human herpes viruses inferring with host immune surveillance.
Several human herpes viruses (HHVs) exert oncogenic potential leading to malignant transformation of infected cells and/or tissues. The molecular processes induced by viral-encoded molecules including microRNAs, peptides, and proteins contributing to immune evasion of the infected host cells are equal to the molecular processes of immune evasion mediated by tumor cells independently of viral infections. Such major immune evasion strategies include (1) the downregulation of proinflammatory cytokines/chemokines as well as the induction of anti-inflammatory cytokines/chemokines, (2) the downregulation of major histocompatibility complex (MHC) class Ia directly as well as indirectly by downregulation of the components involved in the antigen processing, and (3) the downregulation of stress-induced ligands for activating receptors on immune effector cells with NKG2D leading the way. Furthermore, (4) immune modulatory molecules like MHC class Ib molecules and programmed cell death1 ligand 1 can be upregulated on infections with certain herpes viruses. This review article focuses on the known molecular mechanisms of HHVs modulating the above-mentioned possibilities for immune surveillance and even postulates a temporal order linking regular tumor immunology with basic virology and offering putatively novel insights for targeting HHVs.


Application of induced pluripotent stem cells in generation of a tissue-engineered tooth-like structure.
Stem cells, such as adult stem cells or embryonic stem cells, are the most important seed cells employed in tooth tissue engineering. Even though dental-derived stem cells are a good source of seed cells for such procedures, they are not often used in clinical applications because of the limited supply. Induced pluripotent stem (iPS) cells, with their high proliferation and differentiation ability, are now considered a promising alternative. The objectives of this study were to assess the role of iPS cells in tooth tissue engineering. We used real-time polymerase chain reaction to confirm that mouse iPS (miPS) cells can be induced to express both odontogenic and osteogenic gene profiles. We then established a tooth germ model and transplanted the recombinant tooth germ into a mouse subrenal capsule for 4 weeks to reproduce early-tooth organogenesis. After 4 weeks, hematoxylin and eosin staining results showed newly formed bone-like and dental pulp-like areas. Further immunohistochemical staining confirmed that osteopontin was present in the apical part of the tooth-like structure. These results demonstrate that miPS cells have the potential to differentiate into odontogenic cells, confirming that they could be a new source of seed cells for use in tooth tissue engineering.


Transcriptional regulation of mithramycin biosynthesis in Streptomyces argillaceus: dual role as activator and repressor of the PadR-like regulator MtrY.
The mithramycin biosynthesis gene cluster of Streptomyces argillaceus ATCC 12956 contains 34 ORFs and includes two putative regulatory genes (mtmR and mtrY), which encode proteins of the SARP (Streptomyces antibiotic regulatory protein) and PadR transcriptional regulator families, respectively. MtmR was proposed to behave as a positive regulator of mithramycin biosynthesis. Inactivation and overexpression of mtrY indicated that it is also a positive regulator of mithramycin biosynthesis, being non-essential but required to maintain high levels of mithramycin production in the producer strain. Transcriptional analyses by reverse transcription PCR and quantitative real-time PCR of mithramycin genes, and promoter-probe assays in S. argillaceus polyketide synthase and regulatory mutants and the WT strain, and in the heterologous host Streptomyces albus, were carried out to analyse the role of MtmR and MtrY in the regulation of the mithramycin gene cluster. These experiments revealed that MtmR had a positive role, activating expression of at least six polycistronic units (mtmR-mtmE, mtmQ-mtmTII, mtmX-mtmY, mtmV-mtmTIII, mtmW-mtmMI and mtmGI-mtrB) and one monocistronic unit (mtmGII) in the mithramycin gene cluster. However, MtrY played a dual role in the mithramycin gene cluster: (i) repressing the expression of resistance genes and its coding gene itself by controlling the activity of the mtrYp promoter that directs expression of the regulator mtrY and resistance genes, with this repression being released in the presence of mithramycin; and (ii) enhancing the expression of mithramycin biosynthesis genes when mithramycin is present, by interacting with the mtmRp promoter that controls expression of the mtmR regulator, amongst others.


[Food reward circuitry in obese patients].
Besides hormonal regulation of appetite and satiety, food intake depends on the activity of certain brain systems. Functional imaging studies are useful to better understand this central regulation of energy intake. Obesity is associated with increased brain responses to food stimuli at the level of the reward system. More specifically, studies have shown in obese individuals an increased motivation to obtain food reward as well as a decrease in pleasure during its actual consumption. Food consumption may be, in some instances, comparable to addiction, and be reflected by irresistible cravings for certain foods.


Cerium oxide nanoparticles at the nano-bio interface: size-dependent cellular uptake.
The authors investigated the role of different size and morphology of cerium oxide nanoparticles (CNPs) in cellular uptake and internalization at the nano-bio interface. Atomic force microscopy (AFM) has been utilized to record changes in the membrane elasticity as a function of ceria particle morphology and concentration. Young's Modulus was estimated in presence and absence of CNPs of different sizes by gauging the membrane elasticity of CCL30 (squamous cell carcinoma) cells. Significant change in Young's Modulus was observed for CNP treatments at higher concentrations, while minimum membrane disruption was observed at lower concentrations. Studies using blocking agents specific to energy-dependent cellular internalization pathways indicated passive cellular uptake for smaller CNPs (3-5 nm). Other observations showed that larger CNPs were unable to permeate the cell membrane, which indicates an active uptake mechanism by the cell membrane. The ability of smaller CNPs (3-5 nm) to permeate the cell membrane without energy consumption by uptake pathways suggests potential for use as nanovectors for the delivery of bioactive molecules. Specifically, the passive uptake mechanism allows for the delivery of surface-bound molecules directly to the cytoplasm, avoiding the extreme chemical conditions of endosomal pathways.


A VPS33A-binding motif on syntaxin 17 controls autophagy completion in mammalian cells.
Autophagy is an intracellular degradation pathway that transports cytoplasmic material to the lysosome for hydrolysis. It is completed by SNARE-mediated fusion of the autophagosome and endolysosome membranes. This process must be carefully regulated to maintain the organization of the membrane system and prevent mistargeted degradation. As yet, models of autophagosomal fusion have not been verified within a cellular context because of difficulties with assessing protein interactions in situ Here, we used high-resolution fluorescence lifetime imaging (FLIM)-FRET of HeLa cells to identify protein interactions within the spatiotemporal framework of the cell. We show that autophagosomal syntaxin 17 (Stx17) heterotrimerizes with synaptosome-associated protein 29 (SNAP29) and vesicle-associated membrane protein 7 (VAMP7) in situ, highlighting a functional role for VAMP7 in autophagosome clearance that has previously been sidelined in favor of a role for VAMP8. Additionally, we identified multimodal regulation of SNARE assembly by the Sec1/Munc18 (SM) protein VPS33A, mirroring other syntaxin-SM interactions and therefore suggesting a unified model of SM regulation. Contrary to current theoretical models, we found that the Stx17 N-peptide appears to interact in a positionally conserved, but mechanistically divergent manner with VPS33A, providing a late "go, no-go" step for autophagic fusion via a phosphoserine master-switch. Our findings suggest that Stx17 fusion competency is regulated by a phosphosite in its N-peptide, representing a previously unknown regulatory step in mammalian autophagy.


Infection with Trypanosoma Cruzi Chagas and Characterization of Human Habitats of Triatoma Picturata (Usinger) in Western Mexico.
Chagas disease is one of the most important vector-borne diseases in Latin America. Triatoma picturata (Usinger), distributed in western Mexico, is one of the most important vectors of Trypanosoma cruzi Chagas. Knowing the type and materials used for building homes could lead to improved methods for controlling triatomines by focusing efforts on controlling every species of triatomine in its specific microhabitat. Houses in three studied localities of western Mexico that harbored T. picturata were characterized, as well as two entomological indices. Infestation Index values varied from 10.8% to 51.9% in the three localities, whereas Natural Infection Index values varied from 18.1% to 35.2%. Characteristics of houses invaded by T. picturata also varied. In Juan Gil Preciado, with the highest Entomological Index values, most houses were built of adobe walls with a roof of clay tiles and a dirt floor, and included the presence of domestic animals. Our data indicate that the potential risk of infection with T. cruzi differs markedly for inhabitants of the three studied localities, which demonstrates the importance of studying local populations of triatomines. Our study should contribute to decision-making regarding triatomine control efforts by providing profiles of houses that are more susceptible to triatomine invasion.


Disease prevention and health promotion in urban areas: CDC's perspective.
The mission of the Centers for Disease Control and Prevention (CDC) is to prevent disease, injury, and premature death and to promote quality of life. This mission applies to all Americans, especially to the poor and underserved. As so many people who are impoverished live in America's urban areas, the CDC has a unique and specific interest in the health problems of our urban population. The CDC has established five priorities: (1) strengthen essential public health services, (2) enrich capacity to respond to urgent threats to health, (3) develop a nationwide prevention network and program, (4) promote women's health, and (5) invest in our nation's youth. Each of these priorities will contribute to improving the health of people living in urban areas. The CDC has recently undertaken numerous initiatives to address health promotion and disease prevention issues in the urban setting. Future directions for the CDC lie in better understanding the role of socioeconomic and cultural factors in promoting health and how resources within urban areas can be used to promote health. The CDC needs to explore potential relationships with various types of partners. Solving urban health problems requires actions from many federal agencies as well as from state and local organizations.


