Control efficacy and joint toxicity of metaflumizone mixed with chlorantraniliprole or indoxacarb against the fall armyworm, Spodoptera frugiperda.
The fall armyworm (FAW), Spodoptera frugiperda is the main destructive pest of grain crops, and has led to substantial economic losses worldwide. Chemical pesticides are the most effective way to manage FAW. Here, a laboratory test using an artificial diet-incorporated assay was conducted to determine the toxicity of five insecticides and the joint effect of the binary combination insecticides to FAW larvae. A field plot test using foliar spray was carried out to assess the control efficacy of metaflumizone mixed with chlorantraniliprole or indoxacarb against FAW. The bioassay results showed that metaflumizone had a stronger insecticidal effect than indoxacarb toward FAW larvae. Furthermore, the mixture of metaflumizone and chlorantraniliprole in a volume ratio of 3:7 had the strongest synergistic effect against FAW, with a co-toxicity coefficient (CTC) of 317.18. The best synergistic effect for mixtures of metaflumizone and indoxacarb was observed at a 1:9 volume ratio, with a CTC of 185.98. However, there was an antagonistic effect of metaflumizone mixed with emamectin benzoate and with lufenuron, because the co-toxic factor was less than -20 at volume ratios of 8:2 and 9:1, respectively. According to the results of the field trial, metaflumizone mixed with chlorantraniliprole or indoxacarb at a 50% reduction of the application rate can effectively control FAW with efficacy ranging from 77.73% to 94.65% 1-7 days postapplication. Overall, our findings suggest that metaflumizone and its binary combination insecticides can be utilized in FAW integrated pest management programs. © 2022 Society of Chemical Industry.


Multivariate Statistical Analysis and Odor-Taste Network To Reveal Odor-Taste Associations.
Odor-taste association has been successfully applied to enhance taste perception in foods with low sugar or low salt content. Nevertheless, selecting odor descriptors with a given associated taste remains a challenge. In the aim to look for odors able to enhance some specific taste, we tested different multivariate analyses to find links between taste descriptors and odor descriptors, starting from a set of data previously obtained using gas chromatography/olfactometry-associated taste: 68 odorant zones described with 41 odor descriptors and 4 taste-associated descriptors (sweetness, saltiness, bitterness, and sourness). A partial least square analysis allowed for identification of odors associated with a specific taste. For instance, odors described as either fruity, sweet, strawberry, candy, floral, or orange are associated with sweetness, while odors described as either toasted, potato, sulfur, or mushroom are associated with saltiness. A network representation allowed for visualization of the links between odor and taste descriptors. As an example, a positive association was found between butter odor and both saltiness and sweetness. Our approach provided a visualization tool of the links between odor and taste description and could be used to select odor-active molecules with a potential taste enhancement effect based on their odor descriptors.


Protocol for the setup and use of a human choroid plexus endothelial-epithelial two-cell-type in vitro model.
Choroid plexus, located in brain ventricles, is the site of blood-cerebrospinal fluid barrier that contains endothelial cells and an epithelial monolayer separated by stroma. We established a two-cell-type model of the human choroid plexus consisting of immortalized endothelial cells (iHCPEnC) and epithelial papilloma (HIBCPP) cells grown on opposite sides of filter supports. In this protocol, we describe the preparation of this model, the measurement of transepithelial electrical resistance (TEER), and immunofluorescence imaging-based analysis to determine the barrier function. For complete details on the use and execution of this protocol, please refer to Muranyi et al. (2022).


Ambivalence and adherence to preventive measures during the COVID-19 pandemic: Data from the U.S. and Germany.
This paper presents three datasets (.csv) providing raw data of three surveys about self-reported behavior, attitudes, and emotions regarding the COVID-19 pandemic. Data for Study 1 comes from a German sample, while data for Study 2 and Study X come from U.S. samples. For each survey, data was collected online through different survey software. The surveys contained items concerning self-reported ambivalence (two measures) regarding the COVID-19 pandemic and preventive measures to reduce the spread of the coronavirus, self-reported adherence to these preventive measures, and sociodemographic variables. Data can be used for re-analyses and exploratory purposes and comparisons between German and U.S. citizens in the domain of adherence, attitudes, and emotions.


