Effects of a WeChat-based multimodal psychoeducational intervention on psychological well-being and quality of life in acute leukaemia patients in China: a randomised controlled trial.
The treatment and side effects of chemotherapy for acute leukaemia (AL) may cause both physical and psychological symptoms in patients. This study evaluated the effects of a WeChat-based multimodal psychoeducational intervention (ICARE programme) on fatigue, distress, anxiety, depression, and quality of life (QoL) among adult AL patients. In total, 72 participants were randomly assigned either to an intervention or control group (n = 36), respectively, from two large tertiary hospitals in Fuzhou, China (from April to December 2019). Data were collected at baseline, post-intervention, and after a 4-week follow-up using the Brief Fatigue Inventory, Distress Thermometer, Hospital Anxiety and Depression Scale, and Functional Assessment of Cancer Therapy-leukaemia. Descriptive statistics was used to summarise the sociodemographic and clinical characteristics of the participants and a linear mixed model was used to analyse the score changes. Between the two groups, there were statistically significant improvements in fatigue, distress, anxiety, depression, physical well-being, social/family well-being, emotional well-being, functional well-being (all p < 0.001), and leukaemia-specific subscale (p = 0.001). The difference over time was significant for leukaemia-specific subscale and fatigue, both (p < 0.001), anxiety (p = 0.001), and social/family well-being (p = 0.005). The interaction effects were significant for fatigue, distress, anxiety, physical well-being, social/family well-being, and emotional well-being, all (p < 0.001), depression (p = 0.019), leukaemia-specific subscale (p = 0.008), and total QoL score (p = 0.004). WeChat-based multimodal psychoeducational intervention demonstrated a significant effect in reducing fatigue, distress, anxiety, depression, and QoL in AL patients. This ICARE programme contributed to continuing care to support AL patients. The ICARE programme can improve the mental health and QoL of AL patients. The application of WeChat-based psychoeducational interventions have significant potential to benefit cancer patients due to their reach and can be an added value to routine care.


Advancement flap procedure in Crohn and non-Crohn perineal fistulas: a simple surgical approach.
Rectal flap advancement is still a part of therapeutic management of anal fistulas. Data on the outcome of rectal flap advancement in patients with Crohn's disease (CD) is scarce. Our objective was to ascertain rates of failure of rectal flap advancement and to determine predictive factors for failure, with a special focus on CD METHOD: The patients' details, the characteristics of the fistula and the main clinical and therapeutic events were prospectively assessed among patients who underwent rectal flap advancement. All patients had a partial-thickness rectal flap advancement. Failure of primary rectal flap advancement was defined as the occurrence of at least one of the following: abscess, discharge, visible external opening, further drainage procedure. The rates of failure of rectal flap and the predictive factors of failure were assessed. Eighty-seven patients (34 patients with CD) were included. The median (interquartile range) follow-up was 13.3 (3.8-38.1) months. The cumulative failure rates were 15.9% (10.3-23.6), 23.0% (16.0-31.8), 31.6% (22.9-41.8) and 41.3% (30.5-53.0) at 3, 6, 12 and 24 months respectively. These data were comparable in Crohn's patients. Those with a supralevator fistula [hazard ratio 2.53 (1.01-7.71), P = 0.0476] and patients who had fewer than two fistula drainages before rectal flap [hazard ratio 3.19 (1.40-8.23), P = 0.005] were associated with higher rectal flap failure rates. In CD patients, the absence of biological therapy at referral was predictive of failure. Rectal flap advancement is a satisfactory option for the therapeutic management of anal fistula, including CD populations. Fistula drainage is needed before performing this surgical technique.


Deciphering glioma epitranscriptome: focus on RNA modifications.
Gliomas are highly malignant tumors accounting for the majority of brain neoplasms. They are characterized by nuclear atypia, high mitotic rate and cellular polymorphism that often contributes to aggressiveness and resistance to standard therapy. They often associate with challenging treatment approaches and poor outcomes. New treatment strategies or regimens to improve the efficacy of glioma treatment require a deeper understanding of glioma occurrence and development as well as elucidation of their molecular biological characteristics. Recent studies have revealed RNA modifications as a key regulatory mechanism involved in tumorigenesis, tumor progression, immune regulation, and response to therapy. The present review discusses research advances on several RNA modifications involved in glioma progression and tumor microenvironment (TME) immunoregulation as well as in the development of adaptive drug resistance, summarizing current progress on major RNA modification targeting strategies.


Modification of cyclin A expression by hepatitis B virus DNA integration in a hepatocellular carcinoma.
We have previously reported the identification of a hepatitis B virus (HBV) DNA integration in an intron of the cyclin A gene in an early hepatocellular carcinoma (HCC) and the isolation of human cyclin A cDNA. We have now constructed a cDNA library from the tumor and isolated several hybrid HBV-cyclin A cDNAs from it. The hybrid cDNAs encode an HBV-cyclin A fusion protein. In the chimeric protein, the N-terminus of cyclin A, including the signals for cyclin degradation, is deleted and replaced by viral PreS2/S sequences, transcription being initiated from the viral PreS2/S promoter. This chimeric protein is undegradable in an in vitro cyclin degradation assay. Northern blot analyses showed strong expression of the hybrid transcripts in the tumor, while cyclin A- or HBV-specific transcripts were not detected in the non-tumorous liver of the same patient. Thus, HBV DNA integration in the cyclin A gene resulted in a strong expression of hybrid HBV-cyclin A transcripts encoding a stabilized cyclin A. This chimeric protein may play an important role in the development of the tumor.


The effect of long-term high-frequency stimulation on capillary density and fibre types in rabbit fast muscles.
Rabbit fast muscles (tibialis anterior, t.a.; extensor digitorum longus, e.d.l.; and peroneal muscles) were stimulated for up to 28 days by electrodes implanted in the vicinity of the lateral popliteal (peroneal) nerve for 8 h/day, using either intermittent high-frequency (three trains at 40 Hz/min, each 5 s duration), or continuous stimulation at 10 Hz. This did not result in muscle hypertrophy even after 28 days. Capillary density (number of capillaries/mm2) was increased in e.d.l. from 251 +/- 3 to 366 +/- 6 after 14 days of stimulation and from 251 +/- 3 to 514 +/- 13 after 28 days of stimulation at 40 Hz. In t.a., capillary density increased from 373 +/- 5 to 583 +/- 10 after 14 days of stimulation at 40 Hz. The capillary/fibre ratio increased in e.d.l. from 1.25 +/- 0.02 to 1.86 +/- 0.04 at 14 days and to 2.07 +/- 0.06 at 28 days. In t.a., capillary/fibre ratio increased from 1.40 +/- 0.03 to 1.83 +/- 0.05 at 14 days. All these changes were significant (P less than 0.0005). Analysis of capillary density, capillary/fibre ratio, fibre areas and proportion of different fibre types in muscles stimulated for shorter periods showed no changes in capillary density, capillary/fibre ratio or fibre areas in e.d.l. or t.a. stimulated for 4 days; there was a decrease in the proportion of fast glycolytic fibres from 42 to 32% (P less than 0.0025) and increase in fast oxidative from 37.6 to 41.2% in e.d.l. Muscles stimulated for 7 days showed increases in capillary density and capillary/fibre ratio in fast predominantly glycolytic fibres in e.d.l., and a decrease in capillary density in fast and slow oxidative fibres in t.a. This was partly due to the increase in fibre areas in these groups (capillary/fibre ratio in t.a. was not significantly changed). No changes were observed in fibre areas in e.d.l. Stimulation at 10 Hz produced increase in capillary/fibre ratio in the vicinity of glycolytic fibres after only 4 days. High-frequency intermittent stimulation leads to a massive capillary growth which starts first in the muscle with a higher proportion of glycolytic fibres (e.d.l.), has a later onset than continuous low-frequency stimulation, and may be due to a combination of high blood flow and metabolic factors.


A transgenic inducible GFP extracellular-vesicle reporter (TIGER) mouse illuminates neonatal cortical astrocytes as a source of immunomodulatory extracellular vesicles.
Extracellular vesicles (EVs) are cellular derived particles found throughout the body in nearly all tissues and bodily fluids. EVs contain biological molecules including small RNAs and protein. EVs are proposed to be transferred between cells, notably, cells of the immune system. Tools that allow for in vivo EV labeling while retaining the ability to resolve cellular sources and timing of release are required for a full understanding of EV functions. Fluorescent EV fusion proteins are useful for the study of EV biogenesis, release, and identification of EV cellular recipients. Among the most plentiful and frequently identified EV proteins is CD9, a tetraspanin protein. A transgenic mouse containing a CRE-recombinase inducible CAG promoter driven CD9 protein fused to Turbo-GFP derived from the copepod Pontellina plumata was generated as an EV reporter. The transgenic inducible GFP EV reporter (TIGER) mouse was electroporated with CAG-CRE plasmids or crossed with tamoxifen inducible CAG-CRE-ERT2 or nestin-CRE-ERT2 mice. CD9-GFP labeled cells included glutamine synthetase and glial fibrillary acidic protein positive astrocytes. Cortical astrocytes released ~136 nm EVs that contained CD9. Intraventricular injected EVs were taken up by CD11b/IBA1 positive microglia surrounding the lateral ventricles. Neonatal electroporation and shRNA mediated knockdown of Rab27a in dorsal subventricular zone NSCs and astrocytes increased the number of CD11b/IBA1 positive rounded microglia. Neonatal astrocyte EVs had a unique small RNA signature comprised of morphogenic miRNAs that induce microglia cytokine release. The results from this study demonstrate that inducible CD9-GFP mice will provide the EV community with a tool that allows for EV labeling in a cell-type specific manner while simultaneously allowing in vivo experimentation and provides evidence that EVs are required immunomodulators of the developing nervous system.


Synthesis and structural study of variously oxidized diastereomeric 5'-dimethoxytrityl-thymidine-3'-O-[O-(2-cyanoethyl)-N,N-diisopropyl]-phosphoramidite derivatives. Comparison of the effects of the P=O, P=S, and P=Se functions on the NMR spectral and chromatographic properties.
R(P)- and S(P)-diastereomers of 5'-dimethoxytrityl-thymidine-3'-O-[O-(2-cyanoethyl)-N,N-diisopropyl]-phosphoramidite (T-CED) were separated by silica gel chromatography. Oxidation of both isomers with H(2)O(2), elemental sulfur and selenium, respectively, resulted in the corresponding oxidized analogues in nearly quantitative yields. All reactions were found to proceed with retention of P-configuration. This was confirmed by thorough NMR analysis which, in addition, aimed to study the spectral properties of the diastereomers with special respect to differences in the heteroatom effect of the O, S and Se atoms, double-bonded to the phosphorus, on the vicinal carbon-phosphorus couplings. It was found that the changes in the DeltaJ (=(3)J(P,C4') - (3)J(P,C2')) values were basically induced by the electronegativity of the heteroatoms, rather than differences in the rotational preferences about the C3'-O3' bond. The impact of the benzene solvent on the above couplings is also discussed. The effect of these heteroatoms on the chromatographic (normal and reverse phase HPLC) behavior of the compounds was also investigated and the reverse phase HPLC profiles showed an unambiguous correlation between the electronegativity of the heteroatoms and the chromatographic mobility of the analogues.


