Vasopressin-induced intracellular redistribution of protein kinase D in intestinal epithelial cells.
The spatio-temporal changes of signaling molecules in response to G protein-coupled receptors (GPCR) stimulation is a poorly understood process in intestinal epithelial cells. Here we investigate the dynamic mechanisms associated with GPCR signaling in living rat intestinal epithelial cells by characterizing the intracellular translocation of protein kinase D (PKD), a serine/threonine protein kinase involved in mitogenic signaling in intestinal epithelial cells. Analysis of the intracellular steady-state distribution of green fluorescent protein (GFP)-tagged PKD indicated that in non-stimulated IEC-18 cells, GFP-PKD is predominantly cytoplasmic. However, cell stimulation with the GPCR agonist vasopressin induces a rapid translocation of GFP-PKD from the cytosol to the plasma membrane that is accompanied by its activation via protein kinase C (PKC)-mediated process and posterior plasma membrane dissociation. Subsequently, active PKD is imported into the nuclei where it transiently accumulates before being exported into the cytosol by a mechanism that requires a competent Crm1 nuclear export pathway. These findings provide evidence for a mechanism by which PKC coordinates in intestinal epithelial cells the translocation and activation of PKD in response to vasopressin-induced GPCR activation.


The choroid plexus and cerebral vasculature as target sites for cadmium following acute exposure in neonatal and adult mice: an autoradiographic and gamma counting study.
The relationship between postnatal age at time of cadmium (Cd) exposure, and the retention and distribution of Cd in the central nervous system (CNS) was studied using gamma counting and autoradiography. A single intraperitoneal dose of Cd2+ (84 micrograms/kg or 750 micrograms/kg) containing radioactive 109Cd, was administered on postnatal day 0, 7, 14, or 42. Animals were then killed at various times post exposure (1-115 days) and retention and distribution determined. Maximum retention of Cd in the brain (calculated as a percentage of administered dose) occurred 1-24 days after exposure. Following exposure on day 0, 7, 14, or 42, maximum retention was 1.2%, 1.6%, 0.4%, or 0.09%, respectively. Cd retention after 114 days was 0.3%, 1.0%, 0.1%, or 0.04% for the respective days of exposure. For the carrier-added group maximum retention was higher with corresponding figures of 2.3%, 1.6%, 1.4%, or 0.07% and retention after 114 days was also elevated 0.6%, 1.1%, 0.4%, or 0.04%. The autoradiographic studies indicated that the choroid plexus was the prime target for Cd uptake in the CNS for all age groups, with the blood vessels a target in the early postnatal period.


Oxygen binding to cobalt(II) proto-, deutero- and meso-porphyrin IX dimethyl ester complexes in organic solvents.
The binding of oxygen to cobalt(II) meso, deutero- and proto-porphyrin IX dimethyl esters complexed with pyridine or 2-methylimidazole was investigated at -10 degress - -60 degrees C in toluene or DMF solution, and the thermodynamic data related with the binding were presented. The oxygen affinity of cobalt meso-porphyrin complex was larger by the factor of 2.0-1.4 than those of the other complexes where oxygen affinities were not explained by a simple electron-withdrawing capability of 2,4-substituents of the porphyrin ring. The oxygen binding property was, generally, dependent on the solvent, suggesting that the solvation affects appreciably the oxygen binding to the complexes. The oxygen affinities of cobalt porphyrin complexes in various organic solvents were compared with those of their apomyoglobin complexes. The differences of oxygen affinities between both systems decreased with increasing the size of 2,4-substituents, and it was in the following order on 2,4-substituted porphyrins: Deutero greater than Proto greater than Meso. It was suggested that the 2,4-substitutent effect on the oxygen affinity of cobalt myoglobin complexes was not only caused by the direct electronic effect on the central cobalt atom, but also controlled by the stereochemical interaction between apomyoglobin and the porphyrin.


Production and characterization of a halo-, solvent-, thermo-tolerant alkaline lipase by Staphylococcus arlettae JPBW-1, isolated from rock salt mine.
Studies on lipase production and characterization were carried out with a bacterial strain Staphylococcus arlettae JPBW-1 isolated from rock salt mine, Darang, HP, India. Higher lipase activity has been obtained using 10 % inoculum with 5 % of soybean oil as carbon source utilizing a pH 8.0 in 3 h at 35 °C and 100 rpm through submerged fermentation. Partially purified S. arlettae lipase has been found to be active over a broad range of temperature (30-90 °C), pH (7.0-12.0) and NaCl concentration (0-20 %). It has shown extreme stability with solvents such as benzene, xylene, n-hexane, methanol, ethanol and toluene up to 30 % (v/v). The lipase activity has been found to be inhibited by metal ions of K(+), Co(2+) and Fe (2+) and stimulated by Mn(2+), Ca(2+) and Hg(2+). Lipase activity has been diminished with denaturants, but enhanced effect has been observed with surfactants, such as Tween 80, Tween 40 and chelator EDTA. The K m and V max values were found to be 7.05 mM and 2.67 mmol/min, respectively. Thus, the lipase from S. arlettae may have considerable potential for industrial application from the perspectives of its tolerance towards industrial extreme conditions of pH, temperature, salt and solvent.


The relationships among total body fat, bone mineral content and bone marrow adipose tissue in early-pubertal girls.
Investigation of the physiologic relevance of bone marrow adipose tissue (BMAT) during growth may promote understanding of the bone-fat axis and confluence with metabolic factors. The objective of this pilot investigation was two-fold: (1) to evaluate the relationships among total body fat, bone mineral content (BMC) and femoral BMAT during childhood and underlying metabolic determinants and (2) to determine if the relationships differ by race. Participants included white and non-Hispanic black girls (n=59) ages 4-10 years. Femoral BMAT volume was measured by magnetic resonance imaging, BMC and body fat by dual-energy X-ray absorptiometry. Metabolic parameters were assessed in the fasted state. Total fat and BMC were positively associated with BMAT; however, simultaneous inclusion of BMC and body fat in the statistical model attenuated the association between BMC and BMAT. Differences in BMAT volume were observed, non-Hispanic black girls exhibiting marginally greater BMAT at age eight (P=0.05) and white girls exhibiting greater BMAT at age ten (P<0.001). Metabolic parameters conferred differential impact by race, such that, a positive association for BMAT and leptin (P=0.02) and adiponectin (P=0.002) in white girls while BMAT and insulin were inversely related in non-Hispanic black girls (P=0.008). Our findings revealed a positive relationship between BMAT, body fat and BMC, although body fat, respective to leptin, contributed partly to the relationship between BMAT and BMC. Despite large differences in total fat between non-Hispanic black and white, the relationship between BMAT and BMC was similar to white girls. However, this relationship appeared to be impacted through different mechanisms according to race.


Endovascular treatment of brain-stem arteriovenous malformations: safety and efficacy.
Our purpose was to evaluate the safety and efficacy of endovascular treatment of brain-stem arteriovenous malformations (AVMs), reviewing six cases managed in the last 5 years. There were four patients who presented with bleeding, one with a progressive neurological deficit and one with obstructive hydrocephalus. Of the six patients, one showed 100%, one 90%, two 75% and two about 50% angiographic obliteration of the AVM after embolisation; the volume decreased about 75% on average. Five patients had a good outcome and one an acceptable outcome, with a mild postprocedure neurological deficit; none had further bleeding during midterm follow-up. Endovascular management of a brain-stem AVM may be an alternative to treatment such as radiosurgery and microsurgery in selected cases. It may be not as risky as previously thought. Embolisation can reduce the size of the AVM and possibly make it more treatable by radiosurgery and decrease the possibility of radiation injury.


Separation and detection of DNA by capillary electrophoresis.
The use of capillary electrophoresis for the separation and detection of nucleic acids has been investigated. Lab-model instruments have been built, using commercially available UV absorbance and fluorescence detectors which were modified for use with 50-100 microns I.D. fused-silica capillary tubing. The sensitivity of these instruments (signal-to-noise ratio = 3) was measured as 15 micrograms/ml for fluorescence detection of ethidium bromide-stained herring-sperm DNA and 3 micrograms/ml for UV absorbance detection. With the former instruments a variety of strategies has been used to attain rapid separations of bases, oligonucleotides, restriction fragments and whole phage, viral and plasmid DNAs.


A unique case of gliomatosis peritonei in a man, following a retroperitoneal teratoma.
We present an unusual case of a 56-year-old man presenting with abdominal swelling. Imaging revealed a large abdominal 23 cm cystic mass, which radiologically appeared to be related to the small bowel. There was an attempted surgical removal by the general surgeons. It was histologically confirmed as a retroperitoneal cystic teratoma with immature neural elements with incomplete resection margins. Residual disease was found at re-imaging 3 months later and a further block dissection was performed, with histology confirming recurrence. Thirteen months later, imaging revealed recurrent disease with peritoneal involvement. At laparoscopic exploration, there was peritoneal seeding, and biopsies confirmed a diagnosis of gliomatosis peritonei, secondary to the retroperitoneal teratoma. The patient proceeded to have combination chemotherapy to achieve stable disease on imaging. A month after completion, sadly, the disease progressed; the patient received best supportive care.


The Impact of Small RNA Interference Against Homer1 on Rats with Type 2 Diabetes and ERK Phosphorylation.
The objective of the study is to evaluate Homer1 expression in rats with Type 2 diabetes mellitus (T2DM) and investigate the mechanism by which Homer1 influences the pathogenesis of diabetes through study on rat model with decreased Homer1 expression. Rat model of T2DM was constructed and blood insulin concentration was measured. Homer1 mRNA and protein expressions in rat pancreatic tissue were determined using RT-PCR as well as Western blotting. Homer1 expression in human monocytic THP-1 cells was interfered using short hairpin RNA, and its effect on phosphorylation of extracellular signal-regulated kinase (ERK) was assessed. Fasting glucose concentration in rat model of T2DM was significantly higher than that of normal rats (13.1 ± 2.4 vs 5.1 ± 1.1 mmol/L), and fasting blood insulin concentration of diabetic group was significantly lower than that of normal group (13.6 ± 1.9 18.3 ± 2.2 mIU/L) (P < 0.05). Homer1 mRNA and protein expressions in pancreatic tissue of rats with T2DM were significantly higher than those of normal rats (P < 0.05). Level of ERK phosphorylation in pancreatic tissue of rats with T2DM was significantly higher than that of normal rats. Homer1 mRNA level in rat pancreatic tissue of T2DM was positively correlated with the area of pancreatic islets (r = 0.526, P = 0.014). Homer1 mRNA level was significantly inhibited in high-glucose and high-fat stimulated human monotypic THP-1 cells with interfered Homer1. Compared with controls, P-ERK phosphorylation was significantly decreased in THP-1 cells with interfered Homer1 (P < 0.05). Homer1 can promote the progression of T2DM, which may be achieved through affecting ERK phosphorylation.


