PTGS2 (COX-2) -765 G > C functional promoter polymorphism and its association with risk and lymph node metastasis in nasopharyngeal carcinoma.
Cyclooxygenase-2 (Cox-2) is a key enzyme in the conversion of arachidonic acid to prostaglandins that has been shown to have a particular importance in the progression of several malignancies including nasopharyngeal carcinoma (NPC). In the current report, we designed a case-controlled study to evaluate the susceptibility and prognostic implications of the functional -765 G > C genetic variation in NPC. A PCR and restriction fragment length polymorphism analysis was used to determine the polymorphism in a Tunisian population of patients with NPC (n = 180) and in healthy control subjects (n = 169). A higher risk for NPC was observed for carriers of COX-2 -765 C allele (OR = 1.76; P = 0.01). This association remains significant after adjustments for age and sex (OR = 1.89; P = 0.008). Regarding prognostic indicators, a significant association was found between -765 C allele carriers and the presence of lymph node metastasis (OR = 2.28; P = 0.01), as well as, with tumor stage (OR = 2.73; P = 0.03). This is the first report on the studies of COX-2 SNPs in NPC and our data suggest that this genetic variant may play a role in mediating susceptibility to NPC, as well as, in neoplastic progression, a finding which further supports the involvement of COX-2 in NPC etiology.


Effectiveness of Chinese herbal medicine in treating liver fibrosis: a systematic review and meta-analysis of randomized controlled trials.
The studies on the effectiveness of Chinese herbal medicines (CHM) in treating liver fibrosis (LF) were not consistent. This study aims to systematically review the effectiveness of CHM on treating LF patients. Databases including MEDLINE, AMED, EMBASE, The Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, TCMOnline, Chinese Biomedical Literature Database, and Chinese Medical Current Contents were searched up to March 2011. Randomized controlled trials (RCTs) involving LF patients receiving CHM, Western medicine, combined CHM and Western medicine compared with placebo, Western medicine or no intervention were included. LF markers including serum hyaluronic acid (HA), laminin (LN), procollagen type III (PC-III), type IV collagen (IV-C), matrix metalloproteinase (MMP), and tissue inhibitors of metalloproteinase (TIMP) were measured as primary outcomes. Liver biochemistry, including alanine aminotransferase (ALT) and aspartarte aminotransferase (AST), and improvement of related clinical symptoms were measured as secondary outcomes. Risk of bias of allocation sequence, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases were assessed. Twenty-three RCTs with 2123 participants were analyzed in subgroups of types of comparison and study quality. Fifteen studies were graded as good quality. CHM alone and combined with Western medicine showed significant improvements in HA, LN, PC-III and IV-C compared with Western medicine alone. However, there were no significant differences observed between CHM and placebo treatments. The current inconclusive results in determining the effectiveness of CHM treatment on LF, due to the poor methodological quality and high heterogeneity of the studies, suggests that large RCTs using standardized Chinese medicine syndrome diagnosis and CHM formulae with longer follow-up are required for further evaluation.


Comparative study of surface plasmon resonance, electrochemical and electroassisted chemiluminescence methods based immunosensor for the determination of antibodies against human growth hormone.
An indirect immunoassay format with human growth hormone (hGH) immobilized on the self-assembled monolayer (SAM) modified surface plasmon resonance (SPR) chip has been shown to detect specific anti-hGH antibodies using the combination of three different physical phenomena in the same channel of the SPR analyzer. For the enhancement of analytical signal and sensitivity of the immunosensor horseradish peroxidase (HRP) labeled secondary antibodies, specifically interacting with the formed immune complexes, were used. The electroassisted chemiluminescence (ECL) protocol offered the limit of detection (LOD) as low as 0.061 nM and this result was very similar to that obtained by SPR, which was 0.051 nM. In the case of anti-hGH detection using pulsed amperometry (PA) with 3,3',5,5'-tetramethylbenzidine (TMB) and H(2)O(2) in the electrochemical system the LOD was the lowest - 0.027 nm. Lower reproducibility of the analytical signal and higher limit of detection was observed using cyclic voltammetry (CV) where LOD was 0.056 nM. PA detection shows 1.89, 2.07 and 2.26 times higher sensitivity if compared with SPR, CV and ECL, respectively. This work demonstrates successful simultaneous exploitation of several techniques to detect the specific anti-hGH antibodies using indirect immunoassay format on the same area of the SPR-chip.


"I'm a Mother Who Always Tries to Give My Children Hope"-Refugee Women's Experiences of Their Children's Mental Health.
Background: The prevalence of mental health problems is high among refugee children. Childhood mental health problems have long-term negative consequences and costs both for the individual child and society. The present study aimed to explore refugee parents' experiences of their children's mental health. Methodology: A qualitative explorative study was conducted. Data were collected through semistructured interviews with nine refugee mothers who have been in Sweden less than 5 years and with at least one child in the ages 8-14 years. Data were analyzed inductively using thematic network analysis. Results: The global theme that emerged from the analysis was Navigating the moving landscape of forced migration, which described the refugee mothers' experiences of the previous adversity the family went through, the ongoing transition in the new context, and, lastly, the pathways to promote their children's mental health. Two organizing themes described mothers' and children's navigation of the forced migration: Previous adverse events and new suffering and Promoting children's well-being. Mothers described aggression and frequent conflicts, or refusal to play or eat, in their children related to living conditions at asylum centres and social isolation. This improved when children started school and possibilities of social relations increased. Mothers' own mental health and lack of language skills could also have a negative impact on the children. To focus on the present and have hope of the future was helpful to the children. Encouragement and social support from parents, teachers, and friends promoted children's well-being. Conclusion: The role of the host country in the promotion of the mental health of refugee children is emphasized. Interventions aimed to improve peer relations and reduce discrimination are needed, and these point to the school as a potential arena for positive change. Parental support groups were also mentioned as helpful in understanding the children's need for support.


Evaporation and canopy characteristics of coniferous forests and grasslands.
Canopy-scale evaporation rate (E) and derived surface and aerodynamic conductances for the transfer of water vapour (gs and ga, respectively) are reviewed for coniferous forests and grasslands. Despite the extremes of canopy structure, the two vegetation types have similar maximum hourly evaporation rates (E max) and maximum surface conductances (gsmax) (medians = 0.46 mm h-1 and 22 mm s-1). However, on a daily basis, median E max of coniferous forest (4.0 mm d-1) is significantly lower than that of grassland (4.6 mm d-1). Additionally, a representative value of ga for coniferous forest (200 mm s-1) is an order of magnitude more than the corresponding value for grassland (25 mm s-1). The proportional sensitivity of E, calculated by the Penman-Monteith equation, to changes in gs is >0.7 for coniferous forest, but as low as 0.3 for grassland. The proportional sensitivity of E to changes in ga is generally ±0.15 or less.Boundary-line relationships between gs and light and air saturation deficit (D) vary considerably. Attainment of gsmax occurs at a much lower irradiance for coniferous forest than for grassland (15 versus about 45% of full sunlight). Relationships between gs and D measured above the canopy appear to be fairly uniform for coniferous forest, but are variable for grassland. More uniform relationships may be found for surfaces with relatively small ga, like grassland, by using D at the evaporating surface (D0) as the independent variable rather than D at a reference point above the surface. An analytical expression is given for determining D0 from measurable quantities. Evaporation rate also depends on the availability of water in the root zone.Below a critical value of soil water storage, the ratio of evaporation rate to the available energy tends to decrease sharply and linearly with decreasing soil water content. At the lowest value of soil water content, this ratio declines by up to a factor of 4 from the non-soil-water-limiting plateau. Knowledge about functional rooting depth of different plant species remains rather limited. Ignorance of this important variable makes it generally difficult to obtain accurate estimates of seasonal evaporation from terrestrial ecosystems.


Characterization of hemicellulases from thermophilic fungi.
The thermophilic fungi Thermomyces lanuginosus, Malbranchea cinnamomea, Myceliophthora fergusii and the thermotolerant Aspergillus terreus were cultivated on various carbon sources, and hemicellulolytic and cellulolytic enzyme profiles were evaluated. All fungi could grow on locust bean galactomannan (LBG), Solka floc, wheat bran and pectin, except T. lanuginosus, which failed to utilize LBG for growth. Different levels of cellulase and hemicellulase activities were produced by these fungal strains. Depending on the carbon source, variable ratios of thermostable hydrolytic enzymes were obtained, which may be useful in various applications. All strains were found to secrete xylanolytic and mannanolytic enzymes. Generally, LBG was the most efficient carbon source to induce mannanase activities, although T. lanuginosus was able to produce mannanase only on wheat bran as a carbon source. Xylanolytic activities were usually highest on wheat bran medium, but in contrast to other investigated fungi, xylanase production by M. fergusii was enhanced on pectin medium. Preliminary thermostability screening indicated that among the investigated species, thermotolerant glycosidases can be found. Some of the accessory activities, including the α-arabinosidase activity, were surprisingly high. The capability of the produced enzymes to improve the hydrolysis of lignocellulosic pretreated substrate was evaluated and revealed potential for these enzymes.


Scurvy: historical review and current diagnostic approach.
Scurvy, a deficiency of vitamin C, now most often occurs in disadvantaged groups seen frequently in EDs: alcoholics with poor nutrition, the isolated elderly, and the institutionalized. Its prominent clinical features are lethargy; purpuric lesions, especially affecting the legs; myalgia; and, in advancing disease, bleeding from the gums with little provocation. Common misdiagnoses are vasculitis, blood dyscrasias, and ulcerative gingivitis. Untreated, scurvy is inevitably fatal as a result of infection or sudden death. Fortunately, individuals with scurvy, even those with advanced disease, respond favorably to administration of vitamin C.


Immunological protein profiling of first-episode psychosis patients identifies CSF and blood biomarkers correlating with disease severity.
Immune activation is suggested to play an important role in psychosis. In this study, a large number of immune-related proteins were analyzed to obtain a more comprehensive picture of immune aberrations in schizophrenia. Ninety-two immune markers were analyzed by the Olink Protein Extension Assay (Inflammatory Panel) in plasma and cerebrospinal fluid (CSF) from 77 first-episode psychosis (FEP) patients (of which 43 later received the diagnosis of schizophrenia) and 56 healthy controls, all recruited from the Karolinska Schizophrenia Project (KaSP), Stockholm, Sweden. Differential analysis showed that 12 of 92 inflammatory proteins were significantly higher in the plasma of FEP patients (n = 77) than in controls, and several proteins were positively correlated with disease severity. Patients from the same cohort diagnosed with schizophrenia (n = 43), showed significantly higher levels of 15 plasma proteins compared to controls whereas those not receiving this diagnosis showed no significant differences. The presently used OLINK inflammatory panel allowed the detection of only 47 CSF proteins of which only CD5 differed between patients and controls. The levels of several peripheral immune markers, particularly those interfering with WNT/β-catenin signaling, were significantly higher in patients with FEP than in healthy controls and associated with illness severity.


