Nanomaterials in the Environment Acquire an "Eco-Corona" Impacting their Toxicity to Daphnia Magna-a Call for Updating Toxicity Testing Policies.
Nanomaterials (NMs) are particles with at least one dimension between 1 and 100 nm and a large surface area to volume ratio, providing them with exceptional qualities that are exploited in a variety of industrial fields. Deposition of NMs into environmental waters during or after use leads to the adsorption of an ecological (eco-) corona, whereby a layer of natural biomolecules coats the NM changing its stability, identity and ultimately toxicity. The eco-corona is not currently incorporated into ecotoxicity tests, although it has been shown to alter the interactions of NMs with organisms such as Daphnia magna (D. magna). Here, the literature on environmental biomolecule interactions with NMs is synthesized and a framework for understanding the eco-corona composition and its role in modulating NMs ecotoxicity is presented, utilizing D. magna as a model. The importance of including biomolecules as part of the current international efforts to update the standard testing protocols for NMs, is highlighted. Facilitating the formation of an eco-corona prior to NMs ecotoxicity testing will ensure that signaling pathways perturbed by the NMs are real rather than being associated with the damage arising from reactive NM surfaces "acquiring" a corona by pulling biomolecules from the organism's surface.


Determination of selenium in human spermatozoa and prostasomes using base digestion and electrothermal atomic absorption spectrophotometry.
A method for the determination of selenium in human spermatozoa and prostasomes is described. The samples were digested with 25% (w/v) tetramethylammonium hydroxide (TMAH) in methanol and analyzed by atomic absorption spectrometry with electrothermal atomization and Zeeman background correction (ET-AAS). Nickel was used as a matrix modifier. Calibration was performed using the matrix-based calibration curve. The TMAH-digestion method agreed well with a conventional digestion procedure using concentrated nitric acid. The TMAH-digestion does not require heating or strong acids and it was suitable for small biological samples. The average recovery of added selenium in spermatozoan digests was 95.1 +/- 5.2% (n = 5). The coefficient of variation was 9.1% (n = 21). The accuracy of the method tested with the NBS standard 1577 (bovine liver, certified at 1.1 +/- 0.1 micrograms Se/g) resulted in a value of 0.98 +/- 0.10 micrograms Se/g (n = 16). The method was further tested in an interlaboratory comparison study.


Regulation of naïve and memory T-cell homeostasis.
Recent work has confirmed the existence of homeostatic mechanisms that regulate the overall size and composition of the mature T-cell pool. Homeostatic mechanisms not only control total T-cell numbers but appear to act differently on naïve vs. memory cells. The roles of self-MHC/peptide ligands and certain cytokines in T-cell homeostasis are discussed.


Ziprasidone.
▴ Ziprasidone is a novel antipsychotic drug. It has high affinity for serotonin 5-HT(2) and dopamine D(2) receptors in vitro, with an 11-fold higher affinity for 5-HT(2) than for D(2) receptors, suggestive of a low potential for inducing motor disturbance [including extrapyramidal symptoms (EPS)].▴ The effects of ziprasidone in receptor binding studies reflected its in vitro pharmacology, with more potent effects against 5-HT(2) receptor- than against D(2) receptor-mediated behaviour.▴ Because ziprasidone inhibits serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (norepinephrine) reuptake, it may have anxiolytic and antidepressant effects.▴ Data from phase II and III clinical trials have shown ziprasidone to be effective in reducing the positive and negative symptoms of, and depression associated with, schizophrenia, and in reducing anxiety in patients about to undergo dental surgery.▴ Ziprasidone was generally well tolerated in phase II and III clinical trials, with somnolence and nausea being the most frequently reported adverse events in placebo-controlled studies. Motor disturbances, including EPS, were infrequently observed.


Immune-mediated mesangial cell injury--biosynthesis and function of prostanoids.
We studied the formation of cyclo-oxygenase products in a rat model of mesangial cell injury, in order to determine a possible role of prostaglandin E2 (PGE2), prostaglandin I2 (determined as 6-keto-PGF1 alpha and thromboxane A2 (TxA2) in immune-mediated glomerular disease. Selective immune-mediated mesangial cell injury was induced by i.v. administration of a rabbit anti-rat thymocyte antiserum (ATS). Intravenous ATS leads to immune deposits in the mesangium followed by mesangiolysis and the infiltration of polymorphonuclear granulocytes and monocytes. Glomerular TxB2 formation two hours (292 +/- 27 pg/mg/min) and 48 hours (396 +/- 69 pg/mg/min) following antibody was significantly (P less than 0.05) higher compared to animals receiving non-antibody rabbit IgG (TxB2: 2 hr 143 +/- 13; 48 hr 171 +/- 32 pg/mg/min). Treatment with cobra venom factor (CVF) and the reduction of glomerular monocyte infiltration inhibited the increase of glomerular TxB2 formation significantly. Depletion of granulocytes with a rabbit anti-rat granulocyte serum had no effect on glomerular prostanoid formation following ATS. Glomerular PGE2 and 6-keto PGF1 alpha production was not altered following ATS. Inulin clearance in rats with immune-mediated mesangial cell injury was significantly (P less than 0.001) lower at two hours (456 +/- 24 microliters/min/100 g body wt) and 48 hours (433 +/- 54 microliters/min/100 g body wt) compared to their corresponding control animals which were treated with non-antibody IgG (2 hr: 914 +/- 51; 48 hr: 694 +/- 79 microliters/min/100 g body wt).(ABSTRACT TRUNCATED AT 250 WORDS)


Addressing extreme size mismatch in pediatric intestinal transplantation: Outcomes of intestinal length reduction.
Bench liver reduction, with or without intestinal length reduction (LR) (coupled with delayed closure and abdominal wall prostheses), has been a strategy adopted by our program for small children due to the limited availability of size-matched donors. This report describes the short, medium, and long-term outcomes of this graft reduction strategy. A single-center, retrospective analysis of children that underwent intestinal transplantation (April 1993 to December 2020) was performed. Patients were grouped according to whether they received an intestinal graft of full length (FL) or following LR. Overall, 105 intestinal transplants were performed. The LR group (n = 10) was younger (14.5 months vs. 40.0 months, p = .012) and smaller (8.7 kg vs. 13.0 kg, p = .032) compared to the FL group (n = 95). Similar abdominal closure rates were achieved after LR, without any increase in abdominal compartment syndrome (1/10 vs. 7/95, p = .806). The 90-day graft and patient survival were similar (9/10, 90% vs. 83/95, 86%; p = .810). Medium and long-term graft survival at 1 year (8/10, 80% vs. 65/90, 71%; p = .599), and 5 years (5/10, 50% vs. 42/84, 50%; p = 1.00) was similar. LR of intestinal grafts appears to be a safe strategy for infants and small children requiring intestinal transplantation. This technique should be considered in the situation of significant size mismatch of intestine containing grafts.


TREM2 and Microglia Contribute to the Synaptic Plasticity: from Physiology to Pathology.
Synapses are bridges for information transmission in the central nervous system (CNS), and synaptic plasticity is fundamental for the normal function of synapses, contributing substantially to learning and memory. Numerous studies have proven that microglia can participate in the occurrence and progression of neurodegenerative diseases (NDDs), such as Alzheimer's disease (AD), by regulating synaptic plasticity. In this review, we summarize the main characteristics of synapses and synaptic plasticity under physiological and pathological conditions. We elaborate the origin and development of microglia and the two well-known microglial signaling pathways that regulate synaptic plasticity. We also highlight the unique role of triggering receptor expressed on myeloid cells 2 (TREM2) in microglia-mediated regulation of synaptic plasticity and its relationship with AD. Finally, we propose four possible ways in which TREM2 is involved in regulating synaptic plasticity. This review will help researchers understand how NDDs develop from the perspective of synaptic plasticity.


Tbf1 or not Tbf1?
In this issue of Molecular Cell, Hogues et al. (2008) demonstrate a wholesale shift in the key regulatory protein involved in ribosomal protein (RP) synthesis during the evolution of S. cerevisiae and, en passant, raise interesting questions about the relationship between RP genes and telomeres.


Transplantation of adult Trichinella spiralis between hosts: worm survival and immunological characteristics of the host--parasite relationship.
A technique for the transplantation of Trichinella spiralis worms directly into the host intestine is described. Infections established by the direct transfer of adult worms were essentially normal both in terms of their survival and reproduction and in their stimulation of, and susceptibility to, host immune responses. Worms transplanted from NIH mouse donors at intervals after infection had an equal ability to survive in the recipient, even when taken from the donor shortly before or during the process of worm expulsion, showing that expulsion does not require worms to be irreversibly damaged. It was noted, however, that after 7 days in the donor the ability of the worm to reproduce in the recipient was temporarily impaired.


Bisphenol A Represses Dopaminergic Neuron Differentiation from Human Embryonic Stem Cells through Downregulating the Expression of Insulin-like Growth Factor 1.
Bisphenol A (BPA) is a ubiquitous compound emerging as a possible toxicant during embryonic development. Human embryonic stem cell (hESC) promises a valuable model for evaluating the effects of environmental chemicals on human prenatal development. In our study, 1 μM BPA were applied to hESC-derived embryoid bodies (hEBs) and effects of BPA on neural cell differentiation were investigated. The expression level of insulin-like growth factor 1 (IGF-1) and marker genes for ectoderm, neuron progenitor cells, and dopaminergic (DA) neurons were all repressed upon BPA exposure. The population of hESC-derived neural precursor cells (NPCs) and DA neurons were decreased. Furthermore, yield of DA neuron-secreted tyrosine hydroxylase (TH) and dopamine were also reduced. When recombinant IGF-1 supplied, BPA-caused repressions were partially or completely relieved. Our further methylation microarray analysis indicated that there was a higher methylation level on the promoter of SRY-related HMG-box 5 (SOX5), a possible enhancer of IGF-1. Consistently, next quantitative polymerase chain reaction (qPCR) results confirmed that SOX5 expression was downregulated. Our investigation suggests that BPA represses DA neuron differentiation mainly through downregulating IGF-1 expression, which may attribute to the altered methylation level on the promoter of IGF-1 upstream genes. Our findings first elaborate the mechanism of IGF-1-mediated BPA effects on neuronal differentiation, which is helpful to illuminate the unique mechanism of BPA toxicity on prenatal neurodevelopment.


