Is the Chronic Kidney Disease Epidemiology Collaboration four-level race equation better than the cystatin C equation?
To evaluate the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) four-level race equation in the assessment of glomerular filtration rate (GFR) in Chinese people with chronic kidney disease (CKD), which was published in 2011, compared with the cystatin C-based GFR estimation equation (CysC GFR) and the combination of CysC and serum creatinine equation (CysC-Scr GFR). The CKD-EPI four-level race equation estimated GFR (CKD-EPI GFR) was compared with the CysC GFR and CysC-Scr GFR. Three equations were compared with body surface area (BSA) standardized GFR (sGFR), which was measured by (99m) Tc-DTPA renal dynamic imaging method in 111 CKD cases. A statistically significant correlation was found between sGFR and CKD-EPI GFR, CysC GFR and CysC-Scr GFR. Three estimated GFR (eGFR) equations of 30% accuracy were 58.6%, 56.8% and 63.5%, respectively. Average deviations of eGFR from sGFR were 2.34, 1.19, and 1.32 (mL/min per 1.73 m(2)) (P > 0.05), respectively. There was no significant deviation in the CKD from stages 1 to 5 in CKD-EPI GFR and CysC-Scr GFR. However, when estimated by CysC GFR, the deviation was increased, with the value of 12.41 mL/min per 1.73 m(2) (P= 0.002) in CKD stage 5. Our results showed that in a Chinese population with CKD, CKD-EPI GFR, CysC GFR and CysC-Scr GFR of bias and overall accuracy of 30% were very similar. There was little advantage in adding Asian coefficient to modifying the CKD-EPI equation. CysC GFR overestimated GFR in patients with CKD stages 4 and 5.


Induction of micronuclei by mitomycin C and colchicine in the marine mussel Mytilus galloprovincialis.
The frequencies of micronuclei (MNi) in the gill cells of the mussel Mytilus galloprovincialis were determined over a long period (up to 28 days) following a 48-h treatment with colchicine. The frequency of MNi at the end of treatment was significantly higher than in controls and 24 h later it had increased even more. After this period, the frequency of MNi rapidly declined until a plateau level was reached on day 2-3, which was significantly higher than the control baseline level, and persisted until the end of the experiment (28th day). In the same cell system we previously reported a persistence of an increased frequency of MNi after treatment with mitomycin C (MMC) (Majone et al., 1987). In order to establish the origin of MNi, the difference between their size distribution in MMC- and colchicine-treated animals was determined at the end of treatment as well as during the plateau phase. The difference was statistically significant (P less than 0.001) at the end of treatment, the MNi induced by MMC being smaller than those induced by colchicine. However, the difference during the plateau phase was not statistically significant. Human CREST antikinetochore fluorescent antibodies reacted with chromosome centromeres of Mytilus and were applied to gill cells at the end of a 48-h treatment with MMC or colchicine. About 60% of the MNi induced by colchicine but only 30% of those produced by MMC reacted positively with the fluorescent antibodies. This result indicates that the majority of MNi observed at the end of a 48-h treatment with MMC or colchicine originate, respectively, from acentric chromosome fragments and from whole lagging chromosomes.


A Rare Case of Multilocular Thymic Cyst with Follicular Lymphoid Hyperplasia: Radiologic and Histopathologic Features.
Multilocular thymic cysts are rare and acquired lesions induced by an inflammatory arising within the thymus. We report a rare case of multilocular thymic cyst with follicular lymphoid hyperplasia in a 59-year-old female. Chest CT and MRI revealed a large multilocular cystic mass, which contains thick septa and nodules in the thymus. F-18 FDG PET/CT showed almost no FDG uptake of the multilocular cystic mass but moderate FDG uptake of the solid nodules. Extended total thymectomy was performed. Histopathological findings revealed follicular lymphoid hyperplasia of thymic tissue but no neoplastic lesion. Based on these findings, diagnosis of multilocular thymic cyst with follicular lymphoid hyperplasia was made. This is a rare case that preoperatively was difficult to diagnose.


Cellular and immunometabolic mechanisms of inflammation in depression: Preliminary findings from single cell RNA sequencing and a tribute to Bruce McEwen.
Inflammation is associated with symptoms of anhedonia, a core feature of major depression (MD). We have shown that MD patients with high inflammation as measured by plasma C-reactive protein (CRP) and anhedonia display gene signatures of metabolic reprograming (e.g., shift to glycolysis) necessary to sustain cellular immune activation. To gain preliminary insight into the immune cell subsets and transcriptomic signatures that underlie increased inflammation and its relationship with behavior in MD at the single-cell (sc) level, herein we conducted scRNA-Seq on peripheral blood mononuclear cells from a subset of medically-stable, unmedicated MD outpatients. Three MD patients with high CRP (>3 mg/L) before and two weeks after anti-inflammatory challenge with the tumor necrosis factor antagonist infliximab and three patients with low CRP (≤3 mg/L) were studied. Cell clusters were identified using a Single Cell Wizard pipeline, followed by pathway analysis. CD14+ and CD16+ monocytes were more abundant in MD patients with high CRP and were reduced by 29% and 55% respectively after infliximab treatment. Within CD14+ and CD16+ monocytes, genes upregulated in high CRP patients were enriched for inflammatory (phagocytosis, complement, leukocyte migration) and immunometabolic (hypoxia-inducible factor [HIF]-1, aerobic glycolysis) pathways. Shifts in CD4+ T cell subsets included ∼30% and ∼10% lower abundance of CD4+ central memory (TCM) and naïve cells and ∼50% increase in effector memory-like (TEM-like) cells in high versus low CRP patients. TCM cells of high CRP patients displayed downregulation of the oxidative phosphorylation (OXPHOS) pathway, a main energy source in this cell type. Following infliximab, changes in the number of CD14+ monocytes and CD4+ TEM-like cells predicted improvements in anhedonia scores (r = 1.0, p < 0.001). In sum, monocytes and CD4+ T cells from MD patients with increased inflammation exhibited immunometabolic reprograming in association with symptoms of anhedonia. These findings are the first step toward determining the cellular and molecular immune pathways associated with inflammatory phenotypes in MD, which may lead to novel immunomodulatory treatments of psychiatric illnesses with increased inflammation.


Positive Predictive Value of Non-Traumatic Bleeding Diagnoses in the Danish National Patient Register.
The majority of bleeding diagnoses in the Danish National Patient Registry have not been validated despite extensive use in epidemiological research. Therefore, we examined the positive predictive value (PPV) of non-traumatic bleeding diagnoses in the Danish National Patient Registry. Population-based validation study. Based on a manual review of electronic medical records, we estimated the PPV of diagnostic coding (International Classification of Diseases, Tenth Revision (ICD-10)) for non-traumatic bleeding for all patients ≥65 years of age with any hospital contact in the North Denmark Region during March-December 2019 as registered in the Danish National Patient Registry. We calculated PPVs and associated 95% confidence intervals (CI) for non-traumatic bleeding diagnoses overall and stratified according to primary or secondary diagnosis, and according to major anatomical sites. A total of 907 electronic medical records were available for review. The population mean age was 79.33 years (standard deviation (SD)=7.73) and 57.6% were males. Primary bleeding diagnoses accounted for 766 of the records and 141 were secondary bleeding diagnoses. The overall PPV for bleeding diagnoses was 94.0% (95% CI: 92.3-95.4). The PPV was 98.7% (95% CI: 97.6-99.3) for the primary diagnoses and 68.8% (95% CI: 60.7-75.9) for the secondary diagnoses. When stratified according to subgroups of major anatomical sites, the PPVs ranged between 94.1% and 100% for the primary diagnoses, and between 53.8% and 100% for secondary diagnoses. The overall validity of non-traumatic bleeding diagnoses in the Danish National Patient Registry is high and considered acceptable for epidemiological research. However, PPVs were substantially higher for primary than for secondary diagnosis.


Performance and usability evaluation of a mobile health data capture application in clinical cancer trials follow-up.
Mobile health data capture applications (mHDA's) may improve communication between healthcare providers and patients. However, there is limited literature about the use of mHDA's facilitating clinical trials. In this study, the effectiveness of an application, supporting follow-up visits of cancer trial participants was investigated. Twenty participants were provided with an e-questionnaire via the mHDA. Participants rated the usability of the application as high performing (mean Systems Usability Scale 87 points). The research team rated the mHDA as highly applicable and efficient in preparing visits. Anamnesis, physical examination and agreement on further policy were performed within an average of 31 min.


Efficacy of 100 mg of double-bolus alteplase in achieving complete perfusion in the treatment of acute myocardial infarction.
The purpose of this study was to assess the efficacy of 150 mg of aspirin plus 100 mg of alteplase, administered as two intravenous bolus injections of 50 mg each given 30 min apart, and followed by intravenous heparin, on infarct-related coronary artery patency (Thrombolysis in Myocardial Infarction [TIMI] flow grade 3). Previous workers have shown in animals that reducing the duration of an infusion of recombinant tissue-type plasminogen activator increases the initial rate of thrombolysis, resulting in high early infarct-related coronary artery patency rates. The logical progression of this idea is bolus administration. Consecutive patients presenting up to 6 h from the onset of symptoms were recruited for the study. Angiography was performed at 60 and 90 min after the first bolus and between 19 to 48 h after study entry. Patients were followed up for 1 month. At 60 min, angiography revealed infarct-related coronary artery patency of TIMI flow grade 3 in 55 (86%) of 64 patients (95% confidence interval [CI] 75% to 93%) and TIMI flow grade 2 or 3 in 58 (91%) of 64 patients (95% CI 81% to 97%). At 90 min, infarct-related artery patency of TIMI flow grade 3 was achieved in 74 (88%) of 84 patients (95% CI 79% to 94%) and TIMI flow grade 2 or 3 in 78 (93%) of 84 patients (95% CI 85% to 97%). Two patients (2.4%) had early angiographic reocclusion whereas 10 (11.9%) had late reinfarction. Bleeding episodes were mostly minor, and there was no cerebrovascular bleeding. Five patients (6.0%) died within 1 month of the acute myocardial infarction. In 84 patients with acute myocardial infarction, administration of 100 mg of double-bolus (2 x 50 mg) alteplase, aspirin and heparin is associated with remarkably high early infarct-related coronary artery patency rates (TIMI flow grade 3) of 86% and 88%, respectively, at 60 and 90 min.


