How does IPM 3.0 look like (and why do we need it in Africa)?
The concept of Integrated Pest Management (IPM) was introduced sixty years ago to curb the overuse of agricultural pesticides, whereby its simplest version (IPM 1.0) was aiming at reducing the frequency of applications. Gradually, agro-ecological principles, such as biological control and habitat management, were included in IPM 2.0. However, throughout this time, smallholder farmers did not improve their decision-making skills and continue to use hazardous pesticides as their first control option. We are therefore proposing a new paradigm - IPM 3.0 - anchored on 3 pillars: 1) real-time farmer access to decision-making, 2) pest-management options relying on science-driven and nature-based approaches, and 3) the integration of genomic approaches, biopesticides, and habitat-management practices. We are convinced that this new paradigm based on technological advances, involvement of youth, gender-responsiveness, and climate resilience will be a game changer. However, this can only become effective through redeployment of public funding and stronger policy support.


Building Resilient Food Systems in Africa.
Climate change constitutes a significant threat to food security and poverty reduction in Africa, and the food system is severely off target in meeting development goals. Policy response should focus on investing in agricultural public goods, scaling up digital solutions, and developing innovative finance mechanisms to enhance resilience.


[Research of bimingan granule on dendritic cell in allergic rhinitis mice].
To investigate the mechanism. We isolate the mouse bone marrow cells and cultured with rGM-CSF and rIL-4 to stimulate bone marrow cells to transfer to immature dendritic cells. And then the immature dendritic cells were costimulated with ILPS and different concentrations of Bimingan Granule. MHC II, CD80, CD86 were detected by flow cytometer and TNF-alpha, IL-1beta, IL-6 and IL-10 were quantified by ELISA. Our results showed that Bimingan Granule may significantly inhibit the differentiation of immature dendritic cells to mature dendritic cells.


Molecular and clinical insights of matrix metalloproteinases into cancer spread and potential therapeutic interventions.
Matrix metalloproteinases (MMPs) are the group of enzymes that belong to the family of zinc dependent endopeptidases. These proteases degrade collagen and other important proteins in extracellular matrix (ECM) and regulate cytoskeletal proteins, growth factors, chemokines and cytokines, thereby play significant role during organogenesis and normal tissue turnover. Recent studies highlight the tumorigenic functions of MMPs by modulating tumor microenvironment. Dysregulated MMPs/TIMPs cause an imbalance in crucial cell signals, and lead to serious pathological conditions related to inflammation, uncontrolled cell growth, ECM degradation, increased cell migration, cell death resistance, replicative immortality and the establishment of metastatic niche at secondary sites. Recently established correlation between the higher expression of active MMPs and cancer aggressiveness makes them probable target candidate of cancer diagnosis, prognosis and therapy. The present review focuses on the tumourigenic functions of MMPs and recent advancements in the development of MMP inhibitors of therapeutic potential in cancer treatment.


Calcium-Alginate Tissue Gels (CATG): Proof-of-concept biomaterial development.
Hydrogels are desirable materials to the field of forensic science and offer many advantages for use as tissue simulants in research and training scenarios. In this work, we demonstrate a proof-of-concept study for our biomaterial described as the Calcium-Alginate Tissue Gel (CATG). CATG biomaterials integrate functional DNA strands designed to amplify with known human primer sets for genetic profiling. Our range of CATG materials demonstrate successful DNA extraction, PCR amplification and genotyping when both fresh and aged for 21 days. The rheological properties of the CATGs were measured and the incorporation of DNA into the CATGs was assessed. Overall, the CATGs demonstrated increased viscoelastic behavior with the addition of DNA. In addition, two methods of sampling were considered, where it was found that cutting a sample of the dried CATG produced higher allele peak heights in the genotype compared to swabbing. Overall, our CATG biomaterials can be designed for multiple applications in forensic science with tunable properties for various training and research needs.


G2, G3, and complete basis set calculations of the thermodynamic properties of cis- and trans-triazene.
Following our recent study on triazane, we present a follow-up study on the thermodynamic properties of triazane's unsaturated analog, triazene. We predict optimized structural parameters, vibrational frequencies, enthalpies of formation, enthalpies of combustion, specific enthalpies of combustion, and proton affinities. Our results indicate that the cis form of triazene has a specific enthalpy of combustion of -15.2 kJ g(-1) and the trans form has a specific enthalpy of combustion of -14.7 kJ g(-1).


Ultrastructural Alterations in Granular Neurons of the Dentate Fascia Caused by Intrahippocampal Injection of Beta-Amyloid 1-42.
The deposition of beta-amyloid (Aβ) in the brain is detected in Alzheimer's disease and during ageing. Until now, ultrastructural studies of changes caused by Aβ in the dentate gyrus are very scarce. The effects of Aβ 1-42 injection into the CA1 field of rat hippocampus were studied by electron microscopy. In 2 weeks after injection of aggregated Aβ in low concentrations, destructive changes were seen in the structure of dentate gyrus cells, which consisted in a decrease in the number of dentate gyrus neurons and axo-dendritic synapses. These changes were accompanied by enlargement of the endoplasmic reticulum cisterns and widening of the active zones of synapses. Thus, injection of aggregated Aβ 1-42 into the hippocampus led to irreversible (a decrease in the number of neurons and axo-dendritic synapses, agglutination of synthetic vesicles) and adaptive changes (an increase in the sizes of endoplasmic reticulum cisterns and active zones of synapses) in dentate gyrus neurons aimed at the maintenance of functional activity of the nervous system.


Current status, advances, challenges and perspectives on biosensors for COVID-19 diagnosis in resource-limited settings.
As the COVID-19 pandemic has profoundly impacted human life, prompt diagnostic tests are becoming an essential part of the social activities. However, the expensive and time-consuming laboratory-based traditional methods do not suffice the enormous needs for massive number of tests, especially in resource-limited settings. Therefore, more affordable, rapid, sensitive and specific field-practical diagnostic devices play an important role in the fight against the disease. In this review, we present the current status and advances in the biosensing technologies for diagnosing COVID-19, ranging from commercial achievements to research developments. Starting from a brief introduction to the disease biomarkers, this review summarizes the working principles of the biosensing technologies, followed by a review of the commercial products and research advances in academia. We recapitulate the literatures with a wide scope of bio/marker detections, embracing nucleic acids, viral proteins, human immune responses, and other potential bio/markers. Further, the challenges and perspectives for their employment in future point-of-care applications are discussed, with an extended appraisal on the practical strategies to enlarge the testing capability without high cost. This critical review provides a comprehensive insight into the diagnostic tools for COVID-19 and will encourage the industry and academia in the field of diagnostic biosensing for future evolvement to large-scale point-of-care screening of COVID-19.


Geophagic lead nephropathy: case report.
An adult presenting with anemia and seizures was found to have lead poisoning. Chelation therapy undertaken before the source of exposure was known was accompanied by clinical improvement. Recurrence of an excessive body lead burden despite chelation led to the discovery of pica for lead-contaminated garden soil. Lead nephropathy progressed when the geophagia was resumed.


Isolation of Yeasts from Guajillo Pepper (Capsicum annuum L.) Fermentation and Study of Some Probiotic Characteristics.
Three yeast strains were isolated from the spontaneous fermentation of guajillo pepper: Hanseniaspora opuntiae, Pichia kudriavzevii, and Wickerhamomyces anomalus, which were identified by amplification of the ITS/5.8S ribosomal DNA. Some probiotic characteristics of these strains were evaluated and compared with one commercial probiotic yeast (Saccharomyces boulardii). The survival percentage of all the yeasts was similar to that of the commercial product. They showed different hydrophobicity characteristics with hydrocarbons, autoaggregation > 90%, and characteristics of co-aggregation with pathogenic microorganisms. The adhesion capacity to mucin of the three yeast samples was similar to the reference yeast. The antioxidant activity of the yeasts varied between 155 and 178 μM Trolox equivalents. All exhibited cholesterol reduction capacity, and W. anomalus was able to decrease up to 83% of cholesterol after 48 h of incubation. The 7.5-fold concentrated H. opuntiae supernatant had antimicrobial activity against Salmonella enterica ser. Typhimurium ATCC 14028 and Candida albicans ENCBDM2; tests suggest this activity against S. Typhimurium is due to a proteinaceous metabolite with a weight between 10 and 30 kDa. Among the yeasts, P. kudriavzevii exhibited the highest protective effect on the viability of Lactobacillus casei Shirota in gastric and intestinal conditions. These results suggest that yeasts isolated from guajillo pepper may have a probiotic potential.


Autonomic dysfunction in COVID-19 patients receiving mechanical ventilation: A cross-sectional study.
Coronavirus disease 2019 (COVID-19) can damage cardiac tissue by increasing troponin levels and inducing arrhythmias, myocarditis, and acute coronary syndrome. To analyze the impact of COVID-19 on cardiac autonomic control in mechanically ventilated intensive care unit (ICU) patients. This cross-sectional analytical study of ICU patients of both sexes receiving mechanical ventilation was conducted in a tertiary hospital. Patients were divided into COVID-19-positive (COVID(+)) and COVID-19-negative (COVID(-)) groups. Clinical data were collected and heart rate variability (HRV) records obtained using a heart rate monitor. The study sample comprised 82 subjects: 36 (44%) in the COVID(-) group (58.3% female; median age, 64.5 years) and 46 (56%) in the COVID(+) group (39.1% females; median age, 57.5 years). The HRV indices were lower than the reference values. An intergroup comparison identified no statistically significant differences in the mean normal-to-normal (NN) interval, standard deviation of the NN interval, or root mean square of successive differences in NN intervals. The COVID(+) group had an increased low frequency (P = 0.05), reduced high frequency (P = 0.045), and increased low frequency/high frequency (LF/HF) ratio (P = 0.048). There was a weak positive correlation between LF/HF and length of stay in the COVID(+) group. Patients who received mechanical ventilation had lower overall HRV indices. COVID(+) patients who received mechanical ventilation had lower vagal HRV components. These findings likely indicate clinical applicability, as autonomic control impairments are associated with a greater risk of cardiac death.


