A study on community older people's willingness to use smart home-an extended technology acceptance model with intergenerational relationships.
Despite the potential of smart home technology to promote sustainable lifestyles, the adoption rate among older adults remains relatively low. This study aims to investigate the influence of intergenerational relationships on the acceptance of smart home services among seniors. A survey was conducted among 298 older adults in China, and data were analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). Ten predictor variables were examined to assess their impact on the willingness to use smart home services. Intergenerational relationships significantly influenced the utilization of smart home services among older adults. Specifically, intergenerational instrumental support had a direct positive effect on the behavioral intention to use smart homes. Additionally, intergenerational emotional and financial support affected life satisfaction, which subsequently influenced the behavioral intention to use smart homes. The assistance and guidance provided by younger generations play a crucial role in shaping the willingness of older adults to adopt smart home technology. Intergenerational support can contribute positively to enabling aging individuals to age in place through the utilization of technology.


A five-factor biomarker profile obtained week 4-12 of treatment for improved prognostication in metastatic renal cell carcinoma: Results from DARENCA study 2.
Several biomarkers of treatment efficacy have been associated with a better prognosis in patients with metastatic renal cell carcinoma (mRCC). The prognostic significance of biomarkers in the early treatment phase is unclear. In a complete national cohort of mRCC patients receiving first-line tyrosine kinase inhibitors (TKI) or interleukin-2 based immunotherapy (IT) from 2006 to 2010, overall survival (OS) was analysed for baseline International mRCC Database Consortium (IMDC) classification factors and on-treatment time-dependent biomarkers obtained day 1 each cycle week 4-12 after treatment initiation with multivariate analysis and bootstrap validation. A total of 735 patients received first-line TKI (59%) or IT (41%). Median OS was overall 14.0 months and 33.4, 18.5, and 5.8 months for baseline IMDC favourable, intermediate, and poor risk groups, respectively (p < 0.0001). Systolic blood pressure ≥140 mmHg, neutrophils < lower level of normal (LLN), platelets < LLN, sodium ≥ LLN, and LDH ≤1.5 times upper level of normal after treatment initiation were significantly associated with favourable OS independent of baseline IMDC risk group in multivariate analyses stratified for TKI and IT (p ≤ 0.04). Concordance (C)-index for IMDC classification alone was 0.625 (95% CI 0.59-0.66) and combined with the five-factor biomarker profile 0.683 (95% CI 0.64-0.72). For patients with good (3-5 factors) and poor (0-2 factors) biomarker profile median OS were 23.5 and 9.6 months, respectively (p < 0.0001). Adding the five-factor biomarker profile significantly improved prognostication in IMDC intermediate (25.7 vs. 12.0 months, p < 0.0001) and poor (12.8 vs. 6.4 months, p < 0.0001) risk groups. A trend was seen in IMDC favourable risk group (38.9 vs. 28.7 months, p = 0.112). On-treatment hypertension, neutropenia, thrombocytopenia, LDH below 1.5 times upper level of normal, and normal sodium, obtained week 4-12 of treatment, are independent biomarkers of favourable outcome in mRCC, independent of treatment type.


Antibiotic resistance in Lactococcus species from bovine milk: presence of a mutated multidrug transporter mdt(A) gene in susceptible Lactococcus garvieae strains.
A total of 72 Lactococcus strains (41 Lactococcus lactis and 31 Lactococcus garvieae) isolated from bovine milk were tested for susceptibility to 17 antibiotics and screened for the presence of antibiotic resistance genes using a microarray. Resistance to tetracycline, clindamycin, erythromycin, streptomycin, nitrofurantoin were found. The tetracycline-resistant L. garvieae and L. lactis harbored tet(M) and tet(S). L. lactis that were resistant to clindamycin were also resistant to erythromycin and possessed the erm(B) gene. The multidrug transporter mdt(A), originally described in L. lactis, was detected for the first time in L. garvieae and does not confer decreased susceptibility to erythromycin nor tetracycline in this species. Mdt(A) of L. garvieae contains one mutation in each antiporter motif C, which is known to play an essential role in drug efflux antiporters. This suggests that the mutations found in the C-motifs of Mdt(A) from L. garvieae may be responsible for susceptibility. The study revealed the presence of antibiotic resistance genes in non-pathogenic and pathogenic lactococci from bovine milk, including a mutated multidrug transporter in L. garvieae.


[Use of the indices of the kallikrein-kinin system of the blood in evaluating the efficacy of the prevention and treatment of postoperative purulent complications in oncologic patients].
The kallikrein-kinin system of the blood was studied in 59 patients with tumours of the abdominal cavity and small pelvis. In 33 patients, the postoperative course was complicated by wound suppuration, formation of intraabdominal and pelvic abscesses. It was established, that the development of purulent complications was accompanied by regular activation of the system of proteolysis and increase in the blood level of the middle molecular mass substances. The changes in the indices of kallikrein-kinin system can serve as an additional criterium of the effectiveness of treatment and prophylaxis of postoperative complications.


A threshold membrane potential accounts for controversial effects of fatty acids on mitochondrial oxidative phosphorylation.
The uncoupling effect of free fatty acids on oxidative phosphorylation in mitochondria has been known for more than 35 years. The mechanism of action, however, remains controversial. In this report the physicochemical basis of uncoupling was elucidated by studying the effect of free fatty acids on the proton permeability and membrane potential of proteoliposomes containing reconstituted cytochrome c oxidase (COX). A threshold membrane potential of about 125 mV was identified for fatty acid-induced proton permeability. Only above this potential do free fatty acids translocate protons across the biological membrane. The data explain the controversial effects of long-chain fatty acids on oxidative phosphorylation as well as their role on non-shivering thermogenesis in larger mammals.


Subgenual cingulate connectivity as a treatment predictor during low-frequency right dorsolateral prefrontal rTMS: A concurrent TMS-fMRI study.
Repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC) is effective in alleviating treatment-resistant depression (TRD). It has been proposed that regions within the left DLPFC that are anti-correlated with the right subgenual anterior cingulate cortex (sgACC) may represent optimal individualized target sites for high-frequency left rTMS (HFL). This study aimed to explore the effects of low-frequency right rTMS (LFR) on left sgACC connectivity during concurrent TMS-fMRI. 34 TRD patients underwent an imaging session that included both a resting-state fMRI run (rs-fMRI0) and a run during which LFR was applied to the right DLPFC (TMS-fMRI). Participants subsequently completed four weeks of LFR treatment. The left sgACC functional connectivity was compared between the rs-fMRI0 run and TMS-fMRI run. Personalized e-fields and a region-of-interest approach were used to calculate overlap of left sgACC functional connectivity at the TMS target and to assess for a relationship with treatment effects. TMS-fMRI increased left sgACC functional connectivity to parietal regions within the ventral attention network; differences were not significantly associated with clinical improvements. Personalized e-fields were not significant in predicting treatment outcomes (p = 0.18). This was the first study to examine left sgACC anti-correlation with the right DLPFC during an LFR rTMS protocol. In contrast to studies that targeted the left DLPFC, we did not find that higher anti-correlation was associated with clinical outcomes. Our results suggest that the antidepressant mechanism of action of LFR to the right DLPFC may be different than for HFL.


Expression of carbohydrate binding protein 35 in human fibroblasts: comparisons between cells with different proliferative capacities.
Carbohydrate Binding Protein 35 (CBP35) is a galactose-specific lectin found in the nucleus and cytoplasm of mouse 3T3 fibroblasts. In these cultures, the level of expression and nuclear localization of CBP35 was correlated with the proliferative state of the cells. CBP35 is also found in human fibroblasts. We have compared the expression and localization of CBP35 in human fibroblasts of different replicative capacities: young (passage 11), intermediate (passage 19), and old (passage 33) SL66 cells, and fibroblasts derived from a patient with Werner's syndrome. The results indicate that the expression of CBP35 in cells with either age-acquired or congenital replicative deficiencies was unresponsive to serum stimulation, in contrast with that found in young normal human fibroblasts and in 3T3 cells.


The teratogenic effects of imatinib mesylate on rat fetuses.
Imatinib mesylate, a selective tyrosine kinase inhibitor, is the first line treatment against chronic myelogenous leukemia and gastrointestinal stromal tumors. The aim of the present study is to investigate the effects of imatinib mesylate on the pregnant rats and their fetuses. Pregnant rats were divided into three groups; the first group served as a control group. The second and third groups were orally administered imatinib at doses of 36 mg/kg body weight or 54 mg/kg b.wt. on gestation days (SDs) 6 through 13 or SDs 13 through 19, respectively. All animals were sacrificed on the 20th day of gestation. Treatment with imatinib caused a reduction of maternal body weight gain, uterine and placental weights, increased rate of abortion and fetal resorptions. High dose of imatinib caused fetal congenital deformities represented in harelip, contraction of the fore limbs, and paralysis of the hind limbs, exencephaly, encephalocoele and distended abdominal wall, besides occurrence of wavy ribs and absence of other ribs in addition to skeletal growth retardation and lack of ossification of the most skeletal elements. The present work concluded that imatinib is teratogenic when given orally to pregnant rats at 54 mg/kg b.wt. and causes direct maternal or developmental toxicity.


Harnessing the Immune System Against Leukemia: Monoclonal Antibodies and Checkpoint Strategies for AML.
Acute myeloid leukemia (AML) is the most common leukemia among adults and is associated with a poor prognosis, especially in patients with adverse prognostic factors, older age, or relapsed disease. The last decade has seen a surge in successful immune-based therapies in various solid tumors; however, the role of immune therapies in AML remains poorly defined. This chapter describes the rationale, clinical data, and toxicity profiles of immune-based therapeutic modalities in AML including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, chimeric antigen receptor (CAR)-T cells, and checkpoint blockade via blockade of PD1/PDL1 or CTLA4. Monoclonal antibodies commonly used in AML therapy target highly expressed "leukemia" surface antigens and include (1) naked antibodies against common myeloid markers such as anti-CD33 (e.g., lintuzumab), (2) antibody-drug conjugates linked to either, (a) a highly potent toxin such as calicheamicin, pyrrolobenzodiazepine, maytansine, or others in various anti-CD33 (gemtuzumab ozogamicin, SGN 33A), anti-123 (SL-401), and anti-CD56 (lorvotuzumab mertansine) formulations, or (b) radioactive particles, such as 131I, 213Bi, or 225Ac-labeled anti-CD33 or CD45 antibodies. Novel monoclonal antibodies that recruit and promote proximity-induced cytotoxicity of tumor cells by T cells (bispecific T-cell engager [BiTE] such as anti CD33/CD3, e.g., AMG 330) or block immune checkpoint pathways such as CTLA4 (e.g., ipilimumab) or PD1/PD-L1 (e.g., nivolumab) unleashing the patients T cells to fight leukemic cells are being evaluated in clinical trials in patients with AML. The numerous ongoing clinical trials with immunotherapies in AML will improve our understanding of the biology of AML and allow us to determine the best approaches to immunotherapy in AML.