Nitrite-induced alterations in sex steroids and thyroid hormones of Labeo rohita juveniles: effects of dietary vitamin E and L-tryptophan.
An experiment was conducted to study the effect of sub-lethal nitrite exposure on sex steroids (testosterone and estradiol), cortisol and thyroid hormones (T3 and T4) of Labeo rohita juveniles. Fishes previously fed with normal or elevated levels of vitamin E (VE) and tryptophan for 60 days were exposed to sub-lethal nitrite for another 45 days with same feeding regime. There were nine treatment groups, viz. VE0TRP0-N, VE0TRP0+N, VE100TRP0-N, VE100TRP0+N, VE100TRP0.75+N, VE100TRP1.5+N, VE150TRP0+N, VE300TRP0+N and VE200TRP1+N. Except the groups VE0TRP0-N and VE100TRP0-N, all other groups were exposed to nitrite. At the end of the 45 days of nitrite exposure, serum samples were assayed for sex steroids, cortisol and thyroid hormones. The serum T3 and T4 levels decreased to the extent of 84.5 and 94.06%, respectively, upon nitrite exposure. Dietary supplementation with additional amounts of VE and tryptophan appears to reduce the decline of the production of T4. The serum testosterone and estradiol decreased 97.31 and 92.86%, respectively, upon nitrite exposure. Supplementation with additional amounts of VE was found to reverse nitrite-induced inhibition of testosterone and estradiol production. Serum cortisol increased upon nitrite exposure and unexposed (VE100-N) group showed lower levels, which were comparable to groups fed with elevated levels of VE. The overall results of the present study revealed that environmental nitrites have a negative impact on steroidogenesis, which can be overcome by dietary supplementation of elevated amounts of VE (minimum of 150 mg VE Kg diet(-1)) and to a lesser extent by tryptophan (only at the level of 1.5% of the diet).


Colon-cancer liver metastasis is effectively targeted by recombinant methioninase (rMETase) in an orthotopic mouse model.
Colorectal cancer liver metastasis (CCLM) is the most frequent cause of death of colorectal cancer. Development of novel new effective therapy is needed for CCLM patients to improve outcome. The aim of the present study was to investigate the efficacy of recombinant methioninase (rMETase) on a CCLM orthotopic mouse model of liver metastasis established using the human colon cancer cell line HT29 expressing red fluorescent protein (RFP). Orthotopic CCLM nude mouse models were randomized into two groups: control group (n = 6, PBS 200 µl, i.p., daily); rMETase group (n = 6, 100 units/200 µl, i.p., daily). Tumor volume was measured on day 0 and day 15. Body weight was measured twice a week. All mice were sacrificed on day 15. rMETase significantly inhibited the increase of the liver metastasis as determined by RFP fluorescence area and intensity (p = 0.016 and 0.015, respectively). There was no significant difference of body weight between either group on any day. The present study suggests that rMETase has future potential therapy for CCLM in the clinic.


Perceptual learning: Training together makes us better.
Perceptual learning is often thought to rely primarily on low-level visual areas. A new study shows that learning with a partner can improve perceptual learning performance, demonstrating that higher cognitive processes play a larger role in perceptual learning than previously supposed.


Clonal fibroblastic cell lines established from a heavily exposed atomic bomb survivor.
Two clonal fibroblast cell lines with simple chromosome aberrations-one with del(3)(p24) and the other with t(1;16)(q21;q11.2)-were established from a high dose (5.14 Gy) female atomic bomb survivor by serial culture of skin fibroblasts. These two types of clonal cells showed a more extended life span than did the cells with 44 other types of chromosome aberrations and normal cells. In addition to these results, a prominent clonal population was observed in the peripheral blood cells in this subject. It is assumed that these clonal populations arose in vivo as a result of radiation exposure to the atomic bomb.


The pharmacokinetics of porcine C-peptide after intraperitoneal injection.
Previously, we have demonstrated that there were very low C-Peptide concentrations and normal blood glucose levels when we transplanted encapsulated islets in the abdominal cavity of diabetic nude mice. In addition, the C-peptide concentration in the ascites fluid of the peritoneal cavity was 40 times higher than in the peripheral blood. In this study, we investigated the pharmacokinetics of intraperitoneal porcine C-peptide. To assess the pharmacokinetics of porcine C-peptide, a synthesized porcine C-peptide solution was injected into the peripheral circulation through the tail vein or into the peritoneal cavity in rats at low or high doses of either 200 or 2000 pmol/kg, respectively. Arterial blood samples were collected at time intervals of 1-120 minutes after injection to calculate the terminal elimination half-life (t1/2 ) and area under the time-concentration curve (AUC0-t ). After intraperitoneal C-peptide injection, the highest porcine C-peptide concentration in peripheral blood was only one-fortieth compared to after intravenous injection. The AUC0-t for the intraperitoneal injection was 78% at the low dose and only 39% at the high dose compared to the intravenous injection. This finding indicates that C-peptide remains in the abdominal cavity when intraperitoneally transplanted islets release C-peptide via high glucose stimulation. Porcine C-peptide injected into a peritoneal cavity slowly and incompletely entered peripheral circulation, which resulted in very low concentration in peripheral blood.


Increased QT dispersion in the absence of QT prolongation in patients with Behcet's disease and ventricular arrhythmias.
In Behcet's disease, prominent clinical manifestations include involvement of mucocutaneous, ocular, gastrointestinal, respiratory, neurologic, urogenital, articular and cardiovascular systems. Patients with Behcet's disease have higher incidence of ventricular arrhythmia than healthy subjects. However there is a little information about the mechanism of ventricular arrhythmias in Behcet's disease. The aim of the study was to investigate whether dispersion of ventricular repolarisation was an arrhythmogenic mechanism. QT dispersion parameters were measured in 73 Behcet patients and QT dispersion was defined as the difference between the maximum and minimum QT interval in any of the 12 leads of surface electrocardiogram. Corrected QT dispersion for heart rate was calculated by Bazett's formula. The results were compared with the data from 51 matched controls without a history of cardiac disease. We found QT dispersion was greater in Behcet patients (58+/-12 vs. 37+/-8 ms, P=0.001) as was corrected QT dispersion (81+/-14 vs. 52+/-11 ms, P=0.001). There was no significant difference in minimum or maximum QT intervals between Behcet patients and controls (P>0.05). We found a correlation between QT dispersion and grade of premature ventricular complexes (r=0.7, P=0.002). Our findings suggest that increased dispersion of repolarisation may account for the development of ventricular arrhythmias in Behcet's disease.


High density lipoprotein concentrations after cessation of smoking: the importance of alterations in diet.
Cessation of smoking is followed by a rapid rise in plasma HDL concentrations. An earlier study has demonstrated a significant relationship between the increase in HDL concentrations and spontaneous changes in food intake, specifically an increased fat intake. In this investigation we have dissociated the effects of cessation of smoking as such from those of dietary alterations by monitoring plasma lipid and lipoprotein concentrations after cessation of smoking in 12 subjects whose diet was kept constant during an initial 2-week control period and during 2 weeks following cessation of smoking. Under these conditions plasma HDL-cholesterol levels did not increase significantly (1.01 +/- 0.26 mmol/l (mean +/- SD) before and 1.04 +/- 0.27 mmol/l after cessation of smoking). Similarly, no significant alterations were recorded for other plasma lipid or lipoprotein concentrations. Activities of lipoprotein lipase and hepatic lipase were unchanged throughout the study. These results suggest that the marked rise in HDL concentrations after stopping smoking is largely related to spontaneous changes in dietary habits which occur upon cessation of smoking.


Cellular electrophysiological effects of flecainide on human atrial fibres.
The aim of the study was to examine the electrophysiological characteristics of human atrial specimens collected during heart surgery and to investigate the effects of the class I antiarrhythmic agent flecainide on their electrical activity. Atrial specimens were studied using standard microelectrode techniques, with and without superfused flecainide (5 x 10(-7) M) or the transient outward current inhibitor 4-aminopyridine (0.5 mM). Atrial fragments 0.5-1.0 cm2 were obtained at operation from 34 patients, mean age 30 years. There was no history of previous atrial arrhythmia in any patient and drug therapy was stopped 24 h before surgery. Two types of transmembrane action potential were identified: (1) triangular shaped potentials (group A, classically found in animal models); (2) potentials with a large plateau preceded by a notch (group B). The effect of flecainide was compared on the the two types of action potential. In both, flecainide lessened the depolarisation rate. In group B, but not in group A, it increased the action potential duration at 50% and 90% repolarisation (APD50, APD90) and the effective refractory period. The notch in group B action potentials is generated by transient outward currents (Ito). Inhibition of these currents, either by increasing the pacing rate or by adding 4-aminopyridine, limited the increase in APD50, APD90, and effective refractory period generated by the presence of flecainide. The effects of flecainide on the atrial repolarisation process depend on the shape of the action potential. These effects are more marked in cells with a plateau, where Ito is activated.


Enhanced anticancer efficacy of snake venom combined with silica nanoparticles in a murine model of human multiple myeloma: molecular targets for cell cycle arrest and apoptosis induction.
Multiple myeloma (MM) is a clonal disease of plasma cells that reside in the bone marrow (BM). MM is an incurable disease; thus, screening for novel anti-myeloma drugs remains critically important. We recently described a silica nanoparticle-based snake venom delivery model that targets cancer cells, but not normal cells. Using this model, we demonstrated a strong enhancement of the antitumor activity of snake venom extracted from Walterinnesia aegyptia (WEV) in two breast carcinoma cell lines when the venom was combined with silica nanoparticles (WEV+NP). In the present study, we aimed to delineate the in vivo therapeutic efficacy of WEV+NP in an MM-bearing experimental nude mouse model. We found that treatment with WEV+NP or WEV alone significantly inhibited tumor growth compared to treatment with NP or vehicle. WEV+NP- and WEV-treated cancer cells exhibited marked elevations in oxidative stress and robust reductions in the levels of interleukin-6 (IL-6) and B cell-activating factor (BAFF). WEV+NP also decreased the surface expression of the chemokine receptors CXCR3, CXCR4 and CXCR6 to a greater extent than WEV alone, and WEV+NP subsequently reduced migration in response to the cognate ligands CXCL10, CXCL12 and CXCL16. Furthermore, we found that WEV+NP strongly inhibited insulin-like growth factor 1 (EGF-1)- and IL-6-mediated MM cell proliferation, altered the cell cycle and enhanced the induction of apoptosis of MM cells. In addition, the results of treatment with WEV+NP or WEV alone revealed that the combination of WEV with NP robustly decreased the expression of cyclin D1, Bcl-2 and the phosphorylation of AKT; increased the expression of cyclin B1; altered the mitochondrial membrane potential; increased the activity of caspase-3, -8 and -9; and sensitized MM cells to growth arrest and apoptosis. Our data reveal the therapeutic potential of the nanoparticle-sustained delivery of snake venom to fight cancer cells.