Resolving the CO/CN ligand arrangement in CO-inactivated [FeFe] hydrogenase by first principles density functional theory calculations.
The currently presumed assignment of CO/CN ligands in the structure of the active cluster in CO-inactivated [FeFe] hydrogenase is shown to be inconsistent with the available IR data in the enzyme from Clostridium pasteurianum I. A different arrangement has the correct qualitative and quantitative features, reproducing the observed line spacing and intensities and the observed line shift consequent to inactivation with labeled 13CO instead of 12CO. The new assignment is also consistent with the observed change from rhombic to axial symmetry of the electron paramagnetic resonance g tensor upon inactivation.


Role of the liver for the receptor-mediated catabolism of low-density lipoprotein in the 17 alpha-ethinylestradiol-treated rat.
Effects of ethinylestradiol on LDL catabolism and plasma cholesterol were studied in the rat. Hormone treatment led to a reduction in plasma cholesterol and to an increased receptor-mediated catabolism of LDL in the liver and the adrenals. The liver was the most important organ accounting for more than 95% of the receptor-mediated tissue accumulation of LDL following estrogen treatment. It is concluded that the reduction in plasma cholesterol during treatment with ethinylestradiol is due to the stimulation of LDL receptors in the liver.


Pharmacology of neuronal gene expression.
Pharmacological treatments were used to estimate trans-synaptic regulation of opioid peptide gene expression occuring at specific neurotransmitter receptors. In vitro and in vivo studies have shown that different signal-transduction mechanisms regulate the transcription of proenkephalin, proopiomelanocortin and nerve growth factor mRNA. The activation of receptors coupled to adenylate cyclase elicited the increase of proenkephalin and nerve growth factor gene expression. Therefore, a cAMP-dependent mechanism was suggested to be involved in such regulation. However, the temporal delay between the elevation of the intracellular cAMP content and the increase in nerve growth factor and proenkephalin mRNAs prompted us to investigate whether additional mechanisms associated with the second messenger were operative in the regulation of the expression of these two genes. We report evidence that a protein(s), probably functioning as a trans-acting factor, might be involved in the regulation of nerve growth factor gene transcription. The characterization and isolation of these DNA regulatory proteins will provide the pharmacologist with valuable information for the development of new compounds in the therapy of mental disorders.


DNA flow cytometry, clinical and morphological parameters as prognostic factors for advanced malignant and borderline ovarian tumors.
Patients with malignant ovarian (n = 111) and borderline (n = 8) tumors (FIGO stage III/IV) underwent surgery and chemotherapy and were analyzed clinically (age, residual tumor after surgery) and morphologically (type, grade, psammoma body content), and by means of flow cytometry (DNA ploidy, S-phase fraction). Follow-up was 12-72 months for investigation of survival. Patients under 60 years of age (n = 18) with malignant tumors showed longer survival than patients over 60 (n = 93) (P = 0.078). Residual tumor was relevant for prognosis in malignant tumors only if macroscopically there was no residual disease (n = 13). There were no significant differences between residual tumors less than or equal to 2 cm (n = 61) and greater than 2 cm (n = 37). WHO typing was of little importance for survival analysis. Compared to borderline tumors (n = 8), serous (n = 65), endometrioid (n = 13), nonclassifiable (n = 12), mucinous carcinomas (n = 8), and nonepithelial tumors (n = 12) had a poor prognosis. Psammoma bodies were found in 25 patients with serous carcinomas, 7 of them had a high content. The prognosis for these 7 patients was much better than that for patients with a moderate or low psammoma body content (P = 0.006). Twenty-three epithelial tumors were graded G1, 28 were G2, and 47 were G3. However, grading was considered only as a prognostic factor in serous carcinomas (n = 65) (P = 0.028). A total of 199 DNA histograms from 119 patients were analyzed by flow cytometry (FCM). There were no correlations between tumor type and DNA ploidy or S-phase fraction. Seven of eight borderline tumor and all serous carcinomas with a high content of psammoma bodies were diploid combined with a low (less than or equal to 4%) S-phase fraction. DNA ploidy and S-phase fraction were excellent prognosticators. Of 99 epithelial malignant tumors, 35 were diploid and 64 were aneuploid. An S-phase fraction less than or equal to 4% was found in 39 patients, 4.1-10% in 73 patients, and greater than 10% in 23 patients. Diploid tumors and tumors with a low S-phase fraction showed the best survival (P = 0.007, resp. 0.0001). Our study emphasizes the importance of an accurate histology, including information on psammoma body content, and the importance of DNA flow cytometry. The advantage of FCM is that the results are simple, reproducible, and objective.


Oral processing speed as a key mechanism in the relationship between neurological risk and adaptive functioning in survivors of pediatric brain tumors.
Brain tumor (BT) survivors are at risk for difficulties with adaptive functioning (AF). Recent work has associated neurological risk with poorer AF outcomes using the Neurological Predictor Scale (NPS), a quantification of neurological risk factors. Survivors also have poorer attention, processing speed, and working memory, which are all important for AF. The current study examined whether these cognitive constructs explain the relationship between the NPS and AF in survivors. Ninety-five adult BT survivors and 135 healthy controls were recruited from the Atlanta area. The Oral Symbol Digits Modalities test was used to measure processing speed, Digit Span Backward assessed working memory, and Digit Span Forward measured attention. Informants completed the Scales of Independent Behavior (SIB-R) to measure AF. Group differences and correlations were assessed, and the PROCESS macro for SPSS tested indirect effects. Survivors were significantly lower on AF and cognitive measures compared with controls. Attention span and processing speed had significant indirect effects in relationship between NPS and AF individually, but processing speed was the only variable with a significant indirect effect when all cognitive variables were included in the model. The NPS and processing speed together account for approximately 39% of variance in AF outcomes. BT survivors in our sample have lower AF than controls, and processing speed appears to be particularly important in explaining the relationship between neurological risk and AF. In the future, the development of interventions aimed at increasing young adult independence should target both cognitive processing speed and AF skills.


Modeling "frailty": can a simple feedback model suffice?
This commentary offers several views of frailty, and provides an excerpt of the dynamic model proposed by Varadhan et al., noting that it is of a traditional, causal feedback type. Key features of the authors' model are examined, and some limitations identified. (Other more modern approaches are suggested, but not expanded.) In spite of its simplicity, the deterministic feedback model as presented does indicate that weakened connectivity among feedback loops is a possible basis of frailty. In contrast, a nodal-network style of modeling might emphasize nodal failure as well as (or instead of) connectivity failure as the dynamic signature of frailty.


Complications, mortality, and costs for outpatient and short-stay total knee arthroplasty patients in comparison to standard-stay patients.
The purpose of the present study is to determine the differences in cost, complications, and mortality between knee arthroplasty (TKA) patients who stay the standard 3-4 nights in a hospital compared to patients who undergo an outpatient procedure, a shortened stay or an extended stay. TKA patients were identified in the Medicare 5% sample (1997-2009) and separated into the following groups: outpatient, 1-2 days, 3-4 days, or 5+ days inpatient. At two years, costs associated with the outpatient and the 1-2 day stay groups were $8527 and $1967 lower than the 3-4 day stay group, respectively. Out to 2 years, the outpatient and 1-2 day stay groups reported less pain and stiffness, respectively, though the 1-2 day group also had a higher risk for revision.


Effectiveness of an Interpersonal Psychotherapy (IPT) Group Depression Treatment for Head Start Mothers: A Cluster-Randomized Controlled Trial.
Maternal depression is known to be a serious problem with higher rates among poor and racial/ethnic minority mothers that can have numerous negative impacts on their children. These mothers have less access to effective care and may be wary of traditional mental health care because of the stigma. The purpose of this study was to test whether an adaptation of an Interpersonal Psychotherapy group for perinatal depression could be effective in reducing depressive symptoms of mothers whose children were enrolled in Head Start. Forty-nine mothers, randomized by site, were recruited into the intervention group, 70 into the control group. They were measured on depressive symptoms, parenting stress, parenting behavior, and parent child interaction at intake, at end of the group, and 6 months following. The intervention group was lower in depressive symptoms at the end of treatment with a further decrease 6 months post intervention. There was no change in the control group. The intervention group also improved in parenting stress. The sample size for the intervention group was smaller than desired. This study supports the effectiveness of this 12 session IPT group which was highly effective for a population of Head Start mothers. It is a strategy that can be adapted to other settings that serve low income mothers.


N2-Fixing Microbial Consortia Associated with the Ice Cover of Lake Bonney, Antarctica.
Abstract Nitrogen (N) availability is a key nutritional factor controlling microbial production in Antarctic freshwater and soil habitats. Since there are no significant sources of biologically available N entering these ecosystems, nitrogen fixation may be a major source of "new" N supporting primary and secondary production. The role of N2 fixation was examined in cyanobacteria-dominated microbial aggregates embedded in the permanent ice cover of Lake Bonney, McMurdo Dry Valley (Victoria Land) lakes area, and in cyanobacterial mats found in soils adjacent to the ice edge. Nitrogenase activity was extremely low compared to temperate and tropical systems, but N2 fixation was found at all study sites. N2 fixation occurred under both dark and light conditions, indicating the potential involvement of both phototrophic and heterotrophic diazotrophs. Nitrogenase activity measurements (acetylene reduction assay) and molecular characterization (PCR amplification of nifH fragments) demonstrated a diverse and periodically active (when liquid water is present) diazotrophic community in this arid, nutrient-limited environment. As a result of the close proximity to other microorganisms and the nutritional constraints of this environment, these diazotrophs may be involved in mutually beneficial consortial relationships that enhance their growth when water is available.


Desmin as a marker for canine botryoid rhabdomyosarcomas.
The intermediate filament desmin was present in three canine botryoid rhabdomyosarcomas. The use of desmin as a diagnostic tool may, as in these tumours in man, be of value in the classification of canine sarcomas where the origin of the tumour is not always apparent from routine histological sections.