Knockdown of H19 Attenuates Ox-LDL-induced Vascular Smooth Muscle Cell Proliferation, Migration, and Invasion by Regulating miR-599/PAPPA Axis.
Long noncoding RNAs could participate in the development of atherosclerosis (AS). However, the underlying mechanism by which long noncoding RNA H19 is implicated in AS remains largely unknown. In this study, we investigated the function of H19 on cell proliferation, migration, and invasion in oxidized low-density lipoprotein (ox-LDL)-treated human aortic vascular smooth muscle cells (HA-VSMCs), and on hyperlipidemia response in high-fat diet (HFD)-treated ApoE-/- mice. Moreover, we explored the target interaction among H19, microRNA (miR)-599, and pappalysin 1 (PAPPA). Our results showed that H19 expression was elevated in serum samples of patients with AS and ox-LDL-treated HA-VSMC. H19 silence mitigated ox-LDL-induced proliferation, migration, and invasion of HA-VSMCs. H19 acted as a sponge for miR-599, and miR-599 knockdown reversed the suppressive effect of H19 silence on proliferation, migration, and invasion of HA-VSMCs. PAPPA was a target of miR-599 and attenuated the inhibitive role of miR-599 in HA-VSMC processes. H19 knockdown repressed PAPPA expression by increasing miR-599. Moreover, H19 interference alleviated hyperlipidemia response in HFD-treated ApoE-/- mice. Collectively, knockdown of H19 inhibited proliferation, migration, and invasion of ox-LDL-treated HA-VSMCs and hyperlipidemia response in HFD-treated ApoE-/- mice by regulating miR-599/PAPPA axis, indicating H19 might act as a potential target for the treatment of AS.


Reactive oxygen species derived from the mitochondrial respiratory chain are not responsible for the basal levels of oxidative base modifications observed in nuclear DNA of Mammalian cells.
The mitochondrial electron transport chain (ETC) is the most important source of reactive oxygen species (ROS) in mammalian cells. To assess its relevance to the endogenous generation of oxidative DNA damage in the nucleus, we have compared the background (steady-state) levels of oxidative DNA base modifications sensitive to the repair glycosylase Fpg (mostly 7,8-dihydro-8-oxoguanine) in wild-type HeLa cells and HeLa rho0 cells. The latter are depleted of mitochondrial DNA and therefore are unable to produce ROS in the ETC. Although the levels of ROS measured by flow cytometry and redox-sensitive probes in rho0 cells were only 10-15% those of wild-type cells, steady-state levels of oxidative DNA base modifications were the same as in wild-type cells. Mitochondrial generation of ROS was then stimulated in HeLa wild-type cells using inhibitors interfering with the ETC. Although mitochondrial ROS production was raised up to 6-fold, none of the substances nor their combinations induced additional oxidative base modifications in the nuclear DNA. This was also true for glutathione-depleted cells. The results indicate that the contribution of mitochondria to the endogenously generated background levels of oxidative damage in the nuclear DNA is negligible.


Relationship of meteorological factors and human brucellosis in Hebei province, China.
Brucellosis has always been one of the major public health problems in China. Investigating the influencing factors of brucellosis is conducive to its prevention and control. The incidence trend of brucellosis shows an obvious seasonality, suggesting that there may be a correlation between brucellosis and meteorological factors, but related studies were few. We aimed to use the autoregressive integrated moving average (ARIMA) model to analyze the relationship between meteorological factors and brucellosis. The data of monthly incidence of brucellosis and meteorological factors in Hebei province from January 2004 to December 2015 were collected from the Chinese Public Health Science Data Center and Chinese meteorological data website. An ARIMA model incorporated with covariables was conducted to estimate the effects of meteorological variables on brucellosis. There was a highest peak from May to July every year and an upward trend during the study period. Atmospheric pressure, wind speed, mean temperature, and relative humidity had significant effects on brucellosis. The ARIMA(1,0,0)(1,1,0)12 model with the covariates of atmospheric pressure, wind speed and mean temperature was the optimal model. The results showed that the atmospheric pressure with a 2-month lag (β = -0.004, p = 0.037), the wind speed with a 1-month lag (β = 0.030, p = 0.035), and the mean temperature with a 2-month lag (β = -0.003, p = 0.034) were significant predictors. Our study suggests that atmospheric pressure, wind speed, mean temperature, and relative humidity have a significant impact on brucellosis. Further understanding of its mechanism would help facilitate the monitoring and early warning of brucellosis.


A remarkable response of chronic severe obsessive-compulsive neurosis to phenelzine.
The author describes a 22-year-old male who suffered from chronic severe Obsessive-Compulsive Neurosis (OCN) complicated by frequent depressive episodes. Administering the monoamine oxidase inhibitor phenelzine in high dosage led to complete alleviation of his depression in 10 weeks, and 3 weeks afterwards the OCN was markedly improved. The illness relapsed shortly after discontinuance of the drug.


Congenital pulmonary arteriovenous malformations.
We report the rare case of an 11-year-old boy who presented with intractable hypoxaemia and a pulmonary mass. Investigations revealed this to be a pulmonary arteriovenous malformation. It was entirely confined to the right middle lobe and was successfully treated via a right middle lobectomy. The relevant literature with respect to both diagnosis and treatment is reviewed.


Effect of lysozyme concentration, heating at 90 degrees C, and then incubation at chilled temperatures on growth from spores of non-proteolytic Clostridium botulinum.
The heat treatment necessary to inactivate spores of non-proteolytic Clostridium botulinum in refrigerated, processed foods may be influenced by the occurrence of lysozyme in these foods. Spores of six strains of non-proteolytic Cl. botulinum were inoculated into tubes of an anaerobic meat medium, to give 10(6) spores per tube. Hen egg white lysozyme (0-50 micrograms ml-1 was added, and the tubes were given a heat treatment equivalent to 19.8 min at 90 degrees C, cooled, and incubated at 8 degrees, 12 degrees, 16 degrees and 25 degrees C for up to 93 d. In the absence of added lysozyme, neither growth nor toxin formation were observed. A 6-D inactivation was therefore achieved. In tubes to which lysozyme (5-50 micrograms ml-1 had been added prior to heating, growth and toxin formation were observed. With lysozyme added at 50 micrograms ml-1, growth was first observed after 68 d at 8 degrees C, 31 d at 12 degrees C, 24 d at 16 degrees C, and 9 d at 25 degrees C. Thus, in these circumstances, a heat treatment equivalent to 19.8 min at 90 degrees C was not sufficient, on its own, to give a 6-D inactivation. A combination of the heat treatment, maintenance at less than 12 degrees C, and a shelf-life not more than 4 weeks reduced the risk of growth of non-proteolytic Cl. botulinum by a factor of 10(6).


Prolonged effects of MK-801 in the cat during focal cerebral ischemia and recovery: survival, EEG activity and histopathology.
Previously we reported an improvement in histological outcome in cats treated with MK-801 shortly after the induction of temporary middle cerebral artery occlusion, and examined after 2 h of ischemia followed by 4 h of reperfusion. This study investigates the prolonged effects of the same drug treatment. Focal cerebral ischemia was produced in 34 cats by temporary occlusion of the left middle cerebral artery for 2 h. Stroke severity was determined using the ratio of the EEG amplitude from the ipsilateral to that of the contralateral hemisphere. Thirty minutes after the onset of ischemia, cats were treated i.v. with either 1 mg/kg MK-801 or saline. Electrocortical activity of the animals who survived were followed for 6 days postocclusion at which point they were sacrificed for histopathological analysis. Twelve of the animals died during recovery, of which 4 were MK-801 treated, and 8 were saline controls. The EEG ratios in the non-surviving animals were more depressed than in the animals that survived, whereas the depression in the EEG amplitude in both the treated and the control surviving animals was equal. Among the survivors no reduction in infarct size with MK-801 treatment was observed. Thus treatment with MK-801 in the middle cerebral artery occlusion model in the cat leads to a significant increase in the rate of survival (P < 0.05), but no prolonged improvement in late histopathology, in contrast with acute histological findings using this model. MK-801 treatment may be shifting the stroke model towards the survival of animals with larger infarcts. Histological recovery during prolonged reperfusion may eliminate the early neuroprotective effects seen with MK-801 treatment.


Effects of electrical stimulation of the hunger center in the lateral hypothalamus and food reinforcement on impulse activity of the mylohyoid muscle in rabbits under conditions of hunger and satiety.
Effects of electrical stimulation of the hunger center in the lateral hypothalamus and food reinforcement on impulse activity of mylohyoid muscle were studied in chronic experiments under conditions of hunger and satiety. Threshold stimulation of the lateral hypothalamus in starving and satiated rabbits in the absence of food induced searching behavior associated with burst-like impulse activity with a bimodal distribution of interpulse intervals. Regular spike burst in the mylohyoid muscle during stimulation of the lateral hypothalamus in the absence of food serves as an example of the anticipatory type reaction. Increased food motivation during threshold stimulation of the lateral hypothalamus in starving and satiated rabbits with food offered led to successful food-procuring behavior, during which the frequency of spike bursts in the mylohyoid muscle became comparable with that under conditions of natural foraging behavior stimulated by the need in nutrients. Our results suggest that temporal structure of mylohyoid muscle impulse activity reflects convergent interactions of food-motivation excitation with reinforcement excitation on neurons of the masticatory and deglutitive centers.


Green One-Step Synthesis of Silver Nanoparticles Obtained from Schinus areira Leaf Extract: Characterization and Antibacterial Mechanism Analysis.
The increased emergence of antibiotic-resistant bacteria is a serious health problem worldwide. In this sense, silver nanoparticles (AgNPs) have received increasing attention for their antimicrobial activity. In this context, the goal of this study was to produce AgNPs by a green synthesis protocol using an aqueous leaf extract of Schinus areira as biocomposite to later characterize their antimicrobial action. The nanomaterials obtained were characterized by UV‒vis spectroscopy, DLS, TEM, and Raman, confirming the presence of quasi-spherical AgNPs with a negative surface charge and diameter around 11 nm. Afterward, the minimum inhibitory and bactericidal concentration of the AgNPs against Staphylococcus aureus and Escherichia coli were obtained, showing high antibacterial activity. In both of the examined bacteria, the AgNPs were able to raise intracellular ROS levels. In E. coli, the AgNPs can harm the bacterial membrane as well. Overall, it can be concluded that it was possible to obtain AgNPs with colloidal stability and antibacterial activity against Gram-positive and Gram-negative bacteria. Our findings point to at least two separate mechanisms that can cause cell death, one of which involves bacterial membrane damage and the other of which involves intracellular ROS induction.