Age and sex differences in the impact of the COVID-19 pandemic on mental health and coping mechanisms in Latin American youth.
The COVID-19 pandemic has had negative effects on mental health. Understanding sex and age differences in the perception of stressors, the use of coping strategies, and the prevalence of depression and anxiety can lead to detecting at-risk groups. A cross-sectional online study surveyed perceived stressors, coping strategies, and the PHQ-9 and GAD-7 rating scales for symptoms of depression and anxiety. The study was open from Spring 2020 to Spring 2021 and was aimed at children, adolescents and young adults of Latin America. The survey was completed by 3965 participants (63.8% females). The sample was divided into children (N = 621, 15.7%), adolescents (N = 1123, 28.3%) and young adults (N = 2021, 56%). Moderate to severe symptoms of depression and anxiety were found in 43.53% and 27%, respectively, being more frequent in females. Children of both sexes showed the lowest scores in rating scales. Adult females reported a higher level of stress in regards to pandemic news, having someone close diagnosed with COVID-19,the possibility of getting sick, academic delays, economic impact, and depression, while female adolescents reported a higher level of stress regarding the lockdown, losing contact with peers and anxiety. In juxtaposition, females also reported a higher frequency of positive coping strategies. A multivariate analysis confirmed the association of several variables with the presence of depression and anxiety. A high prevalence of depression and anxiety was found among young people. Specific intervention programs must be created taking into account age and sex differences.


Specific nasopharyngeal Corynebacterium strains serve as gatekeepers against SARS-CoV-2 infection.
The SARS-CoV-2 virus is still causing a worldwide problem. The virus settles primarily on the nasal mucosa, and the infection and its course depend on individual susceptibility. Our aim was to investigate the nasopharynx composition's role in the individual susceptibility. During the first phase of SARS-CoV-2 pandemic, nasopharyngeal microbiome samples of close contact unvaccinated patients were investigated by 16S rRNA analysis and by culturing. The whole genome of cultured Corynebacteria was sequenced. The relative expression of ACE2, TMPRSS2, and cathepsin L on Caco-2 cells and the strength of S1-ACE2 binding were determined in the presence of Corynebacteria. From 55 close contacts exposed to identical SARS-CoV-2 exposure, 26 patients became infected and 29 remained uninfected. The nasopharyngeal microbiome analysis showed significantly higher abundance of Corynebacteria in uninfected group. Corynebacterium accolens could be cultivated only from uninfected individuals and Corynebacterium propinquum from both infected and uninfected. Corynebacteria from uninfected patient significantly reduced the ACE2 and cathepsin L expression. C. accolens significantly reduced the TMPRSS2 expression compared to other Corynebacteria. Furthermore, Corynebacterium spp. weakened the binding of the S1-ACE2. Most C. accolens isolates harbored the TAG lipase LipS1 gene. Based on these results, the presence of Corynebacterium spp. in the nasopharyngeal microbiota, especially C. accolens strains, could reduce the individual susceptibility to SARS-CoV-2 infection by several mechanisms: by downregulation the ACE2, the TMPRSS2 receptors, and cathepsin L in the host; through the inhibition of S1-ACE2 binding; and lipase production. These results suggest the use of C. accolens strains as probiotics in the nasopharynx in the future.


Learning from an epidemiological, population-based study on prescribed medicine use in adults.
The aim of this study was to examine changes in the prevalence of use of prescribed medicines in Australian community samples. In this study, face-to-face interviews were carried out with random, representative samples of South Australian adults, aged ≥15 years. Data on self-reported use of prescribed medicines, most commonly reported categories of prescribed medicines and use of multiple medicines for common body systems were collected. It was not possible to distinguish between medicines prescribed for acute and chronic use. A total of 3015 respondents were interviewed in 2004 and 3034 in 2008, representing participation rates of 76% and 73%. There was no significant increase in the prevalence of use of ≥1 (46.8% vs 47.3%, p = 0.6) or ≥6 medicines (5.7% vs 5.5%, p = 0.7). In both years, the use of medicines was higher in women (56.7% vs 57.5%). On subgroup analyses, a significant reduction in the use of medicines was observed in respondents aged 15-24 (25.0% vs 18.5%, p = 0.01) and ≥65 years (87.7% vs 82.5%, p = 0.01), whereas use in those aged 35-44 years increased significantly (26.4% vs 33.6%, p = 0.01). The number of cardiovascular system agents (23.1% vs 24.6%, p = 0.20) and psychotropic medicines (9.8% vs 10.6%, p = 0.35) used by respondents remained unchanged while use of respiratory (7.2% vs 5.7%, p = 0.01) and musculoskeletal system medicines (8.7% vs 5.6% p= < 0.001) decreased significantly. In presenting what we believe is the first Australian population-based study to compare changes in prescribed medicines across the adult age spectrum, we highlight some key questions to ensure the quality use of medicines. Our findings identify a need to discuss de-prescribing, monitor practices to minimise adverse events and challenge if consumers and prescribers need to consider the costs to governments of medicines.


A successful bridge to recovery with Impella 5.0 and subsequent hybrid cardiac resynchronization therapy in systemic right ventricle failure: a case report.
Impella 5.0 is currently used as a temporary mechanical circulatory support device in cardiogenic shock (CS). However, Impella 5.0 implantation for the systemic right ventricle (sRV) has not been well documented. A 50-year-old man with atrial switch for dextro-transposition of the great arteries was transferred to our hospital for the treatment of embolic acute myocardial infarction of the left main trunk lesion with CS. To stabilize haemodynamics, we implanted Impella 5.0 via the left subclavian artery in the sRV. After optimal medical therapy initiation and gradual weaning of Impella 5.0, Impella 5.0 was successfully explanted. An electrocardiogram was obtained, which showed complete right branch block with a QRS duration of 172 ms. Acute invasive haemodynamic evaluation of cardiac resynchronization therapy (CRT) pacing showed that dP/dt increased from 497 to 605 mmHg/s (21.7% improvement), and hybrid cardiac resynchronization therapy defibrillator (CRTD) with a sRV epicardial lead was subsequently implanted. The patient was discharged without inotropic support. Coronary artery embolism is a rare but serious complication of dextro-transposition of the great arteries after atrial switch operations. Impella 5.0 implantation is a feasible bridge strategy for refractory CS due to sRV failure. Although CRT implantation in patients with sRV is controversial, an acute invasive haemodynamic evaluation can help assess its potential benefits.


A study on the roles of long non-coding RNA and circular RNA in the pulmonary injuries induced by polystyrene microplastics.
Microplastics (MPs) pollution has become a global concern due to its close relation to the environment and human health. Recently, more and more studies have pointed out the existence of MPs in the air, but its potential inhalation toxicity is unclear. Polystyrene Microplastics (PS-MPs) is one of the representative MPs. Besides, non-coding RNA plays crucial roles in regulating gene expression. Therefore, this study aims to provide new insights into the molecular exploration of PS-MPs inhalation. In this study, Sprague Dawley(SD)rats were treated with 100 nm, 500 nm, 1 μm and 2.5 μm PS-MPs for three days. And then intra-tracheal instillation of saline or 100 nm PS-MPs with 0, 0.5, 1 and 2 mg/200 μL were performed in SD rats every two days for two consecutive weeks. The deposition of PS-MPs was observed through immunofluorescence. Lung histological alternations were observed in haematoxylin and eosin (H&E) staining sections. The expressions of pro-inflammatory cytokines were quantified by ELISA and qPCR. Genome-wide transcriptomic profiling of long noncoding RNAs (lncRNAs), circular RNAs (circRNAs) in rats lung were done by ribosomal RNA depleted RNA sequencing and verified by qRT-PCR. We observed that 100 nm and 1 μm PS-MPs could deposite in the lungs. In addition, pathological examination shows alveolar destruction and bronchial epithelium arranged in a mess in PS-MPs groups. Furthermore, the expressions of pro-inflammatory cytokines IL-6, TNF-α and IL-1β were upregulated in PS-MPs exposed rats. Sequencing results showed that 269 circRNAs and 109 lncRNAs were differentially expressed in lung tissue of the saline and PS-MPs exposed rats. The upregulated expressions of lncRNA XLOC_031479, circRNA 014924 and circRNA 006603 and the downregulated expressions of lncRNA XLOC_014188 and circ003982 were identified by qRT-PCR in MPs group. The identified novel circRNAs and lncRNAs may paly important role in the development of lung inflammation caused by PS-MPs.


[Epidemiology of rotavirus infections in a randomized study in various central-southern areas of our country].
The etiology of diarrhea and intestinal deficiency relative to the absorbency of glucose and some enzymes can be found in Rotavirus infection. The epidemiology of this infection has been derived by the authors even if the research was limited to some areas of central-south Italy, analyzing seroimmunologically serums randomly selected. The research outcomes fully explain the first mentioned disease because antibody markers have been founded in most of the examined people.


How we do a bloodless partial splenectomy.
Partial splenectomy and Tru-cut biopsy are not routinely practiced because of the lack of vascular control to arrest bleeding. Using radiofrequency energy to coagulate the resection margin and biopsy tract, a 74-year-old woman with a tumor in the lower pole of the spleen underwent partial splenectomy and Tru-Cut biopsy of the spleen. Hemostasis was excellent. Blood loss was minimal and the patient was discharged with a functioning spleen. This new technique may allow safe and bloodless partial splenic resection and Tru-cut biopsy of the spleen, which might reduce the number of splenectomies performed and the consequent difficulties for the patient that can arise.


Biatrial linear ablation in sustained nonpermanent AF: Results of the substrate modification with ablation and antiarrhythmic drugs in nonpermanent atrial fibrillation (SMAN-PAF) trial.
More advanced atrial fibrillation (AF) is associated with lower success rates after pulmonary vein isolation (PVI), and the optimal ablation strategy is uncertain. To assess the impact of additional linear ablation (lines) compared to PVI alone. In this multicenter randomized controlled trial, 122 patients (mean age 61.9 ± 10.5 years; left atrial diameter 43 ± 6 mm) with persistent AF (PeAF) or sustained (>12 hours) paroxysmal AF (SusPAF) with risk factors for atrial substrate were included and followed up for 12 months. Patients were randomized to PVI-only or PVI + lines (left atrial roof line, mitral isthmus line, and tricuspid isthmus line) group. Holter monitoring was performed at 3, 6, and 12 months and according to symptoms. The primary outcome was atrial tachyarrhythmia recurrence lasting ≥30 seconds. Baseline characteristics were comparable between groups; 61% had PeAF and 39% SusPAF. Successful PVI was achieved for 98% of pulmonary veins, and bidirectional block was obtained in 90% of lines. The primary end point occurred in 38% of the PVI + lines group and 32% of the PVI-only group (P = .50), which was consistent in both PeAF (36% vs 28%; P = .45) and SusPAF (42% vs 39%; P = .86). Compared with the PVI-only group, the PVI + lines group had higher procedure duration (209 ± 52 minutes vs 172 ± 44 minutes; P < .001), ablation time (4352 ± 1084 seconds vs 2503 ± 1061 seconds; P < .001), and radiation exposure (Dose-area product 3992 ± 6496 Gy·cm(2) vs 2106 ± 1679 Gy·cm(2); P = .03). Quality of life (disease-specific Atrial Fibrillation Effect on Quality of Life questionnaire and mental component scale of the Short Form 36 Health Survey) improved significantly during the study but did not differ between groups. Adding lines to wide antral PVI in substrate-based AF requires significantly more ablation, increases procedure duration and radiation dose, but provides no additional clinical benefit.