Can google glass™ technology improve freezing of gait in parkinsonism? A pilot study.
Freezing of gait (FOG) is a disabling phenomenon defined by the periodic absence or reduction of forward progression of the feet despite the intention to walk. We sought to understand whether Google Glass (GG), a lightweight wearable device that provides simultaneous visual-auditory cues, might improve FOG in parkinsonism. Patients with parkinsonism and FOG utilized GG custom-made auditory-visual cue applications: "Walk With Me" and "Unfreeze Me" in a single session intervention. We recorded ambulation time with and without GG under multiple conditions including 25 feet straight walk, dual task of performing serial 7's while straight walking, 180 degree turn after walking 25 feet, and walking through a doorway. FOG and patient experience questionnaires were administered. Using the GG "Walk With Me" program, improvements were noted in the following: average 25 feet straight walk by 0.32 s (SD 2.12); average dual task of serial 7's and 25 feet straight walk by 1.79 s (SD 2.91); and average walk through doorway by 0.59 s (SD 0.81). Average 180 degree turn after 25 feet walk worsened by 1.89 s (SD 10.66). Using the "Unfreeze Me" program, only the average dual task of serial 7's and 25 feet straight walk improved (better by 0.82 s (SD 3.08 sec). All other tasks had worse performance in terms of speed of completion. This feasibility study provides preliminary data suggesting that some walking tasks may improve with GG, which uses various musical dance programs to provide visual and auditory cueing for patients with FOG.IMPLICATIONS FOR REHABILITATIONFreezing of gait in parkinsonian syndromes is a disabling motor block described by patients as having their feet stuck to the floor leading to difficulty in initiation of gait and increased risk for falls.Wearable assistive devices such as Google Glass™ use visual and auditory cueing that may improve gait pattern in patients with freezing of gait.Augmented reality programs using wearable assistive devices are a home-based therapy, with the potential for reinforcing physical therapy techniques; this is especially meaningful during the COVID-19 pandemic when access to both medical and rehabilitative care has been curtailed.


[Effect of electrostimulation of the supraoptic region of the hypothalamus on lipid metabolism and the development of atherosclerosis].
A three-week electrical stimulation of the hypothalamic supraoptic zone in rabbits which were on atherogenic diet for 3 to 8 weeks accelerated and intensified the development of hypercholesterolemia and lipidosis of the coronary arteries, as well as the metabolic changes in the myocardial tissue. The latter changes were expressed in the reduction of the tissue noradrenaline level, diminution of the creatine phosphate content, and an increase of inorganic phosphorus and lactic acid.


Partial trisomy of chromosome no. 1 in two adult brothers due to maternal translocation (1q--;6p+).
Extra chromosome material on the short arm of chromosome no. 6 (46,XY,6p+) was found in two mentally retarded adult half-brothers with mildly dysmorphic features. The phenotypically normal mother had a balanced translocation between the long arm of chromosome no. 1 and the short arm of chromosome no. 6:46,XX,t(1;6)(q32;p25). Thus the two affected brothers were trisomic for the long arm segment of chromosome no. 1, distal to q 32. These patients, with mildly dysmorphic features and mental retardation, represent the first cases of partial trisomy 1q surviving to adult-hood. The clinical and cytogenetic data obtained from eight individuals with partial trisomies for different long arm segments of chromosome no. 1 suggest that partial trisomy of the distal two-thirds of the long arm in characterized by severe malformations, growth retardation, and early death. Conversely, partial trisomy for the distal one-third of the long arm is associated with milder malformations and longer survival time as well as growth and mental retardation.


Time required for commitment to T cell proliferation depends on TCR affinity and cytokine response.
T cell activation and effector functions are determined by the affinity of the interaction between T cell receptor (TCR) and its antigenic peptide MHC (pMHC) ligand. A better understanding of the quantitative aspects of TCR-pMHC affinity-dependent T cell activation is critical for the development of new immunotherapeutic strategies. However, the role of TCR-pMHC affinity in regulating the kinetics of CD8+ T cell commitment to proliferation and differentiation is unknown. Here, we show that the stronger the TCR-pMHC affinity, the shorter the time of T cell-APC co-culture required to commit CD8+ T cells to proliferation. The time threshold for T cell cytokine production is much lower than that for cell proliferation. There is a strong correlation between affinity-dependent differences in AKT phosphorylation and T cell proliferation. The cytokine IL-15 increases the poor proliferation of T cells stimulated with low affinity pMHC, suggesting that pro-inflammatory cytokines can override the affinity-dependent features of T cell proliferation.


Predictors of psychological distress and sleep deprivation in caregivers of stroke survivors.
Caregivers for stroke survivors (CSS) suffer from long hours of care, limited support, and financial difficulties, which often affect their mental health. This study sought to determine the factors affecting psychological distress and sleep duration among CSS. We analyzed cross-sectional data from the 2013 Comprehensive Survey of the Living Conditions for Stroke Survivors and CSS. Linked data from 841 pairs of stroke survivors and CSS were extracted. Kessler's Psychological Distress scale (K6) was used to evaluate psychological distress. CSS who slept less than 5 hours per day were classified as having short sleep duration. Factors predictive of psychological distress and short sleep duration were evaluated using multivariable logistic regression analysis with the forward selection method. The mean (SD) age of the CSS was 65.4 (12.5) years. A total of 5.6% of these caregivers presented with serious psychological distress, and 12.0% were sleep deprived. Serious psychological distress was associated with not having someone to consult with, having subjective symptoms within a few days, and having short sleep duration, while having their own houses reduced the risk of serious psychological distress. Furthermore, short sleep duration was associated with stroke survivors in long-term care levels 4 or 5, not having someone to consult with, participation in sponge baths as part of nursing care activities, and having serious psychological distress. This nationwide survey identified several risk factors for psychological stress and sleep deprivation among CSS and suggests the need for multidimensional approaches to reduce their distress.


