L-glutamine: a major substrate for tumor cells in vivo?
From 65 human breast cancer xenografts investigated, a net glutamine uptake was found in 13 tumors (mean +/- SE: 15.7 +/- 4.5 nmol/g per min) whereas a net release (22.5 +/- 3.3 nmol/g per min) was observed in 40 tumors. In 12 tumors neither a significant net uptake nor a net release was obvious. There is experimental evidence that glutamine is taken up by cancer cells only at arterial concentrations greater than 0.5 mM. Another parameter determining glutamine utilization by tumor cells may be the tissue oxygenation. In hypoxic or anoxic tumor areas, glutamine oxidation is unlikely since oxygen is required for the reoxidation of coenzymes which are reduced in the course of this metabolic pathway. The pronounced net release could be due to proteolysis within the tumors investigated. In ascitic fluid (DS-carcinosarcoma), glutamine accumulated during growth, implicating a reduction in the glutamine consumption rate, proposedly also due to a worsening of the oxygen supply to the suspended tumor cells. Thus, the generally held opinion that L-glutamine is a (if not the) major substrate for the energy metabolism of rapidly growing tumor cells should be reconsidered since evidence for this hypothesis has been derived mainly from in vitro systems with abundant oxygen.


Pentoxifylline protects against loss of function and renal interstitial fibrosis in chronic experimental partial ureteral obstruction.
Tubulointerstitial fibrosis (TIF) is a hallmark of chronic kidney disease resulting from diverse etiologies and predicts severity and progression of the kidney disease. To investigate the pathogenesis of TIF, complete unilateral ureteral obstruction (UUO) is the most widely used animal model. However, UUO precludes evaluation of renal function. In the present study, we created a rat model of chronic partial ureteral obstruction (PUO), which allowed assessment of renal function at different intervals after obstruction. We examined the effects of pentoxifylline (PTF), a phosphodiesterase inhibitor used clinically to treat peripheral artery disease, on renal function and TIF. Studies were performed in sham-PUO rats and rats with 14-day PUO or 30-day PUO receiving vehicle in drinking water or PTF (400 mg/liter in drinking water). At day-14 PUO, glomerular filtration rate (GFR) was markedly and similarly depressed in rats receiving vehicle or PTF as compared with sham-operated rats. However, at day-30 PUO, GFR in rats receiving PTF was significantly higher than that in rats receiving vehicle, approaching the level seen in the sham-operated rats. At day-30 PUO, histologic studies also revealed a marked reduction of TIF in rats treated with PTF as compared with the rats receiving vehicle in drinking water. Western blot analysis demonstrated that at day-30 the expression of α-smooth muscle actin (an indicator of renal fibrosis) in the medulla was significantly reduced in PUO rats treated with PTF. In conclusion, PTF treatment ameliorated renal fibrosis and helped preserve renal function in a rodent model of PUO.


Single quantum emitters in monolayer semiconductors.
Single quantum emitters (SQEs) are at the heart of quantum optics and photonic quantum-information technologies. To date, all the demonstrated solid-state single-photon sources are confined to one-dimensional (1D; ref. 3) or 3D materials. Here, we report a new class of SQEs based on excitons that are spatially localized by defects in 2D tungsten-diselenide (WSe2) monolayers. The optical emission from these SQEs shows narrow linewidths of ∼130 μeV, about two orders of magnitude smaller than those of delocalized valley excitons. Second-order correlation measurements revealed a strong photon antibunching, which unambiguously established the single-photon nature of the emission. The SQE emission shows two non-degenerate transitions, which are cross-linearly polarized. We assign this fine structure to two excitonic eigenmodes whose degeneracy is lifted by a large ∼0.71 meV coupling, probably because of the electron-hole exchange interaction in the presence of anisotropy. Magneto-optical measurements also reveal an exciton g factor of ∼8.7, several times larger than those of delocalized valley excitons. In addition to their fundamental importance, establishing new SQEs in 2D quantum materials could give rise to practical advantages in quantum-information processing, such as an efficient photon extraction and a high integratability and scalability.


Determination of 6s-trans conformation of retinal chromophore in sensory rhodopsin I and phoborhodopsin.
8,16-Ethanoretinal 3 was synthesized from 2-methylcyclohexanone. From the binding experiments of 3 and 8,18-ethanoretinal 2 with apoproteins of sensory rhodopsin I and phoborhodopsin, it was found that retinal was incorporated as 6s-trans conformation in the both proteins.


A one-stage reconstruction of a large defect of the tendo Achilles and the overlying skin.
This presentation describes the simultaneous one-stage reconstruction, in a 14-year-old boy, of a missing fragment of the Achilles tendon and the skin covering the lower and posterior aspect of the leg.


[The reactivation of pulmonary tuberculosis after effective chemotherapy using rifampicin].
The authors present an analysis of dynamic five-year follow-up of 141 patients with freshly detected destructive pulmonary tuberculosis that received treatment with isoniaside and rifampicin in combination with other drugs. It was found that reactivation of pulmonary tuberculosis with the use of rifampicin is observed in 11 +/- 5% of patients and is accompanied by phenomena of not infrequently marked intoxication and chest symptoms and complaints. The importance of timing the main course of chemotherapy (not less than 12 months) and regular prophylactic autumn-spring course of treatment in the prophylaxis of reactivations of pulmonary tuberculosis.


Structural and functional analysis of a novel mutation of CYP21B in a heterozygote carrier of 21-hydroxylase deficiency.
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive disorders and occurs in its non-classical form in up to 6% of hirsute women. We report on a young woman with the clinical diagnosis of non-classical CAH and a novel, heterozygous missense mutation CTG-->GTG in exon 8, codon 317, of the steroid 21-hydroxylase CYP21B and complete loss of pseudogenes. Protein sequences of closely related P450 cytochromes and a homology-based 3D model of CYP21B were used for further functional analyses. We found that the mutated residue is part of a large cluster of hydrophobic residues. This cluster has three important features: (1) it is located directly next to the binding pocket, in close vicinity of the heme-cofactor, (2) all amino acids of the cluster are directly connected to two important binding regions, and (3) the packing within the cluster is very dense. Due to the tight packing in the cluster and its direct connection to the binding pocket region, any changes induced by the mutation of residue 317 can be expected to lead to structural shifts within the binding pocket and can explain the clinically observed impairment of 21-hydroxylase activity. In conclusion, the novel mutation L317V of the steroid 21-hydroxylase gene is associated with reduced steroid 21-hydroxylase activity probably due to structural shifts within the binding pocket and a mild phenotype of steroid 21-hydroxylase deficiency. In addition, the results support previous findings in which heterozygous CYP21 mutations are associated with symptoms of hyperandrogenism in susceptible individuals.


Rapid and sensitive detection of African swine fever virus in pork using recombinase aided amplification combined with QDMs-based test strip.
African swine fever virus (ASFV) is the pathogen of African swine fever, a highly contagious and fatal disease of wild boar and domestic pigs. The flow of ASFV through pork products is more concealed, higher risky, and more difficult to prevent and control. Presently, on-site ASFV detection methods in preclinical infected pigs and circulated pork products are lacking. Here, fluorescent test strip-based rapid ASFV detection method in pork was established combined with recombinase aided amplification (RAA) and quantum dot microspheres (QDMs). This method is specific to ASFV with no cross-reactivity to pseudorabies virus (PRV), porcine circovirus type 2 (PCV2), and porcine reproductive and respiratory syndrome virus (PRRSV). The method also showed highly sensitivity with a detection limit of 1 copy for ASFV plasmid templates containing B646L gene and 100 copies/g for DNA extracts from clinical pork samples within a short detection time of less than 25 min. Additionally, the method showed 99.17% consistency with real-time PCR in the ASFV detection of 120 clinical pork samples. Overall, the QDMs-based test strip method provides specific, sensitive, rapid, and simple detection of ASFV in pork, which may contribute to maintain the food safety of pork products, and facilitate ASFV traceability and prevention. Rapid and sensitive detection of African swine fever virus in pork by QDMs based test strip assay.


Ectopic recurrence craniopharyngioma: series report and literature review.
Craniopharyngioma is a common intracranial tumor located in the sellar-suprasellar region. Due to the involvement of adjacent structures, it can lead to increased intracranial pressure, visual impairment, and endocrine deficiencies. Surgical resection is the primary treatment, but it is a tough challenge to achieve total resection, which will led to the frequency of recurrences and progressions. Among them, distant spread is extremely rare, but important complication, identifying and providing proper therapy, is crucial. We report two cases of ectopic recurrence craniopharyngioma and make a literature review for the published similar case reports. Our literature review revealed 63 cases (including our patient). The onset age in children group and adult group ranges from 2-14 years old (6.70 ± 3.33) to 17-73 years old (40.63 ± 15.58), while the interval year between tumor initiation and ectopic recurrence ranges from 0.17-20 (7.28 ± 6.76) years to 0.3-34 (6.85 ± 7.29). Achieving gross total resection seems not to prevent the ectopic recurrence. The major pathology of ectopic recurrence craniopharyngioma is adamantinomatous type. The most common site of ectopic recurrence is frontal lobe. According to the pathogenesis, 35 cases were seeding along the surgical approach, and 28 cases were seeding via the CSF pathway. Ectopic recurrence craniopharyngioma is rare, but it can lead to serious symptoms. Delicate surgical procedure can help to reduce the risk of ectopic recurrence, and standardized follow-up can provide valuable information for treatment.


Comparison of piecewise structural equation modeling and Bayesian network for de novo construction of a quantitative adverse outcome pathway network.
Quantitative adverse outcome pathway network (qAOPN) is gaining momentum due to its predictive nature, alignment with quantitative risk assessment, and great potential as a computational new approach methodology (NAM) to reduce laboratory animal tests. The present work aimed to demonstrate two advanced modeling approaches, piecewise structural equation modeling (PSEM) and Bayesian network (BN), for de novo qAOPN model construction based on routine ecotoxicological data. A previously published AOP network comprised of four linear AOPs linking excessive reactive oxygen species production to mortality in aquatic organisms was employed as a case study. The demonstrative case study intended to answer: Which linear AOP in the network contributed the most to the AO? Can any of the upstream KEs accurately predict the AO? What are the advantages and limitations of PSEM or BN in qAOPN development? The outcomes from the two approaches showed that both PSEM and BN are suitable for constructing a complex qAOPN based on limited experimental data. Besides quantification of response-response relationships, both approaches could identify the most influencing linear AOP in a complex network and evaluate the predictive ability of the AOP, albeit some discrepancies in predictive ability were identified for the two approaches using this specific dataset. The advantages and limitations of the two approaches for qAOPN construction are discussed in detail, and suggestions on optimal workflows of PSEM and BN are provided to guide future qAOPN development.