Hypokalemic thyrotoxic paralysis: a rare cause of tetraparesis with acute onset in Europeans.
We describe a 21-year-old Italian male affected by hypokalemic tetraparesis with acute onset. In the emergency ward, the patient was agitated, with tachycardia (140/min) and systolic hypertension (180/70 mm Hg). He was not able to flex the lower extremities against a light resistance and furthermore, he was hypotonic and without tendon reflexes. One hour later he developed strength deficit of the upper extremities as well. Biochemical analyses revealed severe hypopotassemia (2.1 meg/l). After administration of 140 meq potassium phosphate, the patient began to improve, and 12 h after the onset he was able to walk normally. Successive investigations documented an undiagnosed case of Graves' disease. Thyrotoxic hypokalemic paralysis has been observed almost only in Asians, however, with this case and others reported, we believe that it should be considered as a cause of muscular paralysis also in Caucasians.


Critical review on the stability of illicit drugs in sewers and wastewater samples.
Wastewater-based epidemiology (WBE) applies advanced analytical methods to quantify drug residues in wastewater with the aim to estimate illicit drug use at the population level. Transformation processes during transport in sewers (chemical and biological reactors) and storage of wastewater samples before analysis are expected to change concentrations of different drugs to varying degrees. Ignoring transformation for drugs with low to medium stability will lead to an unknown degree of systematic under- or overestimation of drug use, which should be avoided. This review aims to summarize the current knowledge related to the stability of commonly investigated drugs and, furthermore, suggest a more effective approach to future experiments. From over 100 WBE studies, around 50 mentioned the importance of stability and 24 included tests in wastewater. Most focused on in-sample stability (i.e., sample preparation, preservation and storage) and some extrapolated to in-sewer stability (i.e., during transport in real sewers). While consistent results were reported for rather stable compounds (e.g., MDMA and methamphetamine), a varying range of stability under different or similar conditions was observed for other compounds (e.g., cocaine, amphetamine and morphine). Wastewater composition can vary considerably over time, and different conditions prevail in different sewer systems. In summary, this indicates that more systematic studies are needed to: i) cover the range of possible conditions in sewers and ii) compare results more objectively. To facilitate the latter, we propose a set of parameters that should be reported for in-sewer stability experiments. Finally, a best practice of sample collection, preservation, and preparation before analysis is suggested in order to minimize transformation during these steps.


Origin of both coronary arteries from the pulmonary artery and aortic coarctation.
Single trunk anomalous origin of both coronary arteries from the pulmonary artery is a rare congenital cardiac anomaly. We report on 2 cases of its association with aortic coarctation, the diagnosis of which in living patients is very difficult. We think that the possibility of this anatomic arrangement should always be considered in patients with isolated aortic coarctation whose clinical condition seems impaired rather than improved after an apparently successful coarctectomy.


HDlive imaging of fetal enteric duplication cyst.
Enteric duplication cysts are rare congenital anomalies, but their antenatal diagnosis is becoming more common because of advances in ultrasonography. With the latest state-of-the-art technology, HDlive facilitates a more realistic anatomical visualization of different fetal organ structures, making diagnosis more precise. We present a case of antenatal HDlive imaging of an enteric duplication cyst. A 26-year-old pregnant Japanese woman was referred to our ultrasound clinic because of a fetal intra-abdominal cyst at 27 weeks of gestation. Two-dimensional (2D) ultrasound revealed a sonolucent, ellipsoid structure in the subhepatic area. Magnetic resonance imaging yielded the same findings. However, irregular internal echoes appeared at 33 weeks of gestation. There was no vascularity on color Doppler. HDlive clearly depicted a more realistic image of the circular mass, which was thick walled, with a large amount of debris inside, and showed no communication with adjacent structures. Careful monitoring was conducted for these unusual findings. A day after delivery, an emergency operation was performed because the infant had sudden signs and symptoms of obstruction. Intra-operative findings were ileus and a necrotic ileal duplication cyst confirmed by histopathologic studies. Complications of enteric duplication cyst can arise at any time of life, and so thorough monitoring may be recommended. The findings of irregular internal echoes and a large amount of debris inside the cyst are relatively characteristic features of a complicated cyst. HDlive gives us additional information on the actual appearance of a complicated cyst that may be difficult to obtain using conventional 2D sonography alone. HDlive can be very useful in the antenatal surveillance of enteric duplication cysts.


[Adaptive capacities of children with different number of congenital morphogenetic variants].
Adaptive capacities were studied in 6-7-year-ol apparently healthy children in relation to the number of congenital morphogenetic variants (CMVs). The most markedly reduced adaptive capacities were revealed in children with 5 CMVs or more.


Balloon pulmonary valvuloplasty in a child with Ebstein's anomaly and valvar pulmonary stenosis.
We performed a balloon pulmonary valvuloplasty in a child with Ebstein's anomaly using the standard technique. The procedure reportedly has not been performed in the face of this defect and, although difficult, was safely and successfully accomplished. In patients with Ebstein's anomaly and right ventricular outflow obstruction compounded by pulmonary valve stenosis, application of this technique may delay the need for surgical intervention.


External Validation of a Five-Tiered CT Algorithm for the Diagnosis of Clear Cell Renal Cell Carcinoma: A Retrospective Five-Reader Study.
BACKGROUND. In 2022, a five-tiered CT algorithm was proposed for predicting whether a small (cT1a) solid renal mass represents clear cell renal cell carcinoma (ccRCC). OBJECTIVE. The purpose of this external validation study was to evaluate the proposed CT algorithm for diagnosis of ccRCC among small solid renal masses. METHODS. This retrospective study included 93 patients (median age, 62 years; 42 women, 51 men) with 97 small solid renal masses that were seen on corticomedullary phase contrast-enhanced CT performed between January 2012 and July 2022 and subsequently underwent surgical resection. Five readers (three attending radiologists, two clinical fellows) independently evaluated masses for the mass-to-cortex corticomedullary attenuation ratio and heterogeneity score; these scores were used to derive the CT score by use of the previously proposed CT algorithm. The CT score's sensitivity, specificity, and PPV for ccRCC were calculated at threshold of 4 or greater, and the NPV for ccRCC was calculated at a threshold of 3 or greater (consistent with thresholds in studies of the MRI-based clear cell likelihood score and the CT algorithm's initial study). The CT score's sensitivity and specificity for papillary RCC were calculated at a threshold of 2 or less. Interreader agreement was assessed using the Gwet agreement coefficient (AC1). RESULTS. Overall, 61 of 97 masses (63%) were malignant and 43 of 97 (44%) were ccRCC. Across readers, CT score had sensitivity ranging from 47% to 95% (pooled sensitivity, 74% [95% CI, 68-80%]), specificity ranging from 19% to 83% (pooled specificity, 59% [95% CI, 52-67%]), PPV ranging from 48% to 76% (pooled PPV, 59% [95% CI, 49-71%]), and NPV ranging from 83% to 100% (pooled NPV, 90% [95% CI, 84-95%]), for ccRCC. A CT score of 2 or less had sensitivity ranging from 44% to 100% and specificity ranging from 77% to 98% for papillary RCC (representing nine of 97 masses). Interreader agreement was substantial for attenuation score (AC1 = 0.70), poor for heterogeneity score (AC1 = 0.17), fair for five-tiered CT score (AC1 = 0.32), and fair for dichotomous CT score at a threshold of 4 or greater (AC1 = 0.24 [95% CI, 0.14-0.33]). CONCLUSION. The five-tiered CT algorithm for evaluation of small solid renal masses was tested in an external sample and showed high NPV for ccRCC. CLINICAL IMPACT. The CT algorithm may be used for risk stratification and patient selection for active surveillance by identifying patients unlikely to have ccRCC.


The influence of oral magnesium sulfate on skin microvasculature blood flow in diabetic rats.
Microvascular disease is a major feature of type1 diabetes and results from long-standing structural and functional changes especially in the skin microvasculature. Magnesium (Mg) deficiency has recently been proposed as a novel factor implicated in the pathogenesis of diabetes complications such as vascular disturbance, but its mechanism of action is not completely elucidated. The present study was designed to determine whether chronic magnesium sulfate administration could control streptozocin-induced diabetes and improve endothelium-dependent and endothelium-independent dilatation, and identify its probable mechanism in the skin microvasculature of diabetic rats. Fifty male Wistar rats (220 ± 10 g) were divided into two diabetic and one control groups. One subgroup of diabetic received magnesium sulfate (10 g/l) in their drinking water, while two other groups had only tap water. Laser Doppler flow meter with iontophoresis was used to measure the relative changes in skin blood flow. We used acetylcholine (Ach), sodium nitroprusside (SNP), and N (w)-nitro-L-arginine (LNNA; NO synthase inhibitor) with magnesium sulfate (0.1 M) in control and experimental animal by microsyringe pump microinjection. SNP- and Ach-induced cutaneous perfusion increased significantly by Mg treatment in the diabetic groups, and local microinjection of magnesium sulfate (0.1 M) increased cutaneous blood flow in all groups (p < 0.01). However, the administration of LNNA prior to magnesium sulfate attenuated (p < 0.05) but not abolished the increase in cutaneous blood flow in diabetic and normal rats. From the results of this study, it may be concluded that Mg could improve skin microvasculature of diabetic rats with potentiation of nitric oxide pathway.


Elevated sister chromatid exchange rate in lymphocytes of subjects treated with arsenic.
An elevated sister chromatid exchange (SCE) rate was found in the lymphocytes of six patients treated with arsenic. All had stigmata of arsenic use as well as biopsy-proven skin cancers. The arsenic exposed patients had a mean of 14.00 SCE/mitosis while 44 normal controls had a mean of 5.8 SCE/mitosis. Chromosome breakage analysis revealed no difference between the two groups. SCE rate has been shown to be elevated in a variety of systems where cell cultures or experimental animals were exposed to known mutagens and carcinogens. We suggest that the relationship carcinogen exposure-elevated SCE rate-cancer may also be valid in humans treated with arsenic.