Factors associated with guideline-concordant use of radiotherapy after mastectomy in the national comprehensive cancer network.
We examined the rates and determinants of appropriate and inappropriate use of postmastectomy radiotherapy (PMRT), as defined by the National Comprehensive Cancer Network (NCCN) practice guidelines, among women with Stage I-II breast cancer (American Joint Committee on Cancer, 5th edition). Using clinical characteristics, 1,620 consecutive patients at eight NCCN institutions who had undergone mastectomy between July 1997 and June 2002 were classified into three cohorts according to whether the guidelines (1) recommended PMRT, (2) recommended against PMRT, or (3) made no definitive PMRT recommendation. We defined the absence of PMRT in the first cohort as underuse and receipt of PMRT in the second cohort as overuse. Multivariate logistic regression analysis was applied to investigate the association of clinical and sociodemographic factors with PMRT. Overall, 23.8% of patients received PMRT. This included 199 (83.6%) of 238 in the "recommend PMRT" cohort, 58 (5.6%) of 1,029 in the "recommend against PMRT" cohort, and 127 (38.6%) of 329 in the "consider PMRT" cohort. The only factor associated with underuse in the "recommend PMRT" cohort was nonreceipt of chemotherapy (odds ratio [OR], 0.08; p <0.0001). In addition to tumor characteristics, the factors associated with overuse in the "recommend against PMRT" cohort included age <50 years (OR, 2.28; p = 0.048), NCCN institution (OR, 1.04-8.29; p = 0.026), higher education (OR, 3.49; p = 0.001), and no reconstructive surgery (OR, 2.44; p = 0.019). The factors associated with PMRT in the "consider PMRT" cohort included NCCN institution (OR, 1.1-9.01; p <0.0001), age <50 years (OR, 2.26; p = 0.041), and tumor characteristics. The results of our study have shown that concordance with definitive treatment guidelines was high. However, when current evidence does not support a definitive recommendation for PMRT, treatment decisions appear to be influenced, not only by patient age and clinical characteristics, but also by institution-specific patterns of care.


A large meconium pseudocyst that developed into the generalized type during the antepartum period.
A fetal intraabdominal cystic mass, measuring 6 cm, was detected at 30 weeks of gestation in a 27-year-old gravida 2 para 1 woman. At 33 weeks of gestation, the cyst disappeared. Ultrasonography showed fetal bowel dilatation, polyhydramnios, and intraabdominal calcifications. Fetal meconium peritonitis was diagnosed prenatally. Because the fetal ileus became worse, a cesarean section was performed at 35 weeks of gestation; a female infant weighing 2,131 g with an Apgar score of 8 was delivered. Six hours after birth, the neonate received an ileostomy. The bowel was reanastomosed 42 days after the initial operation. On postoperative pathology, a meconium pseudocyst was diagnosed. To our knowledge, this is the first report of a large fetal meconium pseudocyst that developed into the generalized type in the uterus during the preterm antepartum period.


Autophagy prolongs survival after NFκB inhibition in B-cell lymphomas.
Autophagy allows cells to survive under conditions of nutrient deprivation. We have demonstrated that autophagy inhibitors are synthetically lethal with NFκB inhibitors in B-cell lymphomas because the NFκB pathway promotes survival by increasing glucose import. When NFκB is inhibited in B-cell lymphoma, glucose import decreases and cells become sensitive to perturbations in mitochondrial metabolism and autophagy. Thus, combined inhibition of autophagy and NFκB drives cells into metabolic crisis accelerating cell death.


An Integrative Review of the Perinatal Experiences of Black Women.
To synthesize the current body of evidence regarding the perinatal experiences of Black women. The databases PubMed, the Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Scopus were searched with the search terms "African American" (in PubMed), "Black" (in Scopus), or "Black" OR "African American" (in CINAHL) AND "pregnancy" AND "experiences." Searches yielded 266 articles published between January 2015 and May 2021. After initial screening, 68 articles were assessed for eligibility, yielding 23 studies that met the inclusion criteria of this review. Studies were reviewed for the perinatal experiences of Black women. Nonresearch articles, systematic reviews, and instrument development articles were removed. Also excluded were articles with a focus on adolescent pregnancy, breastfeeding experiences, and those outside of the perinatal time frame. Analysis showed that Black women continue to report negative experiences in perinatal care and that these negative experiences spanned various sociodemographic characteristics. Although some Black women described positive interactions, many more expressed dissatisfaction with the lack of education, resources, and continuity in care, as well as poor communication. Additionally, experiences of racism and biases in care, mistrust in the health care system, and doubts of the efficacy or necessity of medical treatments exist. Negative perinatal care experiences and dissatisfaction among Black women remain common. Although Black women desire more holistic, naturalistic, and empowering care, Black women first want safe, respectful care and a health care team that removes biases and racism from its system. More research is needed that includes the voices of Black women to understand these experiences and to develop interventions to improve the perinatal care experience. Nurses and other health care providers providing care in the perinatal period must also listen to, trust, and respect Black women.


Corrigendum.
Kwon J-W, Park E-J, Jung S-Y, Sohn HS, Ryu H, Suh HS. 2015. A large national cohort study of the association between bisphosphonates and osteonecrosis of the jaw in patients with osteoporosis: a nested case-control study. J Dent Res. 94(9 Suppl):212S-219S. (Original DOI: 10.1177/0022034515587862).


The association of recreational space with youth smoking in low-socioeconomic status neighborhoods in Santiago, Chile.
This study examines the relationship of neighborhood recreational space with youth smoking in mid- to low-income areas in the capital of Chile, Santiago. A unique data set of adolescents (n = 779, mean age = 14, 51 % male) provided home addresses of study participants which were geocoded and mapped. Satellite maps of neighborhoods were used to identify open spaces for recreational use (e.g., soccer fields and plazas). Thiessen polygons were generated to associate study participants with the nearest available open space using ArcGIS. Regression models, with smoking as a dependent variable, were estimated in which age, sex, family socioeconomic status, peer substance usage, neighborhood crime, and accessibility of open space were covariates. The results show that residential proximity to recreational space was significantly and inversely associated with tobacco consumption among female, but not male, adolescents. Age and neighborhood crime were both positively associated with tobacco consumption among both male and female adolescents. This study suggests that recreational spaces in proximity to residences may have a positive impact on reducing adolescents' inclination to consume tobacco. The relationship of the accessibility to such spaces with smoking appears to vary by adolescents' sex.


IL-10 up-regulates human monocyte phagocytosis in the presence of IL-4 and IFN-gamma.
Interleukin-10 (IL-10), a cytokine produced by type 2 helper T (Th2) cells, inhibits the microbicidal effector function of interferon-gamma (IFN-gamma)-activated macrophages. However, recent observations indicate that IL-10, like IFN-gamma, increases Fc gamma RI expression and Fc gamma R-mediated cytotoxic activity on human monocytes, suggesting that this cytokine cannot be classified purely as a monocyte deactivator. The present study found that incubation for 40 h of human monocytes or monocyte-derived macrophages in the presence of IL-10 caused a significant enhancement of their capacity to ingest particles coated with immunoglobulin G (Fc gamma R-mediated ingestion) or with C3b/C3bi fragments of the complement system (CR1/CR3-mediated ingestion). The number of phagocytosing cells (% phagocytosis) and the number of ingested particles per cell (phagocytic index) were both significantly higher after 40-h incubation of monocytes with IL-10 concentrations > or = 1 U/ml. This up-regulating activity on phagocytosis was completely reversed by anti-IL-10 monoclonal antibody (mAb). As previously reported, IL-10 stimulated Fc gamma RI expression on monocytes but did not induce the expression of Fc gamma RII, Fc gamma RIII, CR1, and CR3. IFN-gamma, like IL-10, up-regulated only Fc gamma RI expression but significantly reduced both Fc gamma R- and CR-mediated ingestion. IL-10 almost completely reversed the IFN-gamma-induced inhibition of both Fc gamma R- and CR-mediated phagocytosis, without concomitant changes in membrane expression of phagocytic receptors. Exposure of monocytes to IL-4 reduced the membrane expression of all three Fc gamma Rs and also inhibited Fc gamma R-mediated ingestion. On the other hand, IL-4 up-regulated both CR3 expression and CR-mediated ingestion on cultured monocytes. IL-10 not only neutralized the down-regulatory effect of IL-4 on Fc gamma R expression but also completely reversed the IL-4-induced suppression of Fc gamma R-mediated phagocytosis. Exposure of monocytes to a combination of IL-10 and IL-4 resulted in a synergistic effect on CR-mediated ingestion, even though no additive effects were observed on CR membrane expression. Finally, culture of monocytes in medium containing anti-IL-10 mAb significantly reduced their capacity to ingest IgG- or C3b/C3bi-coated particles, suggesting a role for endogenously produced IL-10 in the modulation of phagocytosis by human monocytes.(ABSTRACT TRUNCATED AT 400 WORDS)


A rapid and efficient method for the radiosynthesis and purification of [125I]SCH23982.
The radiosynthesis of (1R)-(+)-1-phenyl-3-methyl-7-[125I]iodo-8-hydroxy- 2,3,4,5-tetrahydro-1H-3-benzazepine (commonly referred to as SCH23982) and its use as a high affinity D1 dopamine antagonist ligand have been reported previously. We now provide a simple and inexpensive protocol for the rapid and efficient synthesis of this radioligand based on the Cloramine-T-catalyzed reaction between the commercially available precursor (R)-(+)-1-phenyl-3-methyl- 8-hydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine and carrier-free sodium [125I]iodide. [125I]SCH23982 is separated rapidly (within 20 min) from the precursor and reaction byproducts (e.g., chlorinated precursor, SCH23390) by reverse-phase HPLC on a C-8 column. The major iodinated product has been identified as SCH23982 based on co-chromatography with authentic SCH23982, UV spectral characteristics, and biological activity. The chromatographic effluent containing the active product is adsorbed on a C-18 Sep-Pak cartridge to remove mobile-phase constituents and permit it to be eluted and diluted to the desired concentration; this technique is used also for periodic repurification. Our synthesis protocol results in final purified product that incorporates ca. 50% of the initial 125I (tested using starting quantities of 1-10 mCi Na125I); the final product has a specific activity of ca. 2500 +/- 350 Ci/mmol. Data from in vitro receptor autoradiographic and homogenate studies with this radioligand are consistent with previously reported values in terms of expected receptor distribution, affinity, and density (KD of 1.0 nM, Bmax of 1400 fmol/mg protein in rat striatal membranes).


