Utility of Point-of-Care Lung Ultrasonography for Evaluating Acute Chest Syndrome in Young Patients With Sickle Cell Disease.
Acute chest syndrome is a leading cause of mortality in patients with sickle cell disease (SCD). Because early detection of acute chest syndrome is directly tied to prognosis, young patients with SCD undergo countless chest radiography screenings throughout their lifetime for commonly occurring acute chest syndrome risk factors such as fever, chest pain, or cough. Chest radiography is not an ideal screening method because it is associated with radiation exposure, which accumulates with repeated imaging. Point-of-care lung ultrasonography is a nonradiating imaging modality that has been used to identify other lung pathology and may have a role in SCD. The goal of this study was to determine the accuracy of point-of-care lung ultrasound to identify an infiltrate suggestive of acute chest syndrome in patients with SCD compared to chest radiography as the gold standard. This was a prospective observational study in 2 urban pediatric emergency departments to evaluate the accuracy of point-of-care lung ultrasonography in identifying patients with SCD who were aged 0 to 21 years and had an infiltrate suggestive of acute chest syndrome compared with chest radiography. Clinicians and trainees with point-of-care lung ultrasonographic training obtained informed consent and performed investigational point-of-care lung ultrasonography to evaluate for lung consolidation. A blinded point-of-care lung ultrasonographic expert reviewed results for quality assurance and agreement. Accuracy, sensitivity, specificity, likelihood ratios, and positive and negative predictive value were calculated for point-of-care lung ultrasonography test performance characteristics, with chest radiography as a reference standard. Point-of-care lung ultrasonography was performed on 191 SCD patients with a mean age of 8 years; 41% were female patients, and there was a 17% prevalence of acute chest syndrome. Accuracy of point-of-care lung ultrasonography to detected acute chest syndrome was 92%, sensitivity was 88%, and specificity was 93% compared with that for chest radiography. Point-of-care lung ultrasonography is a feasible alternative to chest radiography for screening for acute chest syndrome in young patients with SCD. Further studies are needed to determine how this test performs within clinical practice.


Effect of hyperosmotic solutions on human brain tumour vasculature.
Reversible opening of the blood-brain barrier (BBB) has been used to increase delivery of chemotherapeutic agents into brain tumours, but it is complicated and requires general anaesthesia. Without affecting the normal BBB, and avoiding the complications of BBB modification by hyperosmotic solution, we tried an adequate minimal BBB disruption in brain tumours. Although the effect of BBB disruption on normal brain has been described, there are no reports of the effect of an impaired BBB on microcirculation. In this study, four patients underwent surgical resection of a glioblastoma multiforme (GM; n = 1), astrocytoma (n = 2), or metastatic brain tumour (n = 1). Epicerebral microcirculation was observed in the operative field. Serial fluorescein microangiograms of the tumour and peritumoural area were obtained before and after BBB disruption was introduced intra-operatively by retrograde infusion of mannitol introducing a catheter via the temporal superficial artery back to the carotid bifurcation. On the initial microangiogram, staining by the fluorescein dye was observed in the GM and metastatic tumour but not in the astrocytoma; no extravasation of fluorescein dye was observed in the peritumoural areas. After BBB disruption, fluorescein perfusion increased and extravasation of fluorescein dye from the venules was observed in the GM and the metastatic tumour and in the peritumoural area of both lesions; BBB disruption started from venules in the peritumoural area without affecting the normal brain. However, such effects were not observed in the astrocytomas after BBB disruption nor in normal brain tissue in any patient. It appears that the integrity of the BBB is less stable in the peritumoural area of GM and metastatic brain tumours than it is in astrocytomas or normal brain. Osmotic BBB disruption may offer a method for achieving global delivery of therapeutic agents to brain tumours and peritumoural areas.


[Interlocking nailing; indication an technique (author's transl)].
This procedure is efficient, inexpensive and technically easy to perform. It can be used for fractures and pseudoarthroses of the femur and tibia.


An interleukin-1 receptor antagonist decreases fibrosis induced by dimethylnitrosamine in rat liver.
The main pathological feature of liver fibrosis is the accumulation of extracellular matrix associated with hyperplasia and activation of perisinusoidal (Ito) cells (PSC) to myofibroblast-like cells. Interleukin-1 enhances collagen synthesis by increasing the proliferative activity of cultured PSC and has been implicated in the pathogenesis of hepatic fibrosis. Interleukin-1 receptor antagonist (IL-1ra) can block the binding of IL-1 to its receptors and act as a natural inhibitor of IL-1. We have examined whether the administration of IL-1ra can interfere with the development of experimental cirrhosis induced by dimethylnitrosamine (DMN). Rats were divided in three groups and received respectively DMN, DMN + IL-1ra and IL-1ra. For each group the collagen content of the hepatic tissue and the volume density of the inflammatory infiltrate were measured. Immunostaining for laminin and alpha-smooth muscle actin were also performed. In animals given DMN + IL-1ra we observed a decreased deposition of laminin and collagen, and a decreased number of laminin-positive PSC and of alpha-smooth muscle actin reactive cells, compared with animals receiving DMN alone. The present findings suggest that the early activation of PSC in vivo is at least in part mediated by IL-1 and confirm that the administration of IL-1ra may be of interest in modifying the biological effects of IL-1.


Intravascular lipoleiomyomatosis: a report of two cases.
Two cases of intravascular leiomyomatosis (IVL) with histologic features of a lipoleiomyoma (LPL) are reported. Both tumors arose from preexisting uterine leiomyomata. One tumor was found incidentally in a uterus removed for leiomyomata. The other tumor extended up the inferior vena cava into the right side of the heart and presented as a cardiac mass. Although LPL is considered to be a benign lesion, IVL recurs in approximately 10% of reported cases, and must be distinguished from low-grade endometrial stromal sarcoma and leiomyosarcoma with vascular invasion. The combination of features in these cases lends support to the theory that IVL may arise by intravascular extension of a preexisting leiomyoma.


Validation of plasma and urinary canrenone for determination of bioavailability of spironolactone--comparison of tablets with solution/suspension.
Data showing a linear relationship between spironolactone dose and the levels of canrenone in plasma and urine are presented to support the use of canrenone levels as a measure of the bioavailability of spironolactone. The bioavailability of a selected batch of spironolactone 25 mg tablets was compared to that of an oral aqueous suspension of spironolactone in a separate balanced cross-over study involving 10 healthy subjects. The tablets were equivalent to suspension as regards area under the plasma concentration-time curve and total urinary excretion of canrenone, the prinicipal unconjugated metabolite of spironolactone. Peak plasma concentrations of canrenone were higher, and were attained significantly earlier, after treatment with spironolactone in suspension. The results indicate that spironolactone was absorbed more rapidly from the suspension, but that the total absorption did not differ between the two formulations.


Aging attenuates the ovarian circadian rhythm.
To study the effect of aging on ovarian circadian rhythm. Human and animal study. University hospital and research laboratory. Human granulosa cells were obtained by follicular aspiration from women undergoing in vitro fertilization (IVF), and ovarian and liver tissues were obtained from female C57BL/6 mice. None. Expression of circadian genes in young and older human granulosa cells and circadian rhythm in ovaries and livers of young and older mice. All examined circadian clock genes in human granulosa cells showed a downward trend in expression with aging, and their mRNA expression levels were negatively correlated with age (P < 0.05). Older patients (≥ 40 years of age) had significantly reduced serum anti-Müllerian hormone (AMH) levels. Except for Rev-erbα, all other examined circadian clock genes were positively correlated with the level of AMH (P < 0.05). The circadian rhythm in the ovaries of older mice (8 months) was changed significantly relative to that in ovaries of young mice (12 weeks), although the circadian rhythm in the livers of older mice was basically consistent with that of young mice. Lower ovarian reserve in older women is partially due to ovarian circadian dysrhythmia as a result of aging.


Impact of dedicated infectious disease teamwork on the treatment and prognosis of patients with diabetic foot infection.
The aim was to develop and evaluate the impact of a new model in which the infectious disease (ID) physician and pharmacist work together to treat diabetic foot infections (DFIs). A quasi-experimental before-after study was conducted. The medical charts of inpatients with DFI admitted between April 1, 2017 and March 31, 2018 were reviewed retrospectively (control group, n = 30). Inpatients diagnosed with DFI between April 1, 2018 and March 31, 2019 were enrolled prospectively as the intervention group and received treatment through dedicated ID teamwork (intervention group, n = 35). The distribution of infection severity and levels of metabolic criteria were similar in the two groups. Compared with the control group, the intervention group received adequate initial empirical treatment more frequently (96.8% vs 43.5%, p < 0.001) and had a shorter median duration of fever (1 day vs 7.5 days, p < 0.001). Rates of healing and relapse within 6 months were similar in the two groups, although the intervention group showed more sites of osteomyelitis (p = 0.036) and a higher percentage of polymicrobial infections (48.6% vs 10.0%, p = 0.001). The early and full participation of ID physicians and pharmacists in the treatment of DFI facilitated targeted antimicrobial treatment and improved patient outcomes.


New pyran derivative with antioxidant and anticancer properties isolated from the probiotic Lactobacillus plantarum H24 strain.
This work was aimed to prepare, isolate and identify antioxidant and cytotoxic compound from the culture filtrate of a probiotic lactobacillus strain. New compound, plantarone (1), together with two known compounds, kojic acid (2) and methyl dodecanoate (3), were isolated from the ethyl acetate extract of the culture filtrate of probiotic Lactobacillus plantarum H24. Their structures were elucidated using spectroscopic methods including 2 D NMR, HRMS analyses. Isolated compounds were screened for antioxidant and cytotoxic activities against Caco-2 colon cancer cells. Compounds 1 and 2 showed lowers DPPH radical scavenging activities (p < 0.05) with IC50 values of 66.3 ± 0.34 μM and 50.2 ± 0.28 μM respectively, compared to standard butylated hydroxyanisole (BHA: IC50 = 44.2 ± 0.24 μM). Whereas only compound 1 showed a good cytotoxicity activity with inhibition value of 60.72 ± 3.55%. Accordingly, L. plantarum H24 could be used to prevent oxidative stress and its injuries, improving human health.


Development of a LC-MS/MS method for the simultaneous determination of sorbic acid, natamycin and tylosin in Dulce de leche.
A simple extraction, rapid routine method for the simultaneous determination of sorbic acid, natamycin and tylosin in Dulce de leche, a traditional South American product, by liquid chromatography-tandem mass spectrometry has been developed and fully validated. The limits of detection were set to 24.41mgkg(-1) (sorbic acid), 0.10mgkg(-1) (natamycin) and 2μgkg(-1) (tylosin). Recoveries ranged from 95% to 110%. Proportionally, internal standardization was more efficient than external standard, resulting in a smaller measurement of uncertainty. In total, 35 commercial samples from Brazil, Argentina and Uruguay have been assessed. The proposed method was tested on other dairy desserts, demonstrating to be versatile. Although tylosin was not detected in any sample, a high rate of non-compliance was found, with 67.39% of samples above the maximum allowed for sorbic acid and a maximum concentration of 2105.36±178.60mgkg(-1). In two samples, natamycin was irregularly found.