[The development of the physicochemical characteristics of the new original nootropic substance TST-9].
Physicochemical properties of the original pharmaceutical substance TST-9 based on the 3,7-diazabicyclo[3.3.1]nonane derivative with the chemical name IUPAC 6-[4methoxy-3-(1H-pyrazol-1-ylmethyl) benzyl]-1,11-dimethyl-3,6,9-triazatricyclo[184.108.40.206]tetradecane-4,8,12-trion, were studied. TST-9 is used as an active substance for the development of the composition and technology for the preparation of an innovative oral drug. The pharmaceutical substance TST-9 is an amorphous white powder, odorless, soluble in chloroform, acetonitrile, methylene chloride, acetone, dimethyl sulfoxide, dimethylformamide and alcohol, sparingly soluble in diethyl ether, dioxane and is very slightly soluble in water, hexane, and heptane. The melting point ranged from 94°C to 96°C without visible decomposition of the substance. The microbiological purity corresponds to category 2.2. Residual organic solvents in the form of chloroform did not exceed 0.006%. The amount of impurities was not more than 0.15%. The loss in mass upon drying was not more than 0.5%. The "identity" was confirmed using nuclear magnetic resonance spectroscopy and HPLC with UV detection. The data obtained in the study will contribute to the further development of the dosage form, the choice of the route of administration and the dosage regimen, as well as the selection of analytical methods for analyzing the quality of the finished dosage form and the effective, high-precision determination of the content of the active substance and its likely decay products.


Effect of Graft Weight to Recipient Body Weight Ratio on Hemodynamic and Metabolic Parameters in Pediatric Liver Transplant: A Retrospective Analysis.
To analyze how graft-weight-to-bodyweight ratio in pediatric liver transplant affects intraoperative and early postoperative hemodynamic and metabolic parameters. We reviewed data from 130 children who underwent liver transplant between 2005 and 2015. Recipients were divided into 2 groups: those with a graft weight to body weight ratio > 4% (large for size) and those with a ratio ≤ 4% (normal for size). Data included demographics, preoperative laboratory findings, intraoperative metabolic and hemodynamic parameters, and intensive care follow-up parameters. Patients in the large-graft-for-size group (>4%) received more colloid solution (57.7 ± 20.1 mL/kg vs 45.1 ± 21.9 mL/kg; P = .08) and higher doses of furosemide (0.7 ± 0.6 mg/kg vs 0.4 ± 0.7 mg/kg; P = .018). They had lower mean pH (7.1 ± 0.1 vs 7.2 ± 0.1; P = .004) and PO2 (115.4 ± 44.6 mm Hg vs 147.6 ± 49.3 mm Hg; P = .004) values, higher blood glucose values (352.8 ± 96.9 mg/dL vs 262.8 ± 88.2 mg/dL; P < .001), and lower mean body temperature (34.8 ± 0.7°C vs 35.2 ± 0.6°C; P = .016) during the neohepatic phase. They received more blood transfusions during both the anhepatic (30.3 ± 24.3 mL/kg vs 18.8 ± 21.8 mL/kg; P = .013) and neohepatic (17.7 ± 20.4 mL/kg vs 10.3 ± 15.5 mL/kg; P = .031) phases and more fresh frozen plasma (13.6 ± 17.6 mL/kg vs 6.2 ± 10.2 mL/kg; P = .012) during the neohepatic phase. They also were more likely to be hypotensive (P < .05) and to receive norepinephrine infusion more often (44% vs 22%; P < .05) intraoperatively. More patients in this group were mechanically ventilated in the intensive care unit (56% vs 31%; P = .035). There were no significant differences between the groups in postoperative acute renal dysfunction, graft rejection or loss, infections, length of intensive care stay, and mortality (P > .05). High graft weight-to-body-weight ratio is associated with adverse metabolic and hemodynamic changes during the intraoperative and early postoperative periods. These results emphasize the importance of using an appropriately sized graft in liver transplant.


Laparoscopic cholecystectomy in pregnancy.
Several recent literature reviews have shown that Laparoscopic cholecystectomy can be performed safely in pregnant females with symptomatic gallbladder disease. We have performed a retrospective analysis of all patients who underwent a cholecystectomy (6,080 patients) from January 1, 1990 until December 31, 1996 at San Pablo Medical Center. Lapa-cholecystecomy was performed in 4,252 (64%) and in the remaining 1,828 (36%) patients, an open cholecystectomy performed. Of the Laparoscopic cases, 5(0.1%) were performed in pregnant females with complicated gallbladder disease(GBD). The diagnosis of GBD was done with an abdominal sonogram. Four of the 5 patients had suffered from gallstones pancreatitis and one acute cholecystitis, prior to the operation. The records of patients were reviewed to secure the following variables, age, pre and post operative course and outcome. Intraoperative cholangiogram performed in 1 patient. No complications were seen in the mother or in the fetus in any of the five cases. Literature was reviewed to assess our reports. Pregnant females with complicated gallbladder disease can be safely managed with Laparoscopic cholecystectomy.


Macrophage migration inhibitory factor (MIF) is critical for the host resistance against Toxoplasma gondii.
Macrophage migration inhibitory factor (MIF) exerts either a protective or a deleterious role in the immune response to different pathogens. We analyzed herein the role of MIF in the host control of toxoplasmosis using MIF(-/-) mice backcrossed to either the BALB/c or the C57BL/6 genetic backgrounds. Both, wild-type (WT) BALB/c and MIF(-/-) BALB/c mice were susceptible to infection with highly virulent RH as well as moderately virulent ME49 strains of T. gondii. MIF(-/-) mice, however, showed greater liver damage and more brain cysts, produced less proinflammatory cytokines, and succumbed significantly faster than WT mice. Bone marrow-derived dendritic cells (BMDCs) from MIF(-/-) mice produced less interleukin-1beta, interleukin-12, and tumor necrosis factor-alpha than WT BMDCs after stimulation with soluble Toxoplasma antigen (STAg). Similar observations were made in CD11c(+) low-density cells isolated from the spleens of MIF(-/-) mice challenged with STAg. MIF(-/-) C57BL/6 mice succumbed to ME49 infection faster than their WT counterparts. C57BL/6 mice that succumbed to infection with the ME49 strain produced less MIF than resistant BALB/c mice similarly infected. Interestingly, an analysis of brains from patients with cerebral toxoplasmosis showed low levels of MIF expression. Together, these findings demonstrate that MIF plays a critical role in mediating host resistance against T. gondii.


Heart rate and suicide: findings from two cohorts of 533 000 Taiwanese and 75 000 Norwegian adults.
To investigate the association of resting heart rate with suicide in two large cohorts. The MJ cohort (Taiwan) included 532 932 adults from a health check-up programme (1994-2008). The HUNT cohort (Norway) included 74 977 adults in the Nord-Trøndelag County study (1984-1986), followed up to 2004. In both cohorts heart rate was measured at baseline, and suicide was ascertained through linkage to cause-of-death registers. Risk of suicide was estimated using Cox proportional hazards models. There were 569 and 188 suicides (average follow-up period of 8.1 and 16.9 years) in the MJ and HUNT cohorts respectively. Sex- and age-adjusted hazard ratio for every 10 beat increase in heart rate per minute was 1.08 (95% Confidence Interval 1.00-1.16) and 1.24 (1.12-1.38) in the MJ and HUNT cohorts, respectively. In the MJ cohort this association was confined to individuals with a history of heart diseases vs. those without such a history (P for interaction = 0.008). In the HUNT cohort the association did not differ by history of heart diseases and was robust to adjustment for health-related life style, medication use, and symptoms of anxiety and depression. Elevated resting heart rate may be a marker of increased suicide risk.


The role of topotecan for extending the platinum-free interval in recurrent ovarian cancer: an in vitro model.
Topotecan, a novel topoisomerase-I inhibitor, is an active agent of second-line chemotherapy for extending the platinum-free interval (PFI) and improving the chances of a response to platinum in recurrent ovarian cancer patients. The aim of this study was to understand the molecular mechanism of topotecan-based second-line chemotherapy through an in vitro cell culture model and to gain clinical insight into sequencing issues for second-line treatment with novel agents versus retreatment with platinum. The human ovarian cancer cell line A2780 and the cisplatin resistance cell line A2780-CR were separately seeded in 6-well cell culture plates and then exposed to multiple concentrations of cisplatin plus paclitaxel or topotecan for 7 days. Surviving cells were recovered and cultured in drug-free media for 3 weeks and then replated in a 96-well microtiter plate. The LD(50) for these cells was determined by a cytotoxic MTT assay after exposure to multiple clinically relevant concentrations of cisplatin or topotecan. Surviving cells were cultured in drug-free media for an additional 4 weeks at which time the LD(50) was reassessed for each cell population by a second MTT assay. Using RT-PCR and Northern blot hybridization to measure mRNA expression, the molecular profile of these cells in terms of resistance was evaluated for the multidrug-resistant gene (MDR-1), multidrug-resistant protein (MRP), Topoisomerase-I, and beta-Actin. The LD(50) to cisplatin was unchanged in A2780-CR cells treated by topotecan. Those A2780-CR cells originally exposed to higher concentrations of cisplatin became more resistant to cisplatin in the MTT assays, while those A2780-CR cell lines treated with a combination of lower cisplatin concentrations and paclitaxel became more sensitive to cisplatin in the MTT assay (P < 0.01). The second MTT assay demonstrated that the LD(50) for cisplatin in every cell line decreased significantly after a 4-week drug-free interval (P < 0.01). There was no difference in the mRNA expression for MRP or topoisomerase-I regardless of cell line, or type or concentration of chemotherapeutic exposure. The mRNA for MDR-1 was uniquely overexpressed in the cisplatin-resistant cell line A2780-CR9 initially treated with low doses of cisplatin and paclitaxel, but was not amplified in A2780 (P < 0.01). The acquired resistance to cisplatin in A2780 is potentially due to P-glycoprotein-mediated multidrug resistance. This acquired resistance to cisplatin is an unstable phenotype in that some cell populations become sensitive after a drug-free interval and topotecan treatment. This reversal of resistance, however, does not appear to be simply due to loss of MDR-1 expression. While in vivo confirmation is required, agents with novel mechanisms of action offer a strategy to extend the platinum-free interval and thereby improve survival in patients with recurrent ovarian cancer.


