Postgraduate nursing students' experiences of simulation training and reflection in end-of-life communication with intensive care patients and their families.
Losing a loved one in the intensive care unit relates to a risk of developing stress and complicated grief. Education in intensive care nursing should cover end-of-life care, and the use of simulation in nursing education is a powerful instrument to develop confidence in end-of-life care. The aim of this study was to explore postgraduate nursing students' experiences with simulation training in end-of-life communication with intensive care patients and their families. Twenty-nine students answered a questionnaire and nine students participated in an interview. Analyses were conducted according to the principles of phenomenography. The result is presented in four categories including the following: the design of the scenario affects learning, uncertainty overshadows learning, intertwining theory and practice contributes to learning, and learning to encounter existential dimensions. The conclusion is that high-fidelity simulation training contributes toward preparing students to be attuned to what it can be like to be a family member in this situation. The scenarios contributed toward preparing the students to engage in end-of-life conversations during clinical placements.


Endotoxin and polycyclic aromatic hydrocarbons in ambient fine particulate matter from Fresno, California initiate human monocyte inflammatory responses mediated by reactive oxygen species.
In urban areas, a correlation between exposure to particulate matter (PM) from air pollution and increased cardiovascular morbidity and mortality has been observed. Components of PM include bacterial contaminants, transition metals, salts, polycyclic aromatic hydrocarbons (PAH), and carbonaceous material, which could interact with various cell types to produce systemic responses when inhaled. We examined the effects of PM collected from Fresno, California on activation of human monocytes and their interaction with vascular endothelium, a key event in atherogenesis. PM exposure increased cytokine expression and secretion from monocytes and enhanced monocyte adhesion to human aortic endothelial cells, both of which were attenuated by neutralizing endotoxin. PM also increased monocyte CYP1a1 expression, and inhibition of the aryl hydrocarbon receptor reduced the CYP1a1 and inflammatory responses. PM-treated monocytes accumulated intracellular reactive oxygen species (ROS), and antioxidants attenuated inflammatory and xenobiotic responses. Finally, supernatants from PM-treated pulmonary microvascular endothelial cells induced monocyte inflammatory responses that were not a consequence of endotoxin transfer. These results suggest that certain components of urban PM, namely endotoxin and PAH, activate circulating monocytes directly or indirectly by first stimulating other cells such as pulmonary endothelial cells, providing several mechanisms by which PM inhalation could induce pulmonary and/or systemic inflammation.


AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts.
Deregulation of the cell cycle has long been recognized as an essential driver of tumorigenesis, and agents that selectively target key cell cycle components continue to hold promise as potential therapeutics. We have developed AZD5438, a 4-(1-isopropyl-2-methylimidazol-5-yl)-2-(4-methylsulphonylanilino) pyrimidine, as a potent inhibitor of cyclin-dependent kinase (cdk) 1, 2, and 9 (IC(50), 16, 6, and 20 nmol/L, respectively). In vitro, AZD5438 showed significant antiproliferative activity in human tumor cell lines (IC(50) range, 0.2-1.7 micromol/L), causing inhibition of the phosphorylation of cdk substrates pRb, nucleolin, protein phosphatase 1a, and RNA polymerase II COOH-terminal domain and blocking cell cycling at G(2)-M, S, and G(1) phases. In vivo, when orally administered at either 50 mg/kg twice daily or 75 mg/kg once daily, AZD5438 inhibited human tumor xenograft growth (maximum percentage tumor growth inhibition, range, 38-153; P < 0.05). In vivo, AZD5438 reduced the proportion of actively cycling cells. Further pharmacodynamic analysis of AZD5438-treated SW620 xenografts showed that efficacious doses of AZD5438 (>40% tumor growth inhibition) maintained suppression of biomarkers, such as phospho-pRbSer(249)/Thr(252), for up to 16 hours following a single oral dose. A comparison of different schedules indicated that chronic daily oral dosing provided optimal cover to ensure antitumor efficacy. These data indicate that broad cdk inhibition may provide an effective method to impair the dysregulated cell cycle that drives tumorigenesis and AZD5438 has the pharmacologic profile that provides an ideal probe to test this premise.


Identification of a new murine eosinophil major basic protein (mMBP) gene: cloning and characterization of mMBP-2.
We have identified a new eosinophil major basic protein gene family member in the mouse and have given it the designation murine major basic protein-2 (mMBP-2). The gene was initially characterized as a unique expressed sequence tag (EST) clone having significant identity to the previously recognized member of this gene family, mMBP-1. The EST was used to screen and isolate mMBP-2 from a bone marrow cDNA library. In addition, a genomic clone of mMBP-2 was isolated and this gene was shown to be physically linked to within 100 kb of mMBP-1 on the central region of mouse chromosome 2. Progressive similarity alignment of the deduced mMBP-2 open reading frame demonstrates the apparent conservation of the "pre-pro-mature" protein structure found in the other known mammalian MBPs. Mature mMBP-2 maintains the cationic nature associated with these proteins with a predicted pI of 9.95. However, unlike the human MBPs, which display a three orders of magnitude charge difference [hMBP-1 (pI 11.4) vs. hMBP-2 (pI 8.7)], mMBP-2 is only slightly less cationic than mMBP-1 (pI 10.5). Expression studies demonstrate that transcription of the mMBP-2 gene parallels mMBP-1 and is confined to hematopoietic compartments engaged in eosinophilopoiesis. Moreover, using mMBP-1 knockout mice and immunohistochemistry with an antisera that recognizes both mMBP-1 and -2, we demonstrate that mMBP-2 protein expression is restricted to eosinophil lineage-committed cells.


A BTB domain-containing gene is upregulated by immune challenge.
20-Hydroxyecdysone (20E) is an important hormone that regulates the development of insects. Although previous evidence revealed that 20E promotes innate immunity in insects, the mechanism involved is still unclear. In this study, the HaBBP gene from Helicoverpa armigera is cloned, which contains BTB (broad-complex, tramtrack, and bric-a-brac), a BACK (BTB and carboxyl-terminus kelch repeats), and PHR (PAM, highwire, and RPM) domains. RT-PCR analysis of HaBBP and western blot analysis of HaBBP show that the mRNA and protein level are higher in the fat body and hemocytes during the molting and metamorphic stages compared with the feeding stage. HaBBP was upregulated by 20E in hemocytes. Knockdown of the 20E receptor EcR-B1 and the heterodimeric partner ultraspiracle protein USP1 in an epidermal cell line (HaEpi) blocked the transcription of HaBBP. HaBBP is distributed in granulocytes and plasmatocytes. Immune stimulation by Escherichia coli caused the upregulation of HaBBP in both hemocytes and fat body. Thus, HaBBP is regulated by the 20E signaling pathway, and is likely involved in the insect innate immunity.


Psychological crisis and emergency intervention for frontline critical care workers during the COVID-19 pandemic.
To explore the main feelings and coping strategies among frontline critical care workers during the first phase of the COVID-19 pandemic and to evaluate the level of satisfaction after a psychological crisis and emergency intervention. The health crisis brought about by the COVID-19 pandemic has exposed critical care workers to an intense physical and emotional burden. Scientific research recommends psychological crisis and emergency interventions during the acute phase to help cope with the situation and prevent emotional side effects. A multicentre descriptive study with mixed qualitative and quantitative data was developed. Healthcare and non-healthcare critical care workers from 16 hospitals were included. Psychological crisis assistance was given (for individuals and groups), both face-to-face and online, with 18 psychologists for two months. Content analysis from the psychologists' session reports after each intervention was performed (COREQ). Satisfaction with the intervention was assessed with an 'ad hoc' 21-item online survey. A total of 553 interventions were carried out (361 individually and 192 in groups). Four themes were identified: 1-Imbalance between occupational demands and resources; 2-Acute stress responses; 3-Personal and professional consequences; and 4-Protection factors. The main protection factor identified was group cohesion and perceived social support. The mean general satisfaction with the intervention was high and 96.2% (n=252) of the participants would recommend it in future. A psychological crisis and emergency intervention helped critical care workers during the COVID-19 pandemic to verbalise and integrate the situation, providing strategies to cope with the experience with a high level of satisfaction from the participants assisted. During the COVID-19 pandemic, support groups guided by psychologists fostered reflection on aspects related to work, interaction with patients and relatives and social support from workmates that help them for coping with stress, share emotions and experiences and feel understood.


Structure and stability of recombinant bovine odorant-binding protein: I. Design and analysis of monomeric mutants.
Bovine odorant-binding protein (bOBP) differs from other lipocalins by lacking the conserved disulfide bond and for being able to form the domain-swapped dimers. To identify structural features responsible for the formation of the bOBP unique dimeric structure and to understand the role of the domain swapping on maintaining the native structure of the protein, structural properties of the recombinant wild type bOBP and its mutant that cannot dimerize via the domain swapping were analyzed. We also looked at the effect of the disulfide bond by designing a monomeric bOBPs with restored disulfide bond which is conserved in other lipocalins. Finally, to understand which features in the microenvironment of the bOBP tryptophan residues play a role in the defining peculiarities of the intrinsic fluorescence of this protein we designed and investigated single-tryptophan mutants of the monomeric bOBP. Our analysis revealed that the insertion of the glycine after the residue 121 of the bOBP prevents domain swapping and generates a stable monomeric protein bOBP-Gly121+. We also show that the restored disulfide bond in the GCC-bOBP mutant leads to the noticeable stabilization of the monomeric structure. Structural and functional analysis revealed that none of the amino acid substitutions introduced to the bOBP affected functional activity of the protein and that the ligand binding leads to the formation of a more compact and stable state of the recombinant bOBP and its mutant monomeric forms. Finally, analysis of the single-tryptophan mutants of the monomeric bOBP gave us a unique possibility to find peculiarities of the microenvironment of tryptophan residues which were not previously described.