Clinical and photobiological characteristics of xeroderma pigmentosum complementation group F: a review of cases from Japan.
A 61-year-old female patient with xeroderma pigmentosum (XP), registered as XP46KO, was assigned to complementation group F by the cell fusion-complementation method. The XP46KO fibroblasts in culture exhibited a defective DNA repair capacity of 10-15% unscheduled DNA synthesis and a 3-fold sensitivity to the lethal effect of 254 nm ultraviolet light compared with normal cells. The patient had mild clinical symptoms consisting of numerous pigmented freckles and a small number of seborrheic keratosis-like papules. She had no skin cancers in the sun-exposed areas of the skin and so far no neurological abnormalities. A review of 11 Japanese group F patients revealed very mild skin symptoms with no ocular or neuro-psychiatric abnormalities. Single skin cancers occurred in only 3 of the 11 patients with an average age of 52 years for their first skin malignancy.


Predictors of Changes in Medication Adherence in Blacks with Hypertension: Moving Beyond Cross-Sectional Data.
Many studies have examined the multiple correlates of non-adherence in Blacks. However, they are largely cross-sectional; thus, these studies are unable to examine their predictive value on long-term medication adherence. The purpose of this study is to examine the predictive role of key psychosocial and interpersonal factors on changes in medication adherence over a 1-year period. Data were collected from 815 Black patients with hypertension followed in community health centers. Hypothesized predictor variables included self-efficacy, depressive symptoms, social support, and patient-provider communication measured at baseline, 6, and 12 months. The dependent variable, medication adherence was assessed at baseline, 6, and 12 months. Latent Growth Modeling was used to evaluate the pathways between the latent predictor variables and medication adherence. Participants were mostly female, low-income, with high school education or less, and mean age of 57 years. At baseline, high self-efficacy was associated with low depressive symptoms (β = -0.22, p = 0.05), collaborative patient-provider communication (β = 0.17, p = 0.006), and better medication adherence (β = 1.04, p < 0.001). More social support and collaborative patient-provider communication were associated with low depressive symptoms (β = -0.08, p = 0.02; β = -0.18, p = 0.01). More social support was positively associated with collaborative patient-provider communication (β = 0.32, p < 0.001). In the longitudinal model, increasing self-efficacy over time predicted improvements in medication adherence 1 year later (β = 1.76, p < 0.001; CFI = 0.95; RMSEA = 0.04; SRMR = 0.04; Chi-Squared Index of Model Fit = 1128.54). Self-efficacy is a key predictor of medication adherence over time in Black patients with hypertension. Initial levels of self-efficacy are influenced by the presence of depressive symptoms as well as the perceived quality of patient-provider communication.


Tandem screening of toxic compounds on GFP-labeled bacteria and cancer cells in microtiter plates.
A 96-well fluorescence-based assay has been developed for the rapid screening of potential cytotoxic and bacteriocidal compounds. The assay is based on detection of green fluorescent protein (GFP) in HeLa human carcinoma cells as well as gram negative (Escherichia coli) and gram positive bacteria (Mycobacterium avium). Addition of a toxic compound to the GFP marked cells resulted in the loss of the GFP fluorescence which was readily detected by fluorometry. Thirty-nine distinct naphthoquinone derivatives were screened and several of these compounds were found to be toxic to all cell types. Apart from differences in overall toxicity, two general types of toxic compounds were detected, those that exhibited toxicity to two or all three of the cell types and those that were primarily toxic to the HeLa cells. Our results demonstrate that the parallel screening of both eukaryotic and prokaryotic cells is not only feasible and reproducible but also cost effective.


[Field 3. Structural and managerial skills for improvement in safety practice. French-speaking Society of Intensive Care. French Society of Anesthesia and Resuscitation].
ICU activity has to be authorized by regional hospital agencies. The structural aspects of ICU have been defined in official text in 2002. Thus, quality related to structural issues should be settled in the next future. The challenge is now focused on team building and managerial skills that should be developed in ICU in order to improve quality and security. Every effort should be developed to improve motivation and self-accomplishment of personnel working in ICU (period of integration for new nurses, basic and continuous education, clear tasks identification, formal interviews). It is important to follow alert indicators (absenteeism, important turn over) in order to detect burn out and take preventive measures. It is necessary to develop a new culture, team-oriented, with common goals. This new quality-security oriented policy must be supported by the institution. The volume-outcome relationship has been demonstrated across a wide range of medical and surgical procedures. On average, higher volume is associated with higher quality and better outcome.