Sex, Race, and Age Differences in Observed Years of Life, Healthy Life, and Able Life among Older Adults in The Cardiovascular Health Study.
Longevity fails to account for health and functional status during aging. We sought to quantify differences in years of total life, years of healthy life, and years of able life among groups defined by age, sex, and race. Primary analysis of a cohort study. 18 years of annual evaluations in four U.S. communities. 5888 men and women aged 65 and older. Years of life were calculated as the time from enrollment to death or 18 years. Years of total, healthy, and able life were determined from self-report during annual or semi-annual contacts. Cumulative years were summed across each of the age and sex groups. White women had the best outcomes for all three measures, followed by white men, non-white women, and non-white men. For example, at the mean age of 73, a white female participant could expect 12.9 years of life, 8.9 of healthy life and 9.5 of able life, while a non-white female could expect 12.6, 7.0, and 8.0 years, respectively. A white male could expect 11.2, 8.1, and 8.9 years of life, healthy life, and able life, and a non-white male 10.3, 6.2, and 7.9 years. Regardless of starting age, individuals of the same race and sex groups spent similar amounts (not proportions) of time in an unhealthy or unable state. Gender had a greater effect on longevity than did race, but race had a greater effect on years spent healthy or able. The mean number of years spent in an unable or sick state was surprisingly independent of the lifespan.


Toxicological approaches to the metabolites of Fusaria. XIII. Hematological changes in mice by a single and repeated administrations of trichothecenes.
A single or repeated administration of trichothecene mycotoxins to mice induced leukocytosis and leukopenia. Acute and sub-acute toxicosis of trichothecenes was characterized by hematological and pathological observations.


Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT.
There is a paucity of data on hepatitis B virus (HBV) DNA levels and histologic lesions in patients with chronic HBV (CHBV) infection and persistently normal alanine aminotransferase (ALT) levels (PNALT). We studied the ALT, HBV DNA levels, and spectrum of histologic lesions in such patients. One thousand three hundred eighty-seven incidentally detected asymptomatic hepatitis B surface antigen (HBsAg)-positive patients with >/=1-year follow-up and either PNALT (n = 189; hepatitis B e antigen [HBeAg(+)], 73; HBeAg(-), 116) or persistently or intermittently elevated ALT (PIEALT; n = 1198; HBeAg(+), 530; HBeAg(-), 668) were included. In the PIEALT and PNALT patients, baseline DNA >/=5-log copies/mL was seen in 73.8% and 60.3% in HBeAg(+) (P = .018) and 76% and 35.3% in HBeAg(-) (P < .001) patients and histologic fibrosis stage >/=2 in 65.5% and 40.2% in HBeAg(+) (P < .001) and 63.9% and 13.8% in HBeAg(-) (P < .001) patients, respectively. Approximately 21% of HBeAg(-) patients with PNALT and HBV DNA <5-log copies/mL had histologically active liver disease (histologic activity index >/=3 and/or fibrosis stage >/=2). A fair proportion of patients with CHBV infection with PNALT have HBV DNA >/=5-log copies/mL and significant histologic fibrosis. Use of ALT and HBV DNA levels without resorting to liver biopsy to define "inactive carrier state" in HBeAg(-) PNALT patients may miss histologically significant disease in a proportion of patients.


Fatigue in primary biliary cirrhosis.
The autoimmune liver disease, primary biliary cirrhosis (PBC), is associated with debilitating fatigue in a significant proportion of patients. The pathogenesis of fatigue in PBC is unclear, but preliminary studies suggest it has central mechanisms and may have peripheral manifestations. Studies are beginning to elucidate the biological associates of fatigue in PBC, particularly sleep disturbance and autonomic dysfunction. Comprehensive studies investigating the pathogenesis of fatigue in PBC are urgently needed as are large-scale prospective outcome studies.


Purification and characterization of an inducible aromatic amino acid-sensitive form of chorismate mutase from Solanum tuberosum L. tubers.
An amino acid-sensitive form of chorismate mutase (CM) has been purified over 1000-fold from disks excised from tubers of Solanum tuberosum L. cv White Rose. Purification was accomplished by chromatography on Matrix Blue A followed by affinity chromatography with tryptophan as ligand. CM assays performed in the absence of tryptophan yielded pH-dependent sigmoidal kinetics. At pH 8.0, sigmoidal kinetics were observed with a Hill coefficient of 1.66 (S0.5 = 188 microM). However, a shift from sigmoidal to hyperbolic kinetics was observed when assays were performed at pH 8.5. Addition of 9 microM tryptophan to the assay resulted in maximum activation of the enzyme with a Ka of 1.2 microM. When assayed in the presence of tryptophan, hyperbolic kinetics were observed over the pH range 6.0-8.0. Addition of tryptophan also decreased the Km for chorismate from 185 to 45 microM. Tryptophan (0.1 mM) completely protected CM from inhibition by phenylalanine (1.8 mM) and tyrosine (1.8 mM). However, in the absence of the activator, phenylalanine and tyrosine exhibited 50% inhibition at 0.80 and 0.68 mM concentrations, respectively. Both phenylalanine and tyrosine competitively inhibited CM activity with Ki values of 550 and 440 mM, respectively. Arogenate (1.0 mM) had no effect on CM activity in either the presence or absence of tryptophan. Analytical isoelectric focusing yielded an isoelectric point of 4.73.


Impending macrosomia: will induction of labour modify the risk of caesarean delivery?
To compare the annual incidence rates of caesarean delivery between induction of labour and expectant management in the setting of macrosomia. This is a retrospective cohort study. Deliveries in the USA in 2003. Singleton births of macrosomic neonates to low-risk nulliparous women at 39 weeks of gestation and beyond. Women who had induction of labour at 39 weeks of gestation with a neonatal birthweight of 4000 ± 125 g (3875-4125 g) were compared with women who delivered (either induced or spontaneous labour) at 40, 41 or 42 weeks (i.e. expectant management), assuming an intrauterine fetal weight gain of 200 g per additional week of gestation. Similar comparisons were made at 40 and 41 weeks of gestation. Chi-square test and multivariable logistic regression analysis were used for statistical comparison. Method of delivery, 5-minute Apgar scores, neonatal injury. There were 132,112 women meeting the study criteria. In women whose labours were induced at 39 weeks and who delivered a neonate with a birthweight of 4000 ± 125 g, the frequency of caesarean was lower compared with women who delivered at a later gestational age (35.2% versus 40.9%; adjusted OR 1.25, 95% CI 1.17-1.33). This trend was maintained at both 40 weeks (36.1% versus 42.6%; adjusted OR 1.31, 95% CI 1.23-1.40) and 41 weeks (38.9% versus 41.8%; adjusted OR 1.16, 95% CI 1.06-1.28) of gestation. In the setting of known birthweight, it appears that induction of labour may reduce the risk of caesarean delivery. Future research should concentrate on clinical and radiological methods to better estimate birthweight to facilitate improved clinical care. These findings deserve examination in a large, prospective, randomised trial.


Clinical significance of serum human epididymis protein 4 in liver fibrosis: An experimental study.
Human epididymis protein 4 (HE4) has been identified as marker for renal fibrosis. Present study aimed to investigate the clinical significance of serum HE4 in liver fibrosis. Serum from 65 liver fibrosis patients, 68 hepatic patients without fibrosis, and 50 controls was collected respectively. Serum HE4 levels were measured by chemiluminescence immunoassay and compared among the groups. The relationships between serum HE4 levels and the clinical characteristics of liver fibrosis were also analyzed. A receiver operator characteristic curve was plotted to investigate the diagnostic efficacy of serum HE4 for liver fibrosis. Child-Pugh (C-P) score and liver fibrosis score were also evaluated. Data were analyzed by statistical software 13.0. Serum HE4 levels were significantly higher in liver fibrosis than that of controls [105.35 (82.64, 164.18) vs 46.2 (39.9, 58.9) pmol L, P = .00] and hepatic patients without liver fibrosis [105.35 (82.64, 164.18) vs 51.00 (44.02, 65.65) pmol L, P < .01]; Serum HE4 levels in liver fibrosis patients with C-P class C were significantly higher than those with C-P class A [143.75 (106.50, 186.08) vs 81.42 (69.73, 99.26) pmol L, P = .005] and C-P class B [143.75 (106.50, 186.08) vs 113.10 (88.92, 169.50) pmol L, P = .01]; the diagnostic sensitivity and specificity of serum HE4 levels for liver fibrosis detection were 87.5% and 81.1%, at a cutoff value of 69 pmol L; Serum HE4 levels in alcoholic liver fibrosis were higher than that of liver fibrosis with hepatitis B virus infection [131.30 (100.67, 228.35) vs 89.46 (73.74, 116.45) pmol L, P < .01]. Serum HE4 was closely correlated with C-P class and might be a potential marker for liver fibrosis.


Pharmacological activity of salvinorin A, the major component of Salvia divinorum.
The hallucinogenic plant Salvia divinorum (i.e., "magic mint") is a member of the Sage family that has been historically used for divination and shamanism by the Mazatecs. Today, S. divinorum has become increasingly popular as a recreational drug for its hallucinogenic effects. The non-nitrogenous diterpene, salvinorin A, the major active component of S. divinorum, is responsible for the hallucinogenic effect of this plant. Here, we described the behavioral effects of salvinorin A in animals including the addictive, antinociception and antidepressant properties of the drug. The present paper also demonstrates the not well recognized (or unclear) mechanisms of action of salvinorin A. The last part of the paper presents information about the legal status of S. divinorum and its derivatives. Taking into account the increasing popularity and consumption of salvinorin A and S. divinorum today, it is important to collect all data on the pharmacological profile of this plant and its products.


Endodontic surgery: an online study guide.
The Editorial Board of the Journal of Endodontics has developed a literature-based study guide of topical areas related to endodontics. This study guide is intended to give the reader a focused review of the essential endodontic literature and does not cite all possible articles related to each topic. Although citing all articles would be comprehensive, it would defeat the idea of a study guide. This section will cover indications and contraindications, surgical anatomy related to endodontics, flap design, root-end resection, the beveled root surface, root-end preparation techniques, root-end filling materials, endodontic surgical aids, endodontic surgical wound healing, incision and drainage, surgical trephination, intentional replantation, endodontic endosseous implants, submergence of roots, transplantation of teeth, and cystic decompression.