Prevalence of Domestic Violence Among Trauma Patients.
Domestic violence is an extremely underreported crime and a growing social problem in the United States. However, the true burden of the problem remains unknown. To assess the reported prevalence of domestic violence among trauma patients. A 6-year (2007-2012) retrospective analysis of the prospectively maintained National Trauma Data Bank. Trauma patients who experienced domestic violence and who presented to trauma centers participating in the National Trauma Data Bank were identified using International Classification of Diseases, Ninth Revision diagnosis codes (995.80-995.85, 995.50, 995.52-995.55, and 995.59) and E codes (E967.0-E967.9). Patients were stratified by age into 3 groups: children (≤18 years), adults (19-54 years), and elderly patients (≥55 years). Trend analysis was performed on April 10, 2014, to assess the reported prevalence of domestic violence over the years. Trauma patients presenting to trauma centers participating in the National Trauma Data Bank. To assess the reported prevalence of domestic violence among trauma patients. A total of 16 575 trauma patients who experienced domestic violence were included. Of these trauma patients, 10 224 (61.7%) were children, 5503 (33.2%) were adults, and 848 (5.1%) were elderly patients. The mean (SD) age was 15.9 (20.6), the mean (SD) Injury Severity Score was 10.9 (9.6), and 8397 (50.7%) were male patients. Head injuries (46.8% of patients) and extremity fractures (31.2% of patients) were the most common injuries. A total of 12 515 patients (75.1%) were discharged home, and the overall mortality rate was 5.9% (n = 980). The overall reported prevalence of domestic violence among trauma patients was 5.7 cases per 1000 trauma center discharges. The prevalence of domestic violence increased among children (14.0 cases per 1000 trauma center discharges in 2007 to 18.5 case per 1000 trauma center discharges in 2012; P = .001) and adults (3.2 cases per 1000 discharges in 2007 to 4.5 cases per 1000 discharges in 2012; P = .001) over the 6-year period and remained unchanged for elderly patients (0.8 cases per 1000 discharges in 2007 to 0.96 cases per 1000 discharges in 2012; P = .09). On subanalysis of adults and elderly patients, the prevalence of domestic violence increased among both female (4.6 cases per 1000 discharges in 2007 to 5.3 cases per 1000 discharges in 2012; P = .001) and male patients (1.5 cases per 1000 discharges in 2007 to 2.8 cases per 1000 discharges in 2012; P = .001). Domestic violence is prevalent among trauma patients. Over the years, the reported prevalence of domestic violence has been increasing among children and adults, and continues to remain high among female trauma patients. A robust mandatory screening for evaluating domestic violence among trauma patients, along with a focused national intervention, is warranted.


Control of expression of the gene for the arginine transporter Cat-1 in rat liver cells by glucocorticoids and insulin.
Hepatic arginine and lysine uptake is partly regulated by changes in the transport activity of a group of cell surface proteins exhibiting properties of the transport system y+. The Cat-1 gene encodes a sodium-independent high-affinity cationic amino acid transporter of the y+ system which is nearly undetectable in the quiescent liver. In this paper we investigate the regulation of expression of Cat-1 in the quiescent rat liver by glucocorticoids and insulin, two hormones which play a critical role in amino acid dependent pathways of hepatic metabolism. Injection of insulin and glucocorticoids resulted in a rapid (15-30 min, 4-5 fold) increase in transcription which returned to basal levels within 4 hours. In contrast to the rapid single peak of transcriptional induction of the Cat-1 gene, the accumulation of the Cat-1 mRNAs occurred transiently with two peaks, the first at 30 minutes and the second at 2-4 hours following hormone treatment. These data indicate that expression of the Cat-1 gene in the quiescent liver can be transiently induced by both transcriptional and post-transcriptional mechanisms. In FTO2B rat hepatoma cells, expression of the gene is constitutive and accumulation of Cat-1 mRNAs in response to dexamethasone and insulin was dependent on transcription and protein synthesis. Furthermore, the accumulation of the basal level of the Cat-1 mRNAs was reduced by 70%, upon treatment of cells with inhibitors of protein synthesis for 6 h, when the transcription rate of the gene did not decrease significantly. We conclude the following: (i) under normal physiologic conditions, expression of the Cat-1 gene in the quiescent liver is negligible, probably to prevent unnecessary transport and metabolism of arginine by the hepatic arginase in the hepatocytes. (ii) in the cases when hepatic cationic amino acid transport is needed, such as following feeding, cellular growth and illness, glucocorticoids and insulin induce expression of the Cat-1 gene in liver cells through induction of transcription and stabilization of the mRNA. (iii) constitutive Cat-1 mRNA accumulation in rat hepatoma cells depends on protein synthesis through a labile regulated factor. Overall, constitutive expression of Cat-1 is associated with hepatic cellular growth and transformation.


A highly sensitive strategy for base excision repair enzyme activity detection based on graphene oxide mediated fluorescence quenching and hybridization chain reaction.
A novel fluorescent nanosensor has been developed by combining super fluorescence quenching ability of graphene oxide and hybridization chain reaction amplification, which enables highly sensitive detection of base excision repair enzyme activity with a wide dynamic range from 0.0001 to 100 U mL(-1) and a detection limit of 0.00006 U mL(-1).


Novel approaches to capturing and using continuous cardiorespiratory physiological data in hospitalized children.
Continuous cardiorespiratory physiological monitoring is a cornerstone of care in hospitalized children. The data generated by monitoring devices coupled with machine learning could transform the way we provide care. This scoping review summarizes existing evidence on novel approaches to continuous cardiorespiratory monitoring in hospitalized children. We aimed to identify opportunities for the development of monitoring technology and the use of machine learning to analyze continuous physiological data to improve the outcomes of hospitalized children. We included original research articles published on or after January 1, 2001, involving novel approaches to collect and use continuous cardiorespiratory physiological data in hospitalized children. OVID Medline, PubMed, and Embase databases were searched. We screened 2909 articles and performed full-text extraction of 105 articles. We identified 58 articles describing novel devices or approaches, which were generally small and single-center. In addition, we identified 47 articles that described the use of continuous physiological data in prediction models, but only 7 integrated multidimensional data (e.g., demographics, laboratory results). We identified three areas for development: (1) further validation of promising novel devices; (2) more studies of models integrating multidimensional data with continuous cardiorespiratory data; and (3) further dissemination, implementation, and validation of prediction models using continuous cardiorespiratory data. IMPACT: We performed a comprehensive scoping review of novel approaches to capture and use continuous cardiorespiratory physiological data for monitoring, diagnosis, providing care, and predicting events in hospitalized infants and children, from novel devices to machine learning-based prediction models. We identified three key areas for future development: (1) further validation of promising novel devices; (2) more studies of models integrating multidimensional data with continuous cardiorespiratory data; and (3) further dissemination, implementation, and validation of prediction models using cardiorespiratory data.


Testosterone and cortisol are negatively associated with ritualized bonding behavior in male macaques.
Neuroendocrine research on the formation of social bonds has primarily focused on the role of nonapeptides. However, steroid hormones often act simultaneously to either inhibit or facilitate bonding. Testosterone is proposed to mediate a trade-off between male mating effort and nurturing behavior; therefore, low levels are predicted during periods of nurturing infant care and social bonding. In species where social bonding and support regulates hypothalamic-pituitary-adrenal axis activity, we also expect glucocorticoid levels to be low during bonding periods. We investigated how immunoreactive urinary testosterone (iuT) and cortisol (iuC) were related to triadic male-infant-male interactions - a ritualized male bonding behavior - as well as infant care in male Barbary macaques (Macaca sylvanus). We collected >3000 h of behavioral observation data during full-day focal animal follows from 14 adult males and quantified iuT and iuC from 650 urine samples. iuT was negatively correlated with rates of triadic interactions within subjects, but positively correlated between subjects. iuC was negatively correlated with triadic interactions both within and between subjects. Time spent caring for infants was positively correlated to both iuT and iuC within subjects, but not between subjects. The observed negative relationship between iuT and triadic interactions within subjects may be beneficial to lower competitive tendencies between adult males and to not inhibit bond formation. However, the positive correlation of iuT with triadic interactions between subjects was unexpected. We speculate that it could be due to a link between triadic interactions and coalition formation. A negative relationship between triadic interactions and iuC could reflect increased bonding and perceived social support as triadic interactions predict future coalition formation in this species, or reflect buffered tensions between males. The positive relationship of iuT and iuC with infant care suggests that the handling of infants may be less nurturing but rather protective or competitive in this species. Measuring steroid hormones in relation to bonding and nurturing can help us interpret behaviors within the ecological contexts that they occur.


Association between HLA B7, DR2 and dysfunction of natural- and antibody-mediated cytotoxicity without connection with the deficient interferon production in multiple sclerosis.
In this study, 133 patients with MS were investigated for HLA-A,B,C,DR antigens, natural killer (NK) cell activity, and antibody-mediated cytotoxicity (ADCC). A higher frequency of HLA B7 and DR2 was found in this group of patients than in the healthy control group, as can be observed in other caucasoid populations as well. In Gypsies living in the same geographic area, almost a complete absence of the disease was observed, corresponding to a lack of B7; however, HLA DR2 was present in 56% of this population. NK activity and ADCC measured against the K-562 tumor cell line was found to be significantly lower in MS patients, most pronounced in the group of male patients. Interferon augmentation of NK activity showed similar impairment in the patient group, and their lymphocytes produced a significantly lower amount of interferon. A correlation was demonstrated between both killer cell function and HLA B7, DR2 in MS patients, however, it was significant only in the case of ADCC and DR2. No other correlations were found in relation to interferon augmentation, interferon production, and HLA antigens. The above finding underscores a possible HLA-linked pathogenetic role of NK and K cell dysfunction in MS. This is consistent with other, similar observations that a possible defect in virus immunity may exist in MS patients.


Radiation-induced spinal cord glioma subsequent to treatment of Hodgkin's disease: case report and review.
Radiation-induced neoplasms of the central nervous system generally present as meningioma or sarcoma. Spinal cord glioma after radiation therapy is rare and half of the cases documented occurred after treatment of Hodgkin's disease.A 39-year-old male presented with a 1-month history of gradually worsening neck ache and paraparesis. The patient had been treated for stage IB Hodgkin's disease 9 years previously with combined therapy: MOPP-ABV and a 40-Gray mediastinal radiotherapy from T1 to T10. Magnetic resonance imaging disclosed an intramedullary lesion from C6 to T2 and histopathological examination from biopsy demonstrated a malignant glioma. Despite chemotherapy and additional radiotherapy, the patient's neurological status worsened and he died 11 months after initial presentation. We suggest a strategy aimed solely at obtaining a tissue diagnosis to differentiate myelitis from tumor, and, in the event of tumor, confirming the strong likelihood of a high histopathological grade. The very limited survival associated with these tumors regardless of therapy advocates palliative therapies without attempting complete resection.


