Antifungal properties of organic extracts of eight Cistus L. species against postharvest citrus sour rot.
The effectiveness of methanol and chloroform extracts of eight Cistaceae species to control citrus sour rot decay, caused by Geotrichum citri-aurantii, was investigated in both in vitro and in vivo conditions. Methanol extracts of these plant species exhibited more interesting activity against G. citri-aurantii, in both in vitro and in vivo conditions, compared with chloroforme extracts. Under in vitro trials, obtained results showed that methanol extracts of all tested plants revealed a highest significant antifungal activity with inhibition zones that ranged between 12·33 and 16·33 mm in diameter. All tested methanol extracts totally inhibited spore germination when tested at 10 mg ml(-1) . Incidence of sour rot was significantly lowered to 11·11% when fruits were treated with Cistus populifolius and Cistus ladanifer methanol extracts compared with 100% in the control. The disease severity was lowered to 5·19% and 6·04% when fruits were treated with the same methanol extracts respectively. The methanol Cistus extracts had sufficient antifungal activities in vitro and in vivo against G. citri-aurantii to consider its use in the citrus industry after it has been tested under production and natural infection conditions. Such natural products therefore represent a viable alternative approaches for sour rot postharvest management of citrus.


Estimation of parameter kmax in fractal analysis of rat brain activity.
We recorded electrocortical activity in anesthetized rats and constructed k(max) new self-similar time series, applying Higuchi's algorithm. The aim of this study was to estimate value of the parameter k(max) in order to obtain fractal dimension values as an optimum measure of biosignal change. After our analysis, electrocortical activity recordings resulted in a family of curves f(k(max)). Three regions could be distinguished 2 < or = k(max) < 8, with a U-shape; 8 < or = k(max) < or = 30, with a steeper quasilinear increase; and k(max) > or = 30, with a smaller slope quasilinear increase. We suggest the optimum region for k(max): 8 < k(max) < 18, specifically k(max) = 8.


Genome-wide profiling of patient-derived glioblastoma stem-like cells reveals recurrent genetic and transcriptomic signatures associated with brain tumors.
Patient-derived cancer cell lines can be very useful to investigate genetic as well as epigenetic mechanisms of transformation and to test new drugs. In this multi-centric study, we performed genomic and transcriptomic characterization of a large set of patient-derived glioblastoma (GBM) stem-like cells (GSCs). 94 (80 I surgery/14 II surgery) and 53 (42 I surgery/11 II surgery) GSCs lines underwent whole exome and trascriptome analysis, respectively. Exome sequencing revealed TP53 as the main mutated gene (41/94 samples, 44%), followed by PTEN (33/94, 35%), RB1 (16/94, 17%) and NF1 (15/94, 16%), among other genes associated to brain tumors. One GSC sample bearing a BRAF p.V600E mutation showed sensitivity in vitro to a BRAF inhibitor. Gene Ontology and Reactome analysis uncovered several biological processes mostly associated to gliogenesis and glial cell differentiation, S - adenosylmethionine metabolic process, mismatch repair and methylation. Comparison of I and II surgery samples disclosed a similar distribution of mutated genes, with an overrepresentation of mutations in mismatch repair, cell cycle, p53 and methylation pathways in I surgery samples, and of mutations in receptor tyrosine kinase and MAPK signaling pathways in II surgery samples. Unsupervised hierarchical clustering of RNA-seq data produced 3 clusters characterized by distinctive sets of up-regulated genes and signaling pathways. The availability of a large set of fully molecularly characterized GCSs represents a valuable public resource to support the advancement of precision oncology for the treatment of GBM.


Dental plaque removal effectiveness of two powered toothbrushes.
To compare the plaque removal efficacy of an experimental powered toothbrush (Crest SpinBrush Pro with redesigned bristle head) versus a control powered toothbrush (Crest SpinBrush Pro) following a single use. This study was a randomized, controlled, examiner-blind, 4-period crossover design that examined plaque removal with the two toothbrushes following a single use. Plaque was scored before and after brushing using the Turesky Modification of the Quigley-Hein Index. A total of 44 subjects provided data that were used in the statistical analysis. Baseline whole-mouth plaque scores averaged 2.177 prior to using the experimental powered toothbrush with redesigned bristles and 2.220 prior to using the control powered toothbrush. The experimental power toothbrush delivered an adjusted (via ANCOVA) mean difference between baseline and post-brushing plaque scores of 0.662 while the control toothbrush delivered an adjusted mean difference of 0.669. The experimental powered toothbrush had, on average, 1.1% lower plaque removal scores than the control toothbrush. The difference between toothbrushes was not statistically significantly different from zero (P = 0.667). A 95% confidence interval on the mean difference in whole-mouth plaque removal scores was calculated and was within plus or minus 6.3% of the control power toothbrush adjusted mean.


Filling a GAP(DH) in asymmetric viral RNA synthesis.
Host proteins, such as RNA-binding proteins, are involved in most steps of replication by positive-strand RNA viruses, including Tomato bushy stunt virus (TBSV). In this issue of Cell Host & Microbe, Wang and Nagy report that efficient replication of TBSV requires GAPDH, a host protein with glycolytic, RNA-binding, and other functions. GAPDH binds TBSV (-)RNA and promotes the normal excess of (+)RNA over (-)RNA products, possibly by selectively retaining (-)RNA templates for copying.


High-dose busulfan and thiotepa followed by autologous stem cell transplantation (ASCT) in previously irradiated medulloblastoma patients: high toxicity and lack of efficacy.
We previously demonstrated that Busulfan-Thiotepa (Bu-Thio) and ASCT effectively treated patients with locally relapsed medulloblastoma after surgery and conventional chemotherapy. We thus evaluated the administration of Bu-Thio in patients relapsing after conventional CNS irradiation. Patients were scheduled to receive Busulfan (600 mg/m(2)) and Thiotepa (900 mg/m(2)) and ASCT. Resection of residual tumour and additional irradiation were performed if necessary and feasible after Bu-Thio. Toxicity was compared to that observed in 35 patients treated without previous CNS irradiation. From 5/88 to 3/02, 15 patients were treated according to this strategy. Toxicity was significantly higher than that observed in unirradiated patients: thrombocytopenia <50,000/mm(3) lasting 56 days (13-732) (P=0.02) and 30 days (4-124), respectively, HVOD (10/15 and 12/35 patients, respectively) (P=0.06), neurological toxicity (8/15 vs 3/35 patients) (P=0.01). Tumour response was assessable in seven patients and consisted in two CR, three PR and two NR. Currently, two of 15 patients are alive with no evidence of disease. In conclusion, the toxicity of Bu-Thio was significantly more severe in previously irradiated patients. In spite of a high response rate, this strategy failed to improve the prognosis of previously irradiated patients with a relapse from a medulloblastoma.


A modified single sucrose gap. Junction potentials and electrotonic potentials in gastrointestinal smooth muscles.
Modifications were made to a rubber membrane type of single sucrose gap apparatus, which facilitated recording of isometric tension in smooth muscle preparations and which allowed electrotonic potentials and junction potentials to be evoked simultaneously. Nonadrenergic, noncholinergic inhibitory junction potentials were recorded from the circular muscle of the rat cecum. The amplitude of the inhibitory junction potential was linearly dependent on membrane potential, and inhibitory junction potential reversal potential was consonant with the expected potassium equilibrium potential. Cholinergic excitatory junction potentials were recorded in a preparation of the guinea pig cecum. It has been discussed as to how this type of modified single sucrose gap will be useful for pharmacological investigations into neuromuscular transmission, in addition to being a useful technique for examining actions of drugs and chemicals on smooth muscles.


Analytical basis for the determination of the lacunar-canalicular permeability of bone using cyclic loading.
An analytical model for the determination of the permeability in the lacunar-canalicular porosity of bone using cyclic loading is described in this contribution. The objective of the analysis presented is to relate the lacunar-canalicular permeability to a particular phase angle that is measurable when the bone is subjected to infinitesimal cyclic strain. The phase angle of interest is the lag angle between the applied strain and the resultant stress. Cyclic strain causes the interstitial fluid to move. This movement is essential for the viability of osteocytes and is believed to play a major role in the bone mechanotransduction mechanism. However, certain bone fluid flow properties, notably the permeability of the lacunar-canalicular porosity, are still not accurately determined. In this paper, formulas for the phase angle as a function of permeability for infinitesimal cyclic strain are presented and mathematical expressions for the storage modulus, loss modulus, and loss tangent are obtained. An accurate determination of the PLC permeability will improve our ability to understand mechanotransduction and mechanosensory mechanisms, which are fundamental to the understanding of how to treat osteoporosis, how to cope with microgravity in long-term manned space flights, and how to increase the longevity of prostheses that are implanted in bone tissue.


Geographic differences in obesity prevalence and its risk factors among Asian Americans: findings from the 2013-2014 California Health Interview Survey.
Geography disparities exist in obesity and obesity related conditions. This study aimed to examine the geographic differences in obesity prevalence and its risk factors among Asian Americans in California. Data (n = 4,000) from the 2013-2014 California Health Interview Survey were used. Obesity (≥27.5 kg/m2) was defined according to the World Health Organization Asian body mass index cut points in Asian groups. Results suggest that 66.5% of Asians lived in urban areas. Among Asian adults, obesity prevalence was highest in Filipinos (33.8%) and lowest in Koreans (12.8%). Compared to rural Vietnamese, obesity prevalence was higher for urban Vietnamese (8.3% vs. 20.2%, p = 0.0318). Weighted multiple logistic regression analyses showed that being 45-64 years (vs. 65 years or above), being Japanese, Filipino, or other Asians (vs. Chinese) were associated with a higher odds of obesity among urban residents; whereas being 18-44 years and being 45-64 years (vs. 65 years or older), being male, having high school education (vs. having graduate education) were associated with a higher odds of obesity among rural residents. Being Vietnamese (vs. Chinese) was associated with 64% decreased odds of obesity only among rural residents (95% confidence interval = 0.14-0.94). The findings show geography disparities in obesity among Asians in California.


Changes in patient weight and the impact of antidiabetic therapy during the first 5 years after diagnosis of diabetes mellitus.
It is generally thought difficult for type 2 diabetic patients to lose weight. We monitored changes in patients' weight during the first 5 years after diabetes diagnosis in relation to initiation of antidiabetic treatment. Data from 711 newly diagnosed diabetic patients aged 40 or over were analysed with a random-effect linear-regression model. Patients were included consecutively from a well-defined patient list in general practice. In 245 patients whose only treatment was advice on diet, an initial weight loss of 6 to 7 kg was largely maintained over 5 years. Patients receiving metformin (n=86) or sulfonylureas (n=330) maintained an average weight loss of 2 to 4 kg that was dependent on age and sex. Patients' weight did not change on initiation of treatment with sulfonylureas or metformin. Over 5 years, median HbA(1c) increased from 7.0 to 7.8% (reference range 5.4-7.4%) in the diet-alone group. HbA(1c) was approximately 1 percentage point higher for most of the other treatment groups. In newly diagnosed type 2 diabetic patients, long-term weight loss was common and weight loss was not affected by sulfonylurea treatment. The measurements in the study are taken from treatment results achieved in the general population of diabetic patients, who are rarely treated in secondary care and seldom the subject of research; the results thus indicate that weight reduction is a practicable treatment in diabetic patients.