Physiologically Based Pharmacokinetic Model-Informed Drug Development for Polatuzumab Vedotin: Label for Drug-Drug Interactions Without Dedicated Clinical Trials.
Model-informed drug development (MIDD) has become an important approach to improving clinical trial efficiency, optimizing drug dosing, and proposing drug labeling in the absence of dedicated clinical trials. For the first time, we developed a physiologically based pharmacokinetic (PBPK) model-based approach to assess CYP3A-mediated drug-drug interaction (DDI) risk for polatuzumab vedotin (Polivy), an anti-CD79b-vc-monomethyl auristatin E (MMAE) antibody-drug conjugate (ADC). The model was developed and verified using data from the existing clinical DDI study for brentuximab vedotin, a similar vc-MMAE ADC. Analogous to the brentuximab vedotin clinical study, polatuzumab vedotin at the proposed labeled dose was predicted to have a limited drug interaction potential with strong CYP3A inhibitor and inducer. Polatuzumab vedotin was also predicted to neither inhibit nor induce CYP3A. The present work demonstrated a high-impact application using a PBPK MIDD approach to predict the CYP3A-mediated DDI to enable drug labeling in the absence of any dedicated clinical DDI study. The key considerations for the PBPK report included in the Biologics License Application/Marketing Authorization Application submission, as well as the strategy and responses to address some of the critical and challenging questions from the health authorities following the submission are also discussed. Our experience and associated perspective using a PBPK approach to ultimately enable a drug interaction label claim for polatuzumab vedotin in lieu of a dedicated clinical DDI study, as well as the interactions with the regulatory agencies, further provides confidence in applying MIDD to accelerate the registration and approval of new drug therapies.


Analysis of gene expression as relevant to cancer cells and circulating tumour cells.
Current literature provides significant evidence to support the concept that there are limited subpopulations of cells within a solid tumour that have increased tumour-initiating potential relative to the total tumour population. Such tumour-initiating cells have been identified in leukaemia and in a variety of solid tumours using different combinations of cell surface markers, suggesting that a tumour-initiating cell heterogeneity exists for each specific tumour. These studies have been extended to endometrial cancer; and herein we present several experimental approaches, both in vitro and in vivo, that can be used to determine whether such populations exist, and if so, to characterize them. These methods are adaptable to the investigation of tumour-initiating cells from other tumour types.


Improved signal-to-noise performance of MultiNet GRAPPA 1 H FID MRSI reconstruction with semi-synthetic calibration data.
To further develop MultiNet GRAPPA, a neural-network-based reconstruction, for lower SNR proton MRSI (1 H MRSI) data using adapted undersampling schemes and improved training sets. 1 H FID-MRSI data and an anatomical image for GRAPPA reconstruction were acquired in two slices in the human brain (n = 6) at 7T. MRSI data were retrospectively undersampled for a 4×, 6×, and 7× acceleration rate. Signal-to-noise, relative error (RE) between accelerated and fully sampled metabolic maps, RMS of the lipid artifacts, and fitting reliability were compared across acceleration rates, to the fully sampled data, and with different kinds and amounts of training images. Training with semi-synthetic images resulted in higher SNR and lower lipid RMS relative to training with acquired images from one or several subjects. SNR increased with the number of semi-synthetic training images and the 4× accelerated data retains ∼30% more SNR than other accelerated data. Spectra reconstructed with 20 semi-synthetic averages retained ∼100% more SNR and had ∼5% lower lipid RMS than those reconstructed with the center k-space points of one image as was originally proposed for very high SNR MRSI data and had higher fitting reliability. The metabolite RE was lowest when training with 20-semi-synthetic training images and highest when training with the center k-space points of one image. MultiNet GRAPPA is feasible with lower SNR 1 H MRSI data if 20-semi-synthetic training images are used at a 4× acceleration rate. This acceleration rate provided the best trade-off between scan time and spectral SNR.


Interaction between erythroblasts and macrophages in vitro: effect of neuraminidase-treatment of erythroblasts and the role of serum factors.
Some factors influencing the interaction in vitro between dimethylsulphoxide-induced Friend leukaemia erythroblasts (IFLE) and syngeneic mouse peritoneal macrophages (M phi) have been investigated. Desialation of erythroblasts by treatment with neuraminidase resulted in a significant increase in their association with and ingestion by M phi. In addition, the interaction with M phi of both neuraminidase-treated and untreated IFLE was found to be influenced by a heat-stable serum factor. gamma-globulin markedly enhanced the weak IFLE-M phi interaction which occurred at low serum concentration suggesting that the heat-stable factor may be an immunoglobulin. Desialation of the IFLE-rendered them agglutinable by peanut lectin which was used as a probe for neuraminidase-induced membrane changes. By contrast, cycloheximide treatment of IFLE which also enhances their interaction with M phi, did not result in the exposure of receptors for this lectin. It is proposed that both desialation and cycloheximide treatment of IFLE lead to secondary alterations in their membrane structure which renders them recognizable by M phi.


Paternal and maternal age as risk factors for psychosis: findings from Denmark, Sweden and Australia.
While the association between increased maternal age and congenital disorders has long been recognized, the offspring of older fathers are also at increased risk of congenital disorders related to DNA errors during spermatogenesis. Recent studies have drawn attention to an association between increased paternal age and increased risk of schizophrenia. The aim of the current study was to examine both paternal and maternal age as risk factors for the broader category of psychosis. We used data from three sources examining psychosis: a population-based cohort study (Denmark), and two case-control studies (Sweden and Australia). When controlling for the effect of maternal age, increased paternal age was significantly associated with increased risk of psychosis in the Danish and Swedish studies. The Australian study found no association between adjusted paternal age and risk of psychosis. When controlling for the effect of paternal age, younger maternal age was associated with an increased risk of psychoses in the Danish study alone. The offspring of older fathers are at increased risk of developing psychosis. The role of paternally derived mutations and/or psychosocial factors associated with older paternal age warrants further research.


Multidisciplinary Diagnosis and Management of a Rare Dysplastic Adenoma Involving a Pancreas Transplant.
A 52-year-old man with a history of type 1 diabetes mellitus with diabetic nephropathy who underwent simultaneous pancreas-kidney transplant over a decade ago presented with small bowel obstruction and was found by enteroscopy to have a carpeted lesion encompassing the small bowel anastomosis in the region of the donor pancreas. As endoscopic mucosal resection was impracticable because of technical limitations, the patient was referred to transplant surgical team for surgical exploration and ultimately required organ resection. This represents a unique presentation of an ampullary adenoma with high-grade dysplasia requiring device-assisted enteroscopy requiring multidisciplinary management.


Successful interruption of seasonal influenza transmission under the COVID-19 rapid response in Zhejiang Province, China.
The objective of this study was to evaluate whether the non-pharmaceutical interventions (NPIs) introduced to curb the spread of coronavirus disease 2019 (COVID-19) also interrupted the transmission of influenza. This is a descriptive epidemiological study. Data on changes in the number of reported influenza cases, number of influenza-like illness (ILI) visits, ILI percentage and influenza virus positivity were compared between the first 18 weeks of 2020 and the same period of 2019. The changes in the weekly average number of influenza cases were statistically significant between 2020 and 2019 (-4319 vs -525 per week; P < 0.05). The slopes of regression lines for the number of ILI visits were also statistically significant between 2020 and 2019 (-911 vs -98 per week; P < 0.05). This study found that the prevalence of influenza was substantially decreased when NPIs were implemented for the containment of COVID-19.


Tumour necrosis factor-alpha in nasal allergy.
Tumour necrosis factor-alpha (TNF-alpha) was measured by enzyme-linked immunosorbent assay and eosinophil cationic protein (ECP) by radio-immunoassay to evaluate TNF-alpha in nasal allergy. There was no significant difference either between the mean concentrations of TNF-alpha in nasal secretions from the patients with perennial nasal allergy and those of normal subjects, or between the TNF-alpha and ECP concentrations. However, reverse transcription polymerase chain reaction showed a specific increase of TNF-alpha mRNA and IFN-gamma mRNA in allergic nasal mucosa after allergen challenge in vitro. These findings suggest a possibility that T cell-derived IFN-gamma up-regulates macrophages to elaborate TNF-alpha, which may play a role in amplifying allergic inflammation in the nose through the cytokine network.


Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial.
S. lavandulaefolia Vahl. (Spanish sage) extracts and constituents have demonstrated anticholinesterase, antioxidant, anti-inflammatory, oestrogenic and CNS depressant (sedative) effects all of which are currently relevant to the treatment of Alzheimer's disease (AD). The essential oil inhibits the enzyme acetylcholinesterase (AChE) from human brain tissue and bovine erythrocyte and individual monoterpenoid constituents inhibit AChE with varying degrees of potency. In vivo AChE inhibition of select brain (striatal and hippocampal over cortical) AChE was obtained following oral administration of the essential oil to rats. In a study in healthy volunteers essential oil administration produced significant effects on cognition. In a pilot open-label study involving oral administration of the essential oil to patients with AD, a significant increase in diastolic and systolic blood pressure was observed in two patients, however this may have been due primarily to preexisting hypertension and there were no abnormalities in other vital signs or blood samples during the trial period. Although an open label trial is not free from practice effects or rater-caregiver expectations, statistically significant differences between baseline and 6 weeks treatment were a reduction in neuropsychiatric symptoms and an improvement in attention.


Priapism.
The evaluation of priapism is unfamiliar to many emergency physicians. Rapid assessment and treatment are essential in the hope of preserving sexual function. A thorough history and physical examination reveal an underlying vascular or neurologic etiology in most cases. Treatment generally consists of adequate oxygenation, hydration, and analgesia, with early urologic consultation.


Efficacy and clinical monitoring strategies for immune checkpoint inhibitors and targeted cytokine immunotherapy for locally advanced and metastatic colorectal cancer.
Colorectal cancer (CRC) is the fourth most common cancer type and is the second leading cause of cancer deaths annually in the United States. Conventional treatment options include postoperative (adjuvant) and preoperative (neoadjuvant) chemotherapy and radiotherapy. Although these treatment modalities have shown to decrease tumor burden, a major limitation to chemothearpy/radiotherapy is the high recurrence rate in patients. Immune-modulation strategies have emerged as a promising new therapeutic avenue to reduce this recurrence rate while minimizing undesirable systemic side effects. This review will focus specifically on the mechanisms of monoclonal antibodies: immune checkpoint inhibitors and cytokines, as well as current drugs approved by the Food and Drug Administration (FDA) and new clinical/pre-clinical trials. Finally, this review will investigate emerging methods used to monitor tumor response post-treatment.


Successful treatment of severe neonatal lobar emphysema by high-frequency oscillatory ventilation.
We successfully used high-frequency oscillatory ventilation (HFOV) for treating severe acquired lobar emphysema in two premature newborn infants (birth weights, 1,450 and 1,300 g). After successful weaning from mechanical ventilation for hyaline membrane disease, they needed additional ventilatory support because they developed severe lobar emphysema compressing the residual lung. In both patients, radiographic signs of lobar emphysema disappeared completely after 3 days of HFOV. Diagnosis and follow-up were confirmed by high-resolution computed tomography. We conclude that HFOV may be a useful noninvasive method for treating severe lobar emphysema.