Neonatal morbidity and outcome of live born premature babies after attempted illegal abortion with misoprostol.
Misoprostol is a synthetic prostaglandin currently employed to induce labor. Association with illegal abortion has been reported; however, neonatal outcome and morbidity after a failed attempt of abortion has not been described. To report the association between misoprostol self-medication and preterm labor and to assess perinatal risk factors, morbidity and early outcomes. We conducted a prospective study of all very low birth weight (VLBW) infants delivered in Hospital Fernando Fonseca, during a 5-year period. VLBW infants were assigned to misoprostol group (MG) when preterm delivery was attributed to misoprostol and matched with newborns with similar gestational age, birth- weight, and gender. During the study period 311 VLBW infants were born. Nineteen belonged to misoprostol group (MG) and 58 were selected for controls. Mothers from MG were significantly younger (21.5 vs 27.5, p = 0.001) and from African origin (74 vs 31%, p = 0.006), had significantly less prenatal care (21 vs 67%, p = 0.000), less antenatal steroids (5 vs 50%, p = 0.001), and were delivered less often by C-section (11 vs 60%, p = 0.000). MG infants had significantly higher rates of patent ductus arteriosus (58 vs 29%, p = 0.031) and chronic lung disease (47 vs 14%, p = 0.026). Mortality rate at 3 months was similar in both groups, but the incidence of abnormal neurodevelopment at 1 year of age was significantly higher in the MG (50 vs 16%, p= 0.02). The worse outcome of MG infants seems to be determined by prenatal, natal, and postnatal factors and we believe that misoprostol is probably a significant adjuvant cofactor.


Inhibition of the cutaneous response to antigen by a thromboxane-synthetase inhibitor (OKY-046) in allergic dogs.
We studied the effect of a selective thromboxane-synthetase inhibitor, sodium (E)-3-[4-(1-imidazolymethyl)-phenyl]-2-propanoate) (OKY-046) on the late-phase response to antigen in ragweed-sensitized dogs. Skin biopsies were performed before and 1, 6, and 24 hours after ragweed injection. OKY-046 was infused (100 micrograms.kg-1.min) from 1 hour before until 6 hours after intracutaneous ragweed in five dogs. The early clinical response to ragweed (wheal at 20 minutes) was not changed by OKY-046. A late-phase response (induration at 6 hours) was not observed in any of the OKY-046-treated dogs but was present at 6 hours in 4/5 dogs without OKY-046. Typical mast cells responded similarly in both groups with progressive degranulation during 24 hours. Maximal degranulation of atypical mast cells was delayed to 6 hours with OKY-046, whereas these cells responded completely at 1 hour without OKY-046. The inflammatory response to ragweed followed the same pattern in both groups, but the numbers of each cell type were decreased with OKY-046. With OKY-046, the cutaneous response to histamine was not changed significantly from baseline at 6 hours but was increased (p less than 0.05) at 24 hours, whereas without OKY-046, histamine response was significantly increased at 6 hours (p less than 0.001) and 24 hours (p less than 0.01). We conclude that OKY-046 alters the antigen-induced response of atypical mast cells, the subsequent cellular and clinical late-phase response, and prevents the increase in histamine response.


Norvaline is accumulated after a down-shift of oxygen in Escherichia coli W3110.
Norvaline is an unusual non-proteinogenic branched-chain amino acid which has been of interest especially during the early enzymological studies on regulatory mutants of the branched-chain amino acid pathway in Serratia marcescens. Only recently norvaline and other modified amino acids of the branched-chain amino acid synthesis pathway got attention again when they were found to be incorporated in minor amounts in heterologous proteins with a high leucine or methionine content. Earlier experiments have convincingly shown that norvaline and norleucine are formed from pyruvate being an alternative substrate of alpha-isopropylmalate synthase, however so far norvaline accumulation was not shown to occur in non-recombinant strains of E. coli. Here we show that oxygen limitation causes norvaline accumulation in E. coli K-12 W3110 during grow in glucose-based mineral salt medium. Norvaline accumulates immediately after a shift to oxygen limitation at high glucose concentration. On the contrary free norvaline is not accumulated in E. coli W3110 in aerobic cultures. The analysis of medium components, supported by transcriptomic studies proposes a purely metabolic overflow mechanism from pyruvate into the branched chain amino acid synthesis pathway, which is further supported by the significant accumulation of pyruvate after the oxygen downshift. The results indicate overflow metabolism from pyruvate as necessary and sufficient, but deregulation of the branched chain amino acid pathway may be an additional modulating parameter. Norvaline synthesis has been so far mainly related to an imbalance of the synthesis of the branched chain amino acids under conditions were pyruvate level is high. Here we show that simply a downshift of oxygen is sufficient to cause norvaline accumulation at a high glucose concentration as a consequence of the accumulation of pyruvate and its direct chain elongation over alpha-ketobutyrate and alpha-ketovalerate.Although the flux to norvaline is low, millimolar concentrations are accumulated in the cultivation broth, which is far above the level which has been discussed for being relevant for misincorporation of norvaline into recombinant proteins. Therefore we believe that our finding is relevant for recombinant protein production but also may even have implications for the physiology of E. coli under oxygen limitation in general.


[Extending preimplantation genetic diagnosis to HLA typing: the French exception].
Umut-Talha, a "sibling savior", was born on 26 January 2011 at Beclère Hospital after embryo selection at the Paris preimplantation genetic diagnosis (PGD) center. His birth revived the controversy over "double PGD". This procedure, authorized in France since 2006, allows couples who already have a child with a serious, incurable genetic disease, to opt for PGD in order to select a healthy embryo that is HLA-matched to the affected sibling and who may thus serve as an ombilical cord blood donor. The procedure is particularly complex and the baby take-home rate is still very low. Double PGD is strictly regulated in France, and candidate couples must first receive individual authorization from the Biomedicine Agency. In our experience, these couples have a strong desire to have children, as reflected by the large number of prior spontaneous pregnancies (25% of couples). Likewise, most of these couples request embryo transfer even when there is no HLA-matched embryo, which accounts for more than half of embryo transfers. The controversy surrounding this practice has flared up again in recent weeks, over the concepts of "designer babies" and "double savior siblings" (the baby is selected to be free of the hereditary disease, and may also serve as a stem cell donor for the affected sibling).


Utilisation and Tolerability of Aliskiren in the Primary Care Setting in England.
Aliskiren (Rasilez), a direct renin inhibitor, is indicated for the treatment of essential hypertension. A postmarketing prescription-event monitoring (PEM) study was conducted in England to monitor the safety and utilization of aliskiren. Summary statistics and event incidence densities were calculated. The cohort consisted of 6385 individuals with a median age of 68 years (interquartile range, 59-76). Aliskiren was largely prescribed for its licensed indication of hypertension (93.3%) and was reported as "effective" by the prescriber in 77.4% of individuals. Frequently reported clinical events during treatment were diarrhea (3.1% of on-treatment events), malaise/lassitude (3.0%), and nausea/vomiting (1.2%), which were also common reasons for treatment cessation. Renal events were rare, with 24 cases probably or possibly related to aliskiren use, and four of which were classified as acute renal failure using RIFLE (Risk Injury Failure Loss End-Stage Kidney Disease) criteria. These results should be used in conjunction with other clinical and pharmacoepidemiologic studies to optimize the safe prescribing of aliskiren.


RN-BSN completion programs: equipping nurses for the future.
The Institute of Medicine has outlined important components needed in nursing education to prepare the nursing workforce of the future. Previously published work on RN to BSN education has focused mainly on mode of delivery. The purpose of this paper is to examine RN to BSN program components for the facilitation of academic progression, innovative mechanisms of student engagement, and the curricular components that prepare graduates to meet future nursing challenges. Academic progression factors discussed include those relevant to recruiting RNs to BSN completion programs and factors important to retaining them through graduation. Recommendations for student engagement include the creation of honors programs, ethics teams, and practicum and service learning experiences. Suggestions for curriculum possibilities specifically address meeting the call of the Institute of Medicine report including content in community/public health, informatics, evidence-based practice, ethics, and health policy.


Sleep disturbance is associated with mild cognitive impairment: a community population-based cross-sectional study.
Sleep is conducive to the elimination of brain metabolites and the recovery of brain function. However, the relationship between sleep disturbance and Mild Cognitive Impairment is not fully been determined. This was a community population-based cross-sectional study. A total of 1,443 participants from a village in the suburbs of Xi'an, China were enrolled in 2017. Sleep quality was evaluated using the Pittsburgh sleep quality index (PSQI), and sleep disturbance was defined as a PSQI score > 5. Mini-Mental State Examination (MMSE) was used to assess cognitive function and Mild Cognitive Impairment(MCI) was defined as the MMSE score less than cutoff values and meets the diagnostic criteria. Univariate and multivariate analyses were used to analyze the relationships between sleep disturbance and MCI. Among 1,443 subjects, 69(4.78%) had MCI, and 830 (57.52%) had sleep disturbance. In bivariate analysis, MCI was associated with sleep disturbance (ρ = 0.094, P<0.001). In the binary logistic regression, MCI was positively associated with the sleep disturbance (OR = 2.027, 95%CI = 1.112-3.698, P = 0.021). In the internal constitution of PSQI, MCI was negatively associated with the habitual sleep efficiency (OR = 0.447, 95%CI = 0.299-0.669, P < 0.001). Compared with waking up before or at 7 am, waking up after 7 am (OR = 0.555, 95%CI = 0.309-0.995, P = 0.048), or 8 am (OR = 0.296, 95%CI = 0.097-0.902, P = 0.032) was probably more likely to have normal cognition. However, people who slept more than 8 h a day might be more likely to suffer from MCI (OR = 5.560, 95%CI = 1.419-21.789, P = 0.014). Sleep disturbance is associated with Mild Cognitive Impairment. However, the causal relationship between them is not clear. It needs to be further studied.