Protein synthesis in Giardia lamblia may involve interaction between a downstream box (DB) in mRNA and an anti-DB in the 16S-like ribosomal RNA.
Giardia lamblia, a parasitic protozoan, has been regarded as one of the most conserved eukaryotes evolved from the prokaryotes. One of its unique features appears to be the unusually short 5'-untranslated regions (UTR) (1-6 nucleotides (nts)) and the apparent absence of 5'-cap structures from its mRNAs. Transfection of the Giardia trophozoites with luciferase-encoding chimeric transcripts, flanked by the 5'- and 3'-ends of giardiavirus (GLV) (+)-strand RNA, indicated that the translational efficiency was enhanced by 5000-fold when the 5'-viral sequence extended 264 nts into the capsid coding region and fused with the luciferase open reading frame (ORF). A 13-nt downstream box (DB) was identified within this region which complements a 15-nt sequence between nts # 1382 and 1396 near the 3'-end of the Giardia 16S-like ribosomal RNA (the anti-DB). Deletion or scrambling of this DB in the mRNA leads to a significant loss of the translational efficiency in Giardia. A Shine-Dalgarno (SD)-like element was also identified at 9-14 nts upstream from the initiation codon in the viral (+)-strand RNA, but alteration of its sequence led to no change in translation. Using the sequence complementary to ribosomal anti-DB to probe the Giardia mRNAs available in the databases, each mRNA was found to contain a putative DB with an average length from 8 to 13 nts. It is thus possible that initiation of translation in Giardia may involve a DB in the coding region of mRNA that may bind to a putative anti-DB in the small ribosomal RNA through base pairing. This mechanism of ribosome recruitment, which finds a potential parallel in Escherichia coli, could illustrate a relatively close distance between Giardia and prokaryotes in terms of translation initiation, and may provide a model for studying the evolution of translation machinery.


Necrotizing fasciitis of the chest wall caused by empyema necessitans following tuberculosis: Case report and literature review.
Empyema is a serious complication characterized by pus and bacteria in the pleural space which may progress to necrosis, cavitation, or fistulas in the thoracic cavity. Infection and trauma are the commonest causes in the developed countries while tuberculosis is the commonest cause of empyema in developing countries. Empyema necessitans is a rare complication of pleural space infections. A 50 years old male patient presented to our hospital with right side chest pain and shortness of breath of 3-week duration. He had completed treatment of pulmonary tuberculosis 6 months ago. The patient was apparently healthy for the last six months after the treatment. The patient was acutely sick looking and has tachycardia with pulse rate of 115, respiratory rate was 36 and arterial oxygen saturation of 80 % with atmospheric air but becomes 96 % with facemask humidified oxygen. Tube thoracostomy and chest wall debridement was done for empyema necessitans with chest wall necrotizing fasciitis. Empyematous collection with time may lead to a more complicated scenario called empyema necessitans. Empyema necessitans is the dissection of puss thru the pleural space and collection in the torso/ free rupture with or without collection of air. The most common cause of empyema globally is untreated parapneumonic effusion. Tuberculosis constitutes for most of the cases of empyema necessitans in third world countries. Debridement and wound care are monumental for the management of necrotizing fasciitis in addition to broad spectrum antibiotics. Timely treatment/drug adherence to pneumonia and tuberculosis decreases the rate of having empyema and subsequent complication. Chest wall necrotizing fasciitis is extremely rare and judicious management with debridement and wound care is appropriate whenever it happens. Broad spectrum antibiotics with drainage are the norm of management of empyema/empyema necessitans.


Thrombotic microangiopathy associated with anticancer and immune system targeting drugs: New insights from real-world data using the WHO pharmacovigilance database.
The worldwide development of immune system targeting/anticancer drugs has revolutionized immuno-oncology, but their implication in thrombotic microangiopathy syndromes (TMA) is increasingly suspected. Using real-world data, the aim of this study was to identify drugs associated with TMA reporting and to describe the evolution of TMA reporting over time with a focus on these drugs. A global disproportionality study was performed using the individual case safety reports (ICSRs) extracted from the World Health Organization (WHO) pharmacovigilance database (VigiBase) from its inception (1968) to April 30, 2022. Of the 31,251,040 ICSRs, 6946 cases of suspected drug-induced TMA were included from 55 countries. The outcome was fatal in 18.2% of cases. A total of 72 immune system targeting/anticancer drugs were associated with significant overreporting, including 17 drugs with a potential new safety concern for TMA. Although the rate of TMA reporting per million of ICSRs has remained fairly stable, an absolute increase in reported cases of suspected drug-induced TMA has been observed over the last decade. The pattern of drugs reported in TMA has evolved with a substantial increase in the proportion of cases involving immune system-targeting drugs/anticancer drugs from 47.3% (205/433) in the period 1992-2001 to 80.7% (3819/4730) in the period 2012-2021. Several recently marketed immune system targeting/anticancer drugs have been identified as potential new drugs associated with TMA, which will require confirmatory studies. The number of drugs associated with TMA reporting markedly increased within the past 10 years, primarily due to innovative anticancer drugs.


Patent ductus arteriosus. Clinical relevance of prostaglandins and prostaglandin inhibitors in PDA pathophysiology and treatment.
This article presents a comprehensive review of the patent ductus arteriosus which so often affects the premature neonate. Included are a discussion of the unique anatomy and physiology of the ductus, a review of the mechanisms involved in normal closure, and factors leading to persistent patency. Various therapeutic options also are discussed, including some new and innovative approaches.


[Treatment of opacification of the posterior crystalline capsule after extracapsular extraction: surgery or laser?].
32 Nd: Yag Laser posterior capsulotomy were compared to 30 surgical decisions. The visual recovery was complete in 56.2% of Yag Laser and in 76% of surgical cases. This results are debated and compared to anterior studies.


The duration of acute kidney injury is an additional parameter to predict 1-year survival in very elderly patients.
Acute kidney injury (AKI) is primarily defined and classified according to the magnitude of the elevation of serum creatinine (Scr). We aimed to determine whether the duration of AKI adds prognostic value in addition to that obtained from the magnitude of injury alone. This retrospective study enrolled very elderly inpatients (≥75 years) in the Chinese PLA General Hospital from January 2007 to December 2018. AKI was stratified by magnitude according to KDIGO stage (1, 2, and 3) and duration (1-2 days, 3-4 days, 5-7 days, and >7 days). The primary outcome was the 1-year mortality after AKI. Multivariable Cox regression analysis was performed to identify covariates associated with the 1-year mortality. The probability of survival was estimated using the Kaplan-Meier method, and curves were compared using the log-rank test. In total, 688 patients were enrolled, with the median age was 88 (84-91) years, and the majority (652, 94.8%) were male. According to the KDIGO criteria, 317 patients (46.1%) had Stage 1 AKI, 169 (24.6%) had Stage 2 AKI, and 202 (29.3%) had Stage 3 AKI. Of the 688 study subjects, 61 (8.9%) with a duration of AKI lasted 1-2 days, 104 (15.1%) with a duration of AKI lasted 3-4 days, 140 (20.3%) with a duration of AKI lasted 5-7 days, and 383 (55.7%) with a duration of AKI lasted >7 days. Within each stage, a longer duration of AKI was slightly associated with a higher rate of 1-year mortality. However, within each of the duration categories, the stage of AKI was significantly associated with 1-year mortality. When considered separately in multivariate analyses, both the duration of AKI (3-4 days: HR=3.184; 95% CI: 1.733-5.853; P <0.001, 5-7 days: HR=1.915; 95% CI: 1.073-3.416; P=0.028; >7 days: HR=1.766; 95% CI: 1.017-3.065; P=0.043) and more advanced AKI stage (Stage 2: HR=3.063; 95% CI: 2.207-4.252; P <0.001; Stage 3: HR=7.333; 95% CI: 5.274-10.197; P <0.001) were independently associated with an increased risk of 1-year mortality. In very elderly AKI patients, both a higher stage and duration were independently associated with an increased risk of 1-year mortality. Hence, the duration of AKI adds additional information to predict long-term mortality.


Topical application of 5-fluorouracil in premalignant lesions of cornea, conjunctiva and eyelid.
Local application of 5-Fluorouracil was practised on 5 patients. In 3 patients with multiple premalignant oculo-cutaneous lesions, two of whom had also premalignant epibulbar lesions, local 5% 5-Fu cream and/or 1% 5-Fu eyedrops were applied. In 2 other patients who had only premalignant lesions on the cornea and conjunctiva, 1% 5-Fu eyedrops were used only. In animal experiments 1% 5-Fu was not found to cause any damage to normal corneal and conjunctival epithelium. The frequency of the applications and the duration of the treatment were dependent on the location and extent of the lesions. Except for easily treatable lesions, caused by the separation of the tumour epithelium, no complications of local 5-Fu treatment were seen. The visual acuity improved in all 4 patients in whom the cornea was affected. In these premalignant conditions the diagnosis and assessment of the therapy were based on exfoliative cytology and biopsies.


Targeting of low ALK antigen density neuroblastoma using AND logic-gate engineered CAR-T cells.
The targeting of solid cancers with chimeric antigen receptor (CAR) T cells faces many technological hurdles, including selection of optimal target antigens. Promising pre-clinical and clinical data of CAR T-cell activity have emerged from targeting surface antigens such as GD2 and B7H3 in childhood cancer neuroblastoma. Anaplastic lymphoma kinase (ALK) is expressed in a majority of neuroblastomas at low antigen density but is largely absent from healthy tissues. To explore an alternate target antigen for neuroblastoma CAR T-cell therapy, the authors generated and screened a single-chain variable fragment library targeting ALK extracellular domain to make a panel of new anti-ALK CAR T-cell constructs. A lead novel CAR T-cell construct was capable of specific cytotoxicity against neuroblastoma cells expressing low levels of ALK, but with only weak cytokine and proliferative T-cell responses. To explore strategies for amplifying ALK CAR T cells, the authors generated a co-CAR approach in which T cells received signal 1 from a first-generation ALK construct and signal 2 from anti-B7H3 or GD2 chimeric co-stimulatory receptors. The co-CAR approach successfully demonstrated the ability to avoid targeting single-antigen-positive targets as a strategy for mitigating on-target off-tumor toxicity. These data provide further proof of concept for ALK as a neuroblastoma CAR T-cell target.