Biomechanical analysis in mandibular advancement and occlusal plane rotation with finite element analysis.
We used finite element analysis to assess stress on the cortical bone and plate fixation system, as well as mandibular resistance after sagittal split ramus osteotomy with different mandibular advancements and rotations of the occlusal plane. Three-dimensional mandibular models were obtained, and 6mm and 12mm advancements were planned associated with linear, clockwise, and counter-clockwise rotation of the angle of the occlusal plane. Each model was then fixed with one or two 2.0mm system plates and secured with four monocortical screws. A total of 12 models were built and subjected to a vertical load in the lower central incisor ranging from 50N to 500N in 50N increments. Results showed that the 12mm advancement was associated with higher stress on the bone and plate surface. Additionally, the models fixed with two plates exhibited lower plate stress than those fixed with a single plate. Counter-clockwise rotation of the angle of the mandibular plane in the 6mm advancement caused more plate stress, which did not occur in the 12mm advancement. This analysis has shown that change in the occlusal plane in large mandibular advancements does not act as an additional stress factor. These findings can help to better understand the tensions on bone and plate surfaces in patients who need large mandibular advancements that are associated with a change in the occlusal plane, and will aid better surgical planning.


Relation of Obstructive Sleep Apnea to Risk of Hospitalization in Patients With Heart Failure and Preserved Ejection Fraction from the National Inpatient Sample.
Obstructive Sleep Apnea (OSA) increases the risk of diastolic dysfunction and heart failure. The impact of OSA on hospitalization for heart failure with preserved ejection fraction (HFpEF) is not well elucidated. We used data from the National Inpatient Sample for the years 2012 to 2014. We identified discharges (age ≥18 years) associated with OSA and HFpEF using the International Classification of Diseases, Ninth Revision, Clinical Modification codes (327.23 and 428.3x), respectively. Propensity score analysis, adjusting for age, gender, race, and comorbidities, compared the rates of admission for HFpEF in patients with OSA to those without OSA. Out of 12,608,637 discharges included, there were 147,463 patients with HFpEF, and 653,762 or 5.2% of all discharges had OSA. The prevalence of OSA in patients with HFpEF was 16.8%. Patients with OSA were older, more likely to be men, more likely to have diabetes, hypertension, history of coronary artery disease, chronic kidney disease, obesity, atrial fibrillation, African-American race, and smoking status. In patients with OSA, HFpEF occurred in 3.8% versus 1.0%, with adjusted odds ratio: 2.2 (95% confidence interval 2.16 to 2.23), p <0.001. Subgroup analysis showed similar results in men and women. After propensity score matching, OSA was associated with increased risk of admission with HFpEF, relative risk = 2.2 (95% confidence interval 2.12 to 2.21). In conclusion, OSA was associated with increased risk of hospitalization for HFpEF.


Changes in diabetes distress among people with type 2 diabetes during a risk screening programme for diabetic kidney disease - Longitudinal observations of the PRIORITY study.
To investigate levels and changes in diabetes distress over the course of the PRIORITY (Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In people with TYpe 2 diabetes and normoalbuminuria) randomised controlled trial of screening for diabetic kidney disease (DKD) risk among people with type 2 diabetes (T2D) at a specialist diabetes clinic in Denmark. Of 436 trial participants with T2D, 216 were invited to complete the 17-item diabetes distress scale at the time of screening (T1, n = 180), immediately after receiving the screening results at 6-8 weeks (T2, n = 169), and at 12 months follow up (T3, n = 107). Linear mixed models were used to explore changes in diabetes distress. No significant changes in diabetes distress were observed between the time of screening, receiving results, and at 12 months. Changes in diabetes distress were not influenced by diabetes empowerment, sense of coherence, or perceived support for diabetes self-management. In contrast to previous studies demonstrating that screening programmes can have negative psychological consequences, our findings indicate that participating in this screening programme for DKD does not influence emotional burden or physician-related distress among people with T2D.


Further studies on the effects of central administration of neuropeptide Y on neuroendocrine function in the male rat: relationship to hypothalamic catecholamines.
Following intraventricular (i.v.t.) administration of increasing doses of neuropeptide Y (NPY; 7.5-750 pmol/rat) the catecholamine levels and turnover were quantitatively measured in discrete hypothalamic regions by means of histofluorometry. In the same rats the adenohypophyseal hormones as well as vasopressin, aldosterone (ALDO) and corticosterone (CORTICO) levels in serum were determined. Neuropeptide Y seems to induce a biphasic change in amine utilization in the tuberoinfundibular dopamine (DA) neurons and in the noradrenergic (NA) utilization in various hypothalamic areas. Thus, the lowest doses seem to inhibit the catecholamine utilization while higher doses seem to enhance it. NPY (250-750 pmol) reduced the serum levels of thyreotropine (TSH), prolactin (PRL) and growth hormone (GH) but increased CORTICO, adrenocorticotropin (ACTH) and ALDO serum levels. In conclusion, it is suggested that the NPY induced changes in DA utilization in the tuberoinfundibular DA neurons may contribute to the NPY induced changes in PRL and TSH secretion. The increases in paraventricular NA utilization may contribute to the increases in ACTH, ALDO and CORTICO secretion induced by NPY. These data give further support for NPY as an important neuroendocrine modulator.