The power of randomization by sex in multilocus genetic evolution.
Many hypotheses have been proposed for how sexual reproduction may facilitate an increase in the population mean fitness, such as the Fisher-Muller theory, Muller's ratchet and others. According to the recently proposed mixability theory, however, sexual recombination shifts the focus of natural selection away from favoring particular genetic combinations of high fitness towards favoring alleles that perform well across different genetic combinations. Mixability theory shows that, in finite populations, because sex essentially randomizes genetic combinations, if one allele performs better than another across the existing combinations of alleles, that allele will likely also perform better overall across a vast space of untested potential genotypes. However, this superiority has been established only for a single-locus diploid model. We show that, in both haploids and diploids, the power of randomization by sex extends to the multilocus case, and becomes substantially stronger with increasing numbers of loci. In addition, we make an explicit comparison between the sexual and asexual cases, showing that sexual recombination is the cause of the randomization effect. That the randomization effect applies to the multilocus case and becomes stronger with increasing numbers of loci suggests that it holds under realistic conditions. One may expect, therefore, that in nature the ability of an allele to perform well in interaction with existing genetic combinations is indicative of how well it will perform in a far larger space of potential combinations that have not yet materialized and been tested. Randomization plays a similar role in a statistical test, where it allows one to draw an inference from the outcome of the test in a small sample about its expected outcome in a larger space of possibilities-i.e., to generalize. Our results are relevant to recent theories examining evolution as a learning process. This article was reviewed by David Ardell and Brian Golding.


A visual identification key utilizing both gestalt and analytic approaches to identification of Carices present in North America (Plantae, Cyperaceae).
Images are a critical part of the identification process because they enable direct, immediate and relatively unmediated comparisons between a specimen being identified and one or more reference specimens. The Carices Interactive Visual Identification Key (CIVIK) is a novel tool for identification of North American Carex species, the largest vascular plant genus in North America, and two less numerous closely-related genera, Cymophyllus and Kobresia. CIVIK incorporates 1288 high-resolution tiled image sets that allow users to zoom in to view minute structures that are crucial at times for identification in these genera. Morphological data are derived from the earlier Carex Interactive Identification Key (CIIK) which in turn used data from the Flora of North America treatments. In this new iteration, images can be viewed in a grid or histogram format, allowing multiple representations of data. In both formats the images are fully zoomable.


Is there a significant interaction effect between apolipoprotein E rs405509 T/T and ε4 genotypes on cognitive impairment and gray matter volume?
Evidence demonstrates that the T allele of the single-nucleotide polymorphism rs405509 in the apolipoprotein E (APOE) promoter is a risk factor for Alzheimer's disease. However, it is unknown whether rs405509 T allele synergizes with the APOE ε4 allele in influencing cognition and brain structure. We analyzed the interaction effect of the rs405509 T allele and the APOE ε4 allele on cognitive ability and brain gray matter volume among elderly people. The subjects were grouped into four groups according to APOE and rs405509 genotypes. Significant interaction effects were found between rs405509 and APOE on general mental status, memory and attention. Analysis of the whole brain gray matter showed a significantly positive interaction effect between rs405509and APOE on the right inferior temporal gyrus and right fusiform gyrus (alphasim correction P < 0.001). In addition, there was a significant relationship between cognitive ability and gray matter volume. The data indicate that the APOE rs405509 T homozygote modulates the effect of APOE ε4 on both cognitive performance and brain gray matter structure.


Meal induced gut hormone secretion is altered in aerobically trained compared to sedentary young healthy males.
Postprandial insulin release is lower in healthy aerobically trained (T) compared to untrained (UT) individuals. This may be mediated by a lower release of the two incretin hormones [glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)] in T. The aim of this study was to assess and compare gut hormone response and satiety changes after a liquid meal intake in young, healthy T and UT males. Postprandial gut hormone release and subjective feelings of hunger, satiety, fullness and prospective food consumption were assessed before and frequently for the following 3 h after a 200 ml liquid meal (1,260 kJ and 27, 41 and 32 energy % as protein, carbohydrates and fat, respectively) in ten T and ten UT young, healthy male subjects. The insulin and GIP responses were markedly lower in T than UT and correlated during the first 30 min after the liquid meal. Baseline GLP-1 concentration was higher in T versus UT, but the response in the following 3 h after a liquid meal was similar in T and UT. Satiety measures did not differ between groups throughout the test. It is possible that in aerobically T subjects, a lower GIP release is partly responsible for a lower postprandial incretin stimulated insulin secretion.


Instillation of 5% Povidone-Iodine Ophthalmic Drops Decreases the Respiratory Rate in Children Undergoing Strabismus Surgery: A Randomized Controlled Trial.
To investigate the effects of topical application of ophthalmic 5% povidone-iodine eye drops, which has been reported to cause apnea in spontaneously breathing children during general anesthesia. The authors conducted a randomized, controlled, single-blinded study comparing the effect of balanced salt solution eye drops and povidone-iodine eye drops on respiration in spontaneously breathing children during general anesthesia with sevoflurane via a laryngeal mask airway. Fifty patients received balanced salt solution eye drops and 50 patients received 5% povidone-iodine eye drops. None of the control patients had a significant change in respiration. Thirty of the 50 (60%) povidone-iodine patients had a slowing of respiration within the first 6 breaths after eye drop instillation (P < .001). The median time of respiratory pause in those 30 patients was 18.5 seconds (range: 4.36 to 96.2 seconds). Among the povidone-iodine patients, children with a history of a prior tonsillectomy and adenoidectomy and/or bilateral myringotomy had a 7.2 times greater chance of experiencing a change in respiration after instillation of the povidone-iodine eye drops. Topical application of 5% povidone-iodine eye drops causes a slowing and pause in spontaneous ventilation in a majority of children prior to strabismus surgery. This may represent activation of the diving reflex. [J Pediatr Ophthalmol Strabismus. 2019;56(6):378-382.].


Dynamic regulation of nucleosome positioning in the human genome.
The positioning of nucleosomes with respect to DNA plays an important role in regulating transcription. However, nucleosome mapping has been performed for only limited genomic regions in humans. We have generated genome-wide maps of nucleosome positions in both resting and activated human CD4+ T cells by direct sequencing of nucleosome ends using the Solexa high-throughput sequencing technique. We find that nucleosome phasing relative to the transcription start sites is directly correlated to RNA polymerase II (Pol II) binding. Furthermore, the first nucleosome downstream of a start site exhibits differential positioning in active and silent genes. TCR signaling induces extensive nucleosome reorganization in promoters and enhancers to allow transcriptional activation or repression. Our results suggest that H2A.Z-containing and modified nucleosomes are preferentially lost from the -1 nucleosome position. Our data provide a comprehensive view of the nucleosome landscape and its dynamic regulation in the human genome.


The importance of uncertainties in scenario analyses--A study on future ecosystem service delivery in Flanders.
Land use is rapidly changing and is significantly affecting ecosystem service delivery all around the world. The socio-economic context and political choices largely determine land use change. This land use change, driven by socio-economic pressures, will impact diverse elements of the environment including, for example, air quality, soil properties, water infiltration and food and wood production, impacts that can be linked to the provisioning of ecosystem services. To gain more insight into the effects of alternative socio-economic developments on ecosystem service delivery, land use change models are being coupled to ecosystem service delivery models to perform scenario analyses. Although the uncertainty of the results of these kind of scenario analyses are generally far from negligible, studies rarely take them into account. In this study, a cellular automaton land use change model is coupled to Bayesian belief network ecosystem service delivery models to facilitate the study of error propagation in scenario analysis. The proposed approach is applied to model the impact of alternative socio-economic developments on ecosystem service delivery in Flanders, Belgium and to assess the impact of land use allocation uncertainty on the uncertainty associated to future ecosystem service delivery. Results suggest that taking into account uncertainties may have an effect on policy recommendations that come out of the scenario analysis. However, in this study, uncertainties in the applied ecosystem service models were dominant, reducing the importance of accounting for land use allocation uncertainty.


Diagnostic value of thyroid imaging reporting and data system combined with BRAFV600E mutation analysis in Bethesda categories III-V thyroid nodules.
Fine needle aspiration biopsy is a crucial method for preoperative diagnosis of thyroid nodules. However, thyroid nodules classified as Bethesda categories III-V cannot obtain definite cytological results. Our aim was to study the diagnostic value of thyroid imaging reporting and data system combined with BRAFV600E mutation analysis in Bethesda categories III-V thyroid nodules, so as to provide more precise direction for the follow-up treatments. A total of 174 Bethesda categories III-V thyroid nodules performed TIRADS and BRAFV600E mutation analysis were included in the study. We retrospectively analyzed the ultrasound features as well as the results of BRAFV600E mutation of the 174 thyroid nodules. In the multiple regression analysis models, ultrasound features including lobulated or irregular margin, punctate echogenic foci, and shape with taller-than-wide were statistically significant in malignant nodules (p < 0.05). The area under the curve of the combination of TIRADS and BRAFV600E increased to 0.925, which were much higher than TIRADS (0.861) and BRAFV600E (0.804) separately. Combined diagnosis was of the greatest value to identify Bethesda III-V thyroid nodules definitely, especially with higher sensitivity (93%) and accuracy (90%).


Seroprevalence of human herpesvirus 8 in human immunodeficiency virus 1-positive and human immunodeficiency virus 1-negative populations in Japan.
To determine the seroprevalence of human herpesvirus 8 (HHV8) among human immunodeficiency virus 1 (HIV-1)-positive (HIV-1+) and HIV-1-negative (HIV-1-) populations in Japan, 276 HIV-1+ patients and 1,000 HIV-1- blood donors were enrolled in this study. Antibodies against HHV8 latency-associated nuclear antigen (LANA) were examined through indirect immunofluorescent assay by using a B-cell line that was infected latently with HHV8 (body cavity-based lymphoma 1). An HHV8- and Epstein-Barr virus-negative B-cell line (Ramos) was used as a control. Thirty-two seropositive cases against LANA (anti-LANA+) were identified among the 276 HIV-1+ patients who were studied. Five cases were foreigners living in Japan. The risk factor of all 27 Japanese cases was unprotected sexual intercourse, and the great majority of these cases (23 in 27; 85%) reported homosexual/bisexual behavior. Anti-LANA+ status correlated with the presence of sexually transmitted diseases, such as amoeba and HBV infection, further suggesting male homosexual behavior as the main route of HHV8 transmission in Japan. Only two LANA+ cases were identified among 1,000 HIV- blood donors in Japan; thus, seroprevalence of HHV8 identified by LANA was estimated to be 0.2% among HIV-1- populations in this country.