Platelet production from induced pluripotent stem cells.
Ex vivo production of human platelets has been pursued as an alternative measure to resolve limitations in the supply and safety of current platelet transfusion products. To this end, induced pluripotent stem cells (iPSCs) are considered an ideal global source, as they are not only pluripotent and self-renewing, but are also available from basically any person, have relatively few ethical issues, and are easy to manipulate. From human iPSCs, megakaryocyte (MK) lines with robust proliferation capacity have been established by the introduction of specified sets of genes. These expandable MKs are also cryopreservable and thus would be suitable as master cells for good manufacturing practice (GMP)-grade production of platelets, assuring availability on demand and safety against blood-borne infections. Meanwhile, developments in bioreactors that physically mimic the in vivo environment and discovery of substances that promote thrombopoiesis have yielded competent platelets with improved efficiency. The derivation of platelets from iPSCs could further resolve transfusion-related alloimmune complications through the manufacturing of autologous products and human leukocyte antigen (HLA)-compatible platelets from stocked homologous HLA-type iPSC libraries or by manipulation of HLAs and human platelet antigens (HPAs). Considering these key advances in the field, HLA-deleted platelets could become a universal product that is manufactured at industrial level to safely fulfill almost all demands. In this review, we provide an overview of the ex vivo production of iPSC-derived platelets toward clinical applications, a production that would revolutionize the blood transfusion system and lead the field of iPSC-based regenerative medicine.


Proximity-sensors on GPS collars reveal fine-scale predator-prey behavior during a predation event: A case study from Scandinavia.
Although the advent of high-resolution GPS tracking technology has helped increase our understanding of individual and multispecies behavior in wildlife systems, detecting and recording direct interactions between free-ranging animals remains difficult. In 2023, we deployed GPS collars equipped with proximity sensors (GPS proximity collars) on brown bears (Ursus arctos) and moose (Alces alces) as part of a multispecies interaction study in central Sweden. On 6 June, 2023, a collar on an adult female moose and a collar on an adult male bear triggered each other's UHF signal and started collecting fine-scale GPS positioning data. The moose collar collected positions every 2 min for 89 min, and the bear collar collected positions every 1 min for 41 min. On 8 June, field personnel visited the site and found a female neonate moose carcass with clear indications of bear bite marks on the head and neck. During the predation event, the bear remained at the carcass while the moose moved back and forth, moving toward the carcass site about five times. The moose was observed via drone with two calves on 24 May and with only one remaining calf on 9 June. This case study describes, to the best of our knowledge, the first instance of a predation event between two free ranging, wild species recorded by GPS proximity collars. Both collars successfully triggered and switched to finer-scaled GPS fix rates when the individuals were in close proximity, producing detailed movement data for both predator and prey during and after a predation event. We suggest that, combined with standard field methodology, GPS proximity collars placed on free-ranging animals offer the ability for researchers to observe direct interactions between multiple individuals and species in the wild without the need for direct visual observation.


Calcium phosphate increases the encapsulation efficiency of hydrophilic drugs (proteins, nucleic acids) into poly(d,l-lactide-co-glycolide acid) nanoparticles for intracellular delivery.
Calcium phosphate/poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles with a diameter below 200 nm, loaded with either nucleic acids or proteins, were synthesized by a water-in-oil-in-water (W1/O/W2) emulsion solvent evaporation technique. The particles were stabilized by polyvinyl alcohol (PVA) and had a negative charge (zeta potential -26 mV). By the addition of calcium phosphate into the inner aqueous phase of the W1/O/W2-emulsion, the encapsulation efficiency of siRNA was increased to 37%, of DNA to 52%, and of bovine serum albumin to 78%, i.e. by a factor of 3 to 10 compared to PLGA nanoparticles without calcium phosphate. Total loadings of 8 μg siRNA, 5 μg DNA and 280 μg fluorescein isothiocyanate-labelled bovine serum albumin (FITC-BSA) per mg of PLGA nanoparticles were achieved by this method. The addition of an outer layer of either chitosan or polyethyleneimine (PEI) reversed the charge of the particles (zeta potential > +30 mV) and improved the cellular uptake as well as the endosomal escape of these particles as demonstrated by confocal laser scanning microscopy. Calcium phosphate-PLGA nanoparticles loaded with DNA encoding for enhanced green fluorescent protein (eGFP-DNA) showed a good transfection efficiency for epithelial cells (HeLa). Gene silencing with HeLa cells expressing eGFP gave knockdown efficiencies of 53% for anionic nanoparticles, of 68% for chitosan-coated cationic nanoparticles, and of 89% for polyethyleneimine-coated cationic nanoparticles.


Vascular risk factors, cardiovascular disease and functional impairment in community-dwelling adults.
Older adults report preservation of functional independence as one of the most important constructs of successful ageing. Vascular risk factors may increase the risk of functional impairment due to clinical and subclinical vascular disease. To describe the association between vascular risk factors and impaired ability to perform daily living activities, independent of established cardiovascular disease. We conducted an analysis of the Clarity Cohort, which is a cross-sectional study of 9,816 community-dwelling Irish adults. Of the total cohort, 3,499 completed standardized self-reported health questionnaires, which included questions on activities of daily living. Functional impairment was defined as self-reported impairment in self-care, mobility or household tasks. Using logistic regression analyses, we determined the association between vascular risk factors and functional impairment, independent of demographics, prior coronary artery disease, stroke, congestive heart failure, and peripheral vascular disease. Functional impairment was reported in 40.4% (n = 1,413) of the cohort overall and in 23% of those with established cardiovascular disease. The mean age was 66.2 ± 10.3 years, 52% of the cohort were aged over 65 and 45.6% were male. Some difficulty with instrumental activities of daily living was reported by 35.4% (n = 1,240) while 29.4% (n = 1,029) reported some difficulty with basic activities of daily living. On multivariable analysis, older age [OR 1.03 (1.02, 1.04) per year], current smoking [OR 1.43 (1.08, 1.89)], atrial fibrillation [OR 1.68 (1.07, 2.65)], former alcohol use [OR 1.87 (1.36, 2.57)] and prior stroke [OR 1.91 (1.24, 2.93)] were associated with an increased risk of functional impairment. Older age leaving education [OR 0.96 (0.94, 0.99)], non-use of alcohol [OR 0.76 (0.61, 0.93)] and increased high-density lipoprotein levels [OR 0.70 (0.56, 0.88)] were associated with reduced risk of functional impairment. Independent of established cardiovascular disease, some vascular risk factors are associated with functional impairment. Modification of these risk factors is expected to have a large impact on preservation of functional independence through prevention of overt and covert vascular disease.


Carotid Doppler velocity measurements and anatomic stenosis: correlation is futile.
Duplex ultrasound with Doppler velocimetry is widely used to evaluate the presence and severity of internal carotid artery stenosis; however, a variety of velocity criteria are currently being applied to classify stenosis severity. The purpose of this study is to compare published Doppler velocity measurements to the severity of internal carotid artery stenosis as assessed by x-ray angiography in order to clarify the relationship between these 2 widely used approaches to assess carotid artery disease. Scatter diagrams or "scattergrams" of correlations between Doppler velocity measurements and stenosis severity as assessed by x-ray contrast angiography were obtained from published articles for native and stented internal carotid arteries. The scattergrams were graphically digitized, combined, and segmented into categories bounded by 50% and 70% diameter reduction. These data were combined and divided into 3 sets representing different velocity parameters: (1) peak systolic velocity, (2) end-diastolic velocity, and (3) the internal carotid artery to common carotid artery peak systolic velocity ratio. The horizontal axis of each scattergram was transformed to form a cumulative distribution function, and thresholds were established for the stenosis categories to assess data variability. Nineteen publications with 22 data sets were identified and included in this analysis. Wide variability was apparent between all 3 velocity parameters and angiographic percent stenosis. The optimal peak systolic velocity thresholds for stenosis in stented carotid arteries were higher than those for native carotid arteries. Within each category of stenosis, the variability of all 3 velocity parameters was significantly lower in stented arteries than in native arteries. Although Doppler velocity criteria have been successfully used to classify the severity of stenosis in both native and stented carotid arteries, the relationship to angiographic stenosis contains significant variability. This analysis of published studies suggests that further refinements in Doppler velocity criteria will not lead to improved correlation with carotid stenosis as demonstrated by angiography.


Ventilatory function in Nigerian coal miners.
Ventilatory capacity has been measured in 675 Nigerian colliery employees classified in three groups according to occupation: coalface workers, other underground workers with low exposure to dust, and surface workers in administrative and clerical jobs. Men with current respiratory symptoms were excluded, as were ex-miners. The faceworkers were a slightly older group who smoked less, and they were presumed to be more active. Faceworkers had a highest forced vital capacities (adjusted for age and stature) but the lowest values for indices reflecting maximal expiratory airflows, (FEV1/FVC, PFR FEF, and FMF). Apparently coalface work is associated with an 8% impairment of maximum expiratory airflow, probably due to dust exposure, but also with a modest enhancement in FVC, possibly due to training of the respiratory muscles. Regression coefficients on age for the airflow indices are significantly more negative in faceworkers than in the other groups. Smoking and duration of service did not significantly affect the pattern of results. FEV1 does not vary among the occupational groups in the colliery, and the mean value is close to that predicted on the basis of reference equations previously obtained for non-miners in Nigeria.


The influence of macrophages and the tumor microenvironment on natural killer cells.
Numerous reviews in the field of NK cell biology dictate the pivotal role that NK cells play in tumor rejection. Although these cell types were originally described based on their cytotoxic ability, we now know that NK cells are not naturally born to kill. Both cellular interactions and the local environment in which the NK cell resides in may influence its cytotoxic functions. Just as organ specific NK cells have distinct phenotypic and functional differences, the tumor is a unique microenvironment in itself. The NK cells originally recruited to the tumor site are able to stimulate immune responses and aid in tumor destruction but eventually become persuaded otherwise by mechanisms of immunosuppression. Here, we review potential mechanisms and players involved in NK cell immunosuppression. In particular the effects of another innate immune player, macrophages, will be addressed in augmenting immunosuppression of NK cells within tumors. Tumor-associated macrophages (TAMs) are the main regulatory population of myeloid cells in the tumor and are characterized by their ability to promote tumor cell proliferation and metastasis. In addition, they express/release immunoregulatory factors which have been shown to directly inhibit NK cell function. Understanding how these two cell types interact in the distinct tumor microenvironment will allow us to consider therapies that target TAMs to promote enhanced NK cell activity.