Impact of COVID-19 on clinical outcomes following total shoulder arthroplasty.
The coronavirus (COVID-19) pandemic has introduced patient stressors and changes to perioperative protocols in total shoulder arthroplasty (TSA). The purpose of this study is to evaluate the short-term effects of the COVID-19 pandemic on various patient outcomes and satisfaction following elective TSA. A retrospective review was performed on 147 patients who underwent primary TSA at a single institution between June 2019 and December 2020. Patients were divided into 2 cohorts: pre-COVID (June 2019-March 2020; n = 74) and post-COVID (April 2020-December 2020; n = 73). No elective TSA were performed between 10 March 2020 and 23 April 2020 at our institution. Data were collected prospectively both pre- and postoperatively. Range of motion (ROM) testing included active abduction, internal rotation, and external rotation. Patient reported outcome measures (PROMs) included global shoulder function, Simple Shoulder Test, American Shoulder and Elbow Surgeons, Visual Analog Scale pain scoring systems, and patient satisfaction. ROM and PROMs were compared at preoperative, 3-month follow-up, and 12-month follow-up intervals. Operative time, length of stay (LOS), 90-day readmission, and 90-day reoperation were also compared. There were no differences in baseline patient characteristics. The operative time, LOS, home discharge rate, readmission, and reoperation did not differ between groups. For both cohorts, the PROMs and ROM improved at each follow-up visit postoperatively. While preoperative abduction, internal rotation, and external rotation were significantly greater in the post-COVID group, all ROM measures were similar at 3-month and 12-month follow-up visits. There was no difference in pain, global function, Simple Shoulder Test, American Shoulder and Elbow Surgeons, or patient satisfaction between groups at all time intervals. Patients undergoing elective TSA amidst the COVID-19 pandemic demonstrate excellent PROMs, ROM, and high satisfaction up to 12-months postoperatively that are comparable to pre-pandemic standards. Operative time, LOS, discharge destination, as well as 90-day readmission and reoperation rates were not impacted by the pandemic. Patients can expect similar outcomes for TSA when comparing pre-COVID to post-COVID as the pandemic continues.


Hexavalent chromium reduction by an actinomycete, arthrobacter crystallopoietes ES 32.
Environmental contamination by hexavalent chromium, Cr(VI), presents a serious public health problem. This study assessed the reduction of Cr(VI) by intact cells and a cell-free extract (CFE) of an actinomycete, Arthrobacter crystallopoietes (strain ES 32), isolated from soil contaminated with dichromate. Both intact cells and CFE of A. crystallopoietes, displayed substantial reduction of Cr(VI). Intact cells reduced about 90% of the Cr(VI) added within 12 h and Cr(VI) was almost completely reduced after 24 h. The KM and Vmax of Cr(VI) bioreduction by intact cells were 2.61 microM and 0.0142 micromol/min/mg protein, respectively. Cell-free chromate reductase of the A. crystallopoietes (ES 32) reduced hexavalent chromium at a KM of 1.78 microM and a Vmax of 0.096 micromol/min/mg protein. The rate constant (k) of chromate reduction was inversely related to Cr(VI) concentration and the half-life (t1/2) of Cr(VI) reduction increased with increasing concentration. A. crystallopoietes produced a periplasmic chromate reductase that was stimulated by NADH. Results indicate that A. crystallopoietes ES 32 can be used to detoxify Cr(VI) in polluted sites, particularly in stressed environments.


Prevalence of and factors associated with early initiation of breastfeeding among women with children aged < 24 months in Kilimanjaro region, northern Tanzania: a community-based cross-sectional study.
Early initiation of breastfeeding offers nutritional and immunological benefits to the newborn, which is critical for health and survival. Understanding factors associated with timely initiation of breastfeeding is crucial for healthcare providers and policy-makers. This study aimed to assess the prevalence and factors associated with early initiation of breastfeeding among mothers with children < 24 months of age in the Kilimanjaro region, Northern Tanzania. This study utilized secondary data from a cross-sectional survey conducted in April 2016 and April 2017 in the Kilimanjaro region. A multistage sampling technique was used to select study participants and interviewed using a questionnaire. A total of 1644 women with children aged < 24 months were analyzed. Modified Poisson regression models were used to determine factors independently associated with early initiation of breastfeeding, within first hour of life. The prevalence of early initiation of breastfeeding in the Kilimanjaro region was 70%, ranging from 64% in Same to 80% in Siha districts. The prevalence of early initiation of breastfeeding was lower among women who initiated prelacteal feeding compared to their counterparts (prevalence ratio [PR] 0.42; 95% Confidence Interval [CI] 0.34, 0.53). Likewise, women living in Same and Hai district had lower prevalence of early initiation of breastfeeding compared to women in Rombo (PR 0.8; 95% CI 0.76, 0.93) and (PR 0.89, 95% CI 0.80, 0.98) respectively. Higher prevalence of early initiation of breastfeeding was found in women with primary education compared to those with secondary education (PR 1.09; 95% CI 1.003, 1.18), and among women with two children compared to one child (PR 1.14, 95% CI 1.03, 1.26). Early initiation of breastfeeding practice was suboptimal in this study. To improve early initiation of breastfeeding, healthcare providers at reproductive and child health clinics and labour wards should discourage women from prelacteal feeding, give more support to women with one child and those with secondary level of education and above. Furthermore, a qualitative study is crucial to understand the reasons for low prevalence of early initiation of breastfeeding in Same and Hai districts.


Traditional Medicinal Oils Sourced from Birds: Anti-inflammatories and Potential Immunoregulants.
This chapter describes medicinal oils of animal origin, used in Africa and Australasia both for nutritional and medicinally for treating pain and inflammation. Analytical studies of composition, bio-efficacy and their remarkable safety are described. For obtaining reproducible benefits, it is very important to introduce Quality Controls whenever possible. These should cover all stages of production, storage and certify the 'truth in their advertising': to help eliminate adulterated products and false claims for purity and potency.


Centrifugal Displacement of Nuclei Reveals Multiple LINC Complex Mechanisms for Homeostatic Nuclear Positioning.
Nuclear movement is critical for developmental events, cell polarity, and migration and is usually mediated by linker of nucleoskeleton and cytoskeleton (LINC) complexes connecting the nucleus to cytoskeletal elements. Compared to active nuclear movement, relatively little is known about homeostatic positioning of nuclei, including whether it is an active process. To explore homeostatic nuclear positioning, we developed a method to displace nuclei in adherent cells using centrifugal force. Nuclei displaced by centrifugation rapidly recentered by mechanisms that depended on cell context. In cell monolayers with wounds oriented orthogonal to the force, nuclei were displaced toward the front and back of the cells on the two sides of the wound. Nuclei recentered from both positions, but at different rates and with different cytoskeletal linkage mechanisms. Rearward recentering was actomyosin, nesprin-2G, and SUN2 dependent, whereas forward recentering was microtubule, dynein, nesprin-2G, and SUN1 dependent. Nesprin-2G engaged actin through its N terminus and microtubules through a novel dynein interacting site near its C terminus. Both activities were necessary to maintain nuclear position in uncentrifuged cells. Thus, even when not moving, nuclei are actively maintained in position by engaging the cytoskeleton through the LINC complex.


Incidence, aetiology, treatment outcome and complications of maxillofacial fractures. A retrospective study from Northern Greece.
To analyse the pattern of maxillofacial injuries and treatment outcomes in Northern Greece. A tertiary referral single centre hospital; retrospective chart review. Demographics, aetiology, fixation technique (Rigid Internal Fixation: RIF; Maxillomandibular Fixation: MMF) post-surgical infections, aesthetics and occlusion were recorded. One thousand and ten males and 229 females were operated between 1998 and 2008. Mean age was 29.6 ± 13. Mean number of plates per patient was 3.96 ± 2.28. For those with midfacial fractures (n = 379) mean was 4.02 ± 2.05. For those with mandibular fractures (n = 333), mean was 2.74 ± 0.94 while those with combined mandible and midface fractures (n = 216) were treated using 5.74 ± 2.87 plates per patient. Among those treated with plates, an unadjusted 22% increased risk for post-surgical infection per plate used (OR = 1.22, 95%CI: 1.13-1.32) was found. Patients with mandibular fractures were more satisfied with their post-surgical facial appearance in contrast to those with midfacial or combined midfacial and mandibular fractures. Female patients were less satisfied with their post-surgical facial appearance than males. This study verified a young males predominance, a shift towards more assault related fractures -especially in females- and similar post-surgical results for MMF and RIF modalities in mandibular fractures. In those patients treated with RIF, placement of fewest plates possible to obtain stability better serves aesthetics at the same time reducing risk for post-surgical infections and malocclusion.


Coverage-dependent changes of cytochrome c transverse location in phospholipid membranes revealed by FRET.
The method of fluorescence resonance energy transfer (FRET) has been employed to monitor cytochrome c interaction with bilayer phospholipid membranes. Liposomes composed of phosphatidylcholine and varying amounts of anionic lipid cardiolipin (CL) were used as model membranes. Trace amount of fluorescent lipid derivative, anthrylvinyl-phosphatidylcholine was incorporated into the membranes to serve energy donor for heme moiety of cytochrome c. Energy transfer efficiency was measured at different lipid and protein concentrations to obtain extensive set of data, which were further analyzed globally in terms of adequate models of protein adsorption and energy transfer on the membrane surface. It has been found that the cytochrome c association with membranes containing 10 mol% CL can be described in terms of equilibrium binding model (yielding dissociation constant Kd = 0.2-0.4 microM and stoichiometry n = 11-13 lipid molecules per protein binding site) combined with FRET model assuming uniform acceptor distribution with the distance of 3.5-3.6 nm between the bilayer midplane and heme moiety of cytochrome c. However, increasing the CL content to 20 or 40 mol% (at low ionic strength) resulted in a different behavior of FRET profiles, inconsistent with the concepts of equilibrium adsorption of cytochrome c at the membrane surface and/or uniform acceptor distribution. To explain this fact, several possibilities are analyzed, including cytochrome c-induced formation of non-bilayer structures and clusters of charged lipids, or changes in the depth of cytochrome c penetration into the bilayer depending on the protein surface density. Additional control experiments have shown that only the latter process can explain the peculiar concentration dependences of FRET at high CL content.