Changes in inflammatory balance correlates with conversion to psychosis among individuals at clinical high-risk: A prospective cohort study.
Previous studies have revealed that the imbalance between Th1 cytokines and Th2 cytokines plays a role in disturbance of cellular responses in the brain during psychosis. Cross-sectional studies have implied that inflammatory cytokine changes emerge in early psychosis, even at the at-risk stage. This study aimed to test the hypothesis that inflammatory imbalance in clinical high-risk (CHR) individuals is associated with an increased risk of future psychosis. A prospective case-control study was performed to assess the Th1(interleukin (IL)-1β)/Th2(IL-6) balance in 84 CHR individuals and 65 age- and sex-matched healthy controls (HC). Serum IL-1β and IL-6 levels were measured by enzyme-linked immunosorbent assay at baseline and 1-year after the completion of the clinical assessment. Sixteen (19.0%) CHR participants converted to full psychosis during the 1-year follow-up period. At baseline, serum IL-1β level was significantly lower in the CHR-converter group - resulting in decreased IL-1β/IL-6 ratios - compared to those of the CHR-non-converter and HC groups. At the 1-year follow-up, IL-1β level had decreased, and IL-1β/IL-6 ratios had decreased in the CHR-non-converter group, such that these were comparable to values in the CHR-converter at this time point. Analysis of the changes in IL-1β/IL-6 ratio between the baseline and 1-year follow-up measurements identified different trajectories in the CHR-converter and CHR-non-converter groups. Our findings demonstrate that a specific pattern of Th1/Th2 imbalance (decreased IL-1β/IL-6 ratios with lower serum IL-1β level) is associated with an increased risk of developing psychosis. Such specific pattern has potential for predicting conversion outcomes and selecting a distinct subgroup of CHR with immune-imbalanced-phenotype, that relevance in precise prevention.


Development and assessment of social and emotional competence through simulated patient consultations.
To determine whether a quantitative tool could be used to measure social emotional competence and whether the development of social emotional competence through a pharmacy practicum course is possible. First-year pharmacy students completed the Social Emotional Development Inventory (SED-I) online and then participated in a series of mock patient consultations on smoking cessation and nonprescription medication. The 212 students enrolled in the course completed the SED-I. Evaluation of students' performance in the clinical cases using a patient counseling assessment form showed that students' social emotional competencies significantly improved. Observer ratings for "influence" and "connection" on the assessment form predicted student performance in the clinical cases. Role-play exercises in which students engage in patient consultations can be used to develop social emotional competence in pharmacy students, and the SED-I and a patient counseling assessment form can be used to assess learning and improvement in this area.


Prognostic significance of KN motif and ankyrin repeat domains 1 (KANK1) in invasive breast cancer.
KN motif and ankyrin repeat domains 1 (KANK1) plays an important role in cytoskeleton maintenance and contributes to the regulation of cell proliferation, adhesion and apoptosis. KANK1 is involved in progression of a variety of solid tumours; however, its role in invasive breast cancer (BC) remains unknown. This study aims to evaluate the clinicopathological and prognostic value of KANK1 expression in operable BC. KANK1 expression was assessed at the transcriptomic level using multiple BC cohorts; the Molecular Taxonomy of BC International Consortium cohort (METABRIC; n = 1980), The Cancer Genome Atlas BC cohort (TCGA; n = 949) and the publicly available BC transcriptomic data hosted by BC Gene-Expression Miner (bc-GenExMiner v4.0) and Kaplan-Meier plotter?. The Nottingham BC cohort (n = 1500) prepared as tissue microarrays was used to assess KANK1 protein expression using immunohistochemistry (IHC). The association between clinicopathological variables and patient outcome was investigated. In the METABRIC cohort, high expression of KANK1 mRNA was associated with characteristics of good prognosis including lower grade, absence of lymphovascular invasion and HER2 negativity (all; p < 0.001) and with better outcome [p = 0.006, Hazards ratio, (HR) 0.70, 95% CI 0.54-0.91]. High KANK1 protein expression was correlated with smaller tumour size and HER2 negativity, and better outcome in terms of longer breast cancer-specific survival [p = 0.013, HR 0.7, 95% CI 0.536-0.893] and time to distant metastasis [p = 0.033, HR 0.65, 95% CI 0.51-0.819]. These results supported that upregulation of KANK1 works as a tumour suppressor gene in BC and is associated with improved patients' outcomes.


Determination of complex polysaccharides by HPAE-PAD in foods: validation using accuracy profile.
The increasing supplementation of foods with carbohydrates substitutes and the growing regulatory requirements for controlling these products, turn into the necessary development and validation of accurate analytical control techniques. This paper presents the simultaneous validation of two close analytical procedures for the determination of sucralose and fructooligosaccharides (FOS) in fruit juices using high-performance anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD). This study consisted in applying the accuracy profile procedure with a three-level validation experimental design. Decision criteria, namely acceptability limits (+/-10%) and proportion of result contained in the calculated tolerance intervals (80%), were decided on a consensus basis with end-users, whereas no official references were available. In conclusion, the proposed analytical procedures were validated over the selected validation domains for fruit juices and came out on very capable techniques. Validation strategy was purposely oriented towards the ease of use in routine and the liability of the methods rather than extreme performances. This objective is consistent with this of contract laboratories which need to reach a known level of guarantee for the results which they produce. In that respect, accuracy profile represents a very convenient tool to ascertain such a goal.


Bioinformatics-guided disproportionality analysis of sevoflurane-induced nephrogenic diabetes insipidus using the FDA Adverse Event Reporting System database.
Sevoflurane is an ether-based inhalational anaesthetic that induces and maintains general anaesthesia. Our study aimed to detect sevoflurane-induced nephrogenic diabetes insipidus using data mining algorithms (DMAs) and molecular docking. The FAERS database was analysed using OpenVigil 2.1 for disproportionality analysis. We analysed FAERS data from 2004 to 2022 to determine the incidence of nephrogenic diabetes insipidus associated with sevoflurane. Reporting odds ratios (RORs) and proportional reporting ratios (PRRs) with 95% confidence intervals were calculated. We also used molecular docking with AutoDock Vina to examine sevoflurane's binding affinity to relevant receptors. A total of 554 nephrogenic diabetes insipidus cases were reported in FAERS, of which 2.5% (14 cases) were associated with sevoflurane. Positive signals were observed for sevoflurane with ROR of 76.012 (95% CI: 44.67-129.35) and PRR of 75.72 (χ2 : 934.688). Of the 14 cases, 50% required hospitalization, 14% resulted in death, and the remaining cases were categorized as other outcomes. Molecular docking analysis showed that sevoflurane exhibited high binding affinity towards AQP2 (4NEF) and AVPR2 (6U1N) with docking scores of -4.9 and -5.3, respectively. Sevoflurane use is significantly associated with the incidence of nephrogenic diabetes insipidus. Healthcare professionals should be cautious when using this medication and report any adverse events to regulatory agencies. Further research is needed to validate these findings and identify risk factors while performing statistical adjustments to prevent false-positives. Clinical monitoring is crucial to validate potential adverse effects of sevoflurane.


The MYC-YBX1 Circuit in Maintaining Stem-like Vincristine-Resistant Cells in Rhabdomyosarcoma.
Rhabdomyosarcoma (RMS) is a pediatric soft tissue sarcoma that causes significant devastation, with no effective therapy for relapsed disease. The mechanisms behind treatment failures are poorly understood. Our study showed that treatment of RMS cells with vincristine led to an increase in CD133-positive stem-like resistant cells. Single cell RNAseq analysis revealed that MYC and YBX1 were among the top-scoring transcription factors in CD133-high expressing cells. Targeting MYC and YBX1 using CRISPR/Cas9 reduced stem-like characteristics and viability of the vincristine-resistant cells. MYC and YBX1 showed mutual regulation, with MYC binding to the YBX1 promoter and YBX1 binding to MYC mRNA. The MYC inhibitor MYC361i synergized with vincristine to reduce tumor growth and stem-like cells in a zebrafish model of RMS. MYC and YBX expression showed a positive correlation in RMS patients, and high MYC expression correlated with poor survival. Targeting the MYC-YBX1 axis holds promise for improving survival in RMS patients.


A phase I study of meta-azidopyrimethamine ethanesulphonate (MZPES)--a new dihydrofolate reductase inhibitor.
A total of 68 patients were treated in a phase I study of meta-azidopyrimethamine ethanesulphonate (MZPES)--a novel lipophilic dihydrofolate reductase (DHFR) antagonist. The dose was increased from 5.4 mg/m2 to 460 mg/m2 given as a 1-h infusion, with 460 mg/m2, 600 mg/m2 and 800 mg/m2 given as a 24-h infusion. The dose-limiting toxicity was nausea and vomiting, which was marked at doses above 360 mg/m2 by 1-h infusion and 600 mg/m2 by 24-h infusion. Above 250 mg/m2 patients also described subjective neurological symptoms, although no objective signs were apparent. Myelosuppression was not consistent at any dose level. No objective responses were seen. In view of the lack of anti-folate activity at toxic levels, no phase II trials are currently proposed; toxicological and in vitro studies will continue.


Women's health, men's health, and gender and health: implications of intersectionality.
Although intersectionality is now recognized in the context of women's health, men's health, and gender and health, its full implications for research, policy, and practice have not yet been interrogated. This paper investigates, from an intersectionality perspective, the common struggles within each field to confront the complex interplay of factors that shape health inequities. Drawing on developments within intersectionality scholarship and various sources of research and policy evidence (including examples from the field of HIV/AIDS), the paper demonstrates the methodological feasibility of intersectionality and in particular, the wide-ranging benefits of de-centering gender through intersectional analyses.