[Extended resection and radiotherapy for primary intraosseous maxillary carcinoma].
Primary intraosseous maxillary carcinoma is a rare squamous cell carcinoma developing from remnants of the odontogenic epithelium. Risk factors are unknown and it may occur at any age. Little epidemiological data is available and few series include a sufficient number of patients. We assessed the prognosis of these tumors after wide exeresis (margin of 2 cm) followed by adjuvant radiotherapy. We reviewed the treatment and outcome data in nine cases of primary intraosseous maxillary carcinoma from 1995 to 2010. The WHO diagnostic criteria were used. We analyzed the demographic, clinical, and radiological data, as well as the type of treatment and the outcome of patients. The gender ratio was 3.5/1, and the mean age 40.2 years. The most frequent presentation was a unilocular osteolytic lesion with an irregular contour, between 24 and 60 mm, in the mandibular angle. Extended tumor resection was performed in all patients. Reconstruction was performed with a fibula flap in seven patients. Five patients underwent adjuvant radiotherapy. The survival rate at 2 years was 100%. The mean follow-up was 6.9 years (2-14 years) at the end of the study. Two patients were treated for a relapse and one died after 3 years of follow-up. The combined treatment was efficient on primary intraosseous maxillary carcinoma. The diagnosis is made with strict clinical, radiological, and histological criteria. The intraosseous location of these tumors requires an early diagnosis and aggressive treatment combining broad exeresis followed by adjuvant radiotherapy to avoid recurrence and have an optimal survival rate.


Handicap as a Measure of Perceived-Health Status in Parkinson's Disease.
Handicap is a patient-centered measure of health status that encompasses the impact of social and physical environment on daily living, having been assessed in advanced and late-stage Parkinson's Disease (PD). To characterize the handicap of a broader sample of patients. A cross-sectional study of 405 PD patients during the MDS-UPDRS Portuguese validation study, using the MDS-UPDRS, Unified Dyskinesias Rating Scale, Nonmotor symptoms questionnaire, PDQ-8 and EQ-5D-3L. Handicap was measured using the London Handicap Scale (LHS). Mean age was 64.42 (±10.3) years, mean disease duration 11.30 (±6.5) years and median HY 2 (IQR, 2-3). Mean LHS was 0.652 (±0.204); "Mobility," "Occupation" and "Physical Independence" were the most affected domains. LHS was significantly worse in patients with longer disease duration, older age and increased disability. In contrast, PDQ-8 did not differentiate age groups. Handicap was significantly correlated with disease duration (r = -0.35), nonmotor experiences of daily living (EDL) (MDS-UPDRS-I) (r = -0.51), motor EDL (MDS-UPDRS-II) (r = -0.69), motor disability (MDS-UPDRS-III) (r = -0.49), axial signs of MDS-UPDRS-III (r = -0.55), HY (r = -0.44), presence of nonmotor symptoms (r = -0.51) and PDQ-8 index (r = -0.64) (all P < 0.05). Motor EDL, MDS-UPDRS-III and PDQ-8 independently predicted Handicap (adjusted R 2 = 0.582; P = 0.007). The LHS was easily completed by patients and caregivers. Patients were mild-moderately handicapped, which was strongly determined by motor disability and its impact on EDL, and poor QoL. Despite correlated, handicap and QoL seem to differ in what they measure, and handicap may have an added value to QoL. Handicap seems to be a good measure of perceived-health status in a broad sample of PD.


Hypoxia induces the dysfunction of human endothelial colony-forming cells via HIF-1α signaling.
Endothelial injury is considered as a trigger of pulmonary vascular lesions in the pathogenesis of hypoxic pulmonary hypertension (HPH). Although endothelial colony-forming cells (ECFCs) have vascular regeneration potential to maintain endothelial integrity, hypoxia-induced precise alteration in ECFCs function remains controversial. This study investigated the impact of hypoxia on human ECFCs function in vitro and the underlying mechanism. We found that hypoxia inhibited ECFCs proliferation, migration and angiogenesis. Compared with no treatment, the expression of hypoxia inducible factor-1α (HIF-1α) in hypoxia-treated ECFCs was increased, with an up-regulation of p27 and a down-regulation of cyclin D1. The over-secreted vascular endothelial growth factor (VEGF) was detected, with the imbalanced expression of fetal liver kinase 1 (flk-1) and fms related tyrosine kinase 1 (flt-1). Hypoxia-induced changes in ECFCs could be reversed by HIF-1α inhibitor KC7F2. These data suggest that HIF-1α holds the key in regulating ECFCs function which may open a new perspective of ECFCs in HPH management.


Aluminium alloyed iron-silicide/silicon solar cells: A simple approach for low cost environmental-friendly photovoltaic technology.
This work demonstrates the fabrication of silicide/silicon based solar cell towards the development of low cost and environmental friendly photovoltaic technology. A heterostructure solar cells using metallic alpha phase (α-phase) aluminum alloyed iron silicide (FeSi(Al)) on n-type silicon is fabricated with an efficiency of 0.8%. The fabricated device has an open circuit voltage and fill-factor of 240 mV and 60%, respectively. Performance of the device was improved by about 7 fold to 5.1% through the interface engineering. The α-phase FeSi(Al)/silicon solar cell devices have promising photovoltaic characteristic with an open circuit voltage, short-circuit current and a fill factor (FF) of 425 mV, 18.5 mA/cm(2), and 64%, respectively. The significant improvement of α-phase FeSi(Al)/n-Si solar cells is due to the formation p(+-)n homojunction through the formation of re-grown crystalline silicon layer (~5-10 nm) at the silicide/silicon interface. Thickness of the regrown silicon layer is crucial for the silicide/silicon based photovoltaic devices. Performance of the α-FeSi(Al)/n-Si solar cells significantly depends on the thickness of α-FeSi(Al) layer and process temperature during the device fabrication. This study will open up new opportunities for the Si based photovoltaic technology using a simple, sustainable, and los cost method.


Calm group. Prevalence of craniomandibular dysfunction in white children with different emotional states.
Malocclusion, oral parafunctions, dentofacial injuries, orthodontic treatment, and emotional states are factors that have been implicated in the etiology of craniomandibular dysfunction. In a sample of 386 white children, the number of children rated by their parents as calm was 250 (108 boys, 142 girls). Malocclusion and oral parafunctions are considered to be the causative factors in this group.


Muscarinic receptor heterogeneity in guinea pig intestinal smooth muscle: binding studies with AF-DX 116.
Muscarinic receptor subtypes in longitudinal and circular smooth muscles of the guinea pig ileum were characterized with the use of the cardioselective antagonist AF-DX 116 in binding competition experiments against 0.3 nM [3H] N-methylscopolamine [( 3H]NMS). This compound recognized a heterogeneous receptor population in both smooth muscles, revealing the existence of different percentages of the cardiac (KD = 92-110 nM) and the glandular (KD = 1150-2541 nM) muscarinic receptor subtypes. These results, together with the low potency displayed by AF-DX 116 to inhibit the agonist-stimulated smooth muscle contraction and salivary secretion allow the suggestion that the glandular muscarinic receptor subtype, showing a low affinity for AF-DX 116, is involved in smooth muscle contraction.


Novel measures of response performance and inhibition in children with ADHD.
Fifteen children with ADHD aged 8 to 12 years and age and gender matched controls performed two different stopping tasks to examine response performance and inhibition and their respective moment-to-moment variability. One task was the well-established stop-signal task, while the other was a novel tracking task where the children tracked a spaceship on the screen until an alarm indicated they should stop. Although performance was discrete in the stop signal task and continuous in the tracking task, in both tasks latencies to the stop signal were significantly slowed in children with ADHD. Go performance and variability did not significantly differ between ADHD and control children in either task. Importantly, stopping latency in the novel spaceship tracking task also was more variable in children with ADHD. As stopping variability cannot be measured using the standard stop signal task, the new task offers compelling support for the heretofore untested prediction that stopping is both slowed and more variable in children with ADHD. The results support a response inhibition impairment in ADHD, whilst limiting the extent of an intra-trial variability deficit.


Internalisation of the mu-opioid receptor by endomorphin-1 and leu-enkephalin is dependant on aromatic amino acid residues.
The opioid receptor system in the central nervous system controls a number of physiological processes, most notably pain. However, most opioids currently available have a variety of side-effects as well as exhibiting tolerance. Tolerance is most likely to be a complex phenomenon, however, the role of receptor internalisation is thought to play a crucial role. In this study, we examined the role of aromaticity in ligand-mediated receptor internalisation of the mu-opioid receptor (MOPR). These studies show that the amount of receptor internalisation may be dependant on the amphiphilicity of the ligand. Specifically, deletion of the C-terminus aromatic residues of endomorphin 1, particularly tryptophan reduces receptor-mediated internalisation whilst the addition of tryptophan within the enkephalin sequence increases receptor internalisation and decreases tolerance.


Immunomodulatory activity seen as a result of photobiomodulation therapy in stimulated primary human fibroblasts.
Oral biofilms burden host responses by induction of inflammatory mediators, exacerbating periodontal inflammation. Photobiomodulation Therapy (PBMT) has been shown to decrease levels of pro-inflammatory cytokines and chemokines. However, optimal wavelengths and exposure doses have not been established. This study investigated the effects of PBMT on human periodontal ligament fibroblasts (hPDLFs) stimulated with inflammatory mediators (LPS, TNF-α, and IL-1β). Cytotoxic effects of laser wavelengths 660 nm and 810 nm were assessed by measuring their effects on cellular dehydrogenase activity. The study was expanded to include 980 nm, 660 nm + 810 nm, and 810 nm + 980 nm. P.g. LPS, TNF-α, and/or IL-1β were added one hour before irradiation, then exposed to laser irradiation to determine the most appropriate stimulus. The levels of INF-γ, IL-6, IL-8, IL-17A/F, and MCP-1 production in stimulated hPDLFs were measured and analyzed. P.g. LPS was a poor stimulus for hPDLFs, while TNF-α and IL-1β significantly elevated the analytes. The 660 nm laser treatment induced pro-inflammatory cytokines when stimulated, while 810 nm exhibited significant suppression. IL-1β was the stimulus of choice and the 810 nm wavelength alone exhibited anti-inflammatory effects for all analytes except IL-8, while the 810 nm in combination with 660 nm and/or 980 nm exhibited effects similar to 810 nm alone. The downregulation of inflammatory mediators by the combination or individual treatment with 810 nm wavelength shows promise for the management of periodontal inflammation. PBMT may lead to the development of a novel approach in the management of periodontal disease.