PI3K/AKT, JNK, and ERK pathways are not crucial for the induction of cholesterol biosynthesis gene transcription in intestinal epithelial cells following treatment with the potato glycoalkaloid alpha-chaconine.
We previously reported that exposure of the intestinal epithelial Caco-2 cell line to noncytotoxic concentrations of potato glycoalkaloids resulted in increased expression of cholesterol biosynthesis genes. Genes involved in mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue (AKT) pathways and their downstream effectors such as Jun, c-Myc, and Fos also were induced. MAPK and PI3K/AKT pathways have been described to regulate the activity of sterol regulatory element binding transcription factors (SREBPs) and consequently the expression of cholesterol biosynthesis genes. In this study, to understand the mechanism of induction of cholesterol biosynthesis upon alpha-chaconine treatment, its effect on SREBP-2 protein levels was investigated. We also examined whether MAPK and PI3K/AKT pathways are required for the observed induction of these genes following exposure of cells to alpha-chaconine. Differentiated Caco-2 cells were pretreated with LY294002 (PI3K inhibitor), PD98059 (MEK1 inhibitor), or SP600125 (JNK inhibitor) or a combination of all inhibitors for 24 h prior to coincubation with 10 microM alpha-chaconine for 6 h. Significant increases in precursor and mature protein levels of SREBP-2 were observed after alpha-chaconine exposure. We also observed that alpha-chaconine treatment resulted in significant phosphorylation of AKT, extracellular signal related protein kinase (ERK), and c-jun N terminal protein kinase (JNK) but not that of p38. In general, the kinase inhibitor experiments revealed that phosphorylation of kinases of PI3K/AKT, ERK, and JNK pathways was not crucial for the induction of expression of cholesterol biosynthesis genes, with the exception of SC5DL. The transcription of this later gene was reduced when all three pathways were inhibited. On the basis of these results, it can be postulated that other mechanisms, which may be independent of the MAPK and PI3K/AKT pathways, including possibly post-translational activation of SREBP-2, may be more pivotal for the induction of cholesterol biosynthesis genes following exposure of intestinal cells to alpha-chaconine.


Predissociation mechanism for the lowest 1 Pi u states of N2.
Separate coupled-channel Schrödinger-equation (CSE) models of the interacting (1)Pi(u) (b,c,o) and (3)Pi(u) (C,C(')) states of N(2) are combined, through the inclusion of spin-orbit interactions, to produce a five-channel CSE model of the N(2) predissociation. Comparison of the model calculations with an experimental database, consisting principally of detailed new measurements of the vibrational and isotopic dependence of the (1)Pi(u) linewidths and lifetimes, provides convincing evidence that the predissociation of the lowest (1)Pi(u) levels in N(2) is primarily an indirect process, involving spin-orbit coupling between the b (1)Pi(u)- and C (3)Pi(u)-state levels, the latter levels themselves heavily predissociated electrostatically by the C(') (3)Pi(u) continuum. The well-known large width of the b(v=3) level in (14)N(2) is caused by an accidental degeneracy with C(v=9). This CSE model provides the first quantitative explanation of the predissociation mechanism for the dipole-accessible (1)Pi(u) states of N(2), and is thus likely to prove useful in the construction of realistic radiative-transfer and photochemical models for nitrogen-rich planetary atmospheres.


[Effect of ubiquitin-proteasome pathway on TRAIL inducing apoptosis].
To determine the influence of ubiquitin-proteasome in regulating the TRAIL-mediated apoptosis. RASF cells and SCID mice were divided into 4 groups treated with PBS,anti-DR5, lactacystin, and anti-DR5 plus lactacystin. The apoptosis of cells was detected with Hoechst 33342 and TUNEL. The effect of caspase inhibitor on cell apoptosis was analysed with Hoechst 33342 and Luminescent ATP Lite. Block ubiquitin-proteasome with lactacystin, a highly specific and irreversible proteasome inhibitor, induced 95% cell apoptosis both in vitro and in vivo. In contrast, there was no apoptosis of cells after the treatment with anti-DR5 antibody or lactacystin alone. The inhibition of ubiquitin-proteasome pathway can sensitize rheumatoid arthritis synovial fibroblast cells to TRAIL- induced apoptosis, and the activation of caspase 8 and caspase 4 is necessary in this process.


Measles outbreak from Hong Kong International Airport to the hospital due to secondary vaccine failure in healthcare workers.
To report an outbreak of measles with epidemiological link between Hong Kong International Airport (HKIA) and a hospital. Epidemiological investigations, patients' measles serology, and phylogenetic analysis of the hemagglutinin (H) and nucleoprotein (N) genes of measles virus isolates were conducted. In total, 29 HKIA staff of diverse ranks and working locations were infected with measles within 1 month. Significantly fewer affected staff had history of travel than non-HKIA-related measles patients [10 of 29 (34.5%) vs 28 of 35 (80%); P < .01]. Of 9 airport staff who could recall detailed exposure history, 6 (66.7%) had visited self-service food premises at HKIA during the incubation period, where food trays, as observed during the epidemiological field investigation, were not washed after use. Furthermore, 1 airport baggage handler who was admitted to hospital A before rash onset infected 2 healthcare workers (HCWs) known to have 2 doses of MMR vaccination with positive measles IgG and lower viral loads in respiratory specimens. Infections in these 2 HCWs warranted contact tracing of another 168 persons (97 patients and 71 HCWs). Phylogenetic comparison of H and N gene sequences confirmed the clonality of outbreak strains. Despite good herd immunity with overall seroprevalence of >95% against measles, major outbreaks of measles occurred among HKIA staff having daily contact with many international pssengers. Lessons from severe acute respiratory syndrome (SARS) and measles outbreaks suggested that an airport can be a strategic epidemic center. Pre-exanthem transmission of measles from airport staff to HCWs with secondary vaccine failure poses a grave challenge to hospital infection control.


Ick Ciliary Kinase Is Essential for Planar Cell Polarity Formation in Inner Ear Hair Cells and Hearing Function.
Cellular asymmetries play crucial roles in development and organ function. The planar cell polarity (PCP) signaling pathway is involved in the establishment of cellular asymmetry within the plane of a cell sheet. Inner ear sensory hair cells (HCs), which have several rows of staircase-like stereocilia and one kinocilium located at the vertex of the stereocilia protruding from the apical surface of each HC, exhibit a typical form of PCP. Although connections between cilia and PCP signaling in vertebrate development have been reported, their precise nature is not well understood. During inner ear development, several ciliary proteins are known to play a role in PCP formation. In the current study, we investigated a functional role for intestinal cell kinase (Ick), which regulates intraflagellar transport (IFT) at the tip of cilia, in the mouse inner ear. A lack of Ick in the developing inner ear resulted in PCP defects in the cochlea, including misorientation or misshaping of stereocilia and aberrant localization of the kinocilium and basal body in the apical and middle turns, leading to auditory dysfunction. We also observed abnormal ciliary localization of Ift88 in both HCs and supporting cells. Together, our results show that Ick ciliary kinase is essential for PCP formation in inner ear HCs, suggesting that ciliary transport regulation is important for PCP signaling.SIGNIFICANCE STATEMENT The cochlea in the inner ear is the hearing organ. Planar cell polarity (PCP) in hair cells (HCs) in the cochlea is essential for mechanotransduction and refers to the asymmetric structure consisting of stereociliary bundles and the kinocilium on the apical surface of the cell body. We reported previously that a ciliary kinase, Ick, regulates intraflagellar transport (IFT). Here, we found that loss of Ick leads to abnormal localization of the IFT component in kinocilia, PCP defects in HCs, and hearing dysfunction. Our study defines the association of ciliary transport regulation with PCP formation in HCs and hearing function.


Shame in the treatment of schizophrenia: theoretical considerations with clinical illustrations.
The phenomenology and dynamics of shame have been largely overlooked in the psychoanalytic and psychological literature. The emerging literature now suggests that shame may play a vital role in autonomy and personality development, symptom formation, character pathology, and interpersonal relationships. This paper attempts to describe shame phenomena and identify shame dynamics. The role of shame in the understanding and treatment of schizophrenic individuals is then demonstrated through reference to the writings of Frieda Fromm-Reichmann and examples from the author's clinical work.


Working Memory and Attention - A Conceptual Analysis and Review.
There is broad agreement that working memory is closely related to attention. This article delineates several theoretical options for conceptualizing this link, and evaluates their viability in light of their theoretical implications and the empirical support they received. A first divide exists between the concept of attention as a limited resource, and the concept of attention as selective information processing. Theories conceptualizing attention as a resource assume that this resource is responsible for the limited capacity of working memory. Three versions of this idea have been proposed: Attention as a resource for storage and processing, a shared resource for perceptual attention and memory maintenance, and a resource for the control of attention. The first of these three is empirically well supported, but the other two are not. By contrast, when attention is understood as a selection mechanism, it is usually not invoked to explain the capacity limit of working memory - rather, researchers ask how different forms of attention interact with working memory, in two areas. The first pertains to attentional selection of the contents of working memory, controlled by mechanisms of filtering out irrelevant stimuli, and removing no-longer relevant representations from working memory. Within working memory contents, a single item is often selected into the focus of attention for processing. The second area pertains to the role of working memory in cognitive control. Working memory contributes to controlling perceptual attention - by holding templates for targets of perceptual selection - and controlling action - by holding task sets to implement our current goals.


[Immunological aspects of endometriosis].
The effect of adherence process on Fallopian tubes and ovaries in late stages endometriosis is clear, but it is more important to understand pathophysiologic mechanism of infertility in minimal, mild endometriosis. Although the etiology of endometriosis is unknown, components of the immune system may be involved and play a central role in the pathogenesis of the disease by immunologically altering the peritoneal microenvironment. Increased number and activity of leucocyte subpopulations in the peritoneal fluid result in cytotoxic effects that exert adverse influence on spermatozoa, oocyte, germ cell interaction, and early embryo development, while cytokine and growth factor secretion stimulates or promotes cellular proliferation of endometriotic tissue in an "immunological tolerance" environment. The immunological aspects of endometriosis, including autocrine or paracrine pathways of intercellular communication, are reviewed.