Quantum chemical modification of indaceno dithiophene-based small acceptor molecules with enhanced photovoltaic aspects for highly efficient organic solar cells.
In this computational work, with the aim of boosting the ultimate efficiency of organic photovoltaic cells, seven small acceptors (IDST1-IDST7) were proposed by altering the terminal-acceptors of reference molecule IDSTR. The optoelectronic characteristics of the IDSTR and IDST1-IDST7 molecules were investigated using the MPW1PW91/6-31G(d,p) level of theory, and solvent-state computations were examined using time-dependent density functional theory (TD-DFT) simulation. Nearly all the investigated photovoltaic aspects of the newly proposed molecules were found to be better than those of the IDSTR molecule e.g. in comparison to IDSTR, IDST1-IDST7 exhibit a narrower bandgap (E gap), lower first excitation energy (E x), and a significant red-shift in the absorbance maxima (λ max). According to the findings, IDST3 has the lowest E x (1.61 eV), the greatest λ max (770 nm), and the shortest E gap (2.09 eV). IDST1-IDST7 molecules have higher electron mobility because their RE of electrons is less than that of IDSTR. Hole mobility of IDST2-IDST7 is higher than that of the reference owing to their lower RE for hole mobility than IDSTR. By coupling with the PTB7-Th donor, the open circuit voltage (V OC) of the investigated acceptor molecules (IDSTR and IDST1-IDST7) was calculated and investigation revealed that IDST4-IDST6 molecules showed higher V OC and fill factor (FF) values than IDSTR molecules. Accordingly, the modified molecules can be seriously evaluated for actual use in the fabrication of OSCs with enhanced photovoltaic and optoelectronic characteristics in light of the findings of this study.


The use of low-calorie sweeteners is associated with self-reported prior intent to lose weight in a representative sample of US adults.
Low-calorie sweeteners (LCSs) are said to be a risk factor for obesity and diabetes. Reverse causality may be an alternative explanation. Data on LCS use, from a single 24-h dietary recall, for a representative sample of 22 231 adults were obtained from 5 cycles of the National Health and Nutrition Examination Survey (1999-2008 NHANES). Retrospective data on intent to lose or maintain weight during the prior 12-months and 10-year weight history were obtained from the weight history questionnaire. Objectively measured heights and weights were obtained from the examination. Primary analyses evaluated the association between intent to lose/maintain weight and use of LCSs and specific LCS product types using survey-weighted generalized linear models. We further evaluated whether body mass index (BMI) may mediate the association between weight loss intent and use of LCSs. The association between 10-year weight history and current LCS use was evaluated using restricted cubic splines. In cross-sectional analyses, LCS use was associated with a higher prevalence of obesity and diabetes. Adults who tried to lose weight during the previous 12 months were more likely to consume LCS beverages (prevalence ratio=1.64, 95% confidence interval (CI) 1.54-1.75), tabletop LCS (prevalence ratio=1.68, 95% CI 1.47-1.91) and LCS foods (prevalence ratio=1.93, 95% CI 1.60-2.33) as compared with those who did not. In mediation analyses, BMI only partially mediated the association between weight control history and the use of LCS beverages, tabletop LCS, but not LCS foods. Current LCS use was further associated with a history of prior weight change (for example, weight loss and gain). LCS use was associated with self-reported intent to lose weight during the previous 12 months. This association was only partially mediated by differences in BMI. Any inference of causality between attempts at weight control and LCS use is tempered by the cross-sectional nature of these data and retrospective self-reports of prior weight loss/maintenance intent.


A simple and high yield purification of Crotalus adamanteus phospholipases A2.
A new, high yield, procedure for the purification of the phospholipases A2 of Crotalus adamanteus venom is described. The procedure involves precipitation of the bulk of venom proteins with 50% isopropanol, precipitation of the enzymes from the isopranol soluble material with neodynium chloride, and final purification on DEAE cellulose. An overall yield of approximately 80% is achieved.


Electrochemical, optical and mass-based immunosensors: A comprehensive review of Bacillus anthracis detection methods.
A biosensor is an analytical device whose main components include transducer and bioreceptor segments. The combination of biological recognition with the ligand is followed by transformation into physical or chemical signals. Many publications describe biological sensors as user-friendly, easy, portable, and less time-consuming than conventional methods. Among major categories of methods for the detection of Bacillus anthracis, such as culture-based microbiological method, polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), microarray-based techniques sensors with bioreceptors have been highlighted which particular emphasis is placed on herein. There are several types of biosensors based on various chemical or physical transducers (e.g., electrochemical, optical, piezoelectric, thermal or magnetic electrodes) and the type of biological materials used (e.g., enzymes, nucleic acids, antibodies, cells, phages or tissues). In recent decades, antibody-based sensors have increasingly gained popularity due to their reliability, sensitivity and rapidness. The fundamental principle of antibody-based sensors is mainly based on the molecular recognition between antigens and antibodies. Therefore, immunosensors that detect B. anthracis surface antigens can provide a rapid tool for detecting anthrax bacilli and spores, especially in situ. This review provides a comprehensive summary of immunosensor-based methods using electrochemical, optical, and mass-based transducers to detect B. anthracis.


Oropharyngeal colonisation with fungi and gram-negative rods in patients treated with radiotherapy of the head and neck.
Twenty-five patients treated for malignant conditions of the head and neck were investigated for the development of oral radiation mucositis as well as oropharyngeal colonisation with fungi and Gram-negative bacilli. The colonisation rate of the patients increased from 20% to 80% during therapy. The patients were colonised mainly with fungi, but also to a lesser extent with Gram-negative bacilli. During radiotherapy free volatile fatty acids in saliva were determined by direct gas-liquid chromatography. The amounts of acetic, butyric and propionic acid decreased during radiotherapy and remained at low levels 6 months after therapy. Radiation induced mucositis was observed in 28% of the patients after 1 week of irradiation. After 3 weeks of therapy all patients showed varying grades of mucositis. In seven of the 19 survivors (36%) erythema was still present 6 months after radiotherapy.


Effect of a high dose of vasopressin on an inhibition avoidance response.
1. This experiment was performed to assess the action of a posttrial high dose of lysine-vasopressin (20.0 I.U./kg) on the maintenance of an inhibitory avoidance response measured in a modified step-through test. 2. In the 24 hr, 48 hr, 72 hr, and 192 hr testings, there was a progressive increase in latencies for control and vasopressin-treated groups. However, in the 384 hr testing, the latency score shown by the experimental group dropped as compared with saline-treated group. 3. These preliminary data suggested there was a non-monotonic time-dependent dose/response curve for behavioral effects of vasopressin.


The incorporation of 32 P into spectrin aggregates following incubation of erythrocytes in 32 P-labelled inorganic phosphate.
32P was incorporated into spectrin by incubation of fresh erythrocytes with 32Pi and glucose. The dimer and tetramer aggregates revealed only covalently-bound incorporation of phosphorus, while a higher aggregate of spectrin revealed both covalent and non-covalent incorporation. The specific activity of the covalently-bound phosphorus in all oligomers was identical, suggesting that the state of association is independent of phosphorylation. The non-covalent incorporation was shown to be due to the association of ATP with this higher aggregate. The nucleotide appers not to be bound directly to spectrin but rather to component 5 (erythrocyte actin) which is also found to be associated with this highly aggregated spectrin structure.


Lipid metabolism and lung cancer.
Lung cancer is currently one of the most serious health issues in developed and developing countries. There are multiple available treatment options; however survival still remains very poor. Despite metabolism alteration being one of the hallmarks described in human cancer, lipid metabolism disorders are less known. They are recently becoming more important in this setting and therefore achieving a deeper knowledge might be helpful to obtain new strategies to accurate diagnosis, estimate prognosis, and develop therapeutic agents based on bioactive compounds such as cerulenin, SCD1, ACLY inhibitors, statins, polyphenolic compounds, etc. The present paper reviews the basis of lipid metabolism in lung cancer and suggests potential biomarkers. Further investigation is crucial to improve our knowledge in this area.


What science means to me: Understanding personal identification with (evolutionary) science using the sociology of (non)religion.
Within science and technology studies, there is an established tradition of examining publics' knowledge of, trust in, access to and engagement with science, but less attention has been paid to whether and why publics identify with science. While this is understandable given the field's interest in bridging gaps between publics and producers of scientific knowledge, it leaves unanswered questions about how science forms part of people's worldviews and fits into cultural politics and conflict. Based on 123 interviews and 16 focus groups with mixed religious and nonreligious publics and scientists in the United Kingdom and Canada, this article utilises approaches from the sociology of (non)religion to delineate varieties of science identification. It maps out 'practical', 'norm-based', 'civilisational' and 'existential' identifications and explores how these interrelate with people's social characteristics. The article illustrates how science identification is typically dependent on a constellation of cultural/political influences rather than just emerging out of interest in science.


Critical behavior in a stochastic model of vector mediated epidemics.
The extreme vulnerability of humans to new and old pathogens is constantly highlighted by unbound outbreaks of epidemics. This vulnerability is both direct, producing illness in humans (dengue, malaria), and also indirect, affecting its supplies (bird and swine flu, Pierce disease, and olive quick decline syndrome). In most cases, the pathogens responsible for an illness spread through vectors. In general, disease evolution may be an uncontrollable propagation or a transient outbreak with limited diffusion. This depends on the physiological parameters of hosts and vectors (susceptibility to the illness, virulence, chronicity of the disease, lifetime of the vectors, etc.). In this perspective and with these motivations, we analyzed a stochastic lattice model able to capture the critical behavior of such epidemics over a limited time horizon and with a finite amount of resources. The model exhibits a critical line of transition that separates spreading and non-spreading phases. The critical line is studied with new analytical methods and direct simulations. Critical exponents are found to be the same as those of dynamical percolation.


MRI of prostatic urethral mucinous urothelial carcinoma: Expanding the differential diagnosis for T2 hyperintense prostatic masses.
We report the case of a 66-year-old previously healthy man presenting with blood and mucus in his urine. Cystoscopy revealed a mass in the prostatic urethra, and endoscopic biopsy showed adenocarcinoma in situ with mucinous features. Endorectal multiparametric prostate MRI demonstrated a 1.9 cm T2 hyperintense mass in the peripheral zone of the left prostatic apex with extension into the urethral lumen. No diffusion restriction or early enhancement was seen in the mass. Radical prostatectomy was performed, and final pathology demonstrated a mucin-producing urothelial adenocarcinoma arising from the prostatic urethra. The peripheral zone T2 hyperintense abnormality correlated with abundant pools of mucin extending into the prostatic stroma and surrounded by neoplastic prostatic glandular cells. We conclude prostatic urethral mucinous urothelial carcinoma should be included in the differential diagnosis for T2 hyperintense prostatic masses.