Associations of Socio-Demographic, Clinical and Biochemical Parameters with Healthcare Cost, Health- and Renal-Related Quality of Life in Hemodialysis Patients: A Clinical Observational Study.
We examined factors associated with healthcare cost, health-related quality of life (HRQOL), and kidney disease quality of life (KDQOL) in hemodialysis patients. We conducted a cross-sectional study on 160 patients from January to April 2019 at a hemodialysis center. Socio-demographic, clinical, and laboratory parameters and quality of life (QOL) (using KDQOL-SF-v1.3) were assessed. Monthly healthcare costs were extracted from the hospital information system. The means of healthcare cost, HRQOL, and KDQOL were VND 9.4 ± 1.6 million, VND 45.1 ± 21.9 and VND 51.3 ± 13.0, respectively. In the multivariate analysis, the healthcare cost was higher in patients with a longer hemodialysis vintage (regression coefficient (B): 0.74; 95% confidence interval (95% CI): 0.25; 1.23), comorbidity (B: 0.77; 95% CI: 0.24; 1.31); and lower in those with a higher hematocrit concentration (B: -0.07; 95% CI: -0.13; -0.01). Patients that lived in urban areas (B: 9.08; 95% CI: 2.30; 15.85) had a better HRQOL; those with a comorbidity (B: -14.20; 95% CI: -21.43; -6.97), and with hypoalbuminemia (B: -9.31; 95% CI: -16.58; -2.04) had a poorer HRQOL. Patients with a higher level of education (B: 5.38~6.29) had a better KDQOL; those with a comorbidity had a poorer KDQOL (B: -6.17; 95% CI: -10.49; -1.85). In conclusion, a longer hemodialysis vintage, a comorbidity and a lower hematocrit concentration were associated with higher healthcare costs. Patients who lived in urban areas had a better HRQOL and a higher level of education led to a better KDQOL. Patients with a comorbidity had a lower HRQOL and KDQOL. Malnourished patients had a lower HRQOL.


Ethanol-sensitive times for the human conceptus.
The world's literature has been scoured to obtain data on 492 examples of the fetal alcohol syndrome (FAS) in the Northern Hemisphere. The seasonally pattern of FAS birth prevalence rates is compared with the seasonality pattern of ethanol intakes to estimate the time-lag between them and hence the timing of ethanol damage during development. It is tentatively suggested, in the light of the data, that this timing might be as late as the 18th-20th week. If this can be substantiated, it would alloy opportunities for preventive measures to be feasible even during pregnancy. Seasonality data have never previously been used to estimate the timing of a sensitive period in prenatal development. The present estimate for ethanol is, however, tentative and should be regarded only as an interesting indicator for future studies.


Prevalence, characteristics and risk factors of imported and local malaria cases in North-Western Province, Zambia: a cross-sectional study.
Imported malaria is a major challenge for countries that are in malaria elimination stage such as Zambia. Legitimate cross-border activities add to the risk of transmission, necessitating determination of prevalence, characteristics and risk factors of imported and local malaria. This cross-sectional study was conducted in 103 consented child and adult patients with clinical malaria symptoms, from selected health facilities in north-western Zambia. Patient demographic data and blood samples for malaria microscopy and full blood count were obtained. Chi-square and penalized logistic regression were performed to describe the characteristics and assess the risk factors of imported and local malaria in North-Western Province. Overall, malaria prevalence was 78.6% with 93.8% Plasmodium falciparum and 6.2% other species. The local cases were 72 (88.9%) while the imported were 9 (11.1%) out of the 81 positive participants. About 98.6% of the local cases were P. falciparum compared to 55.6% (χ2 = 52.4; p < 0.01) P. falciparum among the imported cases. Among the imported cases, 44% were species other than P. falciparum (χ2 = 48; p < 0.01) while among the local cases only 1.4% were. Gametocytes were present in 44% of the imported malaria cases and only in 2.8% of the local cases (χ2 = 48; p < 0.01). About 48.6% of local participants had severe anaemia compared to 33.3% of participants from the two neighbouring countries who had (χ2 = 4.9; p = 0.03). In the final model, only country of residence related positively to presence of species other than P. falciparum (OR = 39.0, CI [5.9, 445.9]; p < 0.01) and presence of gametocytes (OR = 23.1, CI [4.2, 161.6]; p < 0.01). Malaria prevalence in North-Western Province is high, with P. falciparum as the predominant species although importation of Plasmodium ovale and Plasmodium malariae is happening as well. Country of residence of patients is a major risk factor for malaria species and gametocyte presence. The need for enhanced malaria control with specific focus on border controls to detect and treat, for specific diagnosis and treatment according to species obtaining, for further research in the role of species and gametocytaemia in imported malaria, cannot be overemphasized.


Effects of Microhydration on the Mechanisms of Hydrolysis and Cl- Substitution in Reactions of N2 O5 and Seawater.
The reaction of N2 O5 at atmospheric interfaces has recently received considerable attention due to its importance in atmospheric chemistry. N2 O5 reacts preferentially with Cl- to form ClNO2 /NO3 - (Cl- substitution), but can also react with H2 O to form 2HNO3 (hydrolysis). In this paper, we explore these competing reactions in a theoretical study of the clusters N2 O5 /Cl- /nH2 O (n=2-5), resulting in the identification of three reaction motifs. First, we uncovered an SN 2-type Cl- substitution reaction of N2 O5 that occurs very quickly due to low barriers to reaction. Second, we found a low-lying pathway to hydrolysis via a ClNO2 intermediate (two-step hydrolysis). Finally, we found a direct hydrolysis pathway where H2 O attacks N2 O5 (one-step hydrolysis). We find that Cl- substitution is the fastest reaction in every cluster. Between one-step and two-step hydrolysis, we find that one-step hydrolysis barriers are lower, making two-step hydrolysis (via ClNO2 intermediate) likely only when concentrations of Cl- are high.


Evidence for a tonic inhibitory role of nifedipine-sensitive calcium channels in aldosterone biosynthesis.
This study investigated the effects of the calcium channel blockers nifedipine (a dihydropyridine) and verapamil (a papaverine derivative), on aldosterone production utilizing isolation of the early and late phases of aldosterone biosynthesis. Pregnenolone production (the early phase of aldosterone biosynthesis) was assessed in trilostane-treated bovine glomerulosa cells, used to inhibit the conversion of pregnenolone onwards to aldosterone. Conversion of exogenous corticosterone to aldosterone, an index of late phase activity, was assessed using aminoglutethimide to inhibit endogenous aldosterone production. Low concentrations of nifedipine, 10(-11)-10(-9) M, stimulated basal total aldosterone biosynthesis by enhancing the late phase although the early phase was inhibited. In the presence of 12 mM potassium (K+), which is less effective in stimulating aldosterone production than lower K+ concentrations, aldosterone production was enhanced by nifedipine, 10(-8) M, by an effect on the late phase. At K+ 6 and 8 mM, nifedipine, 10(-4) M, inhibited the early phase. Nifedipine 10(-5) inhibited angiotensin II (AII)-stimulated total aldosterone biosynthesis by independent effects on the early and late phases. Verapamil, 10(-4) M, inhibited total and early phase aldosterone production at K+, 4 mM and inhibited both phases at K+, 8 mM, stimulation was not observed using verapamil. Verapamil, 10(-4) M, also inhibited AII-stimulated aldosterone production. Basal and AII-stimulated pregnenolone production were inhibited by verapamil, 10(-4) M (basal) and 10(-6) M (AII-stimulated). These studies using nifedipine have revealed subtle calcium-dependent mechanisms involved in the tonic inhibition of activity in the late phase of aldosterone biosynthesis and the reversal of the inhibitory effect of high K+ concentrations also on the late phase. In addition, the data reported indicate that both AII and K+ independently enhance activity in the early and late phases of aldosterone production by calcium-dependent mechanisms.


[An interdisciplinary unit for major psychiatric/somatic comorbidity: concept and 22 years of experience].
In this article we describe in detail a specialised facility geared toward caring for patients presenting with major psychiatric and somatic comorbidity. Located in a psychiatric hospital, an important feature of the treatment offered in this unit is that psychiatric/psychotherapeutic and somatic care are provided by the same team members. Working in this unit places high demands on the medical team, which must be competent in both fields, especially during emergency situations. Due to the severity of the patients' symptomatology, the unit requires more staff than regular psychiatric wards. Frequent psychiatric diagnoses necessitating the transfer of patients to this ward include delirium associated with internal/neurologic disorders or occurring postoperatively, and affective syndromes and dementia due to general medical conditions. Somatic disorders frequently requiring treatment in this ward include acute cardiovascular syndromes, liver or renal failure, infections, and conditions arising postoperatively or following trauma.


Laryngeal hirudiniasis: an unusual cause of airway obstruction and hemoptysis.
Cases of childhood hemoptysis are rare and usually result from foreign body aspiration or congenital heart or lung diseases. However, human hirudiniasis due to the leech still exists, and could involve the upper airways after drinking infested water from quiet streams and pools. We report the case of a 6-year-old child who presented suffocating at the emergency room after having been misdiagnosed and treated for asthma over a 1-month period. His mother reported he had had recurrent hemoptysis, as well. The child inadvertently drank leech-infested water in a rural area of northern Syria. Surgical removal of the leech resulted in prompt resolution of the symptoms. Although laryngeal hirudiniasis is rare in the developed world, it remains a possible cause of childhood airway obstruction, hemoptysis, and anemia which needs to be considered in patients with a suggestive history.


ETS-related gene (ERG) controls endothelial cell permeability via transcriptional regulation of the claudin 5 (CLDN5) gene.
ETS-related gene (ERG) is a member of the ETS transcription factor family. Our previous studies have shown that ERG expression is highly enriched in endothelial cells (EC) both in vitro and in vivo. ERG expression is markedly repressed in response to inflammatory stimuli. It has been shown that ERG is a positive regulator of several EC-restricted genes including VE-cadherin, endoglin, and von Willebrand factor, and a negative regulator of other genes such as interleukin (IL)-8 and intercellular adhesion molecule (ICAM)-1. In this study we have identified a novel role for ERG in the regulation of EC barrier function. ERG knockdown results in marked increases in EC permeability. This is associated with a significant increase of stress fiber and gap formation in EC. Furthermore, we identify CLDN5 as a downstream target of ERG in EC. Thus, our results suggest that ERG plays a pivotal role in regulating EC barrier function and that this effect is mediated in part through its regulation of CLDN5 gene expression.