Cognitive and brain reserve and the risk of postoperative delirium in older patients: analysis of data from a prospective observational study.
Cognitive and brain reserve theories suggest that aspects of neural architecture or cognitive processes modify the effect of neuropathological processes on cognitive outcomes. Although frequently studied in the context of dementia, reserve in delirium is understudied. Using data from a prospective observational study, we examined the association of three markers of brain reserve (head circumference, MRI-derived brain volume, and leisure time physical activity), five markers of cognitive reserve (education, vocabulary, cognitive activities, cognitive demand of lifetime occupation, and interpersonal demand of lifetime occupation), and the risk of postoperative delirium in 566 older adults (age ≥70 years) free of dementia undergoing scheduled surgery. 135 (24%) of 566 patients developed delirium during the postoperative hospital stay. Of the reserve markers examined, only the Wechsler Test of Adult Reading was associated with the risk of delirium. A 0·5 SD better performance on the Wechsler Test of Adult Reading was associated with a 38% reduction in delirium risk (adjusted risk ratio of 0·62, 95% CI 0·45-0·85; p=0·01). Most markers of reserve failed to predict delirium risk. The exception to this is the Wechsler Test of Adult Reading. Our findings suggest that the reserve markers that are important for delirium might be different from those thought to be important for dementia. National Institute on Aging, National Heart Lung and Blood Institute.


Orthotopic cardiac transplantation for univentricular heart.
The technical aspects of orthotopic cardiac transplantation for univentricular heart in a 22-year-old man are discussed. Abnormal pulmonary artery anatomy resulted in right ventricular failure, which was successfully treated.


IR laser induced spectra in novel crystals CdTe-CuInTe2.
The novel crystalline alloys CdTe-CuInTe2 were synthesized. The photoinduced spectral changes of the anharmonic phonon modes were explored by cw CO2 laser at power about 2 kW in the vicinity of the 1650 cm(-1) mode. The changes of the intensities for principal phonon modes were found. These modes were assigned both to harmonic as well as anharmonic modes. All the measurements are studied after the Ir illumination. The performed quantum chemical calculations with application of the norm-conserving pseudopotential method and Green functions allow to identify the origin of the content dependent anharmonic phonon modes. Some correlation between the intensities of the corresponding phonon modes at about 1600-1700 cm(-1) and the corresponding IR induced changes were found.


A curcumin-analogous fluorescent sensor for cysteine detection with a bilateral-response click-like mechanism.
A novel curcumin-analogous fluorescent sensor, DNP, was developed for cysteine detection with a bilateral-response click-like mechanism. DNP indicated high selectivity and practical sensitivity. It could recognize Cys from other biologically relevant molecules, especially, from GSH and Hcy. The most interesting point was that, with typical azide groups for sensing, DNP indicated a covalent binding procedure with Cys instead of a presupposed simple reduction for reductive sulfide. Moreover, the recognition occurred at both sides of the sensor. DNP could be utilized into the detection of endogenous and exogenous Cys in living cells. Though the specific optical performances of DNP still need optimization, this work supplied novel information for broadening the vision on fluorophores and mechanisms, for the monitoring of Cys and even other sulfur-containing species.


[Structural-functional changes in membranes and external perimembrane layers of erythrocytes in hyperepidermopoiesis].
The coat properties of erythrocytes in hyperepidermopoesis had been studied using the vital quantitative method of the cell coat (outer perimembraneous layer) identification with alcian blue (AB). It is shown that the stage sharpening in psoriasis was accompanied an increase in AB sorption by erythrocytes for 13.2. The qualitative and quantitative gangliosidic spectrum of erythrocytes and serum does change according to the date of chromatography in hyperepidermopoesis. The role of this changes are discussed in pathogenesis of the given disease.


Targeted blocking of CCR2 and CXCR2 improves the efficacy of transarterial chemoembolization of hepatocarcinoma.
Transarterial chemoembolization (TACE) has been shown to prolong survival in patients with unresectable hepatocellular carcinoma (HCC); however, the long-term survival remains dismal. Targeting macrophage and neutrophil infiltration is a promising strategy. The CCL2/CCR2 and CXCLs/CXCR2 axes are required for recruitment of macrophages and neutrophils, respectively, in HCC. We investigated the feasibility of CCL2/CCR2 and CXCLs/CXCR2 as therapeutic targets in combination with TACE for treating HCC. Expression of CCL2/CCR2 and CXCLs/CXCR2 was analyzed in the primary rat HCC model and one HCC cohort. The relationship between expression levels, neutrophil and macrophage infiltration, hepatocarcinogenesis progression in the rat model, and survival of HCC patients was assessed. The anti-tumor effects of blocking the CCL2/CCR2 and CXCLs/CXCR2 axes by CCR2 and CXCR2 antagonists in combination with TACE were evaluated in HCC rats. The numbers of macrophages, neutrophils, and hepatic progenitor cells were further determined to explore the underlying mechanisms. High macrophage and neutrophil infiltration and CXCL8 expression were associated with poor prognosis in the TCGA liver cancer dataset. High expression of CCL2/CCR2 and CXCL8/CXCR2 in clinical HCC specimens was associated with reduced survival. Expression of CCL2/CCR2 and CXCL1/CXCR2 was correlated with hepatocarcinogenesis progression in the primary rat HCC model. Blockade of CCL2/CCR2 and CXCLs/CXCR2 enhanced the anti-tumor effect of TACE treatment in this model. Blocking the CCL2/CCR2 and CXCLs/CXCR2 axes with CCR2 and CXCR2 antagonists in TACE-treated rats reduced macrophage and neutrophil infiltration and hepatic progenitor cell activation and thus overcame TACE resistance in HCC. The results demonstrate the translational potential of immunotherapy targeting the CCL2/CCR2 and CXCLs/CXCR2 axes in combination with TACE therapy for the treatment of HCC.


Prevalence and factors of T-score discordance between hip and spine among middle-aged and elderly Malaysians.
T-score discordance between hip and spine is a common problem in the diagnosis of osteoporosis based on dual-energy X-ray absorptiometry. Not much information on the prevalence and risk factors of this problem is available in Malaysia. Our study found that factors like age, height, physical activity and menopausal status should be taken into account in the diagnosis of osteoporosis. T-score discordance between hip and spine is a common problem in bone mineral density assessment. A difference ≥ 1 standard deviation (SD) (regardless of diagnostic class) is considered minor, and a difference more than one diagnostic class is considered major discordance. This study aimed to determine the prevalence and factors of hip and spine T-score discordance in a population aged ≥ 40 years in Klang Valley, Malaysia. In this cross-sectional study, subjects answered a demographic questionnaire and underwent body composition and bone health assessment using dual-energy X-ray absorptiometry. Chi-square and binary logistic regression analysis were used to assess the prevalence of T-score discordance among the subjects. A total of 786 Malaysians (382 men, 404 women) subjects were recruited. The prevalence of minor and major discordance was 30.3% and 2.3%, respectively. Overall, factors related to T-score discordance were advanced age, decreased height, and being physically active. Sub-analysis showed that decreased height and being physically active predicted T-score discordance in men, being menopausal and Indian (vs Chinese) were predictors in women. T-score discordance between hip and spine is common among Malaysian middle-aged and elderly population. Diagnosis of osteopenia/osteoporosis should be based on the T-score of more than one skeletal site as per the current recommendations.


Posterior fossa neuroblastoma occurring in an elderly man.
A case of a neuroblastoma occurring in the cerebellum of a 73-year-old man is reported. The patient presented with progressive truncal ataxia and was found to have an enhancing tumor mass in the cerebellar vermis. By light microscopy, the tumor was a small cell neoplasm and was similar to medulloblastoma, with areas showing structures suggestive of Homer-Wright pseudorosettes. By electron microscopy and immunoperoxidase techniques, however, the tumor showed convincing evidence of neuronal differentiation. The absence of previous reports of this tumor in the posterior fossa of adults suggests that immunoperoxidase techniques and/or electron microscopy of such small cell tumors may be required for accurate diagnosis.


A Robust Method for Perfusable Microvascular Network Formation In Vitro.
Micropost-based microfluidic devices are widely used for microvascular network (MVN) formation in diverse research fields. However, consistently generating perfusable MVNs of physiological morphology and dimension has proven to be challenging. Here, how initial seeding parameters determine key characteristics of MVN formation is investigated and a robust two-step seeding strategy to generate perfusable physiological MVNs in microfluidic devices is established.


Single-cell transcriptome reveals immunopathological cell composition of skin lesions in subacute cutaneous lupus erythematosus.
Subacute cutaneous lupus erythematosus (SCLE) is a clinical subtype of cutaneous lupus erythematosus with psoriatic-like or annular papules with scaly erythemas, the pathological mechanism of which is poorly understood. To investigate the immune pathogenesis of SCLE, we performed single-cell RNA sequencing (scRNA-seq) of SCLE skin lesions and integrated the scRNA-seq data from skin tissues of healthy controls (HCs). Our results identified expanded fibroblasts and keratinocytes subtypes, abnormally activated lymphocyte and inflammatory M1 macrophages in SCLE. In SCLE, stromal cells, such as keratinocytes and fibroblasts, showed enhanced chemotactic functions for recruiting immune cells. Importantly, interferon-related genes were identified as key intermediate genes in the potential trajectory of fibroblasts, keratinocytes, and B cells from HCs to SCLE. Our investigation provides a comprehensive description of cell composition in SCLE and highlights several important clues for understanding the pathogenesis of SCLE.


Transcriptomic analysis reveals crucial regulatory roles of immediate-early response genes and related signaling pathways in coronavirus infectious bronchitis virus infection.
Coronavirus infection of cells differentially regulates the expression of host genes and their related pathways. In this study, we present the transcriptomic profile of cells infected with gammacoronavirus infectious bronchitis virus (IBV). In IBV-infected human non-small cell lung carcinoma cells (H1299 cells), a total of 1162 differentially expressed genes (DEGs), including 984 upregulated and 178 downregulated genes, was identified. These DEGs were mainly enriched in MAPK and Wnt signaling pathways, and 5 out of the 10 top upregulated genes in all transcripts were immediate-early response genes (IEGs). In addition, the induction of 11 transcripts was validated in IBV-infected H1299 and Vero cells by RT-qPCR. The accuracy, reliability and genericity of the transcriptomic data were demonstrated by functional characterization of these IEGs in cells infected with different coronaviruses in our previous publications. This study provides a reliable transcriptomic profile of host genes and pathways regulated by coronavirus infection.