Choosing Wisely and reducing the simultaneous ordering of erythrocyte sedimentation rate and C-reactive protein testing in a large safety net system.
C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are commonly used inflammatory markers. C-reactive protein is more sensitive and specific for monitoring acute inflammation. However, it is commonly co-ordered with ESR despite recommendations against this. Our objective was to reduce unnecessary ESR orders and ESR/CRP co-ordering rates across a large safety net health system. This was a quality improvement project that used a quasi-experimental pre- and postintervention interrupted time-series regression analysis. Patients with a positive COVID-19 test were excluded. We designed a nonintrusive, normative nudge within the ESR order that recommended against co-ordering ESR and CRP. In addition, a best practice advisory triggered when ESR and CRP were simultaneously ordered. The outcome measures were ESR order rates per 1000 patient days in the inpatient setting and per 1000 patient encounters in the outpatient setting, as well as ESR/CRP co-ordering rates. Inpatient ESR orders decreased from 12.02 preintervention to 5.61 per 1000 patient days (-53.3%, P < .001). Outpatient ESR orders decreased from 6.09 to 4.07 per 1000 patient encounters (-33.2%, P < .001). Relative co-ordering rates decreased by 50%. This electronic health record initiative successfully reduced ESR testing across 11 hospitals and 70 ambulatory centers in a safety net setting.


Metformin restrains ZIKV replication and alleviates virus-induced inflammatory responses in microglia.
The re-emergence of Zika virus (ZIKV) remains a major public health threat that has raised worldwide attention. Accumulating evidence suggests that ZIKV can cause serious pathological changes to the human nervous system, including microcephaly in newborns. Recent studies suggest that metformin, an established treatment for diabetes may play a role in viral infection; however, little is known about the interactions between ZIKV infection and metformin administration. Using fluorescent ZIKV by flow cytometry and immunofluorescence imaging, we found that ZIKV can infect microglia in a dose-dependent manner. Metformin diminished ZIKV replication without the alteration of viral entry and phagocytosis. Our study demonstrated that metformin downregulated ZIKV-induced inflammatory response in microglia in a time- and dose-dependent manner. Our RNA-Seq and qRT-PCR analysis found that type I and III interferons (IFN), such as IFNα2, IFNβ1 and IFNλ3 were upregulated in ZIKV-infected cells by metformin treatment, accompanied with the downregulation of GBP4, OAS1, MX1 and ISG15. Together, our results suggest that metformin-mediated modulation in multiple pathways may attribute to restraining ZIKV infection in microglia, which may provide a potential tool to consider for use in unique clinical circumstances.


Robotic natural orifice transluminal endoscopic surgery (NOTES) hysterectomy as a scarless and gasless surgery.
To report a new surgical technique for hysterectomy using robotic natural orifice transluminal endoscopic surgery (NOTES) as a scarless and gasless procedure. Thirteen consecutive patients with benign uterine disease underwent robotic NOTES hysterectomy at Eulji University Hospital between February 2017 and May 2018. Due to the presence of pelvic adhesions, one of these patients underwent hybrid robotic NOTES hysterectomy with the assistance of isobaric single port laparoscopy; however, there was no conversion to another hysterectomy type such as conventional laparoscopy, laparotomy, or traditional multiport robotic surgery. Median uterine weight was 290 g (range 115-892 g). Median docking and console times were 15 min (range 5-25 min) and 135 min (range 92-215 min), respectively. Mean change in hemoglobin on the first postoperative day was 0.67 ± 0.7 g/dL. Median EBL was 50 mL (20-450 mL). Median postoperative hospital stay was 3 days (3-4 days). No patients experienced postoperative complications such as damage to adjacent organs, re-operation, or vaginal cuff hematoma. Our findings show that robotic NOTES hysterectomy is a feasible and safe scarless and gasless surgical technique. It is an effective, minimally invasive vaginal access alternate to NOTES-assisted vaginal hysterectomy or conventional robotic laparoendoscopic single-site surgery hysterectomy in the surgical management of benign uterine disease. Nevertheless, further prospective controlled studies are needed to determine its full clinical application.


A comparative analysis of the cephalic microbiome: The ocular, aural, nasal/nasopharyngeal, oral and facial dermal niches.
The human face/head supports a highly diverse population of microorganisms across a diverse range of microhabitats. This biogeographical diversity has given rise to selection pressure resulting in the formation of distinct bacterial communities between sites. This review investigates the similarity and differences of microbiomes across the different biogeographies of the human face and discusses a potential pathway for microbial circulation within individuals and within a population to maintain microbiome niches and diversity.


Use of total leukocyte and platelet counts to guide stem cell apheresis in healthy allogeneic donors treated with G-CSF.
Healthy stem cell donors start leukapheresis 4-5 days after starting G-CSF based on the peripheral blood CD34+ cell count (PBCD34). Data from 137 harvests (68 donors) were analyzed to determine correlation between pre-apheresis leukocytes (11.0-94.8x10(9)/l; median 38.8) and platelets (49-374x10(9)/l; median 180), and PBCD34 (3-276/microl; median 40). PBCD34 correlated positively with leukocytes (r=0.48; P<0.0001) and platelets (r=0.40; P<0.0001). When pre-apheresis leukocytes were >or=25 and platelets were >or=100, PBCD34 and CD34+ collection were 5-276/microl (median 57) and 0.5-27.6x10(6)/kg (median 4.7), respectively; significantly higher than PBCD34 of 3-74/microl (median 17) and CD34+ collection of 0.2-8.9 x 10(6)/kg (median 2.2) when leukocytes were <25 and/or platelets were <100. With leukocytes >or=25 and platelets >or=100, PBCD34 was low (<20/microl) 8% of the time, compared to 57% of the time with leukocytes <25 and/or platelets <100 (P<0.0001). Our data suggest that it is not always necessary to measure PBCD34 to guide leukapheresis in healthy donors because pre-apheresis leukocytes and platelets >or=25 and >or=100, respectively, are associated with excellent mobilization. When blood counts do not meet these criteria, PBCD34 should be determined prior to initiation of apheresis.


Leaf temperatures of desert plants.
Temperatures of small leaves of many desert plants are within 3 degrees C of air temperature in contrast to the temperature of Opuntia in the same locale; this plant has a temperature 10 degrees to 16 degrees C above air temperature. Theoretical4 justification for the observation is given based on an energy budget analysis.


Effects of benzodiazepines and pentobarbitone on the gaba-ergic recurrent inhibition of hippocampal neurons.
The actions of benzodiazepines and pentobarbitone on GABA-mediated recurrent inhibition of hippocampal pyramidal neurons were investigated in the immobilized unanaesthetized cat. Extracellular action potentials of single neurons were recorded in regions CA1 or CA2 with 4 M NaCl-containing glass micropipettes. Bicuculline (0.1 mg/kg i.v.) reduced the period of inhibition induced by stimulation of the fimbria and the septum, but fludiazepam and diazepam (0.3--1.0 mg/kg i.v.) and pentobarbitone (15--30 mg/kg i.v.) prolonged the inhibition. The prolongation produced by these compounds was antagonized by the administration of bicuculline (0.3 mg/kg i.v.). The results suggest that these two classes of compounds potentiate GABA-mediated recurrent inhibition in hippocampal neurons in a similar way.


Memory span for heterospecific individuals' odors in an ant, Cataglyphis cursor.
Only recently have researchers studied the ability of ants to learn and remember individual heterospecific odors. Cataglyphis cursor adults have the capacity to learn these odors, but the duration of their memory and the factors that affect its formation remain unknown. We used a habituation/discrimination paradigm to study some of these issues. C. cursor adult workers were familiarized to an anesthetized Camponotus aethiops on four successive encounters. Then they were either isolated or placed with 20 nestmates for a certain length of time before undergoing a discrimination test that consisted of reintroducing the familiar C. aethiops, as well as introducing an unknown member of the same colony. The results showed that adult C. cursor ants can retain in memory a complex individual odor for at least 30 min, as well as differentiate it from the odor of another closely related individual. However, when ants were replaced in a rich social background between the habituation and the discrimination trials, we did not observe a significant discrimination between the known and unknown C. aethiops ants. Our study shows, for the first time, the existence of long-term memory for individual odors in mature ant workers.


Effect of iron and estrogen on melatonin secretion by the chicken pineal gland.
Estrogen effects on pineal secretion of melatonin are controversial. Some feel that estrogen inhibits melatonin output in vitro but not in vivo. Melatonin levels vary with the age in chickens where circulating estrogen levels also vary. Laying hens have minimal melatonin levels and maximal serum iron concentrations. Thus, we reasoned that iron released by estrogen may inhibit melatonin secretion from the chick pineal gland. The present study shows that perifusion of estrogen-treated chick pineal glands with several concentrations of iron greatly inhibited melatonin secretion.


Treatment of hand scalds in the paediatric age group: a novel Biobrane glove.
This article describes a technique to create a novel Biobrane glove to treat superficial circumferential paediatrics hand scalds. It includes step by step instructions and illustrations to demonstrate the application of two sheets of Biobrane to cover the entire hand. This method seems to be more cost-effective than the Biobrane glove distributed by Smith & Nephew.


Isolation and cultivation of candidate phyla radiation Saccharibacteria (TM7) bacteria in coculture with bacterial hosts.
The vast majority of bacteria on earth have not yet been cultivated. There are many bacterial phyla with no cultivated examples including most members of the Candidate Phylum Radiation with the exception of human oral isolates from the phylum Saccharibacteria. The aims of this research were to develop reproducible methods and validate approaches for the cultivation of human oral Saccharibacteria and to identify the conceptual pitfalls that delayed isolation of these bacteria for 20 years after their discovery. Oral samples were dispersed and passed through 0.2 µm membrane filters. The ultrasmall saccharibacterial cells in the filtrate were pelleted, inoculated into broth cultures of potential bacterial host cells and passaged into fresh medium every 2-3 days. Thirty-two isolates representing four species of Saccharibacteria were isolated in stable coculture with three species of host bacteria from the phylum Actinobacteria. Complete genome sequences were obtained for 16 isolates. Human oral Saccharibacteria are obligate bacterial parasites that can be stably passaged in coculture with specific species of host bacteria. Isolating these important members of the human oral microbiome, and many natural environments, requires abandoning many of Koch's concepts and methods and embracing novel microbiological approaches.


