Hybrid 2D Correlation-Based Loss Function for the Correction of Systematic Errors.
We present the derivation of a new kind of loss function from the symmetry rules of synchronous and asynchronous two-dimensional correlation maps. This loss function, which takes into account correlations that are based on causal relations among the members of a series of spectra, can be employed to solve non-linear inverse problems that are plagued by systematic multiplicative errors. This possibility results from the correlation-based loss function being practically insensitive to such systematic errors, which often arise in spectroscopy because sample spectra are usually ratioed against reference spectra. Using dispersion analysis, a sophisticated method of band fitting, of the spectra of poly(methyl methacrylate) films deposited on gold, we demonstrate the applicability and validity of the new loss function. If gold is used as a substrate, experimental spectra are often unphysical, that is, they display reflectance values larger than unity. In such cases, our correlation-based loss function not only helps to achieve accurate fits but also provides corrections to obtain physically meaningful spectra, which leads to results that are superior to conventional correction methods. The validity of the results is checked and proved with help of the results of dispersion analysis of spectra of films of poly(methyl methacrylate) on calcium fluoride (CaF2) and silicon (Si), which do not suffer from the systematic errors.


The 'Kidney' model for optimising feedback in undergraduate clinical communication: A meta-ethnographic systematic review.
Feedback frameworks/models focus on certain aspects of the feedback process, but a coherent and systematic model is lacking. A meta-ethnography was conducted to identify and synthesise guidance for optimising feedback interactions in undergraduate clinical communication simulations. A systematic search of 4 electronic databases and grey literature was conducted. Following Noblit and Hare's seven phases for conducting meta-ethnography, key themes and concepts were synthesised to provide new interpretations of components in effective feedback interactions. 373 publications were identified and 14 included for the final synthesis, which informed the development of a new Feedback Kidney Model. The Model illustrates the interconnections of various components that allow for effective feedback interactions. The main processes include preparation, proactivity, analysis and feedback information, reception and response, and influencing factors. This meta-ethnography moves beyond providing an up-to-date synthesis of feedback guidance to proposing the brand-new Feedback Kidney Model, which can guide medical education and future research into how feedback is co-constructed and utilised to promote learning. Clinical communication should incorporate meta-cognitive training and using this Model will help students better utilise on-site face-to-face feedback to enhance their learning and improve future communication with patients.


Intratubular Large Cell Hyalinizing Sertoli Cell Tumor of the Testes in a 4-Year-Old Male With Peutz-Jeghers Syndrome.
Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder that typically displays familial inheritance. Gastrointestinal polyposis and cutaneous pigmentation is a classic presentation of this syndrome. The reported lifetime cumulative cancer risk in PJS patients is >76% when compared with the general public with females affected more often than males. The prepubertal testicular tumor registry found Sertoli cell tumors (SCTs) to compose approximately 1% of all pediatric solid tumors. Prepubertal testicular masses are relatively rare. Only a small number of SCT cases have been reported in the first decade of life. The concurrence of PJS and feminizing SCTs of the testes is an increasingly recognized cause of prepubertal gynecomastia. The testicular lesions observed in patients with PJS primarily represent multifocal intratubular large cell hyalinizing SCTs with a distinct morphology that differs from large cell calcifying SCTs and sex cord tumors with annular tubules. Here, we describe the diagnosis and treatment course of a 4-year-old male with a SCT of the testes and diagnosis of PJS.


Stoichiometry of N-methyl-D-aspartate receptors within the suprachiasmatic nucleus.
The circadian pacemaker within the suprachiasmatic nucleus (SCN) confers daily rhythms to bodily functions. In nature, the circadian clock will adopt a 24-h period by synchronizing to the solar light/dark cycle. This light entrainment process is mediated, in part, at glutamatergic synapses formed between retinal ganglion afferents and SCN neurons. N-methyl-D-aspartate receptors (NMDARs) located on SCN neurons gate light-induced phase resetting. Despite their importance in circadian physiology, little is known about their functional stoichiometry. We investigated the NR2-subunit composition with whole cell recordings of SCN neurons within the murine hypothalamic brain slice using a combination of subtype-selective NMDAR antagonists and voltage-clamp protocols. We found that extracellular magnesium ([Mg](o)) strongly blocks SCN NMDARs exhibiting affinities and voltage sensitivities associated with NR2A and NR2B subunits. These NMDAR currents were inhibited strongly by NR2B-selective antagonists, Ro 25-6981 (3.5 microM, 55.0 +/- 9.0% block; mean +/- SE) and ifenprodil (10 microM, 55.8 +/- 3.0% block). The current remaining showed decreased [Mg](o) affinities reminiscent of NR2C and NR2D subunits but was highly sensitive to [Zn](o), a potent NR2A blocker, showing a approximately 44.2 +/- 1.1% maximal inhibition at saturating concentrations with an IC(50) of 7.8 +/- 1.1 nM. Considering the selectivity, efficacy, and potency of the drugs used in combination with [Mg](o)-block characteristics of the NMDAR, our data show that both diheteromeric NR2B NMDARs and triheteromeric NR2A NMDARs (paired with an NR2C or NR2D subunits) account for the vast majority of the NMDAR current within the SCN.


Preoperative Transcatheter Arterial Embolization for Spontaneous Rupture of Huge Amebic Liver Abscess with Massive Intraperitoneal Hemorrhage.
An 18-year-old male developed a huge liver abscess with severe anemia over the course of 2 weeks. Abdominal contrast enhanced computed tomography showed ruptured huge liver abscess in the right liver lobe with signs of active hemorrhage (contrast extravasation). Serology examination confirmed amoeba as the suspected pathogen of cause. Angiography was performed followed by transcatheter arterial embolization to localize and control the hemorrhage. Embolization using a combination of polyvinyl alcohol and gelfoam successfully controlled the active hemorrhage. Exploratory laparotomy was performed to evacuate and debride the huge abscess. Metronidazole was given and showed good results. Huge liver abscess size is a predictor of conservative management failure and requires a gradual step-up intervention. The purpose of this paper is to explain the importance of imaging in detecting liver abscess and active hemorrhage along with the role of interventional radiology in this case.


Anniversary paper. Development of x-ray computed tomography: the role of medical physics and AAPM from the 1970s to present.
The AAPM, through its members, meetings, and its flagship journal Medical Physics, has played an important role in the development and growth of x-ray tomography in the last 50 years. From a spate of early articles in the 1970s characterizing the first commercial computed tomography (CT) scanners through the "slice wars" of the 1990s and 2000s, the history of CT and related techniques such as tomosynthesis can readily be traced through the pages of Medical Physics and the annals of the AAPM and RSNA/AAPM Annual Meetings. In this article, the authors intend to give a brief review of the role of Medical Physics and the AAPM in CT and tomosynthesis imaging over the last few decades.


Identification, cloning and expression of rabbit vascular smooth muscle Kv1.5 and comparison with native delayed rectifier K+ current.
1. The molecular basis of voltage-gated, delayed rectifier K+ (KDR) channels in vascular smooth muscle cells is poorly defined. In this study we employed (i) an antibody against Kv1.5 and (ii) a cDNA clone encoding Kv1.5 derived from rabbit portal vein (RPV) to demonstrate Kv1.5 expression in RPV and to compare the properties of RPVKv1.5 expressed in mammalian cells with those of native RPV KDR current. 2. Expression of Kv1.5 channel protein in RPV was demonstrated by (i) immunocytolocalization of an antibody raised against a C-terminal epitope of mouse cardiac Kv1.5 in permeabilized, freshly isolated RPV smooth muscle cells and (ii) isolation of a cDNA clone encoding RPVKv1.5 by reverse transcription-polymerase chain reaction (RT-PCR) using mRNA derived from endothelium-denuded and adventitia-free RPV. 3. RPVKv1.5 cDNA was expressed in mammalian L cells and human embryonic kidney (HEK293) cells and the properties of the expressed channels compared with those of native KDR channels of freshly dispersed myocytes under identical conditions. 4. The kinetics and voltage dependence of activation of L cell-expressed RPVKv1.5 and native KDR current were identical, as were the kinetics of recovery from inactivation and single channel conductance. In contrast, there was little similarity between HEK293 cell-expressed RPVKv1.5 and native KDR current. 5. Inactivation occurred with the same voltage for half-maximal availability, but the kinetics and slope constant for the voltage dependence of inactivation for L cell-expressed RPVKv1.5 and the native current were different: slow time constants were 6.5 +/- 0.6 and 3.5 +/- 0.4 s and slope factors were 4.7 +/- 0.2 and 7.0 +/- 0.8 mV, respectively. 6. This study provides immunofluorescence and functional evidence that Kv1.5 alpha-subunits are a component of native KDR channels of vascular smooth muscle cells of RPV. However, the differences in kinetics and voltage sensitivity of inactivation between L cell- and HEK293 cell-expressed channels and native KDR channels provide functional evidence that vascular KDR current is not due to homomultimers of RPV Kv1.5 alone. The channel structure may be more complex, involving heteromultimers and modulatory Kvbeta-subunits, and/or native KDR current may have other components involving Kvalpha-subunits of other families.


Identification of primary lysosomes in human megakaryocytes and platelets.
The presence of lysosomal enzymes in human platelets is well documented; the identity of the "lysosome," however, has been the subject of some disagreement. In order to determine the time of appearance and subcellular localization of two lysosomal enzymes in megakaryocytes (MK) and platelets, we examined normal human bone marrow and blood by electron microscopy and cytochemistry. Acid phosphatase (AcPase) was present in the Golgi region in the youngest recognizable MK, as well as in those with a considerable degree of cytoplasmic maturation. Heavy reaction product was usually confined to one or two Golgi-associated cisternae and coated vesicles; other Golgi cisternae were sometimes lightly reactive. In mature MK, reaction product was limited to vesicles of variable size, but smaller than alpha-granules. Another lysosomal enzyme, arylsulfatase (AS), was localized in similar small vesicles in MK of all stages; it could not be demonstrated in the Golgi complex. Vesicles containing AS were also found in about 25% of platelet profiles, whereas vesicles containing AcPase were found in only about 15% of platelet profiles. The alpha-granules of all MK and platelets examined were negative for both enzymes. We conclude that the enzyme-containing vesicles in these cells constitute the lysosomes and that they are distinct from other platelet organelles. Since there was no evidence that they had participated in any digestive event, we believe that they are primary lysosomes, whose contents are secreted during platelet aggregation and the release reaction.