Afterimage movement during saccades in the dark.
The spatial values of retinal coordinates are "recalibrated" to the "egocentric" coordinates during and after a saccade within a fraction of a second. We measured the time constant of this retinal coordinate transformation by means of an afterimage technique: our ten subjects performed "auditory" horizontal saccades in total darkness (0.2-4.5 saccades/sec). At a saccade frequency below 1 saccade/sec, the subjects observed saccadic displacement of the foveal afterimage, but the afterimage seemed to arrive at its final position more slowly than the center of gaze (state 1). At saccade frequencies above 1.5 saccades/sec, the perceived amplitude of afterimage displacement decreased with increased saccade frequency (state 2). Above 2 saccades/sec all subjects perceived two stationary afterimages simultaneously at the saccadic end-position (state 3). A further increase in saccade frequency reduced the distance between the two afterimages till only one stationary afterimage was seen in a mid-position between the two auditory targets at a saccade frequency above 3.2-3.5 saccades/sec (state 4). Saccade amplitude remained constant within the frequency range between 0.2 and 4.5 saccades/sec. A one-step or two-step linear model was applied to simulate the experimental data, indicating that the spatial coordinates shift more slowly than the saccadic eye movements.


Pregna-D'-pentarane structure influences progesterone receptor affinity for DNA.
Electrophoretic mobility shift assay was used to determine whether pregna-D'-pentaranes allow progesterone receptor (PR) from rat uterine cytosol to bind hormone response element (HRE)-containing oligonucleotide duplexes and to measure the affinity of this interaction. The formation of DNA-protein complexes in low salt medium was progesterone-related ligand-, temperature-, and PR-dependent, and specific for HRE. The highest affinity of PR to DNA (equilibrium K(a) = 0.420 +/- 0.185 nM(-1)) was found in the presence of the partial agonist/antagonist RU486, while the lowest affinity (K(a) = 0.074 +/- 0.013 nM(-1)) was demonstrated with the full agonist 6alpha-methyl-16alpha,17alpha-cyclohexanoprogesterone. With the exception of the strong full agonist R5020, there was a tendency toward correlation between the induced lower affinity of PR for DNA in the context of tyrosine aminotransferase HRE and the full agonistic activity of tested compounds.


Gastric carcinoma with ovarian metastases in an adolescent.
Gastric carcinoma represents only 0.05% of malignant paediatric gastrointestinal tumours. This condition is associated with a poor prognosis because its rarity and non-specificity of the symptoms usually delay its diagnosis. The authors present a 16-year-old girl with a poorly differentiated gastric carcinoma (signet-ring-cell type) with bilateral ovarian metastases who died of peritoneal carcinomatosis despite extensive surgery and chemotherapy. The epidemiological, clinical, and pathological features of gastric carcinoma in childhood are discussed.


Factors associated with risk for colorectal cancer recurrence after endoscopic resection of T1 tumors.
More information is needed on the long-term outcomes of patients who undergo endoscopic resection of colorectal tumors. We evaluated recurrence of colorectal cancer (CRC) after endoscopic resection or a combination of endoscopic research and surgery for T1 colorectal tumors. We conducted a retrospective study of 389 patients with T1 CRC treated by endoscopic resection from January 1989 to December 2008 in Sapporo, Japan. We compared outcomes between patients who underwent subsequent surgery (ER + SURG, n = 205) and those who did not (ER only, n = 184) and statistically adjusted baseline differences between the groups according to the propensity scores. There was almost no risk of cancer recurrence among patients without indications for surgery recommended by the Japanese Society for Cancer of the Colon and Rectum (these indications include tumors with vertical margins, deep submucosal invasion, lymphatic or venous invasion, poor differentiation, or high-grade budding). Among patients with indications for surgery, the cumulative risks of recurrence (CRRs) were 3.7% in the ER + SURG group and 20.1% in the ER only group (P = .001). However, the patients with only deep submucosal invasion had a low CRR, even without surgery (2.3% in the ER + SURG group and 3.4% in the ER only groups, P = .867). In contrast, patients with indications for surgery other than deep submucosal invasion (high-risk patients) had much better outcomes when they also underwent surgery (CRRs: 5.8% in the ER + SURG group vs 58.0% in the ER only group, P < .001). On the basis of a retrospective study of patients who underwent endoscopic resection for T1 CRC, those with tumors with only submucosal invasion are at low risk for cancer recurrence. However, patients with other high-risk tumor features have greater risks for cancer recurrence and benefit from subsequent surgery.


Alcohol to down-regulate negative and positive emotions: Extending our understanding of the functional role of alcohol in relation to posttraumatic stress disorder.
Functional models of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) underscore the role of internally-driven negative reinforcement. However, with the focus of these models being on negative emotions broadly, there is limited understanding of the effect of alcohol use to down-regulate specific forms of negative emotions or positive emotions generally. Among populations characterized by PTSD, there is growing evidence that positive emotions may elicit aversive reactions and thus be intentionally reduced, including via alcohol use. The current study examined the associations among PTSD symptom severity, alcohol use to down-regulate both negative (i.e., despondency and anger) and positive emotions, and alcohol misuse. Data were collected from 320 trauma-exposed, substance-using individuals in the community (M age = 35.78, 46.9% women). Individuals with greater PTSD symptom severity reported significantly higher alcohol use to down-regulate despondency, anger, and positive emotions, which, in turn, were linked to greater alcohol misuse. Alcohol use may serve to down-regulate both negative (i.e., despondency and anger) and positive emotions, and these functions may help to explain the association of PTSD symptom severity to alcohol misuse. PTSD-AUD models may benefit from specifying a negatively reinforcing function of alcohol use in the context of positive emotions.


Predictors of mortality amongst recipients of implantable cardioverter defibrillators for secondary prevention of cardiac arrest.
Implantable Cardioverter-defibrillators (ICD) reduce mortality in survivors of cardiac arrest (CA). We investigated the predictors of mortality after ICD implantation in survivors of CA. Retrospective review of clinical records and social security death index of all patients who received an ICD in a preexisting database of survivors of CA at the University of Pittsburgh Medical Center was performed. Multivariate analyses using the Cox proportional hazard model were performed with backward elimination to identify independent predictors of the time to death, and Kaplan-Meier curves were plotted. Eighty patients (64 men) with a mean age of 64.4+/-12.5 years were followed for 4.7+/-2.3 years after ICD implantation. Survival rates were 93.8%, 65% and 50% at 1, 5, and 10 years, respectively. Independent predictors of time to death were determined to include age (hazard ratio (HR) = 1.91 per 10-year increase, p = 0.003), serum creatinine > or = 1.3 mg/dL (HR = 2.56, p = 0.004), and QRS width >120 ms (HR = 5.14, p = 0.012). In this sample of ICD recipients secondary to CA, older age, elevated serum creatinine, and wider QRS duration were independent predictors of mortality. The presence of more than one risk factor in the same patient was associated with higher mortality rates. Whether interventions such as biventricular pacing can offset this increase risk of death warrants further investigation.


Cdc42 is required for chondrogenesis and interdigital programmed cell death during limb development.
Cdc42, a member of the Rho subfamily of small GTPases, is known to be a regulator of multiple cellular functions, including cytoskeletal organization, cell migration, proliferation, and apoptosis. However, its tissue-specific roles, especially in mammalian limb development, remain unclear. To investigate the physiological function of Cdc42 during limb development, we generated limb bud mesenchyme-specific inactivated Cdc42 (Cdc42(fl/fl); Prx1-Cre) mice. Cdc42(fl/fl); Prx1-Cre mice demonstrated short limbs and body, abnormal calcification of the cranium, cleft palate, disruption of the xiphoid process, and syndactyly. Severe defects were also found in long bone growth plate cartilage, characterized by loss of columnar organization of chondrocytes, and thickening and massive accumulation of hypertrophic chondrocytes, resulting in delayed endochondral bone formation associated with reduced bone growth. In situ hybridization analysis revealed that expressions of Col10 and Mmp13 were reduced in non-resorbed hypertrophic cartilage, indicating that deletion of Cdc42 inhibited their terminal differentiation. Syndactyly in Cdc42(fl/fl); Prx1-Cre mice was caused by fusion of metacarpals and a failure of interdigital programmed cell death (ID-PCD). Whole mount in situ hybridization analysis of limb buds showed that the expression patterns of Sox9 were ectopic, while those of Bmp2, Msx1, and Msx2, known to promote apoptosis in the interdigital mesenchyme, were down-regulated. These results demonstrate that Cdc42 is essential for chondrogenesis and ID-PCD during limb development.


Moral pedagogy and practical ethics.
Online science and engineering ethics (SEE) education can support appropriate goals for SEE and the highly interactive pedagogy that attains those goals. Recent work in moral psychology suggests pedagogical goals for SEE education that are surprisingly similar to goals enunciated by several panels in SEE. Classroom-based interactive study of SEE cases is a suitable method to achieve these goals. Well-designed cases, with appropriate goals and structure can be easily adapted to courses that have online components. It is less clear that exclusively online methods can support the wide range of goals necessary to good moral pedagogy in SEE, though there seems no a priori reason to rule this out. Only careful, goal-based assessment of online case study SEE teaching can resolve this question.


Protein A immunoadsorption combination with immunosuppressive therapy improves neuropsychiatric systemic lupus erythematosus: A case report.
We described protein A immunoadsorption combination with immunosuppressive treatment improved rapidly a patient with Neuropsychiatric systemic lupus erythematosus.


The serotonin1A receptor: a representative member of the serotonin receptor family.
1. Serotonin is an intrinsically fluorescent biogenic amine that acts as a neurotransmitter and is found in a wide variety of sites in the central and peripheral nervous system. Serotonergic signaling appears to play a key role in the generation and modulation of various cognitive and behavioral functions. 2. Serotonin exerts its diverse actions by binding to distinct cell surface receptors which have been classified into many groups. The serotonin1A (5-HT1A) receptor is the most extensively studied of the serotonin receptors and belongs to the large family of seven transmembrane domain G-protein coupled receptors. 3. The tissue and sub-cellular distribution, structural characteristics, signaling of the serotonin1A receptor and its interaction with G-proteins are discussed. 4. The pharmacology of serotonin1A receptors is reviewed in terms of binding of agonists and antagonists and sensitivity of their binding to guanine nucleotides. 5. Membrane biology of 5-HT1A receptors is presented using the bovine hippocampal serotonin1A receptor as a model system. The ligand binding activity and G-protein coupling of the receptor is modulated by membrane cholesterol thereby indicating the requirement of cholesterol in maintaining the receptor organization and function. This, along with the reported detergent resistance characteristics of the receptor, raises important questions on the role of membrane lipids and domains in the function of this receptor.


Immunomodulatory activities of Cedrela tubiflora leaf aqueous extracts.
Human peripheral blood monocytes and polymorphonuclear leukocytes treated with leaf aqueous extracts of the Meliaceae tree Cedrela tubiflora showed a diminution in both their phagocytic and respiratory burst activities. Besides, the extract inhibited the proliferation of Concanavalin A stimulated lymphocytes. A decrease in the hemolytic capacity of the human complement was also observed. The significance of the inhibitory effect observed over some components of the human immune system closely related with the inflammatory process is discussed.