The role of adverse childhood experiences (ACEs) in predicting academic problems among college students.
The complex associations between adverse childhood experiences (ACEs) and academic performance among college students are not well understood. The following aims were examined in this longitudinal study: the direct association of ACEs on academic problems after 4 years without (1) and with accounting for other academic risk factors (2a), the possible mechanisms linking ACEs and academic problems (2b). First-semester freshmen (N = 268; 71.3% female; Mage = 18.30; 76.9% White, 14.6% Asian, 3.7% Black, 2.6% multiracial, 1.1% Native American, and 1.1% other) were recruited from a Midwestern U.S. university. Participants reported their ACEs, intrinsic motivation, psychological distress, and financial status as first-semester freshmen. Administrative records (i.e., SAT/ACT scores, GPA, courses taken not counted toward degree progress, and graduation) were collected prospectively over 4 years. Structural equation modeling was used to test the research aims. Post-hoc analyses without SAT/ACT scores were conducted. ACEs were associated with academic problems assessed 4 years later, when studied in isolation (β = 0.36, p < .001) but not after adjusting for other risk factors (β = 0.08, p = .278). Psychological distress and SAT/ACT scores during the first semester predicted academic problems 4 years later (β = 0.33 and - 0.38, p < .001). There was an indirect effect of ACEs on academic problems through psychological distress (β = 0.13, p < .001). There is a need to expand mental health services and address barriers to utilization on college campuses.


Capucin does not modify the toxicity of a mutant Huntingtin fragment in vivo.
Genes selectively expressed in the striatum may be involved in the preferential vulnerability of striatal neurons to Huntington's disease (HD). Here, we investigated whether perturbations of Capucin expression, which is enriched in the striatum and downregulated in Huntington's disease models, could modify the neurotoxicity induced by the injection of a lentiviral vector encoding a short N-terminal fragment of mutant Huntingtin (mHtt) into the mouse striatum. Neither constitutive Capucin deficiency in knockout mice nor lentiviral vector-mediated Capucin overexpression in the striatum of adult wild type mice significantly modified vulnerability to the mHtt fragment in vivo, suggesting that Capucin has no impact on mHtt toxicity.


Implications of demographics on future blood supply: a population-based cross-sectional study.
Data on blood recipients are sparse and unconnected to data on blood donors. The objective was to analyze the impact of the demographic change on future blood demand and supply in a German federal state. A population-based cross-sectional study was conducted. For all in-hospital transfused red blood cells (RBCs; n = 95,477), in the German federal state Mecklenburg-Pomerania in 2005, characteristics of the patient and the blood donor (118,406 blood donations) were obtained. Population data were used to predict blood demand and supply until 2020. By 2020 the population increase of those aged 65 years or more (+26.4%) in Mecklenburg-Pomerania will be paralleled by a decrease of the potential donor population (18-68 years; -16.1%). Assuming stable rates per age group until 2020, the demand for in-hospital blood transfusions will increase by approximately 25% (24,000 RBC units) while blood donations will decrease by approximately 27% (32,000 RBC units). The resulting, predicted shortfall is 47% of demand for in-hospital patients (56,000 RBC units). Validation using historical data (1997-2007) showed that the model predicted the RBC demand with a deviation of only 1.2%. Demographic changes are particularly pronounced in former East Germany, but by 2030 most European countries will face a similar situation. The decrease of younger age groups requires an increase of blood donation rates and interdisciplinary approaches to reduce the need for transfusion to maintain sufficient blood supply. Demography is a major determinant of future transfusion demand. All efforts should be made by Western societies to systematically obtain data on blood donors and recipients to develop strategies to meet future blood demand.


Synthesis and antifungal activity of novel sulfoxide derivatives containing trimethoxyphenyl substituted 1,3,4-thiadiazole and 1,3,4-oxadiazole moiety.
Selective oxidation of sulfides 7 or 8 to sulfoxides 9 or 10 is achieved by mCPBA. The structures of the compounds 9 or 10 are confirmed by elemental analysis, IR, and (1)H NMR. The bioassay results showed that title compound 10a possess high antifungal activities with EC(50) values ranging from 19.91 to 63.97 microg/mL. The mechanism of action of 10a against Sclerotinia sclerotiorum was studied. After treating with compound 10a at 100 microg/mL for 12 h, the mycelial reducing sugar, D-GlcNAc, soluble protein and pyruvate content, chitinase activity showed declining tendency.


Treatment of infantile colic with surface active substance (simethicone).
The effect of Simethicone on "colicky" (n = 27) infants was tested in a double-blind cross-over study. Three different parameters were used to measure the efficiency of the treatment: interviews, 24-hour records and behavioral observations. No effects of Simethicone on the symptoms of infantile colic could be demonstrated. However, 67% of the infants improved during the treatment, which could be ascribed to a high-grade placebo-effect.


Forced-exposure trials increase suboptimal choice.
The influence of single option or forced-exposure (FE) trials was studied in the suboptimal choice task. Pigeons chose between an optimal alternative that led to food half of the time and a suboptimal alternative that led to food 20% of the time. Choice of the suboptimal alternative was compared across groups of subjects that received different numbers of FE trials during training. In Experiment 1, subjects received 100% FE trials, 67% FE trials, or only choice trials. Pigeons in the two groups that had FE trials developed extreme preference for the signaled suboptimal alternative over the unsignaled optimal alternative, while pigeons that had no FE trials showed pronounced individual differences. Experiment 2 compared 10% and 90% FE trials. When neither alternative signaled trial outcomes, both groups of subjects strongly preferred the optimal alternative. When the suboptimal alternative provided differential signals, the subjects in the 90% FE group developed strong preference for the suboptimal alternative and subjects in the 10% FE group maintained preference for the optimal alternative. The results of both experiments demonstrate that FE trials can have substantial effects on the development of preference in the suboptimal choice task.


Preventing Retraction With Use of Primary Eyelid Spacer Grafts in Cosmetic Lower Lid Blepharoplasty.
Lower eyelid retraction is a challenging complication that can develop after a cosmetic lower eyelid blepharoplasty. Factors such as proptosis and negative orbital vector may place patients at a higher risk for developing postblepharoplasty retraction. Rather than addressing this complication after it occurs postoperatively, this study focuses on preventing its occurrence through the use of primary eyelid spacer grafts during the initial blepharoplasty. The goal of this study was to review the outcomes of primary eyelid spacer graft placement during the initial cosmetic lower lid blepharoplasty. A retrospective chart review was performed at Emory Eye Center between January 1, 2014, and January 1, 2022. Patients that underwent lower eyelid blepharoplasty with primary eyelid spacer graft placement were identified and included in the study. Fifteen patients with Hertel measurements of >17 and adequate preoperative and postoperative photographs were analyzed. Fifteen patients with exophthalmometry measurements of >17 and adequate preoperative and postoperative photographs were analyzed. The mean change in marginal reflex distance 2 was 0.19 mm (range, -1.05 to 1.24 mm). Two patients developed eyelid retraction at their long-term follow-up. Both patients developed retraction about 2 years after the initial surgery. Although this study was limited by its retrospective nature and had a small sample size, none of these high-risk patients developed immediate post blepharoplasty retraction. Careful preoperative evaluation should be performed to identify these high-risk patients, and placement of a primary eyelid spacer graft during the initial lower eyelid blepharoplasty should be considered in this population.


Delayed gastric emptying following pancreatoduodenectomy with alimentary reconstruction according to Roux-en-Y or Billroth-II.
Delayed gastric emptying (DGE) remains the most frequent complication following pancreatoduodenectomy (PD) with published incidences as high as 61%. The present study investigates the impact of bowel reconstruction techniques on DGE following classic PD (Whipple-Kausch procedure) with pancreatogastrostomy (PG). We included 168 consecutive patients who underwent PD with PG with either Billroth II type (BII, n = 78) or Roux-en-Y type reconstruction (ReY, n = 90) between 2004 and 2015. Excluded were patients with conventional single loop reconstruction after pylorus preserving procedures. DGE was classified according to the 2007 International Study Group of Pancreatic Surgery definition. Patients were analyzed regarding severity of DGE, morbidity and mortality, length of hospital stay and demographic factors. No difference was observed between BII and ReY regarding frequency of DGE. Overall rate for clinically relevant DGE was 30% (ReY) and 26% (BII). BII and ReY did not differ in terms of demographics, morbidity or mortality. DGE significantly prolongs ICU (four vs. two days) and hospital stay (20.5 vs. 14.5 days). Risk factors for DGE development are advanced age, retrocolic reconstruction, postoperative hemorrhage and major complications. The occurrence of DGE can not be influenced by the type of alimentary reconstruction (ReY vs. BII) following classic PD with PG. Old age and major complications could be identified as important risk factors in multivariate analysis. German Clinical Trials Register (DRKS) DRKS00011860 . Registered 14 March 2017.


Independent clonal origin of multiple uterine leiomyomas that was determined by X chromosome inactivation and microsatellite analysis.
In an attempt to clarify the clonality and genetic relationships that are involved in the tumorigenesis of uterine leiomyomas, we used a total of 43 multiple leiomyomas from 14 patients and analyzed the allelic status with 15 microsatellite markers and X chromosome inactivation analysis. We have used a set of 15 microsatellite polymorphism markers mapped on 3q, 7p, 11, and 15q by automated analysis. The X chromosome inactivation was evaluated by the methylation status of the X-linked androgen receptor gene. Loss of heterozygosity analysis showed a different pattern in 7 of the 8 cases with allelic loss for at least 1 of 15 microsatellite markers that were analyzed. A similar loss of heterozygosity findings at 7p22-15 was detected in 3 samples from the same patient. X chromosome inactivation analysis demonstrated the same inactivated allele in all tumors of the 9 of 12 informative patients; different inactivation patterns were observed in 3 cases. Our data support the concept that uterine leiomyomas are derived from a single cell but are generated independently in the uterus. Loss of heterozygosity findings at 7p22-15 are consistent with previous data that suggested the relevance of chromosomal aberrations at 7p that were involved in individual uterine leiomyomas.