Early warning of COVID-19 hotspots using human mobility and web search query data.
COVID-19 has disrupted the global economy and well-being of people at an unprecedented scale and magnitude. To contain the disease, an effective early warning system that predicts the locations of outbreaks is of crucial importance. Studies have shown the effectiveness of using large-scale mobility data to monitor the impacts of non-pharmaceutical interventions (e.g., lockdowns) through population density analysis. However, predicting the locations of potential outbreak occurrence is difficult using mobility data alone. Meanwhile, web search queries have been shown to be good predictors of the disease spread. In this study, we utilize a unique dataset of human mobility trajectories (GPS traces) and web search queries with common user identifiers (> 450 K users), to predict COVID-19 hotspot locations beforehand. More specifically, web search query analysis is conducted to identify users with high risk of COVID-19 contraction, and social contact analysis was further performed on the mobility patterns of these users to quantify the risk of an outbreak. Our approach is empirically tested using data collected from users in Tokyo, Japan. We show that by integrating COVID-19 related web search query analytics with social contact networks, we are able to predict COVID-19 hotspot locations 1-2 weeks beforehand, compared to just using social contact indexes or web search data analysis. This study proposes a novel method that can be used in early warning systems for disease outbreak hotspots, which can assist government agencies to prepare effective strategies to prevent further disease spread. Human mobility data and web search query data linked with common IDs are used to predict COVID-19 outbreaks. High risk social contact index captures both the contact density and COVID-19 contraction risks of individuals. Real world data was collected from 200 K individual users in Tokyo during the COVID-19 pandemic. Experiments showed that the index can be used for microscopic outbreak early warning.


Ferroptosis regulation by methylation in cancer.
Epigenetic regulation plays a critical role in cancer development and progression. Methylation is an important epigenetic modification that influences gene expression by adding a methyl group to nucleic acids and proteins. Ferroptosis is a new form of regulated cell death triggered by the accumulation of iron and lipid peroxidation. Emerging evidence have shown that methylation regulation plays a significant role in the regulation of ferroptosis in cancer. This review aims to explore the methylation regulation of ferroptosis in cancer, including reactive oxygen species and iron bio-logical activity, amino acid and lipid metabolism, and drugs interaction. The findings of this review may provide new insights and strategies for the prevention and treatment of cancer.


Mortality in patients of the Glasgow Blood Pressure Clinic.
The mortality of 3783 non-malignant hypertensive patients attending the Glasgow Blood Pressure Clinic between 1968 and 1983 and followed for an average of 6.5 years was compared with that in three control groups: the general population of Strathclyde a group of 15 422 subjects aged 45-64 years and screened in Renfrew and Paisley between 1972 and 1976, and a group of hypertensives seen in a blood pressure clinic based on general practice in Renfrew. Average blood pressure for men at entry to the Glasgow Clinic was 181/111 mmHg falling to 158/96 mmHg during treatment. Corresponding values for women were 185/109 mmHg and 161/96 mmHg. Seven hundred and fifty clinic patients (451 males) died during follow-up, the commonest causes of death in both sexes being myocardial infarction and stroke. All-cause age-adjusted mortality (deaths per 1000 patient-years) was 41.4 for men and 22.1 for women. At all ages in both sexes and for all levels of initial blood pressure mortality was less in patients whose blood pressure was reduced most. Without a randomized control group it is not certain that lower mortality in those with well controlled blood pressure was due to treatment, although this is the most likely explanation. Cigarette smoking, a history of myocardial infarction, angina or stroke, retinal arterio-venous nipping, raised blood urea, an abnormal electrocardiogram (ECG) and secondary hypertension were associated with increased risk, but heavy alcohol intake, obesity, haematocrit greater than 45%, hypokalaemia and social class were not. Life table analysis showed that, despite some reduction of mortality by treatment, the relative risk to men and women in the clinic remained two- to five-times that of the general population. The benefits of treatment were not such as to restore normal expectation of life even when blood pressure was well controlled. Excess mortality in the clinic could not be explained by difference of smoking habit or social class. This suggests that there is in the hypertensive patients of the Glasgow Clinic an element of irreducible risk, that treatment may be beneficial in some respects but harmful in others, or that patients at particularly high risk are selectively referred to the clinic.


Diazeniumdiolation of protamine sulfate reverses mitogenic effects on smooth muscle cells and fibroblasts.
After vascular interventions, endothelial cells are typically injured or lacking, resulting in decreased NO synthesis to maintain vascular health. Moreover, inflammation as a result of the tissue injury and/or the presence of an implanted foreign polymer such as a vascular graft causes excessive generation of reactive oxygen species (ROS) (e.g., superoxide), which can react with NO. The combination of the above creates a general decline in NO bioavailability, as well as oxidative stress due to less available NO to scavenge ROS. Localized NO delivery is an attractive solution to alleviate these issues; however, NO donors typically exhibit unpredictable NO payload release when using nitrosothiols or the risk of nitrosamine formation for synthetic diazeniumdiolates. The objective of this study was therefore to synthesize an NO donor from a biological peptide that could revert to its native form upon NO release. To this effect, protamine sulfate (PS), an FDA-approved peptide with reported vasodilator and anticoagulant properties, was diazeniumdiolated to form PS/NO. PS/NO showed diazeniumdiolate-characteristic UV peaks and NO release in physiological solutions and was capable of scavenging radicals to decrease oxidative stress. Furthermore, PS/NO selectively inhibits the proliferation of smooth muscle cells and adventitial fibroblasts, thereby reversing reported mitogenic properties of PS. Endothelial cell growth, on the other hand, was promoted by PS/NO. Finally, PS retained its anticoagulant properties upon diazeniumdiolation at clinically relevant concentrations. In conclusion, we have synthesized an NO prodrug from a biological peptide, PS/NO, that selectively inhibits proliferation of smooth muscle cells and fibroblasts, retains anticoagulant properties, and reverts back to its native PS form upon NO payload release.


Voltage-dependent nitrendipine binding to cardiac sarcolemmal vesicles.
The binding of the calcium channel antagonist [3H]nitrendipine (3[H]Ntd) to purified bovine cardiac sarcolemmal vesicles was examined at different membrane potentials. The vesicles were loaded with 150 mM K and exposed to a range of external K concentrations to induce negative internal membrane potentials using N-methyl-D-glucamine or choline to substitute for K. The lipophilic cation [3H]tetraphenylphosphonium was used to quantitate the membrane potential, and the vesicles were capable of maintaining a relatively stable negative inside membrane potential for at least 15 min. Equilibrium binding studies of [3H]Ntd performed on vesicles maintained at a depolarized potential (0 mV) revealed 24.7 +/- 5.6% more high affinity [3H]Ntd-binding sites than were present on vesicles maintained at a hyperpolarized potential (approximately -40 to -50 mV) with N-methyl-D-glucamine substituting for K. There was no significant change in Kd values which were 0.398 +/- 0.069 and 0.388 +/- 0.032 nM, respectively. When choline was used to substitute for K, comparable results were obtained with 19.01 +/- 3.4% more high affinity [3H]Ntd-binding sites under depolarized conditions and no significant change in Kd (0.356 +/- 0.025 and 0.379 +/- 0.030 nM, respectively). Varying the external K concentration resulted in a graded change in [3H]Ntd binding over the same range of external K concentrations which resulted in the greatest change in membrane potential. These findings suggest that the observed effect was due to changes in membrane potential rather than changes in the composition of the incubation medium. Additional control experiments employing choline-loaded vesicles also support the hypothesis that the observed effect was primarily due to changes in membrane potential. The present results are compared with those from electrophysiological studies.


[Clinical characteristics of hereditary cerebrovascular disease in a large family from Colombia].
The cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations of the Notch3 gene in the chromosome 19p13.1. and is characterized by small-vessel disease of the cerebral. The clinical feature consists of migraine, recurrent strokes, mood changes and dementia. To describe the clinical phenotype of a Colombian family with hereditary cerebrovascular disease. We performed one pedigree with 268 individuals, neurologic examination to 57 members and magnetic resonance imaging (MRI) to 25 of them. Clinical analysis strongly support the diagnosis of CADASIL because 12 individuals had suffered recurrent stroke, five of them later developed subcortical dementia. Two patients developed dementia without preceding stroke. All affected individuals by stroke or dementia whom were tested with MRI had white matter hyperintensities and subcortical infarcts (nine cases). Others seven individuals have MRI signal abnormalities like CADASIL, four of them are asymptomatic, one had suffered ischemic transient attacks and two had suffered migraine. Other 22 individuals had only migraine. We outstand the high frequency of MRI signal abnormalities in corpus callosum that we found in five individuals with stroke or dementia, the patient with ischemic transient attack and one asymptomatic patient, either the presence of hearing loss in seven individuals with stroke or dementia. We describe one large family with hereditary cerebrovascular disease characterized by recurrent strokes, subcortical dementia, hearing loss, migraine, and MRI signal abnormalities typed leukoencephalopathy, subcortical infarcts and alterations in corpus callosum. Clinical analysis strongly support the diagnosis of CADASIL.


Account of chemical bonding and enhanced reactivity of vanadium-doped rhodium clusters toward C-H activation: a DFT investigation.
Herein, the chemical bonding of both pristine rhodium (Rhn, 2 ≤ n ≤ 9) and mono-vanadium-doped rhodium (RhmV, 1 ≤ m ≤ 8) clusters was understood by density functional theory. The calculated results provided conclusive evidence that a single vanadium dopant thermodynamically stabilized the rhodium clusters by increasing the interatomic bond orders and henceforth the binding energy. Moreover, an in-depth account of the high bond order of RhmV clusters was presented by analyzing the intracluster bonding orbitals and the orbital composition. In addition, the reaction mechanism and thermodynamic parameters of C-H activation processes on both types of clusters were thoroughly investigated, and the results were compared. This comparison revealed that in addition to thermodynamic stabilization, the vanadium dopant enhanced the reactivity of the cluster toward C-H activation by reducing the activation barrier and endothermicity to a reasonable extent. Thus, the obtained results provide an insight into the structure and bonding of both types of inorganic clusters (Rhn and RhmV) and reveal the potential application of vanadium as a dopant for the enhancement of both stability and catalytic properties of rhodium clusters.