SF-6D versus EQ-5D: reasons for differences in utility scores and impact on reported cost-utility.
The choice of instrument (e.g. EQ-5D vs. SF-6D) can lead to different health-related utility scores, but it is unclear why these differences arise and whether they change cost utility analysis (CUA) results. This paper addresses these issues using a case study where using SF-6D rather EQ-5D led to greater utility gain and a lower cost per QALY for treatment. The paper examines reasons for this difference. This paper finds that an important factor was the inclusion in the SF-6D descriptive system of separate items for "vitality" and "social functioning", not explicitly included in EQ-5D. Further studies are required that examine the impact of the choice of instrument on cost-utility.


Pars compacta of the sexually dimorphic area of the gerbil hypothalamus: postnatal ages at which development responds to testosterone.
The sexually dimorphic area (SDA) of the gerbil hypothalamus contains a dense cell group in males, the SDA pars compacta (SDApc), that is absent in females and that develops under the influence of testosterone. To determine how long SDApc development remains sensitive to testosterone and if it can be fully masculinized, female gerbils were injected with testosterone propionate on various days after birth. Control females and males received the vehicle. SDApc development was assessed when subjects were 2 weeks old. Exposing females to testosterone before they were 3 days old increased both the incidence and the size of the SDApc. Delaying exposure until 3 days after birth prevented these effects. In females that received testosterone daily for 5 days, starting on the day they were born, the incidence and size of the SDApc were the same as in males.


Tumor factors stimulate lysosomal degradation of tumor antigens and undermine their cross-presentation in lung cancer.
Activities of dendritic cells (DCs) that present tumor antigens are often suppressed in tumors. Here we report that this suppression is induced by tumor microenvironment-derived factors, which activate the activating transcription factor-3 (ATF3) transcription factor and downregulate cholesterol 25-hydroxylase (CH25H). Loss of CH25H in antigen presenting cells isolated from human lung tumors is associated with tumor growth and lung cancer progression. Accordingly, mice lacking CH25H in DCs exhibit an accelerated tumor growth, decreased infiltration and impaired activation of intratumoral CD8+ T cells. These mice do not establish measurable long-term immunity against malignant cells that undergo chemotherapy-induced immunogenic cell death. Mechanistically, downregulation of CH25H stimulates membrane fusion between endo-phagosomes and lysosomes, accelerates lysosomal degradation and restricts cross-presentation of tumor antigens in the intratumoral DCs. Administration of STING agonist MSA-2 reduces the lysosomal activity in DCs, restores antigen cross presentation, and increases therapeutic efficacy of PD-1 blockade against tumour challenge in a CH25H-dependent manner. These studies highlight the importance of downregulation of CH25H in DCs for tumor immune evasion and resistance to therapy.


Worsened outcomes of newly diagnosed cancer in patients with recent emergency care visits: A retrospective cohort study of 3699 adults in a safety net health system.
Many patients receive a suspected diagnosis of cancer through an emergency department (ED) visit. Time to treatment for a new diagnosis of cancer is directly associated with improved outcomes with little no describing the ED utilization prior to the diagnosis of cancer. We hypothesize that patients that have an ED visit in proximity to a diagnosis of cancer will have worse outcomes, including mortality. This study is a retrospective cohort study of all patients with cancer diagnosed at Eskenazi Health (Indiana) between 2016 and 2019. Individual health characteristics, ED utilization, cancer types, and mortality were studied. We compared those patients seen in the ED within 6 months prior to their diagnosis (cases) to patients not seen in the ED (controls). A total of 3699 patients with cancer were included, with 1239 cases (33.50%). Patients of black race had higher frequencies in the cases vs. controls (46.57% vs. 40.68%). Lung cancer was the most frequently observed cancer among cases vs. controls (11.70% vs. 5.57%). For the cases, 232 patients were deceased (18.72%) compared with 247 patients among the controls (10.04%, p < 0.0001, OR 2.06 95% confidence interval [CI] 1.70-2.51). An ED visit in past 6 months (OR = 1.73, 95% CI 1.38-2.18) and Medicaid insurance type (versus commercial, OR = 4.16, 95% CI 2.45-7.07) were associated with of mortality. Female gender (OR = 0.76, 95% CI 0.67-0.88), tobacco use (OR = 1.62, 95% CI 138-1.90), and Medicaid insurance type (versus commercial, OR = 2.56, 95% CI 2.07-3.47) were associated with prior ED use. Over one third of patients with cancer were seen in the ED within 6 months prior to their cancer diagnosis. Higher mortality rates were observed for those seen in the ED. Future studies are needed to investigate the association and impact that the ED has on eventual cancer diagnoses and outcomes.


Language preference as a predictor of access to and use of healthcare services among Hispanics in the United States.
The objective of this study was to determine if Spanish language preference was significantly associated with barriers to healthcare services among a nationally representative sample of Hispanic persons in the United States. Cross-sectional analysis of secondary data. Differences in outcomes between those responding in Spanish and those responding in English were tested using chi-square analyses and multiple logistic regression models. Nationally representative sample of US adults responding to the 2005 Behavioral Risk Factor Surveillance System survey. Respondents identifying themselves as Hispanic (n = 20,400). Four health care outcomes including health insurance coverage, having a personal health care provider, forgoing care because of cost, and having a routine check-up within the past five years. Those responding in Spanish were less likely to have healthcare coverage, less likely to have a personal healthcare provider, and less likely to have had a routine check-up within the past five years. No difference was found for indicating that cost was a barrier to receiving care in this model. Disparities in healthcare access exist between Hispanic persons in the United States whose language preference is Spanish and those whose language preference is English. In an effort to achieve Healthy People 2010 goals and to provide care to all persons in the United States, barriers to care, such as language preference, should be addressed more fully in our healthcare system.


Label-free and facile electrochemical biosensing using carbon nanotubes for malondialdehyde detection.
A label-free electrochemical biosensing platform has been developed for the first time using carbon nanotubes for facile detection of malondialdehyde, showing high sensitivity and acceptable selectivity with a low detection limit of 0.047 μmol L(-1) and a linear response ranging from 0.1 to 90 μmol L(-1).


Attractive and repulsive effects of sensory history concurrently shape visual perception.
Sequential effects of environmental stimuli are ubiquitous in most behavioral tasks involving magnitude estimation, memory, decision making, and emotion. The human visual system exploits continuity in the visual environment, which induces two contrasting perceptual phenomena shaping visual perception. Previous work reported that perceptual estimation of a stimulus may be influenced either by attractive serial dependencies or repulsive aftereffects, with a number of experimental variables suggested as factors determining the direction and magnitude of sequential effects. Recent studies have theorized that these two effects concurrently arise in perceptual processing, but empirical evidence that directly supports this hypothesis is lacking, and it remains unclear whether and how attractive and repulsive sequential effects interact in a trial. Here we show that the two effects concurrently modulate estimation behavior in a typical sequence of perceptual tasks. We first demonstrate that observers' estimation error as a function of both the previous stimulus and response cannot be fully described by either attractive or repulsive bias but is instead well captured by a summation of repulsion from the previous stimulus and attraction toward the previous response. We then reveal that the repulsive bias is centered on the observer's sensory encoding of the previous stimulus, which is again repelled away from its own preceding trial, whereas the attractive bias is centered precisely on the previous response, which is the observer's best prediction about the incoming stimuli. Our findings provide strong evidence that sensory encoding is shaped by dynamic tuning of the system to the past stimuli, inducing repulsive aftereffects, and followed by inference incorporating the prediction from the past estimation, leading to attractive serial dependence.


Corrigendum to "Protective effects of chlorogenic acid against ionizing radiation-induced testicular toxicity" [Heliyon 8 (10) (October 2022) Article e10798].
[This corrects the article DOI: 10.1016/j.heliyon.2022.e10798.].


Inexpensive collapsible covered pen with slatted floor for turkeys.
Designed to confine turkeys for fowl cholera research was a collapsible pen with a hinged steel roof, wire sides, and slatted wooden floors. It is inexpensive to build; conserves labor in feeding, watering, and disposal of manure; protects against rain, sun, and predators; provides ventilation against heat; gives easy access to turkeys; and is collapsible


Environmental factors predicting nephritis in systemic lupus erythematosus.
To evaluate social class, ethnic origin, and various endocrine variables as potential risk factors in the development of nephritis in patients with systemic lupus erythematosus (SLE). A cross-sectional survey was carried out of all outpatients with SLE attending the lupus Clinic of St Thomas's Hospital from March to October 1992 using retrospective survival data. The main outcome measure was the duration of SLE before the onset of nephritis. Two hundred and ninety six women and 11 men were studied; the male patients were excluded from the analysis. Univariate analysis showed an increased risk of nephritis in patients with SLE of West Indian origin with 54 v 19% with nephritis at five years, in patients of lower social class, in patients who did not drink alcohol, and in those with a history of fetal loss after the onset of lupus. No significant effect of the age of onset of SLE, use of oral contraceptives, normal pregnancy, or smoking was seen. Multivariate analysis showed that ethnic origin did not influence the risk of nephritis independently of social class. Factors associated with socioeconomic deprivation may increase disease severity in patients with SLE.


The Occurrence of blaCTX-M-15 extended-spectrum β-lactamase Among Clinical Isolates of Klebsiella pneumoniae in Khorramabad, Iran.
During the recent decade, CTX-M-type enzymes, primarily CTX-M-15 extended- spectrum β-lactamase (ESBL) have strikingly developed throughout the world. The objective of this study was to investigate the frequency of CTX-M-type β-lactamases, as well as blaCTXM- 15 among Klebsiella pneumoniae isolates in Khorramabad, Iran. In this cross-sectional study, 60 isolates of K. pneumoniae were collected from selected teaching hospitals in Khorramabad, Iran. ESBLs producing isolates were identified using phenotypic double-disk synergy test. The presence of blaCTX-M-types, as well as blaCTX-M-15 gene, were investigated by PCR method. While the highest resistance rates of isolates were found to nalidixic acid (65%) and trimethoprim/sulfamethoxazole (60%) antibiotics, the least resistance was to imipenem (15%). Moreover, 31(51.7%) isolates were resistant to at least three classes of antibiotics and designated as multidrug resistance (MDR). Fifty-two (86.7%) of 60 isolates were ESBLs positive. Thirty-five (58.3%) isolates harbored CTX-M-type β-lactamases, and also 29 (48.3%) isolates carried blaCTX-M-15. This study presents the first report on the frequency of blaCTX-M-15 in the west of Iran, so that our results showed ESBL of CTX-M-15 may partly account for hydrolyzing thirdgeneration cephalosporins.