The membrane fluidity concept revisited by polarized fluorescence spectroscopy on different model membranes containing unsaturated lipids and sterols.
Quantitative analysis of time-resolved anisotropy measurements of DPH or TMA-DPH in lipid vesicles yields more than one mathematically correct solution. The solutions differ with respect to the average orientation and to the reorientational dynamics of the probe molecules in the bilayer. This leads to quite opposite results regarding the effects of cholesterol on membrane fluidity. One solution predicts an increase in fluidity, the other a decrease. Angle-resolved fluorescence depolarization (AFD) measurements of probes in oriented lipid bilayers enable determination of the average orientation of the probes in the bilayer and, if the fluorescence decay function is known, of the reorientational dynamics. Analysis of AFD measurements of DPH and TMA-DPH show that increasing unsaturation leads to a decrease in molecular order and a decrease in reorientational dynamics (= fluidity) of the probes. At temperatures above the phase transition of the lipids, the addition of cholesterol causes an increase in molecular order and an increase in reorientational dynamics (= fluidity). The plant sterol stigmaterol, which is structurally closely related to cholesterol, has different effects than cholesterol. The effects vary with the structure of the surrounding lipids. The membrane fluidity concept as it was originally proposed by Chapman attempts to describe the structural and dynamic properties of lipids in a membrane using one single parameter indicated as 'membrane fluidity'. Our results show that it is necessary to distinguish between structural parameters describing molecular order and motion parameters describing molecular dynamics, thus supporting a similar suggestion by Seelig and Seelig. In order to be useful, the membrane fluidity concept has to be limited to the parameters describing molecular dynamics.


The role of sarcoplasmic protein in hydrostatic pressure-induced myofibrillar protein denaturation.
To observe the role of sarcoplasmic protein (SP) on myofibrillar protein (MP) denaturation under a hydrostatic pressure (HP), MP isolated from bovine muscle was treated with 300 MPa by increasing concentrations of SP (0, 0.8, 1.6, and 3.2 mg/ml) from bovine. SDS-PAGE patterns of soluble proteins in 0.1M NaCl (pH 7.4) indicated that a protein (about 100 kDa) from MP decreased with increasing concentrations of SP and that a 97 kDa protein from SP observed with 0.1 MPa was not observed with 300 MPa. SDS-PAGE patterns of soluble proteins in 0.6 M NaCl (pH 7.4) and Ca-ATPase activity showed that the denaturation of myosin heavy chain (MHC) was accelerated with increasing SP concentrations with the 300 MPa treatment. Thus, the addition of SP enhanced HP-induced denaturation of MHC and of a protein from MP of about 100 kDa.


Women diagnosed with gestational diabetes mellitus do not carry antibodies against minor islet cell antigens.
Women with gestational diabetes mellitus (GDM) have considerable risk for developing both type 1 and type 2 diabetes in life. Autoantibodies against glutamic acid decarboxylase (GAD65) and tyrosine phosphatase (IA-2) are strongly associated with autoimmune diabetes and can be useful in early identification of the development of type 1 diabetes in women with GDM. On the other hand antibodies against minor islet antigens in adults can be predictors for autoimmune polyendocrine syndrome. The aim of our study was to estimate the prevalence of autoantibodies against minor antigens-tissue transglutaminase (TTG), ICA12, and 21-hydroxylase (21-0H)-in GDM patients from southern India. Eighty-six serum samples from GDM subjects and 114 samples from healthy controls were tested for the presence of GAD65 and IA-2Ab as well as for the presence of 21-OH, TTG, and ICA12Ab by radiobinding assay with in vitro translated recombinant human 35S-GAD65, IA-2, TTG, ICA12, and 21-OH antigens. We observed the presence of GAD65 or IA-2 autoantibodies in 41% (35/86) of GDM patients, while none of the patients tested positive for any of the minor autoantibodies. Our results demonstrate that there is a high prevalence of autoantibodies in GDM subjects that are at higher risk of developing autoimmune diabetes later, but none of the patients carries antibodies against minor antigens, which could predict autoimmune polyendocrine syndrome in adults.


Conservative management of a case of medial epicondylosis in a recreational squash player.
This case study was conducted to evaluate the treatment and management of a patient presenting with medial elbow pain diagnosed as medial epicondylosis. A 35 year old male presented with medial elbow pain of 4-6 weeks duration that worsened after playing squash. A COURSE OF FASCIAL STRIPPING TECHNIQUES WAS INITIATED, INCLUDING: cross friction massage, instrument assisted fascial stripping to the medial epicondyle area and over the belly of the pronator teres muscle, ischemic compression of a trigger point in the pronator teres, active assisted compressions to the trigger point noted in the pronator teres, and mobilizations of the carpals, specifically the scaphoid. Instructions were given to the patient regarding icing the elbow and daily eccentric exercises. At a one year follow up, the patient reported complete resolution of symptoms with no recurrence. Conservative management, including eccentric exercises, mobilizations, and fascial stripping appear to be beneficial in the treatment of medial epicondylosis.


In vitro Antimicrobial Activity of Acne Drugs Against Skin-Associated Bacteria.
Acne is a common skin affliction that involves excess sebum production and modified lipid composition, duct blockage, colonization by bacteria, and inflammation. Acne drugs target one or more of these steps, with antibiotics commonly used to treat the microbial infection for moderate to severe cases. Whilst a number of other acne therapies are purported to possess antimicrobial activity, this has been poorly documented in many cases. We conducted a comparative analysis of the activity of common topical acne drugs against the principal etiological agent associated with acne: the aerotolerant anaerobic Gram-positive organism Propionibacterium acnes (recently renamed as Cutibacterium acnes). We also assessed their impact on other bacteria that could also be affected by topical treatments, including both antibiotic-sensitive and antibiotic-resistant strains, using broth microdilution assay conditions. Drugs designated specifically as antibiotics had the greatest potency, but lost activity against resistant strains. The non-antibiotic acne agents did possess widespread antimicrobial activity, including against resistant strains, but at substantially higher concentrations. Hence, the antimicrobial activity of non-antibiotic acne agents may provide protection against a background of increased drug-resistant bacteria.


Endometrial ossification, an unusual finding in an infertility clinic. A case report.
Ectopic bony endometrial tissue was found accidentally during routine diagnostic laparoscopy and curettage that were part of the examination of a woman with a history of primary infertility for seven years. She conceived two months after the second curettage.


Effect of high potassium diets on the vascular and renal prostaglandin system in stroke-prone spontaneously hypertensive rats.
High potassium (K) diets are known to have a protective effect on the endothelium and the kidney against hypertensive injury independent of blood pressure change. Vasodepressor prostaglandins (PGs) have been shown to be cytoprotective in various tissues. This study investigated the effect of high K diets on the vascular and renal eicosanoid system in stroke-prone spontaneously hypertensive rats (SHRsp). Eicosanoid production by the aorta and eicosanoid content in the renal cortex were examined in SHRsp rats fed high NaCl diets containing either 0.5% K (normal) or 2.1% K (high). Although the high K diet did not affect the blood pressure, SHRsp on the high K diet had less thickening of the aortic wall than SHRsp on the normal K diet (-15%, p < 0.001). The aortic strip of the high K SHRsp produced less vasodepressor PG than that of the normal K SHRsp when they were incubated in a medium (PGI2 -45%, p < 0.003; PGE2 -34%, p < 0.001). Furthermore, when the aorta was perfused in a chamber at hypertensive pressure, again the high K aorta showed reduced PGI2 production as compared with the normal K aorta (intravascular side -52%, p < 0.01). Eicosanoid content in the renal cortex was not significantly different between the normal K and the high K SHRsp (PGI2 79 vs 87 ng/g dry weight; PGE2 214 vs 233 ng/g dry weight). Thus, the high K diet reduced vascular eicosanoid production but did not alter eicosanoid content in the renal cortex. The reduced vascular eicosanoid production in the high K SHRsp may reflect the reduced necessity for cytoprotective vasodepressor PG against vascular injuries.


[Solitary bone cysts of the ulna (author's transl)].
The solitary bone cysts occurs most frequently in the upper humerus and femur in 75% of the cases, and it is very seldom located in the ulna, in 0.5--1.5%. This report deals with the treatment results of two children, five and six years old, suffering from solitary bone cysts of the lower end of the ulna. In one case a subtotal resection of the cyst was carried out and the defect was bridged with an autologous iliac bone graft. In the other case the patient was treated by curettage, and the defect was filled in with an autologous bone graft and cancellous bone out of the tibia. In both cases complete cure of the tumorlike lesion was obtained and no loss of function or deformity of the forearm was observed 12 and 16 years after operation. In the X-ray picture at that time there was no alteration on the length, form or structure of the bone.


Cyclooxygenases and Prostaglandins in Tumor Immunology and Microenvironment of Gastrointestinal Cancer.
Chronic inflammation is a known risk factor for gastrointestinal cancer. The evidence that nonsteroidal anti-inflammatory drugs suppress the incidence, growth, and metastasis of gastrointestinal cancer supports the concept that a nonsteroidal anti-inflammatory drug target, cyclooxygenase, and its downstream bioactive lipid products may provide one of the links between inflammation and cancer. Preclinical studies have demonstrated that the cyclooxygenase-2-prostaglandin E2 pathway can promote gastrointestinal cancer development. Although the role of this pathway in cancer has been investigated extensively for 2 decades, only recent studies have described its effects on host defenses against transformed epithelial cells. Overcoming tumor-immune evasion remains one of the major challenges in cancer immunotherapy. This review summarizes the impacts of the cyclooxygenase-2-prostaglandin E2 pathway on gastrointestinal cancer development. Our focus was to highlight recent advances in our understanding of how this pathway induces tumor immune evasion.


Characteristic analysis of continuous new particle formation events in Hefei: A case study of the May Day holiday in China.
Studying the characteristics of new particle formation (NPF) is conducive to exploring the impact of atmospheric particulate matter on the climate, environment, and human health. The particle number size distributions (5.6-560 nm) of aerosols were measured using a fast mobility particle sizer (FMPS) from 1 to 11 May 2019. The clean atmosphere was one of the basic conditions for the occurrence of this continuous new particle formation events. It started between 9:00 and 12:00, and it mainly ended after 20:00. The growth rate (GR) and condensation sink (CS) values in Hefei were 2.98 ± 0.97 nm·h-1 and (3.0 ± 0.4) × 10-2 s-1, respectively. Back trajectory clustering analysis revealed that the mass concentration of the air masses from the southeastern part of Henan Province and the southern part of Anhui Province surrounding the study area were relatively high. The analysis results of the potential source contribution function (PSCF) and the concentration weighted trajectory (CWT) methods show that in addition to local pollution, the long-distance transport of pollutants in the Yangtze River Delta (YRD) greatly contributed to the accumulation modal particulate concentration in Hefei. Moreover, the population affected by PM2.5 during the observation period reached 8.19 × 104, accounting for 1.08% to the total population in Hefei. The premature death cases associated with PM2.5 reached 8.35 × 102. This study is helpful to understand the main influencing factors of consecutive NPF events and the health risks of fine particles.


On estimating processing variance: commentary and reanalysis of Kail's "Developmental functions for speeds of cognitive processes".
A recent paper by Kail (1988) in this journal appears to contain a significant error in the data analysis. The "goodness-of-fit" coefficients reported which suggest that overall about 94% of the variance can be accounted for by the model seem to be a substantial overestimation as a result of inappropriate procedures for statistical modeling. Using the data made available to us by Kail, we have reanalyzed these results. The corrected values range from 0.9 to 92.1% for the individual tasks with an overall average between 40 and 60%. We suggest that the support for the original conclusions is considerably weaker than reported.