Design, synthesis and the structure-activity relationship of agonists targeting on the ALDH2 catalytic tunnel.
ALDH2, a key enzyme in the alcohol metabolism process, detoxifies several kinds of toxic small molecular aldehydes, which induce severe organ damages. The development of novel Alda-1 type ALDH2 activators was mostly relied on HTS but not rational design so far. To clarify the structure-activity relationship (SAR) of the skeleton of Alda-1 analogs by synthesis of the least number of analogs, we prepared 31 Alda-1 analogs and 3 isoflavone derivatives and evaluated for their ALDH2-activating activity. Among these, the ALDH2-activating activity of mono-halogen-substituted (Cl and Br) N-piperonylbenzamides 3b and 3 k, and non-aromatic amides 8a-8c, were 1.5-2.1 folds higher than that of Alda-1 at 20 μM. The relationship between binding affinity in computer aided molecular docking model and the ALDH2-activating activity assays were clarified as follows: for Alda-1 analogs, with the formation of halogen bonds, the enzyme-activating activity was found to follow a specific regression curve within the range between -5 kcal/mol and -4 kcal/mol. For isoflavone derivatives, the basic moiety on the B ring enhance the activating activity. These results provide a new direction of utilizing computer-aided modeling to design novel ALDH2 agonists in the future.


Ag-NOR staining in mouse sarcoma ascites cells.
In sarcoma cells, the nucleoli are small, ill-defined, and are present in large numbers making it difficult to stain them by classical staining procedures. A modified Ag-NOR technique has been applied to detect the nucleolus and the nucleolar-organizing region in the chromosome of a mouse sarcoma-180 ascites cell-line. The cells were found to have 8-14 nucleolar chromosomes. The nucleoli are present in varying numbers corresponding to the number of nucleolar chromosomes. Silver grains appear as dots at one end of the chromosome. This end is presumed to be the centromeric end as, in normal mice, the NORs are in association with the centromere. However, the centromeres are ATrich, whereas the NORs should be GCrich. This NORs in mouse chromosomes should be placed below the centromere as already shown by the nucleic acid hybridization technique.


Occurrence, source, and risk assessment of neonicotinoid insecticides in the Huai River, China.
Neonicotinoids (NEOs) are the most widely used insecticides in the world. Nevertheless, the occurrence and distribution of NEOs in agricultural areas are not well understood. This study investigated the concentration, sources, ecological risks, and health risks of eight NEOs in the water of the Huai River, which flows through a typical agricultural area in China. The total concentration of NEOs in the river water ranged from 1.02 to 191.2 ng L-1, with an average of 64.1 ng L-1. Thiamethoxam was the dominant compound, with an average relative contribution of 42.5%. The average concentration of the total NEOs in downstream was significantly higher than that in upstream (p < 0.05). This may be related to the intensity of agricultural activities. The riverine NEO fluxes increased by approximately 12 times from the upper site to the lower site. More than 1.3 tons of NEOs in 2022 were transferred into Lake Hongze, the largest regulative lake on the Eastern Route of the South-to-North Water Diversion Project. Nonpoint sources were the major contributor to the total NEO inputs, and water use was the main output pathway. The risk assessment indicated that the individual NEOs in the river water presented low ecological risks. The NEO mixtures would produce chronic risks to aquatic invertebrates in 50% of the sampling sites, which were mostly distributed in downstream. Thus, more attention should be given to the downstream. Based on the Monte Carlo simulation, the health risks of NEOs via water consumption were estimated. The maximum chronic daily intakes were 8.4 × 10-4, 2.25 × 10-4, 1.27 × 10-4, 1.88 × 10-4 mg kg-1 day-1 for boys, girls, men, and women, respectively, which were approximately 2 orders of magnitude lower than the acceptable daily intake. Therefore, river water consumption would not be a concern for the public health.


Postoperative increase in soluble interleukin-2 receptor serum levels as predictor for early recurrence in non-small cell lung carcinoma.
It is known that interleukin-2 (IL-2) plays an important role in the activation of host antitumor immune response. In addition to IL-2 cell surface receptor, a soluble form of IL-2 receptor (SIL-2R) may be released in the blood and potentially be involved in the regulation of IL-2 availability. High SIL-2R levels have been found in patients with lung cancer. The current study evaluated the influence of changes in SIL-2R serum levels during the perioperative period on early relapse rate in patients with operable non-small cell lung cancer. The study included 60 patients (epidermoid carcinoma, 33; adenocarcinoma, 27). Serum levels of SIL-2R were measured with an enzyme immunoassay before surgery and 7 and 30 days after surgery. A surgery-induced increase in SIL-2R levels was seen 7 days after surgery in 38 of 60 patients. On the 30th day after surgery, SIL-2R values were lower than the preoperative values in 32 patients (Group A) or still greater in the other 28 patients (Group B). After a median follow-up of 10 months, relapse occurred in 19 of 60 patients. The relapse rate was significantly higher in Group B than in Group A patients (16 of 28 versus 3 of 32, respectively; P less than 0.001). This difference also was significant in relation to histotype and node status. This study shows that the persistence of increased SIL-2R levels in the postoperative period is associated with a higher early relapse rate in patients with operable non-small cell lung cancer. The impact of SIL-2R levels on relapse suggests that host immune defenses may influence the clinical course of patients with lung cancer. Therefore, the evaluation of SIL-2R in the perioperative period may represent a new prognostic biologic factor in operable non-small cell lung cancer.


Calcium/diacylglycerol-dependent protein kinase and its major 87-kilodalton protein substrate are differentially distributed in rat basal ganglia.
When brain tissue is subjected to subcellular fractionation, both calcium/diacylglycerol-dependent protein kinase (protein kinase C) and an 87-kilodalton (kDa) protein substrate for this enzyme are enriched in the crude nerve terminal fraction. The present study, using chemical and surgical lesions of neurons in the rat neostriatum and substantia nigra, has examined whether the 87-kDa protein is colocalized with protein kinase C in identified neurons and nerve terminals. Our results show that, in the basal ganglia, protein kinase C is highly enriched in local striatal neurons and the striatonigral fibers and terminals. In contrast, the 87-kDa protein appears to be widely and evenly distributed in both neuronal and nonneuronal cells. The 87-kDa protein may therefore mediate functions of protein kinase C not restricted to nerve terminals.


The presence of human papillomavirus in sinonasal papillomas, demonstrated by polymerase chain reaction with consensus primers.
The frequency of human papillomavirus (HPV) in sinonasal papillomas seems to vary considerably. The highest frequencies have been reported by investigators using in situ DNA or RNA hybridization. Few studies have used polymerase chain reaction, and in these reports the frequency of HPV detection is rather low. We have investigated the presence of HPV in sinonasal papillomas using the polymerase chain reaction with a set of degenerated consensus primers, which amplify the vast majority of the known HPV types. Human papillomavirus was found in three of 14 papillomas. By in situ hybridization the same three papillomas were positive for HPV type 6/11.


Effectiveness of a Self-Management Program to Improve Cognition and Quality of Life in Epilepsy: A Pragmatic, Randomized, Multicenter Trial.
We conducted a multisite, pragmatic replication trial at 4 New England epilepsy centers to determine the effectiveness of Home-Based Self-Management and Cognitive Training Changes Lives (HOBSCOTCH) in a real-world setting and to assess feasibility of a virtual intervention. HOBSCOTCH is an 8-session intervention addressing cognitive impairment and quality of life (QoL) for people with epilepsy (PWE). Participants were recruited from epilepsy centers in 4 states and block-randomized into the following groups: in-person HOBSCOTCH (H-IP), virtual HOBSCOTCH (H-V), and waitlist control. Outcome measures were assessed for all groups at baseline, 3 months, and 6 months; intervention groups received long-term follow-up at 9 and 12 months. A total of 108 participants were recruited, of whom 85 were included in this analysis (age at baseline 47.5 ± 11.5 years; 68% female). Participants completing the in-person intervention (H-IP) had a 12.4-point improvement in QoL score compared with controls (p < 0.001). Pairwise comparisons found a 6.2-point treatment effect for subjective cognition in the H-IP group (p < 0.001). There were no meaningful group differences in objective cognition or health care utilization at any time points and the treatment effect for QoL diminished by 6 months. The virtual intervention demonstrated feasibility but did not significantly improve outcomes compared with controls. Within-group analysis found improvements in QoL for both H-V and H-IP. This study replicated the effectiveness of the HOBSCOTCH program in improving QoL for PWE. The study was conducted prior to the COVID-19 pandemic, but the distance-delivered intervention may be particularly well-suited for the current environment. Future research will explore modifications designed to improve the efficacy of H-V and the sustainability of HOBSCOTCH's treatment effect. ClinicalTrials.gov (NCT02394509). This study provides Class III evidence that in-person HOBSCOTCH delivery improved subjective measures of cognition in persons with epilepsy.


The power of language-concordant care: a call to action for medical schools.
We live in a world of incredible linguistic diversity; nearly 7000 languages are spoken globally and at least 350 are spoken in the United States. Language-concordant care enhances trust between patients and physicians, optimizes health outcomes, and advances health equity for diverse populations. However, historical and contemporary trauma have impaired trust between communities of color, including immigrants with limited English proficiency, and physicians in the U.S. Threats to informed consent among patients with limited English proficiency persist today. Language concordance has been shown to improve care and serves as a window to broader social determinants of health that disproportionately yield worse health outcomes among patients with limited English proficiency. Language concordance is also relevant for medical students engaged in health care around the world. Global health experiences among medical and dental students have quadrupled in the last 30 years. Yet, language proficiency and skills to address cultural aspects of clinical care, research and education are lacking in pre-departure trainings. We call on medical schools to increase opportunities for medical language courses and integrate them into the curriculum with evidence-based teaching strategies, content about health equity, and standardized language assessments. The languages offered should reflect the needs of the patient population both where the medical school is located and where the school is engaged globally. Key content areas should include how to conduct a history and physical exam; relevant health inequities that commonly affect patients who speak different languages; cultural sensitivity and humility, particularly around beliefs and practices that affect health and wellbeing; and how to work in language-discordant encounters with interpreters and other modalities. Rigorous language assessment is necessary to ensure equity in communication before allowing students or physicians to use their language skills in clinical encounters. Lastly, global health activities in medical schools should assess for language needs and competency prior to departure. By professionalizing language competency in medical schools, we can improve patients' trust in individual physicians and the profession as a whole; improve patient safety and health outcomes; and advance health equity for those we care for and collaborate with in the U.S. and around the world.


Variations of the superior sagittal sinus and bridging veins in human dissections and computed tomography venography.
The aim of the present study was to examine the superior sagittal sinus (SSS) and bridging veins (BVs) from an anatomical, neurosurgical and radiological perspective. Computed tomography venographies (CTVs) of 30 patients and 9 cadaveric dissections of human SSS were analyzed. CTV and cadavers showed most BVs emptying into the SSS close by (±3 cm) and distal to the coronary suture (74% in CTV, 62% in cadavers). Important anatomical information can be drawn from cerebral CTV for neurosurgical preoperative planning.