Acute obstructive suppurative cholangitis in a man with an enlarged inferior pancreaticoduodenal lymphnode.
A case report of a 55-year-old male, who was seen with epigastric pain and hyperamylasemia, is to be presented. He failed to respond to the intensive antibiotic therapy, and subsequently acute obstructive suppurative cholangitis fully developed. At laparotomy, an inflammatory enlarged inferior pancreaticoduodenal lymphnode, which apparently compressed the common bile duct, was found. To our knowledge, no prior case of acute obstructive suppurative cholangitis provoked by an enlarged lymphnode has been reported. A plea is made for attention to lymphnodes involved by inflammatory or neoplastic disorders, as well as common provoking agents such as calculi.


Impact of ER520, a candidate of selective estrogen receptor modulators, on in vitro cell growth, migration, invasion, angiogenesis and in vivo tumor xenograft of human breast cancer cells.
ER520, a derivative of indenoisoquinoline, is a patented compound. This study was designed to screen its biological properties and to evaluate its antineoplastic and antiangiogenic effect. Western blot was employed to monitor the ERα and ERβ protein expression in human breast cancer MCF-7 cells and endometrial carcinoma Ishikawa cells. MTT assay was employed to determine cell proliferation. Cell adhesion, scratch and Transwell assay were utilized to estimate the ability of cellular adhesion, migration and invasion. ELISA kit was applied to detect the VEGF products in culture medium. In addition, the inhibitory effect of ER520 on the vessel-like construction of HUVEC cells and the angiogenesis of chicken embryos was investigated. The efficiency of ER520 on tumor growth in nude mice was also assessed. ER520 inhibited the expression of ERα in MCF-7 and Ishikawa cells, while it increased ERβ protein level. ER520 also suppressed the proliferation of MCF-7 and Ishikawa cells. Due to its remarkably negative role in cell adhesion, migration and invasion, ER520 showed a potential ability of inhibiting tumor metastasis. Meanwhile, ER520 reduced the VEGF secretion of MCF-7 and Ishikawa cells, prevented the formation of VEGF-stimulated tubular structure and the cell migration of HUVEC cells, and inhibited the angiogenesis of chicken chorioallantoic membrane. Animal experiment also demonstrated that ER520 could frustrate the in vivo tumor growth and the inhibitory ratio was 48.5 % compared with control group. Our findings indicate that ER520 possesses the competence to be a candidate against breast cancer and angiogenesis.


Male Armaments and Reproductive Behavior in "Nutcracker" Camel Crickets (Rhaphidophoridae, Pristoceuthophilus).
Males of many species possess striking weaponry used in intrasexual competition for access to females. Until recently, there were no known cases of male weaponry being used against females in sexual coercion. However, in the camel cricket, Pristoceuthophilus marmoratus, males use modified hind legs to fight with each other and also to trap females and force them to copulate. To determine whether hind leg armaments serve similar fighting and mating functions in morphologically similar congeners, we performed a comparative survey of armament use in intra- and inter-sexual interactions in four additional species of Pristoceuthophilus (P. arizonae and three undescribed species: P. 'Huachuca summer,' P. 'Madera' and P. 'Mt. Pinos'). Intrasexual leg fighting occurred in all species for which trials were performed, and hints of sexual coercion occurred in two species (P. 'Huachuca summer' and P. 'Mt. Pinos'), suggesting additional cases of a uniquely dual-purpose armament. These findings suggest an evolutionary exaptation of hind leg armaments in this genus, wherein an intrasexual fighting weapon took on a secondary function of sexual coercion.


Safety and Efficacy of Combined Transarterial Embolization and Percutaneous Radiofrequency Ablation for Liver Tumors Using Cone-Beam CT and Needle Navigation Software in a Single Session.
To assess the safety and efficacy of single-session transarterial embolization and radiofrequency (RF) ablation for hepatic tumors with the use of needle navigation software. Retrospective analysis was conducted of 24 patients with liver cancer undergoing embolization followed by RF ablation between May 2014 and August 2017. Twelve patients each underwent (i) embolization and computed tomography (CT)-guided RF ablation during different sessions (group 1) and (ii) embolization followed by RF ablation with cone-beam CT and Needle Assist software in 1 session (group 2). Median age (70.5 y [range, 58-78 y] vs 70.5 y [range, 50-82 y]; P = .76) and performance status (0/1) were comparable between groups. Median tumor size was significantly larger in group 2 (2 cm [range, 1.0-7.3 cm] vs 3.2 cm [range, 1.1-9.6 cm]; P < .03). Procedure time, effective dose, and number of scans were examined. Efficacy was assessed by modified Response Evaluation Criteria In Solid Tumors after 1 month. Safety was assessed by Society of Interventional Radiology adverse event classification. Group 1 had a mean of 8.5 CT scans, vs a mean of 5.0 cone-beam CT scans in group 2 (P < .001). Median procedure times were 110 min in group 1 and 199.5 min in group 2 (P < .001). Median effective doses were 68.8 mSv in group 1 and 55.4 mSv in group 2 (P = .38). There was no difference in complete response between groups (66.7% vs 63.6%; P = 1). Transarterial embolization followed by RF ablation with cone-beam CT and needle guidance software in a single session seems to be safe and effective.


Prediction of en-route complications during interfacility transport by outcome predictive scores in ED.
The objective was to determine the accuracy of the outcome predictive scores (Modified Early Warning Score [MEWS]; Hypotension, Low Oxygen Saturation, Low Temperature, Abnormal ECG, Loss of Independence [HOTEL] score; and Simple Clinical Score [SCS]) in predicting en-route complications during interfacility transport (IFT) in emergency department. This was a retrospective cohort study. All IFT cases by ambulances with either nurse-led or physician-led escort, occurring between 1 January 2011 and 31 December 2012, were included. Obstetric and pediatric cases (age < 18 years) were excluded. The condition of patients was quantified by using the predictive scores (MEWS, HOTEL, and SCS) at triage station and on ambulance departure. The accuracy of predictive scores was compared by the receiver operating characteristic (ROC) curves. A total of 659 cases were included. Seventeen cases had en-route complications (2.6%). The complication rate in physician-escorted transport (2.2%) was similar to that in nurse-escorted transport (2.6%). None of the 57 intubated cases had en-route complications. The area under the ROC curve for MEWS was 0.662 (triage) and 0.479 (departure). The accuracy of MEWS at triage was better than that at departure (P = .049). The area under the ROC curve for HOTEL was 0.613 (triage) and 0.597 (departure), and that for SCS was 0.6 (triage) and 0.568 (departure). In general, the predictive scores at triage were better than those on departure. None of the scores had good accuracy in prediction of en-route complications during IFT. MEWS at triage was among the best one already but was not ideal.


Isolation of enterovirus strains from children with preclinical Type 1 diabetes.
To develop methods for isolation of enterovirus strains from subjects with preclinical Type 1 diabetes and evaluate if their presence in stools is associated with beta-cell damage. The study subjects were participants of the Finnish Type 1 Diabetes Prediction and Prevention Study (DIPP). The prospectively followed birth cohort comprised 12 children who turned positive for diabetes-associated autoantibodies during the follow-up (case children) and 53 controls matched for date of birth, sex and HLA-DQB1 alleles. Altogether, 878 stool samples were analysed for the presence of enterovirus RNA by RT-PCR followed by virus isolation and partial sequencing of viral genome. Enterovirus antibodies and RNA were simultaneously analysed from serum. Eleven enterovirus infections were diagnosed in case children and 42 infections in control children by the presence of viral RNA in stools. The proportion of children who were repeatedly enterovirus RNA-positive stools was higher among case than control children (42% vs. 11% of children; P=0.02). Combined serum (antibody and RT-PCR) and stool analyses indicated at least one enterovirus infection in 83% of the case children before the appearance of autoantibodies, while only 42% of the control children had infection by the same age (P=0.006). Twelve enterovirus strains were isolated from case children and 38 strains from control children. This protocol makes it possible to isolate a large number of enterovirus strains from prediabetic subjects. The findings suggest that enterovirus infections may be associated with the beta-cell damaging process.


Trends in Breast Augmentation Research: A Bibliometric Analysis.
Breast augmentation is one of the most demanded procedures in plastic surgery and one of the most commonly performed by plastic surgeons. However, a bibliometric analysis of breast augmentation has not been published in recent years. The current study aimed to use a bibliometric analysis to conduct a qualitative and quantitative evaluation of breast augmentation research and provide the research trends and hotspots in this field. Publications on breast augmentation research were extracted from the Web of Science core collection database. VOSviewer 1.6.18 was used to assess co-authorship, co-occurrence, citation of countries, institutions, authors, and journals, as well as hotspot keywords. On February 8, 2022, 4637 records of breast augmentation research published from 1985 to 2021 were collected. The bulk of the retrieved studies were original research articles (n = 2235, 48.20%). A total of 1053 (22.71%) papers were open access. The annual publication output increased annually. The USA was the driving force in this field and had a strong academic reputation. The top-contributing institution was the University of Texas MD Anderson Cancer Center (2.37%, with 110 publications). Plastic and reconstructive surgery (998 publications, 21.52%) published the most research in this field and was also the most frequently co-cited journal (22,351 citations, total link strength (TLS): 409,301). Clemens MW (68 publications, 1.47%) was the most prolific author, and Spear SL (1456 citations, TLS: 27,231) was the most frequently co-cited author. The research hotspots included the following four aspects: safety and effectiveness of breast implants, implant-based breast reconstruction, breast cancer incidence after breast implantation, and breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL). The research trends were BIA-ALCL, implant-based breast reconstruction, BREAST-Q, acellular dermal matrix, capsular contracture, and autologous fat grafting. The present study provides a panoramic view of breast augmentation research in plastic and reconstructive surgery. This novel comprehensive bibliometric analysis can help researchers and nonresearchers alike to rapidly identify the potential partners, research hotspots, and research trends within their areas of interest. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Protection of methylflavonolamine against acute cerebral ischemia reperfusion injury in rats.
To examine the possible beneficial action of methylflavonolamine (MFA) on cerebral ischemia/reperfusion injury. Acute cerebral ischemia-reperfusion injury was produced by 4-vessel occlusion and subsequent 1-h release. MFA, 20 mg kg-1, was injected intravenously 5 min before occlusion and again before release. The brain water content in the reperfusion group (Rep) was elevated (82.7% +/- 1.1% vs control 79.7% +/- 0.5%, P < 0.01), while MFA alleviated the brain edema (80.9% +/- 0.9% vs Rep, P < 0.01). The CK level of brain tissue in Rep decreased (4.7 +/- 1.4 vs control 8.4 +/- 1.2 U/mg protein, P < 0.01), but MFA restored it (7.2 +/- 1.1 U/mg protein vs Rep, P < 0.01). Reperfusion caused the rise of lipid peroxides (2.3 +/- 0.5 vs control 1.5 +/- 0.4 nmol/mg protein, P < 0.01) and weakened the superoxide dismutase (SOD) (3.1 +/- 1.6 vs control 10.5 +/- 3.9 U/mg protein P < 0.01), MFA reduced the rise of lipid peroxides (1.6 +/- 0.4 nmol/mg protein vs Rep, P < 0.05) and protected the activity of SOD (7.9 +/- 1.6 U/mg protein vs Rep, P < 0.01) in brain. MFA has the protective effects on cerebral ischemia/reperfusion, and these effects are relative to scavenging free radicals and anti-lipid peroxidation.