Comparison of functionality and structural stability of bacteriorhodopsin reconstituted in partially fluorinated dimyristoylphosphatidylcholine liposomes with different perfluoroalkyl chain lengths.
Amphiphilic molecules with one or more perfluoroalkyl groups (Rf, CnF2n+1), which show peculiar interfacial properties, are attracting much attention in membrane protein science. We recently have developed a partially fluorinated dimyristoylphosphatidylcholine (DMPC) with a perfluorobutyl group in the hydrophobic chain terminal (F4-DMPC) and demonstrated that F4-DMPC is a promising material for incorporating membrane proteins. Moreover, we have found out that membrane properties of a series of partially fluorinated DMPCs with different Rf chain lengths (Fn-DMPCs) vary in a significant Rf chain length-dependent manner. In the present study, structural and functional properties of a membrane protein bacteriorhodopsin (bR) in the Fn-DMPC (n = 4, 6, and 8) membranes (bR/Fn-DMPC) are investigated using several physicochemical techniques. Regardless of the Rf chain lengths, bR/Fn-DMPCs retain native-like structural and functional properties at 30 °C, unlike bR molecules in DMPC vesicles. In particular, bR/F6-DMPC, which is in the fluid phase at 30 °C, shows flash-induced transient absorption changes very similar to the native purple membrane (PM) and very high thermal stability of bR trimers comparable to the PM. Structural and functional properties of bR/Fn-DMPCs are discussed compared to the PM and bR/DMPC.


A phase I/II dose-escalation multi-center study to evaluate the safety of infusion of natural killer cells or memory T cells as adoptive therapy in coronavirus pneumonia and/or lymphopenia: RELEASE study protocol.
Moderate/severe cases of COVID-19 present a dysregulated immune system with T cell lymphopenia and a hyper-inflammatory state. This is a study protocol of an open-label, multi-center, double-arm, randomized, dose-finding phase I/II clinical trial to evaluate the safety, tolerability, alloreactivity, and efficacy of the administration of allogeneic memory T cells and natural killer (NK) cells in COVID-19 patients with lymphopenia and/or pneumonia. The aim of the study is to determine the safety and the efficacy of the recommended phase 2 dose (RP2D) of this treatment for patients with moderate/severe COVID-19. In the phase I trial, 18 patients with COVID-19-related pneumonia and/or lymphopenia with no oxygen requirement or with an oxygen need of ≤ 2.5 liters per minute (lpm) in nasal cannula will be assigned to two arms, based on the biology of the donor and the patient. Treatment of arm A consists of the administration of escalating doses of memory T cells, plus standard of care (SoC). Treatment of arm B consists of the administration of escalating doses of NK cells, plus SoC. In the phase II trial, a total of 182 patients with COVID-19-related pneumonia and/or lymphopenia requiring or not oxygen supplementation but without mechanical ventilation will be allocated to arm A or B, considering HLA typing. Within each arm, they will be randomized in a 1:1 ratio. In arm A, patients will receive SoC or RP2D for memory T cells plus the SoC. In arm B, patients will receive SoC or RP2D for NK cells plus the SoC. We hypothesized that SARS-CoV-2-specific memory T-lymphocytes obtained from convalescent donors recovered from COVID-19 can be used as a passive cell immunotherapy to treat pneumonia and lymphopenia in moderate/severe patients. The lymphopenia induced by COVID-19 constitutes a therapeutic window that may facilitate donor engraftment and viral protection until recovery. ClinicalTrials.gov NCT04578210 . First Posted : October 8, 2020.


Corrigendum: TRPC1 Inhibits Cell Proliferation/Invasion and Is Predictive of a Better Prognosis of Esophageal Squamous Cell Carcinoma.
[This corrects the article DOI: 10.3389/fonc.2021.627713.].


Human exposure to endocrine disrupting chemicals: effects on the male and female reproductive systems.
Endocrine disrupting chemicals (EDCs) comprise a group of chemical compounds that have been examined extensively due to the potential harmful effects in the health of human populations. During the past decades, particular focus has been given to the harmful effects of EDCs to the reproductive system. The estimation of human exposure to EDCs can be broadly categorized into occupational and environmental exposure, and has been a major challenge due to the structural diversity of the chemicals that are derived by many different sources at doses below the limit of detection used by conventional methodologies. Animal and in vitro studies have supported the conclusion that endocrine disrupting chemicals affect the hormone dependent pathways responsible for male and female gonadal development, either through direct interaction with hormone receptors or via epigenetic and cell-cycle regulatory modes of action. In human populations, the majority of the studies point towards an association between exposure to EDCs and male and/or female reproduction system disorders, such as infertility, endometriosis, breast cancer, testicular cancer, poor sperm quality and/or function. Despite promising discoveries, a causal relationship between the reproductive disorders and exposure to specific toxicants is yet to be established, due to the complexity of the clinical protocols used, the degree of occupational or environmental exposure, the determination of the variables measured and the sample size of the subjects examined. Future studies should focus on a uniform system of examining human populations with regard to the exposure to specific EDCs and the direct effect on the reproductive system.


Use of cryoprotectors and antioxidants in sturgeon semen cryopreservation.
In recent years, the possibility of increasing the low cryoresistance of sturgeon sperm by using antioxidants in basic cryoprotective media has been studied. The goal of this work was to review the current literature on impact of the cryoprotectors, well-known antioxidants and new multifunctional compounds on the activity indicators and fertilizing capability of sperm, as well as on biomarkers of cryostress. A special attention is given to the radical scavenging activity of studied compounds in relation to the highly reactive oxygen species, to prevent and negate oxidative stress damage of sturgeon sperm. Also, new trends for future research through the application of novel polyfunctional antioxidants to sturgeon sperm cryopreservation were indicated.


Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping.
Transcutaneous auricular vagus nerve stimulation (TaVNS) is a supplementary treatment for gastric symptoms resulting from dysrhythmias. The main objective of this study was to quantify the effects of 10, 40, and 80 Hz TaVNS and sham in healthy individuals in response to a 5-minute water-load (WL5) test. Eighteen healthy volunteers aged between 21 and 55 years (body mass index: 27.1 ± 3.2) were recruited. Each subject fasted for up to eight hours and participated in four 95-minute sessions, which consisted of 30 fasted baseline, 30 minutes TaVNS, WL5, and 30 minutes post-WL5. Heart rate variability was assessed using sternal electrocardiogram. Body-surface gastric mapping and bloating (/10) were recorded. One-way ANOVA with post hoc Tukey test was performed to test the difference between TaVNS protocols in terms of frequency, amplitude, bloating scores, root mean square of the successive differences (RMSSD), and stress index (SI). On average, the subjects consumed 526 ± 160 mL of water, with volume ingested correlated to bloating (mean score 4.1 ± 1.8; r = 0.36, p = 0.029). In general, the reduction in frequency and rhythm stability during the post-WL5 period in sham was normalized by all three TaVNS protocols. Both 40- and 80-Hz protocols also caused increases in amplitude during the stim-only and/or post-WL5 periods. RMSSD increased during the 40-Hz protocol. SI increased during the 10-Hz protocol but decreased during the 40- and 80-Hz protocols. TaVNS proved effective in normalizing gastric dysrhythmias by WL5 in healthy subjects by altering both parasympathetic and sympathetic pathways.


BRAF paradox breakers PLX8394, PLX7904 are more effective against BRAFV600Ε CRC cells compared with the BRAF inhibitor PLX4720 and shown by detailed pathway analysis.
PLX7904 and PLX8394 are novel BRAFV600E inhibitors-BRAFi that are designed to evade the paradoxical MAPK activation, a trait for the name "paradox breakers"-PB. Current FDA approved inhibitors (Vemurafenib, Dabrafenib, Encorafenib) although improved progression-free survival of mtBRAF melanoma patients suffer from this treatment related side effect. mtBRAF Colorectal Cancer (CRC) is resistant to the approved BRAF inhibitors, although combinatorial treatment co-targeting BRAF and EGFR/MEK is offering a promising prospect. In an effort to explore the potential of the novel BRAF inhibitors-PB to impede CRC cell proliferation, they were tested on RKO, HT29 and Colo-205 cells, bearing the BRAFV600E mutation. This study shows that the BRAF paradox breakers PLX7904 and PLX8394 cause a more prolonged MAPK pathway inhibition and achieve a stronger blockage of proliferation and reduced viability than PLX4720, the sister compound of Vemurafenib. In some treatment conditions, cells can undergo apoptosis. Genomic analysis on the more resistant RKO cells treated with PLX7904, PLX8394 and PLX4720 showed similar gene expression pattern, but the alterations imposed by the PB were more intense. Bioinformatic analysis resulted in a short list of genes representing potential master regulators of the cellular response to BRAF inhibitors' treatments. From our results, it is clear that the BRAF paradox breakers present a notable differential regulation of major pathways, like MAPK signalling, apoptosis, cell cycle, or developmental signalling pathways. Combinatorial treatments of BRAFi with Mcl-1 and Notch modulators show a better effect than mono-treatments. Additional pathways could be further exploited in novel efficient combinatorial treatment protocols with BRAFi.


Attitudes toward COVID-19 vaccine mandate: The role of psychological characteristics and partisan self-identification.
Governments around the world are increasingly considering vaccine mandates to curb the spread of COVID-19. In May 2022, we surveyed 394 residents of South Dakota to examine predictors of popular attitudes toward a COVID-19 vaccine mandate. We investigated the role of Big Five personality traits, right-wing authoritarianism, and social dominance orientation, as well as partisan self-identification, evangelical identity, and COVID-19 vaccination status. Results showed that Big Five personality traits (openness and emotional stability), right-wing authoritarianism, social dominance orientation, evangelical identity, and partisan self-identification are linked to attitudes toward a COVID-19 vaccine mandate. Our findings underscore the politicization of the COVID-19 pandemic as well as the impact of dispositional factors on attitudes toward mandatory COVID-19 vaccination.


Comparison of Listeria monocytogenes recoveries from spiked mung bean sprouts by the enrichment methods of three regulatory agencies.
Three selective enrichment methods, the United States Food and Drug Administration's (FDA method), the United States Department of Agriculture Food Safety Inspection Service's (USDA method), and the EN ISO 11290-1 standard method, were assessed for their suitability for recovery of Listeria monocytogenes from spiked mung bean sprouts. Three parameters were evaluated; the enrichment L. monocytogenes population from singly-spiked sprouts, the enrichment L. monocytogenes population from doubly-spiked (L. monocytogenes and Listeria innocua) sprouts, and the population differential resulting from the enrichment of doubly-spiked sprouts. Considerable L. monocytogenes inter-strain variation was observed. The mean enrichment L. monocytogenes populations for singly-spiked sprouts were 6.1 ± 1.2, 4.9 ± 1.2, and 6.9 ± 2.3 log CFU/mL for the FDA, USDA, and EN ISO 11290-1 methods, respectively. The mean L. monocytogenes populations for doubly-spiked sprouts were 4.7 ± 1.1, 5.5 ± 1.3, and 4.6 ± 1.4 log CFU/mL for the FDA, USDA, and ISO 11290-1 enrichment methods, respectively. The corresponding mean population differentials were 2.8 ± 1.1, 3.3 ± 1.3, and 3.6 ± 1.4 Δlog CFU/mL for the same three enrichment methods, respectively. The presence of L. innocua and resident microorganisms on the sprouts negatively impacted final levels of L. monocytogenes with all three enrichment methods.