Clathrin interaction and subcellular localization of Ce-DAB-1, an adaptor for protein secretion in Caenorhabditis elegans.
Growth factors must be secreted appropriately to co-ordinate cell proliferation, specification and movement during development and to control cell numbers and migrations in adult animals. Previous results showed that the secretion of the Caenorhabditis elegans fibroblast growth factor homologue, EGL-17, from vulval precursor cells in vivo involves the cytoplasmic adaptor protein Ce-DAB-1 and two lipoprotein receptors that bind Ce-DAB-1 and EGL-17. Here, we confirm the Ce-DAB-1 requirement for EGL-17 secretion using mutant animals. In vitro, Ce-DAB-1 binds to clathrin and APT-4, the C. elegans homologue of the alpha-adaptin subunit of adaptor protein 2 (AP2), and weakly to the gamma-appendage domains of APT-1 (AP1gamma-adaptin) and APT-9 (GGA protein). In tissue-culture cells, Ce-DAB-1 localizes to various compartments, including AP2-containing vesicles near the cell surface and perinuclear vesicles that contain AP1. The latter also contain Rab8, but not Rab5 or Rab11, as well as proteins en route from the trans Golgi network (TGN) to the surface. In vivo, EGL-17 secretion was inhibited by depletion of apt-1, apt-9 or ce-rab-8 and partially inhibited by RNAi of ce-rab-5, consistent with an important role for these proteins in the secretion of EGL-17 in vivo. These results suggest that Ce-DAB-1 might co-ordinate the assembly of endocytic or secretory vesicles in vivo and may mediate EGL-17 secretion directly, by recruiting clathrin to lipoprotein receptors at the TGN, or indirectly, by affecting lipoprotein receptor endocytosis and recycling.


Mesenteric steal and carotid stenosis relief of symptoms with carotid endarterectomy.
This is a case report of a patient with mesenteric steal, severe carotid stenosis, and cerebral symptoms that occurred with eating. Symptoms occurred when carotid flows were documented to be decreased. Carotid endarterectomy stabilized carotid flows and ameliorated symptoms.


Prolactin and immunomodulation.
To review the recent exploration of the role of prolactin in immune function. Studies published that were identified through a MEDLINE search as well as through the bibliographies of those articles enumerated. Both humoral and cell-mediated immunity are compromised in hypophysectomized rats. The reintroduction of prolactin to these animals restores their immune function. Prolactin receptors have been identified on the membranes of white blood cells; furthermore, lymphocytes have been shown to secrete prolactin. Cyclosporin A directly competes with prolactin for binding to these receptors. This may be one mechanism of the immunosuppressive action of cyclosporin A. In addition to diminished levels, prolactin excess may also result in immunocompromise. This has been demonstrated in lactating female and prolactin-treated male rats, as well as hyperprolactinemic humans. Finally, prolactin abnormalities have been described in a number of immunologic disorders, including systemic lupus erythematosus, adjuvant arthritis, experimental allergic encephalomyelitis, and autoimmune uveitis and thyroid disease. Dopaminergic agents that suppress serum prolactin are now being used in clinical trials to treat a number of autoimmune diseases and to prevent rejection in organ transplant recipients. At physiologic levels, prolactin is trophic for lymphocytes. Either too much, or too little, prolactin may be immunosuppressive. Lymphocytes produce a prolactin-like substance. Prolactin may play a role in a number of autoimmune processes.


Lack of efficacy of monepantel against Teladorsagia circumcincta and Trichostrongylus colubriformis.
After reports of the apparent failure of monepantel to reduce the egg counts of goats on a farm in the lower North Island of New Zealand, faecal egg count reduction tests were conducted in goats and lambs resident on the property, and a confirmatory, slaughter study was conducted using 12 sheep, sourced elsewhere, that were grazed on the farm for approximately 5 weeks. In the egg count reduction test in goats, 8 animals were given monepantel at 3.9 mg/kg (just over 1.5× the sheep dose rate of 2.5mg/kg), whilst four received 7.7 mg/kg (just over 3× the sheep dose). In the egg count reduction test in sheep, 15 lambs were treated with 3.0mg/kg of monepantel. For the confirmatory study, the sheep were housed indoors for 2 weeks before half were treated with 2.9 mg/kg monepantel and the animals were killed for worm counts 9 days later. There was no evidence of efficacy in either egg count reduction test, or in the goats, the two dose rates used appeared equally ineffective. Likewise, there were no significant reductions in egg counts or worm burdens in the slaughter study. Monepantel was ineffective against at least two gastrointestinal nematode species, Teladorsagia circumcincta and Trichostrongylus colubriformis. These findings represent the first report from the field of resistance having developed to the anthelmintic monepantel with severe resistance developing in more than one species after being administered on 17 separate occasions to different stock classes and in less than 2 years of the product first being used on the farm in question.


Spotted fever group Rickettsia and Borrelia sp. cooccurrence in Amblyomma sculptum in the Midwest region of Brazil.
More than 70 tick species are found in Brazil, distributed over five genera and including main vectors of infectious disease agents affecting both animals and humans. The genus Amblyomma is the most relevant for public health in Brazil, wherein Amblyomma aureolatum, Amblyomma ovale and Amblyomma sculptum have been incriminated as vectors of Rickettsia and Borrelia pathogens. The objective of this study was to investigate the presence of Rickettsia spp. and Borrelia spp. in ticks in the Brazilian mid-western savannah. DNA extraction, PCR for Borrelia spp. (flgE gene) and Rickettsia spp. (ompA and gltA genes) and subsequent sequencing were performed. A total of 1875 ticks were collected and identified as A. sculptum except for two Amblyomma coelebs ticks. Molecular evidence for Borrelia spp. and Rickettsia parkeri was found in A. sculptum. This is the first molecular evidence for R. parkeri in A. sculptum ticks in the Midwest region and Borrelia spp. circulating in a tick of the Amblyomma genus in Brazil.


Complementary feeding practices and their determinants among children aged 6-23 months in rural Bangladesh: evidence from Bangladesh Integrated Household Survey (BIHS) 2018-2019 evaluated against WHO/UNICEF guideline -2021.
Appropriate Complementary feeding (CF) practices play a crucial role in determining child nutrition, growth, and development. This study seeks to examine CF practices and their predictors among children aged 6 to 23 months in rural Bangladesh according to the most recently updated WHO/UNICEF guidelines for CF. A total of 665 children aged 6 to 23 months from the Bangladesh Integrated Household Survey (BIHS) 2018-2019 dataset were analyzed. The WHO/UNICEF guidelines for CF were followed to evaluate each of the nine CF practice indicators. We also examined the effect of the child, maternal, household, and community-level factors on different CF components using multiple logistic regression analyses. Approximately two-thirds of the children initiated complementary feeding on time (63.5%) but had zero vegetable or fruit consumption (63.2%). More than half (52.4%) and the majority (86.5%) of children had minimum meal frequency and minimum milk feeding frequency, respectively. On the other hand, the proportion of minimum dietary diversity was quite low (18.3%), as reflected in the alarming prevalence (16.3%) of minimum acceptable diet. Egg and/or flesh food, sweet beverage, and unhealthy food consumption were 23.3%, 2.5%, and 12.2%, respectively. Child age, mothers' education level, antenatal care visit, household food security, monthly household income, and place of residence were found to be associated with CF practices. When compared to results obtained using the previous guideline, the new one has resulted in a lower prevalence of Introduction of solid, semi-solid, or soft foods (ISSF), Minimum dietary diversity (MDD), Minimum meal frequency (MMF), and Minimum acceptable diet (MAD). It is crucial to convey the new knowledge for better child feeding and nutrition as the country prepares to apply the new guideline.


Omission of concurrent chemoradiation after a response to neoadjuvant chemotherapy in locally advanced rectal cancer with a synchronous liver metastasis: a note of caution.
There is clear evidence to support the use of pre-operative concurrent chemo-radiotherapy (CRT) in locally advanced rectal cancer. In the UK, most patients are selected for treatment if the resection margin is predicted to be involved. The selection criteria used includes primary tumours that threaten the resection margins on high-resolution pelvic MRI and low tumours requiring abdominoperineal excision. There is no consensus, however, to guide the treatment of patients who present with advanced rectal disease and synchronous, potentially resectable, metastatic disease. This case illustrates the potential risk of omitting radiation following a good response to neoadjuvant systemic chemotherapy.


An ecological investigation of the capacity to follow simultaneous speech and preferential detection of ones' own name.
Many situations require focusing attention on one speaker, while monitoring the environment for potentially important information. Some have proposed that dividing attention among 2 speakers involves behavioral trade-offs, due to limited cognitive resources. However the severity of these trade-offs, particularly under ecologically-valid circumstances, is not well understood. We investigated the capacity to process simultaneous speech using a dual-task paradigm simulating task-demands and stimuli encountered in real-life. Participants listened to conversational narratives (Narrative Stream) and monitored a stream of announcements (Barista Stream), to detect when their order was called. We measured participants' performance, neural activity, and skin conductance as they engaged in this dual-task. Participants achieved extremely high dual-task accuracy, with no apparent behavioral trade-offs. Moreover, robust neural and physiological responses were observed for target-stimuli in the Barista Stream, alongside significant neural speech-tracking of the Narrative Stream. These results suggest that humans have substantial capacity to process simultaneous speech and do not suffer from insufficient processing resources, at least for this highly ecological task-combination and level of perceptual load. Results also confirmed the ecological validity of the advantage for detecting ones' own name at the behavioral, neural, and physiological level, highlighting the contribution of personal relevance when processing simultaneous speech.


Can light-field photography ease focusing on the scalp and oral cavity?
Capturing a well-focused image using an autofocus camera can be difficult in oral cavity and on a hairy scalp. Light-field digital cameras capture data regarding the color, intensity, and direction of rays of light. Having information regarding direction of rays of light, computer software can be used to focus on different subjects in the field after the image data have been captured. A light-field camera was used to capture the images of the scalp and oral cavity. The related computer software was used to focus on scalp or different parts of oral cavity. The final pictures were compared with pictures taken with conventional, compact, digital cameras. The camera worked well for oral cavity. It also captured the pictures of scalp easily; however, we had to repeat clicking between the hairs on different points to choose the scalp for focusing. A major drawback of the system was the resolution of the resulting pictures that was lower than conventional digital cameras. Light-field digital cameras are fast and easy to use. They can capture more information on the full depth of field compared with conventional cameras. However, the resolution of the pictures is relatively low.