Regional- and agonist-dependent facilitation of human neurogastrointestinal functions by motilin receptor agonists.
Delayed gastric emptying is poorly managed. Motilin agonists are potential treatments but inadequate understanding into how enteric nerve functions are stimulated compromises drug/dose selection. Resolution is hampered by extreme species dependency so methods were developed to study human gastrointestinal neuromuscular activities and the neurobiology of motilin. Protocols to study neuromuscular activities were developed for different regions of human stomach and intestine (71 patients) using circular muscle preparations and electrical field stimulation (EFS) of intrinsic nerves. Other tissues were fixed for immunohistochemistry. EFS evoked contractions and/or relaxations via cholinergic and nitrergic neurons, with additional tachykinergic activity in colon; these were consistent after 154 min (longer if stored overnight). Motilin 1-300 nM and the selective motilin agonist GSK962040 0.1-30 µM acted pre-junctionally to strongly facilitate cholinergic contractions of the antrum (E(max) ≈ 1000% for motilin), with smaller increases in fundus, duodenum and ileum; high concentrations increased baseline muscle tension in fundus and small intestine. There were minimal effects in the colon. In the antrum, cholinergic facilitation by motilin faded irregularly, even with peptidase inhibitors, whereas facilitation by GSK962040 was long lasting. Motilin receptor immunoreactivity was identified in muscle and myenteric plexus predominantly in the upper gut, co-expressed with choline acetyltransferase in neurons. Motilin and GSK962040 strongly facilitated cholinergic activity in the antrum, with lower activity in fundus and small intestine only. Facilitation by motilin was short lived, consistent with participation in migrating motor complexes. Long-lasting facilitation by GSK962040 suggests different receptor interactions and potential for clinical evaluation.


Genetic analyses reveal regional structure and demographic expansion of the predominant tea pest Empoasca onukii (Hemiptera: Cicadellidae) in China.
The tea green leafhopper, Empoasca onukii Matsuda, is the most destructive insect pest of tea plantations in East Asia. Despite its economic importance and previous studies on this species, it remains unclear as to how this small-sized pest can have such wide range. By sequencing three mitochondrial genes and 17 microsatellite loci, we revealed the regional structure and demographic expansion of 59 E. onukii populations in China. Bayesian analysis of population genetic structure (BAPS) on microsatellites identified four genetic groups with spatial discontinuities, while analysis on mitochondrial genes inferred five nested and differentiated clusters. Both the Mantel test and the generalized linear model indicated a significant pattern of isolation by geographic distance in E. onukii populations. Based on the approximate Bayesian computation approach, E. onukii was found to have originated from southwestern China and expanded northward and eastward. While MIGRATE-N and Bayesian stochastic search variable selection (BSSVS) procedure in BEAST confirmed the possible eastward and northward dispersal from Yunnan, they also detected more gene flow from the derived populations in central and southeastern China. Our results suggest that the current distribution and structure of E. onukii is complicatedly influenced by human activities of cultivation, wide dissemination of tea in ancient China as well as recent transportation of tea seedlings for establishing new tea plantations. Insights into genetic differentiation and demographic expansion patterns from this study provide an important basis for the development of area-wide management of the E. onukii populations. © 2022 Society of Chemical Industry.


Fishing in greener waters: Understanding the impact of harmful algal blooms on Lake Erie anglers and the potential for adoption of a forecast model.
Harmful algal blooms (HABs) pose public health risks worldwide, because of the toxins that they can produce. Researchers have explored the impact of HABs on local economies, but know relatively little about the decision-making that informs these behaviors that lead to financial losses. Understanding the factors that inform this decision-making is critical to developing mitigative solutions. This study seeks to understand how HABs in Western Lake Erie affect angler decision-making, before evaluating a possible decision-support tool-a harmful algal bloom forecast known as the Experimental Lake Erie HAB Tracker. The HAB Tracker provides a nowcast and five-day forecast of the spatial distribution and transport of Microcystis, the predominant species of harmful algae in Western Lake Erie. Data collected using focus groups and surveys were coded to identify key themes that influence angler decision-making. The theory of the diffusion of innovations provides an analytical framework to evaluate the potential for widespread adoption of the HAB forecast among Lake Erie anglers. Analysis of emerging themes revealed that Lake Erie anglers face three key decision-points when fishing in HABs: whether to fish, where to fish, and whether to eat the fish. Five primary variables factored into angler decisions on where and whether to fish including 1) perceptions of HAB aesthetics, 2) perceptions of the impact of HABs on angler health, 3) perceptions of the impact of HABs on fish, 4) communication methods, 5) perceptions of HABs by customers of charter captains. Most participants in this study sought to avoid fishing in HABs primarily for aesthetic reasons. Recreational anglers are more likely than charter captains to adopt the HAB Tracker as a decision-support tool, because it is compatible with their information needs and provides a relative advantage over existing sources of information. Charter captains are less likely to adopt the HAB Tracker, because they rely on their existing knowledge and social network for HAB information. If researchers can reduce the complexity of forecast information while increasing its accessibility and reliability, then all anglers will be more likely to adopt a HAB forecast as a decision-support tool while fishing in Lake Erie during bloom season.


Cutaneous manifestations and treatment of arsenic toxicity: A systematic review.
Cutaneous and systemic signs of acute and chronic arsenic poisoning may be vague. Thus, an awareness of these signs is crucial to prevent late or missed diagnoses. This is especially true in non-endemic countries where individuals may present decades after exposure, or may still be ingesting arsenic via a non-classical exposure. Existing literature emphasizes several well-known cutaneous presentations of arsenic toxicity while ignoring the complete clinical spectrum, including several rare tumours of relevance to the dermatologist. This study aims to review the existing literature on dermatological presentations of arsenic toxicity and their management in adults.


Calcium channel blocker use and the risk of prostate cancer.
A recent study suggested that the risk of all cancers, including prostate cancer, is increased by the use of calcium channel blockers. The objective of this study was to determine whether prostate cancer is associated with calcium channel blocker use. A case-control study was conducted in Massachusetts using cases diagnosed from December 1992 through February 1995. Cases were men identified by tumor registrars who were less than 70 years old with newly diagnosed prostate cancer. Controls were men with no history of prostate cancer or symptoms of undiagnosed prostate cancer, and were matched to the cases on precinct of residence and half-decade of age. A total of 1217 cases of prostate cancer and 1400 community controls are included in this analysis. Data were collected by telephone interview. Multiple logistic regression was used to estimate relative risks for calcium channel blockers use while controlling for confounding. The relative risk for prostate cancer for any use of calcium channel blockers relative to nonuse was 1.2 (95% confidence interval [CI], 0.9-1.5). There was no evidence of a trend according to duration of use. When the analysis was confined to symptomatic men, the relative risk estimate was 1.1 (0.8-1.4) overall and 1.2 (0.8-1.7) among those aged 65 to 69 years. Relative risk estimates for the use of other classes of antihypertensive drugs among symptomatic men were close to 1.0; the corresponding estimates among asymptomatic men were generally further from 1.0. These findings suggest that calcium channel blockers do not increase the risk of prostate cancer. The differences in the relative risk estimates between symptomatic and asymptomatic men are compatible with detection bias. Because of the widespread use of Prostate-Specific Antigen testing for early detection of prostate cancer, potential detection bias needs to be considered in future studies of prostate cancer.


The effect of pregnancy on the natural history of diabetic retinopathy and nephropathy.
Retinopathy and nephropathy are complications of diabetes mellitus that can affect women of reproductive age. This article focuses on the effect of pregnancy on the risk of progression of microvascular disease, both during gestation and at long-term follow-up. Fortunately, with intensive medical surveillance and appropriate interventions, most women with types 1 and 2 diabetes mellitus can be offered an optimistic prognosis for child bearing.


Incidence of Disability in Frail Older Persons With or Without Slow Walking Speed.
To identify the differences of incidence of disability between frail older persons with and without slow walking speed. Prospective cohort study. Japanese community. A total of l4,081 older adults aged ≥65 years living in the community, participated in a baseline assessment and were followed for incidence of disability for 29.5 months. Care-needs certification in the national long-term care insurance system of Japan, physical frailty (slow walking speed, muscle weakness, exhaustion, low activity, weight loss), adjusted for several potential confounders such as demographic characteristics; Kaplan-Meier survival curves for incident disability by physical frailty with and without slow walking speed. During the follow-up period, 198 participants (4.9%) were certified as requiring long-term care insurance in accordance with incident disability. Participants who had prefrailty without slow walking speed (hazard ratio 1.86, 95% confidence interval 1.19-2.92), prefrailty with slow walking speed (3.62, 2.19-5.96), frailty without slow walking speed (4.33, 2.00-9.39), and frailty with slow walking speed (4.68, 2.72-8.05) at the baseline assessment had an increased risk of incident disability compared with nonfrail participants. In stratified analyses, frail older men and frail participants with low cognitive performance had the highest risk of incidence of disability. The presence of frailty or even prefrailty when older adults showed slow walking speed increased the risk of future disability in community-dwelling older adults.


Assessment of sperm using mRNA microarray technology.
The aim of this work is to review the need for new diagnostic tools for sperm, the relevance of sperm mRNA in reproductive success, and the potential of a state-of-the-art microarray-based diagnostic tool for improving reproductive results.


Strategies of myocardial protection for operation in chronic model of cyanotic heart disease.
Cyanotic congenital hearts have an increased susceptibility to ischemia and subsequent reperfusion. The role of platelet-activating factor antagonism and mechanical neutrophil depletion with leukocyte-depleting filters for control of ischemia-reperfusion injury was assessed in corrective surgical procedures for cyanotic heart disease. A swine model of cyanotic heart disease was evaluated with three study groups: a control group; a group given a platelet-activating factor antagonist (PAFA group); and a group with leukocyte-depleting filtration (LDF group). The cyanotic model was created with a left atrial appendage-pulmonary artery fistula with peripheral banding through a left anterior thoracotomy in weanling swine. The experimental procedure was performed 5 to 7 weeks later when body weight was greater than 20 kg and oxygen saturation was 85% or less. The corrective procedure was performed through a median sternotomy on cardiopulmonary bypass with repair of the shunt. Myocardial protection was accomplished with hypothermic blood-crystalloid (4:1) cardioplegia; the period of ischemic arrest was 90 minutes. In the PAFA group, the platelet-activating factor antagonist CV-6209 was delivered intravenously 15 to 20 minutes before aortic cross-clamping. In the LDF group, Pall leukocyte-depleting filters were used in the CPB arterial line. Hemodynamic data were taken before operation and 10 and 30 minutes after CPB with impedance ventriculography. There were four deaths in the control group within 30 minutes after CPB; all animals in the treated groups survived longer than 60 minutes (p < 0.05). The ventricular assessment of end-systolic elastance revealed superior performance in the LDF group 30 minutes after CPB compared with the control group (p < 0.05) (controls, 4.0+/-9; PAFA group, 6.5+/-3.7; and LDF group, 12.0+/-4.6). Both leukocyte-depleting filters and platelet-activating factor antagonism provided myocardial protection, and the filters afforded superior postoperative myocardial contractility.