NUDT1: A potential independent predictor for the prognosis of patients with oral squamous cell carcinoma.
The current study was aimed to investigate the association of nudix hydrolase 1 (NUDT1) levels with the prognosis of oral squamous cell carcinoma (OSCC) patients. Western immunoblotting and qRT-PCR were used to detect the protein and mRNA levels of NUDT1 in 31 cases of OSCC and normal tissues. The paraffin-embedded 62 cases of OSCC and 18 normal tissues were collected, and the pathological alterations were assessed by immunohistochemistry. The prognosis of all patients was followed up. Kaplan-Meier method was used to analyze the survival rate, and Cox regression was used for multivariate analysis. Both the protein and gene levels of NUDT1 were statistically increased (P = .0007 and P < .0001) in the OSCC tissue and had a significant association with the histopathologic grades of OSCC (P < .0001 and P = .0223). Immunohistochemistry detection of NUDT1 in 62 human OSCC tissues and 18 normal control tissues showed that NUDT1 expression was significantly increased in OSCC tissue and showed a strong association with histopathologic grades (P < .0001) and tumor stage (P = .005). Patients with high NUDT1 expression exhibited poorer overall survival rate (OS) and tumor-specific survival rate (TSS) than those with low NUDT1 expression (P < .0001 and P = .0008), and NUDT1 was independent prognostic factors for OS and TSS (P < .0001 and P < .001). The expression level of NUDT1 might be used to predict the prognosis of OSCC patients.


Research on the investment efficiency based on grey correlation-DEA model.
Small and medium-sized enterprises (SMEs) are an important part of stimulating market vitality. In the post-pandemic era, the ability of SMEs to absorb employment plays an important role in stabilizing society and promoting economic growth. This paper selects 226 sample data from 2014 to 2017 measures the investment efficiency of small and medium-sized enterprises and makes a further analysis its influencing factors. Because there is a lag between investment and output. In this paper, the grey correlation analysis is used. Measuring the investment efficiency of SMEs by using BBC-DEA method. The study found that the overall investment efficiency of SMEs is low. Considering from the inside of the enterprise, this paper uses the Tobit model to make an empirical analysis. It is found that the influence of board structure and agency cost on investment efficiency are significantly negative. Growth, ownership concentration, equity incentive, salary incentive, profitability of SMEs have a significant positive effect on the investment efficiency of enterprises.


Two new triterpenoid saponins from the carpophore of Xanthoceras sorbifolia Bunge.
Two new triterpenoid saponins (1, 2) and a known sapogenin (3) were isolated from the dried carpophore of Xanthoceras sorbifolia Bunge. (Sapindaceae), and their structures were established as 3-O-beta-d-glucopyranosyl, 28-O-[alpha-l-rhamnosyl (1 --> 2)]-beta-d-glucopyranosyl 16-deoxybarrin-gtogenol C (1), 3-O-[beta-d-glucopyranosyl(1 --> 6)] 3'-angeloyl)-beta-d-glucopyranosyl, 28-O-[alpha-l-rhamnosyl(1 --> 2)]-beta-d-glucopyranosyl 16-deoxybarringtogenol C (2), 16-deoxybarringtogenol C (3), by spectral and chemical methods. Compounds 1 and 2 were found to have activity of inhibiting the proliferation of two human tumour cell lines while compound 3 was inactive.


Addition of Flucytosine to Fluconazole for the Treatment of Cryptococcal Meningitis in Africa: A Multicountry Cost-effectiveness Analysis.
Mortality from cryptococcal meningitis remains very high in Africa. In the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) trial, 2 weeks of fluconazole (FLU) plus flucytosine (5FC) was as effective and less costly than 2 weeks of amphotericin-based regimens. However, many African settings treat with FLU monotherapy, and the cost-effectiveness of adding 5FC to FLU is uncertain. The effectiveness and costs of FLU+5FC were taken from ACTA, which included a costing analysis at the Zambian site. The effectiveness of FLU was derived from cohorts of consecutively enrolled patients, managed in respects other than drug therapy, as were participants in ACTA. FLU costs were derived from costs of FLU+5FC in ACTA, by subtracting 5FC drug and monitoring costs. The cost-effectiveness of FLU+5FC vs FLU alone was measured as the incremental cost-effectiveness ratio (ICER). A probabilistic sensitivity analysis assessed uncertainties and a bivariate deterministic sensitivity analysis examined the impact of varying mortality and 5FC drug costs on the ICER. The mean costs per patient were US $847 (95% confidence interval [CI] $776-927) for FLU+5FC, and US $628 (95% CI $557-709) for FLU. The 10-week mortality rate was 35.1% (95% CI 28.9-41.7%) with FLU+5FC and 53.8% (95% CI 43.1-64.1%) with FLU. At the current 5FC price of US $1.30 per 500 mg tablet, the ICER of 5FC+FLU versus FLU alone was US $65 (95% CI $28-208) per life-year saved. Reducing the 5FC cost to between US $0.80 and US $0.40 per 500 mg resulted in an ICER between US $44 and US $28 per life-year saved. The addition of 5FC to FLU is cost-effective for cryptococcal meningitis treatment in Africa and, if made available widely, could substantially reduce mortality rates among human immunodeficiency virus-infected persons in Africa.


Therapeutic drug monitoring: a comprehensive and critical review of analytical methods for anticonvulsive drugs.
In the last 20 years, there has been considerable improvement in the determination of anticonvulsive drugs in body fluids. Gas-liquid chromatography, high-performance liquid chromatography and immunological methods (radio-, enzyme-, fluoro-, and nephelo-immunoassays) have progressively supplanted spectrophotometry and thin-layer chromatography. As the number of publications shows, these methods have included a great variety of procedures. At present, gas-liquid chromatography and enzyme-immunoassays are routinely performed, awaiting a wider spread of liquid chromatography and other immunological techniques. This paper is a comprehensive review of the analytical literature on the determination of phenobarbitone, primidone, phenytoin, carbamazepine, valproic acid, ethosuximide, clonazepam, and some of their metabolites in physiological fluids. Gas-liquid chromatographic methods are more particularly reviewed. In order to facilitate the choice between these procedures, a critical selection of the techniques is given and recommendations are made. Emphasis is laid on technical problems encountered with the assays, as well as the need for a rigorous analytical assessment and internal and external quality controls. This review is completed by considerations on the determination of the free drug fraction and on sample collection and storage.


Sympathetic control of substance P releasing enteric neurones in the guinea pig ileum.
The contractile response of the isolated guinea-pig ileum to cholecystokinin octapeptide (CCK-8) that remained in the presence of atropine was greatly inhibited by the substance P antagonist D-Pro2,D-Trp7,9-substance P. This indicates that the atropine-resistant contraction to CCK-8 is mediated by the release of substance P from enteric neurones. Activation of alpha-adrenergic receptors by noradrenaline, clonidine or mesenteric sympathetic nerve stimulation inhibited the atropine-resistant contraction to CCK-8 but did not affect the contractile effect of substance P. It is concluded that alpha-adrenergic receptors exert an inhibitory influence on the release of substance P from enteric neurones.


A critical examination of trends in outcomes over the last decade.
The past decade has seen substantial improvements in end-stage renal disease (ESRD) outcomes, especially mortality, in the United States. Incidence rates for treated ESRD have doubled for most age groups, probably because of improved survival among high-risk populations, such as patients with diabetes and hypertension. The ESRD patient population is becoming older and has a greater incidence of diabetes because of changes in the types of patients starting treatment. The number of patients added to the waiting list each year for transplants has increased dramatically, whereas the number of transplantations performed annually has remained relatively constant. Although transplantation is consequently less available than before, transplant survival, both of the patient and the graft, has improved dramatically. Length of stay for hospitalizations has decreased. Both dialysis mortality and all ESRD mortality have decreased. It is important to monitor such statistics to try and modify adverse trends in outcomes for patients with ESRD. The ability to monitor patient outcomes through national databases has improved greatly during the last decade. Large-scale population-based studies of practices and outcomes for patients with ESRD offer a potent addition to the previously available arsenal of research tools, which was previously dominated by studies from single or few institutions and more expensive randomized clinical trials.


Development of a Specific Latex Agglutination Test to Detect Antibodies of Enterovirus 71.
A latex agglutination test (LAT) was developed for the rapid detection of antibodies against the VP1 or VP1 proteins of Enterovirus 71 (EV71). The proteins of interest including prokaryotically expressed VP1 and two strains of anti-VP1 monoclonal antibody (McAb) against EV71 were covalently linked to carboxylated latex using ethyl-dimethyl-amino-propyl carbodiimide (EDC) to prepare sensitized latex beads. LAT was evaluated by an enzyme-linked immunosorbent assay (ELISA) as a reference test. The VP1-LAT showed a sensitivity of 87.0%, specificity of 88.9%, and an agreement ratio of 90.0% in detecting VP1 in 100 serum samples from experimentally infected mice, whereas these values were 86.8, 96.7, and 93.3%, respectively, for 608 clinical human serum samples. The VP1-LAT has advantages over other assays in terms of low cost, rapidity, chemical stability, high sensitivity, repeatability, and specificity. The LAT established in the present study is a rapid and simple test suitable for field monitoring of antibodies against VP1-EV71.


Gas chromatography-electron capture detection determination of Dacthal and its di-acid metabolite in soil after ultrasound-assisted extraction and in situ focused microwave-assisted derivatization.
A quantitative method for the determination of Dacthal and its di-acid metabolite in soil has been developed by coupling ultrasound-assisted extraction and microwave-assisted derivatization of the analytes prior to gas chromatography-electron capture detection for individual separation and measurement. The main factors affecting both extraction efficiency and derivatization were optimized by experimental design methodology. The proposed approach allows extraction of these pollutants from spiked sediment and soil with efficiencies similar to those provided by the reference method but with a drastic reduction of both the extraction and derivatization times. The repeatability of the analyses, expressed as RSD, of Dacthal and its di-acid metabolite was 4.6% and 5.4%, respectively; meanwhile, the RSD for within-laboratory reproducibility was 8.7% and 9.2%, respectively.


Transcription complex stability and chromatin dynamics in vivo.
Distant regulatory sequences affect transcription through long-range chromatin interactions. Visualization of transcriptional activity of genes that compete for distant elements, using the globin locus as a model, has revealed the dynamics of chromatin interactions in vivo. Multiple genes appear to be transcribed alternately rather than at the same time to generate several messenger RNAs in one cell. The regulator may stably complex with one gene at a time and switch back and forth between genes in a flip-flop mechanism.


Heparin detection based on the fluorescent turn-on probe of amino carbon quantum dots.
Amino-rich carbon quantum dots (CDs) were synthesized by hydrothermal treatment of ethylene glycol, glucose and polyethyleneimine. CDs have green fluorescence (excitation/emission peaks 435 nm/515 nm) and can be enhanced by the addition of heparin (Hep). A linear relationship between fluorescence intensity and heparin concentration was observed. The fluorescence turn-on probe used for Hep detection showed a very large detection range of 0.02-16 μM, covering different therapeutic ranges in clinical applications. The probe exhibited an ultra-low detection limit of 0.007 nM.