Food neophobia across the life course: Pooling data from five national cross-sectional surveys in Ireland.
Food neophobia describes a reluctance to eat novel foods. Levels of food neophobia vary throughout life and are thought to peak in childhood. However, the trajectory of food neophobia across the life course is not fully clear. Using data from five national cross-sectional surveys in Ireland we explored levels of food neophobia in males and females aged 1-87 years. In addition, we assessed the influence of sociodemographic factors, breastfeeding and parental food neophobia on food neophobia. Food neophobia was measured using the Food Neophobia Scale in adults and adolescents and with the Children's Eating Behaviour Questionnaire in preschool and school aged children. A total of 3246 participants (female, 49.9%) were included. Food neophobia increased with age from 1 to ∼6 years, then decreased until early adulthood where it remained stable until increasing with age in older adults (>54 years). In adults, lower education level, social class and rural residency were associated with higher food neophobia. When preschool and school aged children surveys were pooled (ages 1-12), higher food neophobia was seen in males, children with lower parental education and those who were not breastfed. Sociodemographic factors were not significantly associated with food neophobia in adolescents. Breastfeeding duration was negatively associated with food neophobia in children and adolescents and parental food neophobia was positively associated with child's food neophobia in preschool and school aged children. The influence of socioeconomic factors was more pronounced in adults than in children or adolescents. However, sociodemographic factors only explained a small proportion of the variation in food neophobia across all ages. Longitudinal studies are needed to understand how changes in age or socioeconomic circumstance influence food neophobia at an individual level.


Ascorbate transport in cultured cat retinal pigment epithelial cells.
Transport of ascorbate by primary cultures of cat retinal pigment epithelial cells (RPE) was studied. Confluent primary cultures were incubated with 10-500 microM L-[carboxyl-14C] ascorbic acid in balanced salt solution (BSS) at 37 degrees C for 1 to 40 min. The uptake of radioactive ascorbate followed saturation kinetics with a Km of 42 microM and Vmax of 117 pmol min-1 microgram-1 DNA. Cells incubated with 10 microM radioactive ascorbate for 40 min showed a ratio of intracellular to extracellular radioactive ascorbate of greater than 40. The transport of ascorbate was sodium- and energy-dependent. Replacement of 150 mM NaCl in BSS with 150 mM LiCl reduced ascorbate uptake significantly. Ouabain, 2,4-dinitrophenol, alpha-D-glucose, 3-O-methyl-D-glucose, and the ascorbate analogues, D-isoascorbate and dehydroascorbate, each inhibited ascorbate uptake into RPE cells. The efflux of radioactivity into the incubation media was slow when cells were preloaded with either 50- or 500 microM radioactive ascorbate, but increased when cells preloaded with 50 microM ascorbate were incubated in the presence of excess non-radioactive ascorbate. These studies demonstrated that a sodium-dependent carrier system is involved in transport of ascorbate in primary cultures of cat RPE.


COVID-19 Vaccine Acceptance in Pregnant Women in the United States: A Systematic Review and Meta-Analysis.
Purpose: Pregnant women are vulnerable to Coronavirus Disease 2019 (COVID-19) complications, yet may hesitate to get vaccinated. It is important to identify racial/ethnic and other individual characteristics associated with COVID-19 vaccine acceptance in the United States during pregnancy. Methods: We searched PubMed, Embase, and Web of Science for articles published through January 2023 for keywords/terms related to immunization, COVID-19, and pregnancy, and performed a systematic review and meta-analysis to examine characteristics associated with vaccine acceptance. Results: Of 1,592 articles, 23 met inclusion criteria (focused on pregnant women in the United States, and their willingness or hesitation to vaccinate). Twenty-two of the studies examined receipt of ≥1 COVID-19 vaccine dose and/or intention to vaccinate, while one examined vaccine hesitancy. Vaccine acceptance rates ranged from 7% to 78.3%. Meta-analyses demonstrated that compared with Whites, Hispanics (odds ratios [OR] 0.72; 95% confidence interval [CI] 0.58-0.91) and Blacks (OR 0.44; 95% CI 0.30-0.63) had less COVID-19 vaccine acceptance, while Asians (OR 1.78; 95% CI 1.10-2.88) had greater vaccine acceptance. College graduation or more (OR 3.25; 95% CI 2.53-4.17), receipt or intention to receive the influenza vaccine (OR 3.46; 95% CI 2.22-5.41), and at least part-time employment (OR 2.12; 95% CI 1.66-2.72) were significantly associated with vaccine acceptance. Conclusions: COVID-19 vaccine nonacceptance in pregnant women is associated with Hispanic ethnicity and Black race, while acceptance is associated with Asian race, college education or more, at least part-time employment, and acceptance of the influenza vaccine. Future COVID-19 vaccination campaigns can target identified subgroups of pregnant women who are less likely to accept vaccination.


The perceived role of ward-based primary healthcare outreach teams in rural KwaZulu-Natal, South Africa.
The aim of ward-based outreach teams (WBOTs) is to improve access to primary healthcare (PHC) services including health promotion and disease prevention in South Africa. Limited information is available in South Africa on user perceptions of services provided by WBOTs in rural households. The study aimed to explore community awareness and perception of WBOTs, as well people's motivation to engage and use WBOT services. The study was conducted between July and September 2015 in iLembe district, KwaZulu-Natal. This was exploratory-descriptive qualitative research. Purposive sampling technique was used in this study. A total of 16 key informant interviews and 4 focus group discussions were conducted. The voice recordings were transcribed in isiZulu and translated into English. Four themes emerged from the data analysis, namely bringing services closer, organising services, expanding services and forming bridges. Respondents demonstrated insightful knowledge and understanding of services provided by WBOTs. They expressed an appreciation of the way WBOT services brought healthcare closer to people and serve to bridge the gap between the community and local healthcare facilities. Respondents identified unclear WBOT work schedules and the failure to carry medication other than vitamin A as the main challenges. However, WBOTs did deliver medication for controlled chronic patients in their households. The study suggests that WBOTs provide a commendable service, but need to expand their service package to further increase access to PHC services and cater for community health needs.


Amelioration of streptozotocin-induced diabetes in mice using human islet cells derived from long-term culture in vitro.
Long-term maintenance of the phenotype of beta cells in vitro is difficult. The objective of this study was to examine an in vitro method for preserving the capacity of adult human beta cells to express insulin. We evaluated the use of long-term cultured islet cells for the treatment of diabetic SCID mice. Human islets were isolated from cadaveric donors. The islets were cultured as monolayers and clusters in repeating cycles for 4 months. Thereafter, the cells were tested in vitro for their capacity to express insulin and to secrete insulin in response to glucose challenge. Finally, the cluster-cultured cells were transplanted under the kidney capsule and into the kidney tissue in streptozotocin (STZ)-induced diabetic SCID mice. Approximately 3.6% of cultured islet cells in cluster phase expressed insulin at 4 months and this was confirmed using immuno-gold-labeling electron microscopy. The cultured islet cells secreted insulin in response to glucose challenge in a dose-dependent manner. After transplantation, the islet cells redifferentiated and generated >20% insulin positive cells. The 4-month cultured cells rendered the blood glucose level near normal in mild diabetic mice (7.25 mM+/-1.595 vs. 15.225 mM+/-2.55, P<0.0025). It is possible to preserve the capacity of adult human islets to express insulin over a 4-month period in vitro, and this capacity was enhanced significantly by transplantation into SCID mice. The described system will be useful in studies of beta cell proliferation and differentiation.


Low bone mass and postfall fracture risk among elderly nursing home men.
To study postfall fracture risk in relation to bone mineral density. The study was conducted in men residing in nursing homes. A total of 212 men above the age of 65 years were recruited, and of these, 172 satisfied the inclusion criteria of the study. Among them, 82 were less than 85 years old, and 90 were at least 85 years old. Bone mineral density (BMD) of the calcaneus was measured, using the Lunar PIXI Bone Densitometer (version 1.43) and charts were reviewed for age, falls, and fractures. The values of BMD were expressed as T-scores, and the Lunar criteria equivalents of T-scores were used (T-scores more than -0.6 for normal BMD, -0.6 to -1.6 for osteopenia, and below -1.6 for osteoporosis). The median age of all participants was 84 years (range 65 to 102 years), and their mean T-score at the calcaneus was -1.51. In about 51% of them, the T-score was in the osteoporotic range. For subjects less than 85 years old, the mean T-score was -1.19, and for those 85 years and older, the mean T-score was -1.81; the mean bone density of those in the older old group was significantly lower than those in the younger old group if there was a history of a fracture. Analysis by age quartiles showed a progressive decline in BMD with advancing age. About 53% of the subjects who fell (37.2%) sustained a nontraumatic fracture. Among them, 67.6% had osteoporosis. At any given age after age 65, men who sustained a postfall fracture had a significantly lower BMD than those who did not sustain a postfall fracture.


Metal complexes of 4,6-O-ethylidene-β-d-glucopyranosylamine derivatives and their application in organic synthesis.
Glycosylamine derivatives of 4,6-O-ethylidene-d-glucose have been used for complexing the alkali, alkaline earth and transition metal ions. Three different series of ligands have been reported where N-(o-carboxyphenyl)-4,6-O-ethylidene-β-d-glucopyranosylamine has been used for complexing the diamagnetic (Li+, Na+, K+, Mg2+, Ca2+, Ba2+, Zn2+, Cd2+, Hg2+) metal ions. N-(2-Hydroxybenzoyl)-L-alanyl-4,6-O-ethylidene-β-d-glucopyranosylamine selectively interacts with molecular cupric acetate and the adduct acts as a catalyst in selective oxidation of primary and secondary alcohols into their corresponding carbonyl compounds. Salicylidene derivatives of 4,6-O-ethylidene-β-d-glucopyranosylamine have been used in complexing Ni2+, Cu2+, Zn2+, VO2+, MoO22+ and UO22+ metal ions, where Cu(II) and Mo(VI) complexes have been further used in the organic synthesis. Dinuclear copper complex exhibited catecholase like activity and also catalyzed the oxidation of primary and secondary alcohols selectively into their corresponding carbonyl compounds. Trinuclear copper complex has been reported to activate the C-Cl bond of solvent chloroform in the presence of mild organic bases below room temperature. Mo(VI) complex has been used as a catalyst for epoxidation, organic sulfide oxidation and synthesis of bis(indolyl)methanes.