Non-technical skills for urological surgeons (NoTSUS): development and evaluation of curriculum and assessment scale.
In the last decade non-technical skills (NTS) have emerged as a vital area for improvement within surgery. This study aims to develop and evaluate a Non-technical Skills for Urological Surgeons (NoTSUS) training curriculum and assessment scale. This international, longitudinal and observational study began with a 3-round Delphi methodology to refine curriculum contents and rating scale. Sessions with up to four participants were delivered where each candidate undertook an independent scenario within the validated full immersion simulation environment. Candidates were assessed using both the NoTSS (Non-technical Skills for Surgeons) and NoTSUS rating scales by NTS-trained and non-trained experts. A post-training evaluation survey was distributed. 62 participants comprising trainees (n = 43) and specialists (n = 19) undertook the NoTSUS course. The NoTSS and NoTSUS scales correlated well, with a mean difference of 3.3 in the overall total (p = 0.10, r = 0.53). However, there was significant differences in scores between the NoTSS-trained and non-trained raters (n = 28, p = 0.03). A one-way ANOVA test revealed significant improvement throughout the four simulation scenarios in each session (p = 0.02). The NoTSUS curriculum received positive feedback from participants and demonstrated educational value and acceptability. The NoTSUS curriculum has demonstrated high educational value for NTS training aimed at urologists, with marked improvement throughout sessions. Correlation of NoTSUS and NoTSS scales proves its suitability for evaluating NTS in future training. Demonstration of inter-rater reliability indicates that the scale is reliable for use in assessment by expert faculty members. Furthermore, qualitative feedback from participants suggests gain of transferrable skills over the course.


Attenuating effects of melatonin on pilocarpine-induced seizures in rats.
Daily melatonin (10-50 mg/kg, i.p.) treatment at 08.30 h or 17.00 h for 1 week of female rats (2-months-old) increased the latency to the appearance of the first convulsion in the pilocarpine-induced seizure model. Other behavior parameters remained unaltered. The anticonvulsant effect of melatonin seemed to be more intense at the light-dark transition. Moreover, the effect of repeated melatonin treatment was also age-related, since it showed a lower threshold in 2-month-old than in 21-day-old rats, and the acute treatment was not efficient. [3H]N-methylscopolamine binding was unaltered in the hippocampus and striatum of adult rats after the association of melatonin and pilocarpine. While muscarinic binding was unaltered in adult rats, it increased in the hippocampus of young rats in the presence of melatonin (50 mg/kg) and pilocarpine, and did not change in the striatum. Melatonin partially recovered [3H]GABA binding in the hippocampus in the presence of pilocarpine-induced seizures, and intensified pilocarpine effects in the striatum of adult rats.


Playing God and the intrinsic value of life: moral problems for synthetic biology?
Most of the reports on synthetic biology include not only familiar topics like biosafety and biosecurity but also a chapter on 'ethical concerns'; a variety of diffuse topics that are interrelated in some way or another. This article deals with these 'ethical concerns'. In particular it addresses issues such as the intrinsic value of life and how to deal with 'artificial life', and the fear that synthetic biologists are tampering with nature or playing God. Its aim is to analyse what exactly is the nature of the concerns and what rationale may lie behind them. The analysis concludes that the above-mentioned worries do not give genuine cause for serious concern. In the best possible way they are interpreted as slippery slope arguments, yet arguments of this type need to be handled with care. It is argued that although we are urged to be especially vigilant we do not have sufficiently cogent reasons to assume that synthetic biology will cause such fundamental hazards as to warrant restricting or refraining from research in this field.


Study on mineral elements in Salvia roborwskii from the Qinghai-Tibet Plateau.
The contents of trace elements, including aluminum, barium, beryllium, calcium, cobaltium, chromium, copper, iron, potassium, lanthanum, lithium, magnesium, manganese, sodium, nickel, phosphorus, lead, sulfur, silicon, titanium, vanadium, and zinc, were determined by ICP-AES. The mean concentrations of the 22 elements were as follows: K>Ca>Mg>Fe>Al>Na>S>P>Ba>Ti>Mn>Zn>Sr>Cu>Ni=Cr>Pb>V>Li=La>Co>Be. Principal components analysis of SPSS was applied to study the characteristic elements in Salvia roborwskii. Five principal components which accounted for 89.288% of the total variance were extracted from the original data. The first factor accounted for 56.401% of the total variance, which meant that aluminum, barium, beryllium, calcium, and cobaltium were the characteristic elements in S. roborwskii. This useful new method was used to evaluate the quality of S. roborwskii, and to provide the scientific foundation for its utilization and further research.


Breakfast and lunch meal skipping patterns among fourth-grade children from selected public schools in urban, suburban, and rural maryland.
The objective of this study was to describe breakfast and lunch consumption patterns of fourth-grade students from selected public schools in Maryland and how they differ by geographic location. Data were collected from a sample of 540 fourth-grade public school children (46% male, 62% white; mean age=9 years) from three geographically distinct regions of Maryland (30% rural, 30% suburban, and 40% urban). Data on breakfast and lunch consumption were collected using an in-classroom questionnaire. chi(2) tests were used to compare skipping meal behavior by geographic location. Twenty percent of fourth-grade students reported skipping breakfast and/or lunch at least three times per week. Urban students were more than twice as likely to skip breakfast and to eat school-prepared meals compared with suburban and rural students. Dietitians in all regions need to explore new ways to encourage regular meal consumption among students in their schools.


Utility of duplex ultrasound in detecting and grading de novo femoropopliteal lesions.
Digital subtraction angiography (DSA) is the gold standard for diagnosing lower extremity (LE) arterial lesions. However, duplex ultrasound (DUS) is a widely used, safe, and noninvasive method of detecting LE lesions. The purpose of this study was to establish DUS criteria for detecting and grading de novo stenotic lesions in the femoropopliteal arterial segment. A prospective database was established including all patients who underwent LE endovascular interventions between 2004 and 2009. Patients with de novo stenotic lesions in the femoropopliteal segment were selected. DUS and DSA data pairs ≤30 days apart were analyzed. Peak systolic velocity (PSV; cm/s), velocity ratio (Vr), and DSA stenosis were noted. Linear regression and receiver operator characteristic (ROC) curves were used. Two hundred seventy-five lesions in 200 patients were analyzed. Indications were claudication (50.5%), rest pain (12.5%), and tissue loss (37.0%). Mean time interval between DUS and DSA was 24 days. Both PSV (R = .80, R(2) = .641; P < .001) and Vr (R = .73, R(2) = .546; P < .001) showed strong correlation with the degree of angiographic stenosis. ROC analysis showed that to detect ≥70% stenosis, a PSV of 200 cm/s had 89.2% sensitivity and 89.7% specificity, and a Vr of 2.0 had 88.7% sensitivity and 90.2% specificity. Similarly, to differentiate between <50% and ≥50% stenosis, PSV of 150 cm/s and Vr of 1.5 were highly specific and predictive. Combining PSV 200 cm/s and Vr 2.0 for ≥70% stenosis gave 79.0% sensitivity, 99.0% specificity, 99.0% positive predictive value, and 85.0% negative predictive value. DUS shows a strong agreement with angiography and has good accuracy in detecting femoropopliteal lesions. We propose DUS criteria of PSV 200 cm/s and Vr 2.0 to differentiate between <70% and ≥70% de novo stenosis in the femoropopliteal arterial segment.


Diffusion-weighted magnetic resonance imaging in patients with unilateral prostate cancer on extended prostate biopsy: predictive accuracy of laterality and implications for hemi-ablative therapy.
We evaluated the ability of extended prostate biopsy to detect unilateral prostate cancer and assessed the incremental diagnostic benefit of diffusion-weighted magnetic resonance imaging to predict unilateral prostate cancer. A total of 130 patients with prostate cancer detected by extended pattern prostate biopsy underwent magnetic resonance imaging before radical prostatectomy. Tumor laterality on extended prostate biopsy was compared with the corresponding lobe on the radical prostatectomy specimen. In patients with unilateral prostate cancer on biopsy we calculated the probability of a tumor in the contralateral lobe on magnetic resonance images and calculated area under the receiver operating characteristics curve. We compared the diagnostic accuracy of combined T2-weighted and diffusion-weighted magnetic resonance images to that of T2-weighted magnetic resonance images alone. Of the 130 patients 88 (67.7%) had unilateral disease on extended prostate biopsy. Radical prostatectomy pathology showed that 19% of these patients had unilateral disease but 81% had bilateral disease. Area under the receiver operating characteristics curve of combined diffusion-weighted and T2-weighted magnetic resonance imaging was greater than that of T2-weighted magnetic resonance imaging alone (0.814, 95% CI 0.716-0.889 vs 0.510, 95% CI 0.401-0.618). T2-weighted plus diffusion-weighted magnetic resonance imaging had significantly higher sensitivity (84.1% vs 61.9%, p = 0.003) and specificity (72.0% vs 36.0%, p = 0.004) to predict cancer in the contralateral lobe than T2-weighted magnetic resonance alone. Extended prostate biopsy cannot accurately determine prostate cancer unilaterality. Diffusion-weighted magnetic resonance combined with T2-weighted magnetic resonance imaging has an incremental diagnostic benefit to predict unilateral prostate cancer.


Expression of the tyrosine phosphatase SRC homology 2 domain-containing protein tyrosine phosphatase 1 determines T cell activation threshold and severity of experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is a CD4 Th1-mediated inflammatory demyelinating disorder of the CNS and a well-established animal model for multiple sclerosis. Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1) is a cytosolic tyrosine phosphatase that is involved in regulating the T cell activation cascade from signals initiated through the TCR. To study the role of SHP-1 in EAE pathogenesis, we immunized B10.PL mice heterozygous for deletion of the SHP-1 gene (me(v+/-)) and B10.PL wild-type mice with the immunodominant epitope of myelin basic protein (MBP Ac1-11). T cell proliferation and IFN-gamma production were significantly increased in me(v+/-) mice after immunization with MBP Ac1-11. The frequency of MBP Ac1-11-specific CD4 T cells, analyzed by staining with fluorescently labeled tetramers (MBP1-11[4Y]: I-A(u) complexes), was increased in the draining lymph node cells of me(v+/-) mice compared with wild-type mice. In addition, me(v+/-) mice developed a more severe course of EAE with epitope spreading to proteolipid protein peptide 43-64. Finally, expansion of MBP Ac1-11-specific T cells in response to Ag was enhanced in me(v+/-) T cells, particularly at lower Ag concentrations. These data demonstrate that the level of SHP-1 plays an important role in regulating the activation threshold of autoreactive T cells.