Resilience and sustainability: Similarities and differences in environmental management applications.
In recent years there have been many disparate uses of the terms sustainability and resilience, with some framing sustainability and resilience as the same concept, and others claiming them to be entirely different and unrelated. To investigate similarities, differences, and current management frameworks for increasing sustainability and resilience, a literature review was undertaken that focused on integrated use of sustainability and resilience in an environmental management context. Sustainability was defined through the triple bottom line of environmental, social and economic system considerations. Resilience was viewed as the ability of a system to prepare for threats, absorb impacts, recover and adapt following persistent stress or a disruptive event. Three generalized management frameworks for organizing sustainability and resilience were found to dominate the literature: (1) resilience as a component of sustainability, (2) sustainability as a component of resilience, and (3) resilience and sustainability as separate objectives. Implementations of these frameworks were found to have common goals of providing benefits to people and the environment under normal and extreme operating conditions, with the best examples building on similarities and minimizing conflicts between resilience and sustainability.


Type I interferonopathies in pediatric rheumatology.
Defective regulation of type I interferon response is associated with severe inflammatory phenotypes and autoimmunity. Type I interferonopathies are a clinically heterogenic group of Mendelian diseases with a constitutive activation of this pathway that might present as atypical, severe, early onset rheumatic diseases. Skin vasculopathy with chilblains and livedo reticularis, interstitial lung disease, and panniculitis are common. Recent studies have implicated abnormal responses to nucleic acid stimuli or defective regulation of downstream effector molecules in disease pathogenesis. As observed for IL1-β and autoinflammatory diseases, knowledge of the defects responsible for type I interferonopathies will likely promote the development of targeted therapy.


Retinal OCT findings in acute central retinal artery occlusion of varying severity at different disease stages - a retrospective, observational study.
To study the optical coherence tomography (OCT) changes in eyes with acute central retinal artery occlusion (CRAO) of different severity and at different disease stages. The study included acute CRAO cases of < 7 days duration, imaged on OCT at various time points. Based on the OCT findings at presentation, cases were classified into three severity groups: mild, moderate, and severe. OCT scans were evaluated and classified into four-time intervals based on symptom duration. There were 39 eyes from 38 patients with acute CRAO who underwent 96 OCT scans. At presentation, the study had 11, 16, and 12 cases of mild, moderate, and severe CRAO, respectively. Middle retinal layer opacification was more common in mild CRAO cases, which caused inner retinal layer thinning over time. Moderate CRAO cases had total inner retinal layer opacification, which resulted in retinal thinning over time. Prominent middle limiting membrane (p-MLM) sign was seen in mild and moderate CRAO eyes while were not visualised in severe CRAO. This sign gradually faded out over time. Other OCT findings in higher grades of CRAO included inner retinal fluid, neurosensory detachment, internal limiting membrane detachment, hyperreflective foci, and posterior vitreous opacities. Regardless of the CRAO grade, the final end-point seen was inner retinal layer thinning over time. OCT in CRAO is a useful for determining the severity of retinal ischemia, disease stage, tissue damage mechanism, and final visual outcome. More prospective studies analysing a larger number of cases at fixed time points will be required in the future. Trial Registration Number: Not applicable.


Dissecting the immune landscape of tumor draining lymph nodes in melanoma with high-plex spatially resolved protein detection.
In melanoma patients, microscopic tumor in the sentinel lymph-node biopsy (SLN) increases the risk of distant metastases, but the transition from tumor in the SLN to metastatic disease remains poorly understood. Fluorescent staining for CD3, CD20, CD11c, and DNA was performed on SLN tissue and matching primary tumors. Regions of interest (ROI) were then chosen geometrically (e.g., tumor) or by fluorescent cell subset markers (e.g., CD11c). Each ROI was further analyzed using NanoString Digital Spatial Profiling high-resolution multiplex profiling. Digital counts for 59-panel immune-related proteins were collected and normalized to account for system variation and ROI area. Tumor regions of SLNs had variable infiltration of CD3 cells among patients. The patient with overall survival (OS) > 8 years had the most CD11c- and CD3-expressing cells infiltrating the SLN tumor region. All patients had CD11c (dendritic cell, DC) infiltration into the SLN tumor region. Selecting ROI by specific cell subtype, we compared protein expression of CD11c cells between tumor and non-tumor/normal tissue SLN regions. Known markers of DC activation such as CD86, HLA-DR, and OX40L were lowest on CD11c cells within SLN tumor for the patient with OS < 1 year and highest on the patient with OS > 8 years. We demonstrate the feasibility of profiling the protein expression of CD11c cells within the SLN tumor. Identifying early regulators of melanoma control when the disease is microscopically detected in the SLN is beneficial and requires follow-up studies in a larger cohort of patients.


Identification of a high frequency of chromosomal rearrangements in the centromeric regions of prostate cancer patients.
The aim of the present investigation was to study the major chromosomal aberrations (CA) like deletion, translocation, inversion and mosaic in prostate cancer patients of Tamilnadu, Southern India. Totally 45 blood samples were collected from various hospitals in Tamilnadu, Southern India. Equal numbers of normal healthy subjects were chosen after signing a consent form. Volunteers provided blood samples (5 ml) to establish leukocyte cultures. Cytogenetic studies were performed by using Giemsa-banding technique and finally the results were ensured by spectral karyotyping (SKY) technique. In the present investigation, major CA like deletion, translocation, inversion and mosaic were identified in experimental subjects. Results showed frequent CA in chromosomes 1, 3, 5, 6, 7, 9, 13, 16, 18 and X. In comparison with experimental subjects, the control subjects exhibited very low levels of major CA (P<0.05). In the present study, the high frequency of centromeric rearrangements indicates a potential role for mitotic irregularities associated with the centromere in prostate cancer tumorigenesis. Identification of chromosome alterations may be helpful in understanding the molecular basis of the disease in better manner.


The acoustic communities: Definition, description and ecological role.
An acoustic community is defined as an aggregation of species that produces sound by using internal or extra-body sound-producing tools. Such communities occur in aquatic (freshwater and marine) and terrestrial environments. An acoustic community is the biophonic component of a soundtope and is characterized by its acoustic signature, which results from the distribution of sonic information associated with signal amplitude and frequency. Distinct acoustic communities can be described according to habitat, the frequency range of the acoustic signals, and the time of day or the season. Near and far fields can be identified empirically, thus the acoustic community can be used as a proxy for biodiversity richness. The importance of ecoacoustic research is rapidly growing due to the increasing awareness of the intrusion of anthropogenic sounds (technophonies) into natural and human-modified ecosystems and the urgent need to adopt more efficient predictive tools to compensate for the effects of climate change. The concept of an acoustic community provides an operational scale for a non-intrusive biodiversity survey and analysis that can be carried out using new passive audio recording technology, coupled with methods of vast data processing and storage.


Unilateral eyelid swelling, proptosis and diplopia as initial manifestation of acute myeloid leukemia.
Myeloid sarcoma is a tumor of immature myeloid cells occurring in many extramedullary sites, orbit being one of them where the tumor may occur prior to or after the diagnosis of underlying disease. We report a case of a 17-year-old male who presented with upper eyelid swelling, proptosis and diplopia after presumed blunt trauma without any other clinical signs and symptoms. Initial imaging suggested possibility of subperiosteal hematoma. Magnetic resonance imaging studies demonstrated a solid tumor. Complete excision of the tumor and histopathologic diagnosis revealed evidence of acute myeloid leukemia (AML). There were no other sites indicating any tumoral process; however, bone marrow aspirate revealed an evidence of systemic disease. After chemotherapy and allogenic bone marrow transplant, the patient had complete remission of his disease. An episode of graft vs host reaction resulting in severe dry eyes along with skin eruptions was treated successfully by immunosuppression and topical lubrication without any visual or systemic sequela. This case emphasizes on the need for an aggressive work-up for any unusual orbital lesion in the absence of any explainable etiology. Further, AML may be suspected in the cases of orbital tumors even in the absence of systemic manifestations of leukemia at any age.


Ovarian cancer: Deaf and hearing women's knowledge before and after an educational video.
Members of the Deaf community report language and cultural barriers to accessing health information and care. This study evaluated whether an ovarian cancer education video in American Sign Language with English captioning and voice-over could close the anticipated knowledge gap between Deaf and hearing women's cancer knowledge. Consented Deaf (n = 55) and hearing (n = 52) women's General, Ovarian, and Total Cancer Knowledge were assessed before and after viewing the video. At baseline, hearing women demonstrated significantly higher General, Ovarian, and Total Cancer Knowledge scores than Deaf women. By the post-test, all of Deaf women's knowledge scores had increased, closing the baseline gap. However, hearing women's post-video knowledge had also increased, thereby creating a new knowledge gap. The ovarian cancer education video offers an effective method to increase ovarian and general cancer knowledge for Deaf and hearing women.


Human THP-1 monocyte uptake and cellular disposition of 14C-grepafloxacin.
Uptake of (14)C-grepafloxacin into human mononuclear (THP-1) cells was determined at pH 7.4, 6.8, or 5.0 over a 4-log antibiotic concentration. Grepafloxacin was taken up by THP-1 monocytes rapidly by both a passive and an active transport mechanism at pH 7.4. Its uptake was initially linear, with equilibrium being reached after approximately 1 h. Efflux followed first-order clearance and was complete within 1 h, suggesting no longterm sequestering of the antibiotic occurred. Neither cell number nor serum protein binding appeared to have any effect on antibiotic uptake. High intracellular concentrations were achieved and the ratios of cellular to extracellular antibiotic concentration (IC/EC) were between 529 and 644 at 0.04 micro g/ml at pH 7.4 and 6.8, suggesting that monocytes may contain sufficient levels of grepafloxacin for affecting bacteriostatic killing. Grepafloxacin disposition within the THP-1 monocytes showed large amounts present in the nucleus and cell sap in stimulated and unstimulated cells, and its presence was evenly distributed throughout the cytosol, nuclei, lysosomes, mitochondria, and ribosomes. After stimulation by zymogen A, Staphylococcus aureus, or Streptococcus pneumoniae, increased amounts of grepafloxacin were found within THP-1 monocytes and isolated phagosome vacuoles. No antibiotic sequestration occurred inside stimulated monocytes, although a sufficient intracellular grepafloxacin concentration was available to kill phagocytized bacteria. Metabolic inhibitors, suppressors of K(+)/Cl(-) and Cl(-) transporters, inhibitors of the phagocytic process, low temperature, and low pH inhibited grepafloxacin uptake by THP-1 monocytes.