[Differential diagnosis of primary hyperaldosteronism and indications for surgery].
Primary hyperaldosteronism (PHA) is a clinical syndrome that develops as a result of the excessive production of aldosterone by the adrenal cortex and manifests itself as low-corinine hyperaldosteronemia in combination with arterial hypertension (AH). To date, there is no single universally accepted classification of PHA. Most often they use classification according to the nosological principle.


Longitudinal evaluation of motor function in patients who underwent prenatal or postnatal neural tube defect repair.
To compare the evolution of motor function from mid-gestation to 12 months of age between prenatally and postnatally repaired cases of open neural tube defect (ONTD). This was a retrospective cohort study of all fetuses that underwent prenatal (fetoscopic or open hysterotomy) or postnatal ONTD repair at a single institution between November 2011 and December 2018. The anatomical level of the lesion was defined as the upper bony spinal defect at initial magnetic resonance imaging assessment. Prenatal motor function of the lower extremities was evaluated by ultrasound according to the metameric level of the neurological lesion, based on the methodology of Carreras et al. Fetal motor function was assessed at referral, at 6 weeks after surgery in prenatally repaired cases or 6 weeks after referral in postnatally repaired cases (6-week follow-up) and at the last scan before delivery. In addition, motor function was assessed by a detailed neurological examination at birth and 12 months of age. First sacral (S1) neurological level of the lesion was considered as intact motor function. For statistical comparisons, we attributed numerical scores to each neurological level and motor function was expressed as median (range) neurological level. Motor function (as numerical score) and the proportion of cases with intact motor function and with motor function two or more levels better than expected based on the anatomical level of the lesion were compared between the prenatal- and postnatal-repair groups. Fetal motor function was compared to the anatomical level of the lesion at referral and a better motor function was defined when it was two or more levels better than the anatomical level of the lesion. To assess the evolution of motor function, we compared motor function at referral with that at each follow-up assessment using paired t-tests. We included 127 patients with ONTD, of whom 93 underwent prenatal (51 fetoscopic and 42 open hysterotomy) and 34 postnatal repair. At the time of referral, cases in the prenatal- and postnatal-repair groups presented with a similar anatomical level of lesion (L3 (T9-S1) vs L3 (T7-S1); P = 0.52), similar motor function (S1 (L1-S1) vs S1 (L1-S1); P = 0.52) and a similar proportion of cases with intact motor function (81% vs 79%; P = 0.88) and with motor function two or more levels better than expected based on the anatomical level of the lesion (62% vs 74%; P = 0.24). When compared with prenatally repaired cases, postnatally repaired cases showed worse motor function at birth (S1 (L1-S1) vs L4 (L1-S1); P < 0.01) and at 12 months of age (S1 (L1-S1) vs L4 (L1-S1); P < 0.01). In the prenatal-repair group, motor function remained stable from the time of referral to 12 months of age (P = 0.26). Furthermore, the proportion of patients with intact motor function at referral (81% (75/93)) was similar to that at the 6-week follow-up (74% (64/87)), at the last scan before birth (74% (42/57)), at birth (68% (63/93)) and at 12 months of age (67% (39/58)) in the prenatal-repair group. In the postnatal-repair group, worse motor function, starting from the third trimester to 12 months of age, was observed. The proportion of patients with intact motor function at referral (79% (27/34)) was similar to that at 6-week follow-up (80% (12/15); P = 0.92), but was lower at the last assessment before birth (25% (2/8); P < 0.01), at birth (24% (8/34); P < 0.01) and at 12 months of age (28% (7/25); P < 0.01). Similar findings were noted when assessing the evolution of the proportion of cases with motor function two or more levels better than expected based on the anatomical level of the lesion in each group. Infants with ONTD that underwent postnatal repair had worse motor function at birth and at 12 months of age than at mid-gestation and when compared with infants that underwent prenatal ONTD repair. Prenatal motor function assessment by ultrasound is an adequate tool to identify those infants who should have a good clinical motor function after delivery. Information obtained by fetal motor function assessment can have an important role for patient counseling and case selection for surgery. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.


FTIR, FT-Raman spectra and ab initio DFT vibrational analysis of 2,4-dichloro-6-nitrophenol.
The FTIR and FT-Raman spectra of 2,4-dichloro-6-nitrophenol (2,4-DC6NP) has been recorded in the region 4000-400 cm(-1) and 3500-100 cm(-1), respectively. The optimized geometry, frequency and intensity of the vibrational bands of (2,4-DC6NP) were obtained by the ab initio and DFT levels of theory with complete relaxation in the potential energy surface using 6-31G(d,p) and 6-311+G(d,p) basis sets. The harmonic vibrational frequencies were calculated and the scaled values have been compared with experimental FTIR and FT-Raman spectra. The observed and the calculated frequencies are found to be in good agreement. The experimental spectra also coincide satisfactorily with those of theoretically constructed bar type spectrograms.


Low-cost disposable Poly(ethyleneimine)-Functionalized Carbon Nanofibers Coated Cellulose Paper as efficient solid phase extraction sorbent material for the extraction of Parahydroxybenzoates from environmental waters.
Parahydroxybenzoates (parabens) are considered as emerging environmental contaminants because of their extensive usage in our daily life products, causing parabens contamination into environmental water systems and lead to toxic effects on environmental health. This study describes a greener extraction method using a new cationic polymer poly (ethyleneimine) functionalized acid-treated carbon nanofibers (PEI-CNFs) coated cellulose paper (CP) as solid-phase extraction (SPE) sorbent material for the extraction of parabens from environmental water samples. The fabrication of PEI-CNFs modified CP was confirmed using field-emission scanning electron microscope, transmission electron microscopy, and fourier-transformer infrared spectroscopy techniques. Various factors affecting the adsorption and desorption of parabens on PEI-CNFs@CP and its extraction efficiencies were studied using HPLC-UV analysis. Under the optimal experimental conditions, maximum extraction efficiencies were achieved for four target parabens, and PEI-CNFs@CP/HPLC-UV method exhibited excellent linearities ranged from 0.5-50 ng mL-1 with regression coefficient values were between 0.9952-0.9970. The presented method showed good sensitivity with quantification limits between 0.5-0.75 ng mL-1 and detection limits between 0.1-0.25 ng mL-1. The developed technique was applied for the real sample analysis (river, lake, domestic sewage water, and drinking tap water). The spiked recovery revealed good recoveries between 86.8-116.0% with RSD less than 8.8% for all the water samples. These results proved that it a simple, fast, efficient, low-cost, and eco-friendly method for the extraction and determination of parabens in environmental water samples and can be applied as a routine analytical tool in environmental monitoring and quality control laboratories.


Antcin K targets NLRP3 to suppress neuroinflammation and improve the neurological behaviors of mice with depression.
We aimed to explored the role of Antcin K in resisting depression and its targets. LPS/IFN-γwas used to induce the activation of microglial BV2 cells. Following Antcin K pretreatment, the proportion of M1 cells was determined using flow cytometry (FCM), the expression of cytokines was measured through ELISA, and that of CDb and NLRP3 was analyzed by cell fluorescence staining. The protein levels were detected by Western-blot assay. After NLRP3 was knocked down in BV2 cells (BV2-nlrp3-/-), the M1 polarization level was detected with Antcin K treatment. The targeted binding relation of Antcin K with NLRP3 was confirmed through small molecule-protein docking and co-immunoprecipitation assay. The chronic unpredictable stress model (CUMS) was constructed to mimic the depression mice. After the administration of Antcin K, the neurological behavior of CUMS mice were detected by open-field test (OFT), elevated plus maze, forced swimming test (FST), and tail suspension test (TST). In addition, the expression of CD11b and IBA-1 was detected through histochemical staining, and the tissue pathological changes were detected by H&E staining. Antcin K suppressed the M1 polarization of BV2 cells and reduced the expression of inflammatory factors. Meanwhile, NLRP3 exhibited targeted binding relation with Antcin K, and Antcin K lost its effect after NLRP3 knockdown. In the CUMS mouse model, Antcin K improved the depression status and neurological behaviors in mice, and decreased central neuroinflammation and microglial cell polarization. Antcin K targets NLRP3 to suppress microglial cell polarization, alleviate central inflammation in mice and improve their neurological behaviors.


Facile Synthesis, Characterization, and Photocatalytic Evaluation of In2O3/SnO2 Microsphere Photocatalyst for Efficient Degradation of Rhodamine B.
The tin dioxide (SnO2) photocatalyst has a broad application prospect in the degradation of toxic organic pollutants. In this study, micron-sized spherical SnO2 and flower indium oxide (In2O3) structures were prepared by a simple hydrothermal method, and the In2O3/SnO2 composite samples were prepared by a "two-step method". Using Rhodamine B (RhB) as a model organic pollutant, the photocatalytic performance of the In2O3/SnO2 composites was studied. The photocurrent density of 1.0 wt.% In2O3/SnO2 was twice that of pure SnO2 or In2O3, and the degradation rate was as high as 97% after 240 min irradiation (87% after 120 min irradiation). The reaction rate was five times that of SnO2 and nine times that of In2O3. Combined with the trapping experiment, the transient photocurrent response, and the corresponding characterization of active substances, the possible degradation mechanism was that the addition of In2O3 inhibited the efficiency of electron-hole pair recombination, accelerated the electron transfer and enhanced the photocatalytic activity.


A Multiscale, Systems-Level, Neuropharmacological Model of Cortico-Basal Ganglia System for Arm Reaching Under Normal, Parkinsonian, and Levodopa Medication Conditions.
In order to understand the link between substantia nigra pars compacta (SNc) cell loss and Parkinson's disease (PD) symptoms, we developed a multiscale computational model that can replicate the symptoms at the behavioural level by incorporating the key cellular and molecular mechanisms underlying PD pathology. There is a modelling tradition that links dopamine to reward and uses reinforcement learning (RL) concepts to model the basal ganglia. In our model, we replace the abstract representations of reward with the realistic variable of extracellular DA released by a network of SNc cells and incorporate it in the RL-based behavioural model, which simulates the arm reaching task. Our results successfully replicated the impact of SNc cell loss and levodopa (L-DOPA) medication on reaching performance. It also shows the side effects of medication, such as wearing off and peak dosage dyskinesias. The model demonstrates how differential dopaminergic axonal degeneration in basal ganglia results in various cardinal symptoms of PD. It was able to predict the optimum L-DOPA medication dosage for varying degrees of cell loss. The proposed model has a potential clinical application where drug dosage can be optimised as per patient characteristics.