The need for mouse models in osteoporosis genetics research.
Osteoporosis, the progressive loss of bone mass resulting in fragility fractures, affects ∼75 million people in the United States, Europe and Japan. Bone mineral density (BMD) correlates with fracture risk and is widely used in clinical settings to predict fracture. Numerous studies have demonstrated that peak bone mass is highly heritable and consequently a number of genome-wide association studies (GWASs) have been conducted to identify the genes that regulate BMD. Traditional intercross mapping in the mouse has met with limited successes in the field of skeletal biology. With the advent of human GWAS, questions have arisen about the continued need for mouse models in genetics research. However, significant advances have been made in the field of mouse genetics, including new genetics resource populations and loci mapping techniques, which enable gene-level mapping resolution. In this review, we discuss the need for mouse models to help understand the skeletal biology underlying novel human GWAS findings, how loci discovered in the mouse can be used to complement GWAS analysis and highlight the recent advances made in the field of skeletal biology from the use of these new and developing resources. We conclude this paper with a discussion of the need for systems-level approaches in the skeletal biology field, with an emphasis on the need for pathway and network analyses.


Accelerated dynamic contrast enhanced MRI based on region of interest compressed sensing.
Magnetic Resonance Imaging (MRI) provides excellent soft tissue contrast with one significant limitation of slow data acquisition. Dynamic Contrast Enhanced MRI (DCE-MRI) is one of the widely employed techniques to estimate tumor tissue physiological parameters using contrast agents. DCE-MRI data acquisition and reconstruction requires high spatiotemporal resolution, especially during the post-contrast phase. The region of Interest Compressed Sensing (ROICS) is based on Compressed Sensing (CS) framework and works on the hypothesis that limiting CS to an ROI can achieve superior CS performance. In this work, ROICS has been demonstrated on breast DCE-MRI data at chosen acceleration factors and the results are compared with conventional CS implementation. Normalized Root Mean Square Error (NRMSE) was calculated to compare ROICS with CS quantitatively. CS and ROICS reconstructed images were used to compare Ktrans and ve values derived using standard Tofts Model (TM). This also validated the superior performance of ROICS over conventional CS. ROICS generated Concentration Time Curves (CTC's) at chosen acceleration factors follow similar trend as the ground truth data as compared to CS. Both qualitative and quantitative analyses show that ROICS outperforms CS particularly at acceleration factors of 5× and above.


Psychosocial predictors of weight loss and psychological adjustment following bariatric surgery and a weight-loss program: the mediating role of emotional eating.
To examine a structural equation model of the effects of personal and interpersonal factors on treatment outcome of bariatric surgery and weight-loss program. Forty-four participants of the surgery group and 47 participants of the diet group completed questionnaires before treatment and 1 year afterward. Predictor measures are as follows: social support, motivation for control, sense of control, self-esteem, neuroticism, fear of intimacy, and emotional eating (EE). Weight loss, quality of life, and mental health. Neurotic predisposition (NP), a latent variable indicated by neuroticism, low self-esteem, and fear of intimacy, had an effect on weight loss that was fully mediated by EE. NP also had an effect on quality of life improvement that was fully mediated by EE and weight loss in both treatment groups. Both NP and EE predict outcome of obesity treatments, but EE is the more proximal variable that mediates the effect of NP.


MetaGen: reference-free learning with multiple metagenomic samples.
A major goal of metagenomics is to identify and study the entire collection of microbial species in a set of targeted samples. We describe a statistical metagenomic algorithm that simultaneously identifies microbial species and estimates their abundances without using reference genomes. As a trade-off, we require multiple metagenomic samples, usually ≥10 samples, to get highly accurate binning results. Compared to reference-free methods based primarily on k-mer distributions or coverage information, the proposed approach achieves a higher species binning accuracy and is particularly powerful when sequencing coverage is low. We demonstrated the performance of this new method through both simulation and real metagenomic studies. The MetaGen software is available at https://github.com/BioAlgs/MetaGen .


A review of the biological and clinical characteristics of luminal-like oestrogen receptor-positive breast cancer.
Global gene expression profiling (GEP) studies of breast cancer have identified distinct biological classes with different clinical and therapeutic implications. Oestrogen receptor (ER) has been found to be a central marker of the molecular signature. GEP studies have consistently recognized a molecularly distinct class of tumours that is characterized by high-level expression of ER and other biomarkers recognized to be characteristic of normal luminal cells of the breast. This class is the largest of the GEP-defined molecular subclasses, comprising 60-70% of breast cancer cases. Moreover, it has been proposed that this group of tumours is composed of at least two subclasses distinguished by differing GEP profiles. At present, there is no consensus on the definition of the luminal subclasses and, in clinical practice, luminal-like tumours and ER-positive tumours are frequently considered to be the same. A better understanding of the biological features of luminal tumours could lead to their improved characterization and consistent identification. In this review, we explore the concept and definitions of the luminal-like class of breast carcinoma and their contribution to our understanding of their molecular features, clinical significance and therapeutic implications.


Functional disruption of cell wall invertase inhibitor by genome editing increases sugar content of tomato fruit without decrease fruit weight.
Sugar content is one of the most important quality traits of tomato. Cell wall invertase promotes sucrose unloading in the fruit by maintaining a gradient of sucrose concentration between source leaves and fruits, while invertase inhibitor (INVINH) regulates this process. In this study, knock-out of cell wall INVINH in tomato (SlINVINH1) was performed by genome editing using, CRISPR/Cas9 and Target-AID technologies. Most of the genome-edited lines set higher soluble solid content (SSC) fruit than the original cultivar 'Suzukoma', while fruit weight was different among the genome-edited lines. From these genome-edited lines, three lines (193-3, 199-2, and 247-2), whose SSC was significantly higher than 'Suzukoma' and fruit weight were almost the same as the original cultivar, were selected. The fruit weight and overall plant growth of the two lines were comparable to those of the original cultivar. In contrast, the fructose and glucose contents in the mature fruits of the two lines were significantly higher than those of the original cultivar. The mature fruits of genome edited line 193-3 showed the highest sugar content, and the fructose and glucose contents were 29% and 36% higher than that of the original cultivar, respectively. Whole genome sequence data showed no off-target mutations in the genome-edited lines. Non-target metabolome analysis of mature fruits revealed that fructose was the highest loading factor in principal component analysis (PCA) between the genome-edited line and the original cultivar, and no unexpected metabolites appeared in the genome-edited line. In this study, we succeeded in producing tomato lines with high sugar content without a decrease in fruit weight and deterioration of plant growth by knock-out of SlINVINH1 using genome editing technology. This study showed that functional disruption of SlINVINH1 is an effective approach to produce tomato cultivars with high sugar content.


Cardiac Hemangioma: A Comprehensive Analysis of 200 Cases.
Cardiac hemangioma is a rare clinical entity. An increasing number of cases have been reported in recent years. Most of them were found incidentally at autopsy or during clinical practice, and reported as isolated cases. Our study is the most comprehensive review of cardiac hemangioma to date. The clinical demographics, clinical features, histopathologic features, treatment, and prognosis of 200 cases are reported. Logistic regression analysis was performed to identify the independent predictors of hemangioma-related death and long-term adverse events. We provide a few recommendations for diagnosis and treatment of this uncommon and sometimes lethal disorder.


Carriage of Staphylococcus aureus and inflamed infusion sites with insulin-pump therapy.
The most common complication of continuous subcutaneous insulin infusion (CSII) is inflammation at the infusion site. To determine possible risk factors to these infections, we studied several factors in the management of CSII and compared the pyogenic skin inflammation rate, the carriage rate of Staphylococcus aureus, and the HbA1 level among 50 CSII-treated diabetic patients, 50 diabetic patients on insulin injections, 48 diabetic patients on oral medication, and 40 healthy volunteers. There was no increased carriage rate of S. aureus among CSII-treated patients (42%) as compared with the other groups. An unexpected inverse relationship existed between HbA1 level and carriage rate in the CSII-treated group (HbA1 5-8%, n = 16, 69%; HbA1 8-10% n = 15, 40%; HbA1 greater than 10, n = 19, 21% P = .02). Pyogenic skin inflammations were reported by 24 (48%) CSII-treated patients, of which 18 had infected infusion sites, 6 (12%) insulin injecting patients, 2 (4%) patients on oral medication, and 3 (8%) healthy volunteers (P less than .01). The occurrence of inflamed infusion sites was not associated with carriage of S. aureus, the indwelling time of the needle, or the insulin dosage per day. There was an association, however, with the type of insulin preparation classified according to the added preservative: m-cresol-containing insulin (n = 24, 54%); methyl p-hydroxybenzoate-containing insulin (n = 26, 19%, P = .02). We concluded that the carriage of S. aureus is not increased among diabetic patients on CSII treatment and is not a risk factor in the occurrence of inflammation at the infusion site.(ABSTRACT TRUNCATED AT 250 WORDS)


[Adenomatoid tumor of the epididymis. Report of a new case].
An additional case of adenomatoid tumor of the epididymis is described. This is the second in our experience. A 36-year-old male consulted at our outpatient services for an infertility test. Semen analysis revealed severe oligoteratozoospermia, indicating testicular biopsy and vasostomy. A nodular tumor was found in the body of the epididymis and pathological analysis confirmed adenomatoid tumor. Adenomatoid tumor of the epididymis is a benign tumor of both males and females. Although its etiopathogenesis remains unclear, the mesothelial hypothesis is the most widely accepted. It is silent and incidentally discovered. Definitive diagnosis is by pathological analysis.


A predictive model of rectal tumor response to preoperative radiotherapy using classification and regression tree methods.
The ability to predict rectal tumor response to preoperative radiotherapy before treatment would significantly impact patient selection. In this study, classification and regression tree (CART) methods were used to model tumor response to preoperative conformal high-dose rate brachytherapy by assessing the predictive value of vascular endothelial growth factor (VEGF), Bcl-2, p21, p53, and APAF-1. Immunohistochemistry was used to detect VEGF, Bcl-2, p21, p53, and APAF-1 from 62 pretreatment rectal tumor biopsies. Scores were assigned as percentages of positive tumor cell staining and were used in CART analysis to identify the proteins that best predicted response to radiotherapy. Ten-fold cross-validation was used to prevent overfitting and multiple cross-validation experiments were run to estimate the prediction error. Postoperative pathologic evaluation of the irradiated tumor bed revealed 43 responsive tumors [20 with complete response (T(0)) and 23 with partial response] and 19 nonresponsive tumors. The optimal tree resulting from CART analysis had five terminal nodes with a misclassification rate of 18%. Of the five proteins selected for their predictive value, VEGF and Bcl-2 contributed most to the classification of responsive and nonresponsive tumors. All 10 tumors with no VEGF were completely responsive (T(0)) to radiotherapy; 85% of those with VEGF and negative for Bcl-2 were responsive to therapy. VEGF and Bcl-2 status in pretreatment rectal tumor biopsies may be predictive of response to preoperative high-dose rate brachytherapy.