Alternative splicing downstream of EMT enhances phenotypic plasticity and malignant behavior in colon cancer.
Phenotypic plasticity allows carcinoma cells to transiently acquire the quasi-mesenchymal features necessary to detach from the primary mass and proceed along the invasion-metastasis cascade. A broad spectrum of epigenetic mechanisms is likely to cause the epithelial-to-mesenchymal (EMT) and mesenchymal-to-epithelial (MET) transitions necessary to allow local dissemination and distant metastasis. Here, we report on the role played by alternative splicing (AS) in eliciting phenotypic plasticity in epithelial malignancies with focus on colon cancer. By taking advantage of the coexistence of subpopulations of fully epithelial (EpCAMhi) and quasi-mesenchymal and highly metastatic (EpCAMlo) cells in conventional human cancer cell lines, we here show that the differential expression of ESRP1 and other RNA-binding proteins (RBPs) downstream of the EMT master regulator ZEB1 alters the AS pattern of a broad spectrum of targets including CD44 and NUMB, thus resulting in the generation of specific isoforms functionally associated with increased invasion and metastasis. Additional functional and clinical validation studies indicate that both the newly identified RBPs and the CD44s and NUMB2/4 splicing isoforms promote local invasion and distant metastasis and are associated with poor survival in colon cancer. The systematic elucidation of the spectrum of EMT-related RBPs and AS targets in epithelial cancers, apart from the insights in the mechanisms underlying phenotypic plasticity, will lead to the identification of novel and tumor-specific therapeutic targets.


Prolonged signal-averaged P-wave duration as an intermediate phenotype for familial atrial fibrillation.
This study sought to perform a genome-wide linkage analysis in a large atrial fibrillation (AF) kindred using AF and abnormally prolonged signal-averaged (SA) P-wave duration as the phenotype. Although inherited forms of AF exist, phenotypic complexity has limited efforts to ascertain mutation carriers and thus identify causal genes. The identification of intermediate or endophenotypes may accelerate this effort. A genome-wide linkage analysis was performed in a 4-generation AF kindred of 27 individuals, 8 with AF documented by electrocardiogram. The analysis was performed using AF as the phenotype, and repeated using an abnormally prolonged SA P-wave duration as the phenotype. Linkage analysis and fine mapping generated a maximum multipoint logarithm of the odds (LOD) score of 3.0 at chromosome 5p15 between markers D5S406 and D5S635. Importantly, 8 heterozygous carriers had a prolonged SA P-wave (203 +/- 21 ms) compared with 17 noncarriers (116 +/- 12 ms, p < 0.00001). Using prolonged SA P-wave (conventionally defined as >155 ms) as an endophenotype, a maximum LOD score of 3.6 was obtained in the same region of chromosome 5p15, a span of 5.75 centi-Morgans. In a large AF kindred, we have identified a novel AF locus on chromosome 5p15 and shown that affected individuals with AF and mutation carriers can be identified by a prolonged SA P-wave duration. Importantly, identification of an endophenotype in this kindred not only aided ascertainment of additional family members but also increased the LOD score, providing increased support for linkage at this locus. Identification of the causal gene, mapped to chromosome 5p15, will advance our understanding of the molecular basis of AF.


Co-existence of vasoactive intestinal polypeptide (VIP)- and cholecystokinin (CCK)-like immunoreactivities in thalamocortical neuron in the ventrolateral nucleus of the rat.
Cholecystokinin (CCK)- and/or vasoactive intestinal polypeptide (VIP)-like immunoreactivity (LI) was seen in many thalamocortical VL neurons which were retrogradely labeled with wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected into the frontal cortex of the rat. VIP- or CCK-LI was observed in 70-80% or 50-60% of thalamocortical VL neurons, respectively. Almost all of thalamocortical VL neurons with CCK-LI exhibited VIP-LI.


Necrotizing vasculitis within cutaneous lesions of mycosis fungoides.
Mycosis fungoides is a T cell lymphoma with a predilection for cutaneous involvement. This paper describes the clinical manifestations and histopathologic features of a case of mycosis fungoides with necrotizing vasculitis localized to the lesions of cutaneous lymphoma. Elevated levels of circulating immune complexes were found in this patient. The large numbers of perivascular malignant helper T lymphocytes may have induced immunoglobulin synthesis, resulting in the formation of these complexes followed by deposition in vessel walls and subsequent necrotizing vasculitis. Possible alternative mechanisms include the presence of anti-T cell antibodies, or cytotoxic effector cells.


The Current State of Targeted Muscle Reinnervation: A Systematic Review.
Targeted muscle reinnervation (TMR) is growing in popularity; however, literature evaluating patient characteristics and outcomes is limited. The EMBASE database was queried with the search terms "targeted muscle reinnervation" OR "TMR" AND "outcomes" OR "patient outcomes." Clinical human studies in English were eligible for inclusion, yielding 89 articles. After rigorous exclusion criteria, a total of 13 articles were included in this review. Study data including geographic location, patient demographics, TMR indication, amputation level, number of nerve transfers performed, length of follow-up, and reported outcomes were extracted and analyzed. The included articles represent 338 patients (341 limbs). Average patient age was 47.4 years. Indication for amputation included trauma (n = 125), infection (n = 76) cancer/tumor resection (n = 71), ischemia (n = 18), failed Charcot reconstruction (n = 15), failed hardware (n = 9), burn (n = 4), and CRPS (n = 4). Five studies included upper extremity TMR only, two included lower extremity TMR only, and six included both upper and lower extremity TMR. TMR was performed in an immediate or delayed fashion, with an average of 2.2 nerve transfers performed per limb overall. Average length of follow-up was 22.3 months. In three studies, patients with phantom limb pain undergoing delayed TMR were found to have significant or trending toward significant reduction in pain after TMR using numeric rating scale and patient-reported outcomes measurement information system scales. One article reported 9/10 patients with improved or complete resolution of phantom limb pain after delayed TMR. Three studies found that patients undergoing immediate TMR had lower pain scores compared with non-TMR controls. While there is evidence that TMR reduces neuroma-related pain and improves the quality of life for amputees, further outcomes studies are needed to study the patient experience with TMR on a larger scale. Establishing standardized, validated patient-reported outcomes assessment tools is critical to future investigation in this field.


Selective total removal of a growth-hormone-secreting adenoma: evidence that acromegaly is a primary pituitary disease.
Acromegaly is caused by hypersecretion of growth hormone by the pituitary. There is some debate as to whether the primary etiology of the disease is abnormal hypothalamic stimulation of the pituitary or a primary pituitary tumor. This paper presents a case of acromegaly in which growth hormone dynamics in response to stimulation and suppression tests were abnormal. After transsphenoidal adenomectomy of a small tumor, growth hormone levels returned to normal and suppression and stimulation test results reverted to normal within 1 wk postoperatively and remained normal for 2 yr. The findings suggest that the acromegaly in this case was due to a primary pituitary dysfunction. Microsurgical removal of growth-hormone-secreting tumors provides a unique opportunity to study the etiology of acromegaly.


Missile injury of upper ureter treated by delayed renal autotransplantation and ureteropyelostomy.
We report a case of extensive upper ureteral loss due to a missile injury managed by delayed renal autotransplantation and ureteropyelostomy using the residual lower ureteral segment. The successful outcome attests to the value of this therapeutic strategy in severe traumatic injuries to the ureter secondary to bullet or shrapnel fragments.


The effect of urea moiety in amino acid binding by β-cyclodextrin derivatives: A 1000-fold increase in efficacy comparing to native β-cyclodextrin.
Water soluble amphiphilic anion receptors based on urea-substituted β-cyclodextrin were synthesized via a copper(I) mediated azide-alkyne coupling reaction. The synthetic route was designed to minimize the number of operations of cyclodextrins. Stable products were obtained in 90% yield. They were successfully tested as amino acid receptors, showing excellent affinity constants (103-104M-1) in a highly competitive environment (pH 8 phosphate-buffered water solution). Isothermal titration calorimetry indicated that complex formation strongly depends on the hydrophobic nature of the guest and that the urea moiety of the receptor is necessary to efficiently bind amino acids.


Effect of nitrogen fertilization upon the secondary chemistry and nutritional value of quaking aspen (Populus tremuloides Michx.) leaves for the large aspen tortrix (Choristoneura conflictana (Walker)).
We investigated the effects of nitrogen fertilization upon the concentrations of nitrogen, condensed tannin and phenolic glycosides of young quaking aspen (Populus tremuloides) leaves and the quality of these leaves as food for larvae of the large aspen tortrix (Choristoneura conflictana), a Lepidopteran that periodically defoliates quaking aspen growing in North America. Nitrogen fertilization resulted in decreased concentrations of condensed tannin and phenolic glycosides in aspen leaves and an increase in their nitrogen concentration and value as food for the large aspen tortrix. These results indicate that plant carbon/nutrient balance influences the quality of aspen leaves as food for the large aspen tortrix in two ways, by increasing the concentrations of positive factors (e.g. nitrogen) and decreasing the concentrations of negative factors (eg. carbon-based secondary metabolites) in leaves. Addition of purified aspen leaf condensed tannin and a methanol extract of young aspen leaves that contained condensed tannin and phenolic glycosides to artificial diets at high and low levels of dietary nitrogen supported this hypothesis. Increasing dietary nitrogen increased larval growth whereas increasing the concentrations of condensed tannin and phenolic glycosides decreased growth. Additionally, the methanol extract prevented pupation. These results indicate that future studies of woody plant/insect defoliator interactions must consider plant carbon/nutrient balance as a potentially important control over the nutritional value of foliage for insect herbivores.


Internal motional averaging and three-dimensional structure determination by nuclear magnetic resonance.
Dynamic averaging effects from internal motions on interproton distances estimated from nuclear Overhauser effects (NOE) are determined by using a molecular dynamics simulation of lysozyme. Generalized order parameters measuring angular averaging and radial averaging parameters are calculated. The product of these two parameters describes the full averaging effects on cross-relaxation. Analysis of 2778 non-methyl NOE interactions from the protein interior and surface indicates that distances estimated by assuming a rigid molecule have less than 10% error for 89% of the NOE interactions. However, analysis of 1854 methyl interactions found that only 68% of the distances estimated from cross-relaxation rates would have less than 10% error. Qualitative evaluation of distances according to strong, medium and weak NOE intensities, when used to define only the upper bound for interproton separation, would misassign less than 1% of the distance constraints because of motional averaging. Internal motions do not obscure the identification of secondary structure, although some instances of significant averaging effects were found for interactions in alpha-helical regions. Interresidue NOEs for amino acids more than three residues apart in the primary sequence are more extensively averaged than intraresidue or short-range interresidue NOEs. Intraresidue interactions exhibit a greater degree of angular averaging than those involving interresidue proton pairs. An internal motion does not equally affect all NOE interactions for a particular proton. Thus, incorporation of averaging parameters in nuclear magnetic resonance structure determination procedures must be made on a proton-pair-wise basis. On the basis of the motional averaging results, particular fixed-distance proton pairs in proteins are suggested for use as distance references. A small percentage of NOE pairs localized to three regions of the protein exhibit extreme averaging effects from internal motions. The regions and types of motions involved are described.