Longitudinal population-level HIV epidemiologic and genomic surveillance highlights growing gender disparity of HIV transmission in Uganda.
HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep-sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted: whereas HIV transmission to girls and women (aged 15-24 years) from older men declined by about one-third, transmission to women (aged 25-34 years) from men that were 0-6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programmes to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men's health in Africa.


Catechol-Amyloid Interactions.
This review introduces multifaceted mutual interactions between molecules containing a catechol moiety and aggregation-prone proteins. The complex relationships between these two molecular species have previously been elucidated primarily in a unidirectional manner, as demonstrated in cases involving the development of catechol-based inhibitors for amyloid aggregation and the elucidation of the role of functional amyloid fibers in melanin biosynthesis. This review aims to consolidate scattered clues pertaining to catechol-based amyloid inhibitors, functional amyloid scaffold of melanin biosynthesis, and chemically designed peptide fibers for providing chemical insights into the role of the local three-dimensional orientation of functional groups in manifesting such interactions. These orientations may play crucial, yet undiscovered, roles in various supramolecular structures.


Accelerator-Based Tests of Shielding Effectiveness of Different Materials and Multilayers using High-Energy Light and Heavy Ions.
The roadmap for space exploration foresees longer journeys and further excursions outside low-Earth orbit as well as the establishment of permanent outposts on other celestial bodies, such as the Moon or Mars. The design of spacecrafts and habitats depends heavily on the mission scenario and must consider the radiation protection properties of the structural components as well as dedicated shielding. In fact, short- and long-term effects caused by exposure to cosmic radiation are now considered among the main health risks of space travel. One of the current strategies is to find multifunctional materials that combine excellent mechanical properties with a high shielding effectiveness to minimize the overall load. In this work, the shielding effectiveness of a wide variety of single and multilayer materials of interest for different mission scenarios has been characterized. In the experimental campaign, reference and innovative materials, as well as simulants of Moon and Mars in situ resources, were irradiated with 1,000 MeV/u 4He, 430 MeV/u 12C and 962-972 MeV/u 56Fe. The results are presented in terms of Bragg curves and dose reduction per unit area density. To isolate the shielding effectiveness only due to nuclear fragmentation, a correction for the energy loss in the material is also considered. These findings indicate that the best shield is lithium hydride, which performs even better than polyethylene. However, the technical feasibility of shielding needs to be investigated. The classification of all materials in terms of shielding effectiveness is not influenced by the ion species, but the value changes dramatically depending on the beam energy. The output of this investigation represents a useful database for benchmarking Monte Carlo and deterministic transport codes used for space radiation transport calculations. These findings also contribute to recommendations for optimizing the design of space vessels and habitats in different radiation environments.


Immunomodulation of classical and non-classical HLA molecules by ionizing radiation.
Radiotherapy has been employed for the treatment of oncological patients for nearly a century, and together with surgery and chemotherapy, radiation oncology constitutes one of the three pillars of cancer therapy. Ionizing radiation has complex effects on neoplastic cells and on tumor microenvironment: beyond its action as a direct cytotoxic agent, tumor irradiation triggers a series of alterations in tumoral cells, which includes the de novo synthesis of particular proteins and the up/down-regulation of cell surface molecules. Additionally, ionizing radiation may induce the release of "danger signals" which may, in turn lead to cellular and molecular responses by the immune system. This immunomodulatory action of ionizing radiation highlights the importance of the combined use (radiotherapy plus immunotherapy) for cancer healing. Major histocompatibility complex antigens (also called Human Leukocyte Antigens, HLA in humans) are one of those molecules whose expression is modulated after irradiation. This review summarizes the modulatory properties of ionizing radiation on the expression of HLA class I (classical and non-classical) and class II molecules, with special emphasis in non-classical HLA-I molecules.


An analysis of the determinants of anaemia in pregnant women in rural Malawi--a basis for action.
Haematological data are presented on 4104 pregnant women attending the antenatal-care facilities of two hospitals in a rural area in southern Malawi. In this area, malaria transmission is perennial and there is a high prevalence of HIV infection. The local women are exposed to drought and food shortages but experience high fertility rates. Mean (S.D.) haemoglobin (Hb) concentration was significantly lower in the primigravidae [8.7 (1.60 g/dl] than in the secundigravidae [9.1 (1.5) g/dl; P < 0.0001] or multigravidae [9.2 (1.5) g/dl; P < 0.0001]. Primigravidae also experienced significantly more iron deficiency and malaria than secundi- or multi-gravidae. For all parity groups, the lowest mean Hb levels were observed between 26-30 weeks' gestation. In primigravidae peak prevalence of malaria occurred between 16-20 weeks' gestation (38.6%) and peak prevalence of moderately severe anaemia (< 8 g Hb/dl) between 26-30 weeks' (35.7%). Multigravidae showed little variation in the prevalence of anaemia, iron deficiency and malaria with gestational age. Peak prevalences of malaria were observed in April, in the post-rainy season, with values of 51.4%, 56.0% and 25.3% for primi-, secundi- and multi-gravidae, respectively. Peak prevalences of iron deficiency occurred between April and May and those of moderately severe anaemia between May and June. Mean Hb was lower in adolescent primigravidae than in any other group of pregnant women [8.6 (1.5) g/dl], including the non-adolescent primigravidae [8.9 (1.6) g/dl; P = 0.008]. Other factors significantly associated with increased risk of moderately severe anaemia in primigravidae were illiteracy and poor nutritional status (i.e. body mass index < 18.5 kg/m2 and mid-upper-arm circumference < 23 cm). After forward, step-wise, regression analysis of relative risk (RR) factors and their 95% confidence intervals (CI), variables associated with an increased risk for moderately severe anaemia were iron deficiency (RR = 4.2; CI = 3.0-6.0) and malaria parasitaemia (RR = 1.9; CI = 1.3-2.7) in primigravidae, iron deficiency (RR = 4.1; CI = 2.7-6.3) and mid-upper-arm-circumference < 23 cm (RR = 1.8; CI = 1.1-3.0) in secundigravidae, and iron deficiency in multigravidae (RR = 3.1; CI = 4.3-6.9).


Study of anabolic activity of dry extracts of leaves and rhizomes of Iris hungarica on a model of hydrocortisone-induced protein catabolism.
This article presents the results of the study of the anabolic effect of dry extracts of Iris hungarica leaves and rhizomes on the model of hydrocortisoneinduced protein catabolism. Previous studies have established the presence of anabolic activity of dry extracts of Iris hungarica leaves and rhizomes in intact animals. Therefore, it was reasonable to study the effect of the experimental extracts on the state of protein metabolism, which is regulated by glucocorticoids. The model of hydrocortisoneinduced protein catabolism was used to determine anabolic activity for dry extracts of Iris hungarica leaves and rhizomes at a dose of 150 mg/kg by monitoring the recovery of body weight and the increase in the total protein in the cardiac muscle of rats and in muscle tissue homogenate, which is aimed to promote myofibrillar hypertrophy. Dry extract of Iris hungarica rhizomes reduced urea excretion, normalized metabolism, restored nitrogen balance, and inhibited protein catabolism. The results indicate that dry extract of Iris hungarica has the ability to correct protein metabolism, which is regulated in part by glucocorticoids, due to the high content of isoflavonoids and amino acids, and suggest that there is a potential use for this herbal product in the development of a new drug aimed at correcting protein metabolism and muscular atrophy.


Ultrastructural study of hemangiomas. 5. Glomus tumor (Masson).
The fine structure of four cases of glomus tumor was described. All of the cases showed a solid type, and the glomus cells were shown to be typical or modified smooth muscle cells. Our conclusion is that the glomus cells are not derived from pericytes, but from smooth muscle cells of vascular part of the glomus, and are thought to be a specialized smooth muscle cell tumor.


Loneliness in adults: Evidence-based research and interventions for NPs.
Loneliness is a complex psychophysiologic concept, a health risk factor, and a worrisome trend across the globe. This article reviews the latest research on the negative health effects associated with loneliness. Evidence-based NP interventions aimed at improving patients' perceived social connections are also explored.


Evaluating the complexation behavior and regeneration of boron selective glucaminium-based ionic liquids when used as extraction solvents.
Glucaminium-based ionic liquids are a new class of solvents capable of extracting boron-species from water with high efficiency. The complexation behavior of these ILs with borate was thoroughly studied using (11)B NMR. Two different complexes, namely, monochelate complex and bischelate complex, were observed. (11)B NMR was used extensively to determine the formation constants for monochelate and bischelate complexes. The IL concentration was observed to have a significant effect on the IL-borate complexes. Using an in situ dispersive liquid-liquid microextraction (in situ DLLME) method, the extraction efficiency for boron species was increased dramatically when lithium bis[(trifluoromethyl)sulfonyl]imide (LiNTf(2)) was used as the metathesis salt in an aqueous solution containing 0.1M sodium chloride. IL regeneration after extraction was achieved using 0.1M hydrochloric acid. The extraction efficiency of boron species was consistent when the IL was employed after three regeneration cycles. The selectivity of the IL for boron species in synthetic seawater samples was similar to performing the same extraction from Milli-Q water samples.


Dose optimization of contrast-enhanced carotid MR angiography.
The purpose of this work was to compare the diagnostic performance of a single-contrast or a double-contrast dose of carotid contrast-enhanced MR angiography (MRA). One-hundred nineteen patients (mean age 65+/-14.4 years) underwent carotid contrast-enhanced MRA with a standardized protocol (repetition time/echo 3.73 ms/1.38 ms, flip-angle 25 degrees, acquisition-time 19 s, voxel size 1.2 x 1.2 x 0.9 mm3) on a 1.5-T scanner (Sonata, Siemens-Medical-Systems) using a neck phased-array coil. Contrast agent was administered intravenously at a rate of 3.0 ml/s, either as a single dose (n=57; 0.1 mmol/kg body weight) or as a double dose (n=62; 0.2 mmol/kg body weight) of meglumine gadoterate (0.5 M/l), followed by 30 ml saline. Qualitative image analysis was performed on maximum intensity projections using a five-point scale. Signal intensities were measured at three different vascular levels on both sides to assess the contrast-to-noise ratios (CNRs). Image quality was rated as good or excellent in all cases. A double dose did not influence the efficacy of carotid enhancement (CNR single dose 69.12+/-19.8; CNR double dose 70.01+/-20.7; p = 0.81) compared with a single dose. In both dose groups the mean CNRs were inversely related to bodyweight, despite adjusted contrast volumes (p=0.0005). Double-dose contrast-enhanced carotid MRA is not superior to single-dose MRA, as overall diagnostic performance and quantitative contrast enhancement are equal. Being more cost-efficient, a single-dose administration of contrast agent is recommended for MRA of the carotid arteries.