Trochlear Morphology Development: Study of Normal Pediatric Knee MRIs.
Trochlear dysplasia is a known risk factor for patellar dislocations yet normal trochlea development is not well described. This study will define the articular cartilage (AC) and subchondral trochlear morphology development in pediatric patients using magnetic resonance imaging (MRI) evaluation. A retrospective knee MRI review included patients aged 3 to 16 years with nonpatellofemoral-related diagnoses. International classification of diseases-9/International classification of diseases-10 codes were used to identify eligible study patients. Measurements of the trochlea were made on the basis of previously established methods using the axial MRI just distal to the physis at the deepest portion of the trochlear groove. Three linear [lateral trochlear height (LTH), medial trochlear height (MTH), and central trochlear height (CTH)] and 3 angular [sulcus angle (SA), lateral trochlear slope (LTS), and medial trochlear slope (MTS)] were made at AC and subchondral bone (SCB). The 12 measurements were made independently by 2 study authors. Inter-rater reliability was assessed using an interclass correlation coefficient for absolute agreement to the average of the scores. Trochlea measurements were summarized across age quartiles defined as first quartile (age, 5.1 to 8.3 y), second quartile (8.3 to 11.5 y), third quartile (11.5 to 14.3 y), fourth quartile (14.3to 16.9 y). Associations between age and trochlea measures were assessed using linear regression with Huber-White-adjusted SEs to account for clustering from a small number of patients (N=16) with >1 MRI. In total, 246 knee MRIs from 230 patients were included in this study; 113 patients (51%) were female, whereas 117 (49%) were male. A total of 116 MRIs (47%) were of the left knee and 130 (53%) were right knee. The average patient age was 11.4±3.4 years. Inter-rater agreement was high across all measures with interclass correlation coefficient values >0.7. Mean values for measurements are presented by age quartiles. LTH, MTH, and CTH showed a linear increase with age (range, 2 to 2.6 cm/y; P<0.001). SA, LTS, MTS measured at AC showed no change with age (P>0.05); however, LTS and MTS measured at SCB showed significant increases with age (0.6 and 0.9 degrees/y; P<0.001), whereas SA showed a decrease with age (-1.4 degrees/y; P<0.001). There were no significant differences found in the age associations by laterality, left versus right. There were no sex differences in the age associations for SA, LTS (P>0.05); however, for MTH, LTH, and CTH, males were found to have a significantly greater growth rate (P<0.001). This study found an increase in AC and SCB MTH, LTH, and CTH over time, as well as an increase in SCB LTS and MTS, with a decrease in SA. However, AC of the LTS and SA remained constant, with no significant change throughout growth. This normative data indicate that the LTS and SA of AC are predictors of final trochlea shape in normal development. Final trochlear morphologic development is nearly complete around age 12 years, with no significant changes occurring thereafter.


Efficient photocleavage of DNA utilising water-soluble lipid membrane-incorporated [60]fullerenes prepared using a [60]fullerene exchange method.
Various types of lipid membrane-incorporated C60 with high C60 concentrations can be prepared easily in several hours using the C60 exchange method and the photocleaving activity of cationic lipid membrane-incorporated C60 was appreciably higher than that of the C60.gamma-CDx complex.


Automated image segmentation method to analyse skeletal muscle cross section in exercise-induced regenerating myofibers.
Skeletal muscle is an adaptive tissue with the ability to regenerate in response to exercise training. Cross-sectional area (CSA) quantification, as a main parameter to assess muscle regeneration capability, is highly tedious and time-consuming, necessitating an accurate and automated approach to analysis. Although several excellent programs are available to automate analysis of muscle histology, they fail to efficiently and accurately measure CSA in regenerating myofibers in response to exercise training. Here, we have developed a novel fully-automated image segmentation method based on neutrosophic set algorithms to analyse whole skeletal muscle cross sections in exercise-induced regenerating myofibers, referred as MyoView, designed to obtain accurate fiber size and distribution measurements. MyoView provides relatively efficient, accurate, and reliable measurements for CSA quantification and detecting different myofibers, myonuclei and satellite cells in response to the post-exercise regenerating process. We showed that MyoView is comparable with manual quantification. We also showed that MyoView is more accurate and efficient to measure CSA in post-exercise regenerating myofibers as compared with Open-CSAM, MuscleJ, SMASH and MyoVision. Furthermore, we demonstrated that to obtain an accurate CSA quantification of exercise-induced regenerating myofibers, whole muscle cross-section analysis is an essential part, especially for the measurement of different fiber-types. We present MyoView as a new tool to quantify CSA, myonuclei and satellite cells in skeletal muscle from any experimental condition including exercise-induced regenerating myofibers.


Identification of GPR99 protein as a potential third cysteinyl leukotriene receptor with a preference for leukotriene E4 ligand.
The cysteinyl leukotrienes (cys-LTs), leukotriene C4 (LTC4), a conjugation product of glutathione and eicosatetraenoic acid, and its metabolites, LTD4 and LTE4, are lipid mediators of smooth muscle constriction and inflammation in asthma. LTD4 is the most potent ligand for the type 1 cys-LT receptor (CysLT1R), and LTC4 and LTD4 have similar lesser potency for CysLT2R, whereas LTE4 has little potency for either receptor. Cysltr1/Cysltr2(-/-) mice, lacking the two defined receptors, exhibited a comparable dose-dependent vascular leak to intradermal injection of LTC4 or LTD4 and an augmented response to LTE4 as compared with WT mice. As LTE4 retains a cysteine residue and might provide recognition via a dicarboxylic acid structure, we screened cDNAs within the P2Y nucleotide receptor family containing CysLTRs and dicarboxylic acid receptors with trans-activator reporter gene assays. GPR99, previously described as an oxoglutarate receptor (Oxgr1), showed both a functional and a binding response to LTE4 in these transfectants. We generated Gpr99(-/-) and Gpr99/Cysltr1/Cysltr2(-/-) mice for comparison with WT and Cysltr1/Cysltr2(-/-) mice. Strikingly, GPR99 deficiency in the Cysltr1/Cysltr2(-/-) mice virtually eliminated the vascular leak in response to the cys-LT ligands, indicating GPR99 as a potential CysLT3R active in the Cysltr1/Cysltr2(-/-) mice. Importantly, the Gpr99(-/-) mice showed a dose-dependent loss of LTE4-mediated vascular permeability, but not to LTC4 or LTD4, revealing a preference of GPR99 for LTE4 even when CysLT1R is present. As LTE4 is the predominant cys-LT species in inflamed tissues, GPR99 may provide a new therapeutic target.


Successful treatment of cherry red spot-myoclonus syndrome with 5-hydroxytryptophan.
A 14-year-old Saudi boy with cherry red spot-myoclonus syndrome and documented neuraminidase deficiency responded well to titrated doses of 5-hydroxytryptophan as an add-on treatment.


Further cardiac transplant procedures in patients with heterotopic heart transplants.
Seven patients with heterotopic heart transplants have undergone further heart transplant procedures. In 5, the first heterotopically placed donor heart was excised and replaced with the second donor heart. In 2, the first heterotopic donor heart was left in situ and the patient's own heart (then nonfunctioning) was excised and replaced by the second donor heart; thus, these patients underwent orthotopic transplantation and were left with two donor hearts. The decision to perform retransplantation in a patient undergoing irreversible acute rejection is usually straightforward, but the timing of a further transplant procedure in a patient with advanced graft arteriosclerosis may present a difficult problem. Two of the 7 patients in this series died of infectious complications within the first 3 months after retransplantation. A third patient acutely rejected the second donor heart within 5 days, but survived an additional 17 months with the support of his own cardiomyopathic heart. Four patients remain alive and well between 5 and 36 months following the second transplant and between 17 and 54 months following the first transplant procedure.


Preparation of S14161 and its analogues and the discovery of 6-bromo-8-ethoxy-3-nitro-2H-chromene as a more potent antitumor agent in vitro.
The small chemical compound 8-ethoxy-2-(4-fluorophenyl)-3-nitro-2H-chromene (S14161) was recently identified as an inhibitor of the phosphoinositide 3-kinase (PI3K). In the present study, we designed a novel synthesis of S14161 and prepared a series of its analogues via the oxa-Michael-Henry reaction in the presence of catalytic amounts of l-proline and triethylamine. Further structural simplification led to the identification of 6-bromo-8-ethoxy-3-nitro-2H-chromene (BENC-511) that exhibited potent antiproliferative activities against a panel of 12 tumor cell lines. Compared with S14161, BENC-511 was more potent in blocking the AKT phosphorylation and inducing cancer cell apoptosis. BENC-511 also displayed more potent effects on human umbilical vein epithelial cells (HUVEC) migration, suggesting its anti-angiogenesis activity.


Corticotropin releasing factor-like immunoreactivity in sensory ganglia and capsaicin sensitive neurons of the rat central nervous system: colocalization with other neuropeptides.
Immunohistochemistry and radioimmunoassay (RIA) revealed that corticotropin releasing factor (CRF)-like immunoreactivity was found to be colocalized with substance P (SP)-, somatostatin (SST)- and leu-enkephalin (LENK)-like immunoreactivity in the dorsal root- and trigeminal ganglia, the dorsal horn of the spinal cord (laminae I and II), the substantia gelatinosa, and at the lateral border of the spinal nucleus and in the tractus spinalis of the trigeminal nerve. These peptides were also located in fast blue labeled cells of the trigeminal ganglion following injection of the dye into the spinal trigeminal area. This indicates that there are possible sensory projections of these peptides into the spinal trigeminal area. Capsaicin treatment of neonatal rats resulted in a marked decrease in the density of CRF-, SP-, VIP- and CCK-containing neurons in the above mentioned hindbrain areas, whereas SST- and LENK-immunoreactivity were not changed. RIA revealed that, compared to controls, CRF, SP and VIP concentrations in these areas were decreased in rats pretreated with capsaicin, while SST levels were increased; CCK and LENK levels were unchanged. It is concluded that the primary afferent neurons of the nucleus and tractus spinalis of the trigeminal nerve are richly endowed with a number of peptides some of which are sensitive to capsaicin action. The close anatomical proximity of these peptide containing neurons suggests the possibility of a coexistance of one or more of these substances.