Effect of phospholipases on chronic opiate action in neuroblastoma X glioma NG108-15 hybrid cells.
Chronic treatment of neuroblastoma X glioma NG108-15 hybrid cells with opiate agonist resulted in loss of the acute opiate inhibition of adenylate cyclase activity with a concomitant increase in the enzymatic activity observable on addition of the antagonist naloxone. The role of membrane lipids in the cellular expression of these chronic opiate effects was investigated by the hydrolysis of phospholipids with various lipases. Treatment with phospholipase C from Clostridium welchii produced an enzyme concentration-dependent decrease of prostaglandin E1-stimulated adenylate cyclase activity in control or etorphine-treated (1 microM for 4 h) hybrid cells. In addition, incubation of hybrid cells with phospholipase C concentrations of greater than or equal to 0.5 U/ml completely abolished the compensatory increase in adenylate cyclase activity after chronic opiate treatment. This attenuation of the increase in adenylate cyclase activity by phospholipase C could be prevented by inclusion of phosphatidylcholine but not of phosphatidic acid during the enzymatic incubations. The specificity of the phospholipids involved in expression of the chronic opiate effect could be demonstrated further by the absence of effect exhibited by phospholipase C from Bacillus cereus and phospholipase D. Hydrolysis of the acyl side chains of phospholipids with phospholipase A2 did not alter the chronic opiate effect after removal of lysophosphatides with bovine serum albumin. Because the guanylylimidodiphosphate- and NaF-sensitive adenylate cyclase activities were not affected by these phospholipase treatments, the expression of the compensatory increase in adenylate cyclase activity is mediated via an increase in the coupling between hormonal receptor and adenylate cyclase with the participation of the polar head groups of the phospholipids and not the hydrophobic side chains.


An examination of cancer literacy among Appalachian versus non-Appalachian Kentucky college students.
Examine factors contributing to high rates of Appalachian female cancer incidences and mortalities by examining cancer literacy and associated sociological influences among Appalachian university students. This study evaluated Appalachian and non-Appalachian undergraduate students in Eastern Kentucky. A Qualtrics survey was disseminated which categorized questions into three parts: demographic, female focused cancer literacy, and cancer care access. Overall cancer literacy was low (67.45%, 139 respondents); no difference was found in Appalachian standing. Male students had lower scores (p < 0.05), and both cancer-related majors (p < 0.001) and enhanced academic years (p < 0.05) improved cancer literacy. Limited awareness of mobile cancer screening units was found across respondents, along with, decreased access to health services indicated by Appalachian students (p < 0.05). College students represent a population in need of enhanced cancer education. Improving knowledge about accessing healthcare including cancer screenings could reduce Appalachian cancer rates.


Mitogen-activated protein kinases regulate platelet-activating factor-induced hyperpermeability.
The authors tested the hypothesis that p42/44- (ERK-1/2) and/or p38-mitogen-activated protein kinases (MAPK) are in vivo regulatory elements in the platelet-activating factor (PAF) activated signaling cascade that stimulates microvascular hyperpermeability. FITC-dextran 70 was used as the macromolecular tracer for microvascular permeability in the mouse mesenteric fat tissue. Interstitial integrated optical intensity (IOI) was used as an index of permeability. An application of 10(-7) M PAF increased IOI from 23.1 +/- 3.6 to 70.8 +/- 7.4 (mean +/- SEM). Inhibition of ERK-1/2 with 3 microM and 30 microM AG126 reduced IOI to 32.3 +/- 2.5. Similarly, inhibition of p38-MAPK with 6 nM, 60 nM and 600 nM SB203580 lowered IOI to 29.1 +/- 2.4. The results demonstrate that ERK-1/2 and p38MAPK participate in the signaling cascade that regulates PAF-induced microvascular hyperpermeability in vivo.


4,4',5,5'-Tetra-kis(benzyl-sulfan-yl)tetra-thia-fulvalene.
The asymmetric unit of the title compound, C(34)H(28)S(8), contains two crystallographically independent half-mol-ecules. The mol-ecules lie on centers of inversion. The four benzene rings of each mol-ecule are substantially twisted from the planes of the 1,3-dithiole rings, forming dihedral angles of 43.6 (2) and 61.4 (1)° in one mol-ecule and 54.2 (1) and 65.2 (1)° in the other.


Exercise-Induced Muscle Damage in Postmenopausal Well-Trained Women.
Sex hormone deprivation derived from menopause may affect exercise-induced muscle damage (EIMD). No studies have previously evaluated this response between postmpenopausal and premenopausal eumenorrheic women over the menstrual cycle. Postmenopausal women will present higher EIMD markers than premenopausal women, especially in comparison with the menstrual cycle phases where sex hormone concentrations are higher. Cross-sectional study. Level 3. Thirteen postmenopausal and 19 eumenorrheic women, all of them resistance-trained, performed an eccentric squat-based exercise. The postmenopausal group performed 1 bout of exercise, while the eumenorrheic group performed 3 bouts coinciding with the early follicular, late follicular, and mid-luteal phases ot their menstrual cycle. Muscle soreness, countermovement jump, creatine kinase (CK), myoglobin, lactate dehydrogenase, interleukin-6, tumor necrosis factor-α, and C-reactive protein were evaluated before and postexercise. The expected differences in sex hormones were observed between groups (P < 0.001) according to their reproductive status. Postexercise increases in CK, myoglobin, and muscle soreness (168.2 ± 45.5 U/L, 123.1 ± 41.5 µg/L, and 20.7 ± 21.3 mm, respectively) were observed in comparison with baseline (136.2 ± 45.5 U/L, 76.9 ± 13.8 µg/L, and 2.7 ± 4.2 mm, respectively). Myoglobin values at baseline in postmenopausal women were higher compared with premenopausal women in the aforementioned menstrual cycle phases, respectively (62.8 ± 8.2, 60.4 ± 7.2, and 60.1 ± 10.6 µg/L; P < 0.001 for all comparisons), which was supported by large effect sizes (0.72-1.08 standardized d units). No postexercise differences were observed between groups in any markers (P > 0.05). Despite higher resting levels of myoglobin and lower strength values in postmenopausal than in premenopausal women, EIMD was similar between both reproductive profiles. This suggests a potential benefit of being physically active despite aging and sex hormone deprivation. Sex hormone deprivation derived from menopause seems not to influence muscle damage reponse to eccentric exercise in resistance-trained postmenopausal women.


Structural characterization and serological specificities of lipopolysaccharides from Salmonella enterica serovar Gallinarum biovar Pullorum standard, intermediate and variant antigenic type strains.
The structure and serological specificities of the lipopolysaccharides (LPSs) from Salmonella enterica serovar Gallinarum biovar Pullorum were studied to provide an improved basis for the distinction between antigenic types and the development of improved diagnostic tests. The structure of the LPS O-polysaccharide (O-PS) from S. Pullorum standard, intermediate and variant antigenic type strains was determined by mass spectrometry, nuclear magnetic resonance spectroscopy and chemical analysis. The LPS of the three strains shared a common structural repeating oligosaccharide unit containing d-mannose, l-rhamnose, d-galactose and d-tyvelose (1:1:1:1). The O-PS of the variant type LPS contained an additional d-glucose residue linked to the O-4 position of the d-galactose residue. The O-PS of the intermediate type LPS was partially the same as that of the variant LPS, however, the molar ratio of the d-glucose component was lower with respect to the other glycose components. Serological specificities of the three antigenic type LPSs were examined with anti-S. Pullorum LPS monoclonal antibodies (Mabs). On immunoblots, Mabs to the standard type O-PS reacted with high molecular mass (HMM) and low molecular mass (LMM) LPS from the standard strain, and with LMM but not HMM LPS from the variant strain. Monoclonal antibodies to the variant type O-PS reacted with HMM but not LMM LPS from the variant strain, and did not react with HMM or LMM LPS from the standard strain. On ELISA, the standard, intermediate and variant antigenic type strains were differentiated by the relative reactivity with the anti-LPS O-PS Mabs. Several of the anti-LPS O-PS Mabs were specific for S. Pullorum and other serogroup D1 Salmonella, and are potentially useful for the development of improved diagnostic tests for these organisms.


Prospective evaluation of concomitant tumour bed boost with whole breast irradiation in patients with locally advanced breast cancer undergoing breast-conserving therapy.
To evaluate prospectively the feasibility of concomitant weekly tumour bed electron boost along with whole breast radiotherapy (RT) following breast-conserving therapy (BCT) in patients with locally advanced breast cancer (LABC) with the aim of reducing overall treatment time. Thirty patients with LABC suitable for BCT following neoadjuvant chemotherapy (CAF/CEF) were accrued in the study. Conventional RT (CRT) to the whole breast was delivered 5 days a week to a dose of 50Gy using 6-10MV photons. In addition, an electron boost to the tumour bed was delivered every Saturday, eventually delivering 5 such weekly fractions to a boost dose of 12.5Gy. Patients were evaluated for acute reactions during the treatment and cosmetic evaluation was done before, at the end of radiation therapy and at follow up by 2 independent observers blinded to each other. The study population (concomitant boost (CB) group) was compared with a similar cohort of 32 patients treated conventionally with tumour bed boost of 15Gy in 6 fractions delivered after the completion of whole breast irradiation (CRT group). All patients completed RT within the stipulated time with no grade IV skin toxicity in either group. At conclusion of RT, in the CB group, confluent moist desquamation (grade III) developed within the tumour bed region in 1 patient (3.3%) and outside tumour bed region in 3 patients (10%). In the CRT group, 3 and 4 patients (9.4% and 12%) developed moist desquamation within and outside the tumour bed regions, respectively. CB did not affect the global cosmesis as compared with CRT group (p=0.23) at the end of 3 years. Concomitant tumour bed boost along with whole breast RT appears to be safe and feasible in a select group of patients. As the treatment is completed earlier by 6-10 days than conventional practice, it has favourable time and resource implications, particularly attractive for patients travelling long distances for treatment. Based on these encouraging results, we are planning to confirm the results in an appropriately designed and powered randomised trial.


Anesthetic management of the pediatric patient undergoing solid organ transplantation.
Solid organ transplantation is now routinely performed at many institutions. Pediatric organ recipients present difficult challenges to pediatric anesthesiologists. Physiologic, anatomic, and pharmacologic derangements in this population may make both the surgical procedure and the anesthetic management complicated. This article presents an overview of the unique problems and the strategies to solve them in this population.