Brain death significantly reduces isolated pancreatic islet yields and functionality in vitro and in vivo after transplantation in rats.
Although approximately 1 million islets exist in the adult human pancreas, current pancreas preservation and islet isolation techniques recover <50%. Presently, cadaveric donors remain the sole source of pancreatic tissue for transplantation. Brain death is characterized by activation of proinflammatory cytokines and organ injury during preservation and reperfusion. In this study, we assessed the effects of brain death on islet isolation yields and functionality. Brain death was induced in male 250- to 350-g Lewis rats by inflation of a Fogarty catheter placed intracranially. The rats were mechanically ventilated for 2, 4, and 6 h before removal of the pancreas (n = 6). In controls, the catheter was not inflated (n = 6). Shortly after brain death induction, a significant increase in serum tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6 was demonstrated in a time-dependent manner. Upregulation of TNF-alpha, IL-1beta, and IL-6 mRNA was noted in the pancreas. Brain death donors presented lower insulin release after glucose stimulation assessed by in situ perfusion of the pancreas. Islet recovery was reduced in brain death donors compared with controls (at 6 h 602.3 +/- 233.4 vs. 1,792.5 +/- 325.4 islet equivalents, respectively; P < 0.05). Islet viability assessed in dissociated islet cells and in intact cultured islets was reduced in islets recovered from brain death donors, an effect associated with higher nuclear activities of NF-kappaB p50, c-Jun, and ATF-2. Islet functionality evaluated in vitro by static incubation and in vivo after intraportal transplantation in syngeneic streptozotocin-induced diabetic rats was significantly reduced in preparations obtained from brain death donors. In conclusion, brain death significantly reduced islet yields and functionality. These observations may lead to strategies to reduce the effects of brain death on pancreatic islets and improve the results in clinical transplantation.


Synthesis and evaluation of antiproliferative microtubule-destabilising combretastatin A-4 piperazine conjugates.
Microtubules are a validated clinical target for the treatment of many cancers. We describe the design, synthesis, biochemical evaluation, and molecular modelling studies of a series of analogues of the microtubule-destabilising agent, combretastatin A-4 (CA-4). Our series of 33 novel compounds contain the CA-4 core structure with modifications to the stilbene linking group, and are predominantly piperazine derivatives. Synthesis was achieved in a two-step process by firstly obtaining the acrylic acid via a Perkin reaction using microwave enhanced synthesis, followed by coupling using either DCC or Mukaiyama's reagent. All target compounds were screened for antiproliferative activity in MCF-7 breast cancer cells. Hydroxyl derivative (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-phenylpiperazin-1-yl)-2-(3,4,5-trimethoxyphenyl) propenone (4m) displayed potent antiproliferative activity (IC50 = 190 nM). Two amino-containing derivatives, (E)-3-(3-amino-4-methoxyphenyl)-1-(4-phenylpiperazin-1-yl)-2-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (4q) and (E)-3-(3-amino-4-methoxyphenyl)-1-(4-(p-tolyl)piperazin-1-yl)-2-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (4x), were the most potent with IC50 values of 130 nM and 83 nM respectively. Representative compounds were shown to depolymerise tubulin, induce G2/M arrest and apoptosis in MCF-7 cells but not peripheral blood mononuclear cells, and induce cleavage of the DNA repair enzyme poly ADP ribose polymerase (PARP) in MCF-7 cells. Modelling studies predict that the compounds bind to tubulin within the colchicine-binding site. These compounds are a valuable addition to the library of CA-4 analogues and 4m, 4q and 4x will be developed further as novel, water-soluble molecules targeting microtubules.


Localization of active pathways in peripheral nerves: a simulation study.
A methodology is investigated for determining the location of active pathways in a peripheral nerve using measurements from a multicontact cuff electrode. The problem is treated as an inverse problem of source localization and solved using the sLORETA algorithm, developed for the electroencephalogram/magnetoencephalogram source localization problem. Simulated measurements are generated corresponding to action potentials traveling along either one or three pathways in a rat sciatic nerve. The performance of the proposed methodology using these measurements is evaluated in terms of localization error, missed pathways, and spurious pathways. The source localization performance when assuming an idealized nerve anatomy is compared to that when the correct anatomy is known. The effect of a spatio-temporal constraint based on the nerve anatomy and electrophysiology is also investigated. The approach in its present form was not found to be sufficiently reliable for subfascicular localization in practice, due to mean localization errors in the 140-180 mum range, high numbers of spurious pathways, and low resolution. Nonetheless, the constraints were shown to produce a marked reduction in the number of spurious pathways. Conditions under which the source localization approach may be useful for peripheral nerves are discussed.


Folate and vitamin B(6) intake and risk of acute myocardial infarction in Italy.
Folate and vitamin B6 intake has been associated with reduced risk of coronary heart disease, but studies are not consistent. The relation between folate and vitamin B6 intake and the risk of acute myocardial infarction (AMI) was assessed in a Mediterranean population. A hospital-based case-control study was conducted in Milan, Italy, between 1995 and 1999. Information was collected by interviewer-administered questionnaires. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) were obtained by multiple logistic regression models. Cases were 507 patients with a first episode of nonfatal AMI, and controls were 478 patients admitted to hospital for acute conditions. Compared to patients in the lowest tertile of intake, the ORs for those in the highest tertile were 0.56 (95% CI 0.35-0.88) for folate and 0.34 (95% CI 0.19-0.60) for vitamin B6. The OR was consistently below unity in strata of sex, age, alcohol, methionine, tobacco smoking, coffee, hypertension and family history of AMI; the inverse association was apparently stronger for vitamin B6 in regular alcohol drinkers than in no or occasional drinkers. Compared to subjects with a low intake of both micronutrients, the OR was 0.29 for those with a high intake of both. Compared to subjects reporting no or occasional alcohol drinking and low methionine and folate intake, the OR was 0.28 in regular drinkers with high methionine and high folate intake. The corresponding value for vitamin B6 was 0.25. A high intake of folates, vitamin B6 and their combination is inversely associated with AMI risk. Partly supported by "Ministero della Salute" (Contract No. 177, RF 2001).


The impact of adolescent stress on nicotine use and affective disorders in rodent models.
Recent findings indicate that stress exposure during adolescence contributes to the development of both nicotine use and affective disorders, suggesting a potential shared biological pathway. One key system that may mediate the association between adolescent stress and nicotine or affective outcomes is the hypothalamic-pituitary-adrenal (HPA) axis. Here we reviewed evidence regarding the effects of adolescent stress on nicotine responses and affective phenotypes and the role of the HPA-axis in these relationships. Literature indicates that stress, possibly via HPA-axis dysfunction, is a risk factor for both nicotine use and affective disorders. In rodent models, adolescent stress modulates behavioural responses to nicotine and increases the likelihood of affective disorders. The exact role that the HPA-axis plays in altering nicotine sensitivity and affective disorder development after adolescent stress remains unclear. However, it appears likely that adolescent stress-induced nicotine use and affective disorders are precipitated by repetitive activation of a hyperactive HPA-axis. Together, these preclinical studies indicate that adolescent stress is a risk factor for nicotine use and anxiety/depression phenotypes. The findings summarized here suggest that the HPA-axis mediates this relationship. Future studies that pharmacologically manipulate the HPA-axis during and after adolescent stress are critical to elucidate the exact role that the HPA-axis plays in the development of nicotine use and affective disorders following adolescent stress.


[Psychosocial rehabilitation at the dawn of the 21st century: III: Interdisciplinary evaluation method and bio-psycho-social schedule].
During the past 20 years, therapeutic and rehabilitative modalities in the field of psychosocial rehabilitation have been diversified in becoming more specific. We have the possibility to offer individualized rehabilitation programs as well as in the general field of socio-professional goals as in the clinical field according to the patients' needs and personal assets. The content of these programs associates various forms of specialized medical and paramedical services. The indications are established trough a careful assessment. The rehabilitation unit of the University Department of Psychiatry in Lausanne has developed a multidisciplinary assessment method based on the bio-psychosocial integrative model and the vulnerability-stress model in integrating the level of experience of Wood for the analysis of the psychosocial functioning. This results in a structured assessment program, which leads to a multidisciplinary comprehensive assessment (difficulties versus adaptative resources).


The role of granzyme B in murine models of acute graft-versus-host disease and graft rejection.
A complete molecular description of the syndromes of graft-versus-host disease (GVHD) and graft rejection could have a significant impact on clinical bone marrow transplantation. Recent in vitro experiments (Heusel et al, Cell 76:977, 1994 and Shresta et al, Proc Natl Acad Sci USA 92:5679, 1995) have shown that the putative mediators of these two syndromes, cytotoxic lymphocytes (CTL) and natural killer (NK) cells, respectively, initiate a program of cell death (apoptosis) in susceptible target tissues in a manner critically dependent on the serine protease Granzyme B (gzm B). In the present study, we have analyzed the phenotype of gzm B-deficient mice using experimental transplant models designed to isolate their CD8+ CTL, CD4+ CTL, and NK compartments. We found a significant impairment in class I-dependent GVHD mediated by gzm B -/- CD8+ CTL, whereas class II-dependent GVHD was not altered using gzm B -/- CD4+ effectors. In a hybrid resistance model, gzm B -/- hosts rejected haplo-identical marrow grafts as efficiently as did their wild-type littermates. This result is surprising in light of a severe defect in the ability of gzm B -/- NK cells to induce apoptosis in susceptible targets in vitro. These in vivo data define significant role for gzm B in cytotoxicity mediated by CD8+ CTL, but not by CD4+ CTL. Furthermore, these results do not support a model of hybrid resistance in which NK cells play a pivotal role.


An Education-Based Text Messaging Program to Improve Nurses' Knowledge, Attitude, and Practice Related to Nosocomial Infections in Intensive Care Settings.
Nosocomial infection (NI) is common in health care settings. Educational strategies such as mobile teaching methods for health care providers may help to resolve this problem. This pilot study assessed the influence of a text messaging program to improve intensive care unit nurses' knowledge, attitude, and practice related to NI prevention. In this single-group experimental study, 32 nurses received an educational intervention via short text messages on their cell phones. Information on knowledge, attitude, and practice regarding NI prevention was collected using a standard scale. Preventive messages about NI were prepared and sent to participants during a 2-month trial. Results were assessed 2 weeks after the intervention, and data were analyzed by paired t test. Knowledge, attitude, and practice of participants increased by 17%, 3%, and 9%, respectively, from baseline to follow up. The average score on the knowledge dimension was lower than for other components. Knowledge components such as hand hygiene, work safety, and protective equipment increased to a lesser degree from pre- to posttest, compared with other aspects (p < .05 versus p < .001). An education-based program operating through short text messages may be a useful in-service training strategy for intensive care unit nurses. [J Contin Educ Nurs. 2019;50(5):211-217.].