Digesters as heat storage: Effects of the digester temperature on the process stability, sludge liquor quality, and the dewaterability.
Variation of the digester temperature during the year enables the operation of digesters as seasonal heat storage contributing to a holistic heat management at water resource recovery facilities. Full- and lab-scale process data were conducted to examine the effect of the digester temperature on process stability, sludge liquor quality, and dewaterability. Both full- and lab-scale digesters show a stable anaerobic degradation process with a hydraulic retention time of more than 20 days and organic load rates up to 2.2-kg COD/(m3 ·day) at temperatures between 33 and 53°C. The concentrations of soluble COD and ammonium-nitrogen in the sludge liquor digested at 53°C are 2.6 to 5.8 times and 1.3 times higher, respectively, than in the sludge liquor digested at 37°C. Dewatering tests show an enhancement of the dewaterability but a clear increase in the polymer demand at increased digester temperature. PRACTITIONER POINTS: Digesters can operate as seasonal heat storage within mesophilic and thermophilic temperatures Stable anaerobic degradation process for HRT above 20 days Maintenance of process stability as well as quantity and quality of biogas Increase of soluble COD in sludge liquor at higher temperatures Better dewaterability but higher demand for polymers with increasing temperature.


Incidence and predictors of bleeding complications after percutaneous coronary intervention.
Bleeding complications remain one of the most important challenges in percutaneous coronary intervention (PCI), particularly in Asians who are known to be vulnerable to the use of antiplatelets or anticoagulants. However, the incidence and predictors of bleeding complications after PCI have not been thoroughly investigated in Japan. We studied 13,075 consecutive patients in a Japanese multicenter PCI registry (Japan Cardiovascular Database - Keio interhospital Cardiovascular Study: JCD-KiCS) from September 2008 to March 2014. Multivariate logistic regression analysis was performed to investigate independent predictors of bleeding complications, and to create three risk prediction models for bleeding events. Model 1 included patients' characteristics alone. In model 2, we added patients' clinical presentation. Model 3 included covariates in model 2 along with angiographic and technical factors. Model discrimination was assessed using the area under the receiver operating curve (AUC). Overall, bleeding complications, according to the pre-specified US National Cardiovascular Data Registry criteria, were observed in 402 patients (3.1%). Independent predictors of bleeding complications included age, female gender, previous PCI, previous heart failure, hemodialysis (variables included in model 1), ST-elevation and non-ST-elevation myocardial infarction, cardiogenic shock (added in model 2), transradial intervention, use of intra-aortic balloon pumping or a rotablator, and PCI for chronic total occlusion (added in model 3). Above all, previous PCI and transradial intervention were inverse predictors of bleeding. The predictability of the risk models improved as the number of variables increased, with AUC of 0.667, 0.747, and 0.791 for models 1, 2, and 3, respectively. The incidence of bleeding complications among Japanese PCI patients was approximately 3% in standard nomenclature, which is equivalent to that of other international registries. Patients' characteristics, clinical presentation, and angiographic and technical factors all independently contributed to its prediction.


Continuity of care and clinical outcome: a prospective cohort study.
Continuity of care is a central objective of community psychiatric services, but there is no consensus about its measurement. We developed measures of continuity of care suitable for routine use, and measured continuity and individual patient outcome over a period in which community services were developing. One hundred patients with severe mental illness receiving continuing care from two sectorised services were sampled and interviewed. Data were collected concerning their care over 20 months prior to interview. After 20 months prospective follow-up, they were re-interviewed. Continuity was defined as: perceived accessibility of services and knowledge about them, the number of keyworkers in a defined period of time, and the proportion of time out of contact with services. Continuity of care improved significantly on all measures over the period of the study. Individual patient outcome also improved, but in multiple regression models including clinical and demographic variables, measures of continuity were not significant predictors of outcome. Continuity was similar for white and non-white patients. Simple measures of continuity are useful in evaluating changes in the process of care, but they are not straightforwardly related to individual outcome.


Early NICU discharge of very low birth weight infants: a critical review and analysis.
Early neonatal intensive care unit (NICU) discharge has been advocated for selected preterm infants to reduce both the adverse environment of prolonged hospital stay and to encourage earlier parental involvement by empowering parents to contribute to the ongoing care of their infant, and thereby reducing costs of care. Randomized trials and descriptive experiences of early discharge programs are critically reviewed over the last 30 years, and the key elements necessary for successful early discharge are reviewed and defined. Early discharge is clearly achievable for a large number of infants. Variations in neonatal care practices are reviewed since these variations have been documented to influence NICU stay. Management of apnea of prematurity and feeding practices is documented to significantly influence NICU length of stay, as is timing of discharge based on institutional factors. Developmentally centered care, use of nutritional supplements pre- and postdischarge, hearing screening programs, evaluation for retinopathy of prematurity, evaluation for apnea and bradycardia events, and cardiopulmonary stability while in a car seat all influence timing of discharge. Programs of early hospital discharge with home nursing and neonatologist support have been successful in lowering the length of NICU stay. However, trends in length of stay in NICUs indicate that for infants >750 g at birth over the last decade there have been insignificant reductions in length of hospital stay. Thus, because of the increase in the percentage of low birth weight infants in the US, there remain opportunities to improve on variations in care that will be translated to fewer NICU days in hospitals for selected infants. Several professional guidelines are summarized, and standards of care as related to discharge of premature infants are reviewed.


Organization factors influencing nurse ability to prevent and detect adverse drug events in public hospitals using a patient safety model.
The objective of this study was to measure organization factors that can influence the ability of nursing staff to prevent and detect ADEs in public hospitals using Systems Engineering Initiative for Patient Safety (SEIPS) model. This was a multi-center cross-sectional study. The study included a self-administered paper-based survey which was distributed and collected between October through December 2019. The study participants were nurses from 11 public hospitals located in two Iraqi provinces. Binary logistic regression was used to measure the relationship between the independent SEIPS factors (persons, organizations, tools, tasks, and environments) and the incidence of ADEs (outcome variable). The study recruited 603 nurses (68.3% men) from 11 public hospitals across two provinces. Less than half (48.8%) of the nurses received enough training to detect ADEs, 43.1% had adequate experience to detect ADEs, and 69.8% had to report ADEs in a special record. More than three-quarters (78.4%) believed that their jobs need fast work. Two of the five SEIPS model domains had significant negative association with the incidence of ADEs including organization (nurse-physician collaboration) and nurse experience in ADE detection. Nursing staff face several challenges to prevent and minimize ADEs including shortages in nurses, inadequate nurse experience in ADE detection, no training for ADE detection was received, fear of reporting ADEs, and a lack in monitoring equipment. Increasing nurse/patient ratio and providing more monitoring equipment and training courses can minimize ADEs and enhance their detection.


Perivascular location and phenotypic heterogeneity of microglial cells in the rat brain.
Employing immunohistochemical techniques and a panel of monoclonal antibodies that recognize rat cells of monocyte/macrophage lineage, we have demonstrated that cells labeled with these antibodies are widely distributed throughout the parenchyma of the rat brain. These cells have a remarkable microglial morphology and form phenotypically heterogenous populations. Double immunoperoxidase staining with the monoclonal antibody and anti-von Willebrand factor antiserum, which recognizes vascular endothelial cells, revealed that these cells are located exclusively at perivascular sites in the adult brain. These observations indicate that the microglial cells are perivascular cells of the monocyte/macrophage lineage, and may be intimately involved in various immunopathogenic conditions of the central nervous system.


The ultrastructure and histochemistry of the mesenteric connective tissue of the cockroach Periplaneta americana L. (Insecta, Dictyoptera).
The thick layer of collagenous connective tissue around the mesenteron of the cockroach Periplaneta americana has been examined by light microscopy, electron microscopy and histochemical techniques. This sheath, connected to the mesenteric epithelium by a basal lamina and traversed by longitudinal and circular musculature, tracheae and nerves, contains numerous collagen fibrils, elastic fibers, fibroblasts and rare hemocytes. Development starts during the first instars with the production of connective tissue material by fibroblasts. Glycosaminoglycans have been observed with the use of various histochemical reactions, in particular alcian blue staining, metachromasia and enzymatic digestion. The reactions indicate the presence of hyaluronic acid in the various instars, the appearance and increase of sulphated components during development, and the presence of neutral glycoproteins.


Exon redefinition by a point mutation within exon 5 of the glucose-6-phosphatase gene is the major cause of glycogen storage disease type 1a in Japan.
Glycogen storage disease (GSD) type 1a (von Gierke disease) is an autosomal recessive disorder caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase). We have identified a novel mutation in the G6Pase gene of a individual with GSD type 1a. The cDNA from the patient's liver revealed a 91-nt deletion in exon 5. The genomic DNA from the patient's white blood cells revealed no deletion or mutation at the splicing junction of intron 4 and exon 5. The 3' splicing occurred 91 bp from the 5' site of exon 5 (at position 732 in the coding region), causing a substitution of a single nucleotide (G to T) at position 727 in the coding region. Further confirmation of the missplicing was obtained by transient expression of allelic minigene constructs into animal cells. Another eight unrelated families of nine Japanese patients were all found to have this mutation. This mutation is a new type of splicing mutation in the G6Pase gene, and 91% of patients and carriers suffering from GSD1a in Japan are detectable with this splicing mutation.


Prediction models for eye irritation potential based on endpoints of the HETCAM and neutral red uptake tests.
The aim of this study was to explore the possibility of distinguishing between eye irritants (I; EU risk phrases R36 and R41) and nonirritants (NI), by using in vitro endpoints of the hen's egg test on the chorioallantoic membrane (the HETCAM test) and the neutral red uptake (NRU) test. Prediction models were derived by applying binary logistic regression to the in vitro data for these endpoints, which were taken from the report of a German validation study on the use of the HETCAM and 3T3 NRU tests as alternatives to the Draize eye irritation test. Whereas the validation study led to the conclusion that the combined use of the two tests enables a satisfactory discrimination between severe (R41) and nonsevere (NI, R36) eye irritants, the results of the present study indicate that the two in vitro tests can also be used to discriminate between nonirritants (NI) and irritants (R36 and R41).


Use of intravenous lipid emulsions for treating certain poisoning cases in small animals.
Intravenous lipid emulsion (ILE) infusions have become an emerging treatment modality in managing intoxications of veterinary patients. The advantages of ILE include an apparent wide margin of safety, relatively low cost, long shelf-life, and ease of administration. Based on limited case and anecdotal reports, ILEs have shown promise in the management of toxicoses from a variety of lipophilic agents, including drugs and pesticides. More studies are needed to determine optimum dosing regimens and identify potential adverse effects from the antidotal use of ILE in veterinary medicine.