Concatenation of two molecular switches via a Fe(II)/Fe(III) couple.
[reaction: see text] Modulation of the fluorescein fluorescence in the presence of spiropyran and ferric ion by light was observed. Such fluorescence modulation was due to the low oxidation potential of complex MC.Fe(2+), which made the electron transfer from MC.Fe(2+) to Flu(+)()(*)() thermodynamically favorable. As a result, the communication between two molecular switches based on fluorescein and spiropyan, respectively, was realized via the reversible Fe(III)/Fe(II) redox couple. The communicating behavior corresponds well to the function of an INHIBIT logic gate.


Late breeding season definitive prebasic molt in males, and late breeding season brood care by females, in central California Wilson's warblers.
I made observations of a central California population of Wilson's Warbler, Cardellina pusilla, after July 1 over 10 breeding seasons. I sighted males in definitive prebasic molt from July 4 (in 2007) to September 1 (in 1999). Most territorial males molted on their breeding territories, and individual molt lasted up to 46 days. Following prebasic molt, territorial males engaged in subdued "post-molt singing," which lasted about 7 days in some males, and which I first heard on August 13 (in 2004) and last heard on September 6 (in 1999). I sighted no female in definitive prebasic molt, or in fresh basic plumage, during the study. Of 13 females sighted ≥ July 21, 11 were in late breeding season uniparental brood care, and I could not rule out late brood care for the other two. Most, and possibly all, females not engaged in late season uniparental brood care apparently vacated their breeding territories before July 21. This departure was much earlier than for resident males, the last of which I sighted on September 10 (in 1999). Early-departing females presumably underwent prebasic molt after July 21 at locations not known. Remaining late-nesting females must have molted much later than resident males and likely later than early-departing females, and at locations unknown. I last sighted two uniparental brood-tending females, still in worn plumage, on August 26 and 29, respectively. Two unique findings of this study are a male/female difference in location of prebasic molt, and a likely dichotomy of prebasic molt timing between females leaving their breeding territories early and those remaining in uniparental brood care. Another finding, post-molt singing in most and possible all territorial males, is a largely unrecognized behavior, but one previously reported in several passerine species. Post-molt singing may reliably indicate completion of prebasic molt.


Psychoeducation improves hepatitis C virus treatment during opioid substitution therapy: a controlled, prospective multicenter trial.
People who inject drugs (PWID) have a high prevalence of hepatitis C virus (HCV) infection. However, PWID are considered "difficult to treat," requiring a specifically adapted treatment setting, including psychosocial support. In this prospective, German trial, the impact of psychoeducation (PE) on retention and sustained virologic response (SVR) during HCV therapy among PWID was evaluated. We included 198 patients in opiate substitution therapy, who fulfilled indications for antiviral treatment. All patients received pegylated interferon alfa-2a and ribavirin therapy. Patients in the intervention group (n = 82) received manualized PE sessions. In patients with HCV genotype 1 or 4 (GT 1/4), PE was associated with increased treatment completion (76% vs 55%, P = .038), whereas PE had no such effect among GT 2/3 patients, who showed fewer dropouts and higher SVR rates. Among GT 1/4 patients, a minimum of 5 PE sessions was associated with increased SVR (71% vs 48%, P = .037). Multivariate regression analyses confirmed the impact of PE in GT 1/4 and revealed further predictors for retention and SVR, such as preexisting mental distress and adverse events. In patients with a higher risk of dropout due to GT 1/4 or mental distress, PE was shown to improve retention and SVR. PE is an effective supportive intervention for HCV therapy among PWID.


Cisplatin concurrent chemoradiotherapy vs adjuvant radiation in stage IB/IIA cervical cancer with intermediate risk factors, treated with radical surgery: a retrospective study.
To determine if postoperative cisplatin concurrent chemoradiotherapy (CCRT) improves the outcome in stage IA/IIB cervical cancer patients with intermediate risk factors, when compared with radiation therapy (RT) alone, and identify the potential eligible populations for this treatment. We reviewed medical records of 1,240 patients with stage IA/IIB cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy in our hospital between January 2008 and December 2011. Of the 1,240 patients, 436 displayed 1 or more intermediate risk factors. Of these, we screened 306 patients who underwent RT only or CCRT. We analyzed the effects of CCRT on survival and prognosis. The 5-year progress-free survival (PFS) in the CCRT group was superior to that in the RT-only group (96.0% vs 89.0%, respectively; P=0.031). The 5-year overall survivals (OSs) were not different between the 2 groups (P=0.141). Compared with RT-only group, CCRT did not improve PFS or OS in patients with 1 risk factor, large tumor size, or deep stromal invasion (P>0.05). Compared with RT-only group, CCRT improved PFS (97.9% vs 82.8%; P=0.017) but did not increase OS (97.9% vs 89.7%; P=0.109) in patients with lymphovascular space invasion plus deep stromal invasion/large tumor size. OS (92.3% vs 70.6%; P=0.048) and PFS (92.3% vs 64.7%; P=0.020) in the CCRT group were superior to those in the RT-only group with 3 risk factors. Compared with RT-only group, CCRT was an independent prognostic factor for favorable PFS (hazard ratio [HR] =0.238; 95% CI =0.0827-0.697, P=0.009) and OS (HR =0.192; 95% CI =0.069-0.533, P=0.002). Postoperative CCRT improved survival in stage IA/IIB cervical cancer patients with intermediate risk factors. Patients with 2 or more intermediate risk factors, including lymphovascular space invasion, may benefit from CCRT.


Effect of Semecarpus anacardium nuts on lipid peroxidation.
Alcoholic extract of pericarp showed significant protection against FeSO4 induced lipid peroxidation, as compared with whole native nut and seeds. Mechanism of action may be through metal chelation or activation of endogenous antioxidant enzymes, because the extract did not show hydroxyl and super oxide anion scavenging property. Further in vitro experiments against FeSO4, it did not maintain the level of reduced glutathione.


Phenomenally high molar extinction coefficient sensitizer with "donor-acceptor" ligands for dye-sensitized solar cell applications.
A phenomenally high molar extinction coefficient heteroleptic ruthenium(II) complex [Ru(4,4'-carboxylic acid-2,2'-bipyridine)(4,4'-(4-{4-methyl-2,5-bis[3-methylbutoxy]styryl}-2,5-bis[3-methylbutoxy]-2,2'-bipyridine)(NCS) 2] ( DCSC13) was synthesized by incorporating donor-acceptor ligands. The absorption spectrum of the DCSC13 sensitizer is dominated by metal-to-ligand charge-transfer transitions (MLCT) in the visible region, with absorption maxima appearing at 442 and 554 nm. The lowest MLCT absorption bands are red-shifted, and the molar extinction coefficients of these bands are significantly higher at 72,100 and 30,600 M(-1) cm(-1), respectively, when compared to those of the analogous [Ru(4,4'-carboxylic acid-2,2'-bipyridine)(4,4'-dimethyl-2,2'-bipyridine)(NCS)2] (N820) sensitizer. The DCSC13 complex, when anchored on nanocrystalline TiO 2 films, exhibited increased short-circuit photocurrent and consequent power-conversion efficiency when compared with the N820 sensitizer.


Primary healthcare teams' views on using mortality data to review clinical policies.
A UK-wide scheme to monitor mortality in general practices has been recommended to improve safety. A monitoring scheme might also have a role in improving quality by informing clinical policies. This study investigated the views of primary care teams on the desirable characteristics of mortality data to help them review and plan their clinical policies. 10 general practices in Leicestershire, UK. Development of a format for presentation of mortality data for primary care teams, presentations of the data to team meetings, and subsequent interviews of 16 general practitioners and nurses to identify issues about the improvement and use of the data for informing clinical policies. The presentation was important in helping teams to understand the data. Comparisons should be between practices with similar patient populations, and information provided on deaths from diseases potentially amenable to prevention through clinical intervention. Practice teams used the data in reflecting on their own clinical care. Presentation of data about mortality in practice populations can enable practices to reflect on their clinical policies. The proposed national scheme for monitoring mortality should provide data in a format that helps teams to improve the quality of care as well as improve patient safety.


Structure and Properties of Composite Fibers Based on Chitosan and Single-Walled Carbon Nanotubes for Peripheral Nerve Regeneration.
This study focused on a potential application of electrically conductive, biocompatible, bioresorbable fibers for tubular conduits aimed at the regeneration of peripheral nerves. The conducting, mechanical, and biological properties of composite fibers based on chitosan and single-walled carbon nanotubes were investigated in this paper. It was shown that introducing 0.5 wt.% of SWCNT into the composite fibers facilitated the formation of a denser fiber structure, resulting in improved strength (σ = 260 MPa) and elastic (E = 14 GPa) characteristics. Additionally, the composite fibers were found to be biocompatible and did not cause significant inflammation or deformation during in vivo studies. A thin layer of connective tissue formed around the fiber.