A single-center, retrospective analysis to compare the efficacy and safety of filgrastim-sndz to filgrastim for prophylaxis of chemotherapy-induced neutropenia and for neutrophil recovery following autologous stem cell transplantation.
Filgrastim-sndz (Zarxio®) was approved by the FDA in March 2015 as a biosimilar product of its reference product, filgrastim (Neupogen®) for all five indications. The NCCN Clinical Practice Guidelines has incorporated filgrastim-sndz into its recommendations as a category 1 recommendation for use in settings of febrile neutropenia, myelosuppressive chemotherapy administration, and post-hematopoietic stem cell transplant (HSCT). As a cost-saving initiative, our institution switched from filgrastim to filgrastim-sndz for all indications starting in March 2016. The purpose of this study was to assess for any difference in clinical or safety outcomes between filgrastim and filgrastim-sndz. This is an IRB-approved, single institution, 1-year retrospective chart review (September 2015 to August 2016) conducted in hospitalized adults who received either filgrastim or filgrastim-sndz either for prophylaxis of chemotherapy-induced myelosuppression or for neutrophil recovery after autologous HSCT. Our data showed no differences in duration of G-CSF therapy (7.96 vs. 8.5 days, P = 0.36), white blood count (WBC) (8.99 vs. 8.04, P = 0.28), absolute neutrophil count (ANC) (7.62 vs. 6.91 × 109/L, P = 0.36) at the time of granulocyte-colony stimulating factor (G-CSF) discontinuation, or safety of filgrastim and filgrastim-sndz. The efficacy and safety of filgrastim and filgrastim-sndz were similar for prophylaxis of chemotherapy-induced neutropenia and neutrophil recovery post-autologous HSCT.


Expression of c-met proto-oncogene in COS cells induces the signal transducing high-affinity receptor for hepatocyte growth factor.
By transfection of the expression plasmid containing a human c-met cDNA into COS-7 cells, high-affinity binding sites specific for HGF with a Kd value of 30 pM were newly detected. Furthermore, only in the c-met transfected COS-7 cells, but not in the control COS-7 cells, DNA synthesis was markedly induced in response to HGF. Thus, transient expression of exogenous c-met cDNA resulted in the appearance of high-affinity receptor for HGF and conversion of the normally non-responsive COS-7 cells into the HGF-responsive cells. These results provide evidence for identifying the c-met product as a signal transducing high-affinity receptor for HGF.


Imaging and histological features of tumor biopsy sample predict aggressive intrasegmental recurrence of hepatocellular carcinoma after radiofrequency ablation.
Aggressive intrasegmental recurrence (AIR) is a form of local recurrence associated with a dismal prognosis and defined by multiple nodules or by an infiltrative mass with a tumor thrombus, occurring in the treated segment, after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). We aimed to identify radiological and/or histological characteristics of tumor biopsy predictive of AIR. We retrospectively analyzed patients treated by No-Touch multi-bipolar RFA (mbpRFA) for a first HCC with a systematic per-procedural tumor biopsy positive for diagnosis of HCC. The first recurrence was classified as non-aggressive local recurrence, AIR or intrahepatic distant recurrence. 212 patients were included (168 men; mean age 67.1 years; mean tumor size 28.6 mm, 181 cirrhosis). AIR occurred in 21/212 patients (10%) and was associated with a higher risk of death (57% in patients with AIR vs 30% without AIR, p = 0.0001). Non-smooth tumor margins, observed in 21% of the patients and macro-trabecular massive histological subtype, observed in 12% of the patients were independently related to a higher risk of AIR (HR: 3.7[1.57;9.06], p = 0.002 and HR:3.8[2.47;10], p = 0.005 respectively). Non smooth margins at imaging and macro-trabecular massive histological subtype are associated with AIR and could be considered as aggressive features useful to stratify therapeutic strategy.


[Preparation and identification of monoclonal antibodies against human apoptosis-related protein TFAR19].
To obtain mouse anti-human TFAR19 monoclonal antibodies for further study of the structure and function of the apoptosis-related protein TFAR19. BALB/c mice were immunized with recombinant human TFAR19, hybridoma cells were screened by cell fusion and subcloning approach. The monoclonal antibodies were identified by ELISA and Western blotting. Three hybridoma cells (C1, C10, 2C12) stable in secreting anti-TFAR19 monoclonal antibodies were obtained. The monoclonal antibodies showed high specificity and high titer to TFAR19 with various affinity. All of them belong to IgG1 subclass. These monoclonal antibodies could bind specifically to TFAR19 protein.


Trends of endodontic and periapical status in adult Danish populations from 1997 to 2009: A repeated cross-sectional study.
To compare the endodontic and periapical status of two similar adult Danish populations examined in 1997-1998 and 2007-2009, respectively. Two populations from Aarhus County, Denmark (age range: 20-64 years) were randomly selected using the Danish Civil Registration System. Full-mouth intraoral radiographs (14 periapical, 2 bitewing) of 616 individuals in 1997-1998 (C1: 16 018 teeth) and 398 individuals in 2007-2009 (C2: 10 668 teeth) were taken to ascertain the number of teeth, presence of root fillings (RFs) and apical periodontitis (AP) using the periapical index (PAI). T-tests with unequal variances were used to assess differences between C1 and C2 with respect to age and the number of teeth. Multivariable and multinomial logistic regression analyses were used to assess the effect of cohort, age and tooth type on the prevalence and relative frequency of RFs and AP. Mean age and mean number of teeth were higher in C2 than C1 (age; C1: 42.3 years, C2: 44.6 years; p = .003), (teeth; C1: 26.0, C2: 26.8; p < .001). The prevalence of root filled teeth was lower in C2 than C1 (C1: 51.8%, C2: 45.0%; p = .03); however, the prevalence of AP was similar (C1: 42.0%, C2: 45.0%). The relative frequency of root filled teeth was lower in C2 than C1 (C1: 4.8%, C2: 3.6%; p = .004), although the individuals were older in C2. The relative frequency of AP was similar in the two cohorts (C1: 3.3%, C2: 3.6%; p = .42). The relative frequency of AP in non-root filled teeth doubled from 0.9% in C1 to 1.8% in C2. C2 had higher PAI scores than C1 for root filled and non-root filled teeth, despite age correction (p ≤ .0007). Two similar general Danish populations examined, respectively, in 1997-1998 and 2007-2009, were associated with a decreasing trend in the prevalence and relative frequency of RFs over the decade. There was no difference in relative frequency of AP in root filled teeth, but an increase in relative frequency of AP in non-root filled teeth. Further population-based studies including analysis of non-root filled teeth using the full-scale PAI and quality assessment of restorations are recommended.


Promise and challenges for discovering transcranial magnetic stimulation induced "numbsense"-Commentary on Ro & Koenig (2021).
The notion that behavioral responses to stimuli can be mediated by separate unconscious and conscious sensory pathways remains popular, but also hotly debated. Recently, Ro and Koenig (2021) reported that when activity in somatosensory cortex was interfered with transcranial magnetic stimulation (TMS), participants could discriminate tactile stimuli they reported not consciously feeling. The study launches an interesting new area of research, helping to uncover mechanisms of unconscious perception that possibly generalize across different sensory modalities. However, we argue here that the study by Ro and Koenig also has several significant shortcomings, and it fails to provide evidence that pathways bypassing primary somatosensory cortex enable unconscious tactile discrimination. By referring to numerous studies investigating TMS-induced blindsight, we outline challenges in demonstrating unconscious sensory pathways using TMS. By facing to these challenges, research investigating TMS-induced numbsense has potential to stimulate progress in stubborn debates and reveal modality-general mechanisms of unconscious perception.


Up-regulation of glucosylceramide synthase in urinary bladder neoplasms.
To investigate the relationships between the clinicopathologic features and the expression of GCS in bladder cancer. Using immunohistochemistry and Western blotting method, 75 bladder cancer specimens were tested for expression of GCS. The correlation of GCS with clinicopathologic features of the patients was analyzed in combination with clinical data. Statistics analyses were done with SPSS 13.0 software, χ(2) test, Fisher's exact test, Kaplan-Meier method, Log-rank test. High and low level expression of GCS explored by immunohistochemistry were 61.3 (46/75) and 39.6 (29/75), respectively. The high expression group (n = 46) showed a significant correlation with high histologic grade (P = 0.021) and tended to show (P = 0.045) that up-expression of GCS was positive related to BNs with lymph node metastasis among the various clinicopathologic characteristics. The overall 5-year survival and disease-free survival rates were 39.5% and 18.4%, respectively. Mean overall survival time was 60.3 months for the low expression group and 45.1 months for the high expression group. Mean disease-free survival was 36.2 months for the low-expression group and 27.3 months for the high-expression group. Our study suggested that up-regulation of GCS might make an aggressive choice of surgical therapy. A high expression of GCS seemed to be an indicator of poor prognosis.


[Settlement fraud from the viewpoint of the defendant].
When a physician by attempting to gain an illegal financial advantage for himself or another person damages the property of somebody in such a way that he produces or maintains an error under false pretense or distortion or suppression of facts, the physician is guilty of fraud. The attempt is a criminal offense. Following terms are discussed in this paper: illegal financial advantage, damage of property, intent, and status proceedings.


Is continuous positive airway pressure therapy in COVID-19 associated with an increased rate of pulmonary barotrauma?
An increased incidence of pulmonary barotrauma in patients receiving CPAP for #COVID19 pneumonia was observed during the second peak of infections at this centre in the UK https://bit.ly/3qeSTp9.


Chemical structure, Salmonella mutagenicity and extent of carcinogenicity as indicators of genotoxic carcinogenesis among 222 chemicals tested in rodents by the U.S. NCI/NTP.
A survey has been conducted of 222 chemicals evaluated for carcinogenicity in mice and rats by the United States NCI/NTP. The structure of each chemical has been assessed for potential electrophilic (DNA-reactive) sites, its mutagenicity to Salmonella recorded, and the level of its carcinogenicity to rodents tabulated. Correlations among these 3 parameters were then sought. A strong association exists among chemical structure (S/A), mutagenicity to Salmonella (Salm.) and the extent and sites of rodent tumorigenicity among the 222 compounds. Thus, a approximately 90% correlation exists between S/A and Salm. across the 115 carcinogens, the 24 equivocal carcinogens and the 83 non-carcinogens. This indicates the Salmonella assay to be a sensitive method of detecting intrinsic genotoxicity in a chemical. Concordance between S/A and Salm. have therefore been employed as an index of genotoxicity, and use of this index reveals two groups of carcinogens within the database, genotoxic and putatively non-genotoxic. These two broad groups are characterized by different overall carcinogenicity profiles. Thus, 16 tissues were subject to carcinogenesis only by genotoxins, chief among which were the stomach, Zymbal's glands, lung, subcutaneous tissue and circulatory system. Conclusions of carcinogenicity in these 16 tissues comprised 31% of the individual chemical/tissue reports of carcinogenicity. In contrast, both genotoxins and non-genotoxins were active in the remaining 13 tissues, chief among which was the mouse liver which accounted for 24% of all chemical/tissue reports of carcinogenicity. Further, the group of 70 carcinogens reported to be active in both species and/or in 2 or more tissues contained a higher proportion of Salmonella mutagens (70%) than observed for the group of 45 single-species/single-tissue carcinogens (39%). 30% of the 83 non-carcinogens were mutagenic to Salmonella. This confirms earlier observations that a significant proportion of in vitro genotoxins are non-carcinogenic, probably due to their non-absorption or preferential detoxification in vivo. Also, only 30% of the mouse liver-specific carcinogens were mutagenic to Salmonella. This is consistent with tumors being induced in this tissue (and to a lesser extent in other tissues of the mouse and rat) by mechanisms not dependent upon direct interaction of the test chemical with DNA. Detection of 103 of the 115 carcinogens could be achieved by use of only male rats and female mice.(ABSTRACT TRUNCATED AT 400 WORDS)


Internet access: the impact on nurses and PAMs.
An outline of a research project into the use of the internet on hospital wards and its impact on nurses and professionals allied to medicine.