AluScan: a method for genome-wide scanning of sequence and structure variations in the human genome.
To complement next-generation sequencing technologies, there is a pressing need for efficient pre-sequencing capture methods with reduced costs and DNA requirement. The Alu family of short interspersed nucleotide elements is the most abundant type of transposable elements in the human genome and a recognized source of genome instability. With over one million Alu elements distributed throughout the genome, they are well positioned to facilitate genome-wide sequence amplification and capture of regions likely to harbor genetic variation hotspots of biological relevance. Here we report on the use of inter-Alu PCR with an enhanced range of amplicons in conjunction with next-generation sequencing to generate an Alu-anchored scan, or 'AluScan', of DNA sequences between Alu transposons, where Alu consensus sequence-based 'H-type' PCR primers that elongate outward from the head of an Alu element are combined with 'T-type' primers elongating from the poly-A containing tail to achieve huge amplicon range. To illustrate the method, glioma DNA was compared with white blood cell control DNA of the same patient by means of AluScan. The over 10 Mb sequences obtained, derived from more than 8,000 genes spread over all the chromosomes, revealed a highly reproducible capture of genomic sequences enriched in genic sequences and cancer candidate gene regions. Requiring only sub-micrograms of sample DNA, the power of AluScan as a discovery tool for genetic variations was demonstrated by the identification of 357 instances of loss of heterozygosity, 341 somatic indels, 274 somatic SNVs, and seven potential somatic SNV hotspots between control and glioma DNA. AluScan, implemented with just a small number of H-type and T-type inter-Alu PCR primers, provides an effective capture of a diversity of genome-wide sequences for analysis. The method, by enabling an examination of gene-enriched regions containing exons, introns, and intergenic sequences with modest capture and sequencing costs, computation workload and DNA sample requirement is particularly well suited for accelerating the discovery of somatic mutations, as well as analysis of disease-predisposing germline polymorphisms, by making possible the comparative genome-wide scanning of DNA sequences from large human cohorts.


Screening for defined cystic fibrosis mutations by solid-phase minisequencing.
We have developed a rapid method for the quantitative detection of point mutations and deletions. In this minisequencing method, enzymatically amplified DNA, 5'-biotinylated in one strand, is bound to a solid phase and denatured. A detection primer, constructed to end immediately before the mutation, is annealed to the immobilized single-stranded template and elongated with a single, labeled deoxynucleoside residue. We have applied the solid-phase minisequencing method to the detection of the major mutation, delta F508, causing cystic fibrosis (CF). In the presence of the allele with the delta F508 mutation, [3H]dTTP is incorporated; with the nonmutated allele, [3H]dCTP is incorporated. Thus, samples from heterozygous individuals allow the incorporation of both labels. The method was evaluated by analyzing 59 coded DNA specimens collected from 20 Finnish CF patients and their parents. The ratio of [3H]C to [3H]T gave unambiguously the allele combination. The solid-phase minisequencing method was also applicable to the analysis of three CF mutations simultaneously, i.e., delta F508, G542X, and G551D. We conclude that the microtiter-plate-based minisequencing test is an accurate method for the screening of defined sequence alterations in the CF gene.


Angiogenesis alteration by defibrotide: implications for its mechanism of action in severe hepatic veno-occlusive disease.
Defibrotide (DF) is a mixture of porcine-derived single-stranded phosphodiester oligonucleotides (9-80-mer; average, 50-mer) that has been successfully used to treat severe hepatic veno-occlusive disease (sVOD) with multiorgan failure (MOF) in patients who have received cytotoxic chemotherapy in preparation for bone marrow transplantation. However, its mechanism of action is unknown. Herein, we show that DF and phosphodiester oligonucleotides can bind to heparin-binding proteins (eg, basic fibroblast growth factor [bFGF] but not vascular endothelial growth factor [VEGF] 165) with low nanomolar affinity. This binding occurred in a length- and concentration-dependent manner. DF can mobilize proangiogenic factors such as bFGF from their depot or storage sites on bovine corneal endothelial matrix. However, these molecules do not interfere with high-affinity binding of bFGF to FGFR1 IIIc but can replace heparin as a required cofactor for binding and hence cellular mitogenesis. DF also protects bFGF against digestion by trypsin and chymotrypsin and from air oxidation. In addition, DF binds to collagen I with low nanomolar affinity and can promote human microvascular endothelial cell-1 (HMEC-1) cell mitogenesis and tubular morphogenesis in three-dimensional collagen I gels. Thus, our data suggest that DF may provide a stimulus to the sinusoidal endothelium of a liver that has suffered a severe angiotoxic event, thus helping to ameliorate the clinical sVOD/MOF syndrome.


[Nurses' experience of caring for dying patients in hospitals].
To develop a substantive theory that represents hospital nurses' experience on caring for dying patients. Grounded theory method guided the data collection and analysis. A purposeful sample of 15 hospital nurses participated during the period of 2001-2002. The data were collected by semi-structured individual interviews. All interviews were audio taped and transcribed verbatim. Constant comparative analysis was employed to analyze the data. "Putting oneself into shape while being faithful to feelings and emotions" emerged as the basic social-psychological process. Three different phases were identified: being faithful to own feelings and behaviors; putting oneself into shape; and mourning death. The first phase includes the categories of "establishing trust relationships" and "sympathizing with dying patients and their family members." The second phase consists of "controlling feelings," "adjusting ethical conflicts," and "providing best patient-care," and "helping family accept the death." And the third phase consists of "overcoming sadness" and "releasing other negative feelings." The result of this study will help health professionals develop efficient support programs that support nurses caring for dying patients in hospitals. Further study needs to be done to verify findings.


Calix[4]arene-Derived 2D Covalent Organic Framework with an Electron Donor-Acceptor Structure: A Visible-Light-Driven Photocatalyst.
The calixarenes are ideal building blocks for constructing photocatalytic covalent organic frameworks (COFs), owing to their electron-rich and bowl-shaped π cavities that endow them with electron-donating and adsorption properties. However, the synthesis and structural confirmation of COFs based on calixarenes are still challenging due to their structural flexibility and conformational diversity. In this study, a calix[4]arene-derived 2D COF is synthesized using 5,11,17,23-tetrakis(p-formyl)-25,26,27,28-tetrahydroxycalix[4]arene (CHO-C4A) as the electron donor and 4,7-bis(4-aminophenyl)-2,1,3-benzothiadiazole (BTD) as the acceptor. The powder X-ray diffraction data and theoretical simulation of crystal structure indicate that COF-C4A-BTD exhibits high crystallinity and features a non-interpenetrating undulating 2D layered structure with AA-stacking. The density functional theory theoretical calculation, transient-state photocurrent tests, and electrochemical impedance spectroscopy confirm the intramolecular charge transfer behavior of COF-C4A-BTD with a donor-acceptor structure, leading to its superior visible-light-driven photocatalytic activity. COF-C4A-BTD exhibits a narrow band gap of 1.99 eV and a conduction band energy of -0.37 V versus normal hydrogen electrode. The appropriate energy band structure can facilitate the participation of ·O2- and h+ . COF-C4A-BTD demonstrates high efficacy in removing organic pollutants, such as bisphenol A, rhodamine B, and methylene blue, with removal rates of 66%, 85%, and 99% respectively.


Frequency and significance of delta antibody in acute and chronic hepatitis B. A United States experience.
Of 560 hepatitis B surface antigen-positive patients who were tested for antibody to hepatitis delta-antigen by blocking radioimmunoassay, 29 (5%) were seropositive. Patients with chronic active hepatitis had a greater frequency of seropositivity than those with chronic persistent hepatitis (26% vs. 0%, p less than 0.05), and patients with symptomatic chronic disease harbored the antibody more commonly than asymptomatic counterparts (14% vs. 2%, p less than 0.01) or patients with acute hepatitis (14% vs. 1%, p less than 0.02). Of 8 patients with acute fulminant hepatitis, including 6 who died of liver failure, none were seropositive. Antibody was detected in drug users, dialysis patients, hemophiliacs, and transfusion recipients; in 17 patients, however, including 3 homosexuals, it occurred sporadically. Samples harvested in 1969 contained delta-antibody. Antibody was found in most ethnic groups, including Orientals, where it occurred only in relocated Vietnamese. We conclude that delta-antibody is detected infrequently in a diverse referral population within the United States. Seropositivity is associated with symptomatic chronic disease and histologic findings of chronic active hepatitis. Homosexuals and resettled Vietnamese are susceptible to sporadic delta-infection.


The impact of three carbapenems at a single-day dose on intestinal colonization resistance against carbapenem-resistant Klebsiella pneumoniae.
The intestinal colonization of carbapenem-resistant Klebsiella pneumoniae (CRKP) is an important source of clinical infection. Our research showed that even single-day dose use of carbapenems caused CRKP colonization and continuous bacterial shedding, which reminds clinical doctors to prescribe carbapenems cautiously. Whenever possible, ertapenem should be the preferred choice over other carbapenems especially when the identified or highly suspected pathogens can be effectively targeted by ertapenem.


Permutation and Grouping Methods for Sharpening Gaussian Process Approximations.
Vecchia's approximate likelihood for Gaussian process parameters depends on how the observations are ordered, which has been cited as a deficiency. This article takes the alternative standpoint that the ordering can be tuned to sharpen the approximations. Indeed, the first part of the paper includes a systematic study of how ordering affects the accuracy of Vecchia's approximation. We demonstrate the surprising result that random orderings can give dramatically sharper approximations than default coordinate-based orderings. Additional ordering schemes are described and analyzed numerically, including orderings capable of improving on random orderings. The second contribution of this paper is a new automatic method for grouping calculations of components of the approximation. The grouping methods simultaneously improve approximation accuracy and reduce computational burden. In common settings, reordering combined with grouping reduces Kullback-Leibler divergence from the target model by more than a factor of 60 compared to ungrouped approximations with default ordering. The claims are supported by theory and numerical results with comparisons to other approximations, including tapered covariances and stochastic partial differential equations. Computational details are provided, including the use of the approximations for prediction and conditional simulation. An application to space-time satellite data is presented.