Glucocorticoids preserve the t-tubular system in ventricular cardiomyocytes by upregulation of autophagic flux.
A major contributor to contractile dysfunction in heart failure is remodelling and loss of the cardiomyocyte transverse tubular system (t-system), but underlying mechanisms and signalling pathways remain elusive. It has been shown that dexamethasone promotes t-tubule development in stem cell-derived cardiomyocytes and that cardiomyocyte-specific glucocorticoid receptor (GR) knockout (GRKO) leads to heart failure. Here, we studied if the t-system is altered in GRKO hearts and if GR signalling is required for t-system preservation in adult cardiomyocytes. Confocal and 3D STED microscopy of myocardium from cardiomyocyte-specific GRKO mice revealed decreased t-system density and increased distances between ryanodine receptors (RyR) and L-type Ca2+ channels (LTCC). Because t-system remodelling and heart failure are intertwined, we investigated the underlying mechanisms in vitro. Ventricular cardiomyocytes from failing human and healthy adult rat hearts cultured in the absence of glucocorticoids (CTRL) showed distinctively lower t-system density than cells treated with dexamethasone (EC50 1.1 nM) or corticosterone. The GR antagonist mifepristone abrogated the effect of dexamethasone. Dexamethasone improved RyR-LTCC coupling and synchrony of intracellular Ca2+ release, but did not alter expression levels of t-system-associated proteins junctophilin-2 (JPH2), bridging integrator-1 (BIN1) or caveolin-3 (CAV3). Rather, dexamethasone upregulated LC3B and increased autophagic flux. The broad-spectrum protein kinase inhibitor staurosporine prevented dexamethasone-induced upregulation of autophagy and t-system preservation, and autophagy inhibitors bafilomycin A and chloroquine accelerated t-system loss. Conversely, induction of autophagy by rapamycin or amino acid starvation preserved the t-system. These findings suggest that GR signalling and autophagy are critically involved in t-system preservation and remodelling in the heart.


Patent term extension systems differentiate Japanese and US drug lifecycle management.
Drug lifecycle management (LCM) contributes to maximizing drug discovery investment returns. After initial drug approval, additional approvals can be sought for novel indications and formulations to extend product marketability. Patents provide additional barriers to entry and patent term extension systems facilitate extension of these. Several aspects of the US and Japanese patent term extension systems differ. Therefore, we compared both systems using a drug LCM case study to highlight the differences. Our findings indicate that the extension of multiple drug patents on multiple occasions in Japan produces a more complicated range of extended patent protections, compared with the US system.


The bigger the healthier: are the limits of BMI risk changing over time?
The body mass index (BMI) is often used as a predictor of overweight and obesity. There is, however, an important debate among international specialists as to what the risk limits should be, and where the cut-off points should be located. In the United States, for instance, adults with a BMI between 25 and 30 are considered overweight, while adults with a BMI of 30 or higher are considered obese. Nevertheless some researchers, especially in developing countries, claim that the limits established for the US are too permissive, and that the threshold to define obese adults should be set lower for other nationalities and ethnicities. This paper analyzes the mortality risks for different BMI levels of two populations of American adult men. The first population lived during the last quarter of the 19th century and the early 20th century. These men were drawn from a random sample of Union Army veterans who fought during the American Civil War (1861-1865). A contemporary sample of men was drawn from the first wave of the National Health and Nutrition Examination Survey (NHANES I) conducted between 1971 and 1975. The results indicate that the frontier of overweight and obesity are expanding over time, such that the potential risk is nowadays associated with higher levels of BMI. The finding may imply that differences in BMI cut-off points are not only cross ethnic, but also occur for similar ethnicities across time.


Mycophenolate mofetil is inferior to tacrolimus in sustaining remission in children with idiopathic steroid-resistant nephrotic syndrome.
Studies of nephrotic syndrome show that substitution of calcineurin inhibitors by mycophenolate mofetil (MMF) enables sustained remission and corticosteroid sparing and avoids therapy associated adverse effects. However, controlled studies in patients with steroid resistance are lacking. Here we examined the effect of switching from therapy with tacrolimus to MMF on disease course in an open-label, one-to-one randomized, controlled trial on children (one to 18 years old), recently diagnosed with steroid-resistant nephrotic syndrome, at a referral center in India. Following six months of therapy with tacrolimus, patients with complete or partial remission were randomly assigned such that 29 received MMF while 31 received tacrolimus along with tapering prednisolone on alternate days for 12 months. On intention-to-treat analyses, the proportion of patients with a favorable outcome (sustained remission, infrequent relapses) at one year was significantly lower (44.8%) in the MMF group than in the tacrolimus group (90.3%). The incidence of relapses was significantly higher for patients treated with MMF than tacrolimus (mean difference: 1.05 relapses per person-year). While there was no difference in the proportion of patients with sustained remission, the risk of recurrence of steroid resistance was significantly higher for patients receiving MMF compared to tacrolimus (mean difference: 20.7%). Compared to tacrolimus, patients receiving MMF had a significantly (71%) lower likelihood of a favorable outcome and significantly increased risk of treatment failure (frequent relapses, steroid resistance). Thus, replacing tacrolimus with MMF after six months of tacrolimus therapy for steroid-resistant nephrotic syndrome in children is associated with significant risk of frequent relapses or recurrence of resistance. These findings have implications for guiding the duration of therapy with tacrolimus for steroid-resistant nephrotic syndrome.


Clinical Utility of SNP Array Analysis in Prenatal Diagnosis: A Cohort Study of 5000 Pregnancies.
Single nucleotide polymorphism array (SNP-array) has been introduced for prenatal diagnosis. We aimed to evaluate the clinical value of SNP-array in the diagnosis of fetal chromosomal anomalies. A retrospective study was conducted on 5000 cases tested by SNP-array, and the results of 4022 cases analyzed by both karyotyping and SNP-array were compared. SNP-array analysis of 5000 samples revealed that the overall abnormality detection rate by SNP-array was 12.3%, and the overall detection rate of clinically significant copy number variations (CNVs) by SNP-array was 2.6%. SNP-array identified clinically significant submicroscopic CNVs in 4.5% fetuses with anomaly on ultrasonography, in 1.6% of fetuses with advanced maternal age (AMA), in 2.5% of fetuses with abnormal result on maternal serum screening, in 2.9% of fetuses with abnormal non-invasive prenatal testing (NIPT) results and in 3.0% of fetuses with other indications. Of the 4022 samples analyzed by both karyotyping and SNP-array, SNP-array could identify all the aneuploidy and triploidy detected by karyotyping but did not identify balanced structural chromosomal abnormalities and low-level mosaicism detected by karyotyping. SNP-array could additionally identify clinically significant submicroscopic CNVs, and we recommend the combination of SNP-array analysis and karyotyping in prenatal diagnosis.


A nationwide investigation of radiation therapy event reporting-and-learning systems: Can standards be improved?
Variation exists between event reporting-and-learning systems utilised in radiation therapy. Due to the impact of errors associated with this field of medicine, evidence-based and rigorous systems are imperative. The implementation of such systems facilitates the reactive enhancement of patient safety following an event. The purpose of this study was to evaluate Irish event reporting-and-learning procedures against the current literature using a developed evidence-based process map, and to propose recommendations as to how the national standard could be improved. Radiation Therapy Service Managers of all Irish radiation therapy institutions (n = 12) were invited to participate in an anonymous online questionnaire. Included in the questionnaire was a reporting-and-learning process map developed from evidence-based literature, which was used to assess the institution's practice through the use of vignettes. Frequency analysis of closed-ended questions and thematic analysis of open-ended questions was performed to assess the data. A 91.7% response rate was achieved. The following areas were found to have the most variation with the evidence-based process map: event classification, external reporting, and dissemination of lessons-learned to a wider audience. Recommendations to standardise practice were made. Opportunities for improvement exist within event reporting-and-learning systems of Irish radiation therapy institutions and recommendations have been made on these. These findings can provide learning for other countries with similar reporting systems.


Abdominal wound healing in jaundiced patients.
Abdominal wound healing was studied in 48 patients undergoing laparotomy for jaundice and 281 anicteric patients undergoing elective operations for cholelithiasis at the Sheffield Royal Infirmary during the period 1967 to 1976. Wound dehiscence or incisional hernia occurred in 27.1 per cent of jaundiced patients and in 4.3 per cent of anicteric patients (P less than 0.001). There was a slightly higher incidence of dehiscence and herniation in deeply icteric patients (plasma bilirubin greater than 170 mu mol/l), but patients who developed these complications did not appear to have a more severe degree of malnutrition or impaired liver function. The results of the study suggest that malignant disease may be an important factor in the pathogenesis of wound complications in jaundiced patients. Wound dehiscence or incisional hernia occurred in 59.1 per cent of patients with obstructive jaundice resulting from malignant disease but patients with jaundice resulting from biliary stones or benign pathology did not develop these complications.


Biodegradation of poly (ε-caprolactone) (PCL) film and foam plastic by Pseudozyma japonica sp. nov., a novel cutinolytic ustilaginomycetous yeast species.
Aliphatic polyesters poly (ε-caprolactone) (PCL) and foam plastic have been shown to be biodegradable by microorganisms, which possess cutinolytic enzymes. Pseudozyma japonica-Y7-09, showed both high growth and enzyme activity on Yeast malt (YM) medium fed with PCL film than on YM medium. The hydrolytic enzyme activity of the culture on p-nitrophenyl butyrate indicated the occurrence of cutinase enzyme. This activity was confirmed by the degradation of PCL film which reached to the maximum (93.33 %) at 15 days and the degradation of foam plastic which reached 43.2 % at 30 days. These results suggest that the extracellular cutinase enzyme of Pseudozyma japonica-Y7-09 may be useful for the biological degradation of plastic wastes.


Ketogenic diet attenuates aging-associated myocardial remodeling and dysfunction in mice.
Cardiac aging is manifested as unfavorable geometric and functional alterations in heart. The current work was to test whether a ketogenic diet (KD) impacted aging-associated myocardial remodeling and dysfunction in mice and investigate the underlying mechanism. The young and aged male mice were fed with KD or standard chow for four months. Echocardiography results revealed that KD decreased left ventricular end systolic diameter (LVESD) and increased fractional shortening in aged mice. With KD feeding, aged mice exhibited reduced cardiomyocyte cross-sectional area, fibrosis, and mRNA expression of atrial natriuretic peptide (ANP), Col1A1 and alpha smooth muscle actin (α-SMA) in myocardium. KD enhanced activities of superoxide dismutase 2 (SOD2), glutathione peroxidase (GPx) and catalase, and reduced the levels of malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) in myocardium of aged mice. KD led to a downregulation of expression of C/EBP homologous protein (CHOP), glucose regulated protein 78 (GRP78), cleaved activated transcription factor 6 (ATF6), and spliced X box-binding protein 1 (XBP-1 s) in myocardium of aged mice. KD in aged mice reduced mitochondrial reactive oxygen species (ROS) formation, enhanced mitochondrial ATP production and mitochondrial membrane potential (MMP), and preserved activity of complex III and electron-coupling capacities between complexes I and III and between complexes II and III in myocardium. Importantly, KD in aged mice promoted autophagic flux, evidenced by reduced protein expression of p62 and enhanced protein expression of lysosome-associated membrane protein-2 (Lamp2) in myocardium. In conclusion, long-time KD intake delayed cardiac aging in male mice, possibly through abating oxidative stress, improving mitochondrial function, and promoting autophagic flux.