Thelephantins D-H: five p-terphenyl derivatives from the inedible mushroom Thelephora aurantiotincta.
Five p-terphenyl derivatives named thelephantins D-H (1-5) together with nine known compounds, thelephantins A-C (6-8), ganbajunin E (9), p-hydroxylbenzoic acid (10), ganbajunin C (11), thelephorin A (12), 2-O-methylatromentin (13) and atromentin (14), were isolated from the methanolic extract of fruit bodies of the Thelephoraceous Basidiomycete Thelephora aurantiotincta. Their structures were elucidated by high-resolution MS, 2D NMR, IR and UV spectroscopic analysis.


Bayesian networks: a new method for the modeling of bibliographic knowledge: application to fall risk assessment in geriatric patients.
Falls in geriatry are associated with important morbidity, mortality and high healthcare costs. Because of the large number of variables related to the risk of falling, determining patients at risk is a difficult challenge. The aim of this work was to validate a tool to detect patients with high risk of fall using only bibliographic knowledge. Thirty articles corresponding to 160 studies were used to modelize fall risk. A retrospective case-control cohort including 288 patients (88 ± 7 years) and a prospective cohort including 106 patients (89 ± 6 years) from two geriatric hospitals were used to validate the performances of our model. We identified 26 variables associated with an increased risk of fall. These variables were split into illnesses, medications, and environment. The combination of the three associated scores gives a global fall score. The sensitivity and the specificity were 31.4, 81.6, 38.5, and 90 %, respectively, for the retrospective and the prospective cohort. The performances of the model are similar to results observed with already existing prediction tools using model adjustment to data from numerous cohort studies. This work demonstrates that knowledge from the literature can be synthesized with Bayesian networks.


Is 24-h sperm motility a useful IVF measure when male infertility is not apparent?
To examine the relationship of 24-h sperm motility between post insemination and fertilization in vitro, in a population with no apparent semen abnormalities. A retrospective study from July 1998 to June 2000. Four hundred and seventy-one consecutive in-vitro fertilization (IVF) cycles for which the primary diagnosis was not male infertility (total motility count > 40 x 106) were studied. Linear regression was used to examine the general relation between 24-h sperm motility and IVF. The cohort with 0% 24-h motility was compared with all other cycles using the t-test and the chi2-test. Test quality was assessed using the positive likelihood ratio. Overall fertilization was 58 +/- 16%. There were 45/471 cycles (9.5%) with zero fertilization. Linear regression of percent fertilization vs. 24-h motility showed no relationship (r = 0.01). The cohort with 0% 24-h motility had a lower fertilization rate 29 +/- 19% (P = 0.05), and had a higher incidence of no fertilization 7/21 (P = 0.01). The positive likelihood ratio was 4.6. Zero 24-h motility indicates occult male infertility, and a positive result indicates a fair to good test. Overall there was no relationship between sperm survival at 24 h post insemination and fertilization in vitro. However, 0% 24-h sperm motility was associated with reduced fertilization


Entomopathogenic Fungi in Biological Plant Protection: The Machinery of Multicomponent System Interactions.
Plant protection faces a growing number of challenges, partly stemming from intensification of plant cultivation to ensure food security for a rapidly growing global population [...].


A randomised double blind trial comparing misoprostol or placebo in the management of early miscarriage.
To study if misoprostol 400 microg, administered vaginally, increased the successful resolution of early miscarriage compared with placebo. Randomised, double blind placebo controlled study. Sahlgrenska University Hospital, Göteborg, Sweden. One hundred and twenty-six women seeking medical attention for early miscarriage. Women with a non-viable, first trimester miscarriage were randomised to vaginal administration of misoprostol 400 microg or placebo. Main outcome measure was the proportion of successful complete resolution of miscarriage. Secondary outcomes were incidence of infection, bleeding, gastrointestinal side effects, pain, use of analgesics and length of sick leave between groups. Sixty-four patients were randomised to misoprostol and 62 to placebo. Eighty-one percent in the misoprostol and 52% in the placebo group had a complete miscarriage within one week of the primary visit (RR 1.57; 95% CI 1.20-2.06). Patients in the misoprostol group reported more pain as assessed on a visual analogue scale (60.4 [31.0] vs 43.8 [37.1] mm; P < 0.007) and required analgesics more often (83%vs 61%, RR 1.35; 95% CI 1.08-1.70). There were no significant differences in the occurrence of gastrointestinal side effects, infection, reduction in haemoglobin or sick leave between the groups. Treatment with 400 mug misoprostol administered vaginally increased the success rate of resolvement of uncomplicated early miscarriages compared with placebo. However, women who received misoprostol experienced more pain and required more analgesics than those who did not.


Echo reference standards in ophthalmic ultrasonography.
The use of different echo standards in ophthalmic ultrasonography is discussed. The acoustical properties of the W38 Hema reflector made out of soft corneal contact lens material are determined and verified in several independent measurements. It is shown that this material meets the requirements for plane echo interfaces which are mandatory for reflectors considered to serve as echo standards. A conversion diagram is given for echo references presently used in ophthalmic ultrasonography. Finally, an example for an application of the W38 reflector in performance control and calibration measurements on ultrasonic instruments is presented.


Publisher Correction: Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Spatial geochemical structure of soft sediment on shallow littoral of the Gulf of Antalya, the eastern Mediterranean Sea.
The concentrations of heavy metals in soft sediments of the Manavgat and Lara regions in Antalya, Türkiye were investigated to assess contamination levels and their potential sources, followed by multivariate statistical analysis and generation of spatial distribution maps. Results showed low contamination levels for As, Zn, and Cu, moderate contamination for Pb, Ni, and Mn, and very high accumulation for Co and Cr. Geoaccumulation index (Igeo) and contamination factor (CF) analyses revealed moderate enrichment for Mn and low enrichment for As, indicating no human-induced contamination in Cu, Pb, Zn, Mn, and As, while Ni, Co, and Cr originated mainly from agriculture. The maximum modified degree of contamination (mCd) value was at an extreme high level, with an average mCd of 4.12 indicating high contamination. Maximum pollution load index (PLI) value was 3.13, indicating high-grade pollution and an average value of 1.7 indicating moderate pollution.


Chromatin Condensation and Enucleation in Red Blood Cells: An Open Question.
Differentiating erythroid cells undergo dramatic changes in morphology, with reduction in cell size, chromatin and nuclear condensation, and enucleation. In this issue of Developmental Cell, Zhao et al. (2016) show that these events are associated with the formation of transient, recurring nuclear openings and selective histone release mediated by caspase-3.


Towards quantitative cutoffs for insomnia: how current diagnostic criteria mischaracterize remission.
Although sleep symptoms of insomnia can be quantified, none of the current diagnostic systems stipulate quantitative cutoffs for sleep-onset latency (SOL) or wake time after sleep onset (WASO). Diagnoses are based instead on idiographic patient reports of "difficulty" falling/staying asleep. Therefore, we examined whether remission of insomnia as per the diagnostic criteria results from a normalization of quantitative sleep disturbance, or if it is simply reflective of tolerance to sleep symptoms. This study involved a yearlong prospective investigation of 649 adults (48.1 ± 11.6 years; 69.3% female) with DSM-5-based insomnia. Participants completed measures of sleep disturbance, perceived sleep-related distress, daytime sleepiness, functional impairment, and workplace productivity at baseline and follow-up one year later. A total of 271 participants no longer met the DSM-5-based insomnia criteria at follow-up. However, 66% of these remitters reported ≥31 min of SOL and/or WASO. Daytime impairment in this subgroup of remitters was no different from that among individuals who met the diagnostic criteria at both baseline and follow-up (ie, chronic insomniacs). By contrast, follow-up impairment was significantly lower (F = 12.3; P < 0.01) among remitters whose sleep disturbance returned below empirically derived quantitative cutoffs (both SOL and WASO <31 min) than in chronic insomniacs. This is the first study on the long-term course of insomnia based on the newly established DSM-5 criteria. A troubling implication of findings is that a majority of insomniacs stop meeting the diagnostic criteria despite continued sleep disturbance and impairment. "Remission" in these cases is attributable instead to tolerance of sleep symptoms. Incorporating quantitative criteria into current diagnoses may offer a more sensitive assay of treatment needs.


Ineffective peripheral tissue perfusion: Clinical validation in patients with hypertensive cardiomiopathy.
To validate defining characteristics of ineffective peripheral tissue perfusion using vasomotor function assessment. Twenty-four patients with hypertensive cardiomiopathy were evaluated for 18 defining characteristics of ineffective peripheral tissue perfusion and underwent vasomotor function assessment with induction of reactive hyperemia, intra-arterial infusion of acetylcholine, and pulse wave velocity measurement. The Student's t test and Kruskall-Wallis test were used to assess the significance of relationships between defining characteristics and vasomotor function data. Diminished lower extremity pulses were associated with diminished forearm blood flow during acetylcholine infusion; left ventricular overload, intermittent claudication, and diminished skin moisture were associated with elevated pulse wave velocity values. The defining characteristics of ineffective peripheral tissue perfusion were highly associated with vasomotor function data as "gold standards" for that diagnosis. Nurses should be able to accurately assess diminished lower extremity pulses, intermittent claudication, and diminished skin moisture as relevant characteristics of ineffective peripheral tissue perfusion in patients with hypertensive cardiomiopathy.