Outcomes and costs of implantable cardioverter-defibrillators for primary prevention of sudden cardiac death among the elderly.
The clinical outcomes and costs of implantable cardioverter-defibrillators (ICDs) used for primary prevention of sudden cardiac death in nonexperimental settings are uncertain. The purpose of this study was to measure the health outcomes and costs among a nationally representative cohort of elderly, primary-prevention ICD recipients. We collected health-care cost and utilization data from all Medicare beneficiaries hospitalized for congestive heart failure (CHF) who had received primary-prevention ICDs between October 2003 and September 2005 as well as propensity-score-matched control Medicare beneficiaries hospitalized for CHF during the same period. A multivariable Cox proportional hazards model was fitted to the cohort, which comprised 7125 ICD recipients and 7125 controls and which was followed through December 2005. Medicare claims in the first year inclusive of the index hospitalization were used to assess differences in health-care costs. ICD receipt was associated with a significant reduction in mortality (adjusted hazard ratio = 0.62, 95% confidence interval 0.58-0.67). ICD patients had higher median hospital costs in the first 30 days after initial hospitalization (median difference = $41,542, P <.001) and at 1 year (median difference = $41,503, P <.001) as well as higher outpatient and physician costs at 6 months (median difference = $1828, P <.001). ICD implantation was associated with reduced mortality in a nonexperimental, elderly, primary-prevention patient population hospitalized for CHF. The additional health-care costs of ICD implantation were substantial but comparable to published cost-effectiveness models that have projected ICDs to be cost-effective.


Isolation of exosomes by differential centrifugation: Theoretical analysis of a commonly used protocol.
Exosomes, small (40-100 nm) extracellular membranous vesicles, attract enormous research interest because they are carriers of disease markers and a prospective delivery system for therapeutic agents. Differential centrifugation, the prevalent method of exosome isolation, frequently produces dissimilar and improper results because of the faulty practice of using a common centrifugation protocol with different rotors. Moreover, as recommended by suppliers, adjusting the centrifugation duration according to rotor K-factors does not work for "fixed-angle" rotors. For both types of rotors--"swinging bucket" and "fixed-angle"--we express the theoretically expected proportion of pelleted vesicles of a given size and the "cut-off" size of completely sedimented vesicles as dependent on the centrifugation force and duration and the sedimentation path-lengths. The proper centrifugation conditions can be selected using relatively simple theoretical estimates of the "cut-off" sizes of vesicles. Experimental verification on exosomes isolated from HT29 cell culture supernatant confirmed the main theoretical statements. Measured by the nanoparticle tracking analysis (NTA) technique, the concentration and size distribution of the vesicles after centrifugation agree with those theoretically expected. To simplify this "cut-off"-size-based adjustment of centrifugation protocol for any rotor, we developed a web-calculator.


Forging ahead: the 2003 APA Division 30 definition of hypnosis.
The article describes the rationale for and the process of developing a new definition of hypnosis by the Society of Psychological Hypnosis, Division 30 of the American Psychological Association. Both theoretical and practical implications led to the production of the definition, which is targeted toward informing clinicians, researchers, and the lay public alike. The definition is presented at the conclusion of the article.


Therapeutic Endoscopy and the Esophagus: State of the Art and Future Directions.
Therapeutic gastrointestinal endoscopy is rapidly evolving, and this evolution is quite apparent for esophageal diseases. Minimally invasive endoluminal therapy now allows outpatient treatment of many esophageal diseases that were traditionally managed surgically. In this review article, we explore the most exciting new developments. We discuss the use of peroral endoscopic myotomy for treatment of achalasia and other related diseases, as well as the modifications that have allowed its use in treatment of Zenker diverticulum. We cover endoscopic treatment of gastroesophageal reflux disease and Barrett's esophagus. Further, we explore advanced endoscopic resection techniques.


Dynamic CT perfusion imaging with acetazolamide challenge for the preprocedural evaluation of a patient with symptomatic middle cerebral artery occlusive disease.
We describe the use of a CT-based method of cerebral perfusion imaging, dynamic CT perfusion imaging, for the pre- and postprocedural assessment of cerebral blood flow in a patient with symptomatic middle cerebral artery occlusive disease who underwent balloon angioplasty with stent placement in the affected artery. Dynamic CT perfusion imaging represents a widely available and minimally invasive alternative to other available methods of cerebral perfusion imaging.


Multiple Step-section Frozen Section sentinel lymph node biopsy--a review of 717 patients.
Sentinel Lymph Node Biopsy (SLNB) is the standard of care for axillary staging in breast cancer. Multiple Step-section Frozen Section (MSFS) analysis is used in our institution for SLNB. This is performed intra-operatively by freezing sentinel lymph nodes to obtain multiple step-sections which are examined histologically for evidence of metastases. Patients whose sentinel lymph nodes contained macrometastases proceeded to an axillary node clearance during the same operation. 717 patients over a two and a half year period had MSFS analysis. With regards to macrometastases, MSFS analysis had a sensitivity of 93.8%, a specificity of 99.3%, a positive-predictive value of 97.4% and a negative-predictive value of 98.2%. MSFS analysis of sentinel lymph nodes is a safe and accurate procedure. It is a relatively cost-effective alternative to molecular technologies relying on DNA amplification and more accurate than standard frozen section or touch-prep cytology.


Coagulation abnormalities, bleeding, thrombosis, and management of patients with acute liver failure in Australia and New Zealand.
To study the management of coagulation and hematological derangements among severe acute liver failure (ALF) patients in Australia and New Zealand liver transplant intensive care units (ICUs). Analysis of key baseline characteristics, etiology, coagulation and hematological tests, use of blood products, thrombotic complications, and clinical outcomes during the first ICU week. We studied 62 ALF patients. The first day median peak international normalized ratio was 5.5 (inter-quartile range [IQR] 3.8-8.7), median longest activated partial thromboplastin time was 62 s (IQR 44-87), and median lowest fibrinogen was 1.1 (IQR 0.8-1.6) g/L. Fibrinogen was only measured in 85% of patients, which was less than other tests (P < 0.0001). Median initial lowest platelet count was 83 (IQR 41-122) × 109 /L. Overall, 58% of patients received fresh frozen plasma, 40% cryoprecipitate, 35% platelets, and 15% prothrombin complex concentrate. Patients with bleeding complications (19%) had more severe overall hypofibrinogenemia and thrombocytopenia. Thrombotic complications were less common (10% of patients), were not associated with consistent patterns of abnormal hemostasis, and were not immediately preceded by clotting factor administration and half occurred only after liver transplantation surgery. In ALF patients admitted to dedicated Australia and New Zealand ICUs, fibrinogen was measured less frequently than other coagulation parameters but, together with platelets, appeared more relevant to bleeding risk. Blood products and procoagulant factors were administered to most patients at variable levels of hemostatic derangement, and bleeding complications were more common than thrombotic complications. This epidemiologic information and practice variability provide baseline data for the design and powering of interventional studies.


A full-scale tracing study of "ghost peaks" encountered in impurity analysis of budesonide based on experimental operation inspection-liquid chromatography/mass spectrometry fingerprint-mechanism based stress studies integrated strategy.
Budesonide is an active pharmaceutical ingredient used in various dosage forms of finished products for the treatment of asthma. During the process of drug development, unbiased analysis of related substances is of utmost significance for both pharmaceutical research and quality control purposes. In this work, the official method documented in the United States Pharmacopoeia was selected to determine the related substances of budesonide considering the pros and cons of critical chromatographic parameters, compared to the European Pharmacopoeia. In doing so, several unpredictable interference peaks, namely "ghost peaks", were observed occasionally during analysis. A strategy that integrated information derived from experimental operation inspection, liquid chromatography/mass spectrometry fingerprint analysis, and mechanism-based stress studies was then proposed for comprehensively and quickly exploring those non-degradable and degradable peaks. Some ghost peaks were found to originate from nylon syringe filter, illumination, and alkali borosilicate glass high-performance liquid chromatography vials. Besides, degradation pathways under alkaline conditions were also unraveled through liquid chromatography-mass spectrometry qualitative analysis. Overall, an optimization of the analytical methodology based on the United States Pharmacopoeia for its application in impurity analysis of budesonide and corresponding formulations was carried out with the design of experiments, by which "ghost peaks" could be suppressed or prevented. The results obtained herein are not only crucial to studies on budesonide's stability or degradation kinetics but also contribute to clarifying the impurity research of other drugs.


Comparison of HPV 16/18 Genotyping and p16/Ki67 Dual Staining for Detection of High-Grade Cervical Lesion in Patients with Low-Grade Cervical Smears.
To triage low-grade cervical smears (ASCUS/LSIL) by HPV 16/18 genotyping and dual staining with p16/Ki67 and to compare the sensitivity and specificity of these two triage methods for detection of high-grade cervical intraepithelial neoplasia (HGCIN). In this prospective cross-sectional study, we evaluated a total of 89 women with low-grade smears (54 ASCUS, 35 LSIL) recruited from a tertiary care hospital. All patients underwent colposcopy guided cervical biopsy. Histopathology was used as gold standard. All samples were subjected to HPV 16/18 genotyping (excluding 9) using DNA PCR and p16/Ki67 dual staining (excluding 4) using Roche® kit. We then compared the two triage methods to detect high-grade cervical lesions. Overall, in all low-grade smears sensitivity, specificity and accuracy of HPV 16/18 genotyping, was found to be 66.7%, 77.1% and 76.2% respectively (p = 0.03). In low-grade smears sensitivity, specificity and accuracy of dual staining, was found to be 66.7%, 84.8% and 83.5% respectively (p = 0.01). Overall, in all low-grade smears the sensitivity of the two tests was comparable. However, dual staining had a higher specificity and accuracy than HPV 16/18 genotyping. It was concluded that both are effective triage methods but dual staining had a better performance than HPV 16/18 genotyping.


Microvascular damage following experimental sinus-vein thrombosis in rats.
We evaluated effects of thrombosis of the superior sagittal sinus, its bridging and cortical veins (SVT) on the cerebral microvasculature in rats. Cryosections of brains ( n=7) were examined for venous infarction and microvascular basal lamina damage 3 h after SVT by immunohistochemical staining of microtubule-associated protein 2 and collagen type IV. Microvessels in the infarctions showed a decrease in the number (23.5+/-6.1%, P<0.002) and the total area (24.9+/-6.5%, P<0.011) of collagen type IV-positive vessels in contrast to control areas (21.7+/-12.4%, P<0.007; and 26.3+/-15.1%, P<0.026 in contrast to control areas of unoperated animals). This study showed a significant alteration of the cerebral microvasculature in SVT, which might contribute to edema and hemorrhagic transformation.