A case report of three synchronous stage I malignant neoplasms.
A patient with three synchronous, Stage I neoplasms of the ovary, kidney, and lung, who underwent resection of all lesions at the same operative procedure, is presented. The incidence of multiple primary malignancies and the prognosis for Stage I cancers of the ovary, kidney, and lung are reviewed.


Development and optimisation of a flow injection assay for fluticasone propionate using an asymmetrical design and the variable-size simplex algorithm.
A flow injection analysis method is described to determine fluticasone propionate, based upon a novel adaptation of the reaction of o-phthalaldehyde with a thiol and a primary amine. The method, which allows both UV and fluorescence detection, has been optimised using experimental design. First a screening is executed to select the significant factors and in a second step these factors are optimised with the variable-size simplex algorithm. In the screening step, a two-level fractional factorial design is compared with an asymmetrical design containing the same number of experiments, but in which one factor is at three levels. It was found that in both designs the same significant variables are detected for the two-level factors, but that for the three-level factor the asymmetrical design confirms an expectation of having a (local) optimum in the examined domain, whilst from the two-level design this is not at all apparent. Complete optimisation was carried out for both UV and fluorescence detection. The two detection methods did not have the same significant variables. For the UV detection, the temperature and the pH adjustment on-line (concentration of sodium hydroxide and amount of boric acid) were the most critical parameters. For the fluorimetric detection the temperature and the fraction of methanol were critical. Moreover the conditions found to be optimal are different for both detection methods.


Engineering the hydrophobic residues of a GH11 xylanase impacts its adsorption onto lignin and its thermostability.
This study aimed to characterise the parameters governing the non-specific adsorption of a xylanase from Thermobacillus xylanilyticus (Tx-Xyn11) onto lignin isolated from maize stems. Such adsorption may be due to hydrophobic interactions between Tx-Xyn11 and lignin. Our strategy was to mutate hydrophobic residues present on the surface of Tx- Xyn11 into non-hydrophobic residues. Three mutants (P1, P2, and P3) with altered hydrophobic regions were produced and characterised. The thermostability of the P1 mutant was largely decreased compared with the thermostable Tx-Xyn11. The rate of adsorbed enzyme onto lignin was reduced to a similar extent for the P1 and P2 mutants, whereas the adsorption of the P3 mutant was less affected compared with that of Tx-Xyn11. When considered separately, the hydrophobic residues did not affect xylanase adsorption onto lignin. The addition of Tween 20 also led to the decreased adsorption of Tx-Xyn11 onto lignin. These results suggest that hydrophobic interactions are a key parameter in the interaction of Tx-Xyn11 with isolated lignin.


Cognitive-enhancing and antioxidant activities of inhaled coriander volatile oil in amyloid β(1-42) rat model of Alzheimer's disease.
Coriandrum sativum L., commonly known as coriander and belonging to the Apiaceae family is cultivated throughout the world for its nutritional value. In traditional medicine, coriander is recommended for the relief of pain, anxiety, flatulence, loss of appetite and convulsions. In the present study, the effects of inhaled coriander volatile oil (1% and 3%, daily, for 21days) extracted from C. sativum var. microcarpum on spatial memory performance were assessed in an Aβ(1-42) rat model of Alzheimer's disease. The Aβ(1-42)-treated rats exhibited the following: decrease of spontaneous alternations percentage within Y-maze task and increase of working memory errors, reference memory errors and time taken to consume all five baits within radial arm maze task. Exposure to coriander volatile oil significantly improved these parameters, suggesting positive effects on spatial memory formation. Assessments of oxidative stress markers in the hippocampal tissue of Aβ(1-42)-treated rats showed a significant increase of superoxide dismutase (SOD), lactate dehydrogenase (LDH) and a decrease of glutathione peroxidase (GPX) specific activities along with an elevation of malondialdehyde (MDA) level. Coriander volatile oil significantly decreased SOD and LDH specific activities, increased GPX specific activity and attenuated the increased MDA level. Also, DNA cleavage patterns were absent in the coriander rats, thus suggesting antiapoptotic activity of the volatile oil. Therefore, our results suggest that exposure to coriander volatile oil ameliorates Aβ(1-42)-induced spatial memory impairment by attenuation of the oxidative stress in the rat hippocampus.


Factors affecting statin uptake among people living with HIV: primary care provider perspectives.
Cardiovascular disease (CVD) is a major cause of morbidity and mortality among people living with HIV (PLWH), but statin therapy, safe and effective for PLWH, is under-prescribed. This study examined clinic leadership and provider perceptions of factors associated with statin prescribing for PLWH receiving care in eight community health clinics across Los Angeles, California. We conducted semi-structured telephone interviews with clinic leadership and providers across community health clinics participating in a larger study (INSPIRE) aimed at improving statin prescribing through education and feedback. Clinics included federally qualified health centers (N = 5), community clinics (N = 1) and county-run ambulatory care clinics (N = 2). Leadership and providers enrolled in INSPIRE (N = 39) were invited to participate in an interview. We used the Consolidated Framework for Implementation Research (CFIR) to structure our interview guide and analysis. We used standard qualitative content analysis methods to identify themes within CFIR categories; we also assessed current CVD risk assessment and statin-prescribing practices. Participants were clinic leaders (n = 6), primary care physicians with and without an HIV specialization (N = 6, N = 6, respectively), infectious diseases specialists (N = 12), nurse practitioners, physician assistants and registered nurses (N = 7). Ninety-five percent of providers from INSPIRE participated in an interview. We found that CVD risk assessment for PLWH is standard practice but that there is variation in risk assessment practices and that providers are unsure whether or how to adjust the risk threshold to account for HIV. Time, clinic and patient priorities impede ability to conduct CVD risk assessment with PLWH. Providers desire more data and standard practice guidance on prescribing statins for PLWH, including estimates of the effect of HIV on CVD, how to adjust the CVD risk threshold to account for HIV, which statins are best for people on antiretroviral therapy and on shared decision-making around prescribing statins to PLWH. While CVD risk assessment and statin prescribing fits within the mission and workflow of primary care, clinics may need to emphasize CVD risk assessment and statins as priorities in order to improve uptake.


Calreticulin synthetic peptide analogues: anti-peptide antibodies in autoimmune rheumatic diseases.
Autoantibodies in sera from patients with systemic lupus erythematosus (SLE) and onchocerciasis recognize calreticulin (CaR), a calcium-binding protein, as antigen. In this study we present the immunological properties of two synthetic peptides prepared to correspond to the 1-24 and 7-24 amino acid sequence of CaR. In contrast to information previously reported for the recombinant protein, the CaR-peptide analogues appeared immunoreactive to anti-Ro/SSA autoimmune sera. Human sera from patients with SLE, Sjögren's syndrome (SS), rheumatoid arthritis (RA), as well as mixed connective tissue disease (MCTD), demonstrated a positive autoimmune response (binding of antibodies), to the CaR-peptide analogues. These findings suggest that anti-calreticulin autoantibodies are not restricted to any disease specificity.


Inhibition of Shc/Grb2 protein-protein interaction suppresses growth of B104-1-1 tumors xenografted in nude mice.
Actinomycin D was revealed as an inhibitor of Shc/Grb2 interaction in cell lines from our recent study. Shc and Grb2 proteins are important molecules in Ras signaling pathways leading to cellular differentiation and proliferation, which require dramatic morphological changes. It was detected by transmission electron microscopy that actinomycin D induced significant changes in cellular ultrastructures of B104-1-1 cells and confirmed that the changes were due to inhibition of Shc/Grb2 interaction by actinomycin D rather than its inhibitory effect on transcription. Because actinomycin D was dispersed mainly in cytoplasm and Shc peptide (synthetic 13 amino acid tyrosine phosphorylated polypeptide) successfully displaced actinomycin D binding to its cellular targets while the other polypeptide from PDGF receptor could not. We examined the effect of actinomycin D on growth of B104-1-1 tumor xenografted in nude mice. Tumor growth was inhibited in vivo after treatment with this inhibitor. Efficacy was correlated with a reduction in the levels of Shc/Grb2 binding in excised tumors. These results suggest that actinomycin D inhibited Shc/Grb2 interaction in B104-1-1 tumor xenografted in nude mice.


Increasing HDL-cholesterol and prevention of atherosclerosis: A critical perspective.
The relationship between atherosclerosis and HDL is more complex than between LDL and atherosclerosis. Low HDL-cholesterol is associated with atherosclerotic disease not in a causal way but because low HDL-cholesterol reflects an increased concentration of triglyceride-rich lipoproteins. At the same time the functionality of the HDL system plays an important role in atherosclerosis prevention (for example by mediating reverse cholesterol transport). However, these two observations are not directly linked to each other. Therefore therapeutic strategies must either aim at decreasing the concentration of triglyceride-rich lipoproteins (and thereby increase HDL-cholesterol concentration) or at improving HDL function (which may or may not affect HDL-cholesterol concentration). Simply increasing HDL-cholesterol concentration without improving function or decreasing triglyceride-rich lipoproteins will not be beneficial with respect to atherosclerosis prevention.


Pain-Related Brain Activity Evoked by Active and Dynamic Arm Movement: Delayed-Onset Muscle Soreness as a Promising Model for Studying Movement-Related Pain in Humans.
To demonstrate delayed-onset muscle soreness (DOMS) is a suitable model for the study of movement-evoked pain, we attempted to identify brain regions specifically involved in pain evoked by active and dynamic movement under DOMS condition. Twelve healthy volunteers DOMS was induced in the left upper-arm flexor muscles by an eccentric elbow contraction exercise. Movement-evoked pain in the affected muscles was evaluated just before (day 0) and after (days 1-7 and 30) the exercise using a visual analog scale. Subjects underwent functional magnetic resonance imaging scans while performing repeated elbow flexion on day 2 (DOMS condition) and day 30 (painless condition). We compared brain activity between the DOMS and painless conditions. Movement-evoked pain reached peak intensity on day 2 and disappeared by day 30 in all subjects. No subject felt pain at rest on either of these days. Contralateral primary motor cortex (M1), parietal operculum and bilateral presupplementary motor area (pre-SMA) showed greater activity during active and dynamic arm movement with DOMS than during the same movement without pain. There was no difference in activation of brain regions known collectively as the "pain matrix," except for the parietal operculum, between the two conditions. Active and dynamic movement with pain selectively evoked activation of M1, pre-SMA, and parietal operculum, as assessed using DOMS. Our results demonstrate that DOMS is a promising experimental model for the study of movement-evoked pain in humans.