Wavelength dependency of photoparoxysmal responses in photosensitive nonepileptic subjects.
Using specially made optical filters, we analyzed the wavelength dependency of photoparoxysmal responses (PPRs) in five photosensitive nonepileptic subjects. The wavelength spectrum around 700 nm (680-700 nm) was estimated as the only visible spectrum essential for eliciting PPRs in two normal trichromat nonepileptic subjects, although the effect of some wavelength spectra (360-400 nm and 520-580 nm) was uncertain. The wavelength dependency of PPRs in two photosensitive nonepileptic subjects was the same as that found in some patients with photosensitive idiopathic generalized epilepsy.


Pattern of hemodynamic impairment in multiple sclerosis: dynamic susceptibility contrast perfusion MR imaging at 3.0 T.
This study aimed to determine regional pattern of tissue perfusion in the normal-appearing white matter (NAWM) of patients with primary-progressive (PP), relapsing-remitting (RR) multiple sclerosis (MS) and healthy controls, and to investigate the association between perfusion abnormalities and clinical disability. Using dynamic susceptibility contrast (DSC) perfusion MRI at 3 T, we studied 22 patients with clinically definite MS, 11 with PP-MS and 11 with RR-MS and 11 age- and gender-matched healthy volunteers. The MRI protocol included axial dual-echo, dynamic susceptibility contrast enhanced (DSC) T2*-weighted and post-contrast T1-weighted images. Absolute cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the periventricular, frontal, occipital NAWM and in the splenium of the corpus callosum. Compared to controls, CBF and CBV were significantly lower in all NAWM regions in both PP-MS patients (p values from <0.0001 to 0.001) and RR-MS (p values from <0.0001 to 0.020). Compared to RR-MS, PP-MS patients showed significantly lower CBF in the periventricular NAWM (p=0.002) and lower CBV in the periventricular and frontal NAWM (p values: 0.0029 and 0.022). EDSS was significantly correlated with the periventricular CBF (r=-0.48, p=0.0016) and with the periventricular and frontal CBV (r=-0.42, p=0.015; r=-0.35, p=0.038, respectively). This study suggests that the hemodynamic abnormalities of NAWM have clinical relevance in patients with MS. DSC perfusion MRI might provide a relevant objective measure of disease activity and treatment efficacy.


[High ileus with a prolonged course].
The authors describe the atypical development of a so-called high ileus caused by a bulky phytobezoar made up of tropical fruit. it is of interest that the organism managed to cope for two months relatively well with a condition described in surgical practice as acute abdomen where urgent or at least acute intervention is essential. The authors draw attention to pitfalls of out-patient care which may involve risk of delay due to incomplete evaluation by the specialists involved. This risk is particularly great during the present period of restructuring of the health services "hunting for a"high point score".


The myelin-associated oligodendrocytic basic protein region MOBP15-36 encompasses the immunodominant major encephalitogenic epitope(s) for SJL/J mice and predicted epitope(s) for multiple sclerosis-associated HLA-DRB1*1501.
Autoimmune response to the myelin-associated oligodendrocytic basic protein (MOBP), a CNS-specific myelin constituent, was recently suggested to play a role in the pathogenesis of multiple sclerosis (MS). The pathogenic autoimmune response to MOBP and the associated pathology in the CNS have not yet been fully investigated. In this study, we have characterized the clinical manifestations, pathology, T cell epitope-specificity, and TCRs associated with experimental autoimmune encephalomyelitis (EAE) induced in SJL/J mice with recombinant mouse MOBP (long isoform, 170 aa). Analysis of encephalitogenic MOBP-reactive T cells for reactivity to overlapping MOBP peptides defined MOBP15-36 as their major immunodominant epitope. Accordingly, MOBP15-36 was demonstrated to be the major encephalitogenic MOBP epitope for SJL/J mice, inducing severe/chronic clinical EAE associated with intense perivascular and parenchymal infiltrations, widespread demyelination, axonal loss, and remarkable optic neuritis. Molecular modeling of the interaction of I-A(s) with MOBP15-36, together with analysis of the MOBP15-36-specific T cell response to truncated peptides, suggests MOBP20-28 as the core sequence for I-A(s)-restricted recognition of the encephalitogenic region MOBP15-36. Although highly focused in their epitope specificity, the encephalitogenic MOBP-reactive T cells displayed a widespread usage of TCR Vbeta genes. These results would therefore favor epitope-directed, rather than TCR-targeted, approaches to therapy of MOBP-associated pathogenic autoimmunity. Localization by molecular modeling of a potential HLA-DRB1*1501-associated MOBP epitope within the encephalitogenic MOBP15-36 sequence suggests the potential relevance of T cell reactivity against MOBP15-36 to MS. The reactivity to MOBP15-36 detected in MS shown here and in another study further emphasizes the potential significance of this epitope for MS.


Helicobacter pylori Treatment and Gastric Cancer Risk After Endoscopic Resection of Dysplasia: A Nationwide Cohort Study.
The study investigated the association between Helicobacter pylori treatment and the risk of gastric cancer after endoscopic resection of gastric dysplasia. Patients who received endoscopic resection for gastric dysplasia between 2010 and 2020 from Korean nationwide insurance data were included. We verified the occurrence of new-onset gastric cancer and metachronous gastric neoplasm, which encompasses both cancer and dysplasia, >1 year after the index endoscopic resection. Newly diagnosed gastric cancer ≥3 years and ≥5 years was regarded as late-onset gastric cancer. A multivariable Cox regression model with H pylori treatment status as a time-dependent covariate was used to determine the risk of gastric cancer and metachronous gastric neoplasms. Gastric dysplasia in 69,722 patients was treated with endoscopy, and 49.5% were administered H pylori therapy. During the median 5.6 years of follow-up, gastric cancer developed in 2406 patients and metachronous gastric neoplasms developed in 3342 patients. Receiving H pylori therapy was closely related to lower gastric cancer risk (adjusted hazard ratio [aHR], 0.88; 95% confidence interval [CI], 0.80-0.96). H pylori treatment also significantly decreased metachronous gastric neoplasm development (aHR, 0.76; 95% CI, 0.70-0.82). Furthermore, H pylori therapy showed a prominent protective effect for late-onset gastric cancer development at ≥3 years (aHR, 0.84; 95% CI, 0.75-0.94) and ≥5 years (aHR, 0.80; 95% CI, 0.68-0.95). In this nationwide cohort, H pylori therapy after endoscopic resection of gastric dysplasia was associated with a reduced risk of gastric cancer and metachronous gastric neoplasm occurrence.


Reducing the genetic code induces massive rearrangement of the proteome.
Expanding the genetic code is an important aim of synthetic biology, but some organisms developed naturally expanded genetic codes long ago over the course of evolution. Less than 1% of all sequenced genomes encode an operon that reassigns the stop codon UAG to pyrrolysine (Pyl), a genetic code variant that results from the biosynthesis of Pyl-tRNA(Pyl). To understand the selective advantage of genetically encoding more than 20 amino acids, we constructed a markerless tRNA(Pyl) deletion strain of Methanosarcina acetivorans (ΔpylT) that cannot decode UAG as Pyl or grow on trimethylamine. Phenotypic defects in the ΔpylT strain were evident in minimal medium containing methanol. Proteomic analyses of wild type (WT) M. acetivorans and ΔpylT cells identified 841 proteins from >7,000 significant peptides detected by MS/MS. Protein production from UAG-containing mRNAs was verified for 19 proteins. Translation of UAG codons was verified by MS/MS for eight proteins, including identification of a Pyl residue in PylB, which catalyzes the first step of Pyl biosynthesis. Deletion of tRNA(Pyl) globally altered the proteome, leading to >300 differentially abundant proteins. Reduction of the genetic code from 21 to 20 amino acids led to significant down-regulation in translation initiation factors, amino acid metabolism, and methanogenesis from methanol, which was offset by a compensatory (100-fold) up-regulation in dimethyl sulfide metabolic enzymes. The data show how a natural proteome adapts to genetic code reduction and indicate that the selective value of an expanded genetic code is related to carbon source range and metabolic efficiency.


[Vaskuläre Dyspnoe: Pulmonale Hypertonie].
Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure > 20 mmHg [1] [2]. Echocardiography is used to screen for pulmonary hypertension, but right heart catheterization is required to confirm the diagnosis. Right heart catheterization is used to measure hemodynamic parameters such as pulmonary arterial pressures and pulmonary artery wedge pressure (PAWP), which normally corresponds to the left ventricular end-diastolic pressure. In addition, cardiac output (CO) is measured using the direct Fick method or thermodilution. The pulmonary vascular resistance (PVR) can be derived from these values. Precapillary PH is defined by PAWP ≤15 mmHg and PVR >2 WU (wood units), postcapillary PH is defined by increased PAWP > 15 mmHg with PVR 2 WU due to passive backflow [3]. However, there are also combined pre- and post-capillary PH with a PAWP > 15 mmHg and elevated PVR > 2 WU. Supportive therapies for all forms of PH include diuretics, supplemental oxygen in case of hypoxemia, gentle exercise under specialized supervision, and anticoagulants for some forms. Specific drug or interventional therapies are available only for pulmonary vascular disease subgroups pulmonary arterial hypertension (group 1) and chronic thromboembolic PH (CTEPH, group 4), while for PH due to heart and lung diseases (groups 2 and 3) as well as mixed forms the therapy of the underlying disease is of major importance. Drug therapy for pulmonary vascular diseases includes endothelin receptor antagonists, phosphodiesterase-5 inhibitors and prostanoids. CTEPH requires clarification regarding surgical pulmonary endarterectomy or interventional balloon angioplasty [4]. Since the diagnosis and therapy of PH is very complex, it must be carried out in an experienced center.