Correction to: International prospective observational cohort study of Zika in infants and pregnancy (ZIP study): study protocol.
Following publication of the original article [1], the author mentioned that two additional NIH staff were involved in the development of the protocol who did not receive recognition in the Acknowledgments section in their published article.


Preparation of single donor platelet with low antibody titers for all patients.
Platelet concentrates from ABO-identical donors are the components of choice for patients. However, since inventories are generally insufficient and because there is usually a relative abundance of group O donors, perfect matches are not always possible. It is therefore the accepted practice for platelets to be transfused out of the ABO group when ABO-identical platelets are unavailable. Notwithstanding, the transfusion of platelets containing high titers of antibodies to the antigens on the red blood cells of the patient can cause clinically significant hemolysis. The way to improve the safety of group O platelets has focused on defining a safe level of antibodies or reducing the volume of incompatible plasma. In the current study, 107 group O single donor platelets (SDP) were modified after collecting the platelet pellet in a bag. The AB plasma was added instead of the donor's own plasma. The direct agglutination titers of anti-A/anti-B in the original group O SDPs' plasma were performed by doing a gel test, resulting in from 1:4 to 1:1024. The prevalence of high titers (i.e., at least 1:64 in our study) was relatively high, ∼63% for anti-A and 78% for anti-B. The titer of residual anti-A/anti-B in the modified SDPs ranged from negative to 1:8. In most of the modified SDPs anti-A/anti-B could not be detected in the plasma (58.9% and 52.3%, respectively). The results indicate that our modified SDPs have very low titers; that is, acting as a universal SDP which is safe for all ABO patients. This modified SDP form is a more convenient way to overcome the risk from incompatible plasma or loss of platelets during the process of volume reduction and can help effectively manage our inventory.


Effect of amylopectin on the rheological properties of aqueous dispersions of starch-sodium palmitate complexes.
Aqueous dispersions of normal and high-amylose corn starch were steam jet cooked and blended with aqueous solutions of sodium palmitate to give starch containing amylose-sodium palmitate inclusion complexes. Partial conversion of complexed sodium palmitate to palmitic acid by addition of acetic acid led to the formation of gels. Blends of inclusion complexes prepared from normal and high-amylose corn starch were used to vary the amylose:amylopectin ratio of the gels, and the linear viscoelastic moduli were found to decrease with decreasing amylose:amylopectin ratio. Precipitation of the complexed starch at low pH showed that most of the amylopectin was not part of the gel network. The elastic modulus of the gels was shown to decrease sharply between 74 and 85 °C, and the transition temperature increased strongly with decreasing amylose:amylopectin ratio.


Hemolymph ion composition and volume changes in the supralittoral isopod Ligia pallasii Brandt, during molt.
We analyzed ion composition and volume of the hemolymph of Ligia pallasii in four different stages of the molt cycle using capillary electrophoresis and 3H-inulin. The main ions in the hemolymph were Na+, K+, Mg2+ , Ca2+, and Cl-. The Ca2+ concentration increased significantly during the molt by 47% from intermolt to intramolt and by 37% from intermolt to postmolt, probably due to resorption of Ca2+ from the cuticle and sternal CaCO3 deposits. The K+ concentration increased significantly by 20% during molt. The hemolymph volume normalized to the dry mass of the animals decreased by 36% from intermolt to late premolt. This was due to a reduction in the hemolymph volume and to an increase in dry mass of the animals during premolt. A sudden increase in the hemolymph volume occurring between late premolt and intramolt served to expand the cuticle. Since the Na+, K+, Mg2+, and Cl- concentrations did not change significantly from late premolt to intramolt, the increase in hemolymph volume suggests an uptake of seawater rather than freshwater.


Adaptation process of the skin graft to vaginal mucosa after McIndoe vaginoplasty.
There are many methods of treatment of vaginal agenesis. In this study, patients who underwent McIndoe vaginoplasty were evaluated for development of vaginal mucosa. Vaginal pH measurements, smears, and punch biopsies were obtained from seven patients postoperatively at 3, 6, and 12 months after having McIndoe vaginoplasty. Neovaginal smears indicated no specific data for mucosal development at the 3rd and 6th month after the operation. However, Doderlein bacilli were determined at the 12th month. Histopathological examination of punch biopsies revealed dermal and subdermal thickening at the 3rd month, partial adaptation to mucosa at 6th month, and full adaptation to mucosa at 12th month. Also normal vaginal pH levels were recorded at the 12th month. As a result of the adaptation process, the split thickness skin graft acquired both histological and physiological characteristics of normal vaginal mucosa. Also, neovaginal epithelium was evaluated to be macroscopically similar to normal vaginal mucosa, 12 months after the operation.


Translation of type C viral RNAs in Xenopus laevis oocytes: evidence that the 120,000-molecular-weight polyprotein expressed in Abelson leukemia virus-transformed cells is virus coded.
The genomic RNA of Abelson leukemia virus (AbLV) has been purified and translated in Xenopus laevis oocytes. The primary AbLV-specific protein synthesized is a polyprotein corresponding in molecular weight and immunological properties to a previously described p15 and p12 containing 110,000- to 130,000-molecular-weight polyprotein expressed in AbLV-transformed cells. In contrast, translation of woolly monkey sarcoma virus genomic RNA resulted in symthesis of a 55,000-molecular-weight polyprotein consisting of woolly helper virus p30, p15, and p12. These findings demonstrate the value of the X. laevis oocyte in vitro system for studies of translational products of replication-defective transforming viruses and establish the virus-coded nature of the nonstructural component of the 110,000- to 130,000-molecular-weight polyprotein expressed in AbLV-transformed cells.


Purification and characterization of a small (7.3 kDa) putative lipid transfer protein from maize seeds.
The present study reports, for the first time in literature, the purification and biochemical characterization of a small basic protein from maize seeds similar to plant lipid transfer proteins-2, named mLTP2. The mLTP2 consists of 70 amino acid residues and has an M(r) of 7303.83, determined by electrospray ionization mass spectrometry. The primary structure of mLTP2 was determined by automated Edman degradation of the intact protein and peptides obtained from digestions with trypsin and by C-terminal sequencing using carboxypeptidase Y. The mLTP2 exhibits high sequence similarity (51-44% identical positions) with other plant LTP2s previously described.


Updated posters to help manage medical emergencies in the dental practice.
Medical emergencies can occur in the dental practice. Medical Emergencies in the Dental Practice and Emergency Drugs in the Dental Practice posters have been designed to help dental practitioners to respond effectively and safely to a medical emergency. These posters, endorsed by the British Dental Association, are included with this issue of the British Dental Journal. Further copies can be downloaded from: https://www.walsallhealthcare.nhs.uk/medical-education.aspx.


Gram type-specific broad-range PCR amplification for rapid detection of 62 pathogenic bacteria.
Broad-range PCR has proven to be useful for the detection of bacteria. A set of broad-range PCR primers directed against conserved regions in the 16S rRNA gene was designed to specifically amplify either gram-positive or gram-negative bacteria. The gram type-specific broad-range PCR correctly classified all 62 pathogenic species tested.


Iron overload suppresses hippocampal neurogenesis in adult mice: Implication for iron dysregulation-linked neurological diseases.
Adult hippocampal neurogenesis is an important player in brain homeostasis and its impairment participates in neurological diseases. Iron overload has emerged as an irreversible factor of brain aging, and is also closely related to degenerative disorders, including cognitive dysfunction. However, whether brain iron overload alters hippocampal neurogenesis has not been reported. We investigated the effect of elevated iron content on adult hippocampal neurogenesis and explored the underlying mechanism. Mouse models with hippocampal iron overload were generated. Neurogenesis in hippocampus and expression levels of related molecules were assessed. Iron accumulation in hippocampus remarkably impaired the differentiation of neural stem cells, resulting in a significant decrease in newborn neurons. The damage was possibly attributed to iron-induced downregulation of proprotein convertase furin and subsequently decreased maturation of brain-derived neurotrophic factor (BDNF), thus contributing to memory decline and anxiety-like behavior of mice. Supportively, knockdown of furin indeed suppressed hippocampal neurogenesis, while furin overexpression restored the impairment. These findings demonstrated that iron overload damaged hippocampal neurogenesis likely via iron-furin-BDNF pathway. This study provides new insights into potential mechanisms on iron-induced neurotoxicity and the causes of neurogenesis injury and renders modulating iron homeostasis and furin expression as novel therapeutic strategies for treatment of neurological diseases.


The effectiveness of retinoic acid treatment in bladder cancer: impact on recurrence, survival and TGFalpha and VEGF as end-point biomarkers.
Being best-studied superficial bladder cancer (SBC) chemopreventives, retinoids' negative studies and toxicity were stumbling. With proper understanding of retinoid metabolism, we aimed at investigating combined ketoconazole (a strong inhibitor of retinoic acid-catabolizing cytochrome P450s) all-trans retinoic acid (Keto-atRA) SBC treatment. VEGF and TGFalpha levels are end-point pathogenetic biomarkers involved in early SBC. Keto-atRA treatment significantly improved survival time and decreased recurrence rate compared to control disease group, with tolerable and reversible side-effects. Treatment normalized induced levels of VEGF and TGFalpha with a positive correlation between these cytokines. Seven days after TURT visible tumor(s), combined atRA 1 mg/kg for five days a week + Keto 200 mg twice daily for five days a week for three months were given to 16 patients with SBC stages Ta and T1 with various grades. Three months follow up/20 months used white light cystoscopy and urinary cytology. Recurrence rate and survival time were compared to a retrospective group of 25 patients of comparable age, stage and grade with TURT as sole treatment for SBC. VEGF and TGFalpha were measured in urine and serum of 12 normal subjects and treated patients. Samples were collected just before TURT, one week after TURT, at the end of one month and at the end of three months of treatment. The combination and schedule used for Keto-atRA therapy effectively reduced recurrence rate and increased survival time of SBC patients probably through reduction of VEGF and TGFalpha as major mitogenic/angiogenic factors; possibly by eliminating malignant cells that produce them.