Controlled-release granules for the delivery of pymetrozine to roots of transplanted rice seedlings with decreased phytotoxicity and enhanced control efficacy against paddy planthoppers.
Seedling transplanting is widely used in rice cultivation. Systemic insecticides can be delivered to seedling roots by application through rice seedling boxes before transplanting. The most challenging aspect is to provide long-term control of rice pests and overcome transplanting shock. Precise control of the release rate of insecticide can meet these requirements. Pymetrozine is a promising insecticide used for the control of rice planthoppers resistant to neonicotinoid insecticides. In this study, four controlled-release granular formulations of pymetrozine were prepared based on a mixture of cost-effective and biodegradable kaolin and xanthan gum or a mixture of calcined kaolin and xanthan gum. Fluorescence images showed that different 3D networks were formed in the four granular formulations. The four granular formulations showed different water uptake rates and release rates of pymetrozine in water. Pymetrozine release rate was positively correlated with the water uptake capacity, rather than the water uptake rate of granules. Diffusion was the dominant mechanism for the release of pymetrozine from granules. Pymetrozine was found to reduce the survival of transplanted rice seedlings suffering from transplanting shock. Incorporating pymetrozine in controlled-release granules alleviated this phytotoxicity. The survival rate of rice seedlings in granular pymetrozine treatments ranged 68.8-85.0%, whereas the survival rate was <50% for powdered pymetrozine treatments. Additionally, four prepared granule formulations had a significant control effect on rice planthopper with efficacies ranging from 76.7% to 98.0% 40 days after seedling box treatment. The granule with an intermediate release rate of pymetrozine was shown to be more suitable for seedling box treatment than field application and traditional liquid spraying for the long-term control of paddy planthoppers. © 2021 Society of Chemical Industry.


Longer operative time is associated with higher risk of severe complications after percutaneous nephrolithotomy: analysis of 1511 cases from a Japanese nationwide database.
To evaluate risk factors of severe adverse events after percutaneous nephrolithotomy with an emphasis on operation time, and to develop a nomogram for predicting them. This was an observational retrospective study including 1511 patients who underwent percutaneous nephrolithotomy in 332 hospitals identified from the Japanese Diagnosis Procedure Combination database between 2007 and 2010. Severe adverse events were defined as follows: (i) in-hospital mortality; (ii) postoperative medications including catecholamine, gamma-globulin products, protease inhibitors and medications for disseminated intravascular coagulation; and (iii) postoperative interventions including central vein catheterization, dialysis and mechanical cardiopulmonary support. Univariate and multivariate logistic regression analyses were carried out for the occurrence of severe adverse events, and a nomogram was generated from this model. Overall, 126 severe adverse events (8.34%) were identified. In the multivariate model, a linear trend between severe adverse events and operation time was observed (OR 4.72 for 120-179 min to 17.95 for ≥300 min compared with ≤119 min; each P < 0.05) after adjustment for sex, age, Charlson Comorbidity Index and type of admission. Female sex and emergency admission were also significant risk factors (OR 1.92 and 2.04, respectively), and hospital volume did not reach statistical significance. The nomogram based on these results was well fitted to predict a probability between 0.05 and 0.40 (concordance index 0.696). Longer operation time is a significant and independent risk factor for severe adverse events after percutaneous nephrolithotomy. Our nomogram can be an effective tool for predicting postoperative complications.


Interstitial Keratitis with Corneal Perforation as the Presenting Sign of Systemic Tuberculosis.
Background: Ocular surface and corneal involvement in tuberculosis is seldom seen. We report a patient of pulmonary and presumed ocular tuberculosis with immune keratitis along with corneal perforation as the presenting signs.Methods: A middle-aged male presented with stromal keratitis, deep corneal vascularization, and two corneal perforations. Necrotic Mantoux test and cavitary lesion on computerized tomography of the chest clinched the diagnosis of tuberculosis-related interstitial keratitis.Results: Tubercular interstitial keratitis was successfully managed with antitubercular therapy, oral and topical steroids while cyanoacrylate glue was used to seal the corneal perforations.Conclusions: Although corneal involvement is uncommon in ocular tuberculosis, in patients with interstitial keratitis who respond poorly to conventional therapy, a possibility of systemic tuberculosis should be considered in endemic countries.


Automated electrorotation to reveal dielectric variations related to HER-2/neu overexpression in MCF-7 sublines.
Electrorotation (ROT) is a technique that allows for determination of the dielectric properties of living cells when exposed to a rotating electric field. We evaluated the ROT behavior of MCF/neo and p185(neu) transfectancts MCF/HER2-11 and MCF/HER2-18 to investigate whether differences in HER-2/neu expression were associated with differences in dielectric properties in these cells. P185(neu) was measured by Western blotting in MCF/neo cells and HER-2/neu transfectants MCF/HER2-11 and MCF/HER2-18. ROT spectra and cell membrane-specific capacitance were obtained for each cell line. The mean cell membrane-specific capacitance values for MCF/neo, MCF/HER2-11, and MCF/HER2-18 were 2.09, 1.70, and 2.56 microF/cm(2), respectively. The mean specific capacitance for MCF/neo was significantly different from that for MCF/HER2-11 (P = 0.006) and that for MCF/HER2-18 (P = 0.007). ROT is sufficiently sensitive to detect variations in dielectric properties in breast cancer cell lines overexpressing p185(neu). These differences may be related to the morphological alterations determined by HER-2/neu overexpression.


Humans choose representatives who enforce cooperation in social dilemmas through extortion.
Social dilemmas force players to balance between personal and collective gain. In many dilemmas, such as elected governments negotiating climate-change mitigation measures, the decisions are made not by individual players but by their representatives. However, the behaviour of representatives in social dilemmas has not been investigated experimentally. Here inspired by the negotiations for greenhouse-gas emissions reductions, we experimentally study a collective-risk social dilemma that involves representatives deciding on behalf of their fellow group members. Representatives can be re-elected or voted out after each consecutive collective-risk game. Selfish players are preferentially elected and are hence found most frequently in the 'representatives' treatment. Across all treatments, we identify the selfish players as extortioners. As predicted by our mathematical model, their steadfast strategies enforce cooperation from fair players who finally compensate almost completely the deficit caused by the extortionate co-players. Everybody gains, but the extortionate representatives and their groups gain the most.


[Children in the COVID-19 pandemic and the public health service (ÖGD) : Data and reflections from Frankfurt am Main, Germany].
The measures taken to combat the COVID-19 pandemic have severely restricted the opportunities for the development of children. This paper will discuss the reporting data of children and the public health department's activities against the background of the restrictions of school and leisure time offers as well as sports and club activities. Reporting data from Frankfurt am Main, Hesse, were obtained using a SURVStat query for the calendar weeks 10/2020-28/2021 and from SURVNet (until 30 June 2021). Contact persons (CP) of SARS-CoV‑2 positive persons from schools and daycare centers were screened for SARS-CoV‑2 by PCR test. These results and those of rapid antigen testing, which has been mandatory for schoolchildren since April 2021, are presented. Until Easter break, the age-related seven-day incidence values per 100,000 for children 14 years of age and younger were lower than the overall incidence; it was only higher after rapid antigen-testing was mandatory for schoolchildren. Most children with SARS-CoV‑2 had no or mild symptoms; hospitalization was rarely required and no deaths occurred. Contact tracing in schools and daycare centers found no positive contacts in most cases and rarely more than two. Larger outbreaks did not occur. SARS-CoV‑2 infections in children appear to be less frequent and much less severe than in adults. Hygiene rules and contact management have proven themselves effective during times with high incidences in the local population without mandatory rapid antigen testing - and even with a high proportion of variants of concern (alpha and delta variants) in Germany. Against this background, further restriction of school and daycare operations appears neither necessary nor appropriate.


Treatment of human aggression with major tranquilizers, antidepressants, and newer psychotropic drugs.
Most of the drugs used in the treatment of aggressive syndromes have originally been developed for other clinical applications. Despite significant differences in the pathogenesis of various aggressive disorders, the frequently used "antiaggression" drugs are the major tranquilizers (neuroleptics). If the aggresstion is associated with psychosis, chlorpromazine or haloperidol are the drugs of choice. Aggressive disorders within the acute and chronic brain syndromes are best treated with pericyazine, thioridazine, and thiothixene. In aggressive symptoms of mentally retarded patients, particularly with epileptic syndromes, a new benzazepine (SCH12,679)was found to be very effective. Aggression associated with alcoholism or narcotic addiction showed best response to chlorpormazine and haloperidol. As a general rule, in aggressive patients with clinically known epilepsy, or with abnormal electroencephalographic findings, the major tranquilizers with potent sedative properties should be given with great caution.


Ribosomal RNA turnover and the level of ribonuclease activity in the liver of the pregnant rat.
Studies were undertaken on the turnover of ribosomal RNA and on ribonuclease activity in the liver of the pregnant rat in an attempt to explain the accumulation of liver RNA which occurs during the latter half of pregnancy. Between the 15th and 20th day of gestation the rate constant of degradation, biological half-life and daily rate of synthesis of ribosomal RNA were calculated to be 0.0887, 7.81 days and 6.21 mg per liver per 100g body weight respectively. Corresponding values in non-pregnant rats were 0.123, 5.68 days and 3.47 mg per liver per 100g body weight. The increase in RNA was therefore associated with an increase in its rate of synthesis and a decrease in its rate of breakdown. From the 14th day of pregnancy there was a decrease in alkaline ribonuclease activity and a marked increase in the level of alkaline ribonuclease inhibitor. The activity of acid ribonuclease was found to increase and that of acid phosphatase to decrease during this period.


Differing haemodynamic and catecholamine responses to exercise in three groups with peripheralautonomic dysfunction: insulin-dependent diabetes mellitus, familial amyloid polyneuropathy and pure autonomic failure.
The haemodynamic and catecholamine responses to supine exercise, and the effect on standing blood pressure (BP), were studied in three groups with peripheral autonomic dysfunction; insulin-dependent diabetes mellitus (IDDM), familial amyloid polyneuropathy (FAP) and pure autonomic failure (PAF). Healthy normal subjects were studied as controls. With exercise, BP increased in controls, was unchanged in IDDM and FAP, and fell in PAF. Heart rate (HR) increased more in controls than IDDM, FAP or PAF. Cardiac index (CI) increased less in IDDM than controls, FAP or PAF. Systemic vascular resistance (SVR) fell similarly in controls and IDDM, with a greater fall in FAP and PAF. Plasma noradrenaline increased in controls and IDDM only; plasma adrenaline did not change and plasma dopamine was undetectable in all groups. On standing, BP was unchanged in controls; BP fell pre- and post-exercise in IDDM, FAP and PAF, with a significantly greater fall post-exercise in FAP and PAF. In conclusion, the haemodynamic responses to supine exercise and to standing after exercise differed in the three groups with peripheral autonomic dysfunction. These differences, and also the similarities, between different forms of peripheral autonomic dysfunction, may be of relevance to the clinical assessment and therapy of these patients.