Clinician communication after discovery of a soft marker of aneuploidy during pregnancy: A mixed methods assessment of a communication workshop.
Soft markers of aneuploidy are common findings on obstetric ultrasounds but disclosure often increases patient anxiety. It is unknown whether communication training affects patient experience of soft marker disclosure. Our objective was to evaluate clinician experience of a simulation-based communication workshop and assess workshop influence on patient anxiety, understanding, and perception of communication quality. We implemented a communication workshop for clinicians at an academic institution in 2019, and assessed clinician anxiety and confidence with counseling before and after. To assess effect of the workshop on patients, we surveyed pregnant people before and after workshop implementation for whom an echogenic intracardiac focus, choroid plexus cyst, or urinary tract dilation was identified. The primary outcome was anxiety. Some respondents completed a semi-structured interview. Interviews were analyzed using thematic analysis. Twelve clinicians participated. Twenty-one out of 49 eligible patients (43%) completed a survey before the workshop and 40 out of 90 eligible patients (44%) completed a survey after. The risk of high anxiety after was similar to before the workshop (aRR 1.7, 95% CI 0.6-4.2). Twenty patients were recruited for an interview. Qualitative analysis revealed that patients' backgrounds, emotional impact of the conversation and clinician manner influenced perception of communication quality. While a single clinician workshop did not affect patient anxiety, clinician manner and personalization play a large role in perception of counseling about soft markers of aneuploidy.


Circulating tumor cells correlating with Ki-67 predicts the prognosis of bladder cancer patients.
To investigate the value of circulating tumor cells (CTCs) and Ki-67 in predicting the prognosis of bladder cancer. Here, we tested CTC counts and Ki-67 levels to assess patient prognosis. 84 patients with bladder cancer who underwent surgery were included in this study. Peripheral blood CTCs were detected by SE-iFISH technology before and after surgery, and Ki-67 levels were analyzed by immunohistochemistry. The association between CTCs and Ki-67 and the combination of the two was analyzed to predict the prognosis of patients. 76 out of 84 patients (90.5%) were positive. ROC curve analysis showed that preoperative and postoperative CTC counts = 4 and 2 were the best thresholds for predicting patient recurrence or death. In multivariate analysis, high postoperative CTC count (≥ 2) (P < 0.001) and Ki-67 high expression (≥ 15%) (P < 0.001) were independent poor prognostic factors for PFS in bladder cancer patients. In addition, the study found that Ki-67 levels were positively correlated with high postoperative CTC counts, Bladder cancer patients with Ki-67 high expression and high postoperative CTC counts were associated with extremely poor progression-free survival. Ki-67 high expression is associated with high postoperative CTC counts, both of which predict poor prognosis in bladder cancer patients.


Markerless robotic pedicle screw placement based on structured light tracking.
Most existing robot systems for pedicle screw placement rely on optical markers to establish the spatial relationship between the surgical tool and the surgical path. Marker installation and registration are time-consuming, and error may also accumulate along the complicated coordinate transformation chain. Therefore, we proposed a markerless structured light-based method to simplify the surgery workflow and the coordinate transformation chain. Firstly, a structured light camera is used to directly track both the surgical tool and the bone anatomy without using markers. Secondly, a markerless "two-direction" approach for robot-camera registration together with a feedback robot control method is developed. Lastly, a prototype system is built and examined with precision validation experiments and pedicle screw drilling experiments. Precision validation experiments show satisfactory positioning accuracy of the system. In drilling experiments, 42 paths were drilled on three synthesized cervical vertebrae phantoms and all the paths successfully went through the pedicles. The mean position error of the entry point was 0.28 ± 0.16 mm, and the mean angle error was 0.49 ± 0.24°, which can meet the clinical requirement. The results show the feasibility of the proposed structured light-based method for pedicle screw placement, which has a simple workflow and can achieve good accuracy without using optical markers.


Vitreal penetration of oral moxifloxacin in humans.
To investigate the vitreal penetration of moxifloxacin after oral administration. Prospective, nonrandomized clinical series. Twenty-four patients (mean age = 62.8 years) undergoing elective pars plana vitrectomy were assigned to a dosing group: control (n = 3), which received no medication; single-dose (n = 11), which received one 400 mg oral dose of moxifloxacin 3 hours before surgery; and five-dose (n = 10), which received one 400 mg dose on each of the 4 days preceding surgery and a fifth dose 3 hours before surgery. Vitreous samples were obtained and analyzed. Control, below quantifiable levels; single-dose, 0.572 +/- 0.239 microg/mL; and five-dose, 1.200 +/- 0.645 microg/mL. Five doses of oral moxifloxacin lead to higher intravitreal drug concentrations than single-dose administration. Both regimens, however, achieve levels that exceed the MIC90 of many bacteria implicated in postoperative endophthalmitis.