[Mass data and psychoacoustic interpretations of patients with 8-channel cochlear implants (author's transl)].
Six patients are described following insertion of an 8-channel cochlear implant. The prosthesis was modified from the Vocoder technique, and was implanted by a simplified method of the procedure previously reported by us. In addition to the perception of background noise as well as the differentiation of periodicity and frequencies, a distinct improvement of the patients' speech discriminations could be observed with this technique.


Emergency laparoscopic repair of a paraesophageal hernia.
A 63-year-old male with a previously documented paraesophageal hernia presented with acute severe epigastric pain and bloating. He was taken urgently to the operating room for laparoscopic exploration. The hernia sac was reduced with difficulty owing to extensive adhesions and the incarcerated portion of the stomach was mottled and blue. After 10 min of observation the stomach began to resume a normal appearance. The anterior crura were approximated and an anterior gastropexy was performed. The patient was discharged on the 3rd postoperative day and has been asymptomatic since. Paraesophageal hernias with evidence of impending gastric necrosis can be approached laparoscopically as long as basic principles are observed.


Reconstitution of the malate/aspartate shuttle from mitochondria.
The isolated aspartate/glutamate carrier and oxoglutarate carrier from mitochondria were coreconstituted into phospholipid vesicles. Reconstitution of the functionally active carrier proteins with high protein/lipid ratios was achieved by detergent removal on hydrophobic ion-exchange columns. A simplified version of the mitochondrial malate/aspartate shuttle was constructed by inclusion of glutamate-oxaloacetate transaminase and the substrates aspartate and oxaloacetate within the interior of the liposomes. Addition of external glutamate led to internal production of oxoglutarate which could be exchanged against externally added labeled malate. The reconstitution procedure was characterized with respect to the optimum ratio of reconstituted carrier proteins, the lipid concentration, and the concentration of internal substrates.


Spinal correction in patients with Fukuyama congenital muscular dystrophy.
Fukuyama congenital muscular dystrophy (FCMD) is one of the most common congenital progressive muscular dystrophies in Japan. Some patients develop a severe spinal deformity that leads to an unstable sitting position or pain. Since 2008, we have treated FCMD using posterior spinal fusion. This study reports the short-term clinical and radiographic results of posterior spinal correction and fusion in FCMD. We retrospectively reviewed 11 consecutive FCMD patients, average age 13 years old, treated with posterior spinal instrumentation and fusion between 2008 and 2015. All patients were non-ambulatory and complained about difficulty sitting and/or buttock pain. Posterior spinal correction was performed to halt progression of spinal deformity and improve their sitting balance. Assessment was performed clinically and with radiological measurements at a mean follow up period of 34.5 months. To evaluate functional status of patients after surgery objectively, a Muscular Dystrophy Spine Questionnaire (MDSQ) was obtained at the final follow up. The mean height, weight and body mass index of the patients were 144.1 ± 11.8 cm, 26.5 ± 8.7 kg and 12.5 ± 2.6 kg/m2. The average intensive care unit stay was 1.3 days. Five patients had complications related to surgery. The mean preoperative major Cobb angle and pelvic obliquity (PO) were 65.5 ± 41.7° and 31.4 ± 28.9°, respectively, were corrected to 34.4 ± 29.7° and 20.0 ± 18.7° just after the surgery, and were maintained at 35.1 ± 29.9° and 20.5 ± 21.1° at the final follow up. The average MDSQ score was 35.8 ± 13.2 at the final follow up. Posterior spinal correction and fusion in FCMD achieved good radiographic results and clinical improvement with acceptable perioperative complications. FCMD patients are mentally impaired and physically small, so post-operative observation and close attention to perioperative complications are critical.


Usefulness of bee bread and capped brood for the assessment of monocyclic aromatic hydrocarbon levels in the environment.
Monitoring airborne pollutants, like aromatic hydrocarbons, are raising more and more concerns recently. Various sampling techniques and methods are known to collect, measure, and analyse environmental pollution levels based on honey bee bodies or bee product samples. Although honey bees are studied in detail and sampling methods are becoming more and more sophisticated biological samples may significantly differ in pollutant accumulation, showing a wide range of pollution levels even in the same site and environment. We have compared the pollution levels of honey bee capped brood and bee bread (pollen collected by honey bees and deposited in the hive) originating from four sites during two years of study and twelve honey bee families near various pollution sources emitting monocyclic aromatic hydrocarbons (BTEX) to the environment. Our result showed, that the environmental monitoring of BTEX can be based on sampling honey bees, and bee bread in particular. However, we found a significant difference in the uptake of these pollutants regarding sample type. Pollen collected as a food source revealed consistently higher levels of BTEX than bee brood, as well as some other differences in pollution levels between samples and between seasons, as opposed to capped brood. Based on our results, we suggest that for measuring and monitoring of BTEX pollution in the environment the use of bee bread is a valuable source of information.


Biopharmaceutical characterization of oral controlled/modified-release drug products. In vitro/in vivo correlation of roxatidine.
From the marketed drug product Roxane(R) 75 mg C/MR capsules (roxatidine controlled/modified-release capsules), an in vitro/in vivo comparison was performed to demonstrate a 1:1 correlation between in vitro and in vivo dissolution, and, furthermore, to ensure bioequivalence of the roxatidine controlled/modified-release (C/MR) capsules exhibiting dissolution profiles within the defined acceptance criteria. This 1:1 in vitro/in vivo comparison was calculated using a model independent numerical deconvolution method. The high degree of correlation is extremely rare, nevertheless it allows to omit the testing of clinical side batches for the setting of acceptance criteria for the in vitro dissolution of roxatidine controlled/modified-release (C/MR) capsules. The 1:1 in vitro/in vivo correlation can be explained by the biopharmaceutical characteristics of the drug substance as well as the drug product, that is, pH-independent high solubility of the drug substance as well as dissolution which is independent of pH and agitation. These facts lead to a controlled/modified-release formulation. Therefore, it is important to keep in mind that in most cases in which a pH-dependent solubility/dissolution as well as permeability characteristics can be found, a 1:1 in vitro/in vivo correlation could not be expected.


Influenza Vaccination and Other Factors Related to the Development of Influenza-Like Illness Among Patients on Chronic Hemodialysis in a Japanese Dialysis Facility.
The present study was conducted to evaluate the protective effect of seasonal influenza vaccination on the development of influenza-like illness (ILI), as well as to investigate factors related to the development of ILI among patients in a Japanese dialysis facility. One hundred eighty-three hemodialysis (HD) patients were followed up from November 2008 to March 2009. During the follow-up period, 17 patients developed ILI. We compared the characteristics of these 17 patients to patients without ILI. Compared to the non-ILI group (N = 166), the ILI group (N = 17) showed a non-significantly lower rate of influenza vaccination (70.6% vs. 86.7%, P = 0.07), while any other factor did not differ between the two groups. Influenza vaccination tended to reduce the risk of ILI (Odds ratio = 0.37, 95% CI = 0.12 to 1.14, P = 0.07). The findings of the present study suggested that the influenza vaccine was 60% effective to prevent ILI among HD patients, although the effectiveness was not statistically significant.


Understanding Why Residents May Inaccurately Log Their Role in Operations: A Look at the 2013 In-Training Examination Survey.
With increased time and quality pressures, it may be more difficult for residents in cardiothoracic surgery residency programs to get independent operative experience. That may lead residents to inaccurately report their role as "surgeon" to meet American Board of Thoracic Surgery (ABTS) case requirements. The 2013 In-Training Examination surveyed 312 cardiothoracic surgery residents and was used to contrast residents in traditional 2-year and 3-year cardiothoracic surgery residencies (traditional, n = 216) with those in 6-year integrated or 3+4-year programs (integrated, n = 96). Traditional program residents reported a higher percentage of cases that met the ABTS criteria of surgeon than did integrated program residents (p = 0.05) but were less likely to meet requirements if all cases were logged accurately (p = 0.03). The majority of residents in each program believed that their case log accurately reflected their experience as "surgeon." Residents who tended to log cases incorrectly had lower self-reported 2012 In-Training Examination percentiles, were less likely to meet case requirements if logged properly, and felt less prepared for board examinations and eventual practice compared with residents who logged cases correctly (all p < 0.001). Residents who believed they would not meet case requirements if logged correctly cited limited surgical opportunities, poor case diversity, and a compromised training environment but not the 80-hour work week, excessive simulation, or disproportionate number of complex cases as causes. Overall cardiothoracic surgery residents appear to be satisfied with their training. There were specific subsets of trainees in both traditional and Integrated programs that are misrepresenting their role on cases because they otherwise may not meet the requirements.


Synthesis and characterization of well-defined hydrogel matrices and their application to intestinal stem cell and organoid culture.
Growing cells within an extracellular matrix-like 3D gel is required for, or can improve, the growth of many cell types ex vivo. Here, we describe a protocol for the generation of well-defined matrices for the culture of intestinal stem cells (ISCs) and intestinal organoids. These matrices comprise a poly(ethylene glycol) (PEG) hydrogel backbone functionalized with minimal adhesion cues including RGD (Arg-Gly-Asp), which is sufficient for ISC expansion, and laminin-111, which is required for organoid formation. As such, the hydrogels present a defined and reproducible, but also tunable, environment, allowing researches to manipulate physical and chemical parameters, and examine their influence on ISC and organoid growth. Hydrogels are formed by an enzymatic cross-linking reaction of multiarm PEG precursors bearing glutamine- and lysine-containing peptides. PEG precursors containing either stable or hydrolytically degradable moieties are used to produce mechanically softening hydrogels, which are used for the expansion of ISCs or the formation of organoids, respectively. We also provide protocols for immunofluorescence analysis of cellular structures grown within these matrices, as well as for their dissociation and retrieval of cells for downstream use. Hydrogel precursors can be produced and their mechanical properties characterized to ascertain stiffness within 5-7 d. Hydrogel formation for ISC expansion or organoid formation takes 1-2 h. The materials described here can be readily adapted for the culture of other types of normal or transformed organoid structures.