Preliminary Study of Coping, Perceived Control, and Depressive Symptoms in Youth with Sickle Cell Anemia.
The primary objective of this study was to test perceived controllability of stressors as a moderator of the association between coping and depressive symptoms in children and adolescents with sickle cell anemia (SCA). Twenty-eight children and adolescents (Mage = 11.71, SD = 4.31; 60.7% female) with SCA were enrolled. Caregivers provided reports of child and adolescent coping using the Response to Stress Questionnaire (RSQ), perceived control of stressors using the RSQ, and depressive symptoms using the Child Behavior Checklist. Children and adolescents also completed Wechsler assessments of working memory and verbal comprehension. Secondary control coping (i.e., cognitive reappraisal, positive thinking, acceptance, and distraction) was a significant predictor of depressive symptoms such that greater use of secondary control coping was related to fewer reported depressive symptoms when accounting for perceived control of stress and neurocognitive variables. Furthermore, perceived control of peer-related stress was a significant moderator of the association between secondary control coping and depressive symptoms such that there was a significant negative association of secondary control coping with depressive symptoms only for low perceived control. Secondary control coping may be particularly helpful for reducing depressive symptoms when adolescents' peer-related stressors are perceived as uncontrollable. Interventions to reduce internalizing problems in this population should consider teaching children and adolescents secondary control coping skills in addition to skills in identifying uncontrollable sources of stress.


Labware additives identified to be selective monoamine oxidase-B inhibitors.
Plastic labware is used in all processes of modern pharmaceutical research, including compound storage and biological assays. The use of these plastics has created vast increases in productivity and cost savings as experiments moved from glass test tubes and capillary pipettes to plastic microplates and multichannel liquid handlers. One consequence of the use of plastic labware, however, is the potential release of contaminants and their resultant effects on biological assays. We report herein the identification of biologically active substances released from a commonly used plastic microplate. The active contaminants were identified by gas chromatography-mass spectroscopy as dodecan-1-ol, dodecyl 3-(3-dodecoxy-3-oxopropyl)sulfanylpropanoate, and dodecanoic acid, and they were found to be selective monoamine oxidase-B inhibitors.


Demonstration of shared epitopes between bacterial proteins and HLA class-I proteins using monoclonal antibodies.
Monoclonal antibodies were used to identify the presence of epitopes on bacterial proteins which are cross-reactive with HLA-B27. Anti-HLA-B27 monoclonals, B27M2 and YE-2 reacted with a major protein of approximately 35 kDa, which was found to be OMPA. On some strains a 19 KDa protein was also seen. Anti-Shigella flexneri monoclonals were also developed which reacted with a 36 kDa protein and a 19 kDa protein. The 36 kDa protein was OMPF. These antibodies also reacted with a synthetic peptide representing amino acids 63-83 of the B*2705 sequence. These results support a potential role for molecular mimicry in the spondyloarthropathies.


Dendrimers as potential drug carriers. Part I. Solubilization of non-steroidal anti-inflammatory drugs in the presence of polyamidoamine dendrimers.
The aqueous solubility of non-steroidal anti-inflammatory drugs (NSAIDs) Ketoprofen, Ibuprofen, Diflunisal and Naproxen were measured in the presence of the ethylenediamine (EDA) core polyamidoamine (PAMAM) dendrimers at 37 degrees C. The effect of concentration and generation of the PAMAM dendrimers has been investigated. Results showed that the solubility of NSAIDs in the PAMAM dendrimer solutions was approximately proportional to dendrimer concentration; the solubility of NSAIDs in higher generation PAMAM solutions was in fact higher that those in lower ones; the order of increased solubility of NSAIDs in PAMAM dendrimers at a constant dendrimer concentration and generation was Naproxen>Ketoprofen>Ibuprofen>Diflunisal. Under suitable conditions PAMAM dendrimers can be highly effective used to enhance the solubility of NSAIDs.


Synthesis of biopterin and related pterin glycosides.
Certain pterins having a hydroxyalkyl side chain at C-6 have been found as glycosidic forms in certain prokaryotes, such as 2'-O-(α-D-glucopyranosyl)biopterin from various kinds of cyanobacteria, and limipterin from a green sulfur photosynthetic bacterium. Synthetic studies on glycosides of biopterin and related pterins have been made in view of the structural proof as well as for closer examination of their biological activities and functions. The syntheses of these natural pterin glycosides have effectively been achieved, mostly through appropriately protected N(2) -(N,N-dimethylaminomethylene)-3-[2-(4-nitrophenyl)ethyl]pterin derivatives as glycosyl acceptors, and are reviewed here.


A propensity scale for type II polyproline helices (PPII): aromatic amino acids in proline-rich sequences strongly disfavor PPII due to proline-aromatic interactions.
Type II polyproline helices (PPII) are a fundamental secondary structure of proteins, common in globular and nonglobular regions and important in cellular signaling. We developed a propensity scale for PPII using a host-guest system with sequence Ac-GPPXPPGY-NH(2), where X represents any amino acid. We found that proline has the highest PPII propensity, but most other amino acids display significant PPII propensities. The PPII propensity of leucine was the highest of all propensities of non-proline residues. Alanine and residues with linear side chains displayed the next highest PPII propensities. Three classes of residues displayed lower PPII propensities: β-branched amino acids (Thr, Val, and Ile), short amino acids with polar side chains (Asn, protonated Asp, Ser, Thr, and Cys), and aromatic amino acids (Phe, Tyr, and Trp). tert-Leucine particularly disfavored PPII. The basis of the low PPII propensities of aromatic amino acids in this context was significant cis-trans isomerism, with proline-rich peptides containing aromatic residues exhibiting 45-60% cis amide bonds, due to Pro-cis-Pro-aromatic and aromatic-cis-Pro amide bonds.


Stress echocardiography in contemporary clinical cardiology: practical considerations and accreditation.
Stress echocardiography is a widely utilised test in patients with known or suspected coronary artery disease (CAD), valvular heart disease and cardiomyopathies. Its advantages include the ubiquitous availability of echocardiography, lack of ionising radiation, choice of physiological or pharmacological stressors, good diagnostic accuracy and robust supporting evidence base. SE has evolved significantly as a technique over the past three decades and has benefitted considerably from improvements in overall image quality (superior resolution), machine technology (e.g. digital cine-loop acquisition and side-by-side image display) and development of second-generation ultrasound contrast agents that have improved reader confidence and diagnostic accuracy. The purpose of this article is to review the breadth of SE in contemporary clinical cardiology and discuss the recently launched British Society of Echocardiography (BSE) Stress Echocardiography accreditation scheme.


A New Active Contours Approach for Finger Extensor Tendon Segmentation in Ultrasound Images Using Prior Knowledge and Phase Symmetry.
This work proposes a new approach for the segmentation of the extensor tendon in ultrasound images of the second metacarpophalangeal joint (MCPJ). The MCPJ is known to be frequently involved in early stages of rheumatic diseases like rheumatoid arthritis. The early detection and follow up of these diseases is important to start and adapt the treatments properly and, in that way, preventing irreversible damage of the joints. This work relies on an active contours framework, preceded by a phase symmetry preprocessing and with prior knowledge energies, to automatically identify the extensor tendon. Active contours methods are widely used in ultrasound images because of their robustness to speckle noise and ability to join unconnected smaller regions into a coherent shape. The tendon is formulated as a line so open ended active contours were used. Phase symmetry highlights the tendon, by setting a proper scale range and angle span. The distance between structures and the tendon slope were also included to enforce the model based on anatomical characteristics. And finally, the concavity measures were used because, given the anatomy of the finger, we know that the tendon line should have less than two concavities. To solve the active contours energy minimization a genetic algorithm approach was used. Several energy metric configurations were compared using the modified Hausdorff distance and results showed that this segmentation is not only possible, but exhibits errors smaller than 0.5 mm with a confidence of 95% with the phase symmetry preprocessing and energies based on the line neighborhood, area ratio, slope, and concavity measurements.


Study of the interactions between avian myeloblastosis virus reverse transcriptase and primer tRNA. Affinity labeling and inactivation of the enzyme by periodate-treated tRNATrp.
Reverse transcriptase from avian myeloblastosis virus can react with periodate-treated primer tRNATrp (beef) to form a Schiff's base between an epsilon-NH2 lysine group within the active center of the enzyme and the dialdehyde derivative of the 3' terminal ribose of tRNA. In the presence of cyanoborohydride the reversible imminium moiety of the Schiff's base is reduced to a more stable adduct. Non-primer tRNAs were not able to reduce the extent of primer fixation to the enzyme. Complete inactivation of the enzyme was attained when the ratio enzyme:tRNA in the complex was 1:1. When the 1:1 adduct was analyzed by polyacrylamide gel electrophoresis, radioactivity from the terminal adenosine of tRNA was found exclusively associated with the alpha subunit. At longer times of labeling the beta subunit was also found linked to the oxidized primer tRNA.