Assessing the uranium DGT-available fraction in model solutions.
The uranium speciation in humic acid (HA) and fulvic acid (FA) model solutions was investigated by diffusive gradients in thin films (DGT). A reference solution was used to normalize the DGT data from different samples. This approach was used to assess uranium DGT-available fraction (FU), which was calculated from experimental data and reflect both the mobility and lability of uranium species. FU decreased with increasing HA or FA concentrations, because more uranium was able to bind the strong binding sites of HA or FA. When copper was spiked, FU increased due to the competition between copper and uranium. In HA model solutions, an increase of ionic strength could increase FU, and when pH was greater than 7, FU increased significantly. The DGT uptake factor (φ), which can be obtained from data fitting, is the ratio of the product of diffusion coefficient and lability degree of the unknown sample to that of the reference solution. In U-HA-NaHCO3 solutions, UO2(CO3)22- had a relatively high φ value and might be the most DGT-available species. This approach allows the comparison of DGT data from different samples, and combining with a data fitting procedure, it can be used to investigate the distribution of metal species.


Migraine patients' experiences with and expectations from physiotherapy.
Neck pain is prevalent in migraine and a common reason to receive physiotherapy. There is no information as to the type of modalities patients receive and whether these are perceived as effective and matching expectations. A survey was designed with closed and open-ended questions allowing for quantitative evaluation and qualitative insights into experiences and expectations. The survey was available online from June-November 2021 and was disseminated in the German migraine league (patient organization) and via social media. Open questions were summarized using qualitative content analysis. Differences between receiving and not receiving physiotherapy were analyzed through Chi2 or Fisher's Test. Categories within groups through Chi2-goodness-of-fit-test and multivariate logistic regression indicated perceived clinical improvement. 149 (123 received physiotherapy) patients completed the questionnaire. Patients receiving physiotherapy had higher pain intensity (p < 0.001) and migraine frequency (p = 0.017). Most participants received 6 sessions or less (38%) (past 12 months) of manual therapy (82%) and soft-tissue techniques (61%). 63% perceived benefits after manual therapy, and 50% after soft-tissue techniques. Logistic regression revealed that ictal and interictal neck pain (OR: 9.12 and 6.41, respectively) and receiving manual therapy (OR: 5.52) are associated with improvement. Mat exercises and higher migraine frequency increased the odds for no improvement or worsening (OR: 0.25 and 0.65, respectively). Expectations included individualized and targeted treatment from a specialized physiotherapist (39%), easier access, more and longer sessions (28%), manual therapy (78%), soft-tissue techniques (72%) and education (26%). sThis first study on migraine patients' views on physiotherapy can serve as insight for researchers for future studies and clinicians to improve future care.


Metabolic rate and life stage of the mites Tetranychus cinnabarinus boisd. (Prostigmata) and Phytoseiulus persimilis A-H. (Mesostigmata).
Respiration rates (oxygen uptake per individual) of the herbivorous mite Tetranychus cinnabarinus Boisd. and of the predatory mite Phytoseiulus persimilis A-H. were measured at 25°C for all life stages, including eggs, using a Cartesian Diver micro-respirometer.Metabolic rates (oxygen uptake per unit weight) ranged between 0.27 and 2.32 nl O2 μg-1 live weight h-1 in T. cinnabarinus, and between 0.99 and 3.69 nl O2 μg-1 live weight h-1 in P. persimilis. The difference in metabolic rate ranges is attributed to different modes of life. The metabolic rates of both species are higher than those of comparable mite species, which is attributed to their small size, rapid development and limited sclerotization.Respiration-body weight regression gave the single equation log10 R=-0.091+1.213 log10 W for all post-embryonic stages of T. cinnabarinus but two equations for P. persimilis of log10 R=0.394+1.116 log10 W for gravid females and log10 R=0.880+0.348 log10 W for all non-reproducing post-embryonic stages. The single respiration-body weight relationship for T. cinnabarinus reflects the continuous growth pattern of this species, and the two relationships for P. persimilis reflect the accelerated growth following fertilization. The significance of these results for invertebrate population metabolism studies is discussed.


Glaucoma Knowledge and Disease Severity in a Veteran Population: The Medication Adherence in Glaucoma to Improve Care (MAGIC) Study.
To assess the relationship between glaucoma knowledge and disease severity. Substudy of a randomized controlled trial at a single Veterans Affairs (VA) eye clinic. Veterans with medically treated open-angle glaucoma who self-reported poor medication adherence. Participants completed a glaucoma knowledge assessment using the 10-question National Eye Health Education Program (NEHEP) Eye-Q Test on glaucoma knowledge. Disease severity was determined using visual field criteria. Multiple linear regression was used to assess the association of NEHEP Eye-Q score and disease severity, adjusting for age, number of glaucoma medications, race, sex, and VA Care Assessment Needs (CAN) score. In this cross-sectional, preintervention analysis, the main outcome was glaucoma knowledge as measured by the NEHEP Eye-Q Test. Among the 200 study participants, glaucoma severity was mild in 53 (27%), moderate in 56 (28%), severe in 74 (37%), and indeterminant in 17 (9%). The NEHEP Eye-Q scores were low across all severity levels. Scored out of 10, the mean (standard deviation) NEHEP Eye-Q scores were 6.06 (1.57) for mild, 6.21 (1.47) for moderate, 6.28 (1.82) for severe, and 5.88 (1.93) for indeterminate stage. There was no evidence of a significant association between NEHEP scores and disease severity categories (P = 0.78). A regression model did not identify a significant estimated association between NEHEP Eye-Q scores and disease severity after adjusting for age, CAN risk score, number of glaucoma medications, race, and sex. There was no difference in level of glaucoma knowledge based on disease severity. Education-based interventions may benefit patients across all glaucoma stages. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Nodular thyroid disease and cancer.
Different possibilities of solitary or multinodular involvement of the thyroid gland are described. Because of the broad spectrum of malignancy there exists a controversy and widespread divergence of opinion regarding the incidence, malignancy, classification and treatment of thyroid cancer.