Clinical validation of surface-enhanced Raman scattering-based immunoassays in the early diagnosis of rheumatoid arthritis.
We assessed the clinical feasibility of conducting immunoassays based on surface-enhanced Raman scattering (SERS) in the early diagnosis of rheumatoid arthritis (RA). An autoantibody against citrullinated peptide (anti-CCP) was used as a biomarker, magnetic beads conjugated with CCP were used as substrates, and the SERS nanotags were comprised of anti-human IgG-conjugated hollow gold nanospheres (HGNs). We were able to determine the anti-CCP serum levels successfully by observing the distinctive Raman intensities corresponding to the SERS nanotags. At high concentrations of anti-CCP (>25 U/mL), the results obtained from the SERS assay confirmed those obtained via an ELISA-based assay. Nevertheless, quantitation via our SERS-based assay is significantly more accurate at low concentrations (<25 U/mL). In this study, we compared the results of an anti-CCP assay of 74 clinical blood samples obtained from the SERS-based assay to that of a commercial ELISA kit. The results of the anti-CCP-positive group (n = 31, >25 U/mL) revealed a good correlation between the ELISA and SERS-based assays. However, in the anti-CCP-negative group (n = 43, <25 U/mL), the SERS-based assay was shown to be more reproducible. Accordingly, we suggest that SERS-based assays are novel and potentially useful tools in the early diagnosis of RA.


Methanol bioconversion in Methylotuvimicrobium buryatense 5GB1C through self-cycling fermentation.
Methanol is an abundant and low-cost next-generation carbon source. While many species of methanotrophic bacteria can convert methanol into valuable bioproducts in bioreactors, Methylotuvimicrobium buryatense 5GB1C stands out as one of the most promising strains for industrialization. It has a short doubling time compared to most methanotrophs, remarkable resilience against contamination, and a suite of tools enabling genetic engineering. When approaching industrial applications, growing M. buryatense 5GB1C on methanol using common batch reactor operation has important limitations; for example methanol toxicity leads to mediocre biomass productivity. Advanced bioreactor operation strategies, such as fed-batch and self-cycling fermentation, have the potential to greatly improve the industrial prospects of methanotrophs growing on methanol. Herein, implementation of fed-batch operation led to a 26-fold increase in biomass density, while two different self-cycling fermentation (SCF) strategies led to 3-fold and 10-fold increases in volumetric biomass productivity. Interestingly, while synchronization is a typical trait of microbial populations undergoing SCF, M. buryatense 5GB1C cultures growing under this mode of operation led to stable, reproducible cycles but no significant synchronization.


ECMO PAL: using deep neural networks for survival prediction in venoarterial extracorporeal membrane oxygenation.
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a complex and high-risk life support modality used in severe cardiorespiratory failure. ECMO survival scores are used clinically for patient prognostication and outcomes risk adjustment. This study aims to create the first artificial intelligence (AI)-driven ECMO survival score to predict in-hospital mortality based on a large international patient cohort. A deep neural network, ECMO Predictive Algorithm (ECMO PAL) was trained on a retrospective cohort of 18,167 patients from the international Extracorporeal Life Support Organisation (ELSO) registry (2017-2020), and performance was measured using fivefold cross-validation. External validation was performed on all adult registry patients from 2021 (N = 5015) and compared against existing prognostication scores: SAVE, Modified SAVE, and ECMO ACCEPTS for predicting in-hospital mortality. Mean age was 56.8 ± 15.1 years, with 66.7% of patients being male and 50.2% having a pre-ECMO cardiac arrest. Cross-validation demonstrated an inhospital mortality sensitivity and precision of 82.1 ± 0.2% and 77.6 ± 0.2%, respectively. Validation accuracy was only 2.8% lower than training accuracy, reducing from 75.5% to 72.7% [99% confidence interval (CI) 71.1-74.3%]. ECMO PAL accuracy outperformed the ECMO ACCEPTS (54.7%), SAVE (61.1%), and Modified SAVE (62%) scores. ECMO PAL is the first AI-powered ECMO survival score trained and validated on large international patient cohorts. ECMO PAL demonstrated high generalisability across ECMO regions and outperformed existing, widely used scores. Beyond ECMO, this study highlights how large international registry data can be leveraged for AI prognostication for complex critical care therapies.


Ultrastructural alteration of glomerular anionic sites in nephrotic patients.
The relationship of glomerular anionic sites to proteinuria was examined ultrastructurally in human nephrotic syndrome. The anionic sites were analysed morphometrically in patients with minimal-change nephrotic syndrome (MCNS, 11 patients) and in other glomerulonephritides complicated with nephrotic syndrome (4 patients) by the high-iron diamine-thiocarbohydrazide-silver proteinate method. The anionic sites in MCNS patients in remission (7 patients) were normal. In contrast, the anionic sites in nephrotic patients with MCNS (4 patients) and the other glomerulonephritides were decreased in number. Moreover, smaller and irregularly distributed anionic sites or the greater loss of them from the paramesangial region were observed in the nephrotic patients. The loss of glomerular anionic sites may induce structural alteration of the glomerular basement membrane and mesangial matrix. The loss and structural abnormalities of glomerular anionic sites in nephrotic patients may be one of the mechanisms responsible for massive proteinuria.


Human epidermal growth factor receptor-2 expression in locally advanced rectal cancer: association with response to neoadjuvant therapy and prognosis.
The aim of this study was to determine whether pretreatment status of human epidermal growth factor receptor-2 (HER-2) could predict pathologic response to neoadjuvant chemoradiotherapy (nCRT) and outcomes for patients with locally advanced rectal cancer (LARC). A total of 119 patients diagnosed with LARC received standardized multimodal treatment. Their HER-2 status was determined in pretreatment biopsies by immunohistochemistry (IHC) and FISH. Tumor response was assessed in resected regimens using the tumor regression grade system and TNM staging system. Twenty-two cases in 119 patients assessed as IHC3+ or IHC2+ plus gene-amplified were determined as HER-2 positive. Positive HER-2 status was not associated with any pretreatment clinicopathologic parameters (P > 0.05). HER-2 status could not predict pathologic response to nCRT based on downstaging (P = 0.210) and tumor regression grade (P = 0.085) but it provides us with a trend that HER-2-positive tumors may be resistant to nCRT. Positive HER-2 status was significantly associated with poor 5-year disease-free survival (P = 0.015) and 5-year overall survival (P = 0.026). It can act as a worse prognostic factor for LARC patients.


Managing COVID-19 in pregnant women.
Principles of management of COVID-19 in the general population apply in pregnancy with few exceptions. Clinical inertia can lead to preventable morbidity and mortality. COVID-19 vaccines are safe and should be recommended at any stage of pregnancy. https://bit.ly/3Rj8nWr.


Interleukin 4 promotes the growth of tumor-infiltrating lymphocytes cytotoxic for human autologous melanoma.
Addition of IL-4 (1,000 U/ml) to either high or low concentrations of IL-2 augmented tumor-infiltrating lymphocytes (TIL) growth from human melanoma. Weekly restimulation with irradiated tumor cells in conjunction with IL-4 allowed enhanced growth of TIL. With low-dose IL-2 (10 U/ml) and IL-4, expanded TIL had little cytolytic activity against Daudi or allogeneic tumors. Further, IL-4 augmented the total lytic activity against autologous tumors in most cases. With high-dose IL-2 (1,000 U/ml), IL-4 addition decreased nonspecific killing activity against Daudi or allogeneic melanomas in many cases, and reciprocally augmented cytolytic activity against the autologous melanoma in many cases. This suggests the possible use of IL-4 in cancer therapy, especially in adoptive cellular immunotherapy using TIL or in conjunction with IL-2 administration.


[Is there a possibility of paraplacental oxygenation of fetal blood? First results of an investigation with fluorocarbon (author's transl)].
By checking the cardiotropic effect on fetal rabbits we tried to find out weather there is a possibility of paraplacental oxygenation of fetal blood. Amniotic caves of nine fetal rabbits of 28th or 29th day of gestation are perfused with Perfluorobutyltetrahydrofuran (FX 80, 3 M Comp., St. Paul, Minn., USA) continuously. This was done by double blind investigation. The fetal heart rate is written by Hewlett-Packard-cardiotocograph. Therefore we use modificated EEG-electrodes. 48 h before we cut the spinal cord of the pregnant animals just for analgesie. So we exclude the influence of analgesics or narcotics. After complete interruption of uterine blood supply you can find an initial reduction of fetal heart rate. Using fluorocarbon we notice an increasing or stabilisation of fetal heart rate of all rabbit fetus. In comparison with control animals the difference is high significant. The cardial survival rate of four fetal rabbits treated with fluorocarbon is prolonged up to 50 min. During this time all "fluorocarbon fetus" never died earlier than the control animals. Lots of new questions are provoked by our results. One has to find an answer.


Inhibition of mucin secretion in a colonic adenocarcinoma cell line by DIDS and potassium channel blockers.
The factors which influence the exocytosis of mucins are not well characterized. Since the physical properties of mucins may be affected significantly by the co-secretion of electrolytes and water, we studied the relationship between ion movement and mucin secretion in T84 cells, a human colonic adenocarcinoma cell line which has been well characterized with respect to apical chloride secretion. Secretion of mucin was assessed by immunoassay of mucin appearing in the medium within 30 min of stimulation. Cells were grown on plastic in DMEM/Ham's F12 medium and experiments were carried out at 70% confluence. Mucin secretion was stimulated by the calcium ionophore A23187, or A23187 plus vasoactive intestinal polypeptide. Stimulated mucin secretion was not affected by loop diuretics (furosemide (1 x 10(-3) M) or bumetanide (1 x 10(-4) M)), with or without the addition of ouabain (5 x 10(-5) M) and amiloride (1 x 10(-5) M), making it unlikely that transcellular chloride movements in necessary for mucin secretion. However, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; (1 x 10(-5) and 5 x 10(-5) M) and three potassium channel blockers BaCl2 (1 x 10(-3) and 5 x 10(-3) M), tetraethylammonium chloride (1 x 10(-2) M) and quinine (5 x 10(-4) M) inhibited mucin secretion. A DIDS-sensitive chloride channel or chloride/bicarbonate exchanger and a Ca2(+)-dependent potassium channel may play important roles in mucin secretion. Since plasma membranes are sparingly permeable to DIDS, the DIDS-sensitive site is likely to be on the apical plasma membrane, perhaps at an initiation locus for exocytosis.