Plasma exchange as rescue therapy in multiple organ failure including acute renal failure.
To describe the outcome of using a rescue therapy including plasma exchange given to patients with a progressive acute disseminated intravascular coagulation and multiple organ dysfunction syndrome. Retrospective study. University and county hospital. Included were 76 consecutive patients (41 men and 35 women) treated with plasma exchange as rescue therapy besides optimal conventional therapy during a progressive course of disseminated intravascular coagulation and multiple organ dysfunction syndrome, including acute renal failure. Of the 76 patients, 66% needed dialysis. The distribution was hemodialysis in 76%, continuous arteriovenous hemofiltration in 36%, continuous venovenous hemodialysis in 12%, and peritoneal dialysis in 24%. The median organ-failure score was 5 (range, 1-6). Seventy-two percent required mechanical ventilation; septic shock was present in 88%. The median septic shock score was 4 (range, 2-4). Nine patients had another reason than sepsis for the multiple organ dysfunction syndrome. Plasma exchange (centrifugation technique) was performed until disseminated intravascular coagulation was reversed (median, two times; range, 1-14). Besides antibiotics and fluid administration, most patients received heparin or low molecular weight heparin (77%), steroids (87%), and inotropes (88%). More than one vasoactive drug was used in 57% of the patients. Eighty-two percent of the patients survived and could leave the hospital. The previously observed survival rates by others for this category of patients would be <20%, and thus, the outcome in this study is significantly better. Plasma exchange using plasma as replacement may, in addition to conventional intensive care, help to reverse severe progressive disseminated intravascular coagulation and multiple organ dysfunction syndrome and improve survival.


Rapid screening of polychlorinated biphenyls in sediments using non-equilibrium solid-phase microextraction and fast gas chromatography with electron-capture detection.
A rapid method for the screening of polychlorinated biphenyls (PCBs) in sediment samples is described. Analytes are concentrated on a poly(dimethylsiloxane) (PDMS) solid-phase microextraction (SPME) fibre, separated using a narrow-bore gas chromatography column (10 m x 0.1mm I.D.) and determined with a micro-electron-capture detector (micro-ECD). The narrow-bore column showed a similar separation efficiency to a conventional capillary one (30 m x 0.32 mm I.D.) and allowed a 3 times reduction in the analysis time. Moreover, thermal desorption of SPME fibres in the narrow-bore column did not produce any degradation in the quality of separations when compared to the split injection mode. The use of an oxidative sample treatment was mandatory to remove sulphur interferences in the chromatograms and increase the yield of PCBs during SPME for short sampling times. Under optimised conditions, a fraction of sediment (0.1-0.5 g) was mixed with 5 ml of a 0.2M potassium permanganate solution and 0.5 ml of sulphuric acid 6M in a 22 ml closed vessel. Sample treatment and headspace SPME of PCBs were performed simultaneously for 10 min at 100 degrees C. Globally, the whole analytical procedure takes about 20 min and presents quantification limits between 0.5 and 1.3 ng/g. Accuracy was evaluated by analysing a reference sediment sample with certified concentrations of several PCBs.


The effects of a modest dose of alcohol on executive functioning and prospective memory.
Acute alcohol intoxication selectively impairs executive functioning and prospective memory (PM). Much previous researches in this area have used laboratory‐based tasks that may not mimic functions that individuals with dysexecutive syndrome have problems with in their everyday life. The present study aimed to assess the effects of a modest dose of alcohol on executive functioning and PM using a virtual reality task and investigate the role of executive planning in PM performance. Forty healthy participants were administered 0.4 g/kg alcohol or matched placebo in a double‐blind design. Executive function and PM were assessed using the Jansari-Agnew-Akesson-Murphy (JAAM) task, requiring participants to play the role of an office worker. Alcohol intoxication selectively impaired executive function and PM. The participants in the alcohol condition performed worse on the planning, prioritisation, creativity and adaptability executive subscales and also on the time‐based and event‐based PM tasks. However, alcohol did not impair the selection executive function task or the action‐based PM task. The results provide further support for the effects of alcohol on executive functioning and PM. In addition, the results suggest that such deficits may be present at relatively modest doses of alcohol and in the absence of a subjective feeling of intoxication.


Preparation of Doxorubicin Liposomes by Remote Loading Method.
Doxorubicin liposome is one of the most important nano-drug formulations. DOXIL, the first FDA-approved doxorubicin liposomes, is also the first nano-drug product in market. Since it was approved in 1995, DOXIL have been widely used in the treatment of various tumors. Several important technologies used in the development of doxorubicin liposomes, especially the remote loading technology, have an extremely important impact on the later liposome research and development. This article describes a protocol to prepare doxorubicin liposomes by remote loading in a laboratory.


Exposure driven dose escalation design with overdose control: Concept and first real life experience in an oncology phase I trial.
Escalation With Overdose Control (EWOC) designs are increasingly used to ensure dose-toxicity curve of investigational oncology drugs is efficiently characterized during dose escalation steps. We propose a novel EWOC-based method that integrates the longitudinal pharmacokinetic (PK) data of individual patients in a Bayesian forecasting exposure-safety framework. The method, called exposure-driven EWOC (ED-EWOC), relies on a population PK model coupled with a Bayesian logistic regression model to make dose recommendation for the next cohort of patients. We applied ED-EWOC to a real oncology clinical trial in parallel to a traditional EWOC approach. We found that for comparable priors, ED-EWOC dose recommendations were equivalent to the one suggested by EWOC when PK is dose proportional with low inter-individual variability. This case example demonstrates that ED-EWOC is logistically feasible during a trial conduct when PK bioanalysis can be expedited in the dose escalation phase. Overall, we anticipate that exposure-guided Bayesian designs could benefit patients and drug developers to identify the optimal dose steps of novel compounds entering the clinic with suspected liability in PK or that exhibit large inter-individual variability.


Apical region correction and global balance: a 3-rods surgical strategy for the treatment of severe and rigid scoliosis.
The treatment of severe and rigid scoliosis is challenging. We developed a surgical strategy for severe and rigid scoliosis since 2014. This study aimed to retrospectively analyze the safety and efficacy of apical region correction and global balance with 3 rods as a surgical strategy for the treatment of severe and rigid scoliosis. A retrospective study was performed for patients with severe and rigid scoliosis who underwent one-stage posterior corrective operation using the apical region correction and global balance with 3 rods surgical strategy between February 2014 and April 2020. The inclusion criteria were as follows: [1] Cobb angle > 90°; [2] flexibility < 30%; [3] a minimum 2-year follow-up. Patients were excluded if they had a history of traction or spinal surgery. Coronal and sagittal parameters, including Cobb angle, flexibility, apex vertebra translation, trunk shift (TS), thoracic kyphosis, lumbar lordosis, and sagittal vertical axis (SVA) were measured preoperatively, postoperatively and at the final follow-up. The Scoliosis Research Society 22-item questionnaire was administered preoperatively and at the final follow-up. During the operation, one slightly-bent short rod was placed into the concave side of apical region and correction was achieved by rod-rotation and distraction. Two pre-bent long rods were placed into both sides of the scoliosis and global balance was improved by leveling the proximal thoracic vertebrae and distal lumbar vertebrae. A total of 41 patients were included, with an average age of 20 years (range, 12-49 years) and follow-up of 34 months (range, 24-58 months). Postoperative correction rate was 53% for scoliosis. There were 14 patients with normal kyphosis before surgery, and 28 patients with normal kyphosis at the last follow-up. 88% of the patients (23/26) with preoperative coronal imbalance (TS > 20 mm) restored coronal balance at the final follow-up. 87% of the patients (14/16) with preoperative sagittal imbalance (SVA > 40 mm) restored sagittal balance at the final follow-up. The mean operation time and blood loss were 286 min and 941 mL, respectively. No patients had neurological complications or implant failure. The surgical strategy of apical region correction and global balance with 3 rods is a safe and effective alternative for the surgical treatment of severe and rigid scoliosis.


State of iron repletion and cadmium tissue accumulation as a function of growth in young rats after oral cadmium exposure.
To check the hypothesis that adequate dietary iron supplementation reduces cadmium retention and cadmium-induced anaemia during fast growth, three different dietary iron concentrations (6 mg/kg = iron-deficient; 55 mg/kg = marginal iron supply; 180 mg/kg = luxurious iron supply) were offered to growing rats. Four groups of rats at different age (44 days approximately = 150 +/- 6 g, 49 days approximately = 180 +/- 3 g, 57 days approximately = 220 +/- 4 g, and 84 days approximately = 295 9 g) received a diet with 55 mg Fe/kg which is a marginal iron-supply during growth. Six animals in each age group were exposed to 10 mg Cd/l as CdCl2 in the drinking water for 1 week; six animals in each age group received no cadmium. In the youngest and oldest groups additional 6 animals were exposed to the same cadmium dose but received an iron-deficient (6 mg Fe/kg) and an iron-adequate diet (180 mg Fe/kg) together with corresponding controls. The state of iron repletion was monitored by the tissue iron content in liver, kidney, and duodenum as well as by the concentrations of haemoglobin, plasma iron and plasma transferrin. The youngest animals showed the highest percent weight increases. Cadmium administration influenced neither growth rates nor food and water intake. At a dietary iron content of 55 mg/kg, iron repletion was negatively correlated to growth while the cadmium content in liver and kidney showed a positive correlation. At fast growth, a dietary iron content of 6 mg/kg lead to iron-deficiency anaemia and high cadmium retention. At all dietary iron concentrations, cadmium retention as well as the cadmium-related reduction in haemoglobin concentration was significantly higher at fast growth. Adequate dietary iron supplementation reduced cadmium retention and cadmium-induced anaemia significantly. Thus, the delicate balance between iron supply and the increased iron demand during growth can be disturbed within one week by a daily cadmium intake as low as 0.7-1.3 mg Cd/kg body weight.


Partial trisomy 16q resulting from maternal translocation 11p/16q.
A 3 1/2-year-old male with partial trisomy of the long arm of chromosome 16 resulting from a maternal balanced translocation 11p;16q is described. Clinical findings are compared with similar case reports from the literature.


Deregulated expression of promyelocytic leukemia zinc finger protein in B-cell chronic lymphocytic leukemias does not affect cyclin A expression.
The promyelocytic leukemia zinc finger (PLZF) gene encodes a transcription factor expressed in myeloid, lymphoid and CD34(+) progenitor cells. Structurally related to BCL-6, which is involved in human lymphoma, PLZF may have a role in proliferation, differentiation and survival of hematopoietic cells, that could be mediated by transcriptional repression of the cyclin A gene. Quantitative competitive reverse transcription-polymerase chain reaction was used to measure the levels of expression of PLZF and cyclin A in normal leukocyte subsets (including CD19(+) lymphocytes, n=21) and malignant B lymphocytes (including B-chronic lymphocytic leukemias [B-CLL], n=63). Results obtained with this method were confirmed by Western and Northern blot analysis. Transactivation assays were performed using an expression construct for PLZF and two cyclin A promoter luciferase reporters in an Epstein-Barr virus (EBV)-transformed B-cell line. Cyclin A expression, cell growth kinetics, and cell cycle were analysed in stable clones of the Burkitt lymphoma (BL) B-cell line DG75 with inducible expression of PLZF, generated using the tetracycline-regulated expression system. Expression of PLZF was 100-fold downregulated in 90% B-CLL (56/63) compared to normal B lymphocytes (P<0.001). B-CLL patients with the highest levels of PLZF had a poorer survival (P<0.013). In transactivation assays, PLZF inhibited the activity of the cyclin A reporters by 50%, demonstrating that PLZF can repress cyclin A expression in non-malignant B lymphocytes. However, in B-CLL patients, the level of cyclin A expression was found to be within the normal range. Altered PLZF function in B lymphoid malignancies was further corroborated in the PLZF-regulatable DG75 clones, where induction of PLZF expression did not significantly alter the levels of cyclin A expression, the cell growth kinetics, or the cell cycle phase distribution. The lower survival of patients with the highest levels of PLZF suggests that this protein may be a marker of progression in B-CLL. The absence of co-ordinated regulation of PLZF and cyclin A genes in B-CLL and in a malignant B-cell line may indicate a loss of cyclin A control by PLZF in B-CLL and other B-cell disorders. Deregulation of PLZF could thus play a role in B-cell malignancy.