Potential molecular mechanism underlying the harmed haemopoiesis upon Benzo[a]pyrene exposure in Chlamys farreri.
Benzo[a]pyrene (B[a]P), a ubiquitous contamination in the marine environments, has the potential to impact the immune response of bivalves by affecting the hemocyte parameters, especially total hemocyte count (THC). THC is mainly determined by haematopoietic mechanisms and apoptosis of hemocytes. Many studies have found that B[a]P can influence the proliferation and differentiation of hemocytes. However, the link between the toxic mechanisms of haematopoietic and environmental pollutants is not explicitly stated. This study is to investigate the toxic effects of B[a]P on haematopoietic mechanisms in C. farreri. Through the tissue expression distribution experiment and EDU assay, gill is identified as a potential haematopoietic tissue in C. farreri. Subsequently, the scallops were exposed to B[a]P (0.05, 0.5, 5 μg/L) for 1d, 3d, 6d, 10d and 15d. Then BPDE content, DNA damage, gene expression of haematopoietic factors and haematopoietic related pathways were determined in gill and hemocytes. The results showed that the expression of CDK2 was significantly decreased under B[a]P exposure through three pathways: RYR/IP3-calcium, BPDE-CHK1 and Notch pathway, resulting in cell cycle arrest. In addition, B[a]P also significantly reduced the number of proliferating hemocytes by affecting the Wnt pathway. Meanwhile, B[a]P can significantly increase the content of ROS, causing a downregulation of FOXO gene expression. The gene expression of Notch pathway and ERK pathway was also detected. The present study suggested that B[a]P disturbed differentiation by multiple pathways. Furthermore, the expression of SOX11 and CD9 were significantly decreased, which directly indicated that differentiation of hemocytes was disturbed. In addition, phagocytosis, phenoloxidase activity and THC were also significant decreased. In summary, the impairment of haematopoietic activity in C. farreri further causes immunotoxicity under B[a]P exposure. This study will improve our understanding of the immunotoxicity mechanism of bivalve under B[a]P exposure.


[Clinical study on primary repair for bile duct injury during laparoscopic cholecystectomy].
To evaluate the place of primary repair of bile duct injury during laparoscopic cholecystectomy (LC). Between 1994 and 2004, 53 of a total 14 302 cases were identified with bile duct injury. The indication, methods and outcome of primary repair for 17 cases of bile duct injury were analyzed. Forty-Two of 53 cases of bile duct injury were identified at the time of operation, thirty three involved a tear of the common, hepatic or right hepatic bile duct, and 17 cases received primary repair. Drainage tubes were placed in 7 cases, and biliary drainage through the cystic duct was performed in 10 cases. All patients recovered well and got out of bed within 6 hours postoperatively. The alimentary tract recovered in 24 hours after operation in all cases, and their mean hospitalization was 4.6 days. Sixteen patients were followed up, and no stricture of bile duct was found. Repair of bile duct injury during LC is safe and effective in selected cases.


Fluorescence correlation spectroscopy with autofluorescent proteins.
Fluorescence correlation spectroscopy (FCS) is a versatile technique operating at the single-molecule level, that successfully meets many challenges of modern biological research. Based on the detection of mobile fluorescent molecules diffusing in and out of a diffraction-limited laser focus, the method allows to resolve particle dynamics within cells and their compartments. Previous FCS studies have described various parameters of protein function, namely mobility, transport and localization phenomena, enzymatic turnovers of biochemical substrates and molecular association and dissociation reactions. Recent progress in the application of FCS to intracellular systems has particularly taken advantage of detecting autofluorescent proteins and their genetically encoded fusions to cellular proteins. This review discusses recent applications of FCS analysis with and on fluorescent proteins, particularly highlighting chemical and physical properties. Inherent limitations of the presented approaches are discussed in detail and strategies for optimisation of experimental systems outlined.