MicroRNAs: Emerging Regulators of Metastatic Bone Disease in Breast Cancer.
Bone metastasis is a frequent complication in patients with advanced breast cancer. Once in the bone, cancer cells disrupt the tightly regulated cellular balance within the bone microenvironment, leading to excessive bone destruction and further tumor growth. Physiological and pathological interactions in the bone marrow are mediated by cell-cell contacts and secreted molecules that include soluble proteins as well as RNA molecules. MicroRNAs (miRNAs) are short non-coding RNAs that post-transcriptionally interfere with their target messenger RNA (mRNA) and subsequently reduce protein abundance. Since their discovery, miRNAs have been identified as critical regulators of physiological and pathological processes, including breast cancer and associated metastatic bone disease. Depending on their targets, miRNAs can exhibit pro-tumorigenic or anti-tumorigenic functions and serve as diagnostic and prognostic biomarkers. These properties have encouraged pre-clinical and clinical development programs to investigate miRNAs as biomarkers and therapeutic targets in various diseases, including metastatic cancers. In this review, we discuss the role of miRNAs in metastatic bone disease with a focus on breast cancer and the bone microenvironment and elaborate on their potential use for diagnostic and therapeutic purposes in metastatic bone disease and beyond.


Co-Immunoprecipitation of Macrophage Migration Inhibitory Factor.
Immunoprecipitation is a technique which enables a macromolecule of interest to be isolated from heterogenous mixtures (particularly cell lysates). However, the immunoprecipitation of protein(s) can be challenging, with multiple variations of the basic technique required for successful antigenic pull-down. This depends on the target of interest, cell source, and localization. Here, immunoprecipitation of MIF from mouse and human macrophage cell lysates is described, which is both reliable and replicable, derived from multiple optimization experiments.


Human betaine-homocysteine methyltransferase (BHMT) and BHMT2: common gene sequence variation and functional characterization.
Betaine-homocysteine methyltransferase (BHMT) catalyzes the remethylation of homocysteine. BHMT2 encodes a protein 73% identical in amino acid sequence to BHMT, but the function of BHMT2 remains unclear. We set out to identify and functionally characterize common genetic variation in BHMT and BHMT2. Specifically, we sequenced exons, exon-intron splice junctions and the 5'-flanking regions (5'-FRs) of BHMT and BHMT2 using 240 DNA samples from four ethnic groups. Twenty-five single nucleotide polymorphisms (SNPs), including 4 nonsynonymous SNPs, and 39 SNPs, including 4 nonsynonymous, were observed in BHMT and BHMT2, respectively. BHMT wild type (WT) and variant allozymes were expressed in COS-1 cells. Variant allozymes showed no significant differences from WT in levels of enzyme activity or immunoreactive protein, but there were statistically significant differences in apparent K(m) values. Luciferase reporter gene constructs were created for the three most common BHMT 5'-FR haplotypes, and significant variation was observed in the ability of these constructs to drive transcription. Although BHMT2 mRNA has been observed in human liver and kidney, expression of the protein has not been reported. We were unable to express BHMT2 in mammalian cells, and the protein aggregated after bacterial expression. Furthermore, BHMT2 was rapidly degraded in a rabbit reticulocyte lysate, but it could be stabilized by cotransfection of COS-1 cells with BHMT and, after cotransfection, it coprecipitated with BHMT. These studies have defined common genetic variation in BHMT and BHMT2 and functionally characterized BHMT SNPs. They may also help to explain why BHMT2 has not previously been defined functionally.


A network mechanism underlying hippocampal seizure-like synchronous oscillations.
The hippocampus is a remarkable neural structure that displays a variety of synchronous oscillations that may be physiological or pathophysiological, such as theta rhythms and epileptic seizures. Electrically induced seizure-like afterdischarges are an excellent system for elucidating the network mechanisms underlying neuronal synchronization and rhythm generation of epileptic synchronous oscillations in extremely hyperactive hippocampal networks. In this Update Article, we review key findings of studies on these electrically induced seizure-like afterdischarges in vitro. During these afterdischarges, GABAergic responses become transiently depolarizing and even excitatory as chloride rapidly accumulates postsynaptically in pyramidal cells. Glutamate and potassium enhance this transient GABAergic excitation. Neuronal synchronization of afterdischarge is achieved by GABAergic and glutamatergic excitation of pyramidal cells and interneurons localized in the stratum pyramidale and stratum oriens. Rhythm generation in seizure-like synchronous oscillations is not yet understood but is the subject of intensive study.


Case report and review of delayed-interval delivery for dichorionic, diamniotic twins with normal development.
We report a case of delayed-interval delivery of a dichorionic, diamniotic twin pregnancy with the survival of both twins. The patient presented at 22 weeks and 1 day of gestation with vaginal bleeding and preterm labor. Five days later, the first twin was born. The second twin remained in utero. The management consisted of careful monitoring of both maternal and fetal status. Nine days later, the second twin was delivered vaginally. Both twins received full resuscitation and immediate life-support intervention; at 7 years of age both twins exhibited normal development.


Perimetry: a need for standardization.
Luminance measurements of targets and backgrounds revealed differences for various types of perimetric instruments. A lack of uniform testing conditions for instruments of the same design was also noted. Of the instruments measured, hemispheric-projection perimeters seemed to provide the most repeatable test conditions.


Meconium has no lecithin or sphingomyelin but affects the lecithin/sphingomyelin ratio.
Although a few studies have evaluated the effect of meconium on the lecithin/sphingomyelin ratio for testing of fetal lung maturity, to date these studies have assessed only the lecithin-sphingomyelin ratio of amniotic fluid contaminated with meconium. The purpose of this study was (1) to determine whether meconium by itself has a lecithin/sphingomyelin ratio and, if so, (2) to determine whether the lecithin/sphingomyelin ratio is constant. A lecithin/sphingomyelin ratio was obtained by standard thin-layer chromatography on the first meconium stool of 20 neonates between 31 weeks and term. A quantitative assay was then performed on a sample from each gestational age (7 samples ranging from 31 weeks to term) to confirm the presence of lecithin and sphingomyelin. The 20 samples had atypical thin-layer chromatographic migratory patterns in the zones for lecithin and sphingomyelin. The presumed lecithin/sphingomyelin ratios ranged from 1.1 to 3.6, with no correlation with gestational age. However, the quantitative assay did not detect the presence of lecithin or sphingomyelin in any of the analyzed samples. Meconium does not appear to contain lecithin or sphingomyelin but has an unidentified moiety whose migratory pattern, as shown by qualitative standard thin-layer chromatography, is similar to that of lecithin with sphingomyelin. Therefore the presence of meconium in amniotic fluid may falsely raise or lower the lecithin/sphingomyelin ratio and confuse fetal lung maturity interpretations.


Comprehensive sequencing of the myocilin gene in a selected cohort of severe primary open-angle glaucoma patients.
Primary open-angle glaucoma (POAG) is the most common form of glaucoma, prevalent in approximately 1-2% of Caucasians in the UK over the age of 40. It is characterised by an open anterior chamber angle, raised intraocular pressure (IOP) and optic nerve damage leading to loss of sight. The myocilin gene (MYOC) is the most common glaucoma-causing gene, accounting for ~2% of British POAG cases. 358 patients were selected for next generation sequencing (NGS) with the following selection criteria: Caucasian ethnicity, intraocular pressure (IOP) 21-40 mm Hg, cup:disc ratio ≥0.6 and visual field mean deviation ≤-3. The entire MYOC gene (17,321 bp) was captured including the promoter, introns, UTRs and coding exons. We identify 12 exonic variants (one stop-gain, five missense and six synonymous variants), two promoter variants, 133 intronic variants, two 3' UTR variants and 23 intergenic variants. Four known or predicted pathogenic exonic variants (p.R126W, p.K216K, p.Q368* and p.T419A) were identified across 11 patients, which accounts for 3.07% of this POAG cohort. This is the first time that the entire region of MYOC has been sequenced and variants reported for a cohort of POAG patients.


Calcifications within the duct of Wirsung in calcific pancreatitis.
A review of abdominal radiographs of 50 patients with the clinical diagnosis of chronic pancreatitis showed calcific pancreatitis in 27 patients. Ten patients had severe pain associated with weight loss. Five had obstruction of the duct of Wirsung: one by a pseudocyst and four by large stones near the ampulla of Vater. The radiologic workup presented emphasizes the need to study the duct of Wirsung in patients with chronic pancreatitis to guide the surgical approach for relief of intractavle pain. Theories regarding the pathophysiology of calcium deposition and stone formation and migration are reviewed.


Gene expression profiles of spleen, liver, and head kidney in turbot (Scophthalmus maximus) along the infection process with Philasterides dicentrarchi using an immune-enriched oligo-microarray.
We evaluated the expression profiles of turbot in spleen, liver, and head kidney across five temporal points of the Philasterides dicentrarchi infection process using an 8x15K Agilent oligo-microarray. The microarray included 2,176 different fivefold replicated gene probes designed from a turbot 3' sequenced EST database. We were able to identify 221 differentially expressed (DE) genes (8.1% of the whole microarray), 113 in spleen, 83 in liver, and 90 in head kidney, in at least 1 of the 5 temporal points sampled for each organ. Most of these genes could be annotated (83.0%) and functionally categorized using GO terms (69.1%) after the additional sequencing of DE genes from the 5' end. Many DE genes were related to innate and acquired immune functions. A high proportion of DE genes were organ-specific (70.6%), although their associated GO functions showed notable similarities in the three organs. The most striking difference in functional distribution was observed between the up- and downregulated gene groups. Upregulated genes were mostly associated to immune functions, while downregulated ones mainly involved metabolism-related genes. Genetic response appeared clustered in a few groups of genes with similar expression profiles along the temporal series. The information obtained will aid to understand the turbot immune response and will specifically be valuable to develop strategies of defense to P. dicentrarchi to achieve more resistant broodstocks for turbot industry.


Sorokiniol: a new enzymes inhibitory metabolite from fungal endophyte Bipolaris sorokiniana LK12.
Medicinal plants harboring endophytic fungi could carry significant potential for producing bioactive secondary metabolites. Endophytic fungi serve as alternate source of interesting compounds in their natural and modified synthetic forms to treat different diseases. In this regard, endophytic microflora associated with alkaloid-rich medicinal plants Rhazya stricta is least known. We isolated one new bioactive compound sorokiniol (1) along with two known cyclic peptides BZR-cotoxin I (2) and BZR-cotoxin IV (3) from fungal endophyte Bipolaris sorokiniana LK12. The structures of the isolated new and known compounds were elucidated through spectroscopic data, including 1D and 2D NMR ((1)H, (13)C, HSQC, HMBC, and NOESY), mass, and UV. The known peptides (2-3) were characterized by ESI-MS, MS/MS, and by comparing the NMR data with the literature. The isolated metabolites were assayed for their role against enzyme inhibition. Compound 1 was significantly inhibitory towards acetyl cholinestrase while the other compounds (2-3) had moderate anti-lipid peroxidation and urease activities. The present results suggest that the endophytic microorganism associated with indigenously important medicinal plants can offer a rich source of biologically active chemical constituents which could help in discovering enzyme inhibitory lead drugs.