Country report on multimedia and Internet for children and youth in Taiwan.
The actions of Taiwan government for promoting information education have being carried out since 1996. The main goal is to educate students of primary school and high school about the basic information knowledge and the internet. The actual actions will be described. There are many kind of multimedia CD titles in Taiwan market right now. The major types of multimedia CD titles will be discussed. And the difficulties of developing materials of CD titles will be discussed.


In vivo study on combined toxicity of Metarhizium anisopliae (Deuteromycotina: Hyphomycetes) strain ESC-1 with sublethal doses of chlorpyrifos, propetamphos, and cyfluthrin against German cockroach (Dictyoptera: Blattellidae).
The effect of Metarhizium anisopliae (Metschnikoff) Sorokin strain ESC-1 alone and in combination with sublethal doses of commercial formulations of chlorpyrifos, propetamphos and cyfluthrin on mortality of CSMA strain of German cockroach, Blattella germanica (L.), was determined by conducting in vivo studies that included 3 bioassays. Spores of M. anisopliae cultured on SDAY media had germination of >90%. Based on bioassay 1, doses ranging from 0.5 to 300 ppm of chlorpyrifos and propetamphos, and 0.05 to 40 ppm of cyfluthrin were selected for bioassays 2 and 3. Cockroach mortality ranged from 5 to 20% for insecticides alone and 48 to 70% for insecticides + M. anisopliae in bioassay 2. In bioassay 3, mortality ranged from 15 to 60% for insecticides and 57.5 to 92.5% for insecticides + M. anisopliae. Percentage of cockroach mortality resulting from insecticide + M. anisopliae combinations was significantly higher than insecticide alone. Mortality was also significantly higher in certain insecticide + M. anisopliae combinations than M. anisopliae alone. There was no significant interaction between M. anisopliae and insecticides with their concentrations in bioassay 2, indicating an additive effect. But in bioassay 3, a significant interaction was observed when M. anisopliae was combined with multiple insecticide concentrations. The interaction indicated an additive effect for chlorpyrifos and cyfluthrin, and a synergistic effect for propetamphos. There were significant differences in LT50 among various treatment combinations. M. anisopliae alone or insecticide + M. anisopliae combinations did not affect body weight in treated German cockroaches.


Euthymic patients with bipolar disorder show decreased reward learning in a probabilistic reward task.
Bipolar disorder (BPD) features cycling mood states ranging from depression to mania with intermittent phases of euthymia. Bipolar disorder subjects often show excessive goal-directed and pleasure-seeking behavior during manic episodes and reduced hedonic capacity during depressive episodes, indicating that BPD might involve altered reward processing. Our goal was to test the hypothesis that BPD is characterized by impairments in adjusting behavior as a function of prior reinforcement history, particularly in the presence of residual anhedonic symptoms. Eighteen medicated BPD subjects and 25 demographically matched comparison subjects performed a probabilistic reward task. To identify putative dysfunctions in reward processing irrespective of mood state, primary analyses focused on euthymic BPD subjects (n = 13). With signal-detection methodologies, response bias toward a more frequently rewarded stimulus was used to objectively assess the participants' propensity to modulate behavior as a function of reinforcement history. Relative to comparison subjects, euthymic BPD subjects showed a reduced and delayed acquisition of response bias toward the more frequently rewarded stimulus, which was partially due to increased sensitivity to single rewards of the disadvantageous stimulus. Analyses considering the entire BPD sample revealed that reduced reward learning correlated with self-reported anhedonic symptoms, even after adjusting for residual manic and anxious symptoms and general distress. The present study provides preliminary evidence indicating that BPD, even during euthymic states, is characterized by dysfunctional reward learning in situations requiring integration of reinforcement information over time and thus offers initial insights about the potential source of dysfunctional reward processing in this disorder.


Comprehensive Profile of Pathogens and Antimicrobial Resistance in Conjunctivitis Cases from Niger.
Infectious conjunctivitis outbreaks remain a public health burden. This study focuses on the pathogen and antimicrobial resistance (AMR) profiles identified in Niger. Sixty-two patients with acute infectious conjunctivitis who presented to health posts were enrolled from December 2021 to May 2022. Nasal and conjunctival swabs were obtained from each patient. Unbiased RNA deep sequencing (RNA-seq) was used to identify associated pathogens. A pathogen was identified in 39 patients (63%; 95% CI, 50-74). Of those, an RNA virus was detected in 23 patients (59%; 95% CI, 43-73). RNA viruses were diverse and included human coronaviruses (HCoVs): SARS-CoV-2, HCoV-229E, HCoV-HKU1, and HCoV-OC43. A DNA virus was identified in 11 patients (28%; 95% CI, 17-44). Of those, four patients had a coinfection with an RNA virus and two patients had a coinfection with both an RNA virus and a bacterium. DNA viruses were predominantly human herpesvirus (cytomegalovirus, Epstein-Barr virus, human herpesvirus 8) and human adenovirus species B, C, and F. Eighteen patients (46%; 95% CI, 32-61) had a bacteria-associated infection that included Haemophilus influenza, Haemophilus aegyptius, Staphylococcus aureus, Streptococcus pneumoniae, and Moraxella spp. Antimicrobial resistance determinants were detected in either the conjunctiva or nasal samples of 20 patients (32%; 95% CI, 22-45) and were found to be more diverse in the nose (Shannon alpha diversity, 1.12 [95% CI, 1.05-1.26] versus 1.02 [95% CI, 1.00-1.05], P = 0.01). These results suggest the potential utility of leveraging RNA-seq to surveil pathogens and AMR for ocular infections.


Examining reproducibility in psychology: A hybrid method for combining a statistically significant original study and a replication.
The unrealistically high rate of positive results within psychology has increased the attention to replication research. However, researchers who conduct a replication and want to statistically combine the results of their replication with a statistically significant original study encounter problems when using traditional meta-analysis techniques. The original study's effect size is most probably overestimated because it is statistically significant, and this bias is not taken into consideration in traditional meta-analysis. We have developed a hybrid method that does take the statistical significance of an original study into account and enables (a) accurate effect size estimation, (b) estimation of a confidence interval, and (c) testing of the null hypothesis of no effect. We analytically approximate the performance of the hybrid method and describe its statistical properties. By applying the hybrid method to data from the Reproducibility Project: Psychology (Open Science Collaboration, 2015), we demonstrate that the conclusions based on the hybrid method are often in line with those of the replication, suggesting that many published psychological studies have smaller effect sizes than those reported in the original study, and that some effects may even be absent. We offer hands-on guidelines for how to statistically combine an original study and replication, and have developed a Web-based application ( https://rvanaert.shinyapps.io/hybrid ) for applying the hybrid method.


Studies of the variability of the genes encoding the insulin-like growth factor I receptor and its ligand in relation to type 2 diabetes mellitus.
Insulin-like growth factor I (IGF-I) is an important regulator of many aspects of growth, differentiation, and development, and as low birth weight has been associated with impaired glucose tolerance and overt type 2 diabetes in adult life, we considered the genes encoding the IGF-I and the IGF-I receptor (IGF-IR) as candidates for low birth weight, insulin resistance, and type 2 diabetes. Here we report the mutational analysis of the coding regions of the IGF-I and IGF-IR performed on genomic DNA from probands of 82 Danish type 2 diabetic families. No mutations predicting changes in the amino acid sequences of the IGF-I or IGF-IR genes were detected, but several silent and intronic polymorphisms were found. The impact of the most prevalent polymorphism, GAG1013GAA of the IGF-IR, was evaluated in a population-based sample of 349 young healthy subjects, where the variant had an allele frequency of 0.44 (95% confidence interval, 0.40-0.48). No significant relationships between this variant and birth weight, birth length, or insulin sensitivity index were detected. In addition, we did not observe any significant differences in allelic frequencies of the codon 1013 variant between 395 type 2 diabetic patients (allele frequency, 0.52; 95% confidence interval, 0.49-0.55) and 238 matched glucose-tolerant control subjects (allelic frequency, 0.47; 95% confidence interval, 0.43-0.50). In conclusion, variability in the coding regions of IGF-I and the IGF-IR does not associate with reduced birth weight, insulin sensitivity index, or type 2 diabetes in the Danish population.


Synthesis, antimicrobial, anticancer evaluation and QSAR studies of 3/4-bromo benzohydrazide derivatives.
A series 3/4-bromo-N'-(substituted benzylidene/furan-2-ylmethylene/5-oxopentylidene/3- phenylallylidene)benzohydrazides (1-23) was synthesized and characterized by physicochemical and spectral means. The synthesized compounds were screened for their antimicrobial and anticancer potentials. Antimicrobial activity results indicated that compound 12 (pMICam = 1.67 μM/ml) was the most potent antimicrobial agent. The synthesized benzohydrazides were also having good anticancer potential and compound 22 (IC50 = 1.20 μM μM) was found to be the most potent anticancer agent which was more potent than standard drugs, tetrandrine (IC50 = 1.53) and 5- fluorouracil (IC50 = 4.6 μM). QSAR studies indicated that antimicrobial activity of synthesized compounds was best described by electronic parameter, total energy (Te) and topological parameters, valance zero order molecular connectivity index ((0)χ(v)) and Wiener index (W).