Bilinear modeling of EMG signals to extract user-independent features for multiuser myoelectric interface.
In this study, we propose a multiuser myoelectric interface that can easily adapt to novel users. When a user performs different motions (e.g., grasping and pinching), different electromyography (EMG) signals are measured. When different users perform the same motion (e.g., grasping), different EMG signals are also measured. Therefore, designing a myoelectric interface that can be used by multiple users to perform multiple motions is difficult. To cope with this problem, we propose for EMG signals a bilinear model that is composed of two linear factors: 1) user dependent and 2) motion dependent. By decomposing the EMG signals into these two factors, the extracted motion-dependent factors can be used as user-independent features. We can construct a motion classifier on the extracted feature space to develop the multiuser interface. For novel users, the proposed adaptation method estimates the user-dependent factor through only a few interactions. The bilinear EMG model with the estimated user-dependent factor can extract the user-independent features from the novel user data. We applied our proposed method to a recognition task of five hand gestures for robotic hand control using four-channel EMG signals measured from subject forearms. Our method resulted in 73% accuracy, which was statistically significantly different from the accuracy of standard nonmultiuser interfaces, as the result of a two-sample t -test at a significance level of 1%.


Emergence of Monkeypox as the Most Important Orthopoxvirus Infection in Humans.
Monkeypox is an emerging zoonotic disease recognized as the most important orthopoxvirus infection in humans in the smallpox post-eradication era. The clinical presentation of monkeypox is similar to the one of smallpox. The case fatality rate of monkeypox (10%) lies between the case fatality rate of variola major (30%) and variola minor (1%). The disease is endemic in the Democratic Republic of the Congo, but other countries of Central and West Africa either reported cases of monkeypox in humans or circulation in wildlife. The disease was also imported once into the USA. The disease has always been considered rare and self-limiting, however recent sporadic reports suggest otherwise. Unfortunately, the collected data is limited, dispersed and often incomplete. Therefore, the objective of this review is to trace all reported human monkeypox outbreaks and relevant epidemiological information. The frequency and geographical spread of human monkeypox cases have increased in recent years, and there are huge gaps in our understanding of the disease's emergence, epidemiology, and ecology. The monkeypox virus is considered a high threat pathogen causing a disease of public health importance. Therefore, there is an urgent need to focus on building surveillance capacities which will provide valuable information for designing appropriate prevention, preparedness and response activities.


Dietary effects of distillers dried grains with solubles on performance and milk composition of lactating sows.
A study was conducted to evaluate the dietary effect of adding increasing concentrations of distillers dried grains with solubles (DDGS) to corn- and soybean meal-based sow lactation diets on sow and litter performance, energy and N digestibility, plasma urea N (PUN), and milk fat and protein concentrations. Mixed-parity sows [n = 307; 221 ± 15 kg of BW, 4.54 parities, litter size of 10.6, and litter weight at birth (alive) of 15.14 kg] were assigned randomly to 1 of 5 dietary treatments: control (CON; corn-soybean meal); 10, 20, and 30% DDGS; and 30% DDGS high-protein (HP) diets. Sows were moved to farrowing rooms on d 109 of gestation and were fed the dietary treatments until weaning. Within each treatment group, feces and urine for energy and N digestibility analysis (from d 10 to 12 of lactation) and blood for PUN analysis and milk fat and protein concentrations (on d 0 and 19 of lactation) were collected from 6 randomly chosen parity 3 to 5 sows. There were no dietary effects (P = 0.10) of DDGS on ADFI of sows and sow backfat change. However, sows fed 30% DDGS HP lost more BW compared with sows fed CON (P < 0.05). There were no dietary effects (P = 0.71) of DDGS on preweaning mortality of piglets, litter weight gain, and piglet ADG. Dietary treatments did not affect (P > 0.05) DE, ME, N retention, or N digestibility of the diets. There were no differences in the concentrations of fat and protein in milk at weaning (d 19) among dietary treatments. Sows fed 20 and 30% DDGS had less (P < 0.05) PUN at weaning (d 19) than sows fed CON and 30% DDGS HP. Inclusion of up to 30% DDGS in a lactation diet did not affect (P > 0.05) sow and litter performance, DE and ME contents of the diets, N retention and digestibility, and milk composition compared with sows fed a corn-soybean meal CON diet. It was concluded that addition of up to 30% DDGS in a lactation diet will support satisfactory sow and litter performance.


New N(4)-substituted piperazine naphthamide derivatives as BACE-1 inhibitors.
Synthesis and enzymatic evaluation of new series of N(4)-substituted piperazine naphthamide derivatives as BACE-1 inhibitors for the treatment of Alzheimer's disease are reported.


Tensile strength of carbyne chains in varied chemical environments and structural lengths.
Carbyne and carbyne-based low-dimensional structures are promising for several applications including ultra-compact circuits and purification devices. Designing any applied carbyne-based structure requires a fundamental understanding of the mechanical strength of carbyne chains with different lengths at different temperatures and operating chemical environment. Here we use molecular dynamics simulations to investigate the strength of carbyne chains with different lengths at different temperatures. A theoretical framework based on statistical mechanics and molecular dynamics results is presented, proving a fast and insightful method for predicting the rupture force and its physical mechanism. The effect of water molecules' interaction is also studied on the mechanical properties and it is shown that both the tensile strength and rupture strain are improved by the water interaction. The results of this work can be used for designing and analyzing the robustness and reliability of various carbyne-based materials and applied devices for varies working conditions.


Genetic polymorphisms of CYP2B6 is a risk of metabolic associated fatty liver disease in Chinese population.
The expression and activity of cytochrome P450 2B6 (CYP2B6) may be related to the metabolic associated fat liver disease (MAFLD). Since constitutive androstane receptor (CAR) is a classic transcriptional regulator of CYP2B6, and the single nucleotide polymorphisms (SNPs) of CYP2B6 and CAR are both associated with adverse reactions of efavirenz, we hypothesized that genetic polymorphisms of CAR might also result in additional interindividual variability in CYP2B6. This study was devoted to explore the association between CYP2B6 and CAR SNPs and susceptibility to MAFLD. A total of 590 objects of study (118 with MAFLD and 472 healthy control) between December 2014 and April 2018 were retrospectively enrolled. Twenty-two selected SNPs in CYP2B6 and CAR were genotyped with a custom-designed 48-plex SNP Scan TM® Kit. The frequencies of the alleles, genotypes and genetic models of the variants were compared between the two groups. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated. The T allele of rs3745274 in CYP2B6 was associated with a decreased risk for MAFLD (OR 0.610; 95% CI: 0.451-0.825, p = 0.001) which was still statistically significant after adjusting with Bonferroni method(p = 0.014) The allele, genotype and genetic model frequencies were similar in the two groups for the other twenty-one SNPs (all P > 0.05). There were no multiplicative or additive interactions between the SNPs. Our study revealed that rs3745274 variants in CYP2B6 is associated with susceptibility to MAFLD in the Han Chinese population.


Retinoblastoma in transgenic mice.
Retinoblastoma, a malignancy of the eye occurring in young children, has been widely studied as a model for genetic predisposition to cancer. This disease is caused by mutations in both alleles of an anti-oncogene (the retinoblastoma gene, Rb) that inactivate or eliminate the Rb encoded protein, p105Rb (refs 1 and 2). Here we report that expression of a viral oncogene, the simian virus 40 T antigen, in the retina of transgenic mice produces heritable ocular tumours with histological, ultrastructural and immunohistochemical features identical to those of human retinoblastoma. Furthermore, we demonstrate a specific association between p105Rb and T antigen in mouse retinoblastoma tumour cells. Thus, the occurrence of these tumours is in vivo evidence for oncogenesis due to the ocular-specific expression of an Rb-binding oncoprotein that can functionally inactivate the Rb protein. As an animal model for heritable retinoblastoma, these mice should allow the study of the ontogeny, pathogenesis and treatment of this malignant disease.


Role of antibodies to galactocerebroside in experimental allergic encephalomyelitis.
The possible role of antibodies to galactocerebroside was investigated in AS rats with experimental allergic encephalomyelitis (EAE) induced by guinea-pig spinal cord. Passive immunization with rat or rabbit antiserum to galactocerebroside did not protect rats from EAE. Active immunization with galactocerebroside before the encephalitogenic challenge produced antibody to galactocerebroside but also failed to protect rats from EAE. These experiments did not support previous suggestions that antibodies to galactocerebroside are protective.


Expanding Access to the Intrauterine Device in Public Health Facilities in Ethiopia: A Mixed-Methods Study.
In Ethiopia, modern contraceptive prevalence among currently married women nearly tripled over the last decade, but the method mix remains skewed toward short-acting methods. Since 2011, the Integrated Family Health Program (IFHP+), jointly implemented by Pathfinder International and John Snow Inc., has supported the Federal Ministry of Health to introduce intrauterine devices (IUDs) in more than 800 health centers across 4 regions to improve access to a wider range of methods. Between March and August 2014, Pathfinder conducted a mixed-methods study in 40 purposively selected health centers to assess shifts in the contraceptive method mix following introduction of IUDs using data from family planning registers; determine the characteristics of IUD users through a cross-sectional survey of 2,943 family planning clients who accepted the IUD; explore reasons for method discontinuation among 165 clients seeking IUD removal services; and identify facilitators and barriers to IUD use through focus group discussions (N = 115 clients) and key informant interviews (N = 36 providers, facility heads, and health office heads). Introduction of IUDs into the 40 health centers participating in the study was correlated with a statistically significant increase in the contribution of all long-acting reversible contraceptives (LARCs)-both IUDs and implants-to the method mix, from 6.9% in 2011 to 20.5% in 2014 (P<.001). Our study found that latent demand for the IUD was more prevalent than anticipated and that the method was acceptable to a broad cross-section of women. Of the 2,943 women who sought IUDs during the 6-month study period, 18.0% were new contraceptive users (i.e., those using a contraceptive method for the first time ever), 44.7% reported no educational attainment, 62.5% were from rural areas, and 59.3% were younger than 30 years old, with almost 3 in 10 (27.7%) under the age of 25. The most commonly cited reason for seeking IUD removal services was a desire to become pregnant (43% of women). Qualitative data indicated that while acceptability of the method is growing, limited community awareness, myths and misconceptions about the IUD, and infrastructure deficits at health centers must be addressed to further expand access to a broad range of contraceptive methods.