Invasive Scopulariopsis in the immunocompromised host.
Opportunistic infections with fungal organisms have been well described in patients undergoing intensive chemotherapy and bone marrow transplantation. In two patients, invasive infections with the saprophyte Scopulariopsis developed either following intensive chemotherapy or bone marrow transplant. Fungal disease persisted in both patients despite resection of the primary focus and prolonged treatment with the usual antifungal agents, and contributed to the death of one patient.


Xenograft of human pluripotent stem cell-derived cardiac lineage cells on zebrafish embryo heart.
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) are a promising cell source for regenerative medicine and drug discovery. However, the use of animal models for studying human cardiomyocytes derived from hiPSCs in vivo is limited and challenging. Given the shared properties between humans and zebrafish, their ethical advantages over mammalian models, and their immature immune system that is rejection-free against xenografted human cells, zebrafish provide a suitable alternative model for xenograft studies. We microinjected fluorescence-labeled cardiac lineage cells derived from hiPSCs, specifically mesoderm or cardiac mesoderm cells, into the yolk and the area proximal to the outflow tract of the linear heart at 24 hours post-fertilization (hpf). The cells injected into the yolk survived and did not migrate to other tissues. In contrast, the cells injected contiguous with the outflow tract of the linear heart migrated into the pericardial cavity and heart. After 1 day post injection (1 dpi, 22-24 hpi), the injected cells migrated into the pericardial cavity and heart. Importantly, we observed heartbeat-like movements of some injected cells in the zebrafish heart after 1 dpi. These results suggested successful xenografting of hiPSC-derived cardiac lineage cells into the zebrafish embryo heart. Thus, we developed a valuable tool using zebrafish embryos as a model organism for investigating the molecular and cellular mechanisms involved in the grafting process. This is essential in developing cell transplantation-based cardiac therapeutics as well as for drug testing, notably contributing to advancements in the field of cardio-medicine.


A rare case of dermatofibrosarcoma protuberans of the forefoot.
Dermatofibrosarcoma protuberans is an extremely rare, potentially malignant tumor type that usually presents on the trunk or proximal extremities. The clinical presentation includes a gradually enlarging painless plaque-like or nodular lesion of the skin with surrounding red to blue discoloration. The diagnosis is based on clinical presentation, computed tomography or magnetic resonance imaging, and biopsy with histologic analysis. An early and timely diagnosis improves chances of complete surgical resection thus improving prognosis. Herein, we present a rare case of dermatofibrosarcoma protuberans with the hopes that its addition to the literature will aid in the earlier recognition of future patients and help prevent this potentially curable disease from becoming deadly.


Falsely elevated anti-tissue transglutaminase antibodies in patients with immunoproliferative small intestinal diseases: A case series.
Immunoproliferative small intestinal disease (IPSID) is an uncommon disease of the small intestine. There is a similarity in the clinical presentations of enteropathic diseases, including celiac disease, tropical sprue, IPSID, and Whipple's disease. A differentiation between them is based on the use of a highly specific serological test for celiac disease and specific histological characteristics. We found that IgA-anti-tissue transglutaminase antibody (IgA-tTG Ab) is falsely elevated in a subset of patients with IPSID. The levels of IgA-tTG Ab fall with the treatment of IPSID. The healthcare professional should be aware of the conditions that lead to a false-positive anti-tTG Ab. Intestinal mucosal biopsies even in the presence of anti-tTG Ab should be done in endemic regions as they provide an opportunity for making a diagnosis of alternative and uncommon diseases before the diagnosis of celiac disease.


The impacts of vertical off-centring, tube voltage, and phantom size on computed tomography numbers: An experimental study.
This experimental study explored the effect of vertical off-centring on computed tomography (CT) numbers in combination with various tube voltages and phantom sizes for two CT units. CIRS Model 062 Electron Density and system performance phantoms were imaged on Siemens Emotion 16-slice CT and GEMINI-GXL scanners, respectively. Uniformity and accuracy were evaluated as a function of vertical off-centring (20, 40, 60, and 80 mm above the gantry isocentre) using different water phantom sizes (18, 20, and 30 cm) and tube voltages (80, 90, 110, 120, 130 and 140 kVp). Vertical off-centring and phantom size accounted for 92% of the recorded variance and the resultant change in CT numbers. The uniformity test recorded maximum changes of 14 and 27.2 HU for peripheral ROIs across the X- and Y-axes for an 80 mm phantom shift above the gantry isocentre on the GEMINI GXL and Siemens scanners, respectively. The absolute CT number differences between the superior and inferior ROIs were 13.7 HU for the 30 cm phantom and 4.8 HU for the 20 cm phantom for 80 mm vertical off-centring. The largest differences were observed at lower tube voltages. It is essential to highlight the significance of CT number variation in clinical decision-making. Phantom off-centring affected the uniformity of these numbers, which were further impacted by the ROI position in this experimental study. CT number variation was more evident in peripheral phantom areas, lower tube voltages and larger phantom sizes. CT number is observed to be a variable under certain common conditions. This significantly impacts several applications where clinical decisions depend on CT number accuracy for tissue lesion characterisation.


Glucocorticoid receptor gene (NR3C1) is hypermethylated in adult males with aggressive behaviour.
Aggressive behaviour is a serious threat to the personal safety and property of others due to the potential that the assailant may hurt people, himself/herself or objects, and aggression has always been one of the focuses of research and concern. Accumulating evidence suggests that the hypothalamic-pituitary-adrenal (HPA) axis plays a major role in the development, elicitation, enhancement and genetic susceptibility of aggressive behaviour in humans and animals. GR (NR3C1) plays a crucial role in controlling HPA activity, which directly affects aggressive behaviour. Here, we investigated the methylation state of the NR3C1 gene promoter region and its role in aggressive behaviour in adult males for the first time by applying a case-control approach (N = 106 controls, N = 104 patients). Methylation of NR3C1 was measured in peripheral blood samples at exons 1D, 1B and 1F via sodium bisulfite treatment combined with the MethylTarget method. Methylation of the NR3C1 gene was significantly correlated with aggressive behaviour, and the methylation levels of 1D, 1B and 1F were upregulated in the aggressive behaviour group, intentional injury subgroup and robbery subgroup, and the significance varied. In addition, multiple CpG sites were found to be significantly associated with aggressive behaviour. These results suggest that epigenetic aberrations of NR3C1 are associated with aggressive behaviour, and epigenetic processes might mediate aggressive behaviour by affecting the activity of the HPA axis. This correlative study between DNA methylation of the NR3C1 gene and aggressive behaviour in patients may be helpful for forensic assessments.


Waveguide integrated superconducting single-photon detectors implemented as near-perfect absorbers of coherent radiation.
At the core of an ideal single-photon detector is an active material that absorbs and converts every incident photon to a discriminable signal. A large active material favours efficient absorption, but often at the expense of conversion efficiency, noise, speed and timing accuracy. In this work, short (8.5 μm long) and narrow (8 × 35 nm(2)) U-shaped NbTiN nanowires atop silicon-on-insulator waveguides are embedded in asymmetric nanobeam cavities that render them as near-perfect absorbers despite their small volume. At 2.05 K, when biased at 0.9 of the critical current, the resulting superconducting single-photon detectors achieve a near-unity on-chip quantum efficiency for ∼1,545 nm photons, an intrinsic dark count rate <0.1 Hz, a reset time of ∼7 ns, and a timing jitter of ∼55 ps full-width at half-maximum. Such ultracompact, high-performance detectors are essential for progress in integrated quantum optics.


Pre-B-cell-colony-enhancing factor is critically involved in thrombin-induced lung endothelial cell barrier dysregulation.
Prior genomic and genetic studies identified pre-B-cell colony-enhancing factor (PBEF) as a novel candidate gene and biomarker in acute lung injury (ALI). As increased vascular permeability is a cardinal feature of ALI, we assessed the role of PBEF in in vitro vascular barrier regulation using confluent human pulmonary artery endothelial cell (HPAEC) monolayers. Reductions in PBEF protein expression (>70%) by siRNA significantly attenuated EC barrier dysfunction induced by the potent edemagenic agent, thrombin, reflected by reductions in transendothelial electric resistance (TER, approximately 60% reduction). Furthermore, PBEF siRNA blunted thrombin-mediated increases in Ca(2+) entry, polymerized actin formation, and myosin light chain phosphorylation, events critical to the thrombin-mediated permeability response. Finally, PBEF siRNA also significantly inhibited thrombin-stimulated increase of IL-8 secretion in HPAEC, a chemokine known to induce actin fiber formation and intercellular gap formation of endothelial cells. Taken together, these studies demonstrate that PBEF may be required for complete expression of the thrombin-induced inflammatory response and reveal potentially novel role for PBEF in the regulation of EC Ca(2+)-dependent cytoskeletal rearrangement and endothelial barrier dysfunction. Ongoing studies will continue to address the molecular mechanisms by which PBEF contributes to ALI susceptibility.


Modeling of nitrate concentration in groundwater using artificial intelligence approach--a case study of Gaza coastal aquifer.
Nitrate concentration in groundwater is influenced by complex and interrelated variables, leading to great difficulty during the modeling process. The objectives of this study are (1) to evaluate the performance of two artificial intelligence (AI) techniques, namely artificial neural networks and support vector machine, in modeling groundwater nitrate concentration using scant input data, as well as (2) to assess the effect of data clustering as a pre-modeling technique on the developed models' performance. The AI models were developed using data from 22 municipal wells of the Gaza coastal aquifer in Palestine from 2000 to 2010. Results indicated high simulation performance, with the correlation coefficient and the mean average percentage error of the best model reaching 0.996 and 7 %, respectively. The variables that strongly influenced groundwater nitrate concentration were previous nitrate concentration, groundwater recharge, and on-ground nitrogen load of each land use land cover category in the well's vicinity. The results also demonstrated the merit of performing clustering of input data prior to the application of AI models. With their high performance and simplicity, the developed AI models can be effectively utilized to assess the effects of future management scenarios on groundwater nitrate concentration, leading to more reasonable groundwater resources management and decision-making.