Vascular reactivity is altered in the placentas of fetuses with congenital diaphragmatic hernia.
Infants with congenital diaphragmatic hernia (CDH) often develop pulmonary hypertension but frequently fail to respond to vasodilator therapy, for instance because of an altered pulmonary vasoreactivity. Investigating such alterations in vivo is impossible. We hypothesised that these alterations are also present in fetoplacental vessels, since both vasculatures are exposed to the same circulating factors (e.g. endothelin-1) and respond similarly to certain stimuli (e.g. hypoxia). As proof-of-concept, we compared fetoplacental vasoreactivity between healthy and CDH-affected placentas. Fetoplacental vascular function of healthy and antenatally diagnosed left-sided CDH fetuses was assessed by wire myography. Placental expression of enzymes and receptors involved in the altered vasoreactive pathways was measured using quantitative PCR. CDH arteries (n = 6) constricted more strongly to thromboxane A2 agonist U46619 (p < 0.001) and dilated less to bradykinin (p = 0.01) and nitric oxide (NO)-donor sodium nitroprusside (p = 0.04) than healthy arteries (n = 8). Vasodilation to prostacyclin analogue iloprost and adenylate cyclase stimulator forskolin, and vasoconstriction to endothelin-1 were not different between both groups. Angiotensin II did not induce vasoconstriction. Phosphodiesterase inhibitors sildenafil and milrinone did not affect responses to sodium nitroprusside, forskolin, or U46619. The mRNA expression of guanylate cyclase 1 soluble subunit alpha 1 (p = 0.003) and protein kinase cyclic guanine monophosphate (cGMP)-dependent 1 (p = 0.02) were reduced in CDH versus healthy placentas. The identified changes in the thromboxane and NO-cGMP pathways in the fetoplacental vasculature correspond with currently described alterations in the pulmonary vasculature in CDH. Therefore, fetoplacental arteries may provide an opportunity to predict pulmonary therapeutic responses in infants with CDH.


Posterior-only multilevel modified vertebral column resection for extremely severe Pott's kyphotic deformity.
Extremely severe Pott's kyphotic deformity cannot be completely corrected by conventional techniques, including vertebral body resection, Smith-Peterson, pedicle subtraction osteotomy or even vertebral column resection (VCR). The authors developed a new technique combining transpedicular eggshell osteotomies and VCR as multilevel modified vertebral column resection (MVCR) through a single posterior approach for surgical treatment of Pott's kyphosis with Konstam's angle beyond 90 degrees. A total of 9 patients (6 males, 3 females) in our institution with severe Pott's kyphosis who underwent single-stage posterior-only multilevel MVCR were retrospectively reviewed. The candidates for multilevel MVCR were those with a sharp, angular kyphosis in the lower thoracic or upper lumbar spine with a Konstam's angle beyond 90 degrees. The follow-up averaged 30.6 months (ranging from 21 to 50 months). Fusion status was evaluated at each follow-up by CT three-dimensional reconstruction images. An average of 2.5 vertebrae was removed in each case (ranging from 2 to 4 vertebrae). A mean of 7 vertebrae were fused (ranging from 6 to 11 vertebrae). The mean duration of surgery was 285 min (ranging from 246 to 400 min), the average intraoperative blood loss was 2,933 ml (ranging from 2,000 to 6,000 ml). The mean preoperative kyphus was 100.3 degrees (ranging from 90 degrees to 132 degrees ). The mean kyphosis in the immediate postoperative period was 15.9 degrees (ranging from 4 degrees to 30 degrees) with an average postoperative kyphos correction of 84.4 degrees (ranging from 63 degrees to 126 degrees). Fusion of the resection site was confirmed on radiographs in all patients at the minimum 12 months follow-up. No pseudoarthrosis was found. No loosening or breakage of pedicle screws occurred. A single-stage posterior-only multilevel MVCR is an effective way to correct extremely severe Pott's kyphosis with Konstam's angle beyond 90 degrees.


Safe and efficient in vivo hematopoietic stem cell transduction in nonhuman primates using HDAd5/35++ vectors.
We tested a new in vivo hematopoietic stem cell (HSC) transduction/selection approach in rhesus macaques using HSC-tropic, integrating, helper-dependent adenovirus vectors (HDAd5/35++) designed for the expression of human γ-globin in red blood cells (RBCs) to treat hemoglobinopathies. We show that HDAd5/35++ vectors preferentially transduce HSCs in vivo after intravenous injection into granulocyte colony-stimulating factor (G-CSF)/AMD3100-mobilized animals and that transduced cells return to the bone marrow and spleen. The approach was well tolerated, and the activation of proinflammatory cytokines that are usually associated with intravenous adenovirus vector injection was successfully blunted by pre-treatment with dexamethasone in combination with interleukin (IL)-1 and IL-6 receptor blockers. Using our MGMTP140K-based in vivo selection approach, γ-globin+ RBCs increased in all animals with levels up to 90%. After selection, the percentage of γ-globin+ RBCs declined, most likely due to an immune response against human transgene products. Our biodistribution data indicate that γ-globin+ RBCs in the periphery were mostly derived from mobilized HSCs that homed to the spleen. Integration site analysis revealed a polyclonal pattern and no genotoxicity related to transgene integrations. This is the first proof-of-concept study in nonhuman primates to show that in vivo HSC gene therapy could be feasible in humans without the need for high-dose chemotherapy conditioning and HSC transplantation.


Infliximab-based self-healing hydrogel composite scaffold enhances stem cell survival, engraftment, and function in rheumatoid arthritis treatment.
Rheumatoid arthritis (RA) is a severe inflammatory autoimmune disease, but its treatment has been very difficult. Recently, stem cell-based therapies have opened up possibilities for the treatment of RA. However, the hostile RA pathological conditions impede the survival and differentiation of transplanted cells, and it remains challenging to fabricate a suitable biomaterial for the improvement of stem cells survival, engraftment, and function. Here we construct an optimal scaffold for RA management through the integration of 3D printed porous metal scaffolds (3DPMS) and infliximab-based hydrogels. The presence of rigid 3DPMS is appropriate for repairing large-scale bone defects caused by RA, while the designed infliximab-based hydrogels are introduced because of their self-healable, anti-inflammatory, biocompatible, and biodegradable properties. We demonstrate that the bioengineered composite scaffolds support adipose-derived mesenchymal stem cells (ADSCs) proliferation, differentiation, and extracellular matrix production in vitro. The composite scaffolds, along with ADSCs, are then implanted into the critical-sized bone defect in the RA rabbit model. In vivo results prove that the bioengineered composite scaffolds are able to down-regulate inflammatory cytokines, rebuild damaged cartilage, as well as improve subchondral bone repair. To the best of the authors' knowledge, this is the first time that using the antirheumatic drug to construct hydrogels for stem cell-based therapies, and this inorganic-organic hybrid system has the potential to alter the landscape of RA study.


New muscle growth in denervated extraocular muscle.
Current therapies for paralytic ocular motility disorders often provide less than satisfactory results. Promising new techniques of nerve grafting and muscle transplantation used to treat muscle paralysis elsewhere in the body may have application to the ocular motor system. In studying a procedure designed to reinnervate paretic extraocular muscle (e.o.m.), we produced not only the expected nerve growth but also abundant new muscle growth. A considerable amount of this muscle growth occurred within the axon depleted nerve fascicles of the paretic muscle, suggesting that this structure was a particularly good matrix for muscle fiber growth. These observations suggest that new, entire neuromuscular units may be induced to grow in the plane of a paretic muscle if appropriate surface characteristics can be established.


On the Way to Become a Natural Killer Cell.
Natural Killer (NK) cells are innate lymphocytes playing pivotal roles in host defense and immune-surveillance. The homeostatic modulation of germ-line encoded/non-rearranged activating and inhibitory NK cell receptors (NKRs) determines the capability of these innate lymphocytes to either spare "self" cells or to kill viral-infected, tumor-transformed and heterologous cell targets. However, despite being discovered more than 40 years ago, several aspects of NK cell biology remain unknown or are still being debated. In particular, our knowledge of human NK cell ontogenesis and differentiation is still in its infancy as the majority of our experimental evidence on this topic mainly comes from findings obtained in vitro or with animal models in vivo. Although both the generation and the maintenance of human NK cells are sustained by hematopoietic stem cells (HSCs), the precise site(s) of NK cell development are still poorly defined. Indeed, HSCs and hematopoietic precursors are localized in different anatomical compartments that also change their ontogenic commitments before and after birth as well as in aging. Currently, the main site of NK cell generation and maturation in adulthood is considered the bone marrow, where their interactions with stromal cells, cytokines, growth factors, and other soluble molecules support and drive maturation. Different sequential stages of NK cell development have been identified on the basis of the differential expression of specific markers and NKRs as well as on the acquisition of specific effector-functions. All these phenotypic and functional features are key in inducing and regulating homing, activation and tissue-residency of NK cells in different human anatomic sites, where different homeostatic mechanisms ensure a perfect balance between immune tolerance and immune-surveillance. The present review summarizes our current knowledge on human NK cell ontogenesis and on the related pathways orchestrating a proper maturation, functions, and distributions.


Eleven years' data of grassland management in Germany.
The 150 grassland plots were located in three study regions in Germany, 50 in each region. The dataset describes the yearly grassland management for each grassland plot using 116 variables.General information includes plot identifier, study region and survey year. Additionally, grassland plot characteristics describe the presence and starting year of drainage and whether arable farming had taken place 25 years before our assessment, i.e. between 1981 and 2006. In each year, the size of the management unit is given which, in some cases, changed slightly across years.Mowing, grazing and fertilisation were systematically surveyed: Mowing is characterised by mowing frequency (i.e. number of cuts per year), dates of cutting and different technical variables, such as type of machine used or usage of conditioner.For grazing , the livestock species and age (e.g. cattle, horse, sheep), the number of animals, stocking density per hectare and total duration of grazing were recorded. As a derived variable, the mean grazing intensity was then calculated by multiplying the livestock units with the duration of grazing per hectare [LSU days/ha]. Different grazing periods during a year, partly involving different herds, were summed up to an annual grazing intensity for each grassland.For fertilisation , information on the type and amount of different types of fertilisers was recorded separately for mineral and organic fertilisers, such as solid farmland manure, slurry and mash from a bioethanol factory. Our fertilisation measures neglect dung dropped by livestock during grazing. For each type of fertiliser, we calculated its total nitrogen content, derived from chemical analyses by the producer or agricultural guidelines (Table 3).All three management types, mowing, fertilisation and grazing, were used to calculate a combined land use intensity index (LUI) which is frequently used to define a measure for the land use intensity. Here, fertilisation is expressed as total nitrogen per hectare [kg N/ha], but does not consider potassium and phosphorus.Information on additional management practices in grasslands was also recorded including levelling, to tear-up matted grass covers, rolling, to remove surface irregularities, seed addition, to close gaps in the sward. Investigating the relationship between human land use and biodiversity is important to understand if and how humans affect it through the way they manage the land and to develop sustainable land use strategies. Quantifying land use (the 'X' in such graphs) can be difficult as humans manage land using a multitude of actions, all of which may affect biodiversity, yet most studies use rather simple measures of land use, for example, by creating land use categories such as conventional vs. organic agriculture. Here, we provide detailed data on grassland management to allow for detailed analyses and the development of land use theory. The raw data have already been used for > 100 papers on the effect of management on biodiversity (e.g. Manning et al. 2015).