Visceral obesity and hyperinsulinemia modulate the impact of the microsomal triglyceride transfer protein -493G/T polymorphism on plasma lipoprotein levels in men.
The dyslipidemic state of visceral obesity is characterized by increased plasma triglyceride levels, low high-density lipoprotein-cholesterol concentration and alterations in low-density lipoprotein (LDL) composition and concentration. A functional, non-coding microsomal triglyceride transfer protein (MTP) -493G/T polymorphism of the microsomal triglyceride transfer protein gene has been related to variations in LDL-cholesterol levels. To study the effect of the MTP -493G/T polymorphism on lipoprotein levels in visceral obesity and hyperinsulinemia, a total of 227 men were assigned into two groups on the basis of their MTP -493G/T polymorphism, including 121 GG homozygotes and 105 carriers of the T allele (92 GT and 13 TT). The two genotypic groups did not differ for their physiological characteristics nor for lipoprotein--lipid profiles, before and after adjustment for age. However, GG homozygotes were characterized by higher fasting insulin levels than carriers of the T allele (P<0.05). When the two genotypic groups were further divided on the basis of their visceral adipose tissue (AT) accumulation, assessed by computed tomography, we observed that T allele carriers with low levels of visceral AT (<130 cm(2)) had decreased plasma total cholesterol and LDL-apolipoprotein B (LDL-apoB) levels compared to viscerally obese men (P=0.035 and P=0.0001, respectively). Among GG homozygotes, no significant difference were observed. Although not significant, T allele carriers characterized by visceral obesity tended to have smaller, denser LDL particles than T allele carriers characterized by a low accumulation of visceral AT. When subjects were divided on the basis of their fasting insulin levels, it appears that hyperinsulinemic men were characterized by a deteriorated lipoprotein--lipid profile when they were carriers of the T allele compared to normoinsulinemic men. In summary, visceral obesity and hyperinsulinemia modulate the impact of the MTP -493G/T polymorphism on plasma total cholesterol and LDL-apoB levels, as well as on LDL peak particle diameter.


NC10 bacteria promoted methane oxidation coupled to chlorate reduction.
The strictly anaerobic serum bottles were applied to investigate methane oxidation coupled to chlorate (ClO3-) reduction (MO-CR) without exogenous oxygen. 0.35 mM ClO3- was consumed within 20 days at the reduction rate of 17.50 μM/d, over three times than that of ClO4-. Chlorite (ClO2-) was not detected throughout the experiment and the mass recovery of Cl- was over 89%. Isotope tracing results showed most of 13CH4 was oxided to CO2, and the electrons recovery reached to 77.6%. Small amounts of 13CH4 was consumed for DOC production probably through aerobic methane oxidation process, with oxygen generated from disproportionation reaction. In pMMO (key enzyme in aerobic oxidation of methane) inhibition tests, ClO3- reduction rate was slowed to 7. 0 μmol/d by 2 mM C2H2, real-time quantitative PCR also showed the transcript abundance of pMMO and Cld were significantly dropped at the later period of experiment, indicating that the O2 disproportionated from ClO2- was utilized to active CH4. NC10 bacteria Candidatus Methylomirabilis, related closely to oxygenic denitrifiers M. oxyfera, was detected in the system, and got enriched along with chlorate reduction. Several pieces of evidence supported that NC10 bacteria promoted CH4 oxidation coupled to ClO3- reduction, these oxygenic denitrifiers may perform ClO2- disproportionation to produce O2, and then oxidized methane intracellularly.


Identification of a predictive factor for distant metastasis in esophageal squamous cell carcinoma after definitive chemoradiotherapy.
Distant metastasis (DM) after definitive chemoradiotherapy has not been a focus of research in esophageal carcinoma. At present, local-regional control is improving following advances in salvage treatments after definitive chemoradiotherapy. There is a need to focus on suppressing the development of DM. The aim of this study was to identify pre-treatment factors associated with DM after definitive chemoradiotherapy. This study included 144 patients with thoracic esophageal squamous cell carcinoma (Stage I/II/III/IV; 35/17/69/23) (TNM 7th) who underwent definitive chemoradiotherapy; >50 Gy was prescribed to all gross tumors with concurrent administration of 5-fluorouracil ± platinum. Pre-treatment factors included age, gender, performance status, tumor location, T/N/M status, tumor length, size of metastatic lymph nodes (LN size), and the presence of intramural metastasis or multiple primary tumors. The effects of pre-treatment factors on overall survival (OS) and DM were evaluated. The median follow-up period was 48 months. DM occurred as an initial progression in 21 % of patients, and LN size correlated with DM development (hazard ratio [HR] = 5.12; p = 0.0013) and poor OS (HR = 2.20; p = 0.0076) in univariate and multivariate analyses. LN size is a quantitative pre-treatment prognostic factor that should be assessed prior to definitive chemoradiotherapy. Patients with large metastatic lymph nodes are at high risk of DM and should be monitored.


p-Hydroxylcinnamaldehyde from cochinchinamomordica seed reverses resistance to TRAIL in human oesophageal squamous cell carcinoma via the activation of the p38 mitogen-activated protein kinase signalling pathway.
Our previous studies have showed that p-Hydroxylcinnamaldehyde (CMSP) could induce the differentiation of ESCC cells via the cAMP-RhoA-MAPK signalling pathway, which suggests a new potential strategy for ESCC treatment. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in several tumour cells by binding to the death receptors DR4 and DR5. However, TRAIL has little effect on oesophageal squamous cell carcinoma (ESCC) cells due to the loss of the receptors. The present study determined the effect of CMSP, the firstly found chemical constituent of Cochinchinamomordica seed (CMS), on TRAIL-induced apoptosis and its mechanism in ESCC cells. MTS assays were performed to examine the CMSP- and TRAIL-mediated inhibition of ESCC cell growth. Flow cytometry and Hoechst 33258 staining assays were used to detect apoptosis in ESCC cells treated with CMSP combined with TRAIL. Western blotting was used to determine the effect of CMSP on the expression of p38, p-p38, DR4, DR5, Bid and caspase-3/8 in ESCC cells treated with CMSP combined with TRAIL. Additionally, immunodeficient Balb-c/null mouse model was used to determine the chemotherapeutic efficacy of CMSP and TRAIL against ESCC tumour xenograft growth in vivo. We found that the combination of CMSP and TRAIL had a greater inhibitory effect on ESCC cell viability in vitro than CMSP or TRAIL alone. CMSP enhanced the TRAIL-induced apoptosis in ESCC cells by upregulating the expression of DR4 and DR5 via the p38 MAPK signalling pathway. Furthermore, the increased expression of DR4 and DR5 upon TRAIL-induced apoptosis in ESCC cells was mediated at least in part by subsequent caspase-3 and caspase-8 activation. Moreover, the in vivo model showed that tumour growth was significantly slower in CMSP and TRAIL combination-treated mice than in mice treated with CMSP or TRAIL alone. Taken together, our findings indicate that CMSP as an extract from TCM, might be as a potential sensitizer of TRAIL and thus provide a novel strategy for the clinical treatment of ESCC.


Synergism of herbicide toxicity by 5-aminolevulinic acid is related to physiological and ultra-structural disorders in crickweed (Malachium aquaticum L.).
Selection of effective herbicides to control weeds has been one of the major objectives of scientists. This study determines the differential tolerance or susceptibility of crickweed (Malachium aquaticum L.) to various concentration combinations of 5-aminolevulinic acid (ALA) (1, 10 and 100mg/L) and propyl 4-(2-(4,6-dimethoxypyrimidin-2-yloxy)benzylamino)benzoate (ZJ0273) (100, 200, and 500mg/L). ALA was applied as pre- and post-treatment alone or in combination with ZJ0273. Results showed that ZJ0273 stress alone imposed negative effects on M. aquaticum seedling's growth, net photosynthetic rates and SPAD values, and the rate of decline was consistently increased with the increase in ZJ0273 concentration. The ZJ0273 treatment showed a gradual decrease in the activities of antioxidant enzymes peroxidase (POD), superoxide dismutase (SOD), and ascorbate peroxidase (APX), and increase in the accumulation of malondialdehyde (MDA). Changes in chloroplast swelling, increased number of plastoglobuli, disruption of thylakoid, disintegrated mitochondria and turbid nucleoplasm were noticed. Moreover, SDS-PAGE analysis of total proteins revealed that herbicide stress in the leaves was associated with the decrease or disappearance of some protein bands. Further, two-dimensional gel electrophoresis (2-DE) results showed that proteins in different spots were classified into three types for M. aquaticum. These results indicate that the combined treatment of ALA and ZJ0273 synergizes the herbicide toxicity which is different from its independent effects on M. aquaticum and thus, could improve weed control efficacy.


CD7 expression predicts poor disease free survival and post-remission survival in patients with acute myeloid leukemia and normal karyotype.
AML patients with normal karyotype comprise the largest subgroup ( approximately 50%) but have a highly heterogeneous clinical course. By multi-parameter flow cytometry we analyzed CD7 expression along with other phenotypic markers in 185 patients with normal-karyotype AML. CD7 was expressed in 68 (37%) patients. CD7 expression was associated with younger age (P=0.024) but not with sex, WBC count, or extramedullary disease. Patients expressing CD7 had significant shorter disease free (DFS) and post-remission survivals (PRS) than patients without CD7 (DFS of 12 months versus 42 months, P=0.005; PRS of 15 months versus 33 months, P=0.013). We also found that expression of CD34 or HLA-DR was associated with lower CR rate (P=0.0007 and P=0.019, respectively) but did not affect DFS or OS. Furthermore, as for all AML patients, we demonstrated that in the normal karyotypic subgroup, patients with higher WBC counts (>50) and older age (>60 years) had lower CR rate (P=0.003 and P=0.0157, respectively) and shorter OS (P</=0.001 and P=0.007, respectively). Multivariate analysis of age, WBC, CD34, HLA-DR and CD7 showed that CD7 expression was an independent risk factor for DFS (P=0.01) and PRS (P=0.02).