Laryngeal myxoma: a case report and review of the literature.
Myxomas are a rare benign neoplasm of uncertain mesenchymal cell origin, typically involving the heart. Laryngeal myxomas are uncommon, and are usually misdiagnosed as laryngeal polyp. To the best of our knowledge, there are only nine reported cases in the English literature. We report a case of a laryngeal myxoma presenting clinically as a left vocal cord polyp in a 77 year old male, and review the literature related to this rare entity.


Informed choice and its associated factors among women received immediate postpartum long-acting reversible contraceptives at public hospitals in Sidama Regional State, Ethiopia, 2022.
It is crucial to ensure the quality of family planning (FP) services through women's informed choice during the provision of long-acting reversible contraceptives. In Ethiopia, previous studies have focused on the quality of family planning services. However, much emphasis was not given to the informed choice of immediate postpartum long-acting reversible contraceptives (LARCs), particularly in the study area. This study determines the mangnitude of informed choice and associated factors among immediate postpartum women who received long-acting reversible contraceptives. An institution-based cross-sectional study was conducted from July 1 - August 31, 2022, among 373 immediate postpartum women who received long-acting reversible contraceptives at public hospitals in the Sidama regional state, Ethiopia. Women were selected and interviewed using a systematic random sampling technique and via a structured interviewer-administered questionnaire respectively. Data was collected using Kobo Toolbox software and then exported to the Statistical Package for Social science (SPSS) version 25 for analysis. A logistic regression model was used to identify the predictor variables. The magnitude of informed choice of long-acting reversible contraceptives was 23.5% (95% CI (19.6%-27.7%)). The messages through posters about long-acting reversible contraceptives at the facility (AOR 3.6, 95% CI (1.92-6.79), postpartum family planning counseling during antenatal care (AOR 2.8, 95% CI (1.2-6.4), previous contraceptive use (AOR 3.23, 95% CI (1.12-9.33), and being secondary and higher educated (AOR 2.92, 95%CI (1.27-6.73) and (AOR 5.7, 95% CI (2.267-14.669) respectively were factors significantly associated with informed choice during immediate postpartum family planning service. In the current study, nearly one-fourth of women were informed about LARCs. Socio-demographic factors, prior use of contraception, exposure to posters that have messages about long-acting reversible contraceptives, and postpartum family planning counselling during antenatal care are factors that affect the woman's ability to make an informed choice. There should be immediate PPFP counselling that focuses on a full range of contraceptive method choices to facilitate postpartum women's ability to make informed choices.


Convergence and norm estimates of Hermite interpolation at zeros of Chevyshev polynomials.
In this paper, we investigate the simultaneous approximation of a function f(x) and its derivative [Formula: see text] by Hermite interpolation operator [Formula: see text] based on Chevyshev polynomials. We also establish general theorem on extreme points for Hermite interpolation operator. Some results are considered to be an improvement over those obtained in Al-Khaled and Khalil (Numer Funct Anal Optim 21(5-6): 579-588, 2000), while others agrees with Pottinger's results (Pottinger in Z Agnew Math Mech 56: T310-T311, 1976).


Cost-effectiveness of genetic and clinical predictors for choosing combined psychotherapy and pharmacotherapy in major depression.
Predictors of treatment outcome in major depressive disorder (MDD) could contribute to evidence-based therapeutic choices. Combined pharmacotherapy and psychotherapy show increased efficacy but higher cost compared with antidepressant pharmacotherapy; baseline predictors of pharmacotherapy resistance could be used to identify patients more likely to benefit from combined treatment. We performed a proof-of-principle study of the cost-effectiveness of using previously identified pharmacogenetic and clinical risk factors (PGx-CL-R) of antidepressant resistance or clinical risk factors alone (CL-R) to guide the prescription of combined pharmacotherapy and psychotherapy vs pharmacotherapy. The cost-effectiveness of these two strategies was compared with standard care (ST, pharmacotherapy to all subjects) using a three-year Markov model. Model parameters were literature-based estimates of response to pharmacotherapy and combined treatment, costs (UK National Health System) and benefits (quality-adjusted life years [QALYs], one QALY=one year lived in perfect health). CL-R was more cost-effective than PGx-CL-R: the cost of one-QALY improvement was £2341 for CL-R and £3937 for PGx-CL-R compared to ST. PGx-CL-R had similar or better cost-effectiveness compared to CL-R when 1) the cost of genotyping was £100 per subject or less or 2) the PGx-CL-R test had sensitivity ≥ 0.90 and specificity ≥ 0.85. The cost of one-QALY improvement for CL-R was £3664 and of £4110 in two independent samples. lack of validation in large samples from the general population. Using clinical risk factors to predict pharmacotherapy resistance and guide the prescription of pharmacotherapy combined with psychotherapy could be a cost-effective strategy.


Maternal humoral immune response to incompatibility at multiple minor histocompatibility loci in mice.
Mice of the H-2b haplotype were mated with males of the same MHC haplotype, but differing at multiple minor histocompatibility loci. Mice were bled during each pregnancy and at 2-day intervals post-partum. The sera were assayed by indirect immunofluorescence for evidence of a humoral immune response to paternal minor histocompatibility antigens. Alloantibody was first detected in the post-partum period following the third pregnancy, and was also detected during the fourth pregnancy. Thereafter, alloantibody levels dropped and by the post-partum period following the fifth pregnancy, fell to control values. Assays on a panel of cells from mice of different inbred strains revealed specificity of the alloantibody to H-3.1, H-4.1 and H-7.1 antigens. A conventional dye exclusion cytotoxicity test revealed the pregnancy-induced alloantibody did not exhibit complement-dependent cytotoxicity. These findings are discussed in relation to the regulation and functional significance of the humoral immune response in allogeneic pregnancy.


Determination of monoamine neurotransmitters in human urine by carrier-mediated liquid-phase microextraction based on solidification of stripping phase.
A novel method was developed for the analysis of monoamine neurotransmitters (MNTs) in human urine by carrier-mediated liquid-phase microextraction based on solidification of stripping phase method (CM-LPME-SSP) coupled with high performance liquid chromatography-electrochemical detector (HPLC-ECD). By adding an appropriate carrier in organic phase, simultaneous extraction of hydrophilic analytes, MNTs, with high enrichment factors (22.6-36.1 folds) and excellent sample cleanup was achieved. A new strategy, solidifying the aqueous stripping phase in the back-extraction process, was developed to facilitate the collection of the stripping phase as small as a few microliters. Combined with HPLC-ECD analysis, the linear ranges of the established method were 0.015-2.0 μg/mL for NE, E, DA, and 0.020-2.0 μg/mL for 5-HT. The limits of detection and quantification were in the range of 5.5-10.8 ng/mL and 15-20 ng/mL, respectively. The relative recoveries were in the range of 87-108%, with intraday and interday relative standard deviations lower than 13%. This method was successfully applied to analysis of MNTs in real urine.


Adaptive radiations should not be simplified: The case of the danthonioid grasses.
Although much of extant diversity is probably the product of evolutionary radiations, the special case of adaptive radiations has not yet been thoroughly explored. Adaptive radiations are postulated to occur when a lineage is exposed to new ecological opportunities, where it can diversify ecologically. We argue that adaptive radiations have two characteristics. Firstly, the diversification rate accelerates initially, and is then followed by a density-dependent slow-down. Secondly, traits relevant to the new ecological opportunity should evolve at or just before the radiation. We also argue that a correct identification of adaptive radiations is dependent on the phylogenies underlying the diversification dynamics being sampled adequately (i.e. comprehensive species sampling), and that the traits should be treated continuously if they exhibit a biological continuum and not be over-simplified into binary traits. Here, we test the hypothesis that much of the extant diversity of the south-temperate grass subfamily Danthonioideae is the result of two geographically separated but contemporaneous adaptive radiations, in response to Late-Miocene-Pliocene aridification and increasingly seasonal climates. We show that both Pentameris (83 African species) and Rytidosperma (73 Australasian-South American species) exhibit accelerations in diversification rates followed by linear density-dependent declines. We also show that two selected traits show differential evolutionary regimes with different evolutionary optima, and that these are linked to changes in the diversification rate. These results are consistent with these being adaptive, and putatively parallel, radiations. However, by mapping traits over the whole danthonioid phylogeny, it is evident that no identified trait or trait combination is sufficient and necessary for adaptive radiations. Furthermore, we show that simplifying the traits to binary gives a strong but potentially erroneous link between trait shift and diversification rate shift.


Clinical audit comparing radiation dose metrics between WEB and coil embolisation in the treatment of intracranial aneurysms.
Intrasaccular flow disruption is a new and effective endovascular treatment for intracranial aneurysms. While endovascular treatment is a minimally invasive procedure, it does carry a radiation risk. As radiation dose should be kept as low as reasonably achievable (ALARA), the main objective of this study was to analyse KAP (kerma area product), fluoroscopy and procedure time during the treatment of aneurysms treated with coiling and the Woven-EndoBridge (WEB) device. A secondary objective was to look at the reference air kerma (RAK) to determine if the patient receives a dose that could cause tissue effects. KAP, fluoroscopy and procedure time were retrospectively analysed in patients who had an aneurysm treatment. Aneurysms with diameters of 4-11mm, over a four-year period, in the anterior and posterior circulation of the brain were analysed in this study. Patients were treated by coiling or WEB. RAK were summed together in the working projection to give an estimated entrance surface dose (ESD) in cases with the highest KAP. A total of 47 aneurysms treated with WEB and 104 aneurysms treated with coiling techniques met the inclusion criteria. The average KAP was 6884.1 ± 2774.4μGym2 with coiling techniques and 5658.7 ± 1602.5μGym2 with WEB (p=0.006; CI =363-2086μGym2). This demonstrates an 18% reduction with WEB. Mean fluoroscopy time for coiling was 63.5 ± 42.6minutes and 33.8 ± 28.8minutes for WEB (p=<0.001; CI=16-43minutes). Fluoroscopy time was reduced by nearly 50% with WEB. On average, there was a 27-minute reduction of procedure time when using WEB compared to coiling. The RAK determined for the working projections did not exceed the 2Gy threshold for tissue effects. Treatment of aneurysms using the WEB shows a reduction in KAP, fluoroscopy, and procedure time. This study further demonstrates the benefits of intrasaccular flow disruption for treatment of intracranial aneurysms.