Binding properties of a molecular "light switch" ruthenium(II) polypyridyl complex toward double- and triple-helical forms of RNA.
To further develop new luminescent probes for RNA, a new ruthenium(II) polypyridyl complex [Ru(dmb)2dppz-idzo]2+ (dmb = 4,4'-dimethyl-2,2'-bipyridine, dppz-idzo = dppz-imidazolone) has been synthesized and characterized in this study. Binding properties of [Ru(dmb)2dppz-idzo]2+ to RNA duplex poly(A) · poly(U) and triplex poly(U) · poly(A) ∗ poly(U) have been explored by spectroscopic techniques and viscometry experiments. The binding modes of [Ru(dmb)2dppz-idzo]2+ to RNA duplex and triplex are intercalation as revealed from spectral titrations and viscosity experiments, while the binding strength of this complex to duplex structure is significantly greater than that of triplex structure. Fluorescence titrations indicate that [Ru(dmb)2dppz-idzo]2+ can act as a molecular "light switch" for both duplex poly(A) · poly(U) and triplex poly(U) · poly(A) ∗ poly(U), while [Ru(dmb)2dppz-idzo]2+ is more sensitive to poly(A) · poly(U) compared to poly(U) · poly(A) ∗ poly(U) and poly(U). Therefore, this complex can distinguish between RNA duplex, triplex and poly(U), and can as luminescent probes for the three RNAs used in this study. In addition, thermal denaturation studies show that [Ru(dmb)2dppz-idzo]2+ is able to significantly increase the Stabilization of RNA duplex and triplex. The results obtained in this study may contribute to further understanding of the binding of Ru(II) complexes with different structural RNAs.


Randomized controlled trial of an integrated approach to treating insomnia and improving the use of positive airway pressure therapy in veterans with comorbid insomnia disorder and obstructive sleep apnea.
Cognitive behavioral therapy for insomnia (CBTI) for comorbid insomnia and obstructive sleep apnea (OSA) has had mixed results. We integrated CBTI with a positive airway pressure (PAP) adherence program and tested effects on sleep and PAP use. 125 veterans (mean age 63.2, 96% men, 39% non-Hispanic white, 26% black/African American, 18% Hispanic/Latino) with comorbid insomnia and newly-diagnosed OSA (apnea-hypopnea index ≥ 15) were randomized to 5-weekly sessions integrating CBTI with a PAP adherence program provided by a "sleep coach" (with behavioral sleep medicine supervision), or 5-weekly sleep education control sessions. Participants and assessment staff were blinded to group assignment. Outcomes (baseline, 3 and 6 months) included Pittsburgh Sleep Quality Index (PSQI), 7-day sleep diary (sleep onset latency [SOL-D], wake after sleep onset [WASO-D], sleep efficiency [SE-D]), 7-day actigraphy (SE-A), and objective PAP use (hours/night and nights ≥ 4 h). Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), and Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10) were also collected. Compared to controls, intervention participants showed greater improvement (baseline to 3 and 6 months, respectively) in PSQI (-3.2 and -1.7), SOL-D (-16.2 and -15.5 minutes), SE-D (10.5% and 8.5%), SE-A (4.4% and 2.6%) and more 90-day PAP use (1.3 and 0.9 more hours/night, 17.4 and 11.3 more nights PAP ≥ 4 h). 90-day PAP use at 3 months was 3.2 and 1.9 h/night in intervention versus controls. Intervention participants also had greater improvements in ISI, ESS, and FOSQ-10 (all p < 0.05). An intervention integrating CBTI with a PAP adherence program delivered by a supervised sleep coach improved sleep and PAP use in adults with comorbid insomnia and OSA. ClinicalTrials.govStudy name: Novel Treatment of Comorbid Insomnia and Sleep Apnea in Older VeteransURL: https://clinicaltrials.gov/ct2/results?cond=&term=NCT02027558&cntry=&state=&city=&dist=Registration: NCT02027558.


Unsupervised registration for liver CT-MR images based on the multiscale integrated spatial-weight module and dual similarity guidance.
Multimodal registration is a key task in medical image analysis. Due to the large differences of multimodal images in intensity scale and texture pattern, it is a great challenge to design distinctive similarity metrics to guide deep learning-based multimodal image registration. Besides, since the limitation of the small receptive field, existing deep learning-based methods are mainly suitable for small deformation, but helpless for large deformation. To address the above issues, we present an unsupervised multimodal image registration method based on the multiscale integrated spatial-weight module and dual similarity guidance. In this method, a U-shape network with our multiscale integrated spatial-weight module is embedded into a multi-resolution image registration architecture to achieve end-to-end large deformation registration, where the spatial-weight module can effectively highlight the regions with large deformation and aggregate discriminative features, and the multi-resolution architecture further helps to solve the optimization problem of the network in a coarse-to-fine pattern. Furthermore, we introduce a special loss function based on dual similarity, which represents both global gray-scale similarity and local feature similarity, to optimize the unsupervised multimodal registration network. We verified the effectiveness of the proposed method on liver CT-MR images. Experimental results indicate that the proposed method achieves the optimal DSC value and TRE value of 92.70 ± 1.75(%) and 6.52 ± 2.94(mm), compared with other state-of-the-art registration algorithms. The proposed method can accurately estimate the large deformation field by aggregating multiscale features, and achieve higher registration accuracy and fast registration speed. Comparative experiments also demonstrate the effectiveness and generalization ability of the algorithm.


A plant immune protein fights against cancer.
Altered global miRNA abundance is closely related to the occurrence of cancer. Recently, Qi et al. discovered that abnormal 1-nucleotide (nt)-shorter miRNA isoforms are widely accumulated in different human tumors. Ectopic expression of the plant immune protein RNA-dependent RNA polymerase (RDR)-1 can achieve a broad-spectrum antitumor effect by rescuing miRNA defects in cancer cells.


Effects of resin formulation and nanofiller surface treatment on in vitro wear of experimental hybrid resin composite.
While adding nonbonded nanofillers and lowering the viscosity of the resin matrix have shown success in reducing deleterious polymerization stresses in dental composites, their effects on wear resistance is unknown. This study evaluated abrasion and attrition wear of experimental composites with varied resin viscosities [inherent to varied ratios of TEGDMA:UDMA:bis-GMA (47:33:16 wt%; 30:33:33 wt%; 12:33:51 wt%)] and nanofiller surface treatment (12.6 wt% silanated or unsilanated silica: OX-50; 0.04 microm). Specimens (n = 6) were light cured, aged in water at 37 degrees C for 7 days, and evaluated in the new OHSU oral wear simulator (100,000 cycles). Nonbonded nanofiller increased abrasion and attrition in the low and medium viscosity composites. Increase in resin viscosity increased abrasion and attrition in composites containing silanated nanofiller, with equivocal effects in composites containing unsilanated nanofiller. Nonbonded nanofiller can lower the overall wear resistance of some composite formulations. Increasing resin viscosity generally lowers the wear resistance, but had minimal effect on composites containing nonbonded nanofiller.


Investigation of coupled bending of the lumbar spine during dynamic axial rotation of the body.
Little is known about the coupled motions of the spine during functional dynamic motion of the body. This study investigated the in vivo characteristic motion patterns of the human lumbar spine during a dynamic axial rotation of the body. Specifically, the contribution of each motion segment to the lumbar axial rotation and the coupled bending of the vertebrae during the dynamic axial rotation of the body were analyzed. Eight asymptomatic subjects (M/F, 7/1; age, 40-60 years) were recruited. The lumbar segment of each subject was MRI scanned for construction of 3D models of the vertebrae from L2 to S1. The lumbar spine was then imaged using a dual fluoroscopic system while the subject performed a dynamic axial rotation from maximal left to maximal right in a standing position. The 3D vertebral models and the fluoroscopic images were used to reproduce the in vivo vertebral motion. In this study, we analyzed the primary left-right axial rotation, the coupled left-right bending of each vertebral segment from L2 to S1 levels. The primary axial rotations of all segments (L2-S1) followed the direction of the body axial rotation. Contributions of each to the overall segment axial rotation were 6.7° ± 3.0° (27.9 %) for the L2-L3, 4.4° ± 1.2° (18.5 %) for the L3-L4, 6.4° ± 2.2° (26.7 %) for the L4-L5, and 6.4° ± 2.6° (27.0 %) for the L5-S1 vertebral motion segments. The upper segments of L2-L3 and L3-L4 demonstrated a coupled contralateral bending towards the opposite direction of the axial rotation, while the lower segments of L4-L5 and L5-S1 demonstrated a coupled ipsilateral bending motion towards the same direction of the axial rotation. Strong correlation between the primary axial rotation and the coupled bending was found at each vertebral level. We did not observe patterns of coupled flexion/extension rotation with the primary axial rotation. This study demonstrated that a dynamic lumbar axial rotation coupling with lateral bendings is segment-dependent and can create a coordinated dynamic coupling to maintain the global dynamic balance of the body. The results could improve our understanding of the normal physiologic lumbar axial rotation and to establish guidelines for diagnosing pathological lumbar motion.


Growth effects of shading and sedimentation in two tropical seagrass species: Implications for port management and impact assessment.
Seagrass meadows in many parts of the globe are threatened by a range of processes including port development, dredging and land clearing in coastal catchments, which can reduce water clarity and increase sedimentation pressure. As rates of seagrass loss increase, there is an urgent need to understand the potential impacts of development on these critical species. This research compares the effects of shading and burial by fine sand on two seagrass species Zostera muelleri and Halophila ovalis in Port Curtis Bay, an industrial harbour located on the continental margin adjacent to the Great Barrier Reef Heritage Area, Australia. The research finds that shading in combination with burial causes a significant decline in growth rates in both species, but that burial ≥10mm reduces growth rates to a greater extent than shading. The paper concludes by discussing the implications of these findings for port management and impact assessment.


Estrogen Receptor Alpha (ESR1) Single-Nucleotide Polymorphisms (SNPs) Affect Malignant Melanoma Susceptibility and Disease Course.
The incidence of malignant melanoma in the developed world is continuously increasing. We conducted a case-control study in order to evaluate the association between each of the four estrogen receptor alpha polymorphisms (ESR1 single-nucleotide polymorphisms [SNPs] +2464C/T, -4576A/C, +1619A/G, and +6362C/T) and malignant melanoma susceptibility and disease course. The study population consisted of 205 Caucasian patients who were diagnosed as having malignant melanoma and 208 healthy Caucasian controls. Through DNA genotyping, we identified a SNP-dependent malignant melanoma susceptibility as well as a SNP-dependent effect on the course of disease and response to therapy.