Benign and malignant neoplasms of the parotid gland: incidence and histology in the Danish County of Funen.
The present series is comprised of 155 patients from the county of Funen who were operated on for tumors of the parotid gland during the 5-year period, 1978 to 1982. Fifteen cases were malignant, 116 were benign, while no neoplasms were found in 24 cases. The incidence was calculated as 5.8 parotid neoplasms per year per 100,000 inhabitants. Computation of age standardized incidence rates adjusted to European and World Standard populations has been performed. It is stated that the county of Funen is a well-defined area and the series can be regarded to be representative of a certain geographical area. The histological classification was carried out according to the rules of the World Health Organization (WHO) and revealed a remarkably high occurrence of Warthin's tumors, i.e., 27.5%.


Cytotoxic activity of lymphocytes from F 344 rats bearing intraocular tumor derived from human adenovirus 12-induced retinoblastoma-like cell line.
Lymphocyte cytotoxicity using 51Cr releasing assay was investigated in 10 F344 rats bearing intraocular tumor derived from human adenovirus 12 (Ad 12)-induced retinoblastoma -like cell line (EXP-5). Lymphocytes obtained from tumor bored animal (1 X 10(6)/well) incubated with 51Cr-labelled EXP-5 cells (1 X 10(5)/well) for 24 hours, and counted by beta-scintillation counter. The cytotoxic activity of lymphocytes of transplanted animals was higher in 3 out of 10 subjected rats (24-30%) than in 10 rats of control (3-5%). The results support the view that the correspond animal model in its resemblance and suggested that the rats with retinal tumor have concomitant cell-mediated immunity in the early stage of tumor bearing.


Placebo Effects in the Neuroendocrine System: Conditioning of the Oxytocin Responses.
There is evidence that placebo effects may influence hormone secretion. However, few studies have examined placebo effects in the endocrine system, including oxytocin placebo effects. We studied whether it is possible to trigger oxytocin placebo effects using a classical conditioning paradigm. Ninety-nine women were assigned to a conditioned, control, or drug control group. In the two-phase conditioning paradigm, participants in the conditioned and drug control groups received an oxytocin nasal spray combined with a distinctive smell (conditioned stimulus [CS]) for three acquisition days, whereas the control group received placebo spray. Subsequently, the conditioned and control groups received placebo spray with the CS and the drug control group received oxytocin spray for three evocation days. Salivary oxytocin was measured several times during each day. Pain sensitivity and facial evaluation tests previously used in oxytocin research were also administered. On evocation day 1, in the conditioned group, oxytocin significantly increased from baseline to 5 minutes after CS (B[slope] = 19.55, SE = 5.88, p < .001) and remained increased from 5 to 20 (B = -10.42, SE = 5.81, p = .071) and 50 minutes (B = -0.70, SE = 3.37, p = .84). On evocation day 2, a trend for increase in oxytocin was found at 5 minutes (B = 15.22, SE = 8.14, p = .062). No placebo effect was found on evocation day 3 (B = 3.57, SE = 3.26, p = .28). Neither exogenous nor conditioned oxytocin affected pain or facial tasks. Results indicate that oxytocin release can be conditioned and that this response extinguishes over time. Triggering hormonal release by placebo manipulation offers various clinical possibilities, such as enhancing effects of pharmacological treatments or reducing dosages of medications. The study was registered as a clinical trial on www.trialregister.nl (number NTR5596).


Pediatric gastrointestinal stromal tumors.
Gastrointestinal stromal tumors (GISTs) rarely occur in pediatric patients, but increased recognition of adult GIST has led to better awareness of the existence of this entity in the pediatric population. GIST occurring in pediatric patients has a unique biology and clinical behavior and warrants discussion as an independent entity. The generally accepted definition of pediatric GIST is a tumor that is diagnosed at the age of 18 years or younger. This review highlights the clinical features, molecular biology, and clinical management of this rare pediatric entity.


D- and L-amino acids in Antarctic lakes: assessment of a very sensitive HPLC-MS method.
Amino acids represent a fraction of organic matter in marine and freshwater ecosystems, and a source of carbon, nitrogen and energy. L-Amino acids are the most common enantiomers in nature because these chiral forms are used during the biosynthesis of proteins and peptide. To the contrary, the occurrence of D-amino acids is usually linked to the presence of bacteria. We investigated the distribution of L- and D-amino acids in the lacustrine environment of Terra Nova Bay, Antarctica, in order to define their natural composition in this area and to individuate a possible relationship with primary production. A simultaneous chromatographic separation of 40 L- and D-amino acids was performed using a chiral stationary phase based on teicoplainin aglycone (CHIROBIOTIC TAG). The chromatographic separation was coupled to two different mass spectrometers--an LTQ-Orbitrap XL (Thermo Fisher Scientific) and an API 4000 (ABSciex)--in order to investigate their quantitative performance. High-performance liquid chromatography coupled with mass spectrometry methods were evaluated through the estimation of their linear ranges, repeatability, accuracy and detection and quantification limits. The high-resolution mass spectrometer LTQ-Orbitrap XL presented detection limits between 0.4 and 7 μg L (-1), while the triple quadrupole mass spectrometer API 4000 achieved the best detection limits reported in the literature for the quantification of amino acids (between 4 and 200 ng L (-1)). The most sensitive method, HPLC-API 4000, was applied to lake water samples.


Structural analysis of the reducing-end xylose-releasing exo-oligoxylanase Rex8A from Paenibacillus barcinonensis BP-23 deciphers its molecular specificity.
Reducing-end xylose-releasing exo-oligoxylanases (Rex) are GH8 enzymes that depolymerize xylooligosaccharides complementing xylan degradation by endoxylanases in an exo manner. We have studied Paenibacillus barcinonensis Rex8A and showed the release of xylose from xylooligomers decorated with methylglucuronic acid (UXOS) or with arabinose (AXOS). This gives the enzyme a distinctive trait among known Rex, which show activity only on linear xylooligosaccharides. The structure of the enzyme has been solved by X-ray crystallography showing a (α/α)6 folding common to GH8 enzymes. Analysis of inactived Rex8A-E70A complexed with xylotetraose revealed the existence of at least four binding subsites in Rex8A, with the oligosaccharide occupying subsites -3 to +1. The enzyme shows an extended Leu320-His321-Pro322 loop, common to other Rex, which blocks the binding of longer substrates to positive subsites further than +1 and seems responsible for the lack or diminished activity of Rex enzymes on xylan. Mutants with smaller residues in this loop failed to increase Rex8A activity on the polymer. Analysis of the complexes with AXOS showed the accommodation of arabinose at subsite -2, which cannot be allocated at subsite -1. Arabinose substitutions at the xylose O2 or O3 are accommodated by hydrophobic interaction and seem tolerated rather than recognized by Rex8A. A strained binding of the branch is facilitated by the lack of direct polar interactions of the xylose occupying this subsite, its water-mediated links allowing some conformational flexibility of the sugar. The plasticity of Rex8A is a notable property of the enzyme for its application in xylan deconstruction and upgrading. DATABASE: Structural data are available in PDB database under the accession numbers 6SRD (native form), 6TPP (E70A mutant in complex with EDO), 6TOW (E70A in complex with Xyl4), 6SUD (L320A mutant in complex with xylose), 6SHY (L320A/H321S double mutant in complex with EDO), 6TO0 (E70A in complex with AX3), and 6TRH (E70A in complex with AX4).


Prevalence and characteristics of Streptococcus pneumoniae "putative serotype 6E" isolates from Asian countries.
The prevalence, antimicrobial susceptibility, and genotypes of Streptococcus pneumoniae "putative serotype 6E" isolates from Asian countries were investigated. A total of 244 S. pneumoniae serogroup 6 isolates obtained from 11 Asian countries were included in this study. Of the 244 serogroup 6 isolates, 101 (41.4%) were typed as "putative serotype 6E," followed by serotypes 6A, 6B, 6C, and 6D (27.0, 20.1, 5.7, and 5.7%, respectively). Multilocus sequence typing revealed that clonal complex (CC) 90, including ST90 and its variants, was the most prevalent clonal group of "putative serotype 6E" isolates (n = 63; 62.4%). CC146 and CC315 were also found frequently in some of the countries. Most of the "putative serotype 6E" isolates showed very high resistance rates against cefuroxime, erythromycin, azithromycin, clarithromycin, clindamycin, and trimethoprim/sulfamethoxazole, probably due to their highly resistant to antimicrobials clone, CC90. Our results indicate that "putative serotype 6E" is prevalent in Asian countries. The clonal dissemination of "putative serotype 6E" isolates was also identified.


A novel normalization for amide proton transfer CEST MRI to correct for fat signal-induced artifacts: application to human breast cancer imaging.
The application of amide proton transfer (APT) CEST MRI for diagnosis of breast cancer is of emerging interest. However, APT imaging in the human breast is affected by the ubiquitous fat signal preventing a straightforward application of existing acquisition protocols. Although the spectral region of the APT signal does not coincide with fat resonances, the fat signal leads to an incorrect normalization of the Z-spectrum, and therefore to distorted APT effects. In this study, we propose a novel normalization for APT-CEST MRI that corrects for fat signal-induced artifacts in the postprocessing without the need for application of fat saturation schemes or water-fat separation approaches. The novel normalization uses the residual signal at the spectral position of the direct water saturation to estimate the fat contribution. A comprehensive theoretical description of the normalization for an arbitrary phase relation of the water and fat signal is provided. Functionality and applicability of the proposed normalization was demonstrated by in vitro and in vivo experiments. In vitro, an underestimation of the conventional APT contrast of approximately -1.2% per 1% fat fraction was observed. The novel normalization yielded an APT contrast independent of the fat contribution, which was also independent of the water-fat phase relation. This allowed APT imaging in patients with mamma carcinoma corrected for fat signal contribution, field inhomogeneities, spillover dilution, and water relaxation effects. The proposed normalization increases the specificity of APT imaging in tissues with varying fat content and represents a time-efficient and specific absorption rate-efficient alternative to fat saturation and water-fat separation approaches.