Predicting Postherpetic Neuralgia in Patients with Herpes Zoster by Machine Learning: A Retrospective Study.
Postherpetic neuralgia (PHN) is a neuropathic pain secondary to shingles. Studies have shown that early pain intervention can reduce the incidence or intensity of PHN. The aim of this study was to predict whether a patient with acute herpetic neuralgia will develop PHN and to help clinicians make better decisions. Five hundred two patients with shingles were reviewed and classified according to whether they had PHN. The risk factors associated with PHN were determined by univariate analysis. Logistic regression and random forest algorithms were used to do machine learning, and then the prediction accuracies of the two algorithms were compared, choosing the superior one to predict the next 60 new cases. Age, NRS score, rash site, Charlson comorbidity index (CCI) score, antiviral therapy and immunosuppression were found related to the occurrence of PHN. The NRS score was the most closely related factor with an importance of 0.31. As for accuracy, the random forest was 96.24%, better than that of logistic regression in which the accuracy was 92.83%. Then, the random forest model was used to predict 60 newly diagnosed patients with herpes zoster, and the accuracy rate was 88.33% with a 95% confidence interval (CI) of 77.43-95.18%. This study provides an idea and a method in which, by analyzing the data of previous cases, we can develop a predictive model to predict whether patients with shingles will develop PHN.


Sinonasal Undifferentiated Carcinoma.
To provide a comprehensive review of the literature highlighting the recent advances in the diagnosis and management of sinonasal undifferentiated carcinoma (SNUC) RECENT FINDINGS: SNUC usually presents at advanced stage and the prognosis is usually poor with high rates of locoregional recurrence and tendency to metastasize. Special attention should be made in differentiating SNUC from other sinonasal malignancies in order to guide the appropriate treatment accordingly. Multimodality treatment is usually recommended for treating SNUC. The use of neoadjuvant chemotherapy may be associated with improved outcome and can be used to guide the subsequent treatment selection. Despite the recent advances in chemotherapeutic agents, radiation techniques, and surgical approaches, the prognosis and survival outcomes of SNUC remain poor. The addition of induction chemotherapy to the treatment approach followed by definitive local therapy needs to be further studied as it might improve the outcome.


Counseling tools alone do not improve method continuation: further evidence from the decision-making tool for family planning clients and providers in Nicaragua.
The decision-making tool (DMT) was developed by the World Health Organization's Department of Reproductive Health and Research and the Johns Hopkins University Center for Communication Program's staff to promote clients' informed choice and participation in family planning service delivery, to enable providers to apply evidence-based best practices during client-provider interaction and to provide the technical information necessary for optimal delivery of contraceptive methods. This tool has been tested in several countries and been shown to improve the quality of counseling for family planning clients. We conducted intercept and follow-up home interviews with new family planning acceptors in three health departments in Nicaragua to assess the impact of the DMT on method continuation and counseling experiences. The study was a quasi-experimental design with 65 experimental and control clinic sites. Analyses of overall and method-specific contraceptive use rates revealed no differences between experimental and control clinic clients. However, clients in the experimental group reported better counseling experiences than their counterparts in the control group. The authors conclude that sufficient evidence exists that counseling alone - with or without specialized job aids - does not influence contraceptive use rates. A new strategy is needed to help women maintain use of family planning methods.


Does androgen-deprivation therapy accelerate the development of frailty in older men with prostate cancer?: a conceptual review.
The majority of men with prostate cancer are aged > or =65 years. Men, as they age, are more likely to suffer from impaired physical function. The standard treatment for recurrent prostate cancer is androgen-deprivation therapy (ADT). Well-established toxicities from ADT include lean weight loss or sarcopenia, muscle weakness, fatigue, and reduced activity levels. Frailty is a term from geriatrics that describes older individuals with limited physiologic reserve who are at significant risk for adverse outcomes, including falls, disability, hospitalization, and death. An increasingly accepted definition of frailty is a syndrome in which > or =3 of the following are present: unintentional (lean) weight loss > or =10 pounds in the past year, weakness (measured by grip strength), slow walking speed, self-reported exhaustion, and low physical activity. This clinical syndrome overlaps closely with the known toxicities of ADT. In addition, alterations in the inflammatory system, neuroendocrine system, and energy production are associated with this syndrome, as evidenced by biomarkers such as C-reactive protein, interleukin-6, and tumor necrosis factor-alpha. For this article, the authors reviewed the evidence for the effect of ADT on each of the 5 frailty components plus the identified biomarkers, and the evidence indicates that ADT may accelerate the development of frailty in vulnerable older men with prostate cancer. Given the association of frailty with important clinical outcomes such as hospitalization and death, this potential consequence of ADT should be considered carefully when initiating therapy in older patients with recurrent prostate cancer.


APOE ε4 Carriers Have a Greater Propensity to Glycation and sRAGE Which Is Further Influenced by RAGE G82S Polymorphism.
APOE ε4 allele is an established risk factor for Alzheimer's disease and hypercholesterolemia. However, its association with metabolic and genetic risk factors related to glycation is not clear. We tested the hypothesis that, apart from high plasma cholesterol, APOE ε4 carriers may also have higher advanced glycation end products (AGEs) and total soluble extracellular domain of RAGE (sRAGE) and that these biomarkers may be modified by the common Gly82Ser (G82S) polymorphism (rs2070600) in the RAGE gene. To test this, we measured these biomarkers in 172 healthy cognitively normal individuals, of which 32 were APOE ε4 carriers and 140 noncarriers. APOE ε4 carriers showed higher levels of cholesterol (p < .001), glyoxal (p < .001), fluorescent AGEs (p < .001), Nε-carboxymethyllysine (p < .001) and sRAGE (p = .018) when compared to noncarriers. Furthermore, sRAGE was also higher in those that did not carry the A allele of the RAGE gene that codes for serine instead of glycine (p = .034). Our study indicates that APOE ε4 carriers have a greater propensity to glycation than noncarriers which may further increase their risk for diabetes and dementia. The increased sRAGE levels in APOE ε4 carriers suggests a defensive response against AGEs that may be further influenced by the RAGE G82S polymorphism.


Procedure-based nonsurgical management of lumbar zygapophyseal joint cyst-induced radicular pain.
To evaluate the success of fluoroscopically guided, contrast-enhanced lumbar zygapophyseal joint (Z-joint) aspiration and steroid injection combined with transforaminal epidural steroid injections (TFESIs) for the treatment of lumbar Z-joint cyst-induced radicular pain. Retrospective case series with independent follow-up. Institutional, referral center. Twenty-three patients referred to a single provider for procedure-based management of radicular pain believed secondary to lumbar Z-joint cyst. Inclusion criteria consisted of lumbar radicular pain that was consistent with the level and side of the Z-joint cyst as a causative lesion. Eighteen patients were treated with a fluoroscopically guided, contrast-enhanced Z-joint aspiration and steroid injection at the level of the causative cyst coupled with a fluoroscopically guided, contrast-enhanced TFESI over the level of the presumably irritated spinal nerve. Patient satisfaction, and whether or not surgery was performed. Fifty percent of patients treated with the procedure had significant long-term benefit and avoided surgical intervention at an average follow-up of 9.9 months. Fluoroscopically guided, contrast-enhanced spinal procedures as part of an aggressive nonsurgical treatment program are a safe and effective alternative to surgical intervention for lumbar Z-joint cyst-induced radicular pain.


[Aging and regression of cardiac hypertrophy in the hypertensive patient].
This study was aimed at determining factors acting on the regression of left ventricular hypertrophy due to essential hypertension. It was a non-randomized, echocardiographic study of 60 previously untreated hypertensive subjects (20 to 75 years of age). Following a 5-year therapy, the decrease in the left ventricular mass was 14%. Normalization of blood pressure and reversal of left ventricular hypertrophy were obtained in 50% and 58% of patients, respectively. Patients of the non-responder group (non-response being defined as a less than 10% decrease in the left ventricular mass) were older and had a longer history of high blood pressure. A positive correlation was observed between age and decrease in the left ventricular mass, the latter being less marked in older patients. Antihypertensive drugs classes had no influence on reversal of left ventricular hypertrophy. Ageing may be a factor of resistance to the decrease in left ventricular mass with therapy. These results suggest that early screening and management of hypertension are essential.


Actionable tests and treatments for patients with gastrointestinal cancers and historically short median survival times.
Patients have difficult unmet needs when standard chemotherapy produces a median survival of less than 1 year or many patients will experience severe toxicities. Blood tests can predict their survival. Analyses evaluate predictive blood tests to identify patients who often survive 1 and 2 years. A four-test model includes: albumin, absolute neutrophil count, neutrophil-lymphocyte ratio, and lymphocyte-monocyte ratio. Individual tests include: alkaline phosphatase, lymphocytes, white blood count, platelet count, and hemoglobin. Eligible patients have advanced: resistant 3rd line colorectal, and both resistant and new pancreatic and intrahepatic bile duct cancers. Eligibility characteristics include: biopsy-proven, measurable metastatic disease, NCI grade 0-2 blood tests, Karnofsky Score 100-50, and any adult age. Drugs are given at 1/4-1/3 of their standard dosages biweekly: gemcitabine, irinotecan, fluorouracil, leucovorin, and day 2 oxaliplatin every 2 weeks. In case of progression, Docetaxel is added (except colon cancer), with or without Mitomycin C, and next cetuximab (except pancreatic and KRAS BRAF mutation cancers). Bevacizumab is substituted for cetuximab in case of another progression or ineligibility. Consent was written and conforms with Helsinki, IRB, and FDA criteria (FDA #119005). Median survival is 14.5 months. Of 205 patients, 60% survive 12, and 37% survive 24 months (95% CI ± 8%). Survival is > 24, 13, and 3.8 months for patients with 0, 1-2, and 3-4 unfavorable tests, respectively. Individual "favorable and unfavorable" tests predict long and short survival. Neither age nor prior therapy discernibly affects survival. Net rates of clinically significant toxicities are less than 5%. Treatments reproduce predictable, greater than 12 and 24-month chances of survival for the aged and for patients with drug-resistant tumors. Evaluation of blood tests may change practice, expand eligibility, and personalize treatments. Findings support investigation of drug combinations and novel dosages to reverse resistance and improve safety.