Accessibility of tobacco lipid transfer protein cavity revealed by 15N NMR relaxation studies and molecular dynamics simulations.
Plant LTP1 are small helical proteins stabilized by four disulfide bridges and are characterized by the presence of an internal cavity, in which various hydrophobic ligands can be inserted. Recently, we have determined the solution structure of the recombinant tobacco LTP1_1. Unexpectedly, despite a global fold very similar to the structures already known for cereal seed LTP1, its binding properties are different: Tobacco LTP1_1 is able to bind only one monoacylated lipid, whereas cereal LTP1 can bind either one or two. The 3D structure of tobacco LTP1_1 revealed the presence of a hydrophobic cluster, not observed on cereal LTP1 structures, which may hinder one of the two entrances of the cavity defined for wheat LTP1. To better understand the mechanism of lipid entrance for tobacco LTP1_1 and to define the regions of the protein monitoring the accessibility of the cavity, we have complemented our structural data by the study of the internal dynamics of tobacco LTP1_1, using (15)N magnetic relaxation rate data and MD simulations at room and high temperatures. This work allowed us to define two regions of the protein experiencing the largest motions. These two regions delineate a portal that opens up during the simulation constituting a unique entrance of the hydrophobic cavity, in contrast with wheat LTP1 where two routes were detected. The hydrophobic interactions resulting from a few point mutations are strong enough to completely block the second portal so that the accessibility of the cavity is restricted to one entrance, explaining why this particular LTP1 binds only one lipid molecule.


Nonpoint source pollution management for the multipurpose dam watersheds.
Main pollution sources in multipurpose dam watersheds in Korea are highland fields, stream banks, livestock farms, roads, and construction sites. Specifically, highland fields are the major nonpoint pollution sources. Excessive organic chemicals such as fertilizer and pesticide can be exuded from the land, and the area is likely to be eroded by heavy rain. Fallow, conservative cultivation, and covering can be alternatives for soil protection and reinforcement. In addition to these, construction of detour waterways and improvement of irrigation method can minimize the impact of runoff. In the case of slope in 15% degree or more, prohibiting cultivation and restoring the surface is preferred to improving cultivation method in order to control nonpoint pollution sources efficiently.


Experimental allergic encephalomyelitis in male Lewis rats subjected to calorie restriction.
This work analyzes the effect of calorie restriction on the development of experimental allergic encephalomyelitis (EAE) in Lewis rats. Plasma levels of ACTH, corticosterone, prolactin and growth hormone (GH) and mitogenic responses in submaxillary lymph nodes were measured. Male Lewis rats (6 weeks-old) were submitted to a calorie restriction equivalent to 66% of food restriction or to a normal diet. Fifteen days later, rats were injected with complete Freund's adjuvant plus spinal chord homogenate (SCH) or with complete Freund's adjuvant alone. Rats were monitored daily for clinical signs of EAE and were killed on day 15 after immunization. Only rats subjected to normal diet exhibited clinical signs of the disease. The increase in plasma ACTH and corticosterone found after SCH immunization in controls was not detectable in calorie restricted rats. Likewise, the correlation between circulating ACTH and corticosterone was no longer found after calorie restriction. Generally, calorie restriction by itself augmented plasma ACTH or corticosterone and this increase was not further amplified by SCH immunization. Only calorie restricted rats exhibited augmented plasma prolactin levels after SCH immunization, and decreased plasma GH levels regardless of immunization. Calorie restriction depressed the mitogenic response of lymphoid cells to concanavalin A but not to lipopolysaccharide. Calorie restricted rats did not exhibit augmented mitogenic response to concanavalin A following SCH immunization as those found in controls. The results are compatible with the view that the course of EAE can be significantly modified by caloric restriction.


[Peculiarities of clinical manifestations of chronic abdominal ischemia syndrome].
Peculiarities of clinical manifestations of chronic abdominal ischemia syndrome were studied. Clinical diagnostics of this condition encounters difficulties for the lack of pathognomonic symptoms, diversity of symptoms and similarity with other abdominal diseases. The study involving 110 patients with chronic abdominal pain syndrome included assessment of medical histories, duration of the disease, signs of concomitant gastroenetologic pathology (meteorism, colonic dysfunction, reduced body mass, etc.). The data obtained illustrate peculiarities of the clinical picture giving reason to suspect chronic abdominal ischemia syndrome at the early stage of its development. Such features as the absence of treatment effect, increased frequency, duration and severity of abdominal pain, its extension to all parts of the abdomen and association with food intake, colonic dysfunction (meteorism, constipation) and reduced body mass require exclusion of this syndrome in patients with persistent abdominal pain. The data obtained may be used in early diagnostics of chronic abdominal ischemia syndrome and differentiate it from other abdominal diseases.


The quest for equilibrium: exploring the thin red line between bleeding and ischaemic risks in the management of acute coronary syndromes in chronic kidney disease patients.
Coronary artery disease and acute coronary syndrome (ACS) are both common in patients with chronic kidney disease (CKD). CKD patients have higher risks of bleeding and thrombosis. However, they remain under-represented in major randomized clinical trials (RCTs), and there is no medical evidence-based foundation on which to issue specific recommendations about the management of ACS in CKD. CKD patients with ACS frequently are diagnosed later, receive fewer acute interventions and are at increased risk of over-dosage of medications and under-prescription/under-performance of interventional treatments than CKD patients without ACS. The lack of RCTs should not discourage reliance on clinical common sense, while clearer decisional algorithms with better outcomes are a priority for urgent development. Future guidelines should further refine the assessment of CKD with ACS while placing much greater emphasis on the correct dosing of medications based on contemporaneous renal function. Until a strategy is designed with specific measures translated into the actual decrease of bleeding risk, providers will be forced to balance the equilibrium on a thin red line that is not clearly established.


Effects of AT1 receptor blockade on renal injury and mitogen-activated protein activity in Dahl salt-sensitive rats.
The mitogen-activated protein kinase (MAPK) cascade is an important intracellular mediator of angiotensin II (Ang II)-induced cell growth and differentiation. Here, we examined the effect of angiotensin II type 1 receptor (AT1) receptor blockade on renal injury and MAPK activity in Dahl salt-sensitive (DS) rats. DS rats were maintained on a high (H: 8.0%NaCl, N= 8) or low (L: 0.3%NaCl, N= 7) salt diet, or H + candesartan cilexetil (10 to 15 mg/kg/day, N= 8). Urinary protein excretion (UproteinV), renal cortical collagen content, and glomerular injury (assessed by semiquantitative morphometric analysis) were determined after 4-week treatments. Plasma and kidney Ang II levels were measured by radioimmunoassay. Protein levels of AT1 and AT2 receptors in the renal cortical tissues were analyzed by Western-blotting analyses. MAPKs activities, including extracellular signal-regulated kinases (ERK)1/2, c-Jun NH2-terminal kinases (JNK), p38 MAPK, and Big-MAPK-1 (BMK1), were measured by Western-blotting analyses or in vitro kinase assays. DS/H rats showed higher mean blood pressure (MBP), UproteinV, and renal cortical collagen content than DS/L rats. Increased ERK1/2, JNK, and BMK1 activities were observed in renal cortical tissues of DS/H rats (approximately 6.3-, 4.5-, and 2.5-fold, respectively), whereas p38 MAPK activity was unchanged. Plasma Ang II levels were significantly reduced in DS/H rats compared with DS/L rats, whereas kidney Ang II contents and AT1 receptor protein levels were similar. Candesartan did not alter MBP, but significantly reduced UproteinV and collagen content, and ameliorated progressive sclerotic and proliferative glomerular changes. Furthermore, candesartan decreased renal tissue Ang II contents (from 216 +/- 19 to 46 +/- 3 fmol/mL) and ERK1/2, JNK, and BMK1 activities (-45%, -60%, and -70%, respectively) in DS/H rats. In DS hypertensive rats, some of the renoprotective effects of AT1 receptor blockade are accompanied by reductions in intrarenal Ang II contents and MAPK activity, which might not be mediated through arterial pressure changes.


Stability of a thermophilic TIM-barrel enzyme: indole-3-glycerol phosphate synthase from the thermophilic archaeon Sulfolobus solfataricus.
The stability and activity of indole-3-glycerol phosphate synthase from Sulfolobus solfataricus were studied as a function of pH and temperature. In this paper we focus on three points: (1) the long-term stability of the protein to irreversible denaturation at high temperature; (2) the short-term stability of the protein to reversible temperature-driven unfolding; and (3) the dependence of its activity on temperature. Results can be summarized as follows: (a) the same first-order kinetic constant (0.020+/-0.003 min-1) was determined at different pH values (6.5, 8.0 and 9.5) from long-term stability experiments at 80 degrees C; (b) short-term stability experiments revealed different behaviour in two different pH ranges (6.5-8.0, 8.5-9.5), suggesting that the melting temperature is higher at alkaline than at neutral pH; (c) the dependence of activity on temperature was investigated at pH 7.0 and 9.0, and a discontinuity was observed in the Arrhenius plot of kcat values at pH 9.0. We also investigated the stability in the presence of guanidinium chloride at 20 degrees C either at pH 7.0 or at pH 9.0, and we present data that indicate that the unfolding mechanism closely approaches a two-state model at pH 7.0 and a more complex mechanism at pH 9.0. Satisfactory fitting of the equilibrium unfolding transition obtained by fluorescence measurements at pH 9.0 required a model that involves a stable intermediate in addition to the native and unfolded forms. At 20 degrees C the folded conformation is more stable than the unfolded conformation by (14. 7+/-1.2) kJ/mol at pH 7.0 and by (25.5+/-1.8) kJ/mol at pH 9.0.


Non-Invasive Flexible and Stretchable Wearable Sensors With Nano-Based Enhancement for Chronic Disease Care.
Advances in flexible and stretchable electronics, functional nanomaterials, and micro/nano manufacturing have been made in recent years. These advances have accelerated the development of wearable sensors. Wearable sensors, with excellent flexibility, stretchability, durability, and sensitivity, have attractive application prospects in the next generation of personal devices for chronic disease care. Flexible and stretchable wearable sensors play an important role in endowing chronic disease care systems with the capability of long-term and real-time tracking of biomedical signals. These signals are closely associated with human body chronic conditions, such as heart rate, wrist/neck pulse, blood pressure, body temperature, and biofluids information. Monitoring these signals with wearable sensors provides a convenient and non-invasive way for chronic disease diagnoses and health monitoring. In this review, the applications of wearable sensors in chronic disease care are introduced. In addition, this review exploits a comprehensive investigation of requirements for flexibility and stretchability, and methods of nano-based enhancement. Furthermore, recent progress in wearable sensors-including pressure, strain, electrophysiological, electrochemical, temperature, and multifunctional sensors-is presented. Finally, opening research challenges and future directions of flexible and stretchable sensors are discussed.