Assessing attention and impulsivity in the variable stimulus duration and variable intertrial interval rodent continuous performance test schedules using noradrenaline receptor antagonists in female C57BL/6JRj mice.
Noradrenergic dysfunction is associated with disorders of impulsivity and inattention. The rodent continuous performance test (rCPT) quantifies changes in attention and impulsivity. To use NA receptor antagonists to examine the roles of NA on attention and impulsivity behaviours measured in the rCPT variable stimulus duration (vSD) and the variable intertrial interval (vITI) schedules. Two cohorts of 36 female C57BL/6JRj mice were examined separately in the rCPT vSD and vITI schedules. Both cohorts received antagonists of the following adrenoceptors: α1 (doxazosin, DOX: 1.0, 3.0, 10.0 mg/kg), α2 (yohimbine, YOH: 0.1, 0.3, 1.0 mg/kg), and β1/2 (propranolol, PRO: 1.0, 3.0, 10.0 mg/kg) in consecutive balanced Latin square designs with flanking reference measurements. The antagonists were subsequently examined for effects on locomotor activity. DOX showed similar effects in both schedules, improving discriminability and accuracy, and reducing responding and impulsivity, and DOX also reduced locomotor activity. YOH showed prominent effects in the vSD schedule to increase responding and impulsivity, while impairing discriminability and accuracy. YOH did not affect locomotor activity. PRO increased responding and impulsivity, decreased accuracy, but did not affect discriminability or locomotor activity. Antagonism of α2 or β1/2 adrenoceptors caused similar increases in responding and impulsivity and worsened attentional performance, while α1 adrenoceptor antagonism showed the opposite effects. Our results suggest that endogenous NA exerts bidirectional control of most behaviours in the rCPT. The parallel vSD and vITI studies showed a substantial overlap in effects, but also some differences that indicate differing sensitivity towards noradrenergic manipulations.


Overview of published evidence on outcomes with early diagnosis from large US observational studies.
This review describes recent published observational studies that assess the associations between early nutritional status or early asymptomatic diagnosis and outcomes among patients with cystic fibrosis (CF) in the United States. Three national registry-based studies demonstrated an association between nutritional status early in life (1-8 years of age) and subsequent lung function and mortality. These studies lend weight to the hypothesis that improved nutrition in early childhood, which has been associated with diagnosis by means of newborn screening, could lead to improved lung function and survival. Another study examined the association of early asymptomatic diagnosis and outcomes among patients in the US CF Registry and found that, among patients born after 1987, early asymptomatic diagnosis appeared to result in improved lung function as long as 10 years of age. This association was limited to children born after 1987, which suggests that recent improvements in early treatment strategies allowed early diagnosis to lead to more aggressive therapies, resulting in important improvements in pulmonary health. Taken together, these observational studies provide indirect evidence that diagnosis by means of newborn screening may improve the pulmonary health and survival of patients with CF.


Cardio-renal syndrome type 2: epidemiology, pathophysiology, and treatment.
Cardiac and kidney disease are becoming increasingly more prevalent in the population, and may exist concurrently. One of the most important comorbidities in heart failure is renal dysfunction. The pathophysiology of cardio-renal syndromes is complicated, and has been divided into five categories. Cardio-Renal syndrome type 2 is described by chronic cardiac abnormalities resulting in impaired renal function. It is important to recognize this entity and to understand the pathophysiology underlying the cardiac and renal disorders to distinguish best treatment practices. The success in improved outcomes lies in optimization of heart failure therapies.


Changes in insulin sensitivity during GnRH agonist treatment in premenopausal women with leiomyoma.
The purpose of this study was to determine (1) the influence of estrogen deficiency induced by gonadotropin-releasing hormone (GnRH) agonist administration on insulin sensitivity as well as hormones and factors related to insulin resistance and (2) the differences in the influence for these parameters by the degree of basal insulin sensitivity. Thirty-five women diagnosed with leiomyoma were enrolled in this study. Serum levels of fasting glucose, insulin, sex steroid hormones, sex hormone-binding globulin (SHBG), vascular inflammatory markers and cytokines before and at 6months after commencement of GnRH agonist administration were examined. In all women, levels of insulin, glucose and homeostasis model assessment of insulin resistance (HOMA-IR) were not significantly changed. However, in women who had a low HOMA-IR before treatment, levels of insulin, glucose and HOMA-IR showed significant increases and total testosterone level showed a significant decrease. In women who had a high HOMA-IR, levels of insulin, HOMA-IR and SHBG were significantly decreased and levels of highly sensitive C-reactive protein, soluble intercellular adhesion molecule-1, E-selectin and monocyte chemoattractant protein-1 were significantly increased. Change in insulin sensitivity caused by GnRH agonist administration for premenopausal women with leiomyoma differs depending on baseline insulin sensitivity before treatment.


Spotting 'unproven' stem cell therapies in the wild.
Freya Leask explores how to spot an 'unproven' stem cell-based therapy and why producing an effective stem cell-based therapy is so challenging.


Technological advances to extend the echocardiographic imaging of pediatric patients.
Recent technological advances provide significant improvement in the quality of imaging for the acoustically challenged pediatric patient. Although tissue harmonics allow better imaging of the larger or postoperative patient, high-frequency transducers tend to optimize imaging in smaller patients. Miniaturization of transducers and ultrasound systems has lead to the innovative utilization of previously unavailable acoustic windows in a wider variety of settings. Each improvement advances the technology closer to the goal of providing optimal cardiac imaging in nearly all patients under virtually all circumstances.


Assessment of methods to identify sources of interindividual pharmacokinetic variations.
The advantages and limitations of the 2 most commonly used methods to investigate interindividual pharmacokinetic variations are reviewed. The first method is based on pharmacokinetic comparisons made after repeated administration of a model drug such as antipyrine, before, during and after imposition of a carefully controlled environmental perturbation. A principal virtue of the test is the use of each subject as a control. Subjects are usually under near basal conditions with respect to factors capable of altering hepatic drug-metabolising capacity. Exceedingly sensitive, the test yields highly reproducible results. It has been useful as a research tool in identifying environmental factors for which dose-response curves can be generated and compared. However, the test requires careful selection and control of subjects, and it may be hazardous to extrapolate results to subjects under different, non-basal, environmental conditions. This method most frequently involves antipyrine as the test compound, but other drugs can and have been used. The results disclose that many host factors that influence antipyrine disposition also affect the disposition of other drugs metabolised by hepatic mixed-function oxidases. Recent refinement of the antipyrine test involves measurement of the rate constant for formation of each of the 3 main metabolites of antipyrine. Sensitivity and specificity of the test are increased through examination of the effect of each factor on a separate hepatic cytochrome P-450. Due to the labouriousness of this procedure and its requirement for several days of urine collection from each subject, metabolite analysis will probably remain an experimental method not applicable for screening populations. The second method involves a particular model based on multiple regression analysis. Relying on correlations with historical data of a qualitative nature, previous applications of this method have been retrospective, rather than prospective. Several such correlations could not be confirmed in normal subjects under the conditions of a controlled prospective experiment. Thus, prospective studies need to be performed to check results obtained with this method. The model used appears to enjoy certain advantages, including speed, simplicity, and ease of execution.(ABSTRACT TRUNCATED AT 400 WORDS)


A novel composite film derived from cysteic acid and PDDA-functionalized graphene: enhanced sensing material for electrochemical determination of metronidazole.
A novel composite film derived from cysteic acid and poly(diallydimethylammonium chloride)-functionalized graphene (PDDA-GN) was employed as an enhanced electrode material for ultrasensitive determination of metronidazole. The cysteic acid/PDDA-GN composite film was prepared by the electrochemical grafting of cysteic acid onto the PDDA-GN coated glassy carbon electrode (GCE). The cyclic voltammetry investigations reveal that the peak current of metronidazole reduction at the cysteic acid/PDDA-GN/GCE was remarkably enhanced compared to the bare GCE, the cysteic acid/GCE and the PDDA-GN/GCE. This result implies the synergistic electrocatalytic effect of cysteic acid and PDDA-GN. The fabricated sensor shows linear response to metronidazole in the ranges of 10 nM-1 μM and 70 μM-800 μM, with a detection limit of 2.3 nM (S/N=3). The heterogeneous electron transfer rate constant and the diffusion coefficient of metronidazole were further evaluated by rotating disk electrode experiments. Moreover, we applied the present method to the determination of metronidazole in urine and lake water with satisfactory results.


Distribution of tuberculosis cases in the state of Paraná: an ecological study, Brazil, 2018-2021.
to analyze the distribution of tuberculosis cases in the state of Paraná, Brazil, between 2018 and 2021. this was an ecological study using secondary data obtained from compulsory notifications; detection rates per 100,000 inhabitants were described according to health regions in the state; percentage changes between 2018-2019 and 2020-2021 were calculated. a total of 7,099 cases were registered. The highest rates were observed in the health regions of Paranaguá (52.4/100,000 in 2018-2019; 38.2/100,000 in 2020-2021) and Foz do Iguaçu (34.4/100,000 in 2018-2019; 20.5/100,000 in 2020-2021), and the lowest rates in Irati (6.3/100,000 in 2018-2019; 8.8/100,000 in 2020-2021) and Francisco Beltrão (8.5/100,000 in 2018-2019; 7.6/100,000 in 2020-2021); in 2020-2021, it could be seen a decrease in percentage changes in 18 health regions, while there was an increase in four of them, especially Foz do Iguaçu (-40.5%) and Cianorte (+53.6%). high rates were found in the coastal and triple border regions; and there was a decline in detection rates in the pandemic period.


Administering Blood Products Before Selected Interventional Radiology Procedures: Developing, Applying, and Monitoring a Standardized Protocol.
To apply and monitor a single institution's adherence to internally established guidelines for the preoperative administration of platelets and/or fresh frozen plasma (FFP) before a specified subset of minimally invasive interventional radiology (IR) procedures. Beginning in December 2008, we implemented a set of restrictive guidelines for preoperative platelet and/or FFP administration before IR procedures at a single academic hospital. Basing our program on the methodology of Lean Six Sigma, we compared the number and appropriateness of transfusions between the months of January and October in 2008 (prepolicy), again in 2010 (postpolicy), and finally in 2015 (follow-up). Patients with a platelet count less than or equal to 50,000 or an international normalized ratio greater than or equal to 1.7 met criteria for receiving platelets or FFP, respectively, before their IR procedure. For all three periods, we compared the rates of transfusion, hemorrhagic complications, and proportion of appropriate versus inappropriate blood product administration (BPA) per our guidelines. There was a significant increase in the number of appropriate BPAs between 2008 and 2010 from 58% to 76% (P = .021). Between 2010 and 2015, the rate trended up further, from 76% to 88% (P = .051). Overall, between 2008 and 2015, the improvement from 58% to 88% was significant (P < .001). The rate of hemorrhagic complications was extremely low in all three groups. Restrictive guidelines for receiving platelets and FFP administrations before IR procedures can sustainably decrease the rate of overall BPA while increasing the proportion of appropriate BPA without impacting the rate of hemorrhagic complications.