Association between chemerin rs17173608 and rs4721 gene polymorphisms and gestational diabetes mellitus in Iranian pregnant women.
Gestational diabetes mellitus (GDM) is defined as hyperglycemia detected during pregnancy and its risk is increased with obesity. Chemerin, an adipokine, has been proposed as potential mediators of insulin resistance in GDM. This case-control study was designed to assess the relation between chemerin SNPs rs4721 (or rs10278590) and rs17173608 and the development of GDM. One hundred thirty GDM pregnant women with GDM and 160 healthy pregnant women were enrolled in this study. The diagnosis of GDM was based on the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria. Chemerin rs4721 polymorphism gene was amplified through PCR, and SNP was detected using restriction enzyme AluI. Genotyping for chemerin rs17173608 polymorphism was performed by using tetra-amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR). Blood glucose level was measured by an enzymatic method. Our finding showed that the genotypes frequency of chemerin rs4721 polymorphism was significantly different between GDM and non-GDM groups (χ2 = 7.44, P = 0.02). The genotype of rs4721 was significantly associated with GDM in co-dominant and dominant genotypes (GG vs GT, OR = 2.3, 95%CI = 1.24-4.24, P = 0.008, and GG vs GT + TT, OR = 2.21, 95%CI = 1.23-3.99, P = 0.008, respectively). No significant difference was observed in allele frequency between case and control groups (P = 0.62). Moreover, the genotypes and allele frequencies of chemerin rs17173608 polymorphism did not show significant differences between GDM and non-GDM (P > 0.05). We concluded that the genotype of rs4721 was found to contribute significant risk to GDM while genotype of rs17173608 could not predict the risk of GDM.


Post-metamorphic skeletal growth in the sea urchin Paracentrotus lividus and implications for body plan evolution.
Understanding the molecular and cellular processes that underpin animal development are crucial for understanding the diversity of body plans found on the planet today. Because of their abundance in the fossil record, and tractability as a model system in the lab, skeletons provide an ideal experimental model to understand the origins of animal diversity. We herein use molecular and cellular markers to understand the growth and development of the juvenile sea urchin (echinoid) skeleton. We developed a detailed staging scheme based off of the first ~ 4 weeks of post-metamorphic life of the regular echinoid Paracentrotus lividus. We paired this scheme with immunohistochemical staining for neuronal, muscular, and skeletal tissues, and fluorescent assays of skeletal growth and cell proliferation to understand the molecular and cellular mechanisms underlying skeletal growth and development of the sea urchin body plan. Our experiments highlight the role of skeletogenic proteins in accretionary skeletal growth and cell proliferation in the addition of new metameric tissues. Furthermore, this work provides a framework for understanding the developmental evolution of sea urchin body plans on macroevolutionary timescales.


[Intracranial extradural liposarcoma in the posterior fossa--a case report (author's transl)].
A case of liposarcoma, which originated primarily in the left infraauricular area and infiltrated to the posterior fossa, was reported. The patient was a 25-year-old housewife, who was admitted because of symptoms of intracranial hypertension. She showed left facial palsy and deviation of the tongue to the left without any cerebellar signs. Neurological examinations suggested a mass lesion in the posterior fossa. Suboccipital craniectomy was performed and the tumor sized 4 X 4 X 3 cm in the extradural space was partially removed. Microscopically, the tumor consisted of lipoblasts and diagnosed as liposarcoma. Intracranial liposarcoma, whether primary or secondary, is very rare and only several cases have been reported.


[The flavonoids effect against vinblastine, cyclophosphamide and paracetamol toxicity by inhibition of lipid-peroxydation and increasing liver glutathione concentration].
The paracetamol and cyclophosphamid are metabolized in the liver by the cytochrome P450. The formed reactive intermediates are responsible of a hepatocyte depletion of the glutathion and a lipoperoxydation. the vinblastine is also a chemotherapeutic agent hepatotoxic and hematotoxic. Otherwise, flavonoïds are polyphenols substances of plant origin having some biological and anti-oxydative properties. However no information is available on their effects on glutathion and glutathion-s-transferases. In our research, we valued the effect of oral administration of flavonoids (diosmine and quercetine) under shape of propolis extract to 60 mg/kg daily during 14 days, on hematological and hepatic toxicity of a single dose of cyclophosphamide 80 mg/kg by intravenous way, vinblastine 2 mg/kg by intravenous way and the hepatic toxicity of the paracetamol managed by oral way to 200 mg/kg corresponding to 2/3 the DL50 at the rat female albinos wistar. We did a blood numeration, an assessment of serum activities of transaminases and alkali phosphatases as well as quantification of the glutathion and the malondialdehyde (MDA) in liver homogenats of rats treated. Analyses are done at regular intervals; 1, 3, 7 and 14 days after the administration of drugs. In the group of rats treated by the cyclophosphamid paracetamol alone we observed since the 1st day, an increase of lipid peroxide (MDA) of 120% and a downfall of hepatic glutathion including the group receiving the vinblastine (until 210% of reduction). In the same way a severe leucopenia and a thrombopenia (70% of reduction) are observed between the 3rd and the 14th day at rats treated by the chemotherapeutic agents alone (cyclophosphamide and vinblastine). The combination of flavonoids with drugs have clearly reduced the effect of drugs toxicity. Indeed, the aplasic observed with the vinblastine, as well as the leucopenia and thrombopenia of the cyclophosphamide are corrected entirely. In the same way, we noted a restoration of rates of peroxide and glutathion. Flavonoïds seem to act by activation of the turn over of the glutathion and enzymes stimulating particularly glutathion-s-transferases permitting the captation of the reactive metabolites of the studied drugs.


Does natural honey act as an alternative to antibiotics in the semen extender for cryopreservation of crossbred ram semen?
Antibiotics are added to semen extenders to take care of heavy microbial load, however, their continuous use poses a constant threat of developing antibiotic resistance by the common microbes present in the semen. Our hypothesis was that natural honey, having antibacterial activity and rich in fructose could replace the use of antibiotics and fructose in the semen extender. Twenty-four ejaculates from six crossbred rams were obtained and extended with tris-based extender without (control) and with honey at 2.5% (T1), 5% (T2) and 7% (T3). Sperm quality was measured in terms of percentage sperm motility, live sperm count, intact acrosome and hypo-osmotic swelling test (HOST) reacted spermatozoa. The semen samples at post-thaw were also evaluated for total viable count (colony forming units/ml). At post-thaw, control exhibited significantly (P<0.05) higher sperm motility in comparison to T2 and T3. The percent of live sperm count, intact acrosome and HOST reacted spermatozoa were significantly higher (P<0.05) for control than all other treatment groups at post-thaw. Among treatment groups, T1 maintained significantly higher (P<0.05) percentage of live sperm count, intact acrosome and HOST reacted spermatozoa than T2 and T3. The total viable count at post-thaw was significantly lower (P<0.05) for control than all the treatment groups. In conclusion, honey cannot be used as an alternative to antibiotics to take care of heavy microbial load in semen, however, levels up to 2.5% may be supplemented to semen as an energy source.


Patterns of inheritance of colonic polyps.
While the inheritance pattern of familial polyposis coli is established as an autosomal dominant pattern, the expression of the various extracolonic manifestations associated with the neoplastic polyposis is less well understood. The discrete polyp cancer syndrome may not be recognized unless both polyps and colon cancer are considered in the inheritance pattern. The hamartomatous polyps follow a Mendelian-dominant inheritance pattern for the Peutz-Jeghers syndrome, while the inheritance pattern for the juvenile polyposis syndromes is less clear. Cowden's disease appears in a Mendelian dominant pattern, but the occurrence of colonic polyps is less well documented. The ganglioneuromas follow a mendelian dominant inheritance pattern, while the relationship and occurrence of colonic polyps in association with Torre's syndrome is uncertain. The Mendelian dominant inheritance pattern for the cancer family syndrome is documented; the role of colon polyps in this syndrome is less well understood. A further understanding of the inheritance patterns of these various colon polyps will lead to more understanding of the basic disease and help in prevention and early detection for treatment and cure.


Sirolimus use and cancer incidence among US kidney transplant recipients.
Sirolimus has anti-carcinogenic properties and can be included in maintenance immunosuppressive therapy following kidney transplantation. We investigated sirolimus effects on cancer incidence among kidney recipients. The US transplant registry was linked with 15 population-based cancer registries and national pharmacy claims. Recipients contributed sirolimus-exposed time when sirolimus claims were filled, and unexposed time when other immunosuppressant claims were filled without sirolimus. Cox regression was used to estimate associations with overall and specific cancer incidence, excluding nonmelanoma skin cancers (not captured in cancer registries). We included 32,604 kidney transplants (5687 sirolimus-exposed). Overall, cancer incidence was suggestively lower during sirolimus use (hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.70-1.11). Prostate cancer incidence was higher during sirolimus use (HR = 1.86, 95% CI = 1.15-3.02). Incidence of other cancers was similar or lower with sirolimus use, with a 26% decrease overall (HR = 0.74, 95% CI = 0.57-0.96, excluding prostate cancer). Results were similar after adjustment for demographic and clinical characteristics. This modest association does not provide strong evidence that sirolimus prevents posttransplant cancer, but it may be advantageous among kidney recipients with high cancer risk. Increased prostate cancer diagnoses may result from sirolimus effects on screen detection.