A Multidimensional Connectomics- and Radiomics-Based Advanced Machine-Learning Framework to Distinguish Radiation Necrosis from True Progression in Brain Metastases.
We introduce tumor connectomics, a novel MRI-based complex graph theory framework that describes the intricate network of relationships within the tumor and surrounding tissue, and combine this with multiparametric radiomics (mpRad) in a machine-learning approach to distinguish radiation necrosis (RN) from true progression (TP). Pathologically confirmed cases of RN vs. TP in brain metastases treated with SRS were included from a single institution. The region of interest was manually segmented as the single largest diameter of the T1 post-contrast (T1C) lesion plus the corresponding area of T2 FLAIR hyperintensity. There were 40 mpRad features and 6 connectomics features extracted, as well as 5 clinical and treatment factors. We developed an Integrated Radiomics Informatics System (IRIS) based on an Isomap support vector machine (IsoSVM) model to distinguish TP from RN using leave-one-out cross-validation. Class imbalance was resolved with differential misclassification weighting during model training using the IRIS. In total, 135 lesions in 110 patients were analyzed, including 43 cases (31.9%) of pathologically proven RN and 92 cases (68.1%) of TP. The top-performing connectomics features were three centrality measures of degree, betweenness, and eigenvector centralities. Combining these with the 10 top-performing mpRad features, an optimized IsoSVM model was able to produce a sensitivity of 0.87, specificity of 0.84, AUC-ROC of 0.89 (95% CI: 0.82-0.94), and AUC-PR of 0.94 (95% CI: 0.87-0.97).


Diffusion Tensor Tractography of the Cerebellar Peduncles in Prematurely Born 7-Year-Old Children.
The objective of this study was to correlate neurodevelopmental outcome of preterm-born children and their perinatal clinical and imaging characteristics with diffusion magnetic resonance imaging (MRI) measures of the three cerebellar peduncles at age 7. Included in this prospective longitudinal study were 140 preterm-born children (<30 weeks gestation) who underwent neurodevelopmental assessment (IQ, motor, language, working memory) and diffusion-weighted imaging (DWI) at age 7 years. White matter tracts in the superior, middle, and inferior cerebellar peduncles were delineated using regions of interest drawn on T2-weighted images and fractional anisotropy (FA) maps. Diffusion measures (mean diffusivity (MD) and FA) and tract volumes were calculated. Linear regression was used to assess relationships with outcome. The severity of white matter injury in the neonatal period was associated with lower FA in the right superior cerebellar peduncle (SCP) and lower tract volumes of both SCPs and middle cerebellar peduncles (MCPs). In the MCP, higher IQ was associated with lower MD in the whole group and higher FA in right-handed children. In the SCP, lower motor scores were associated with higher MD and higher language scores were associated with higher FA. These associations remained significant in multivariable models. This study adds to the body of literature detailing the importance of cerebellar involvement in cognitive function related to reciprocal connections with supratentorial structures.


Peak left atrial longitudinal strain is associated with all-cause mortality in patients with ventricular functional mitral regurgitation.
Chronic mitral regurgitation promotes left atrial (LA) remodeling. However, the significance of LA dysfunction in the setting of ventricular functional mitral regurgitation (FMR) has not been fully investigated. Our aim was to assess the prognostic impact of peak atrial longitudinal strain (PALS), a surrogate of LA function, in patients with FMR and reduced left ventricular ejection fraction (LVEF). Patients with at least mild ventricular FMR and LVEF < 50% under optimized medical therapy who underwent transthoracic echocardiography at a single center were retrospectively identified in the laboratory database. PALS was assessed by 2D speckle tracking in the apical 4-chamber view and the study population was divided in two groups according to the best cut-off value of PALS, using receiver operating characteristics (ROC) curve analysis. The primary endpoint-point was all-cause mortality. A total of 307 patients (median age 70 years, 77% male) were included. Median LVEF was 35% (IQR: 27 - 40%) and median effective regurgitant orifice area (EROA) was 15mm2 (IQR: 9 - 22mm2). According to current European guidelines, 32 patients had severe FMR (10%). During a median follow-up of 3.5 years (IQR 1.4 - 6.6), 148 patients died. The unadjusted mortality incidence per 100 persons-years increased with progressively lower values of PALS. On multivariable analysis, PALS remained independently associated with all-cause mortality (adjusted hazard ratio 1.052 per % decrease; 95% CI: 1.010 - 1.095; P = 0.016), even after adjustment for several (n = 14) clinical and echocardiographic confounders. PALS is independently associated with all-cause mortality in patients with reduced LVEF and ventricular FMR.


Development of a serum-free medium using computer-assisted factorial design and analysis.
Stepwise screening of media supplements using factorial design and analysis was employed in the development of serum-free medium for a recombinant Chinese hamster ovary cell line. The effects (growth and target protein production) of different combinations were measured at two time points to ensure adequate response. The results were analysed by a computer program specialized in factorial analysis. The formulation deduced from the previous experiment was used as the new basal medium for the next screening. Certain significant nutrients were studied again in a more 'advanced' formulation in order to analyse the potential synergistic effects with new media components. Compared to cells grown in serum-containing medium, cells adapted to the final formulation of the serum-free medium had a comparable growth rate but a four fold increase in the active protein production.


Efficacy and safety of three inflation methods of the laryngeal mask airway Ambu® Auraonce™: a randomized controlled study.
The laryngeal mask airway (LMA) is commonly used for airway management. Cuff hyperinflation has been associated with complications, poor ventilation and increased risk of gastric insufflation. This study was designed to determine the best cuff inflation method of AuraOnce™ LMA during bronchoscopy and EBUS (Endobronquial Ultrasound Bronchoscopy) procedure. We designed a Randomized controlled, doble-blind, clinical trial to compare the efficacy and safety of three cuff inflation methods of AuraOnce™ LMA. 210 consenting patients scheduled for EBUS procedure under general anesthesia, using AuraOnce™ LMA were randomized into three groups depending on cuff insufflation: residual volume (RV), half of the maximum volume (MV), unchanged volume (NV). Parameters regarding intracuff pressure (IP), airway leak pressure (OLP), leakage volume (LV) were assessed, as well as postoperative complications (PC). 201 (95.7%) patients completed the study. Mean IP differed between groups (MV: 59.4 ± 32.4 cm H2O; RV: 75.1 ± 21.1 cm H2O; NV: 83.1 ± 25.5 cmH20; P < 0.01). The incidence of IP > 60 cmH2O was lower in the MV group compared to the other two (MV: 20/65(30.8%); RV:47/69 (68.1%); NV 48/67 (71.6%); p < 0.01). The insertion success rate was 89,6% (180/201) at first attempt, with no difference between groups (p = 0.38). No difference between groups was found either for OLP (p = 0.53), LV (p = 0.26) and PC (p = 0.16). When a cuff manometer is not available, a partial inflation of AuraOnce™ LMA cuff using MV method allows to control intracuff pressure, with no significant changes of OLP and LV compared to RV and NV insufflation method.Registration clinical trial: NCT04769791.


Antimicrobial oral lavage reduces the SARS-CoV-2 load in intubated patients: randomized clinical trial.
The oral cavity can be a reservoir for SARS-CoV-2 and may play a crucial role in the viral transmission in the hospital environment. To investigate whether an oral hygiene protocol with chlorhexidine (CHX) used alone and in combination with hydrogen peroxide (HP) in the intensive care unit was effective in reducing the SARS-CoV-2 viral load in the oral cavity. SARS-CoV-2 viral load was measured on oral fluid samples collected from patients undergoing orotracheal intubation. The study sample was randomly in: CHX group (n = 19) - oral rinse using only 0.12% CHX solution; HP+CHX group (n = 24) - oral rinse with 1.5% HP and 0.12% CHX. The samples were collected before the interventions (T0), immediately (T1), 30 minutes (T2) and 60 minutes (T3) after the procedure. A significant viral load reduction was observed at T1 (mean ± SD:-0.57 ± 0.19 log10;-73.2%;p = 0.022) in the HP+CHX group. No statistically significant differences between any time points were observed in the CHX group. The HP+CHX oral rinses significantly reduced the SARS-CoV-2 viral load in the oral fluid immediately after the procedure. The CHX oral rinse alone did not result in any significant viral load reductions.


Association of adverse childhood experiences with shaking and smothering behaviors among Japanese caregivers.
Shaking and smothering in response to infant crying are life-threatening child abuse. Parental childhood abuse history is known to be one of the most robust risk factors for abusing their offspring. In addition to childhood abuse history, other adverse childhood exposures (ACEs) need to be considered due to co-occurrence. However, few studies have investigated the impact of ACEs on caregivers shaking and smothering their infant. This study aims to investigate the association of ACEs with shaking and smothering among caregivers of infants in Japan. A questionnaire was administered to caregivers participating in a four-month health checkup between September 2013 and August 2014 in Chiba City, Japan, to assess their ACEs (parental death, parental divorce, mentally ill parents, witness of intimate partner violence, physical abuse, neglect, psychological abuse and economic hardship), and shaking and smothering toward their infants (N=4297). Logistic regression analysis was used to examine the cumulative and individual impacts of ACEs on shaking and smothering. Analyses were conducted in 2015. A total of 28.3% reported having experienced at least one ACE during their childhood. We found that only witness of IPV had a significant association with shaking of infant (OR=1.93, 95% CI: 1.03-3.61). The total number of ACEs was not associated with either shaking or smothering. Our findings suggest that shaking and smothering in response to crying can occur regardless of ACEs. Population-based strategies that target all caregivers to prevent shaking and smothering of infants are needed.


Coronary artery bifurcation lesions: a review and update on classification and interventional techniques.
Coronary artery bifurcation lesions pose a particular challenge in the field of interventional cardiology. Coronary bifurcation interventions are associated with higher rate of short- and long-term complications. There are many coronary artery bifurcation lesion classifications published in the literature. The goal of this article is to update and review current schemes of coronary artery bifurcation lesion classifications and interventional techniques.


Bioaccumulation of polybrominated diphenyl ethers by the freshwater benthic amphipod Gammarus pulex.
This study reports on the relationship between polybrominated diphenyl ether (PBDE) levels in water, sediment, and the benthic macroinvertebrate Gammarus pulex, which plays a major ecological role in freshwater ecosystems. Samples were taken in a periurban watershed (near Paris, France), and PBDEs were systematically detected in sediment (≤727 ng g(-1) OC) and G. pulex (≤264 ng g(-1) lipids). PBDEs were also occasionally detected in the water column at low levels (∑ PBDEs < 1.5 ng L(-1)). The log values of bioaccumulation factors were in the range 7.8 ± 0.1-8.3 ± 0.4 L kg(-1) for tetra- and penta-BDEs, which were the only ones quantified in the dissolved phase of river water. Meanwhile, levels of individual tri- to hepta-PBDE congeners in G. pulex generally positively correlated with sediment levels, suggesting an equilibrium situation. Biota-to-sediment accumulation factors (BSAFs) of tri-hepta BDEs were congener specific and were in the range 0.5 ± 0.3-2.6 ± 1.2. For several PBDEs, BSAF values deviated from the expected range, likely because of in vivo metabolism.