MicroRNA-181a Regulates Apoptosis and Autophagy Process in Parkinson's Disease by Inhibiting p38 Mitogen-Activated Protein Kinase (MAPK)/c-Jun N-Terminal Kinases (JNK) Signaling Pathways.
BACKGROUND microRNA (miR)-181a has been reported to be downregulated in Parkinson's disease (PD), but the regulatory mechanism of miR-181a on neuron apoptosis and autophagy is still poorly understood. We aimed to investigate the neuroprotective effects of miR-181a on PD in vitro. MATERIAL AND METHODS Human SK-N-SH neuroblastoma cells were incubated with different concentrations of 1-methyl-4-phenylpyridinium ion (MPP+) to induce the PD model. The expression of miR-181a was then analyzed. After transfection with miR-181a mimic or scramble following MPP+ treatment, the expression of autophagy protein markers (LC3II, LC3I, and Beclin 1) and p38 mitogen-activated protein kinase (MAPK)/c-Jun N-terminal kinases (JNK) signaling proteins (p-p38, p38, p-JNK, and JNK) and cell apoptosis were detected. Furthermore, the cells were transfected with miR-181a inhibitor and cultured in the presence or absence of p38 inhibitor SB203582 or JNK inhibitor SP600125, and the cell apoptosis was tested again. RESULTS The expression of miR-181a was gradually decreased with the increase of MPP+ concentration (P<0.05, P<0.01, or P<0.001). Overexpression of miR-181a significantly decreased the LC3II/LC3I ratio, Beclin 1 expression, cell apoptosis, and the expression of p-p38 and p-JNK compared to the MPP+ + miR-181a scramble group (all P<0.05). In addition, we observed that SB203582 or SP600125 showed no effects on cell apoptosis, but the effects of miR-181a inhibitor on cell apoptosis were reversed by administration of SB203582 or SP600125 compared to the scramble group (P<0.05). CONCLUSIONS Our results suggest that miR-181a regulates apoptosis and autophagy in PD by inhibiting the p38 MAPK/JNK pathway.


[Switch in the synthesis from IgM to IgG in the human lymphoblastoid cell line RPMI-6410t as affected by human sera].
The switch from IgM to IgG in lymphoblastoid cell line RPMI-6410t was induced by human sera. The factor inducing the switch was found in the human placental serum and in the serum of peripheral blood of healthy donors. The switch investigated is induced both in the initial line 6410t and in some IgM+ sublines derived from it. With the help of the cloning method some IgG+ sublines were developed with different IgG-synthesis levels from 6410t line and its IgM+ sublines after inducing the switch in them. Earlier another type of the switch induction from IgM to IgA was observed in the same line and its IgM+-sublines by the factors contained in some batches of fetal calf serum (FCSG+). Thus, the homogeneous IgM+ cell population is shown to be able to pass in vitro though two different stages of differentiation inherent to B lymphocytes in vivo.


Gestational weight gain in obese mothers and associations with fetal growth.
In 2009, the Institute of Medicine recommended gestational weight gains (GWGs) of 5-9 kg for all obese women. Recommendations by severity of obesity were not specified because of a lack of available data. Our objective was to examine associations between GWG and fetal growth in obese women and assess interactions with obesity severity. We used 2004-2006 Pregnancy Nutrition Surveillance System data from 122,327 obese mothers [prepregnant body mass index (BMI; in kg/m(2)) ge 30]. We used logistic regression to estimate measures of fetal growth including small-for-gestational-age, which was defined as birth weight (BW) lt 2 SDs below the sex and race-ethnicity-specific mean BW (SGA(2SD)), and macrosomia (BW ge 4500 g). We tested for interactions between obesity severity (class I: BMI of 30-34.9; class II: BMI of 35.0-39.9; class III: BMI ge 40) and GWG. Obesity severity modified associations between GWG and fetal growth. Compared with weight gains of 5-9 kg, weight loss in class I women significantly increased the odds of SGA(2SD), whereas a GWG from 0.1 to 4.9 kg was not associated with SGA(2SD) and did not decrease the odds of macrosomia. In class II and III women, compared with weight gains of 5-9 kg, a GWG from minus 4.9 to +4.9 kg was not associated with SGA(2SD) but did decrease the odds of macrosomia. Our study suggests a GWG below the Institute of Medicine guidelines may be associated with more favorable BW for all obese women, and GWG may need to be further defined by obesity severity.


Hyphenated Mass Spectrometry Techniques in the Diagnosis of Amyloidosis.
Amyloidoses are a group of diseases caused by the extracellular deposition of proteins forming amyloid fibrils. The amyloidosis is classified according to the main protein or peptide that constitutes the amyloid fibrils. The most effective methods for the diagnosis of amyloidosis are based on mass spectrometry. Mass spectrometry enables confirmation of the identity of the protein precursor of amyloid fibrils in biological samples with very high sensitivity and specificity, which is crucial for proper amyloid typing. Due to the fact that biological samples are very complex, mass spectrometry is usually connected with techniques such as liquid chromatography or capillary electrophoresis, which enable the separation of proteins before MS analysis. Therefore mass spectrometry constitutes an important part of the so called "hyphenated techniques" combining, preferentially in-line, different analytical methods to provide comprehensive information about the studied problem. Hyphenated methods are very useful in the discovery of biomarkers in different types of amyloidosis. In systemic forms of amyloidosis, the analysis of aggregated proteins is usually performed based on the tissues obtained during a biopsy of an affected organ or a subcutaneous adipose tissue. In some cases, when the diagnostic biopsy is not possible due to the fact that amyloid fibrils are formed in organs like the brain (Alzheimer's disease), the study of biomarkers presented in body fluids can be carried out. Currently, large-scale studies are performed to find and validate more effective biomarkers, which can be used in diagnostic procedures. We would like to present the methods connected with mass spectrometry which are used in the diagnosis of amyloidosis based on the analysis of proteins occurring in tissues, blood and cerebrospinal fluid.


Intraoperative consultation for surgery of the genitalia and genitourinary prostheses.
Patients with genitourinary prostheses, especially the hydraulic variety, will be encountered with increasing frequency in the future and present special problems to the urologist who is called in for intraoperative consultation. Knowledge of the design and operation of these devices, as well as certain operative principles unique to these prostheses, permits the urologist to deal effectively with these situations.


Immunolocalization of the Ca2+-activated K+ channel Slo1 in axons and nerve terminals of mammalian brain and cultured neurons.
Ca(2+)-activated voltage-dependent K(+) channels (Slo1, KCa1.1, Maxi-K, or BK channel) play a crucial role in controlling neuronal signaling by coupling channel activity to both membrane depolarization and intracellular Ca(2+) signaling. In mammalian brain, immunolabeling experiments have shown staining for Slo1 channels predominantly localized to axons and presynaptic terminals of neurons. We have developed anti-Slo1 mouse monoclonal antibodies that have been extensively characterized for specificity of staining against recombinant Slo1 in heterologous cells, and native Slo1 in mammalian brain, and definitively by the lack of detectable immunoreactivity against brain samples from Slo1 knockout mice. Here we provide precise immunolocalization of Slo1 in rat brain with one of these monoclonal antibodies and show that Slo1 is accumulated in axons and synaptic terminal zones associated with glutamatergic synapses in hippocampus and GABAergic synapses in cerebellum. By using cultured hippocampal pyramidal neurons as a model system, we show that heterologously expressed Slo1 is initially targeted to the axonal surface membrane, and with further development in culture, become localized in presynaptic terminals. These studies provide new insights into the polarized localization of Slo1 channels in mammalian central neurons and provide further evidence for a key role in regulating neurotransmitter release in glutamatergic and GABAergic terminals.


Characterization of a type IV collagen major cell binding site with affinity to the alpha 1 beta 1 and the alpha 2 beta 1 integrins.
The aim of this investigation was to identify the domains of type IV collagen participating in cell binding and the cell surface receptor involved. A major cell binding site was found in the trimeric cyanogen bromide-derived fragment CB3, located 100 nm away from the NH2 terminus of the molecule, in which the triple-helical conformation is stabilized by interchain disulfide bridges. Cell attachment assays with type IV collagen and CB3 revealed comparable cell binding activities. Antibodies against CB3 inhibited attachment on fragment CB3 completely and on type IV collagen to 80%. The ability to bind cells was strictly conformation dependent. Four trypsin derived fragments of CB3 allowed a closer investigation of the binding site. The smallest, fully active triple-helical fragment was (150)3-amino acid residues long. It contained segments of 27 and 37 residues, respectively, at the NH2 and COOH terminus, which proved to be essential for cell binding. By affinity chromatography on Sepharose-immobilized CB3, two receptor molecules of the integrin family, alpha 1 beta 1 and alpha 2 beta 1, were isolated. Their subunits were identified by sequencing the NH2 termini or by immunoblotting. The availability of fragment CB3 will allow for a more in-depth study of the molecular interaction of a short, well defined triple-helical ligand with collagen receptors alpha 1 beta 1 and alpha 2 beta 1.


Extending SEQenv: a taxa-centric approach to environmental annotations of 16S rDNA sequences.
Understanding how the environment selects a given taxon and the diversity patterns that emerge as a result of environmental filtering can dramatically improve our ability to analyse any environment in depth as well as advancing our knowledge on how the response of different taxa can impact each other and ecosystem functions. Most of the work investigating microbial biogeography has been site-specific, and logical environmental factors, rather than geographical location, may be more influential on microbial diversity. SEQenv, a novel pipeline aiming to provide environmental annotations of sequences emerged to provide a consistent description of the environmental niches using the ENVO ontology. While the pipeline provides a list of environmental terms on the basis of sample datasets and, therefore, the annotations obtained are at the dataset level, it lacks a taxa centric approach to environmental annotation. The work here describes an extension developed to enhance the SEQenv pipeline, which provided the means to directly generate environmental annotations for taxa under different contexts. 16S rDNA amplicon datasets belonging to distinct biomes were selected to illustrate the applicability of the extended SEQenv pipeline. A literature survey of the results demonstrates the immense importance of sequence level environmental annotations by illustrating the distribution of both taxa across environments as well as the various environmental sources of a specific taxon. Significantly enhancing the SEQenv pipeline in the process, this information would be valuable to any biologist seeking to understand the various taxa present in the habitat and the environment they originated from, enabling a more thorough analysis of which lineages are abundant in certain habitats and the recovery of patterns in taxon distribution across different habitats and environmental gradients.