Robot-assisted ultrasound navigation platform for 3D HIFU treatment planning: Initial evaluation for conformal interstitial ablation.
Interstitial Ultrasound-guided High Intensity Focused Ultrasound (USgHIFU) therapy has the potential to deliver ablative treatments which conform to the target tumor. In this study, a robot-assisted US-navigation platform has been developed for 3D US guidance and planning of conformal HIFU ablations. The platform was used to evaluate a conformal therapeutic strategy associated with an interstitial dual-mode USgHIFU catheter prototype (64 elements linear-array, measured central frequency f = 6.5 MHz), developed for the treatment of HepatoCellular Carcinoma (HCC). The platform included a 3D navigation environment communicating in real-time with an open research dual-mode US scanner/HIFU generator and a robotic arm, on which the USgHIFU catheter was mounted. 3D US-navigation was evaluated in vitro for guiding and planning conformal HIFU ablations using a tumor-mimic model in porcine liver. Tumor-mimic volumes were then used as targets for evaluating conformal HIFU treatment planning in simulation. Height tumor-mimics (ovoid- or disc-shaped, sizes: 3-29 cm3) were created and visualized in liver using interstitial 2D US imaging. Robot-assisted spatial manipulation of these images and real-time 3D navigation allowed reconstructions of 3D B-mode US images for accurate tumor-mimic volume estimation (relative error: 4 ± 5%). Sectorial and full-revolution HIFU scanning (angular sectors: 88-360°) could both result in conformal ablations of the tumor volumes, as soon as their radii remained ≤ 24 mm. The presented US navigation-guided HIFU procedure demonstrated advantages for developing conformal interstitial therapies in standard operative rooms. Moreover, the modularity of the developed platform makes it potentially useful for developing other HIFU approaches.


Ascorbic acid 6-palmitate modulates microglia M1/M2 polarization in lipopolysaccharide-stimulated BV-2 cells via PERK/elF2α mediated endoplasmic reticulum stress.
Neuroinflammation-mediated microglia polarization is a major process in various central nervous system (CNS) diseases. Endoplasmic reticulum (ER) stress contributes to the inflammatory signals as well as to microglia polarization in lipopolysaccharide (LPS) induced neuroinflammation. Ascorbic acid 6-palmitate (L-AP) has been broadly used as a dietary antioxidant in foods and demonstrated a strong inhibitory effect on 5-LOX; however, the specific anti-inflammation mechanisms remain unclear. In this study, we investigated the effects and possible mechanisms of L-AP on LPS-induced neuroinflammation in BV-2 cells. Immortalized murine microglia cell line BV-2 cells were employed to assess the effect of L-AP to modulate microglia M1/M2 polarization in vivo, and the molecular mechanism was evaluated by qRT-PCR and Western blotting analysis. Molecular docking was used to predict the binding activity of L-AP with protein kinase R-like ER kinase (PERK). L-AP at 62.5 µM significantly modulated LPS-induced microglia M1/M2 polarization (increases of interleukin (IL)-10 and arginase-1 (Arg-1) transcriptions) independent of cell growth. Besides, L-AP at 62.5 µM significantly down-regulated glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding homologous protein (CHOP) mRNA levels. Similar data were shown in the tunicamycin (TM) induced ER stress cells model. Moreover, the protective effect of L-AP on TM-induced microglia M1/M2 polarization was similar to that of 4-phenyl butyric acid (4-PBA), the ER stress inhibitor. Molecular docking results indicated L-AP might directly bind with PERK, with a binding affinity of -7.7 kcal/mol. A further study unveiled that L-AP notably inhibited LPS-induced PERK/ eukaryotic initiation factor 2α (elf2α) activation. Together, this study revealed that L-AP possessed its effect on the reconstruction of microglia M1/M2 polarization balance in LPS-stimulated BV-2 cells via modulating PERK/elF2α mediated ER stress.


Atypical cells in pathology of endobronchial ultrasound-guided transbronchial biopsy of peripheral pulmonary lesions: incidence and clinical significance.
Atypical cells may occasionally be the only pathologic finding in radial-probe endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB) of peripheral pulmonary lesions (PPLs); however, it is uncertain how often we encounter such a situation and what clinical features can be used to identify these ambiguous PPLs, which are more likely to be malignant. From 2009 to 2016, consecutive patients referred for EBUS-guided TBB of PPLs and with pathology reports indicating atypical cells alone were included. Medical records were reviewed to extract patient demographics, clinical characteristics, procedural details and complications. The primary outcome was the final diagnosis of the PPLs on subsequent investigation. Multivariate logistic regression analysis was used to identify independent factors associated with a final malignant diagnosis. One hundred sixty-five (7.2%) of 2291 patients had non-diagnostic TBB showing atypical cells. Benign and malignant diagnoses were subsequently obtained in 45 (27%) and 120 (73%) patients, respectively. The leading malignancy was lung adenocarcinoma; of note, a variety of benign lesions revealed cellular atypia on pathology, in particular, chronic inflammation, tuberculosis and pneumonia. Multivariate analysis indicated lesion appearance [solid vs. others; odds ratio (OR) 7.93; 95% confidence interval (CI) 2.94-21.40; P < 0.001] and probe position (adjacent to vs. within; OR 3.36; 95% CI 1.11-10.15; P = 0.032) were two significant factors predictive of a final diagnosis of malignancy. One out of 14 EBUS-guided TBB procedures for PPLs exhibited atypical cells on pathology. Meticulous management strategies should be formulated to deal with these instances after taking into consideration lesion appearance, probe position and patient preferences.


Antinociceptive and anti-inflammatory effects of Aloe saponaria Haw on thermal injury in rats.
In Brazil, the plant Aloe saponaria Haw, popularly known as "babosa pintadinha", has been empirically used for its potential effect on thermal injury. Because there are no scientific data confirming its popular use, the aim of the present study was to investigate the effects of Aloe saponaria on nociceptive and inflammatory parameters in a rat model of thermal injury. Adult male Wistar rats were subjected to a thermal injury or sham procedure (immersion in water at 70 or 37°C, respectively, for 5 or 8s). Burned animals were topically treated with vehicle (base cream), sulfadiazine 1% (positive control) or Aloe saponaria cream (0.3%-30%) once a day for 2 or 6 days. Each day, 30min before the treatment, we measured nociceptive (static and dynamic mechanical allodynia, thermal allodynia and spontaneous pain) and inflammatory (paw edema) parameters. Moreover, enzymatic indicators of leukocyte infiltration into burned tissue were also determined 2 or 6 days after the thermal injury. The thermal injury (fist and second-degree) procedure, but not the sham procedure, induced nociception and inflammation from 1 to 6 days after the injury. The topical treatment with Aloe saponaria cream (10%) reduced nociceptive behaviors from day 1 to 6 (peak at day 2), edema at days 5 and 6 (peak at day 6) and myeloperoxidase, N-acetyl-glucosaminidase and eosinoperoxidase activities at day 6. The antinociceptive and anti-inflammatory effects of Aloe saponaria were obtained with doses of 3%-30%, with maximal inhibition obtained with a dose of 10% (reductions of 39±9%, 41±9%, 31±7%, 83±7% and 23±2% for static and dynamic mechanical allodynia, thermal allodynia, spontaneous pain and paw edema, respectively). Our results demonstrate that topically applied Aloe saponaria presented antinociceptive and anti-inflammatory effects in rats subjected to a thermal injury, which supports its traditional use for burn injuries.


Innovative approaches for the treatment of depression: targeting the HPA axis.
Altered activity of the hypothalamic pituitary adrenal (HPA) axis is one of the most commonly observed neuroendocrine abnormalities in patients suffering from major depressive disorder (MDD). Altered cortisol secretion can be found in as many as 80% of depressed patients. This observation has led to intensive clinical and preclinical research aiming to better understand the molecular mechanisms which underlie the alteration of the HPA axis responsiveness in depressive illness. Dysfunctional glucocorticoid receptor (GR) mediated negative feedback regulation of cortisol levels and changes in arginine vasopressin (AVP)/vasopressin V1b receptor and corticotrophin-releasing factor/CRF1 receptor regulation of adrenocotricotrophin (ACTH) release have all been implicated in over-activity of the HPA axis. Agents that intervene with the mechanisms involved in (dys)regulation of cortisol synthesis and release are under investigation as possible therapeutic agents. The current status of some of these approaches is described in this review.


Protein and Long-Chain n-3 Polyunsaturated Fatty Acids Recovered from Herring Brines upon Flocculation and Flotation-A Case Study.
A novel integrated process for recovery of protein-enriched biomasses from 5% presalting brines and spice brines of herring (Clupea harengus) was investigated by combining carrageenan- and/or acid-driven flocculation (F) plus dissolved air flotation (DAF). The F-DAF technique with carrageenan resulted in protein and lipid recoveries from 5% presalting brine of 78 and 38%, respectively. Without flocculation or with only acidification, protein and lipid recoveries in DAF were only 13 and 10%, respectively. Low protein and lipid recoveries, 8-12 and 1.8-8.2%, respectively, were also obtained when spice brine was subjected to only acidification and DAF. The protein content in dry biomasses from 5% presalting brine and spice brine was 36-43 and 13-16%, respectively. The corresponding lipid levels were 23-31 and 9-18%, respectively, with ash levels of 11-20 and 38-45%, respectively. Biomass proteins contained ≤45% essential amino acids, and the lipids had ≤16% long-chain n-3 polyunsaturated fatty acids. Freeze-dried spice brine biomasses were characterized by anchovy- and spice-related sensory attributes. 5% presalting brine biomasses were connected to fish and seafood attributes and showed gel forming capacity. The outlined F-DAF recovery system can thus recover both nutrients and interesting flavors from the herring process waters, which are currently lost from the food chain.


Naturally occurring menopause in cynomolgus monkeys: changes in hormone, lipid, and carbohydrate measures with hormonal status.
Naturally occurring post-menopausal (PM) female cynomolgus monkeys (Macaca fascicularis) were identified. Their sex hormone profile was characterized and compared with younger pre-menopausal females before and after ovariectomy (OVX). PM females had lower estrogens and increased follicle-stimulating hormone (FSH) concentrations. Two PM females had diabetes mellitus and elevated androgens (androstenodione and dihydroepiandrosterone sulfate). Non-diabetic PM females were given parenteral E(2) which normalized FSH, and caused improvements in body weight, plasma lipids and lipoprotein cholesterol. Androgens remained lower with E(2) treatment. OVX induced comparable increases in FSH seen with the PM monkeys, however they had lower body weights, and had higher estrone and androstenodione concentrations. Natural menopause occurs in cynomolgus monkeys and hormone changes with OVX are similar however, differences in sex hormones that can relate to body mass and age may be important. E(2) treatment restored estrogen levels and induced improvements in the lipid profile of PM females.