Endoscopic Removal of an Intramurally Ingrown Foreign Body in the Angular Fold of the Stomach.
Eine 67-jährige Patientin mit chronischer Gastritis stellte sich wegen zunehmenden epigastrischen Schmerzen in der Notaufnahme vor. Auf Grund einer nicht wegweisenden Initialdiagnostik wurde eine Computertomographie des Abdomens durchgeführt. In dieser stellte sich ein Fremdkörper am Magenausgang dar. Unter radiologischer Kontrolle erfolgte ein anspruchsvolles, zeitintensives endoskopisches Freipräparieren des Fremdkörpers. Nach postinterventionellem Abschwellen der Schleimhaut konnte in einer zweiten Sitzung ein Fischknochen geborgen werden. Die aufwendige endoskopische Intervention bewahrte die Patientin vor einer Operation.


Analysis of the brain regions involved in myoclonus produced by intracerebral picrotoxin.
Picrotoxin caused myoclonic jerking of the opposite forelimb when applied to the striatum and the cortical surface of rat brain. Intrastriatal picrotoxin increased [3H]2-deoxyglucose uptake by the ipsilateral frontal cortex, thalamus and subthalamic nucleus. Electrolyte and ibotenic acid lesions made in the globus pallidus prevented striatally evoked myoclonus without affecting the movements elicited from the cortex. Electrolytic lesions in the subthalamic nucleus and thalamus affected striatally evoked myoclonus more than the cortically elicited response. It is concluded that striato-pallidal-thalamic-cortical circuitry is responsible for striatally evoked myoclonus.


Topical vitamin D3 derivatives in treating hyperkeratotic palmoplantar eczema: a report of five patients.
The treatment of hyperkeratotic palmoplantar eczema is notoriously difficult. A considerable number of patients do not or only partially respond to the current treatments such as topical corticosteroids, topical keratolytics, or PUVA therapy. The purpose of this pilot study was to look for an alternative treatment for hyperkeratotic palmoplantar eczema. We treated five patients with topical vitamin D3 derivatives (calcipotriol 50 microg/g and maxacalcitol 25 microg/g ointments). The lesions almost disappeared after 2 to 8 weeks of treatment in four patients and extremely improved with a seven week treatment in one patient. No adverse effect was observed during or after the treatment, and routine laboratory investigations were within normal ranges. When relapses occurred, they responded well to retreatment. Although the study is preliminary, the results suggest that vitamin D3 derivatives offer a safe, effective alternative form of treatment for recalcitrant hyperkeratotic palmoplantar eczema.


Excessive ovarian response is associated with increased expression of interleukin-2 in the periimplantation endometrium.
To evaluate and compare in vivo expression of T helper type 1 (Th1) cytokines in the peri-implantation endometrium of infertile patients between natural and stimulated cycles. An observational study. A tertiary assisted reproduction center. Infertile patients. Uterine flushings and endometrial biopsies were collected 7 days after LH surge in natural cycles or after hCG injection in stimulated cycles. T helper type 1 cytokines were determined by immunolocalization and by ELISA. Natural cycles were classified as group A (n = 17), whereas stimulated cycles with peak serum E(2) of <or=20,000 pmol/L (moderate responders) and with peak serum E(2) of >20,000 pmol/L (excessive responders) were classified as group B (n = 32) and group C (n = 32), respectively. Higher serum E(2) concentration was associated with increased expressions of interleukin (IL)-2 in the endometrium and uterine flushing. Group C demonstrated a statistically significantly higher IL-2 expression in endometrial biopsies by glandular and stromal immunostaining and by ELISA, compared with group A and group B. There was no difference in IL-2 concentration between group A and group B. Interferon-gamma protein concentration was comparable for the three groups. Increased expression of IL-2 in the peri-implantation endometrium may account for the lower implantation rate in excessive responders.


A rapid, direct, quantitative, and label-free detector of cardiac biomarker troponin T using near-infrared fluorescent single-walled carbon nanotube sensors.
Patients with chest pain account for 10% of US emergency room visits according to data from the Center for Disease Control and Prevention (2013). For triage of these patients, cardiac biomarkers troponin I and T are endorsed as standard indicators for acute myocardial infarction (AMI, or heart attack). Thus, there is significant interest in developing a rapid, point-of-care (POC) device for troponin detection. In this work, a rapid, quantitative, and label-free assay, which is specific for cardiac troponin T (cTnT) detection, using fluorescent single-walled carbon nanotubes (SWCNTs), is demonstrated. Chitosan-wrapped carbon nanotubes are cross-linked to form a thin gel that is further functionalized with nitrilotriacetic acid (NTA) moieties. Upon chelation of Ni(2+) , the Ni(2+) -NTA group binds to a hexa-histidine-modified troponin antibody, which specifically recognizes the target protein, troponin T. As the troponin T binds to the antibody, the local environment of the sensor changes, allowing direct troponin detection through intensity changes in SWCNT bandgap fluorescence. This platform represents the first near-infrared SWCNT sensor array for cTnT detection. Detection can be completed within 5 min, demonstrating a linear response to cTnT concentration and an experimental detection limit of 100 ng mL(-1) (2.5 nm). This platform provides a promising new tool for POC AMI detection in the future. Moreover, the work presents two new methods of quantifying the number of amines and carboxylic groups, respectively, in a carbon hydrogel matrices.


Photo-activatable ternary complex based on a multifunctional shielding material for targeted shRNA delivery in cancer treatment.
A photo-activatable ternary complex (PTC) consisting of multifunctional shielding material (MSM) with photosensitizer (PS)-conjugated chondroitin sulfate and polyethyleneimine based binary complexes containing epidermal growth factor receptor (EGFR)-shRNA delivery for CD44 targeted cancer therapy has been developed. The PTC has a negative surface charge of -37.9 mV, and a size of approximately 90 nm, and the ternary complexes were found to be stable against plasma proteins. The stable nanostructure of PTC especially could enable CD44-receptor mediated tumor-targeted delivery and PS-mediated endosomal disruption for efficient gene silencing, and an enhanced rate of cancer cell death was achieved both in vitro and in vivo. This suggests that PTC could represent a promising strategy for the delivery of other therapeutic genes for cancer therapy.


Endogenous free polyamines and their role in fruit set of low and high parthenocarpic ability citrus cultivars.
Endogenous free polyamines (PAs), putrescine, spermidine and spermine, from developing fruitlets of Citrus species (Citrus unshiu Marc. and Citrus clementina Hort ex Tanaka) which differ in their parthenocarpic ability, and from uniflowered leafy and leafless inflorescences differing in their ability to set, have been determined by dansylation and separation of dansyl derivatives by HPLC. No significant differences in PAs content were observed between species or between leafy and leafless inflorescences which, nevertheless, significantly differed in fruit set. However, significant differences in their content were found in developing fruitlets, depending on the preceding flowering intensity of the tree and on the fruitlet load. These results suggest that, in Citrus, PAs may act as a nitrogen source rather than a regulator of fruit set.


The comparison of cell-mediated immunity induced by immunization with porin, viable cells and killed cells of Salmonella typhimurium.
A marked level of cell-mediated immunity (CMI) to Salmonella typhimurium-infection in mice, as determined by acquired resistance, delayed-type hypersensitivity, interleukin-2 production and interferon-gamma production, was induced by immunization with porin or viable cells but not with killed cells of S. typhimurium LT2. When the up-regulation of immune system to each immunogen was studied by comparing increases of Ia-bearing macrophages, the immunization with porin or viable cells, but not killed cells, could stimulate the immune system for more than 14 days. Interleukin-1 (IL-1) production of macrophages to each immunogen was also examined; the result showed that immunization with porin or viable cells could induce a notable level of IL-1 production, while killed cells could not. However, when the abilities to induce these immune responses were compared between UV-killed and heat-killed cells, UV-killed cells were superior to heat-killed cells. These results suggested that the ineffectiveness of immunogen that lacked CMI-inducing ability might be ascribed to the denaturation of antigen and the insufficient inductions of Ia-bearing macrophages and IL-1 production.


Disclosure of genetic risk in the family: A survey of the Flemish general population.
Results from genomic sequencing often have implications not just for patients but also for their relatives. To date, there are no studies in Belgium exploring whether potential relatives would want to be informed of a genetic risk in the family and their preferences on different approaches to disclosure. We surveyed the attitudes of the Flemish general population (n = 407) towards receiving genetic information from their family members, including attitudes towards breaches in confidentiality, preferences for who communicates genetic risk and how the information is communicated, and policy approaches to nondisclosure. Most participants wanted to be informed of their genetic risk and receive genetic testing to confirm their diagnosis. Most preferred to be informed of genetic risk by a close family member, but that when given the choice between a distant family member and a clinician, most participants preferred to be contacted by a clinician. In Belgium there is currently no clear legal pathway for clinicians to directly initiate contact with at-risk relatives, but the responses from members of the Flemish population analyzed in this study indicate that this approach to disclosure of genetic risk deserves further consideration. Our findings indicate that the general population would support legislation allowing clinicians to inform relatives even in cases where the patient did not want to inform them. As this is not currently allowed in Belgium, policy alternatives should be considered.


Pediatric rectal and perineal problems.
Infants and children have surgical disorders of the anus, rectum, and perineum that are largely quite different from the pathology seen in adults. This article presented some of these problems, which physicians encounter, and outlined methods of their management.


Model-based approach and signal detection theory to evaluate the performance of recruitment centers in clinical trials with antidepressant drugs.
The objective of this study was to characterize the performance of each recruitment center in multicenter clinical trials and to provide criteria to discriminate between informative and noninformative centers using the signal detection approach. Data were derived from the GlaxoSmithKline Clinical Trial database on paroxetine and bupropion, totaling 4,016 subjects with major depressive disorders (MDDs) across nine trials. The probability of observing clinically relevant difference of active treatment from placebo was estimated in each center as a function of the placebo Hamilton Depression Rating Scale (HAMD-17) scores at baseline and at week 8. The center's performance was defined using the posterior probability (PP) of detecting a signal of a treatment effect. Only 60% of the centers were classified as informative. In these centers, the signal of treatment effect increased by approximately 80%. The signal detection approach appears to be a useful methodology to rank the performance of recruitment centers and to classify each center as informative or not in respect of detection of clinically relevant signals of efficacy. A further analysis indicated that a minimal sample of four subjects is required in order to predict the typical placebo response in each center.