Erratum: Enhanced Delivery of Oncolytic Adenovirus by Neural Stem Cells for Treatment of Metastatic Ovarian Cancer.
[This corrects the article DOI: 10.1016/j.omto.2018.12.003.].


A Novel Distal Active Flexible Vacuum-assisted Ureteric Access Sheath in Retrograde Intrarenal Surgery.
Retrograde intrarenal surgery (RIRS) is one of the primary treatments for renal stones. The ureteral access sheath (UAS) was widely used in RIRS.1,2 The aim of this paper is to introduce a new UAS, the distal active flexible vacuum-assisted ureteral access sheaths (DAFV-UAS), for the renal calculus during RIRS. A 56-year-old female presented to the outpatient clinics of our hospital with a left renal lower calyx stone. Abdominal CT demonstrated that the left kidney's lower calyx stone size was 10.54 ×10.38 mm, and the mean Hounsfield density was 965HU. After adequate anti-infective treatment, the DAFV-UAS was used in RIRS. No perioperative complications were observed. The left renal stone had been cleared completely. The DAFV-UAS (10/12.5 Fr, 38 cm, creek, Jiangsu, China) includes a good flexibility and deformability tube at the tip, about 10 cm long. It has an active bending function, negative pressure suction function, and the function of convenient flexible ureteroscopy (f-URS) entry and exit of the ureter.3 In this case, the f-URS adopted a 7.5 Fr single-use digital f-URS. The Irrigation method was automated irrigation system, and the flow was 30 mL/min. The suction level was 0.02mpa. With the help of DAFV-UAS, the field of view is always clean, the small gravel particles can be sucked out from the sheath gap, and the larger gravel particles are sucked out by withdrawing the scope intermittently. DAFV-UAS is a promising new device which allows for negative pressure suction directed right at a renal stone and efficient and effective stone clearance.


The impact of ACE2 polymorphisms (rs1978124, rs2285666, and rs2074192) and ACE1 rs1799752 in the mortality rate of COVID-19 in different SARS-CoV-2 variants.
Clinical severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outcomes could be influenced by genetic polymorphisms in angiotensin I-converting enzyme (ACE1) and ACE2. This study aims to examine three polymorphisms (rs1978124, rs2285666, and rs2074192) on the ACE2 gene and ACE1 rs1799752 (I/D) in patients who have coronavirus disease 2019 (COVID-19) with various SARS-CoV-2 variants. Based on polymerase chain reaction-based genotyping, four polymorphisms in the ACE1 and ACE2 genes have been identified in 2023 deceased patients and 2307 recovered patients. The ACE2 rs2074192 TT genotype was associated with the COVID-19 mortality in all three variants, whereas the CT genotype was associated with the Omicron BA.5 and Delta variants. ACE2 rs1978124 TC genotypes were related to COVID-19 mortality in the Omicron BA.5 and Alpha variants, but TT genotypes were related to COVID-19 mortality in the Delta variant. It was found that ACE2 rs2285666 CC genotypes were associated with COVID-19 mortality in Delta and Alpha variants, and CT genotypes in Delta variants. There was an association between ACE1 rs1799752 DD and ID genotypes in the Delta variant and COVID-19 mortality, whereas there was no association in the Alpha or Omicron BA.5 variants. In all variants of SARS-CoV-2, CDCT and TDCT haplotypes were more common. In Omicron BA.5 and Delta, CDCC and TDCC haplotypes were linked with COVID-19 mortality. In addition to COVID-19 mortality, the CICT, TICT, and TICC were significantly correlated. The ACE1/ACE2 polymorphisms had an impact on COVID-19 infection, and these polymorphisms had different effects in various SARS-CoV-2 variants. To confirm these results, however, more research needs to be conducted.


Relationship of alcohol use and facial flushing to blood pressure and HbA1c among Cambodian populations with dysglycemia in the U.S. and in Cambodia.
Facial flushing after drinking alcohol, common among Asians, is a phenotype for genes involved in alcohol metabolism. We investigated cross-sectional associations between flushing, alcohol use, blood pressure (BP) and HbA1c among (n = 287) Cambodians with dysglycemia in Cambodia and in the U.S. Participants were categorized as Abstainers, Flushers who drink, or Non-flushers who drink. Flushers and Non-flushers had similar alcohol use. Flushers had higher BP than Non-flushers and Abstainers, even after controlling for confounders. Findings were similar across countries. Drinkers had higher HbA1c than Abstainers. Future research should examine whether reducing alcohol improves cardiometabolic outcomes.


Nicosulfuron Plus Atrazine Herbicides and Trichogrammatidae (Hymenoptera) in No-Choice Test: Selectivity and Hormesis.
The aim of this study was to evaluate the effect of the herbicide mixture nicosulfuron + atrazine on 10 trichogrammatid species. A female of each trichogrammatid was placed in a test tube (no-choice) with a card with 45 Anagasta kuehniella eggs. Parasitism was allowed over a 48 h period, then the cards were sprayed with a solution containing nicosulfuron (30 g ha-1) + atrazine (1500 g ha-1), besides the control (distilled water). The nicosulfuron + atrazine mixture increased the Trichogramma atopovirilia and T. pretiosum female emergence. The percentage of T. acacioi, T. atopovilia and T. pretiosum male parasitoids emerged was higher in the control, and for T. demoraesi and Trichogrammatoidea annulata with nicosulfuron + atrazine. Sex ratio of the trichogrammatids was similar with nicosulfuron + atrazine.


Childhood brain tumors: current status of clinical trials in newly diagnosed and recurrent disease.
Primary childhood brain tumors are the second most common form of childhood cancer. Though progress in this area has been slow, the field has evolved considerably over the past 10 years. This article focuses on new information that will influence our treatment of the more common pediatric brain tumors.


Synthesis of two-dimensional Ti3C2Tx/Au nanosheets with SERS performance.
This study proposes a new method for the preparation of novel MXenes/metal composites with unique chemical properties using reducing agent action. The effect of the reduction reaction time on the preparation conditions of ${{\rm Ti}_3}{{\rm C}_2}{{\rm T}_x}/{\rm Au}$Ti3C2Tx/Au nanocomposites is studied, and the contribution of the prepared nanocomposites to the surface Raman reinforcement is analyzed. This study further explores the application of MXene in surface-enhanced Raman spectroscopy.


[Proteins of the inflammatory reaction. Definition, physiology and methods for determination].
An inflammatory reaction protein is a protein whose rate of synthesis is greater than its rate of catabolism in the presence of an inflammatory process. This is reflected by an increase in its plasma concentration. In man, orosomucoid, alpha-1 antitrypsin, alpha-1 anti-chymotrypsin, haptoglobin, ceruloplasmin, fibrinogen and C reactive protein (CRP), all conform to this definition. The authors present the principal physicochemical properties of the proteins. However, none of these proteins, on its own, constitutes an ideal marker of inflammation. The authors also propose the use of an inflammatory miniprofile consisting of "CRP, orosomucoid and haptoglobin" to detect, quantify and follow an inflammatory reaction. The authors stress the importance of using a rapid assay technique like immunonephelemetry , which is essential for the clinical usefulness of these proteins. Finally, they discuss the process of synthesis and the biological role of these proteins.


Impairment of spinal motor neurons in spinocerebellar ataxia type 1-knock-in mice.
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by the expansion of polyglutamine repeats in the Ataxin-1 protein. An accumulating body of cerebellar, histological and behavioral analyses has proven that SCA1-knock-in mice (in which the endogenous Atxn1 gene is replaced with mutant Atxn1 that has abnormally expanded 154 CAG repeats) work as a good tool, which resembles the central nervous system pathology of SCA1 patients. However, the peripheral nervous system pathology of the model mice has not been studied despite the fact that the clinical manifestation is also characterized by peripheral involvement. We show here that spinal motor neurons are degenerated in SCA1-knock-in mice. Histologically, some spinal motor neurons of the SCA1-knock-in mice have polyglutamine aggregates in their nuclei and also thinner and demyelinated axons. Electrophysiological examinations of the mice showed slower nerve conduction velocities in spinal motor neurons and lower amplitudes of muscle action potential, compared to wild-type mice. Consistently, the mice displayed decrease in rearing number and total rearing time. These results suggest that the knock-in mice serve as a definite model that reproduces peripheral involvement and are therefore useful for research on the peripheral nervous system pathology in SCA1 patients.


Early perioperative quality of recovery after hip and knee arthroplasty: a retrospective comparative cohort study.
Increasing our knowledge about postoperative global Quality-Of-Recovery (QoR) after THA and TKA is important to improve perioperative medicine, in particular for preoperative patient information and benchmarking of postoperative patient status. This study is a single centre, retrospective cohort study of prospectively collected data, conducted in Strasbourg University Hospital, Strasbourg, France. The main outcome was the modified French version of the QoR-15 (mQoR-15F) score monitored preoperatively, at postoperative day one, three, 14 and 28. We questioned the hypothesis: would THA and TKA recovery patterns differ and would postoperative health status eventually overreach the preoperative reference? The mQoR-15F was statistically higher in the THA group compared to the TKA group in POD 1 and 28 (112 ± 17 vs. 107 ± 17; p < 0.01 and 131 ± 12 vs. 127 ± 15; p = 0.02, respectively). The mean postoperative time delay to reach preoperative mQoR-15F was seven and 16 days for THA and TKA patients, respectively. Early postoperative health status after THA and TKA differs significantly; TKA being associated with a larger early decrease of global health status compared to THA. Both THA and TKA groups global health status overreached preoperative levels after one and two weeks postoperatively. These surgery-specific recovery profiles may favor improved patient information to steer advised operative decision and set specific recovery goals as part of enhanced recovery pathways.


Management of complications of distal radioulnar joint.
The distal radioulnar joint (DRUJ) is a complex structure that participates in forearm rotation and weight-bearing. Myriad disorders affect the DRUJ and present diagnostic and management challenges. Degenerative and posttraumatic arthritis and pain at the DRUJ have been traditionally treated with resection of 1 of the 2 arthritic surfaces. Although the procedure often relieves pain associated with incongruence, it creates a different problem by changing the overall dynamics of the forearm rotation and weight-bearing, resulting in radioulnar convergence and ulnar translation of the carpus. This article focuses on the management of painful radioulnar convergence after distal ulnar resections.