Preclinical Evidence for the Use of Sunitinib Malate in the Treatment of Plexiform Neurofibromas.
Plexiform neurofibromas (pNF) are pathognomonic nerve and soft tissue tumors of neurofibromatosis type I (NF1), which are highly resistant to conventional chemotherapy and associated with significant morbidity/mortality. Disruption of aberrant SCF/c-Kit signaling emanating from the pNF microenvironment induced the first ever objective therapeutic responses in a recent phase 2 trial. Sunitinib malate is a potent, highly selective RTK inhibitor with activity against c-Kit, PDGFR, and VEGFR, which have also been implicated in the pathogenesis of these lesions. Here, we evaluate the efficacy of sunitinib malate in a preclinical Krox20;Nf1(flox/-) pNF murine model. Proliferation, β-hexosaminidase release (degranulation), and Erk1/2 phosphorylation were assessed in sunitinib treated Nf1(+/-) mast cells and fibroblasts, respectively. Krox20;Nf1(flox/-) mice with established pNF were treated sunitinib or PBS-vehicle control for a duration of 12 weeks. pNF metabolic activity was monitored by serial [(18)F]DG-PET/CT imaging. Sunitinib suppressed multiple in vitro gain-in-functions of Nf1(+/-) mast cells and fibroblasts and attenuated Erk1/2 phosphorylation. Sunitinib treated Krox20;Nf1(flox/-) mice exhibited significant reductions in pNF size, tumor number, and FDG uptake compared to control mice. Histopathology revealed reduced tumor cellularity and infiltrating mast cells, markedly diminished collagen deposition, and increased cellular apoptosis in sunitinib treated pNF. Collectively, these results demonstrate the efficacy of sunitinib in reducing tumor burden in Krox20;Nf1(flox/-) mice. These preclinical findings demonstrate the utility of inhibiting multiple RTKs in pNF and provide insights into the design of future clinical trials.


Extended experience with radical prostatectomy for clinical stage T3 prostate cancer: outcome and contemporary morbidity.
Radical prostatectomy for clinical stage T3 prostate cancer has not been widely accepted due to the potential for incomplete excision of the local tumor and high incidence of lymph node metastases. In addition, contemporary morbidity is unknown. We report the long-term results in 812 patients with clinical stage T3 prostate cancer treated with radical prostatectomy. Between 1966 and 1992, 812 patients with clinical stage T3 prostate cancer underwent radical prostatectomy of whom 479 (60%) received adjuvant therapy. Mean patient age was 65 years (range 40 to 78). Mean followup was 4.5 years (range up to 24). Disease was stage pT2c or less in 17% of patients, pT3a to c in 49% and node-positive in 33%. Of the primary tumors pathological Gleason score was 7 or greater in 62%. Crude and cancer-specific survival rates at 5, 10 and 15 years were 86%, 70% and 51%, and 90%, 80% and 69%, respectively. Operative morbidity paralleled that of patients with clinically localized disease (T2c or less). An excellent survival rate with low treatment related morbidity can be achieved by performing primary radical prostatectomy with adjuvant therapy in the patient with clinical stage T3 prostate cancer.


Simple Scoring System that Predicts the Need for Surgical Intervention in Infants with Necrotizing Enterocolitis.
It is difficult to identify those preterm infants who require surgical intervention. This study examined the predictive factors for bowel resection in infants with definitive and advanced necrotizing enterocolitis (NEC). We then developed a scoring system to better predict the need for surgical intervention. A total of 203 infants with modified Bell's stage 2 or higher NEC from January 2018-December 2020 were identified for this study. A retrospective study evaluated the association between several comprehensive variables and surgical intervention using a multiple logistic regression analysis, and then a scoring system was developed based on the sum of coefficients (β). Of the 135 patients who met the inclusion criteria, 57 infants underwent a surgical intervention. The multivariable logistic regression analysis showed that birth weight (regression coefficient, β = 1.30), PCT (β = 2.33), not having received enteral nutrition before the diagnosis of NEC (β = 2.13), acidosis (β = 1.57), respiratory alkalosis (β = 2.42), hypokalemia (β = 2.14), peritonitis (β = 2.87) and coagulation disorders (β = 1.78) were associated with the occurrence of bowel resection. A scoring system ranging from 0-17 was developed based on the total coefficient obtained. It was found that a cut-off score of 5 may distinguish those infants needing surgical intervention from other infants with NEC. We successfully developed a clinical decision-making tool associated with the need for surgical intervention among infants with advanced NEC. The risk scoring system could accurately identify infants who would benefit from surgical intervention.


Non-Hodgkin's lymphomas of follicular center cell type in Osaka, Japan.
Five hundred and nineteen patients with follicular center cell (FCC) tumors in Osaka, Japan were selected for study from 1000 patients with non-Hodgkin's lymphoma (NHL). They were admitted to hospital during 1964-1987, which was divided into three periods 1964-1972 (I), 1973-1979 (II), and 1980-1987 (III) to examine the time trend of FCC tumors. The median age of patients rose from 51 to 55 years of age with an increase in female and extranodal disease patients. The frequency of nodal FCC tumors among all nodal NHL increased from 37.5 to 51.5% (P less than 0.05), but that of extranodal types decreased from 82.9 to 56.8% (P less than 0.01), although the total number showed little change. When the cases were categorized as diffuse type and follicular type, the diffuse type predominated through the period in both nodal and extranodal sites. The frequencies of follicular type among all NHL were 10.2, 6.3, and 8.4% during the periods I, II and III, respectively. These results showed that follicular lymphoma was a minor constituent of NHL in Japan compared to Western countries, and the frequency did not increase from 1964 to 1987. The frequency of FCC tumors in the present series was rather higher than that in Western countries, therefore it is concluded that FCC tumors in Japanese have much less potential for forming a follicular structure than those in patients from Western countries.


Evidence for high affinity prostacyclin binding sites in vascular tissue: radioligand studies with a chemically stable analogue.
Prostacyclin-specific binding sites are described in the muscularis of pig aorta using [3H]ZK 36374, a chemically stable prostacyclin analogue, as radioligand. Under standard incubation conditions [300 micrograms membrane protein in 350 microliter Tris buffer (50 mmoles/l., pH 7.4) containing 3 mM Ca2+ at 37 degrees for 10 min] both association and dissociation were complete within 30 sec, thus not allowing the determination of association or dissociation rate constants. The Scatchard plot was upward convex, whereas the Hill plot was linear, having a slope of 1.9. The equilibrium dissociation constant (KD) was 22.4 nmoles/l. and the specific binding was saturated at 360 fmoles [3H]ZK 36374/mg protein. The reversibility of binding was demonstrated by displacement of bound ligand with ZK 36374, its 5-(Z)-stereoisomer (ZK 36375), PGI2 and PGE1, but not with PGF2 alpha. The data suggest high affinity binding sites for ZK 36374 in the smooth muscle cells of pig aorta for which PGI2 may be the physiological ligand. They also demonstrate a possible co-operativity with two molecules binding simultaneously to two interacting sites.


Epilepsy and brain tumors: implications for treatment.
Primary intraparenchymal tumors of the brain are important etiologic factors in partial or focal epilepsy. Indolent low-grade gliomas may be associated with a long-standing seizure disorder refractory to medical treatment. Surgical resection of the neoplasm and the epileptogenic area may render patients seizure-free. Removal of the tumor alone may also be associated with an excellent survival rate and surgical outcome. Conventional neurosurgical procedures are restricted in patients with tumors that are deep-seated lesions or involve functional cerebral cortex. Computer-assisted stereotactic surgical procedures have been developed for biopsy and resection of intra-axial brain-mass lesions. Stereotactic tumor resection may allow pathological determination of intracranial lesions and produce a worthwhile reduction in seizure activity in some patients with intractable partial epilepsy.


Risk of Acute Kidney Injury After Primary and Revision Total Hip Arthroplasty and Total Knee Arthroplasty Using a Multimodal Approach to Perioperative Pain Control Including Ketorolac and Celecoxib.
Safe and effective perioperative analgesia is instrumental to patient satisfaction and decreasing LOS after TJA. We evaluated rates of acute kidney injury (AKI) in primary and revision TJA using a multimodal pain control regimen including scheduled celecoxib and PRN ketorolac. Postoperative AKI was identified in 43/903 (4.8%) of 903 of patients with adequate preoperative renal function. Those who developed AKI had significantly increased LOS (P < .01), were older, more obese, and more likely to have diabetes (P < .05). With a protocol incorporating NSAIDs in patients without evidence of preoperative renal impairment, there is a 4.8% rate of AKI, which is 2.7 times higher than the reported literature. Acute postoperative kidney injury was significantly correlated with increased LOS and has important patient safety and healthcare-related cost implications.


Identification of novel GLUT inhibitors.
The compound class of 1H-pyrazolo[3,4-d]pyrimidines was identified using HTS as very potent inhibitors of facilitated glucose transporter 1 (GLUT1). Extensive structure-activity relationship studies (SAR) of each ring system of the molecular framework was established revealing essential structural motives (i.e., ortho-methoxy substituted benzene, piperazine and pyrimidine). The selectivity against GLUT2 was excellent and initial in vitro and in vivo pharmacokinetic (PK) studies are encouraging.


Infection Prevention and Control in Three Tertiary Healthcare Facilities in Freetown, Sierra Leone during the COVID-19 Pandemic: More Needs to Be Done!
Infection Prevention and Control (IPC) measures are critical to the reduction in healthcare-associated infections, especially during pandemics, such as that of COVID-19. We conducted a hospital-based cross-sectional study in August 2021 at Connaught Hospital, Princess Christian Maternity Hospital and Ola During Children's Hospital located in Freetown, Sierra Leone. We used the World Health Organization's Infection Prevention and Control Assessment Framework Tool to assess the level of IPC compliance at these healthcare facilities. The overall IPC compliance score at Connaught Hospital was 323.5 of 800 points, 313.5 of 800 at Ola During Children's Hospital, 281 of 800 at Princess Christian Maternity Hospital, implying a 'Basic' IPC compliance grade. These facilities had an IPC program, IPC committees and dedicated IPC focal persons. However, there were several challenges, including access to safe and clean water and insufficient quantities of face masks, examination gloves and aprons. Furthermore, there was no dedicated budget or no healthcare-associated infection (HAI) surveillance, and monitoring/audit of IPC practices were weak. These findings are of concern during the COVID-19 era, and there is an urgent need for both financial and technical support to address the gaps and challenges identified.


Calculation of MRI-induced heating of an implanted medical lead wire with an electric field transfer function.
To develop and demonstrate a method to calculate the temperature rise that is induced by the radio frequency (RF) field in MRI at the electrode of an implanted medical lead. The electric field near the electrode is calculated by integrating the product of the tangential electric field and a transfer function along the length of the lead. The transfer function is numerically calculated with the method of moments. Transfer functions were calculated at 64 MHz for different lengths of model implants in the form of bare wires and insulated wires with 1 cm of wire exposed at one or both ends. Heating at the electrode depends on the magnitude and the phase distribution of the transfer function and the incident electric field along the length of the lead. For a uniform electric field, the electrode heating is maximized for a lead length of approximately one-half a wavelength when the lead is terminated open. The heating can be greater for a worst-case phase distribution of the incident field. The transfer function is proposed as an efficient method to calculate MRI-induced heating at an electrode of a medical lead. Measured temperature rises of a model implant in a phantom were in good agreement with the rises predicted by the transfer function. The transfer function could be numerically or experimentally determined.