Gout.
Gout is a chronic disease of deposition of monosodium urate crystals, which form in the presence of increased urate concentrations. Although environmental factors contribute to hyperuricaemia, renal and gut excretion of urate is central to regulation of serum urate, and genetic factors are important. Activation of the NLRP3 inflammasome and release of interleukin 1β have key roles in initiation of acute gout flares. A "treat to target serum urate" approach is essential for effective gout management; long-term lowering of serum urate to less than 360 μmol/L leads to crystal dissolution and ultimately to suppression of flares. An allopurinol dose-escalation strategy is frequently effective for achieving treatment targets, and several new urate-lowering drugs are also available. Worldwide, rates of initiation and continuation of urate-lowering therapy are very low, and, consequently, achievement of serum urate targets is infrequent. Strategies to improve quality of gout care are needed.


Bioavailable IGF-1 is beneficially associated with biomarkers of endothelial function in young healthy adults: The African-PREDICT study.
Low circulating levels of insulin-like growth factor-1 (IGF-1) are associated with endothelial dysfunction, subsequently leading to the development of cardiovascular disease. To better understand the early phases of vascular deterioration in a young, healthy population, we investigated, cross-sectionally, whether biomarkers of endothelial function (intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand factor antigen (vWFag)) are associated with IGF-1 in a healthy study population forming part of the larger African Prospective study on the Early Detection and Identification of Cardiovascular diseases and Hypertension (African-PREDICT). We included 825 black and white men and women (aged 20-30 years) and determined IGF-1, IGF binding protein-3 (IGFBP-3), ICAM-1, VCAM-1 and vWFag from blood samples. We also measured 24-h blood pressure and health behaviours namely waist circumference, accelerometery, cotinine and gamma glutamyl transferase. We used the IGF-1/IGFBP-3 M ratio as an estimate of bioavailable IGF-1. In multivariable-adjusted regression analyses performed in the total group, VCAM-1 associated positively with IGFBP-3 (β = 0.21; p < .001) and negatively with IGF-1/IGFBP-3 (β = -0.18; p < .001). ICAM-1 showed a borderline negative association with IGF-1 (β = -0.09; p = .054) and IGF-1/IGFBP-3 (β = -0.08; p = .057). vWFag was not associated with IGF-1, IGFBP-3 or bioavailable IGF-1. VCAM-1 is beneficially associated with IGF-1 in a young healthy cohort, independent of sex, ethnicity, blood pressure and health behaviours - thereby confirming the potential importance of bioavailable IGF-1 in early vascular endothelial protection.


Effects of Reiki on anxiety, depression, pain, and physiological factors in community-dwelling older adults.
The purpose of this study was to evaluate the effect of Reiki as an alternative and complementary approach to treating community-dwelling older adults who experience pain, depression, and/or anxiety. Participants (N = 20) were randomly assigned to either an experimental or wait list control group. The pre- and posttest measures included the Hamilton Anxiety Scale, Geriatric Depression Scale-Short Form, Faces Pain Scale, and heart rate and blood pressure. The research design included an experimental component to examine changes in these measures and a descriptive component (semi-structured interview) to elicit information about the experience of having Reiki treatments. Significant differences were observed between the experimental and treatment groups on measures of pain, depression, and anxiety; no changes in heart rate and blood pressure were noted. Content analysis of treatment notes and interviews revealed five broad categories of responses: Relaxation; Improved Physical Symptoms, Mood, and Well-Being; Curiosity and a Desire to Learn More; Enhanced Self-Care; and Sensory and Cognitive Responses to Reiki.


Predictors of reintubation in trauma intensive care unit: qatar experience.
To determine the causes, predictors and outcomes of re-intubation. Retrospective analysis of data collected from the trauma data base registry was conducted to identify the extubation failure cases in Trauma ICU at Hamad General Hospital, the only Level I trauma center in Qatar between January 2009 and December 2010. Demographics, mechanism of Injury, complications, injury severity score (ISS), Glasgow Coma Scale (GCS), ICU-length of stay (LOS), and mortality were analyzed among trauma patients who need reintubation within 48 hrs after extubation (group 1) compared to successfully extubated patients (group 2). A total of 954 patients were admitted to the trauma ICU, of which 343 were intubated orotracheally. The mean age of patients was 32±12 years with male predominance (95%). Motor vehicle crash (41%), pedestrian injury (20%) and falls (18%) were the most common mechanisms of injury. Reintubation (group 1) was required in 24 patients (7%). Patients in group 1 had higher rate of head injury mainly SAH (88%), pneumonia (79%) and pulmonary contusion (58%). The mean ICU-LOS was higher in the reintubated patients (p=0.010) in comparison to group 2. Forty-six percent of reintubated patients required tracheostomy. The mean age, ISS, GCS and tube size was comparable among the two groups. Furthermore, reintubation was not associated with higher mortality rate (p=0.910). However, Ventilator-associated pneumonia (VAP) (odd ratio=3.61 [95% CI 1.25-10.44]; p=0.020) and ventilator days (odd ratio=1.09 [95% CI 1.024-1.153]; p=0.006) were independent predictors of reintubation by multivariate analysis. Re-intubation is associated with increased ICU-LOS and need for tracheostomy. VAP and prolonged intubation are independent predictors of re-intubation. Our finding addresses the value of prevention and early treatment of infection in intubated patients. This study may represent an audit of local practice as well.


Long-term processes in waste deposits.
A conceptual model, which is a unitary and continuous description of the overall processes in waste deposits, has been developed. In the model the most important processes governing the long-term fate of organic matter in landfills and the transport and retention of toxic metals are included. With the model as a base, a number of scenarios with different levels of complexity have been defined and studied in order to carry out long-term assessments of the chemical evolution in waste deposits for industrial and municipal solid waste containing much organic matter and the leaching of toxic metals. The focus of the modelling has been to quantify the important processes occurring after the methane production phase has ceased, i.e. during the humic phase. The scenarios include the main mechanisms based on various transport processes as well as different landfill constructions, e.g. binding capacities of sulfides and humic substances. They also include transport mechanisms by which the reactant oxygen can intrude into a deposit, sorption capacities of hydrous ferric oxides, and pH-buffering reactions, etc. Scoping calculations have shown that the binding capacity of humic substances is sufficient to bind all toxic metals (Cd, Cr, Pb, Zn and Hg). In addition, the humics could also bind a smaller part of Ca, Fe and Al, provided much of the organic waste remain as humic substances. Sulfides on the other hand can bind approximately twice the amount of all toxic metals. The binding capacity of hydrous ferric oxides, which can be formed by oxidation reactions during the humic phase, is estimated to be three times the total content of metals that can sorb on hydrous ferric oxides. In the studied landfill the pH-buffering capacity, primarily represented by calcite, is estimated to be 1 mol/kg dry waste. Quantifications indicate that the alkalinity of the wastes is high enough to buffer the acidity produced by the oxidation of sulfides and by the degradation of organic matter, as well as that added by acid precipitation. Therefore, the main conclusion is that higher remobilisation rates of heavy metals due to lowering of pH are not expected for many thousands of years.


Hypoxia-reoxygenation induces premature senescence in FA bone marrow hematopoietic cells.
Hematopoietic cells are often exposed to transient hypoxia and reoxygenation as they develop and migrate. Given that bone marrow (BM) failure occurred in patients with Fanconi anemia (FA), we reason that hypoxia-then-reoxygenation represents a physiologically relevant stress for FA hematopoietic progenitor/stem cells. Here we show that expansion of Fancc-/- BM cells enriched for progenitor and stem cells was significantly decreased after 2 continuous cycles of hyperoxic-hypoxic-hyperoxic treatments compared with wild-type (WT) BM cells. This inhibition was attributable to a marked decrease of lineage-depleted (Lin-) ScaI- c-kit+ cells and more primitive Lin- ScaI+ c-kit+ cells in Fancc-/- BM cells following reoxygenation. Evaluation of the cell-cycle profile of long-term BM culture (LTBMC) revealed that a vast majority (70.6%) of reoxygenated Fancc-/- LTBMC cells was residing in the G0 and G1 phases compared with 55.8% in WT LTBMC cells. Fancc-/- LTBMC cells stained intensely for SA-beta-galactosidase activity, a biomarker for senescence; this was associated with increased expression of senescence-associated proteins p53 and p21(WAF1/CIP1). Taken together, these results suggest that reoxygenation induces premature senescence in Fancc-/- BM hematopoietic cells by signaling through p53, up-regulating p21, and causing senescent cell-cycle arrest. Thus, reoxygenation-induced premature senescence may be a novel mechanism underlying hematopoietic cell depletion and BM failure in FA.


Construction of minitransposons for constitutive and inducible expression of pertussis toxin in bvg-negative Bordetella bronchiseptica.
Appropriately detoxified pertussis toxin (PT) of Bordetella pertussis is considered to be an essential component of new-generation whooping cough vaccines, but the development of a procedure to obtain high levels of purified toxin has been and continues to be a major difficulty. To produce a system enabling the biological separation of PT from other virulence determinants of B. pertussis and the attainment of high yields of the toxin, minitransposons containing the PT operon were constructed and stably integrated into the chromosome of Bordetella virulence regulatory gene (bvg)-negative Bordetella bronchiseptica ATCC 10580. Since the minitransposons introduced into Bordetella spp. lack the cognate transposase function, they are unable to undergo further transposition events or mediate gene deletions and rearrangements that lead to strain instability. The TnPtacPT minitransposon contains the PT operon under the control of the tac promoter and directs IPTG (isopropyl-beta-D-thiogalactopyranoside)-inducible expression of PT in B. bronchiseptica ATCC 10580. The level of IPTG-induced PT expression was, however, lower than that found for the wild-type B. pertussis Tohama I strain. The TnfusPT minitransposon contains a promoterless PT operon which is only expressed after insertion of the transposon downstream of an appropriately oriented indigenous promoter. After "promoter probing" of B. bronchiseptica with the transposon, clones were screened for PT production by immunoblotting with specific monoclonal antibodies. One clone, designated B. bronchiseptica 10580:: TnfusPT1, expresses significantly higher levels of PT than does B. pertussis Tohama I. The recombinant toxin produced was biologically active in the Chinese hamster ovary cell-clustering assay. High-level expression of PT from a B. bronchiseptica host promoter should provide better yields of the toxin from bacteria not producing other bvg-regulated pathogenesis factors that may play a role in the undesired side effects of current pertussis vaccine preparations.