Isolation of an aminoglycoside receptor from guinea pig inner ear tissues and kidney.
Affinity chromatography was used to isolate aminoglycoside receptors from inner ear tissues and kidney. Neomycin was immobilized on glass beads and served as the stationary phase in column chromatography. Fractionation of an organic tissue extract on this matrix demonstrated two components with high affinity for neomycin: phohphatidyl inositol phosphate and phosphatidyl inositol diphosphate. The toxicity of aminoglycosides is explained on the basis of a drug-interaction with these lipids.


The study of the effect of human chorionic gonadotrophic (HCG) hormone on the survival of adrenal medulla transplant in brain. Preliminary study.
Autologous adrenal cortex was completely dissected off the medulla using microdissection. The adrenal medulla tissue was transplanted to the lateral ventricle in twenty-one adult rats. Group A consisting of ten animals received 200 units of HCG per 100 gram body weight daily for one week and then on every alternate day for seven weeks. The remaining rats (group B) served as control. After eight weeks the brains were removed and a volumetric study was done using histological sections. High pressure liquid chromatography (HPLC) with electrochemical detection for catecholamine assay of the graft was also undertaken. The graft survival in group A was significantly higher (p less than 0.005) than group B. The level of norepinephrine was significantly higher in group A while dopamine was higher in group B. The higher volume of graft tissue in group A suggests that HCG may help in increased survival and growth of the transplanted tissue. Higher levels of norepinephrine in group A would suggest a tendency for such grafts to be active to a greater extent with the treatment of HCG.


Principal component analysis to identify the major contributors to task-activated neurovascular responses.
Consensus on the optimal metrics for neurovascular coupling (NVC) is lacking. The aim of this study was to use principal component analysis (PCA) to determine the most significant contributors to NVC responses in healthy adults (HC), Alzheimer's disease (AD), and mild cognitive impairment (MCI). PCA was applied to three datasets: 1) 69 HC, 2) 30 older HC, 34 AD, and 22 MCI, 3) 1&2 combined. Data were extracted on peak percentage change in cerebral blood flow velocity (CBFv), variance ratio (VR), cross-correlation function peak (CCF), and blood pressure, for five cognitive tasks. An equamax rotation was applied and factors were significant where the eignevalue was ≥1. Rotated factor loadings ≥0.4 determined significant NVC variables. PCA identified 12 significant factors accounting for 78% of variance (all datasets). Contributing variables loaded differently on the factors across the datasets. In datasets 1&2, peak percentage change in CBFv contributed to factors explaining the most variance (45-58%), whereas cognitive test scores, fluency and memory domains contributed the least (15-37%). In the combined dataset, CBFv, CCF and fluency domain contributed the majority (33-43%), whereas VR and attention the least (6-24%). Peak percentage change in CBFv and the visuospatial task consistently accounted for a large proportion of the variance, suggesting these are robust NVC markers for future studies.


Identification of three H1N1 influenza virus groups with natural recombinant genes circulating from 1918 to 2009.
In this study, we identify a recombinant pb1 gene, a recombinant MP segment and a recombinant PA segment. The pb1 gene is recombined from two Eurasia swine H1N1 influenza virus lineages. It belongs to a H1N1 swine clade circulating in Europe and Asia from 1999 to 2009. The mosaic MP segment descends from H7 avian and H1N1 human virus lineages and pertains to a large human H1N1 virus family circulating in Asia, Europe and America from 1918 to 2007. The recombinant PA segment originated from two swine H1N1 lineages is found in a swine H1N1 group prevailing in Asia and Europe from 1999 to 2003. These results collectively falsify the hypothesis that influenza virus do not evolve by homologous recombination. Since recombination not only leads to virus genome diversity but also can alter its host adaptation and pathogenecity; the genetic mechanism should not be neglected in influenza virus surveillance.


Glucose metabolism and internal pH of Lactococcus lactis subsp. lactis cells utilizing NMR spectroscopy.
The metabolism of glucose was studied in Lactococcus lactis subsp. CNRZ 125 by 13C NMR. The initial rate of glucose utilization was higher for exponential phase cells than for stationary phase cells [150 vs 85 nmol g (dry wt)-1 s -1]. 31P NMR was used to determine changes in glycolytic phosphorylated intermediates (fructose-1,6-diphosphate, dihydroxyacetone phosphate and phosphoglycerate). The internal pHs of L. lactis subsp. lactis CNRZ 141 and CNRZ 125 were also measured by 31P NMR as a function of the external pH during growth. When the external pH was 6.8, the internal pHs of strain CNRZ 141 and CNRZ 125 were similar, 7.4. After the external pH had decreased to 5.5, the internal pH of strain CNRZ 141 had declined by 0.6 unit, whereas that of strain CNRZ 125 had decreased by only 0.2 unit of pH.


Temporal relationship between cardiac performance and myocardial uptake of dl-propranolol in man.
1. The temporal relationship between the myocardial arteriovenous difference of plasma propranolol concentration and heart rate and left ventricular dp/dt maximum was examined for 30 min after intravenous administration of 10mg (0.04 mmol) dl-propranolol in nine patients with ischaemic heart disease. 2. Very large positive myocardial a.v. differences of propranolol within the first 5 min became negative after 5 min, indicating a rapid, avid uptake with subsequent release of propranolol from the heart. 3. The heart rate and left ventricular dp/dt maximum increased 1 min after propranolol administration and did not change after the fifth min of the observation period. 4. The data suggest that a large number of unspecific binding sites for propranolol are present in the heart in addition to the specific beta-receptors.


Citric acid and hydrogen sulfide cooperate to mitigate chromium stress in tomato plants by modulating the ascorbate-glutathione cycle, chromium sequestration, and subcellular allocation of chromium.
The study aimed to investigate the role of hydrogen sulfide (H2S) in regulating chromium stress (Cr-S) tolerance of tomato plants treated with citric acid (CA). Prior to the Cr treatment, tomato plants were foliar-fed with CA (100 μM) daily for 3 days. Subsequently, the plants were grown for another ten days in a hydroponic system in a 50 μM Cr (VI) solution. Chromium treatment reduced photosynthetic pigments and plant biomass, but boosted the levels of hydrogen peroxide (H2O2) malondialdehyde (MDA), H2S, phytochelatins (PCs), and glutathione (GSH), electrolyte leakage (EL), and antioxidant enzyme activity in tomato plants. However, the foliar spray of CA mitigated the levels of H2O2, MDA, and EL, promoted plant growth and chlorophyll content, enhanced antioxidant enzymes' activities, and increased H2S production in Cr-S-tomato plants. CA also increased the levels of GSH and PCs, potentially reducing the toxicity of Cr through regulated sequestration. Additionally, the application of sodium hydrogen sulfide (NaHS), a donor of H2S, improved CA-induced Cr stress tolerance. The addition of CA promoted Cr accumulation in root cell wall and leaf vacuoles to suppress its toxicity. To assess the involvement of H2S in CA-mediated Cr-S tolerance, 0.1 mM hypotaurine (HT), an H2S scavenger, was provided to the control and Cr-S-plants along with CA and CA + NaHS. HT reduced the beneficial effects of CA by decreasing H2S production in tomato plants. However, the NaHS addition with CA + HT inverted the adverse impacts of HT, indicating that H2S is required for CA-induced Cr-S tolerance in tomato plants.


Percutaneous carbon dioxide excretion in the newborn infant.
Percutaneous carbon dioxide excretion was studied in 42 newborn infants between 25 and 39 weeks gestation, using a closed skin cell attached to the abdomen. The rate of excretion during the first few days of life was inversely related to gestation, increasing from a mean of 31 ml/m2/h at term to 198 ml/m2/h below 30 weeks gestation. Postnatally there was a rapid fall in the rate of excretion in very preterm infants to values about twice those found at term. The rate of excretion was linearly related to the CO2 diffusion gradient, and zero diffusion would be expected when there was no diffusion gradient. It is estimated that up to 15% of resting CO2 excretion occurs through the skin of very preterm infants, and more if the tissue PCO2 is elevated.


Evolution of reovirus genes: a comparison of serotype 1, 2, and 3 M2 genome segments, which encode the major structural capsid protein mu 1C.
The sequences of the M2 genome segments of reovirus serotypes 1 and 2 are presented and compared with that of the cognate genome segment of reovirus serotype 3. Genome segment M2 encodes protein mu 1, a cleavage product of which, mu 1C, is the major constituent of reovirus particles. The three M2 genome segments exhibit a serotype 1:3 relatedness pattern: the serotype 1 and 3, 1 and 2, and 2 and 3 genome segment pairs exhibit 15, 23, and 23% nucleotide mismatches, respectively. The vast majority of these mismatches (about 87%) occur in third base codon positions that do not cause amino acid changes; as a result the three mu 1 proteins are very highly related (about 97%). The mu 1 proteins are acidic proteins, low in cysteine, histidine, and methionine, and rich in proline; and they possess a rather low predicted alpha-helix content of 27%. The site where protein mu 1 is cleaved to mu 1C is predicted to be between residues 42 and 43 in a highly conserved portion of the molecule. The three M2 genome segments are related significantly more closely than the three S3 genome segments, and much more closely than the three S1 genome segments. We have analyzed the evolutionary divergence patterns of these three genome segments. The rate of mismatch accumulation in third base codon positions is roughly the same for all three genome segments, but the rates of mismatch accumulations in first, and particularly in second, base codon positions are quite different. For the S1 genome segments there is little difference between the rates of mismatch accumulations in all three codon positions, which indicates that retention of function is compatible with very extensive structural flexibility. By contrast, the rates of mismatch accumulations in first and second base codon positions are far less for the S3 genome segments, which encode the nonstructural protein sigma NS, and much lower still for the M2 genome segments, which suggests the existence of very stringent structural constraints for protein mu 1C, which might be expected of a protein that is a capsomer component.


Focus on Radiation Protection Improves Both Correct Behavior and Procedural Performance During Simulation-Based Training - A Randomized Comparison.
To explore whether simulation-based endovascular training with focus on radiation safety could improve correct behavior without jeopardizing the learning of procedural skills. Twenty-four residents without previous endovascular experience completed 10 clinical scenarios on a virtual-reality endovascular simulator with software for peripheral endovascular interventions. Participants were randomized to receive feedback (n = 12) or not (n = 12) on radiation protection (RP) performance after each case. Expert assessments were done at the first, second, fourth, seventh, and 10th case on RP and endovascular skills (ES). Automatic simulator metrics on procedure time, contrast dose, handling errors, and estimated radiation exposure to patient and operator were registered. Outcome metrics were analyzed by two-way mixed analysis of variance pairwise comparisons with independent t-tests. Correlations were explored using Pearson's r for internal consistency reliability. The RP performance was similar in both groups at their first attempt (P = 0.61), but the feedback group significantly outperformed the control group over time (P < 0.001 for all comparisons). The feedback group was however slower to learn the ES at start (P = 0.047 at second performance), but after 7 attempts no difference was shown (P = 0.59). The feedback group used more time (19.5 vs. 15.3 min; P = 0.007) but less contrast (60 vs. 100 mL; P < 0.001). The number of errors was the same in both groups, but all metrics regarding radiation exposure favored the feedback group (P-values from 0.001 to 0.008). Simulation-based training (SBT) is effective to acquire basic endovascular intervention skills and concurrently learn RP behavior when feedback on radiation culture is provided.