Electrophysiologic and behavioral outcomes of cochlear implantation in children with auditory nerve hypoplasia.
Hypoplasia of the auditory nerve (AN) refers to significant narrowing of the VIIIth cranial nerve which could compromise stimulation of the nerve by electrical pulses delivered from a cochlear implant (CI), thereby hindering activity in other parts of the auditory pathways. To compensate, high current levels or increased charge may be required to elicit auditory perception causing current to spread to other cranial nerves and potentially resulting in unwanted myogenic responses. Deficits in central auditory activity could reduce perception of speech and language. In the present study, we measured auditory brainstem responses in children with and without hypoplasia of the AN to answer the following questions. In children with hypoplastic ANs, (a) can CI stimulation evoke typical patterns of activity from the AN and brainstem?, (b) do brainstem responses change with CI experience?, (c) are evoked responses dependent on the size of the AN pathway?, and (d) does auditory development measured by behavioral tests of speech perception develop more slowly than in peers with normal AN diameter? Of 807 children using CIs in our program, 20 (2.5%) were identified as having AN hypoplasia using high-resolution computed tomographic scan and/or magnetic resonance imaging. An age-matched control group of children using CIs with normal AN diameter were recruited to compare electrophysiological and behavioral measures. Radiologic imaging was used to measure the diameter of the internal auditory canal (IAC), auditory nerve canal (ANC), and AN. Electrophysiological testing of the evoked compound action potential and auditory brainstem response was performed at CI activation and every 3 mo after initial testing up to 2 yr. Peak latency and waveform morphology were compared between study and control groups. Tests of speech perception and discrimination were attempted every 12 mo after device activation up to 10 yr. : Hypoplastic AN was identified as moderate to critical stenosis of the IAC, ANC, and AN. Initial electrically evoked compound action potential responses were mostly absent in children with AN hypoplasia. In the time window when electrically evoked auditory brainstem responses would be expected, some responses included single amplitude peaks at normal wave eV latencies, but the majority were abnormal, with peaks at atypical latencies or with no observable wave peaks. All evoked responses were inconsistent over time and did not reflect a typical pattern of auditory brainstem development. Speech perception scores were significantly poorer in the study group compared with controls and did not improve with CI experience. The type of abnormal evoked waveform response was independent of IAC, ANC, or AN diameter and also independent of behavioral outcome measures. : Evoked responses recorded in CI children with AN hypoplasia indicate a high incidence of nonauditory activity with CI use. The range of abnormal responses was not predicted by the severity of the hypoplastic AN or associated structures. This, along with poorer auditory development compared with peers with normal AN diameters, suggests that children with hypoplasia of the AN are poor candidates for cochlear implantation.


Isolation, characterization, and transplantation of bone marrow-derived cell components with hematopoietic stem cell niche properties.
Although the unique role of hematopoietic stem cell (HSC) niche in hematopoiesis has long been recognized, unsuccessful isolation of intact niche units limited their in vitro study, manipulation, and therapeutic application. Here, we isolated cell complexes based on size fractionation from mouse bone marrow (BM), characterized the derived cells, and transplanted them to irradiated mice. These cell complexes were the origin of both BM mesenchymal stem cells and various hematopoietic lineages when kept in appropriate culture conditions. They also had the potential of recruiting circulating HSC. Intraperitoneal transplantation of these structures into irradiated mice not only showed long-lasting hematopoietic multilineage reconstitution, but also could recover the stromal cells of BM. In conclusion, this study for the first time provides evidences on the feasibility and efficacy of transplantation of HSC in association with their native specialized microenvironment. As the molecular cross-talk between HSC and niche is crucial for their proper function, the proposed method could be considered as a novel hematopoietic transplantation strategy.


Ipilimumab in melanoma with limited brain metastases treated with stereotactic radiosurgery.
The anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody ipilimumab has been shown to improve survival in patients with metastatic non-CNS melanoma. The purpose of this study was to investigate the efficacy of CTLA-4 inhibitors in the treatment of metastatic melanoma with limited brain metastases treated with stereotactic radiosurgery (SRS). Between January 2008 and June 2011, 58 patients with limited brain metastases from melanoma were treated with SRS with a median dose of 20 Gy delivered to the 50% isodose line (range, 15-20 Gy). In 25 patients, ipilimumab was administered intravenously at a dose of 3 mg/kg over 90 min every 3 weeks for a median of four doses (range, 1-8). Local control (LC), freedom from new brain metastases, and overall survival (OS) were assessed from the date of the SRS procedure. The median LC, freedom from new brain metastases, and OS for the entire group were 8.7, 4.3, and 5.9 months, respectively. The cause of death was CNS progression in all but eight patients. Six-month LC, freedom from new brain metastases, and OS were 65, 35, and 56%, respectively, for those who received ipilimumab and 63, 47, and 46% for those who did not (P=NS). Intracranial hemorrhage was noted in seven patients who received ipilimumab compared with 10 patients who received SRS alone (P=NS). In this retrospective study, administration of ipilimumab neither increased toxicity nor improved intracerebral disease control in patients with limited brain metastases who received SRS.


Salt parameterization can drastically affect the results from classical atomistic simulations of water desalination by MoS2 nanopores.
Water scarcity is a reality in our world, and scenarios predicted by leading scientists in this area indicate that it will worsen in the next decades. However, new technologies based on low-cost seawater desalination can prevent the worst scenarios, providing fresh water for humanity. With this goal, membranes based on nanoporous materials have been suggested in recent years. One of the materials suggested is MoS2, and classical Molecular Dynamics (MD) simulation is one of the most powerful tools to explore these nanomaterials. However, distinct force fields employed in MD simulations are parameterized based on distinct experimental quantities. In this paper, we compare two models of salt that were built based on distinct properties of water-salt mixtures. One model fits the hydration free energy and lattice properties, and the second fits the crystal density and the density and the dielectric constant of water and salt mixtures. To compare the models, MD simulations for salty water flow through nanopores of two sizes were used - one pore big enough to accommodate hydrated ions, and one smaller in which the ion has to dehydrate to enter - and two rigid water models from the TIP4P family - TIP4P/2005 and TIP4P/ε. Our results indicate that the water permeability and salt rejection by the membrane are more influenced by the salt model than by the water model, especially for the narrow pore. In fact, completely distinct mechanisms were observed, and they are related to the characteristics employed in the ion model parameterization. The results show that not only can the water model influence the outcomes, but the ion model plays a crucial role when the pore is small enough.


Novel regulation of adrenomedullin receptor by PDGF: role of receptor activity modifying protein-3.
Receptor activity modifying protein-3 (RAMP-3) has been shown to complex with the calcitonin receptor-like receptor, establishing a functional receptor for adrenomedullin (AM). AM exhibits potent antiproliferative and antimigratory effects on rat mesangial cells (RMCs). In this study we investigated the effect of platelet-derived growth factor (PDGF) on RAMP-3 expression in RMCs. We show here that PDGF-BB stimulates RAMP-3 mRNA expression in a concentration-dependent manner. Pretreatment with actinomycin-D and alpha-amanitin demonstrates that this effect is independent of new RNA synthesis. Furthermore, PDGF increased the half-life of RAMP-3 mRNA from 66.5 to 331.6 min. Using selective inhibitors, our results also indicate that the increase in RAMP-3 mRNA is mitogen-activated protein kinase (MAPK) kinase (MEK)/MAPK and p38 MAPK dependent. PDGF also caused a corresponding elevation in membrane-associated RAMP-3 protein. Associated with this increase, PDGF pretreatment led to a significantly higher AM-mediated adenylate cyclase activity, suggesting a functional consequence for the PDGF-induced increase in RAMP-3 expression. Taken together, these data identify PDGF-dependent regulation of RAMP-3 expression as a possible mechanism for modulating the responsiveness of the mesangial cell to AM.


An Electrophysiological Study of Cognitive and Emotion Processing in Type I Chiari Malformation.
Type I Chiari malformation (CMI) is a neurological condition in which the cerebellar tonsils descend into the cervical spinal subarachnoid space resulting in cervico-medullary compression. Early case-control investigations have indicated cognitive deficits in the areas of attention, memory, processing speed, and visuospatial function. The present study further examined cognitive and emotional processing deficits associated with CMI using a dual-task paradigm. Nineteen CMI patients were recruited during pre-surgical consultation and 19 matched control participants identified emotional expressions in separate single and asynchronous dual-task designs. To extend earlier behavioral studies of cognitive effects in CMI, we recorded event-related potentials (ERPs) in the dual-task design. Though response times were slower for CMI patients across the two tasks, behavioral and ERP analyses indicated that patients did not differ from matched controls in the ability to allocate attentional resources between the two tasks. P1 ERP component analyses provided no indication of an emotional arousal deficit in our CMI sample while P3 ERP component analyses suggested a CMI-related deficit in emotional regulation. P3 analysis also yielded evidence for a frontalization of neurophysiological activity in CMI patients. Pain and related depression and anxiety factors accounted for CMI deficits in single-task, but not dual-task, response times. Results are consistent with a dysfunctional fronto-parietal attentional network resulting from either the indirect effects of chronic pain or the direct effects of CMI pathophysiology stemming from cervico-medullary compression.