Nasopharyngeal undifferentiated carcinoma with sarcomatoid features: Pitfalls in the immunohistochemistry.
We present a case of an undifferentiated subtype of non-keratinizing squamous cell carcinoma (NK-SCC) with sarcomatoid features in the nasopharynx in a 69-year-old man who was difficult to diagnose due to spindle-shaped malignant cells. He was admitted because of a right nasal obstruction and right headache, and imaging revealed a heterogeneously enhanced irregularly shaped mass at the nasopharynx. Histopathologically, the tumour was partially organised, and the tumour cells were epithelioid or spindle-shaped. Initially, we erroneously diagnosed the tumour as an angiosarcoma owing to its false-negative immunoreaction for cytokeratins and a mistaken interpretation for CD31. After in situ hybridization for Epstein-Barr virus was positive, a consultation and additional immunostaining (including re-staining for cytokeratin with varying dilutions) were performed, and the diagnosis was revised to NK-SCC with sarcomatoid features. We believe that sarcomatoid features may be observed in nasopharyngeal carcinoma and in this case, immunostaining using various epithelial markers is necessary and careful attention should be paid to the interpretation of immunostaining.


[Value of exploring the deep lymphatic system of the lower limbs using lymphoscintigraphy. Preliminary study of 18 patients with arteritis].
Lymphoscintigraphy of lower limbs generally involves bilateral subcutaneous injection of a radioactive colloid into the first or second interdigital space: only the superficial internal saphenous pathway is visualized in this way (superficial lymphoscintigraphy: SL). However, the external saphenous and deep pathways can be explored by an external retromalleolar injection as demonstrated in radiology. Isotopic exploration of the external saphenous pathway and deep lymphatics (deep lymphoscintigraphy: DL) was carried out in 18 patients with arteritis also investigated by SL. The study forms part of a prospective trial of edema developing after femoro-popliteal shunts. The deep lymphatics are correctly and easily visualized, and in about 20% of cases there exist anomalies of distribution of superficial or deep lymphatic flow, morphologic anomalies developing postoperatively in one pathway only, or in both pathways. DL is a simple, reliable method of investigation of deep lymphatics, and complete exploration of lymphatics of lower limbs should include both SL and DL.


Knowledge and participation in mass drug administration against lymphatic filariasis and soil-transmitted helminth infections among the community members in Dar es Salaam, Tanzania.
Although the WHO has made an effort to ensure optimal participation of the community in mass drug administration (MDA) against lymphatic filariasis (LF) and soil-transmitted helminth infections (STHIs), studies are still reporting suboptimal coverage. This study assessed the knowledge and participation of the community in MDA against LF and SHTIs in Tanzania to provide updates on its acceptability. A cross-sectional study was conducted in Dar es Salaam from December 2021 to February 2022 among market vendors. The information regarding demographic characteristics, knowledge and participation in MDA was collected using a questionnaire. Statistical Package for Social science version 26 was used for data analysis. More than half of the participants demonstrated an adequate level of knowledge of LF and STHI, 212 (50.8%) and 267 (64%), respectively. Only 286 (68.5%) reported having heard about MDA against LF and STHIs, out of which 119 (42%) had taken the medication. Of those who disagreed to participate in MDA, 20 (50%) claimed to fear the side effects of the medication. This study found that the community has average knowledge and poor participation in MDA against LF and STHIs. Community sensitization is recommended to increase the participation of the community.


SARS-CoV-2 exploits cellular RAD51 to promote viral propagation: implication of RAD51 inhibitor as a potential drug candidate against COVID-19.
Viruses are constantly evolving to promote propagation in the host. Here, we show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes host RAD51 for replication. Silencing of RAD51 impaired SARS-CoV-2 propagation. Viral RNA colocalized with RAD51 in the cytoplasm of SARS-CoV-2-infected cells, suggesting that both viral RNA and RAD51 may form a replication complex. We, therefore, evaluated RAD51 inhibitors as possible therapeutic agents against SARS-CoV-2. Indeed, RAD51 inhibitors exerted antiviral activities against not only Wuhan but also variants of SARS-CoV-2. Molecular docking model shows that RAD51 inhibitors impede SARS-CoV-2 propagation by interfering with dimerization of RAD51. These data suggest that RAD51 may represent a novel host-based drug target for coronavirus disease 2019 treatment.


The control of the form and function of the ribosomes in androgen-dependent tissues by testosterone.
1. The ribosome content of the rat ventral prostate gland is controlled by the concentrations of circulating androgens and the polyribosomal complement of the total population of ribosomes is acutely dependent on androgenic stimulation. After the administration of testosterone to castrated rats in vivo, there is a pronounced increase in the amounts of heavy (150-240S) polyribosomes. 2. These results are consistent with a pronounced increase in the mRNA and rRNA content of the prostate gland after the administration of testosterone in vivo. 3. From studies conducted both in vitro, the heavy prostate polyribosomes formed after androgenic stimulation are particularly active in protein synthesis. 4. The androgen-stimulated increase in the formation of prostate polyribosomes has a mandatory requirement for sustained RNA and protein synthesis. 5. Since the androgen-mediated increase in prostate polyribosomes may also be suppressed by the concomitant administration of certain anti-androgenic steroids in vivo, the response in polyribosome formation is probably initiated by the binding of a metabolite of testosterone, 5alpha-dihydrotestosterone, in the prostate gland. 6. The relevance of these findings to the pronounced increase in protein synthesis in androgen-dependent tissues after hormonal stimulation is discussed.


Sialylated Glycan Bindings from SARS-CoV-2 Spike Protein to Blood and Endothelial Cells Govern the Severe Morbidities of COVID-19.
Consistent with well-established biochemical properties of coronaviruses, sialylated glycan attachments between SARS-CoV-2 spike protein (SP) and host cells are key to the virus's pathology. SARS-CoV-2 SP attaches to and aggregates red blood cells (RBCs), as shown in many pre-clinical and clinical studies, causing pulmonary and extrapulmonary microthrombi and hypoxia in severe COVID-19 patients. SARS-CoV-2 SP attachments to the heavily sialylated surfaces of platelets (which, like RBCs, have no ACE2) and endothelial cells (having minimal ACE2) compound this vascular damage. Notably, experimentally induced RBC aggregation in vivo causes the same key morbidities as for severe COVID-19, including microvascular occlusion, blood clots, hypoxia and myocarditis. Key risk factors for COVID-19 morbidity, including older age, diabetes and obesity, are all characterized by markedly increased propensity to RBC clumping. For mammalian species, the degree of clinical susceptibility to COVID-19 correlates to RBC aggregability with p = 0.033. Notably, of the five human betacoronaviruses, the two common cold strains express an enzyme that releases glycan attachments, while the deadly SARS, SARS-CoV-2 and MERS do not, although viral loads for COVID-19 and the two common cold infections are similar. These biochemical insights also explain the previously puzzling clinical efficacy of certain generics against COVID-19 and may support the development of future therapeutic strategies for COVID-19 and long COVID patients.


Management of epilepsy in childhood.
Epilepsy is the commonest neurological disorder of children. Between 0.5 and 1% of the childhood population is affected either temporarily or chronically. In the individual it is important to be certain that the diagnosis is correct and thereafter to classify the seizure type(s) and, if possible, the epileptic syndrome. This will facilitate optimal therapeutic intervention and rational management of any associated problems.


Respiratory Viruses and Cystic Fibrosis.
The threat of respiratory virus infection to human health and well-being has been clearly highlighted by the coronavirus disease 2019 (COVID-19) pandemic. For people with cystic fibrosis (CF), the clinical significance of viral infections long predated the emergence of severe acute respiratory syndrome coronavirus 2. This article reviews the epidemiology, diagnosis, and treatment of respiratory virus infection in the context of CF as well as the current understanding of interactions between viruses and other microorganisms in the CF lung. The incidence of respiratory virus infection in CF varies by age with young children typically experiencing more frequent episodes than adolescents and adults. At all ages, respiratory viruses are very common in CF and are associated with pulmonary exacerbations. Respiratory viruses are identified at up to 69% of exacerbations, while viruses are also frequently detected during clinical stability. The full impact of COVID-19 in CF is yet to be established. Early studies found that rates of COVID-19 were lower in CF cohorts than in the general population. The reasons for this are unclear but may be related to the effects of shielding, infection control practices, maintenance CF therapies, or the inflammatory milieu in the CF lung. Observational studies have consistently identified that prior solid organ transplantation is a key risk factor for poor outcomes from COVID-19 in CF. Several key priorities for future research are highlighted. First, the impact of highly effective CFTR modulator therapy on the epidemiology and pathophysiology of viral infections in CF requires investigation. Second, the impact of respiratory viruses on the development and dynamics of the CF lung microbiota is poorly understood and viral infection may have important interactions with bacteria and fungi in the airway. Finally, bacteriophages represent a key focus of future investigation both for their role in transmission of antimicrobial resistance and as a promising treatment modality for multiresistant pathogens.


[Ulcer complications in the county of Funen during 1980-1990. Are there any changes in the frequency of hospitalization following the release of potent ulcer drugs for over-the-counter sale?].
With the object of investigating whether the release of H2-blockers and sucralfate for over-the-counter sale in 1989 in Denmark and the simultaneous discontinuation of the general subsidy for potent ulcer medicine have had any influence on the frequency of hospitalisation for ulcer complications, the number of these were investigated in the County of Funen during a nine-year period prior to these alterations. The number of hospitalisations on account of ulcer complications during the first year after the alterations and thereafter were assessed on the basis of the prior tendency. In addition, the characteristics of the patients were assessed by a retrospective review of the case reports for the one-year periods before and after the alterations in the dispensing rules. The number of hospitalisations on account of ulcer complications in the County of Funen rose by 45% during the period 1.4.1980-31.3.1989. No increases in the number of hospitalisations after the alterations could be demonstrated. The number of patients admitted to Odense Hospital with ulcer complications and their characteristics are, similarly, unchanged after the alterations. Three case histories are, however, registered in which the alterations may have influenced the development of the ulcer complications. There appear to be good ground to continue registration of ulcer complications with the object of investigating the long-term consequences of these alterations particularly if potent ulcer medicine is used to a greater extent as over-the-counter medicine.