Clinical study of transcutaneous vaccination using a hydrogel patch for tetanus and diphtheria.
Transcutaneous immunization (TCI) is a non-invasive and easy-to-use vaccination method. We demonstrated the efficacy and safety of a transcutaneous vaccine formulation using a hydrogel patch in animal experiments. In the present study, we performed a clinical study to apply our TCI formulation for vaccination against tetanus and diphtheria in human. The TCI device was a hydrogel patch (antigen-free) applied to the left brachial medial skin of 22 healthy volunteers for 48 h. Next, the hydrogel patch, containing 2mg tetanus toxoid (TT) and 2mg diphtheria toxoid (DT) as the TCI formulation, was applied to 27 healthy volunteers for 24h and some volunteers were vaccinated again by TCI formulation. For safety assessment, the patch application site was observed to assess local adverse events, and systemic adverse events were determined by a blood test. The antigen-free hydrogel patch and TCI formulation containing TT and DT did not induce local or systemic severe adverse events. For vaccine efficacy estimation, toxoid-specific serum antibody titers were determined by ELISA and the toxin-neutralizing activity of the induced antibody was evaluated in a passive-challenge experiment. The anti-TT IgG titer and the anti-DT IgG titer increased, and a significant effect was detected by paired t-test. The antibody titers were maintained at higher level than that before vaccination for at least 1 year. Moreover, toxoid-specific antibodies were produced by the second vaccination in some subjects. Antibodies induced by application of the TCI formulation neutralized the toxin and prevented toxic death in mice. In addition, changes in the skin condition due to application of the TCI formulation were observed under in vivo confocal Raman spectroscopy. The amount of water and patch components in the stratum corneum increased after application of the TCI formulation, suggesting that the change in the skin condition was related to antigen penetration. These data indicate that this easy-to-use TCI system induces an immune response without severe adverse reactions in humans. This easy-to-use and safe TCI formulation enables mass treatment in an outbreak setting and increased vaccination rates in developing countries, and will greatly contribute to worldwide countermeasures against infectious diseases.


Canine von Willebrand's disease. A heterogeneous group of bleeding disorders.
The term "von Willebrand's disease," refers to a group of inherited bleeding disorders, all of which are caused by a deficiency of the multimeric plasma glycoprotein, von Willebrand factor. The various forms of canine von Willebrand's disease can be categorized into one of three major types: in type I canine von Willebrand's disease, all sizes of von Willebrand factor multimers can be detected in the plasma; in type II canine von Willebrand's disease, only the smaller von Willebrand factor multimers are found in the plasma (larger multimers are absent); and in type III canine von Willebrand's disease, von Willebrand factor is completely absent from the plasma or present in only trace amounts. Von Willebrand's disease is common in dogs, but some forms of the disease are so mild that they are of questionable clinical significance.


ECMELLA 2.0: Single Arterial Access Technique for a Staged Approach in Cardiogenic Shock.
The main drawbacks of venoarterial extracorporeal life support (VA-ECLS) for cardiogenic shock are incomplete left ventricular unloading with concomitant pulmonary edema and vascular access site complications. We describe the staged treatment technique for severe cardiogenic shock with a combination of the Impella 5.0/5.5 (Abiomed Inc, Danvers, MA) and peripheral ECLS (ECMELLA) using a single arterial access in 2 consecutive patients with refinement of the technique in the second case. The arterial cannula was inserted through the same vascular graft in the axillary artery that served as access for the previously implanted microaxial blood pump.


The role of Interleukin 6 inhibitors in therapy of severe COVID-19.
Cytokine storm syndrome (CSS) is a severe complication of inflammatory immune diseases or treatment of malignancies; it may also appear during the progression of COVID-19. CSS is caused by dysregulation of the synthesis of cytokines, including pro-inflammatory, regulatory, and anti-inflammatory cytokines and chemokines, leading to pathologic activation of innate and adaptive (Th1 and Th17 mediated) immunity. Interleukin-6 (IL-6) plays an important role in the pathogenesis of CSS. The significant role of IL-6 in pathogenesis of COVID-19 was confirmed in a range of studies, which showed that the plasma concentration of IL-6 was increased in patients with severe COVID-19. Currently, IL-6 inhibitor therapeutics are not yet approved for the treatment of COVID-19; however, these medicines, including tocilizumab (TCZ) are used off-label for the treatment of patients with severe COVID-19, including life-threatening conditions. The role of IL-6 in the pathogenesis of CSS during COVID-19 is important however, a number of related issues are not yet clear. These issues include the indications for treatment with IL-6 inhibitors, as well as the estimation of risk associated with the disease, outcomes, treatment options, and adverse drug reactions. The development of personalized immunomodulatory therapy, with respect to the role of cytokines in pathogenesis, requires the studies that aimed to find other relevant therapeutic targets for the treatment of CSS in patients with COVID-19. These therapeutic targets include inhibition of IL-1, IL-6, TNFα, GM-CSF, IFNγ, IL-17, IL-18, and also activation of the complement system. The challenge of CSS in patients with COVID-19 is identifying the correct scientific targets and developing clinical trials aimed to evaluate the pathogenesis and treat immune-mediated inflammatory diseases (IMIDs). Hopefully, the significant efforts of scientists and physicians across the globe will improve the prognosis in COVID-19 patients and provide useful information on IMIDs required to support the struggle for treating potential viral outbreaks, and treatment of well-known IMIDs.


Drp1-mediated mitochondrial fission is involved in oxidized low-density lipoprotein-induced AF cella poptosis.
This study aimed to assess the negative effect of oxidized low-density lipoprotein (oxLDL) on annulus fibrosus (AF) cells and decipher the mechanism of action of the process. After treating AF cells with various concentrations (0, 25, 50, 100, and 200 μg/mL) of oxLDL for 24 and 48 hours, their viability was evaluated using cell counting kit-8 and live/dead staining. The percentage of AF cell death was determined with Annexin V/propidium iodide apoptosis staining. The expression of proteins related to the mitochondrial apoptosis pathway was determined using Western blot. Additionally, mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) were assessed with JC-1 staining and dichlorodihydrofluorescein diacetate ormitoSOX probes, respectively. Mitochondrial morphology was observed with a transmission electron microscope. After treatment with oxLDL, AF cell viability decreased, pro-apoptosis proteins (such as Bax, cleaved caspase-9, and cleaved caspase-3) increased, and anti-apoptosis proteins (Bcl-2) declined. Excessive ROS and diminished MMP were also detected during this process, as were enhanced mitochondrial fission and augmented Drp1 expression. Furthermore, knocking down the expression of Drp1 rescued oxLDL-induced AF cell death. Collectively, these results suggest that oxLDL induces AF cell death through a mitochondria-related pathway. Enhanced mitochondrial fission was involved in oxLDL-induced AF cell death. Targeting Drp1, a target for regulating the process of mitochondrial fission, may be a feasible strategy for preventing intervertebral disc degeneration in hyperlipidemia.


[Otoneurosurgical treatment of tumors of the cerebellopontine angle. Apropos of a series of 93 cases].
Authors analyse their experience with the treatment of ninety-three cases of cerebello-pontine angle tumors. A trained team with an otologist and neurosurgeon can obtain best results, both functional and vital. The postero-trans-labyrinthine approach, as described by House and al is used ad the method of choice. Analysis of cases shows that big tumors are frequent and their therapy difficult even if the risk of mortality has been diminished.


The structure and mechanism of the Mycobacterium tuberculosis cyclodityrosine synthetase.
The Mycobacterium tuberculosis enzyme Rv2275 catalyzes the formation of cyclo(L-Tyr-L-Tyr) using two molecules of Tyr-tRNA(Tyr) as substrates. The three-dimensional (3D) structure of Rv2275 was determined to 2.0-Å resolution, revealing that Rv2275 is structurally related to the class Ic aminoacyl-tRNA synthetase family of enzymes. Mutagenesis and radioactive labeling suggests a covalent intermediate in which L-tyrosine is transferred from Tyr-tRNA(Tyr) to an active site serine (Ser88) by transesterification with Glu233 serving as a critical base, catalyzing dipeptide bond formation.


Real-time instance segmentation of surgical instruments using attention and multi-scale feature fusion.
Precise instrument segmentation aids surgeons to navigate the body more easily and increases patient safety. While accurate tracking of surgical instruments in real-time plays a crucial role in minimally invasive computer-assisted surgeries, it is a challenging task to achieve, mainly due to: (1) a complex surgical environment, and (2) model design trade-off in terms of both optimal accuracy and speed. Deep learning gives us the opportunity to learn complex environment from large surgery scene environments and placements of these instruments in real world scenarios. The Robust Medical Instrument Segmentation 2019 challenge (ROBUST-MIS) provides more than 10,000 frames with surgical tools in different clinical settings. In this paper, we propose a light-weight single stage instance segmentation model complemented with a convolutional block attention module for achieving both faster and accurate inference. We further improve accuracy through data augmentation and optimal anchor localization strategies. To our knowledge, this is the first work that explicitly focuses on both real-time performance and improved accuracy. Our approach out-performed top team performances in the most recent edition of ROBUST-MIS challenge with over 44% improvement on area-based multi-instance dice metric MI_DSC and 39% on distance-based multi-instance normalized surface dice MI_NSD. We also demonstrate real-time performance (>60 frames-per-second) with different but competitive variants of our final approach.


Exposure to a sublethal concentration of CdO nanoparticles impairs the vision of the fruit fly (Drosophila melanogaster) by disrupting histamine synthesis and recycling mechanisms.
While there is substantial literature on potential risks associated with exposure to emerging nanomaterials, less is known about the potential effects of hazardous metallic nanoparticles on vision, as well as the mechanisms that underpin them. The fruit fly (Drosophila melanogaster) was used as an in vivo model organism to investigate the effects of exposure to a sublethal concentration (0.03 mg CdO NPs/mL, which was 20% of the LC50) on fly vision and compound eye ultrastructure. First, we observed a reduction in phototaxis response in treated flies but no change in locomotor activity. Because histamine (HA) has been linked to arthropod vision, we investigated HA synthesis, uptake, and recycling as a possible underlying mechanism for the observed adverse effect of CdO NPs on fly vision. This was accomplished by measuring the expression of the histamine decarboxylase (hdc) gene, which encodes the enzyme that converts the amino acid histidine to histamine (HA), as well as the expression of some genes involved in HA-recycling pathways (tan, ebony, Balat, CarT, and Lovit). The results showed that CdO NPs changed the expression levels of hdc, Lovit, tan, and eboney, indicating that HA synthesis, transport, and recycling were disrupted. Furthermore, less histamine immunolabeling was found in the head tissues of CdO NP-treated flies, particularly in the optic lobes. We also observed and quantified CdO NP bioaccumulation in compound eye tissues, which resulted in a number of cytological changes. Phenotypic effects (undersized eyes) have also been observed in the compound eyes of F1 flies. Considering the significance of vision in an organism's survival, the findings of this study are extremely crucial, as long-term exposure to CdO NPs may result in blindness.


An enzyme-linked immunosorbent assay for the determination of human IgG subclass antibodies directed against Branhamella catarrhalis.
An ELISA procedure to determine the distribution of human IgG subclass antibodies directed against the gram-negative bacterium Branhamella catarrhalis has been developed using commercially available monoclonal anti-IgG subclass antibodies. Using whole bacteria as coating antigen the specificity of the assay was determined and showed minimal cross-reactivity with a range of other bacteria. Estimations of IgG1, IgG2, IgG3, IgG4 and total IgG antibodies directed against this antigen were performed. All normal adult sera tested had measurable antibody levels of specific IgG1, IgG2, IgG3 and total IgG. Specific IgG4 was undetectable in the majority of adult sera. These assays will be of value for investigation of both children and adults with suspected immunodeficiency and recurrent upper respiratory tract infection.