The use of a modified [3H]4-DAMP radioligand binding assay with increased selectivity for muscarinic M3 receptor shows that cortical CHRM3 levels are not altered in mood disorders.
[(3)H]4-DAMP is a radioligand that has been used to quantify levels of the muscarinic receptor CHRM3 protein in situ. However, in addition to high affinity binding to CHRM3, [(3)H]4-DAMP binds with low affinity to CHRM1 confounding the potential to discriminate between changes in these two muscarinic receptors. We have developed a [(3)H]4-DAMP binding assay, optimised for measuring CHRM3 protein levels in the cortex, with minimal selectivity towards CHRM1. The selectivity of our assay towards CHRM3 was confirmed using recombinant receptor-expressing, cell lysate preparations. [(3)H]4-DAMP binding levels were similar between wildtype and CHRM1 knockout mice, confirming that the amount of [(3)H]4-DAMP binding to CHRM1 was negligible. We used this assay to measure CHRM3 protein levels in the frontal pole, obtained post-mortem from subjects with bipolar disorder (n = 15), major depressive disorder (n = 15) and matched controls (n = 20) and showed that [(3)H]4-DAMP binding was not altered in either bipolar disorder or major depressive disorder. Western blotting confirmed that CHRM3 protein levels were unchanged in these subjects.


Cerebrospinal fluid pseudocyst presenting as a hepatic mass: a complication of ventriculoperitoneal shunt.
The case of a 3-year-old male child is reported who had a history of congenital hydrocephalus, treated by VP shunting. Severe complications with VP shunting are rare, but in this case the shunt had apparently perforated the liver, causing a pseudocyst to form and subsequent hepatomegaly. The shunt was revised surgically and the pseudocyst resected.


Drinking and Fos-immunoreactivity in rat brain induced by local injection of angiotensin I into the subfornical organ.
Previous studies suggested that angiotensinergic stimulation in the subfornical organ (SFO) has effects on the anterior third ventricle (AV3V) region and the hypothalamus for dipsogenic response and vasopressin release. In this study, Angiotensin I (ANG I) was directly injected into the SFO and this stimulated drinking. Injection of ANG I into the SFO also induced Fos-immunoreactivity (Fos-ir) in the AV3V region and in the vasopressin neurons of the supraoptic and paraventricular nuclei (SON and PVN). Pretreatment of the SFO with either captopril, an ANG converting enzyme inhibitor, or losartan, an AT1 receptor antagonist, abolished both drinking and Fos-ir induced by ANG I. Water intake partially decreased ANG I-induced Fos-ir in the SON and PVN, but not in the other areas. These results indicate that there is an ANG converting system in the SFO and suggest that neurons in the AV3V region and vasopressin cells in the hypothalamus can be regulated by angiotensinergic components in the SFO.


Prevalence of type 2 diabetes mellitus, impaired fasting glucose, general obesity, and abdominal obesity in patients with bipolar disorder: A systematic review and meta-analysis.
The study herein aimed to assess the prevalence of type 2 diabetes mellitus (T2DM), impaired fasting glucose (IFG), as well as general and abdominal obesity in patients with bipolar disorder (BD). We also compared the prevalence of T2DM and general obesity in patients with BD with age- and gender-matched healthy controls. A systematic search of Embase, Medline, PubMed, and APA PsycArticles was conducted from inception to June 2021 without language restrictions. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS) modified for case-control studies. A total of forty-nine studies were included in this analysis. The pooled prevalence of T2DM was 9.6% (95% CI, 7.3-12.2%). Patients with BD had a nearly 1.6 times greater risk of developing T2DM compared to their age- and gender-matched controls (RR=1.57, 95% CI 1.36-1.81, p<0.001). In the present analysis, IFG is defined as a fasting plasma glucose (FPG) ≥ 100 mg/dL (FPG≥100) with a prevalence of 22.4% (95% CI, 16.7-28.7%), or as an FPG equal to or greater than 110 mg/d (FPG≥110) with a prevalence of 14.8% (95% CI, 10.8-19.3%). The prevalence of general obesity (BMI≥30 kg/m2) was 29.0% (95% CI, 22.8-35.6%); the risk of obesity was almost twice the rate reported in patients with BD compared to controls (RR=1.67, 95% CI 1.32-2.12, p<0.001). We also observed that more than half of the BD participants had abdominal obesity (i.e., prevalence of 51.1%; 95% CI, 45.0-57.3%). A significant degree of heterogeneity was detected. Sources of heterogeneity included differences in study designs, inclusion criteria, measurement tools, and data analysis methods. Bipolar disorder is associated with a higher prevalence of T2DM, IFG, general obesity, and abdominal obesity. Type 2 diabetes mellitus and obesity are significantly more prevalent in patients with BD than in their age- and gender-matched controls. CRD42021258431.


First detection of the kdr mutation (L1014F) in the plague vector Xenopsylla cheopis (Siphonaptera: Pulicidae).
The oriental rat flea, Xenopsylla cheopis, is the most efficient vector of the plague. Pyrethroid insecticides such as cypermethrin, cyhalothrin and deltamethrin have been often used to limit plague transmission via controlling the vector during outbreaks. However, this strategy is threatened by the development of insecticide resistance. Understanding the mechanisms underlying pyrethroid resistance is the prerequisite for successful flea control. Partial DNA sequences of X. cheopis voltage gated sodium channel (VGSC) gene were amplified from a total of 111 individuals, collected from a natural plague epidemic foci in Baise City, Guangxi Zhuang Autonomous Region of China. These DNA fragments were sequenced. The frequency and distribution of kdr mutations were assessed in four X. cheopis populations. The origin of kdr mutations was investigated by phylogenetic and network analysis. The classical knockdown resistance (kdr) mutation (L1014F) was detected in four field populations at frequencies ranging between 0.021-0.241. The mutant homozygote was observed only in one of the four populations. Seven haplotypes were identified, with two of them carrying the resistance L1014F mutation. Phylogenetic tree and network analysis indicated that the L1014F allele was not singly originated. Based on polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) profiling, an easy-to-use and accurate molecular assay for screening individual fleas for the L1014F mutation was developed. To our knowledge, this work represents the first report of the L1014F mutation in the plague vector X. cheopis. The incidence of the L1014F allele highlights the need of further studies on the phenotypic effect of this mutation in this plague vector. Early detection and monitoring of insecticide resistance is suggested in order to make effective control strategies in case of plague outbreaks in this region.


Sensitisation to Lepisma saccharina (silverfish) in children with respiratory allergy.
Lepisma saccharina (silverfish) is a common insect which is often found in human dwellings. Our aim was to determine the IgE antibody pattern to this arthropod in children with allergic respiratory symptoms. The individual sera and a pool of selected sera of 45 children with asthma and/or rhinitis were used for an immunoblotting test with an extract of Lepisma saccharina; an immunoblotting inhibition test was performed with extracts of L. saccharina, D. pteronyssinus and cockroach. Between one and ten IgE binding bands were found in the sera of patients. The immunoblotting pattern was clearly different from that of D. pteronyssinus. Inhibition was found with D. pteronys-sinus and cockroach, which proves cross-reactivity between extracts. Allergenicity of Lepisma is demonstrated through in vitro tests. A pathogenic role still remains to be proved, but it should be considered in respiratory allergy, due to primary sensitisation to Lepisma, or to cross-reactivity with other indoor allergens.


Number needed to harm in the post-marketing safety evaluation: results for rosiglitazone and pioglitazone.
Our aim is to investigate the usefulness of metric indices in post-marketing safety evaluations by estimating number needed to harm (NNH) values for cardiovascular (CV) adverse outcomes for rosiglitazone and pioglitazone. Reports from regulatory authorities (RAs) were consulted, and Medline searches were performed to identify studies assessing CV risks [all-cause death, CV death, myocardial infarction (MI), stroke, or congestive heart failure (CHF)] for thiazolidinediones. Meta-analyses were performed to pool evidence from randomized controlled trials (RCTs) and observational studies (OS). NNHs [with 95% confidence intervals (CI)] per year were estimated for CV adverse events. Reports from RAs included two meta-analyses of short-term RCTs, two long-term RCTs (RECORD and PROACTIVE), and a systematic review of OS (n = 29). The Medline search identified six additional OS. Statistically significant NNH values were obtained for the following: (i) rosiglitazone versus control on MI and CHF in the meta-analysis of RCTs (NNH = 16; 95%CI = 10-255; and NNH = 7; 95%CI = 5-16, respectively) and meta-analysis of OS (NNH = 12; 95%CI = 9-20; and NNH = 5; 95%CI = 32-131, respectively) and on CHF in the RECORD (NNH = 6; 95%CI = 4-14); (ii) pioglitazone versus control on CHF (NNH = 11; 95%CI = 6, 403) in the meta-analysis of RCTs and PROACTIVE (NNH = 12; 95%CI = 8-43); and (iii) rosiglitazone versus pioglitazone on MI (NNH = 69; 95%CI = 32-379), stroke (NNH = 36; 95%CI = 20-225), CHF (NNH = 33; 95%CI = 19-47), and all-cause death (NNH = 63; 95%CI = 49-100) in the meta-analysis of OS. The NNH values suggested an increased CV risk with rosiglitazone versus pioglitazone across several sources of information. The inclusion of objective metrics in post-marketing drug's benefit-risk assessments could be of increased value and help RAs to make consistent decisions on drug safety.


Neutron beam therapy in the treatment of advanced head and neck malignancy.
Patients with advanced head and neck cancer continue to present a difficult management problem for the otolaryngologist-head and neck surgeon. This paper discusses the principles of radiation therapy with emphasis on neutron beam therapy as an effective treatment option for advanced malignancy of the head and neck other than squamous cell carcinoma.


Amiodarone used in successful resuscitation after near-fatal flecainide overdose.
We report the case of a 45-year-old woman who had ingested 2000 mg of flecainide with suicidal intent. She developed therapy-resistant ventricular fibrillation (VF) with cardiopulmonary arrest. Cardiopulmonary resuscitation and advanced life support were sustained for 64 min. Following intravenous amiodarone, the patient developed an effective spontaneous rhythm and resumed breathing. An amiodarone infusion was started and continued over a period of 72 h. She recovered completely after 5 days, leaving the hospital without neurological sequelae. Serum flecainide levels approximately 5 h post-ingestion were 850 mg/l. This case report confirms the value of amiodarone in drug-resistant VF, even when the cause may be another antiarrhythmic drug such as flecainide.