Synthesis and evaluation of a C-6 alkylated pyrimidine derivative for the in vivo imaging of HSV1-TK gene expression.
We report on the synthesis, radiolabeling, in vitro and in vivo characterization of N-Me-[(18)F]FHBT (6-(3-[(18)F]fluoro-2-(hydroxymethyl)propyl)-1,5-dimethylpyrimidin-2,4(1H,3H)-dione), a C-6-substituted N-1-methylated pyrimidine derivative as a reporter probe for imaging herpes simplex virus type 1 thymidine kinase (HSV1-TK) expression. N-Me-[(18)F]FHBT was synthesized via a standard nucleophilic substitution reaction followed by acidic cleavage of the methoxytrityl protecting group. Cell uptake was studied in vitro with control HEK293 (human embryonic kidney cells) and HEK293 cells stably transfected with nonmutant HSV1-tk (HEK293TK+ cells). Positron emission tomography (PET) imaging and biodistribution studies of N-Me-[(18)F]FHBT or [(18)F]FHBG were performed in nude mice bearing xenografts of HEK293 control and TK+ cells. N-Me-[(18)F]FHBT was obtained in a two-step reaction in an overall maximal radiochemical yield (decay-corrected) of 5% and a radiochemical purity >96%. The tracer uptake in HSV1-TK containing HEK293TK+ cells was 14.5 times (at 30 min) and 55.4 times (at 240 min) higher than in control HEK293 cells. In mice, N-Me-[(18)F]FHBT and [(18)F]FHBG accumulated significantly and exhibited similar radioactivity levels in the HEK293TK+ xenografts; however, standardized uptake values ratios between HEK293TK+ and HEK293 control xenografts were higher for [(18)F]FHBG than for N-Me-[(18)F]FHBT. Both tracers showed high gall bladder and abdominal activity. The biological evaluations demonstrated the feasibility of using N-methylated C-6-substituted pyrimidine derivative N-Me-[(18)F]FHBT as a PET radiotracer for monitoring HSV1-TK expression in vivo.


Occlusion of Rb+ after extensive tryptic digestion of shark rectal gland Na,K-ATPase.
Na,K-ATPase from rectal glands of Squalus acanthias has been subjected to proteolysis with trypsin. The E1- and E2-forms of the enzyme can be distinguished from the inactivation patterns at low trypsin concentrations, as previously seen with kidney enzyme. Extensive degradation by trypsin in the presence of 5 mM Rb+ yields membrane fragments with a 19 kDa peptide as the major proteolytic fragment of the alpha-subunit. The sequence of the N-terminal 40 residues of this peptide is almost identical to that of a similar proteolytic fragment isolated by Capasso et al. (Capasso, J.M., Hoving, S., Tal, D.M., Goldshleger, R. and Karlish, S.J.D. (1992) J. Biol. Chem. 267, 1150-1158) using kidney Na,K-ATPase. Rb+ occlusion can be fully retained under these circumstances, supporting the findings with kidney enzyme that only minor parts of the alpha-subunit are required to form a functional occlusion-site.


Assessment of the Dynamics of Microbial Community Associated with Tetraselmis suecica Culture under Different LED Lights Using Next-Generation Sequencing.
Tetraselmis is a green algal genus, some of whose species are important in aquaculture as well as biotechnology. In algal culture, fluorescent lamps, traditional light source for culturing algae, are now being replaced by a cost-effective light-emitting diodes (LEDs). In this study, we investigated the effect of LED light of different wavelengths (white, red, yellow, and blue) on the growth of Tetraselmis suecica and its associated microbial community structures using the next-generation sequencing (NGS). The fastest growth rate of T. suecica was shown in the red light, whereas the slowest was in yellow. The highest OTUs (3426) were identified on day 0, whereas the lowest ones (308) were found on day 15 under red light. The top 100 OTUs associated with day 0 and day 5 cultures of T. suecica under the red and yellow LED were compared. Only 26 OTUs were commonly identified among four samples. The highest numbers of unique OTUs were identified at day 0, indicating the high degree of initial microbial diversity of the T. suecica inoculum. The red light-unique OTUs occupied 34.98%, whereas the yellow-specific OTUs accounted for only 2.2%. This result suggested a higher degree of interaction in T. suecica culture under the red light, where stronger photosynthesis occurs. Apparently, the microbial community associated with T. suecica related to the oxygen produced by algal photosynthesis. This result may expand our knowledge about the algaebacteria consortia, which would be useful for various biotechnological applications including wastewater treatment, bioremediation, and sustainable aquaculture.


Localization of acetylcholinesterase-positive neurons projecting to the mouse main olfactory bulb.
In this study a technique for staining brain tissue for both acetylcholinesterase (AChE) and axonally transported horseradish peroxidase conjugated to wheat germ agglutinin (HRP-WGA) has been used to identify and quantitate the AChE-synthesizing neurons that project to the main olfactory bulb (MOB) of the mouse. The primary sites of double stained neurons included the nucleus of the horizontal limb of the diagonal band (including the nucleus basalis and the magnocellular preoptic nucleus), locus coeruleus and the lateral hypothalamic area. The AChE activity in the neurons of the locus coeruleus and lateral hypothalamic area is suggested to be related to possible cholinoceptive function or some other role, but not to cholinergic projections to the MOB. Therefore, the cholinergic projection to the mouse MOB is suggested to originate in the nucleus of the horizontal limb of the diagonal band, an area that, for the purposes of this study, includes the mouse equivalent of the nucleus basalis of Meynert and what has previously been known as the magnocellular preoptic nucleus.


Evolving Clinical Data Strategies and Tactics in Response to Digital Transformation.
Contending with a continuously expanding volume and variety of clinical data poses challenges and opportunities for the industry and clinical data management organizations. Tufts CSDD conducted an online survey aimed at further quantifying and understanding the magnitude and impact that expanded data volume, sources and diversity are having on clinical trials. The survey was distributed between October and December 2019. Responses from a total of 149 individuals were included in the final analysis. The survey found that companies use or pilot from one to six different data sources with the majority of respondents using or piloting 3-4 different sources of data in their clinical trials. The results showed that average times to database lock have increased an average 5 days compared to a 2017 study, possibly as a result of managing an even larger number of data sources. Finally, three key mitigation strategies surfaced as techniques respondents used to tackle expanding data volume, sources, and diversity: the creation of a formalized data strategy, investment in new analytics tools and more sophisticated data technology infrastructures, and the development of new data science disciplines. Without further investments into infrastructure and developments of additional mitigation techniques in this area, database lock cycle times are likely to continue to increase as more and more data supporting a clinical trial are coming from nontraditional, CRF sources. Further research must be done into organizations who are handling these challenges appropriately.


Factors affecting the frequency of hospital trips among a predominantly rural population.
The frequency of hospital trips among the inhabitants of Nigeria's rural areas is affected by several factors. One obvious factor is the distance between potential patients and hospital facilities. And given the paucity of hospital facilities in rural areas, the distance factor is obviously an important one. However, the main focus of this paper is on the effect of some socio-economic and demographic characteristics on the frequency of hospital trips by rural inhabitants. The location of hospitals in close proximity to the user-population does not necessarily guarantee the full utilization of the facilities.


Quantitative autoradiography of [3H]-MK-801 binding sites in mammalian brain.
1. An in vitro receptor autoradiography procedure is described for visualizing binding sites for the excitatory amino acid antagonist radiolabelled MK-801, in rat and gerbil brain sections. 2. Ten micron sections were labelled by incubation at room temperature for 20 min in 30 nM [3H]-MK-801. This was followed by 2 rinses for 20 s in fresh buffer solution. Specifically bound ligand determined with 100 microM unlabelled MK-801 amounted to 55-60% of total. 3. Phencyclidine, (+/-)-SKF 10047, ketamine and 2-aminophosphonovaleric acid (APV) (all 100 microM) prevented the specific binding of [3H]-MK-801. L-Glutamate and N-methyl D-aspartate (NMDA) (100 microM) had no effect. However, L-glutamate prevented the inhibition by APV. 4. The highest concentrations of [3H]-MK-801 binding sites occurred in the hippocampal formation, cerebral cortex, olfactory bulb and thalamus. Very low levels were detected in the brain stem and cerebellum. 5. The distribution of [3H]-MK-801 binding sites was comparable to that of NMDA sites and phencyclidine sites (labelled with [3H]-TCP) but not with high-affinity sigma sites labelled with [3H]-3-PPP. 6. The density of [3H]-MK-801 binding sites in the gerbil hippocampus was examined 1, 2, 6 and 22 days after unilateral carotid artery occlusion for 10 min. Only at 6 and 22 days was the binding reduced (by 36% and 46% respectively) in the CA1 region whereas a significant neuronal loss was apparent at day 2. In CA2 a decrease in binding was only evident at day 22. 7. These results indicate that binding sites for [3H]-MK-801 can be detected in mammalian brain sections by receptor autoradiography. Their distribution supports an association with the NMDA receptor complex and the loss in the hippocampus after carotid artery occlusion indicates their presence on pyramidal cells is vulnerable to ischaemic insult.


Inactivation of bradykinin and kallidin by cathepsin G and mast cell chymase.
Human neutrophil cathepsin G and human skin chymase can inactivate bradykinin by cleavage at the carboxy terminal phenylalanyl-arginyl peptide bond of this polypeptide. The mast cell enzyme is far more effective than cathepsin G, the rates of hydrolysis being comparable to that found for angiotensin I to angiotensin II conversion (C.F. Reilly, D. Tewksbury, N. Schechter, and J. Travis, J. Biological Chemistry 257:8619-8622). This ability to both inactivate bradykinin and accelerate the production of angiotensin II may be of significance in the development of biochemical events associated with inflammation.


The emerging role of the hippo pathway in cell contact inhibition, organ size control, and cancer development in mammals.
The Hippo pathway defined originally in Drosophila melanogaster is conserved in mammals. The fly core components Hippo, Sav, Wts, and Mats are conserved in mammals as Mst1/2, WW45, LATS1/2, and Mob1. The pathway impinges on transcriptional coactivator Yorkie in fly and YAP in mammals to coordinate cell proliferation and apoptosis. Several recent publications establish that the pathway is one major conserved mechanism governing cell contact inhibition, organ size control, and cancer development. This advance opens new vistas in exploring fundamental mechanisms in cell and developmental biology and offers potential targets to interfere with cancer development.