Insecticidal activity of Piper essential oils from the Amazon against the fire ant Solenopsis saevissima (Smith) (Hymenoptera: Formicidae).
Pepper plants in the genus Piper (Piperales: Piperaceae) are common in the Brazilian Amazon and many produce compounds with biological activity against insect pests. We evaluated the insecticidal effect of essential oils from Piper aduncum, Piper marginatum (chemotypes A and B), Piper divaricatum and Piper callosum against workers of the fire ant Solenopsis saevissima (Smith) (Hymenoptera: Formicidae), as well as their chemical composition by gas chromatography and gas chromatography-mass spectrometry. The lowest median lethal concentration (LC50) in 48 h was obtained with the oil of P. aduncum (58.4 mg/L), followed by the oils of P. marginatum types A (122.4 mg/L) and B (167.0 mg/L), P. divaricatum (301.7 mg/L), and P. callosum (312.6 mg/L). The major chemical constituents were dillapiole (64.4%) in the oil of P. aduncum; p-mentha-1(7),8-diene (39.0%), 3,4-methylenedioxypropiophenone (19.0%), and (E)-β-ocimene (9.8%) in P. marginatum chemotype A and (E)-isoosmorhizole (32.2%), (E)-anethole (26.4%), isoosmorhizole (11.2%), and (Z)-anethole (6.0%) in P. marginatum chemotype B; methyleugenol (69.2%) and eugenol (16.2%) in P. divaricatum; and safrole (69.2%), methyleugenol (8.6%), and β-pinene (6.2%) in P. callosum. These chemical constituents have been previously known to possess insecticidal properties.


Metrical differential diagnosis based on location (Part 2). Differential diagnosis among various benign tumors.
An attempt was made to quantify the location of various oral lesions using panoramic radiographs of benign tumors (20 ameloblastomas, 5 myxomas, 26 odontomas, 10 cementomas and 4 osteomas). The metrical data (integers) were obtained from a conversion table and the abscissa values (to the first decimal place) were obtained from the centroid of each of the tumors. Differential diagnosis among these lesions revealed that in the mandible, it is possible to differentiate between ameloblastomas and odontomas or osteomas. Thus, the present findings demonstrate that data on lesion location can be changed into metrical data for differential diagnosis of benign tumors.


Internal mammary artery to coronary artery bypass in paediatric cardiac surgery.
The internal mammary artery is regarded as the optimal conduit for coronary artery bypass grafting in adults. Use of this conduit in paediatric surgery is rare and has been reported mainly in patients with Kawasaki's disease. We report five patients who required internal mammary-coronary artery grafting due to adverse anatomical disposition of the coronary artery. In two cases an internal mammary graft was required during correction of transposition of the great arteries. The other cases involved correction of a left coronary artery arising anomalously from the pulmonary artery. Late angiography shows satisfactory growth and patency of the conduits.


Studies on the neutralization of herpes simplex virus. X. Demonstration of complement-requiring neutralizing (CRN) and slow-reacting CRN (s-CRN) antibodies in late IgG.
A sample of late IgG from a rabbit hyperimmunized with herpes simplex virus was analyzed for neutralizing (N) and complement-requiring neutralizing (CRN) antibodies. In a usual endpoint test, N and CRN titers were 1: 40 and 1: 160, respectively, but when virus-IgG mixtures were incubated at 0 C overnight before addition of complement (C), an endpoint of 1:1280 was obtained. Virus sensitized at 0 C overnight required more C for inactivation than did sensitized virus formed earlier. Sensitization kinetic curve experiments employing a proper initial virus concentration, which permitted differentiation of sensitized viruses requiring different amounts of C, indicated that formation of sensitized virus detectable only with a relatively large amount of C proceeded slowly at IgG dilutions where the ordinary CRN antibody requiring a smaller amount of C was negligible. The results strongly suggested that the IgG sample contained slow-reacting CRN (s-CRN) antibody in excess of the hitherto known CRN antibody. As to the mechanism of formation of s-CRN complexes, experiments failed to prove the occurrence of complexes initially insensitive to C, and it appears more likely that s-CRN antibody has a comparatively low avidity for virus.


Involvement of oxidative stress in bactericidal activity of 2-(2-nitrovinyl) furan against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus.
The involvement of reactive oxygen species and oxidative stress in 2-(2-nitrovinyl) furan mediated bacterial cell death was investigated in Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Time kill assay resulted in significant decrease in the optical density and colony-forming unit (CFU) of E. coli, P. aeruginosa and S. aureus. The level of superoxide anion radical and nitric oxide increased significantly in concentration dependent when compared with dimethyl sulfoxide (DMSO) treated bacteria. Similar concentration dependent increase in the activity of superoxide dismutase and catalase were recorded. The non-enzymatic antioxidant glutathione decreased significantly with a concomitant increase in glutathione disulfide. The level of malondialdehyde and fragmented DNA increased significantly in the bacterial cells treated with 2-(2-nitrovinyl) furan when compared with DMSO treated cells. The CFU of E. coli, P. aeruginosa and S. aureus following exposure to 2-(2-nitrovinyl) furan increased significantly (p < 0.05) in the presence of 2,2' bipyridyl, an Fe chelator, significantly when compared with only 2-(2-nitrovinyl) furan suggesting the involvement of hydroxyl radical in the cell death. The available data from this study showed that 2-(2-nitrovinyl) furan induced oxidative stress in E. coli, P. aeruginosa and S. aureus as evident from elevated levels of superoxide anion radical nitric oxides and antioxidant enzymes.


Respecting tribal traditions in research and publications: voices of five Native American nurse scholars.
A dialogue with five Native American scholars provides insight into conducting research and publishing resulting manuscripts on Native American topics, specifically healing beliefs and practices. This information provides a means to develop sensitivity and create understanding about concerns held by Native Americans regarding sharing certain defined cultural information with those outside the culture. The article identifies salient tribal issues related to research, discusses perspectives important to tribal nations and Native individuals surrounding research, and supplies a base on which to formulate further discussions.


[Proteomic analysis of hepatitis B virus-infected human liver tissues].
To search for the difference of protein molecules expression of HBV infection. Specimens taken from human normal liver tissues (group A), HBV infected human liver tissues which were HBsAg positive, and HBsAg, anti-HBe, and anti-HBc positive in serum (group B) were analysed through the methods of 2-dimensional electrophoresis (2-DE) and matrix-assisted laser-desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS/MS). Totally 1125 plus/minus 56 (n=3) spots were detected in the sample of group A, 1203 plus/minus 42 (n=3) in group B samples. The percent volume of the protein spots was compared to show the proteome alteration in HBV infected human liver tissues. Forty proteins were found to present variations of two or more than two fold in quantity and 22 differentially expressed protein sports were finally identified by MALDI-TOF-MS/MS, including human mitochondrial aldehyde dehydrogenase, haptoglobin Hp2, peroxiredoxin 2, etc. The protein profile of human normal liver tissue and HBV infected liver tissues showed obviously difference.


Facilitators and Challenges to Health Promotion in Black and Latino Churches.
Churches are important assets for the African American and Latino communities. They can play a critical role in health promotion, especially in areas that are under-resourced and in which residents have limited access to health care. A better understanding of health promotion in churches is needed to support and maintain church collaborations and health initiatives that are integrated, data-driven, and culturally appropriate. The purpose of this study is to identify churches' facilitators and challenges to health promotion and to contrast and compare Black and Latino churches of different sizes (< 200 members versus > 200 members). We interviewed leaders of 100 Black and 42 Latino churches in South Los Angeles to assess their history of wellness activities, resources, facilitators, and challenges to conduct health promotion activities. Eighty-three percent of African American and 86% of Latino church leaders reported at least one health activity in the last 12 months. Black and Latino churches of different sizes have similar interests in implementing specific health promotion strategies and face similar challenges. However, we found significant differences in the composition of their congregations, number of paid staff, and the proportions of churches that have a health or wellness ministry and that implement specific wellness strategies. Fifty-seven percent of African American and 43% of Latino church leaders stated that they needed both financial support and professional expertise for health promotion. Our findings highlight the importance of conducting a readiness assessment for identifying intervention content and strategies that fit the intervention context of a church.


[Ecology and epidemiology of tick-borne borreliosis in the Ul'ianovsk region].
The parameters that characterize the affection and spread of ticks in the Ulyanovsk Region are presented. A risk for Ixodes tick-borne borreliosis among the urban population is shown.


Effects of dietary L-citrulline supplementation on nitric oxide synthesis, immune responses and mitochondrial energetics of broilers during heat stress.
L-Citrulline is a non-protein amino acid that promotes arginine recycling and muscle protein synthesis. This study investigated whether L-citrulline can exert these functions in heat-stressed chickens. Arbor acre broilers were fed either basal diets (Control) or basal diets supplemented with 1% L-citrulline (L-Cit). At 28 d old, broilers were subjected to two environmental temperatures, 35 °C for 8 h/d (HS) or 24 °C for 24 h/d (TNZ) for 2 weeks. The experiment was designed as a 2 by 2 factorial arrangement. Results showed that HS increased the core body temperature (CBT) and rectal temperature of broilers compared to the TNZ condition. The CBT and mean CBT decreased by ∼0.5oC in TNZ + L-Cit broilers compared to the TNZ + Control group (P < 0.05). L-Cit supplementation at TNZ significantly (P < 0.05) lowered the plasma malondialdehyde content but this was increased during HS. Exposure to HS significantly (P < 0.05) elevated plasma malondialdehyde compared to TNZ condition. Plasma immunoglobulin A, G, and M were increased (P < 0.05) by TNZ + L-Cit compared to the TNZ + Control group. Plasma nitric oxide and endothelial nitric oxide synthase (NOS) activity was increased during HS, whereas the total and inducible NOS enzymes were decreased. In addition, L-Cit supplementation increased both the inducible and endothelial NOS isoforms (P < 0.05). The mRNA expression of peroxisome proliferator-activated receptor γ coactivator 1-α, avian uncoupling protein, cytochrome C oxidase subunit 3, and ATP synthase F1 subunit beta (ATP5β) in the breast muscle were downregulated (P < 0.05) during HS. However, L-Cit supplementation upregulated the mitochondrial transcription factor A and during HS, L-Cit increased ATP5β expression similar to TNZ housed broilers. Therefore, this study demonstrates that dietary L-Cit can lower the body temperature, decrease lipid peroxidation and promote the immune status of broilers under thermoneutrality. Also, L-Cit would act to promote muscle ATP generation during heat stress in broilers.