Characterisation of mucosal lymphoid aggregates in ulcerative colitis: immune cell phenotype and TcR-gammadelta expression.
A histopathological feature considered indicative of ulcerative colitis (UC) is the so-called basal lymphoid aggregates. Their relevance in the pathogenesis of UC is, however, unknown. We have performed a comprehensive analysis of the immune cells in these aggregates most likely corresponding to the lymphoid follicular hyperplasia also described in other colitides. Resection specimens of UC and normal colon were analysed by immunomorphometry, immunoflow cytometry, and immunoelectron microscopy, using a large panel of monoclonal antibodies. (1) In all cases of UC, colonic lamina propria contained numerous basal aggregates composed of lymphocytes, follicular dendritic cells, and CD80/B7.1 positive dendritic cells. (2) CD4(+)CD28(-) alphabeta T cells and B cells were the dominant cell types in the aggregates. (3) The aggregates contained a large fraction of cells that are normally associated with the epithelium: that is, gammadelta T cells (11 (7)%) and alpha(E)beta(7)(+) cells (26 (13)%). The gammadelta T cells used Vdelta1 and were CD4(-)CD8(-). Immunoelectron microscopy analysis demonstrated TcR-gammadelta internalisation and surface downregulation, indicating that the gammadelta T cells were activated and engaged in the disease process. (4) One third of cells in the aggregates expressed the antiapoptotic protein bcl-2. Basal lymphoid aggregates in UC colon are a consequence of anomalous lymphoid follicular hyperplasia, characterised by abnormal follicular architecture and unusual cell immunophenotypes. The aggregates increase in size with severity of disease, and contain large numbers of apoptosis resistant cells and activated mucosal gammadelta T cells. The latter probably colonise the aggregates as an immunoregulatory response to stressed lymphocytes or as a substitute for defective T helper cells in B cell activation. gammadelta T cells in the aggregates may be characteristic of UC.


[Effects of special mouth care with an aroma solution on oral status and oral cavity microorganism growth in elderly stroke patients].
This study was conducted to examine the effect of oral care with an aroma solution on oral status and oral cavity microorganism growth in elderly patients with stroke. A non-equivalent control group, with a pretest-posttest design was used in this study. The participants were assigned to the experimental group (n=30) that received oral care with an aroma solution or the control group (n=31) that received 0.9% saline solution. To identify the effect of the experimental treatments, objective/subjective assessments of oral status and oral cavity microorganism growth were performed using the oral assessment guide, oral perception guide, and oral swab culture. Data were analyzed using Chi-square test, Fisher's exact test, and t-test with the SPSS version 21.0 program. The objective oral status was significantly lower in the experimental group than in the control group (t= -3.64, p<.001). There was no significant difference between the subjective oral status of the experimental group and control groups (t= -1.24, p=.109). Oral microorganism growth was significantly lower in the experimental group than in the control group (t= -7.39, p<.001). These findings indicate that special mouth care using an aroma solution could be an effective oral health nursing intervention for elderly patients with stroke.


Unpowered scooter injuries in children and risk factors for traumatic brain injuries: An 8-year cross-sectional study using a national registry in South Korea.
Head trauma accounts for a large proportion of unpowered scooter injuries in children. Traumatic brain injury (TBI) is the leading cause of considerable mortality and morbidity in children, who are the main users of unpowered scooters. The aim of this study was to explore the characteristics of unpowered scooter injuries in children and to identify predictors of the occurrence of TBI. A multicentre observational retrospective study was conducted using the Emergency Department-based Injury In-depth Surveillance (EDIIS) database in South Korea. Children aged 2 to 18 years old with unpowered scooter injuries between 2011 and 2018 were eligible for inclusion in this study, and the primary outcome was TBI defined based on the International Classification of Diseases, 10th Revision (ICD-10) code. The annual rate of unpowered scooter injuries per 1,000 injured patients increased throughout the study period from 1.4 in 2011 to 16.4 in 2018 (P for trend < 0.001). Of the 3,892 children who had unpowered scooter injuries, 353 (9.2 %) had TBI. Children were at a higher risk of unpowered scooter TBI if they were aged between 2 and 5 years (adjusted odds ratio [aOR]: 1.37; 95 % confidence interval (CI): 1.09-1.73), were male (aOR: 1.45; 95 % CI: 1.14-1.86), were injured either on sidewalks (aOR: 1.80; 95 % CI: 1.20-2.70) or on driveways (aOR: 2.31; 95 % CI: 1.41-3.79), and experienced a fall (aOR: 1.98; 95 % CI: 1.15-3.43). Additionally, children injured after a blunt force were at a lower risk of TBI (aOR: 0.28; 95 % CI: 0.15-0.53). Unpowered scooter injuries in children are increasing in South Korea. It is essential for younger children riding unpowered scooters to wear helmets and for caregivers to actively supervise their children to prevent TBI.


Plasmonic eigenmodes in individual and bow-tie graphene nanotriangles.
In classical electrodynamics, nanostructured graphene is commonly modeled by the computationally demanding problem of a three-dimensional conducting film of atomic-scale thickness. Here, we propose an efficient alternative two-dimensional electrostatic approach where all calculation procedures are restricted to the graphene sheet. Furthermore, to explore possible quantum effects, we perform tight-binding calculations, adopting a random-phase approximation. We investigate multiple plasmon modes in 20 nm equilateral triangles of graphene, treating the optical response classically as well as quantum mechanically. Compared to the classical plasmonic spectrum which is "blind" to the edge termination, we find that the quantum plasmon frequencies exhibit blueshifts in the case of armchair edge termination of the underlying atomic lattice, while redshifts are found for zigzag edges. Furthermore, we find spectral features in the zigzag case which are associated with electronic edge states not present for armchair termination. Merging pairs of triangles into dimers, plasmon hybridization leads to energy splitting that appears strongest in classical calculations while splitting is lower for armchair edges and even more reduced for zigzag edges. Our various results illustrate a surprising phenomenon: Even 20 nm large graphene structures clearly exhibit quantum plasmonic features due to atomic-scale details in the edge termination.


Elucidation of the inverse trans influence in uranyl and its imido and carbene analogues via quantum chemical simulation.
The inverse trans influence (ITI) is investigated in uranyl, UO22+, and its isoelectronic imido (U(NH)22+) and carbene (U(CH2)22+) analogues at the density functional and complete active space self consistent field levels of theory. The quantum theory of atoms in molecules is employed to quantify, for the first time, the effect of the ITI on covalent bond character and its relationship to bond lengths and complex stability.


Laboratory and clinical evaluation of screening agar plates for detection of carbapenem-resistant Enterobacteriaceae from surveillance rectal swabs.
The increased worldwide spread of carbapenem-resistant Enterobacteriaceae (CRE) emphasizes the need for a sensitive screening procedure to identify these microorganisms. Gastrointestinal carriers may serve as the reservoir for cross-transmission in the health care setting, and thus active surveillance is a key part in preventing the spread of such strains. Three agar-based methods for direct CRE detection from rectal swabs were compared: CHROMagar-KPC (Chrom); MacConkey agar with imipenem at 1 μg/ml (MacI); and MacConkey plates with imipenem, meropenem, and ertapenem disks (MacD). First, we compared the levels of detection (LODs) of 10 molecularly characterized carbapenemase-producing Enterobacteriaceae strains by the three methods. Second, we compared their performance in a surveillance study using rectal swabs (n = 139). The LODs of carbapenemase-producing Enterobacteriaceae strains were influenced by their MICs to carbapenems and were best for MacI, followed by Chrom. The MacD method was able to detect only the strains exhibiting MICs of ≥ 32 μg/ml to at least ertapenem. In the surveillance study, both Chrom and MacI had greater sensitivity (85%) than MacD (76%). However, MacI was the most specific method. In conclusion, MacI appears to be most appropriate medium for the detection of CRE in settings in which multiclonal CRE strains with various MICs to carbapenems are circulating.


Automated selection of DAB-labeled tissue for immunohistochemical quantification.
The increased use of immunohistochemistry (IHC) in both clinical and basic research settings has led to the development of techniques for acquiring quantitative information from immunostains. Staining correlates with absolute protein levels and has been investigated as a clinical tool for patient diagnosis and prognosis. For these reasons, automated imaging methods have been developed in an attempt to standardize IHC analysis. We propose a novel imaging technique in which brightfield images of diaminobenzidene (DAB)-labeled antigens are converted to normalized blue images, allowing automated identification of positively stained tissue. A statistical analysis compared our method with seven previously published imaging techniques by measuring each one's agreement with manual analysis by two observers. Eighteen DAB-stained images showing a range of protein levels were used. Accuracy was assessed by calculating the percentage of pixels misclassified using each technique compared with a manual standard. Bland-Altman analysis was then used to show the extent to which misclassification affected staining quantification. Many of the techniques were inconsistent in classifying DAB staining due to background interference, but our method was statistically the most accurate and consistent across all staining levels.


Social networks among users of mental health day care--predictors of social contacts and confiding relationships.
The social networks of people with mental illness have received much attention, but users of day care services have rarely been considered. Users of day hospitals and day centres were surveyed cross-sectionally. Demographic and illness factors were tested for associations with network size, while intrinsic relationship factors were tested for association with confiding in a network member. There was some evidence that a longer duration of contact with services, more unmet needs, working, living in supported accommodation and needing help with psychotic symptoms were associated with having a larger network, while a longer duration of contact was associated with having more confidantes. Day centre users confided in people who were more likely to be friends or neighbours than professionals, and who were more likely to be the same sex. For people in day care, the stereotype that people with longer-term mental health problems are socially isolated is contradicted by this study. The limited role of professionals in providing confiding relationships is striking.