Robot-Assisted Percutaneous Balloon Compression for Trigeminal Neuralgia: Technique Description and Short-Term Clinical Results.
Percutaneous balloon compression (PBC) is a minimally invasive treatment for trigeminal neuralgia (TG) with a favorable cost-effectiveness ratio, but this technique has a steep learning curve. This study presents our initial clinical experience of robot-assisted PBC using a neurosurgical robot on six consecutive patients with TG. We fixed the patient's head with a skull clamp and connected it with the linkage arms of a Sinovation® neurosurgical robot, which was then registered using four bone fiducials by the robotic pointer. The puncture needle was positioned at the entry point on the skin using a robotic arm and advanced to the target point after the skin had been incised with a pointed surgical blade. This procedure was repeated for a second trajectory. A balloon was then advanced and inflated using 0.3 ml of a contrast agent. Upon injection of 0.6 ml contrast agent, the ganglion was kept compressed for 120 s. After removal of the balloon and puncture needle, compression of the face was performed to achieve hemostasis. All patients achieved immediate pain relief following PBC. No permanent or severe complications were registered, and there was no pain recurrence in any of the patients during the follow-up period. Despite requiring a longer time for preoperative preparation, robot-assisted PBC provided a high degree of accuracy and safety, and it can also shorten the learning curve for surgeons unfamiliar with PBC. Robot-assisted surgical approaches should be further developed and adopted for PBC.


Countermeasure efficacy of apigenin for silicon-ion-induced early damage in blood and bone marrow of exposed C57BL/6J mice.
We investigated the countermeasure efficacy of apigenin (AP), given as a diet supplement, for radiation-induced damage in the hematopoietic tissues collected on day 7 after a total-body exposure of male C57BL/6J mice to 0 or 0.5 Gy of 260 MeV/n silicon (28Si) ions. We gave food with AP at the concentration of 20 mg/kg body weight (bw) (AP20) or without AP (AP0) to mice before and after irradiation. There were four groups of mice (six mice in each): Group 1- Control, i.e. No Radiation (0 Gy) with AP0; Group 2 - Radiation (0.5 Gy) with AP0; Group 3 - No Radiation (0 Gy) with AP20; and Group 4 - Radiation (0.5 Gy) with AP20. The complete blood count (CBC) and differential blood count were performed for each mouse. In the same mouse, an anti-clastogenic activity of AP was evaluated using the in vivo blood-erythrocyte micronucleus (MN) assay. Further in each mouse, bone marrow (BM) cells were collected and used for measuring the levels of activated nuclear factor-kappa B (NF-κB), and pro-inflammatory cytokines (i.e. tumor necrotic factor-alpha (TNF-α), interleukin-1α (IL-1α), IL-1 beta (IL-1β), and IL-6). We used the colony-forming unit assay (CFU-A) as a tool to study the countermeasure efficacy of AP against the harmful effects of 28Si ions on the proliferation of the hematopoietic stem/progenitor cells (HSPCs). Our results showed that AP is highly effective not only in the prevention of leukopenia and thrombocytopenia but also in the enhancement of erythropoiesis and the proliferation of HSPCs. We also observed the potent anti-clastogenic activity of AP given to mice as a diet supplement. Further, we found that AP is very effective in the suppression of activated NF-κB and pro-inflammatory cytokines, suggesting that AP given as a diet supplement protects mice from 28Si-ion-induced damage in the hematopoietic tissues of irradiated male C57BL/6J mice via its anti-inflammation activity.


Structural study on mutant alpha-L-iduronidases: insight into mucopolysaccharidosis type I.
To elucidate the basis of mucopolysaccharidosis type I (MPS I), we constructed structural models of mutant alpha-L: -iduronidases (IDUAs) resulting from 33 amino acid substitutions that lead to MPS I (17 severe, eight intermediate, and eight attenuated). Then, we examined the structural changes in the enzyme protein by calculating the number of atoms affected and determined the root-mean-square distance (RMSD) and the solvent-accessible surface area (ASA). In the severe MPS I group, the number of atoms influenced by a mutation and the average RMSD value were larger than those in the attenuated group, and the residues associated with the mutations identified in the severe group tended to be less solvent accessible than those in the attenuated group. The clinically intermediate phenotype group exhibited intermediate values for the numbers of atoms affected, RMSD, and ASA between those in the severe group and those in the attenuated group. The results indicated that large structural changes had occurred in the core region in the severe MPS I group and small ones on the molecular surface in the attenuated MPS I group. Color imaging revealed the distributions and degrees of the structural changes caused by representative mutations for MPS I. Thus, structural analysis is useful for elucidating the basis of MPS I. As there was a difference in IDUA structural change between the severe MPS I group and the attenuated one, except for a couple of mutations, structural analysis can help predict the clinical outcome of the disease.


Characterization and scatchard binding analysis of adrenal digitalis-like material.
Culture medium conditioned by the adrenocortical tumor cell line Y-1 has been fractionated by HPLC to determine whether the ouabain-like binding activity (OLB) of this medium co-purifies with digoxin immunoreactivity. Furthermore, we have evaluated whether this medium contains the ability to inhibit the ion translocating action of the sodium pump and how this material purifies on HPLC. These activities are not homogenous, however, maximal activity in each assay was found in the same HPLC fraction. The OLB of this fraction was not reduced by alkaline hydrolysis or trypsinization, heating in air at 150 degrees C did reduce activity. Scatchard binding analysis of this fraction indicated the presence of a single class of specific competitive inhibitor of the binding of radiolabelled ouabain to human erythrocytes. The inhibitor showed a Hill coefficient of unity.


Effect of ruthenium red, a ryanodine receptor antagonist in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats.
Diabetes mellitus is considered as a main risk factor for vascular dementia. In the past, we have reported the induction of vascular dementia by experimental diabetes. This study investigates the efficacy of a ruthenium red, a ryanodine receptor antagonist and pioglitazone in the pharmacological interdiction of pancreatectomy diabetes (PaD) induced vascular endothelial dysfunction and subsequent vascular dementia in rats. Attentional set shifting and Morris water-maze test were used for assessment of learning and memory. Vascular endothelial function, blood brain barrier permeability, serum glucose, serum nitrite/nitrate, oxidative stress (viz. aortic superoxide anion, brain thiobarbituric acid reactive species and brain glutathione), brain calcium and inflammation (myeloperoxidase) were also estimated. PaD rats have shown impairment of endothelial function, blood brain barrier permeability, learning and memory along with an increase in brain inflammation, oxidative stress and calcium. Administration of ruthenium red and pioglitazone has significantly attenuated PaD induced impairment of learning, memory, blood brain barrier permeability, endothelial function and biochemical parameters. It may be concluded that ruthenium red, a ryanodine receptor antagonist and pioglitazone, a PPAR-γ agonist may be considered as potent pharmacological agent for the management of PaD induced endothelial dysfunction and subsequent vascular dementia. Ryanodine receptor may be explored further for their possible benefits in vascular dementia.


Cold agglutinin autoimmune hemolytic anemia in nonhematologic malignancies.
Four patients with nonhematologic malignancies had the simultaneous finding of hemolytic anemia due to high-titer cold agglutinins. In each patient, the cold agglutinin had "anti-I" specificity and was of the IgM kappa immunoglobulin class. Although patients with hematologic malignancies not uncommonly have cold agglutinins, the association between these antibodies and nonhematologic malignancies is unusual.


Auscultatory versus oscillometric measurement of blood pressure in octogenarians.
Auscultatory measurement using a sphygmomanometer has been the predominant method for clinical estimation of blood pressure, but it is now rapidly being replaced by oscillometric measurement. To compare blood pressure by auscultatory and oscillometric measurements in patients ≥ 80 years. 100 patients had blood pressure measured by auscultation with a sphygmomanometer and by an electronic device using the oscillometric method. For each patient the mean of two blood pressures with each method measured within 15 min were compared. The mean age of participants was 85.8 years; 55.8% were women. The correlation coefficient for systolic blood pressure was 0.88 and for diastolic 0.79. Differences between auscultatory and oscillometric values were less than 10 mmHg in 70.6% of systolic blood pressures and in 83.2% for diastolic. Arrhythmia and hypertension did not influence the results, and there was no correlation between the magnitude of the differences and the level of blood pressure. Agreement between oscillometric and auscultatory measurements of blood pressure in octogenarians was found to be less than required by validation protocols. However, semi-automatic equipment, which is observer-independent, may be used even in the very elderly, particularly if multiple readings are performed.


Mitochondrial dysfunction in yeast expressing the cytoplasmic male sterility T-urf13 gene from maize: analysis at the population and individual cell level.
The urf13TW gene, which is derived from the mitochondrial T-urf13 gene responsible for Texas cytoplasmic male sterility in maize, was expressed in Saccharomyces cerevisiae by targeting its translation product into mitochondria. Analysis by oxygraphy at the population level revealed that in the presence of methomyl the oxygen uptake of intact yeast cells carrying the targeted protein is strongly stimulated only with ethanol as respiratory substrate and not with glycerol, lactate, pyruvate, or acetate. When malate is the substrate oxidized by isolated mitochondria, interaction between the targeted protein and methomyl results in significant inhibition of oxygen uptake. This inhibition is eliminated and oxygen uptake is stimulated by subsequent addition of NAD+. Using 3,3'-dihexyloxacarbocyanine iodide [DiOC6(3)] as probe, interactive laser scanning and flow cytometry, which permit analysis at the individual cell level, demonstrated that specific staining of the mitochondrial compartment is obtained and that DiOC6(3) fluorescence serves as a measure of the membrane potential. Finally, it was shown that, as in T cytoplasm maize mitochondria, HmT toxin and methomyl dissipate the membrane potential of yeast mitochondria that carry the foreign protein. Furthermore, the results suggest that the HmT toxin and methomyl response is related to the plasmid copy number per cell and that the deleterious effect induced by HmT toxin is stronger than that of methomyl.


Low-Cost, High-Volume Health Services Contribute The Most To Unnecessary Health Spending.
An analysis of data for 2014 about forty-four low-value health services in the Virginia All Payer Claims Database revealed more than $586 million in unnecessary costs. Among these low-value services, those that were low and very low cost ($538 or less per service) were delivered far more frequently than services that were high and very high cost ($539 or more). The combined costs of the former group were nearly twice those of the latter (65 percent versus 35 percent).