Dynamic Measures of Anxiety-Related Threat Bias: Links to Stress Reactivity.
Exaggerated attention to threatening information, or the threat bias, has been implicated in the development and maintenance of anxiety disorders. Recent research has highlighted methodological limitations in threat bias measures, such as temporal insensitivity, leading to the development of novel metrics that capture change and variability in threat bias over time. These metrics, however, have rarely been examined in non-clinical samples. The present study aimed to explore the utility of these trial-level metrics in predicting anxiety-related stress reactivity (stress-induced negative mood state) in trait anxious adults (N = 52). Following a stressor, participants completed the dot probe task to generate threat bias scores. Stress reactivity was measured via stress-induced changes in subjective mood state. More variability in trial-level bias scores and greater bias away from threat (both mean and peak negative trial-level bias scores) predicted increased stress reactivity. The temporal characteristics of threat bias and implications for clinically-relevant measurement are discussed.


Gene flow inferred from seed dispersal and pollinator behaviour compared to DNA analysis of restriction site variation in a patchy population of Lotus corniculatus L.
Gene flow was investigated in a natural population of Lotus corniculatus L. (Fabaceae) using a combination of pollen and seed dispersal studies and a recombinant DNA technique. The population is spatially heterogeneous and grows with Empetrum nigrum. L. corniculatus is pollinated by the pollen-collecting bumblebee Bombus lapidarius L. Most pollinator flights occurred within patches, as bees usually visit nearest-neighbour plants, show no marked directionality, and forage mostly within patches. Gene flow by seeds is also limited, reinforcing the pattern of gene flow within patches. However, 2.6% of pollinator flights are between patches and considerable pollen carryover also occurs. Thus, gene flow between patches is potentially sufficient to retard or prevent genetic differentiation in spite of the patchy sub-structuring of the population. A sub-set of the population was analysed for restriction fragment length polymorphisms (RFLPs) to document the actual gene flow pattern of the population. The DNA analysis revealed significant levels of genetic differentiation between the patches. The level of gene flow that can be inferred from the distribution of genetic variation is surprisingly restricted, as compared to gene flow inferred from pollinator behaviour, and emphasizes that stochastic processes like genetic drift and founder effects may have a strong impact on the prevailing genetic structure.


A case of neuronal intranuclear inclusion disease with recurrent vomiting and without apparent DWI abnormality for the first seven years.
Neuronal intranuclear inclusion disease (NIID) is a rare, neurodegenerative disorder characterized by the presence of eosinophilic hyaline intranuclear inclusions, which are ubiquitin-positive and p62-positive, in neuronal and somatic cells; this can be observed on skin biopsy. Although patients with NIID present with a variety of symptoms that often make the diagnosis difficult, characteristic high-signal intensity of the corticomedullary junction on diffusion-weighted imaging (DWI) often provides a clue to the diagnosis of NIID. We present a case of NIID in a 57-year-old woman who only had recurrent vomiting for four years, which is uncommon as the presenting symptom; moreover, DWI showed no apparent abnormality until a slightly abnormal intensity lesion appeared at the right frontal corticomedullary junction seven years after the first episode of recurrent vomiting. Skin biopsies revealed multiple p62-positive nuclear inclusions, and genetic test showed GGC repeat expansion in NOTCH2NLC; this may form the genetic basis for NIID. Retrospectively, we found that abnormal cerebellar signals besides the vermis in the fluid attenuation inversion recovery (FLAIR) images were detected early-on in the disease. Periodic vomiting may be the only symptom of NIID in the early stages of the disease, and cerebellar abnormalities in FLAIR may serve as an important finding in the diagnosis of NIID, even in the absence of characteristic clinical symptoms or abnormal DWI signals at the cerebral corticomedullary junction.


A rare case of fulminant type 1 diabetes mellitus accompanied by both acute pancreatitis and myocarditis - case report.
Fulminant type 1 diabetes mellitus (FT1D) is a newly established subtype of type 1 diabetes. Its etiology has not been fully elucidated. Several cases with FT1D have exhibited pancreatitis or myocarditis. We report a 31-year-old Japanese woman who showed upper abdominal pain and was admitted to a local hospital. She was initially diagnosed with acute pancreatitis based on serum amylase elevation and swelling of the pancreas on computed tomography. Four days after admission, she developed diabetic ketoacidosis and was transferred to our hospital. Her symptoms and laboratory findings met the FT1D criteria. On the 3rd hospital day, electrocardiography (ECG) showed ST-segment elevation, and serum cardiac enzymes were markedly elevated. Because she exhibited late gadolinium enhancement in the apical wall on contrast-enhanced cardiac magnetic resonance imaging, she was diagnosed as acute myocarditis. Abnormal ECG findings and elevations of biomarkers associated with myocarditis showed improvement on the next day. This is the first case of FT1D accompanied by both pancreatitis and myocarditis and suggests that the pathophysiology of FT1D is related to the common etiology of acute pancreatitis and myocarditis.


Dioxin emission modeling using feature selection and simplified DFR with residual error fitting for the grate-based MSWI process.
Municipal solid waste incineration (MSWI) with grate technology is a widely applied waste-to-energy process in various cities in China. Meanwhile, dioxins (DXN) are emitted at the stack and are the critical environmental indicator for operation optimization control in the MSWI process. However, constructing a high-precision and fast emission model for DXN emission operation optimization control becomes an immediate difficulty. To address the above problem, this research utilizes a novel DXN emission measurement method using simplified deep forest regression (DFR) with residual error fitting (SDFR-ref). First, the high-dimensional process variables are optimally reduced following the mutual information and significance test. Then, a simplified DFR algorithm is established to infer or predict the nonlinearity between the selected process variables and the DXN emission concentration. Moreover, a gradient enhancement strategy in terms of residual error fitting with a step factor is designed to improve the measurement performance in the layer-by-layer learning process. Finally, an actual DXN dataset from 2009 to 2020 of the MSWI plant in Beijing is utilized to verify the SDFR-ref method. Comparison experiments demonstrate the superiority of the proposed method over other methods in terms of measurement accuracy and time consumption.


Longitudinal association of infrapatellar fat pad signal intensity alteration with biochemical biomarkers in knee osteoarthritis.
To explore the longitudinal association of quantitative infrapatellar fat pad (IPFP) signal intensity alteration with OA-related biomarkers. Eighteen OA-related biochemical biomarkers of 600 knee OA participants in the Foundation for the National Institutes of Health OA Biomarkers Consortium (FNIH) study were extracted. The quantitative IPFP signal intensity measures were acquired based on magnetic resonance imaging, including mean value [Mean (IPFP)] and standard deviation [sDev (IPFP)] of the whole IPFP signal intensity, median value [Median (H)] and upper quartile value [UQ (H)] of high signal intensity, the ratio of volume of high signal intensity to volume of whole IPFP signal intensity [Percentage (H)] and Clustering factor (H). The linear mixed-effect model was applied to determine the longitudinal associations between IPFP signal intensity alteration and biochemical biomarkers over 2 years. All IPFP measures except for Clustering factor (H) were positively associated with urine collagenase-cleaved type II collagen neoepitope (uC2C), urine C-terminal cross-linked telopeptide of type II collagen (uCTX-II), urine C-terminal cross-linked telopeptide of type I collagen-α (uCTX-Iα) and urine N-terminal cross-linked telopeptide of type I collagen (uNTX-I). Mean (IPFP), Median (H) and Percentage (H) were positively associated with the nitrated form of an epitope located in the triple helix of type II collagen (Coll2-1 NO2). Mean (IPFP), Median (H) and UQ (H) were positively associated with sCTX-I and uCTX-Iβ. Positive associations between sDev (IPFP), Percentage (H) and serum hyaluronic acid (sHA) were found. Our results suggest a role of IPFP signal intensity alteration in joint tissue remodelling on a molecular level.


Correlation of Venous Blood Gas and Pulse Oximetry With Arterial Blood Gas in the Undifferentiated Critically Ill Patient.
Blood gas analysis is often used to assess acid-base, ventilation, and oxygenation status in critically ill patients. Although arterial blood gas (ABG) analysis remains the gold standard, venous blood gas (VBG) analysis has been shown to correlate with ABG analysis and has been proposed as a safer less invasive alternative to ABG analysis. The purpose of this study was to evaluate the correlation of VBG analysis plus pulse oximetry (SpO2) with ABG analysis. We performed a prospective cohort study of patients in the emergency department (ED) and intensive care unit (ICU) at a single academic tertiary referral center. Patients were eligible for enrollment if the treating physician ordered an ABG. Statistical analysis of VBG, SpO2, and ABG data was done using paired t test, Pearson χ2, and Pearson correlation. There were 156 patients enrolled, and 129 patients completed the study. Of the patients completing the study, 53 (41.1%) were in the ED, 41 (31.8%) were in the medical ICU, and 35 (27.1%) were in the surgical ICU. The mean difference for pH between VBG and ABG was 0.03 (95% confidence interval: 0.03-0.04) with a Pearson correlation of 0.94. The mean difference for pCO2 between VBG and ABG was 4.8 mm Hg (95% confidence interval: 3.7-6.0 mm Hg) with a Pearson correlation of 0.93. The SpO2 correlated well with PaO2 (the partial pressure of oxygen in arterial blood) as predicted by the standard oxygen-hemoglobin dissociation curve. In this population of undifferentiated critically ill patients, pH and pCO2 on VBG analysis correlated with pH and pCO2 on ABG analysis. The SpO2 correlated well with pO2 on ABG analysis. The combination of VBG analysis plus SpO2 provided accurate information on acid-base, ventilation, and oxygenation status for undifferentiated critically ill patients in the ED and ICU.


The effect of packed cells and whole blood transfusions on survival after curative resection for colorectal carcinoma.
The effect of perioperative blood transfusions on survival after curative resection for colorectal carcinoma was studied retrospectively on 270 patients with special emphasis on whole blood transfusion. Eighty-six (32 percent) patients did not receive blood transfusions, whereas the remaining 110 (41 percent) received packed cells and 74 (27 percent) received at least 2 units of whole blood. The recurrence-free and overall 5-year survival rates for the transfused group were 58 and 57 percent, respectively, and for the non-transfused group, 78 and 72 percent, respectively. These differences were highly significant (log rank test, P less than 0.001). The recurrence-free and overall 5-year survival rates for patients who received only whole blood or a combination of whole blood and packed cells was 51 percent, and of those who received only packed cells was 63 percent. The difference was not statistically significant (log rank test, P = 0.08, P = 0.35). Administration of more than 6 units of blood is attended with a significantly worse 5-year disease-free survival rate than administration of a smaller volume. The survival was not decreased if 6 or more units of whole blood were given. The authors conclude that perioperative blood transfusions have a significant detrimental effect on survival after curative resection for colorectal carcinoma. This effect is not enhanced by whole blood transfusions.