Liposomal n-butylidenephthalide protects the drug from oxidation and enhances its antitumor effects in glioblastoma multiforme.
The natural compound n-butylidenephthalide (BP) can pass through the blood-brain barrier to inhibit the growth of glioblastoma multiforme tumors. However, BP has an unstable structure that reduces its antitumor activity and half-life in vivo. The aim of this study is to design a drug delivery system to encapsulate BP to enhance its efficacy by improving its protection and delivery. To protect its structural stability against protein-rich and peroxide solutions, BP was encapsulated into a lipo-PEG-PEI complex (LPPC). Then, the cytotoxicity of BP/LPPC following preincubation in protein-rich, acid/alkaline, and peroxide solutions was analyzed by MTT. Cell uptake of BP/LPPC was also measured by confocal microscopy. The therapeutic effects of BP/LPPC were analyzed in xenograft mice following intratumoral and intravenous injections. When BP was encapsulated in LPPC, its cytotoxicity was maintained following preincubation in protein-rich, acid/alkaline, and peroxide solutions. The cytotoxic activity of encapsulated BP was higher than that of free BP (~4.5- to 8.5-fold). This increased cytotoxic activity of BP/LPPC is attributable to its rapid transport across the cell membrane. In an animal study, a subcutaneously xenografted glioblastoma multiforme mouse that was treated with BP by intratumoral and intravenous administration showed inhibited tumor growth. The same dose of BP/LPPC was significantly more effective in terms of tumor inhibition. LPPC encapsulation technology is able to protect BP's structural stability and enhance its antitumor effects, thus providing a better tool for use in cancer therapy.


Community-based lifestyle modification programme for non-alcoholic fatty liver disease: a randomized controlled trial.
Healthy lifestyle is the most important management of non-alcoholic fatty liver disease (NAFLD). This study aimed at assessing the efficacy of a community-based lifestyle modification programme in the remission of NAFLD. This was a parallel group, superiority, randomized controlled trial. 154 adults with NAFLD identified during population screening were randomized to participate in a dietitian-led lifestyle modification programme at 2 community centres or receive usual care for 12 months. The primary outcome was remission of NAFLD at month 12 as evidenced by intrahepatic triglyceride content (IHTG) of less than 5% by proton-magnetic resonance spectroscopy. 74 patients in the intervention group and 71 patients in the control group completed all study assessments. In an intention-to-treat analysis of all 154 patients, 64% of the patients in the intervention group and 20% in the control group achieved remission of NAFLD (difference between groups 44%; 95% CI 30-58%; p<0.001). The mean (SD) changes in IHTG from baseline to month 12 were -6.7% (6.1%) in the intervention group and -2.1% (6.4%) in the control group (p<0.001). Body weight decreased by 5.6 (4.4) kg and 0.6 (2.5) kg in the two groups, respectively (p<0.001). While 97% of patients with weight loss of more than 10% had remission of NAFLD, 41% of those with weight loss of 3.0-4.9% could also achieve the primary outcome. The community-based lifestyle modification programme is effective in reducing and normalizing liver fat in NAFLD patients.


Lymph node metastasis and tumor-educated immune tolerance: Potential therapeutic targets against distant metastasis.
Lymph node metastasis has been shown to positively associated with the prognosis of many cancers. However, in clinical treatment, lymphadenectomy is not always successful, suggesting that immune cells in the tumor and sentinel lymph nodes still play a pivotal role in tumor immunosuppression. Recent studies had shown that tumors can tolerate immune cells through multiple strategies, including tumor-induced macrophage reprogramming, T cells inactivation, production of B cells pathogenic antibodies and activation of regulatory T cells to promote tumor colonization, growth, and metastasis in lymph nodes. We reviewed the bidirectional effect of immune cells on anti-tumor or promotion of cancer cell metastasis during lymph node metastasis, and the mechanisms by which malignant cancer cells modify immune cells to create a more favorable environment for the growth and survival of cancer cells. Research and treatment strategies focusing on the immune system in lymph nodes and potential immune targets in lymph node metastasis were also be discussed.


Defining the epichromatin epitope.
Epichromatin is identified by immunostaining fixed and permeabilized cells with particular bivalent anti-nucleosome antibodies (mAbs PL2-6 and 1H6). During interphase, epichromatin resides adjacent to the inner nuclear membrane; during mitosis, at the outer surface of mitotic chromosomes. By STED (stimulated emission depletion) microscopy, PL2-6 stained interphase epichromatin is ∼76 nm thick and quite uniform; mitotic epichromatin is more variable in thickness, exhibiting a "wrinkled" surface with an average thickness of ∼78 nm. Co-immunostaining with anti-Ki-67 demonstrates Ki-67 deposition between the PL2-6 "ridges" of mitotic epichromatin. Monovalent papain-derived Fab fragments of PL2-6 yield a strikingly different punctate "chromomeric" immunostaining pattern throughout interphase nuclei and along mitotic chromosome arms. Evidence from electrophoretic mobility shift assay (EMSA) and from analytical ultracentrifugation characterize the Fab/mononucleosome complex, supporting the concept that there are two binding sites per nucleosome. The peptide sequence of the Hv3 region (heavy chain variable region 3) of the PL2-6 antibody binding site strongly resembles other nucleosome acidic patch binding proteins (especially, LANA and CENPC), supporting that the nucleosome acidic patch is included within the epichromatin epitope. It is speculated that the interphase epichromatin epitope is "exposed" with favorable geometric arrangements for binding bivalent PL2-6 at the surface chromatin; whereas, the epitope is "hidden" within internal chromatin. Furthermore, it is suggested that the "exposed" nucleosome surface of mitotic epichromatin may play a role in post-mitotic nuclear envelope reformation.


Pancreas allografts: comparison of three-dimensional rotational angiography with standard digital subtraction angiography.
To define the role of three-dimensional (3D) rotational angiography (RA) for the evaluation of pancreas allografts and compare 3D RA to standard digital subtraction angiography (DSA). DSA and 3D RA were performed in patients with vascular abnormalities diagnosed on contrast medium-enhanced magnetic resonance (MR) angiography. Patency of the allograft vasculature, confidence in the ability to make a therapeutic decision, and value of the study for definition of the optimal projection for an intervention was assessed on a graded scale. Seventeen standard DSA projections (mean, 3.4; range, 2-6) and 10 3D RA images (mean, 2; range, 1-3) were obtained in five patients. An average iodinated contrast agent dose of 14.4 mL (range, 8-22 mL) was administered for DSA. An average CO2 dose of 54 mL (range, 0-120 mL) was administered for 3D RA. Five 3D RA procedures were timed for the arterial phase and five were timed for the arterial and venous phases. Average contrast agent doses were 17.6 mL (range, 11-22 mL) for arterial 3D RA and 24.4 mL (range, 16-34 mL) for arterial- and venous-phase 3D RA. Of 68 vascular segments available for direct comparison of patency, complete concordance was present in 96%. There was no difference in the reviewers' diagnostic confidence (10 +/- 0 for both techniques). Three-dimensional RA was considered significantly superior for planning the optimal projection for intervention (10 +/- 0 for 3D RA vs 7.2 +/- 1.6 for DSA; P = .0052). Three-dimensional RA of pancreatic allografts is feasible and does not differ in accuracy from conventional DSA. It provides similar reviewer confidence in the ability to make an accurate treatment decision, but its key advantage is its superior ability to define the optimal projection for planned endovascular interventions.


myo-inositol action on gerbil intestine: alterations in alkaline phosphatase activity upon phosphatidylinositol depletion and repletion in vivo.
The influence of phosphatidylinositol (PI) on intestinal alkaline phosphatase activity was studied in myo-inositol deficient gerbils. A reduction of membrane PI in intestinal mucosa to 30-40% of the control was produced by feeding female gerbils a myo-inositol-deficient diet containing coconut oil for 2 weeks. As expected, the animals developed typical intestinal lipodystrophy with abnormal fat accumulation. In the PI-depleted animal, intestinal alkaline phosphatase activity was reduced to 20-30% of the control group. The levels of both membranous and soluble enzymes in intestinal mucosa were affected, but there were no changes in liver, kidney and plasma levels. When the lipodystrophic gerbils were given dietary myo-inositol, the complete repletion of intestinal membrane PI to the control level occurred 36 h later, whereas membrane-bound alkaline phosphatase activity in intestine was not restored to the control level until 72 h later. Administration of cycloheximide or actinomycin D did not block this enzyme induction. Lymphatic output of triacylglycerol into the bloodstream was stimulated 10-fold at 18 h of myo-inositol repletion, but there was no parallel increase in the activity of alkaline phosphatase in plasma during this early phase of intestinal recovery. Thus, these data suggest a possible regulatory role of PI in the processing and/or turnover of alkaline phosphatase in vivo, but a negative role of alkaline phosphatase in lipid transport across gerbil intestine.


Contrasting oxygen-effects in the inactivation of ribonuclease A by N.3, (SCN).-2 and .OH radicals.
N.3 exhibits higher efficiency than .OH in the inactivation of RNase in de-acerated (neutral) aqueous solution. In O2-saturated solution the .OH-induced inactivation is enhanced, but N.3 and (SCN).-2 become remarkably inefficient. Our results suggest that semi-oxidized tyrosine, the predominant initial defect induced by N.3 and (SCN).-2 but not by .OH2 can be re-reduced upon reaction with O.-2 or cysteine.


Inflatable penile prostheses for the treatment of erectile dysfunction: an update.
Male erectile dysfunction (ED) is a common medical condition. Three oral medications (sildenafil, vardenafil and tadalafil, all phosphodiesterase type 5 inhibitors) have been developed and approved for the treatment of ED by the US FDA. Extensive worldwide marketing of these medications has raised public awareness of ED, and allowed many previously untreated men to seek and receive effective therapy. A variety of other ED treatments are available and approved by the FDA, including vacuum-constriction devices and intracavernous or intraurethral alprostadil. However, roughly 30-40% of men with ED are not adequately served by these treatments due to their cost, side effects, contraindications, the need to 'time' sexual activity, or lack of satisfactory erectile response. For men who do not respond to less invasive therapy, an inflatable penile prosthesis can provide a satisfying and effective alternative. This article will review and critique the inflatable penile prostheses that are currently available in the USA and the EU for the treatment of ED.


Protein kinase C activity in the spleen of trout (Salmo gairdneri) and the rectal gland of dogfish (Scyliorhinus canicula), and the effects of phosphatidylserine and diacylglycerol containing (n-3) polyunsaturated fatty acids.
1. High speed supernatant fractions of trout spleen and dogfish rectal gland contained 22.5 and 7.2 nmol/min/g tissue of protein kinase C activity respectively. 2. The effect of Ca2+ concentration on the activities with phosphatidylserine (PtdSer) alone, diacylglycerol (DAG) alone and PtdSer and DAG together were determined. Both enzymes required Ca2+ but activity was independent of Ca2+ concentration within the physiological range of 0.1-10 microns. 3. The effect of PtdSer and DAG containing (n - 3) polyunsaturated fatty acids (PUFA) on the activity of protein kinase C from both tissues was examined. Both enzymes were active with all lipids tested and showed little or no discrimination between lipids differing in their contents of (n-3) or (n-6) polyunsaturated fatty acids.