Association of Shunt Type With Arrhythmias After Norwood Procedure.
Transplant-free survival for single right ventricle (RV) lesions remains less than 70% at 3 years. Arrhythmia burden, influence of shunt type at Norwood procedure (RV-to-pulmonary artery shunt [RVPAS] versus Blalock-Taussig shunt [BTS]), and implications for mortality risk are not well defined. The authors performed a single-center retrospective analysis of patients with single RV lesions enrolled in a prospective study of arrhythmias after congenital heart surgery. Fifty-eight patients received a RVPAS and 62 received a BTS, with a median follow-up of 773 days. Overall arrhythmia incidence was 78%, two-thirds of which prompted intervention. Among all types of arrhythmias, only ventricular arrhythmias (VAs) differed by shunt type, which were more common in patients receiving an RVPAS (29% RVPAS versus 14% BTS; p = 0.049). The majority of VAs were transient (69% less than 1 minute), and typically occurred early post-Norwood procedure (median 12 days). No additional variables were associated with development of VAs. Shunt type did not influence transplant-free survival. Within the entire cohort, there was a trend toward increased mortality with prior history of VA (odds ratio, 2.90; 95% confidence interval, 0.99 to 8.90; p = 0.052). For interstage survivors to Glenn palliation, any VA associated with a 14-fold increased risk of death or transplant (hazard ratio, 14.00; 95% confidence interval, 3.66 to 53.40; p < .001). No other tachyarrhythmia or bradyarrhythmia was associated with mortality. In this cohort with single RV lesions and prospective rhythm surveillance, patients receiving an RVPAS at Norwood surgery had an increased incidence of VAs compared with patients with a BTS. VAs correlated with late mortality in patients who survived the interstage period.


Bilateral single ectopic ureters with hypoplastic bladder: how should we treat these challenging entities?
Bilateral single ectopic ureters with hypoplastic bladder are rare and difficult to treat. Urinary diversion (e.g. by ileal conduit) is usually performed because of small bladder capacity. We report a case treated by staged operation without urinary diversion or bladder augmentation. The outcome shows that ureterovesicostomy between the dilated ureter and the bladder is a feasible method to increase capacity for bilateral single ectopic ureters with hypoplastic bladder.


Correlation of Insurance, Race, and Ethnicity with Pathologic Risk in a Controlled Retinoblastoma Cohort: A Children's Oncology Group Study.
To determine whether insurance status, race, and ethnicity correlate with increased retinoblastoma invasiveness as a marker of both risk and time to diagnosis. Retrospective case-control study. All 203 patients from the United States enrolled in the Children's Oncology Group (COG) trial ARET0332, a study of patients with unilateral retinoblastoma requiring enucleation. All surgical specimens underwent pathologic review to determine the presence of well-defined histopathologic features correlating with a higher risk of disease progression. Insurance status, race, and ethnicity were compiled from the study record for each patient. On institutional pathologic review, nonprivate insurance, nonwhite race, and Hispanic ethnicity all correlated significantly with a greater rate of high-risk pathologic findings. Hispanic ethnicity remained a significant predictor on multivariate analysis. On central pathologic review, these correlations remained but did not reach statistical significance. The differences in results from institutional versus central pathologic reviews appeared to be due to a higher likelihood of patients in minority groups of being misclassified as high risk by institutional pathologists. In this controlled study population of patients with retinoblastoma who had central pathologic review, our findings suggest a higher rate of more advanced disease associated with nonprivate insurance, nonwhite race, and Hispanic ethnicity; these findings may be due to delays in diagnosis for these groups. Future work should use direct methods to study the impact of other variables, including English-language proficiency and socioeconomic status. Further effort also should focus on where in the diagnostic process potential delays exist, so that interventions can be designed to overcome barriers to care for these groups. In addition, potential systematic differences in pathologic reads based on demographic variables deserve further study.


Effects of Press Needling combined with general anesthesia on postoperative analgesia in thoracoscopic pulmonary resection for lung cancer: A randomized, single-blind, controlled trial.
To investigate the effects of press needle therapy on postoperative analgesia and other relevant complications in patients undergoing thoracoscopic pulmonary resection. randomized, single-blind, controlled trial SETTING: Teaching hospitals affiliated with universities. Eighty-six patients were randomized into: the Acu group (press-needle group) and the control group MAIN OUTCOME MEASURES: Pain levels 24, 48, and three months after surgery were measured using the numeric rating scale (NRS). Perioperative hemodynamics, total and effective pressing numbers of patient-controlled intravenous analgesia (PCIA), and incidence of postoperative pulmonary complications were recorded. Peripheral blood samples were collected to measure the levels of inflammatory mediators RESULTS: Acu group had significantly lower NRS scores at 24 and 48 h after operation (NRS scores on movement at 24 h after surgery: Acu vs. Control, 3 (2,3) vs. 3 (3,5), Z = -3.393, P < 0.01 and NRS scores on movement at 48 h after surgery: 2 (1,3) vs. 3 (2,5), Z = -3.641, P < 0.01), lower number of PCIA attempts and effective rates (mean total pressing numbers: 4(2,8) vs. 6(3,19), Z = -1.994, P = 0.046 and mean effective pressing numbers: 3(2,8) vs. 6(3,16), Z = -2.116, P = 0.034). The Acu group had significantly reduced IL-1 (14.52 ± 3.84 vs. 16.36 ± 3.30, mean difference (MD): - 1.85, 95% confidence interval (CI): - 3.46, - 0.23, P = 0.026), HIF-1α (10.15 ± 1.71 vs. 10.96 ± 1.73, MD: -0.81, 95% CI: -1.59, -0.04, P = 0.040) and the incidence of pulmonary complications after surgery. Press needles are a non-invasive and feasible adjunctive intervention for postoperative analgesic management in patients undergoing thoracoscopic pulmonary resection.


Changes of HbA1c variability after the switch to a longer-acting insulin analog in people with type 1 diabetes.
This study investigated whether longer-acting basal analogs (insulin degludec and insulin glargine U300) could reduce visit-to-visit hemoglobin A1c (HbA1c) variability in patients with type 1 diabetes. Ninety adults with type 1 diabetes for whom the basal insulin was switched to a longer-acting insulin analog were analyzed retrospectively. The coefficient of variation of HbA1c levels (CV-HbA1c) during the year before and after the switch was compared. The CV-HbA1c after the switch was not significantly different from that before the switch (4.39 ± 2.24% vs 4.25 ± 2.07%; P = 0.506). The linear regression model revealed that CV-HbA1c before the switch was independently associated with the change of CV-HbA1c (regression coefficient per standard deviation = -0.568, P < 0.001), whereas the other variables were not (all P > 0.05). In conclusion, CV-HbA1c remained unchanged after the switch on average, but CV-HbA1c before the switch was associated with the decrease of CV-HbA1c in individuals with type 1 diabetes.


Bricks out of the wall: polysaccharide extramural functions.
Plant polysaccharides are components of plant cell walls and/or store energy. However, this oversimplified classification neglects the fact that some cell wall polysaccharides and glycoproteins can localize outside the relatively sharp boundaries of the apoplastic moiety, where they adopt functions not directly related to the cell wall. Such polysaccharide multifunctionality (or 'moonlighting') is overlooked in current research, and in most cases the underlying mechanisms that give rise to unconventional ex muro trafficking, targeting, and functions of polysaccharides and glycoproteins remain elusive. This review highlights major examples of the extramural occurrence of various glycan cell wall components, discusses the possible significance and implications of these phenomena for plant physiology, and lists exciting open questions to be addressed by future research.


Neurotransmitter control of thyrotropin secretion in the rat.
In rats adapted to a +30 degrees C temperature for one week, transfer to a temperature of +4 degrees C increased immunoassay-able serum TSH from 150-300 ng/ml to 800-2000 ng/ml in 30 min. Since this response, as well as the level of serum TSH without stimulation, were decreased by reserpine, phentolamine, phenoxybenzamine, disulfiram and diethyldithiocarbamate, noradrenaline may be involved in the stimulation of TSH secretion. TRH-induced TSH increased was not blocked by reserpine. 1-Dopa, a noradrenaline precursor, decreased the TSH response to cold; alpha-methyl-p-tyrosine increased the TSH level. Apomorphine decreased the level of serum TSH and inhibited the response to cold. The possibility of a dopaminergic inhibitory factor released from the hypothalamus is discussed. 5-HT has possibly a role in the regulation of TSH secretion, since its precursor 5-HTP decreased the response to cold. No indication was found that acetylcholine is involved.


Atypical gliosis in Müller cells of the slowly degenerating rds mutant mouse retina.
Retinal Müller glial cells are known to undergo reactive changes (gliosis) in various retinal diseases. In virtually all cases studied, an upregulation of glial fibrillary acidic protein (GFAP) and a hypertrophy can be observed. Physiological alterations, such as a strong downregulation of inwardly rectifying K+ (Kir) currents, were found after retinal detachment (man, rabbit) and after ischemia/reperfusion (rat) but not in more slowly progressing retinal degenerations (Borna Disease Virus-infected rats, RCS rats). This led us to hypothesize that Müller cells respond with 'typical' reactive gliosis only to rapid but not to slow retinal degeneration. To test this hypothesis, we studied Müller cells from rds mutant mice (PrphRd2), which show a retinal degeneration of early onset and slow progression, resulting in a complete loss of photoreceptors after 9-12 months. In Müller cells of rds mice, we found immunoreactivity for GFAP, a marker of gliosis in Müller cells, from postnatal day 21 on, accompanied by a moderately increased membrane capacitance (taken as an indicator of hypertrophy), whereas no change in the expression of the Kir4.1 protein occurred in adult rds mice. We failed to observe significant changes in the membrane resistance and the membrane potential of cells from rds mice from first week after birth until 1 year of age. Current densities were decreased in cells from 3- and 5-week old rds mice. Furthermore, as in control cells from wildtype animals, these cells displayed dominant Kir currents, voltage-dependent Na+ currents, and glutamate uptake currents. These data support the idea that in mice as well as previously shown in rats, slow retinal degeneration induces an atypical gliosis of Müller cells.


Multi-omics analysis reveals RNA splicing alterations and their biological and clinical implications in lung adenocarcinoma.
Alternative RNA splicing is one of the most important mechanisms of posttranscriptional gene regulation, which contributes to protein diversity in eukaryotes. It is well known that RNA splicing dysregulation is a critical mechanism in tumor pathogenesis and the rationale for the promising splice-switching therapeutics for cancer treatment. Although we have a comprehensive understanding of DNA mutations, abnormal gene expression profiles, epigenomics, and proteomics in lung adenocarcinoma (LUAD), little is known about its aberrant alternative splicing profiles. Here, based on the multi-omics data generated from over 1000 samples, we systematically studied the RNA splicing alterations in LUAD and revealed their biological and clinical implications. We identified 3688 aberrant alternative splicing events (AASEs) in LUAD, most of which were alternative promoter and exon skip. The specific regulatory roles of RNA binding proteins, somatic mutations, and DNA methylations on AASEs were comprehensively interrogated. We dissected the functional implications of AASEs and concluded that AASEs mainly affected biological processes related to tumor proliferation and metastasis. We also found that one subtype of LUAD with a particular AASEs pattern was immunogenic and had a better prognosis and response rate to immunotherapy. These findings revealed novel events related to tumorigenesis and tumor immune microenvironment and laid the foundation for the development of splice-switching therapies for LUAD.