The Impact of COVID-19 on the Functioning of a Neurosurgical Service at a Tertiary Institute in a Low-Resource Setting.
Objective During the COVID-19 pandemic, certain precautionary measures were implemented to limit its effect, including the cancellation of clinics and elective surgical lists. To determine the impact, if any, of the pandemic on the running of a neurosurgical service, an audit was performed on the volume of referrals, admissions and type of surgeries performed at a tertiary institute in a low-resource setting. Methods An audit of the neurosurgical department's database was performed on the number of referrals, admissions, surgical procedures, and types of procedures done at the San Fernando General Hospital. This was divided into two 15-month periods, pre-pandemic (January 1, 2019 to March 31, 2020) and intra-pandemic (April 1, 2020 - June 30, 2021). Results During the pre-pandemic period (January 1, 2019 - March 31, 2020), 2,597 patients were referred to the service and 309 major procedures were performed. Two thousand and forty-two patients were referred during the intra-pandemic (April 4, 2020 - June 30, 2021) period, with 354 surgeries performed. More external ventricular drains (29 vs 50), craniotomies for trauma (73 vs 98), anterior cervical fusion (42 vs 47), lumbar fusions (9 vs 12), ventriculo-peritoneal shunts (16 vs 19) and aneurysm clipping (10 vs 13) were done during the intra-pandemic period. Conclusion Although elective surgical procedures and clinics were reduced, the number of patients seen and total procedures performed did not vary significantly. The neurosurgical pathology encountered remained constant during the pandemic. This shows the importance of maintaining a fully functional neurosurgical service, as we continue to adapt to the COVID-19 pandemic.


Extensive linear epidermal nevus associated with hemangiomas of bones and vitamin-D-resistant rickets.
The association of connate, left-sided, extensive epidermal verrucous nevus, multiple isolated bone tumors and vitamin-D-resistant rickets since childhood seen in a 20-year-old male patient corresponded to an epidermal nevus syndrome (ENS). However, other organ involvement occasionally associated with ENS could not be found in this patient, and his intraosseous tumors represented histologically benign hemangiomas. Serum analysis revealed hypophosphatemia (together with phosphaturia), decreased levels of 1,25-dihydroxycholecalciferol and elevated levels of alkaline phosphatase indicating hypophosphatemic osteomalacia. Therefore we suppose that vitamin-D-resistant rickets combined with skeletal tumors represents a peculiar type of osteomalacia caused by unilateral mesenchymomas.


Postmenopausal bleeding on hormone replacement therapy: review of the current referral guidelines.
The object of this study was to reassess the current NHS guidelines regarding the type of referrals for patients on hormone replacement therapy (HRT) presenting with postmenopausal bleeding (PMB). The guidelines are published on the following website: < http://www.doh.gov.uk/pub/docs/doh/guidelines.pdf >.


Tumefactive demyelination: an approach to diagnosis and management.
Tumefactive lesions are an uncommon manifestation of demyelinating disease and can pose a diagnostic challenge in patients without a pre-existing diagnosis of multiple sclerosis. Choosing when to biopsy a tumefactive lesion to exclude alternative pathology can be difficult. Other questions include how best to treat an acute attack as well as the optimal timing of therapy to prevent relapse. This article aims to review the available literature for tumefactive demyelination and to propose an approach to diagnosis and management. We argue that disease modifying therapy should be considered for acute tumefactive demyelinating lesions only once criteria of dissemination in time and space are fulfilled and the diagnosis of multiple sclerosis is confirmed.


New positive regulators of lin-12 activity in Caenorhabditis elegans include the BRE-5/Brainiac glycosphingolipid biosynthesis enzyme.
Screens for suppressors of lin-12 hypermorphic alleles in C. elegans have identified core components and modulators of the LIN-12/Notch signaling pathway. Here we describe the recovery of alleles of six new genes from a screen for suppressors of the egg-laying defect associated with elevated lin-12 activity. The molecular identification of one of the new suppressor genes revealed it as bre-5, which had previously been identified in screens for mutations that confer resistance to Bt toxin in C. elegans. bre-5 is the homolog of D. melanogaster brainiac. BRE-5/Brainiac catalyzes a step in the synthesis of glycosphingolipids, components of lipid rafts that are thought to act as platforms for association among certain kinds of membrane-bound proteins. Reducing the activity of several other genes involved in glycosphingolipid biosynthesis also suppresses the effects of constitutive lin-12 activity. Genetic analysis and cell ablation experiments suggest that bre-5 functions prior to ligand-induced ectodomain shedding that activates LIN-12 for signal transduction.


Single-Cell RNA Sequencing in Lung Cancer: Revealing Phenotype Shaping of Stromal Cells in the Microenvironment.
The lung tumor microenvironment, which is composed of heterogeneous cell populations, plays an important role in the progression of lung cancer and is closely related to therapeutic efficacy. Increasing evidence has shown that stromal components play a key role in regulating tumor invasion, metastasis and drug resistance. Therefore, a better understanding of stromal components in the tumor microenvironment is helpful for the diagnosis and treatment of lung cancer. Rapid advances in technology have brought our understanding of disease into the genetic era, and single-cell RNA sequencing has enabled us to describe gene expression profiles with unprecedented resolution, enabling quantitative analysis of gene expression at the single-cell level to reveal the correlations among heterogeneity, signaling pathways, drug resistance and microenvironment molding in lung cancer, which is important for the treatment of this disease. In this paper, several common single-cell RNA sequencing methods and their advantages and disadvantages are briefly introduced to provide a reference for selection of suitable methods. Furthermore, we review the latest progress of single-cell RNA sequencing in the study of stromal cells in the lung tumor microenvironment.


Routine revascularization with resection of infection femoral pseudoaneurysms from substance abuse.
Infected femoral artery pseudoaneurysms in narcotic addicts present challenging management options. Our policy of routine revascularization is based on the concern that a high rate of amputations must follow ligation and resection alone or with selective delayed revascularization. Fifteen of 16 patients with infected pseudoaneurysms of femoral arteries, treated with resection and bypass grafts, were observed from 1 to 44 months. Obturator bypass grafts were used in 10 patients, iliac-femoral grafts in three, axillopopliteal in one, and right external iliac crossover to left popliteal in one patient. One limb, unsalvageable at presentation, was amputated primarily, along with resection of pseudoaneurysm and femoral artery ligation, without bypass grafting. One iliac-femoral graft became infected and then thrombosed 4 months after operation. Unsuitable distal arteries and impending necrosis led to above-knee amputation. One late failure among 15 revascularization attempts (7%) is significantly lower than the 11% to 33% amputation rates reported in the literature with resection of pseudoaneurysm alone and delayed selective revascularization. The other 14 patients had functioning limbs without claudication or rest pain. Our experience indicates that revascularization at the time of resection of infected pseudoaneurysm offers better prospects for limb salvage.


Effect of venting and seating techniques on the cementation of complete coverage restorations.
The incomplete seating of crowns resulting from cementation phenomena is a universal problem for clinicians. This seating error may lead to disturbances in the occlusion, proximal contacts, reduced retention and open margins. Various cementation protocols are practiced, with no established standard that maximizes crown seating and marginal fit. This study investigated the effect of various combinations of venting and cementation seating techniques with the routine use of die relief on the seating of complete gold crowns. Fifty human molars were prepared with a mounted handpiece for complete coverage crowns with a featheredge finish line and six degrees of taper, according to Tylman. Impressions were made, stone dies fabricated, die spacer was applied and the crowns were waxed and cast in type III gold. The respective crowns were placed on the teeth and preloaded. The distance between reference marks on the tooth and crown were measured at four points around each tooth. Zinc phosphate cement was mixed and the crowns were cemented in the following groups: (1) vented, tapping the crown into place with a mallet, (2) non-vented, tapping the crown into place, (3) vented static seating with a 25 kg load, (4) non-vented dynamic seating, (5) non-vented static loading with a 25 kg load. A 25 kg load was then maintained on the crowns during the cement setting time. Distances between reference marks were then measured and the change in post-cementation distances calculated. ANOVA (F = 14.995, p < .0001) and multiple range tests revealed significant differences between the groups. The mean increased post-cementation distances for the seating groups were (microm): 1) 132 +/- 20, 2) 372 +/- 26, 3) 367 +/- 59, 4) 239 +/- 35, 5) 537 +/- 45. The vented tapping technique produced the best seating. The non-vented tapping seating group produced seating not significantly different from the vented static method. The non-vented static group had the worst seating, with a gap four times greater than the vented tapping group.


Strategies to alleviate shortages of nurses in adult social care.
A lack of investment in adult social care has led to major staffing problems in care homes, according to a new report from the National Audit Office, as Emeritus Professor Alan Glasper, University of Southampton, explains.


Synaptic currents at individual connections among stellate cells in rat cerebellar slices.
1. Unitary inhibitory synaptic connections among stellate cells were studied in rat cerebellar slices. Presynaptic action potentials and inhibitory postsynaptic currents (IPSCs) were simultaneously recorded by loose cell-attached and tight-seal whole-cell recording, respectively. 2. Several types of synaptic connections were distinguished on the basis of the shape of the amplitude distribution of successfully evoked currents. For simple synapses, which presumably arise at single release sites, these histograms could be fitted to a single Gaussian (5 cases). In four additional cases a small amplitude component (< 50 pA) was superimposed to a single Gaussian peak. The small events had slow rise times and widely distributed amplitudes. Finally eleven histograms showed two or more Gaussian components and were classified as complex connections. 3. Failure rates ranged from 0.06 to 0.85 for unitary connections (n = 20) and from 0.59 to 0.78 for simple synapses (n = 5). 4. Coefficient of variation values derived from Gaussian fits to simple synapse histograms ranged between 0.20 and 0.38 (n = 5). 5. In simple synapses peak current amplitudes were positively correlated to both current rise time and decay half-width. 6. Intervals between presynaptic action potentials were widely distributed. During stationary periods there was no correlation between interspike interval and amplitude size, success rate or latency. In some experiments, episodes with shorter interspike intervals were observed. During these periods, amplitude and success rate decreased, and the latency increased. Thus, IPSC characteristics depend on the mean frequency of presynaptic spikes, but not on random fluctuations of interspike intervals during stationary periods.