Electromechanical dissociation and its possible role in sudden cardiac death.
Electromechanical dissociation is a rare but important cause of death in some patients with cardiac ischemia. It is a well characterized syndrome involving loss of contractile function of the heart without arrhythmia. Several other clinical syndromes, including massive pulmonary embolism and cardiac rupture, can mimic electromechanical dissociation, so its incidence is difficult to estimate. Experimental studies of early ischemic contractile failure show preservation of adenosine triphosphate levels, and of the calcium ion release mechanism. Intracellular acidosis is temporarily correlated, but direct causality cannot be assigned to the acidosis because of the lack of necessary direct studies. The role of the autonomic nervous system in triggering the sequence of events leading to electromechanical dissociation is unclear and is a promising area for further study.


Deriving probabilistic soil distribution coefficients (Kd). Part 3: Reducing variability of americium Kd best estimates using soil properties and chemical and geological material analogues.
The solid-liquid distribution coefficient (Kd) is a key input parameter in radioecological risk models. However, its large variability hampers its usefulness in modelling transport processes as well as its accuracy in representing soil-radionuclide interactions. To assist in the selection of Kd values and their cumulative distribution functions for study areas without site specific information, a critically reviewed dataset was developed, containing more than 5000 soil Kd entries for 83 elements and an additional 2000 entries of Kd data for 75 elements gathered from a selection of other geological materials. For the specific case of americium (Am), the dataset contained 109 entries for soils and 33 additional entries for sediment and subsoils. The analysis of the Am Kd soil dataset showed that values varied 4-orders of magnitude, and consequently the resulting Am Kd best estimate (geometric mean (GM): 4.6 × 103 L kg-1) lacked sufficient reliability. The objective of this study was to calculate cumulative distribution functions and statistically evaluate this dataset to determine if the Am Kd variability in soils could be reduced by considering various factors, including: 1) measurement methods, 2) key soil properties, 3) the use of chemical analogue data, and 4) the use of analogue data. Accounting for Am Kd experimental method (i.e., sorption vs. desorption; long-vs. short-term experiments) had little effect on reducing variability. However, accounting for key soil factors (i.e., organic matter content (OM), pH, soil texture) succeeded in reducing variability of Am Kd, especially when combining pH and OM. While previous data sets have used 20% OM content as a critical value to distinguish between mineral and organic soils, this study shows that this critical value should be reduced to 10% OM to minimize Am Kd variability. The inclusion in the dataset of Am Kd from other geological materials (e.g., gyttjas, tills, and subsoils) and Kd values from trivalent lanthanides (Ln (III)) and actinides (An (III)) (172 additional entries) did not statistically affect the Am Kd geometric means of the various pH and OM partial datasets. The larger composite dataset (> 310 entries), with both chemical analogues and geological material analogues to address data gaps, increased the statistical power for calculating Kd best estimates with lower variability, thereby enhancing their usefulness for radionuclide risk calculations.


Replantation of multiple digits and hand amputations: four case reports.
This study reports four cases of hand avulsion at the proximal wrist level and multiple digits amputation were received in plastic and hand surgery unit during the year 2007-2008. All patients were male labors between 22-30 years old, and the amputation due to machine injuries. Successful replantation were achieved, after a period of follow up with occupational therapy all patients regain good functional and cosmetic results. This study proves the strong indication of replantation of multiple digits & hand amputations.


[Analysis of community agendas in primary care and factors associated with their implementation].
To describe the community agendas created by the Aragonese Primary Care Teams (PCT), to analyze the characteristics of said PCT, and to explore factors related to their implementation. Descriptive observational study of the community agendas and the Aragonese PCT that have created them since the implementation of the Aragonese Community Care Strategy (ACCS) in 2016 until March 2021. Bivariate and multivariate analysis of the characteristics of these PCT that have created the agenda with respect to those who have not developed it. 75 of the 123 Aragonese PCT (61%) have created the community agenda. 74.7% of them also have an active Health Council. 45 of the 75 agendas are of the advanced type, with 41 PCT that had carried out the zone health diagnosis and 28 PCT that made asset recommendations. It was observed how the creation of the community agenda is related to being a PCT belonging to a semi-urban basic health zone (odds ratio [OR]: 3.02; 95% confidence interval [95% CI]: 1.22-7.47; p=0.017) and that at least one professional would have received specific training (OR: 5.29; 95% CI: 1.09-25.72; p=0.039). The community agenda is a tool that supports the development of community care for PCT. The training provided by the ACCS has been shown to be key to the development of the agendas, and this work must continue, with special emphasis on the PCT belonging to rural or urban basic health zones, since they are the ones that are experiencing the greatest difficulties.


Non-traumatic lower limb amputation in patients with end-stage renal failure on dialysis: an Australian perspective.
End-stage renal failure (ESRF) and dialysis have been identified as a risk factor for lower limb amputations (LLAs). High rate of ESRF amongst the Australian population has been reported, however till date no study has been published identifying magnitude and risk factors of LLA in subjects on renal dialysis. The study aims to document trends in the prevalence and identify risk factors of non-traumatic LLA in Australian patients on dialysis. A retrospective review of all patients (218) who attended the regional dialysis center between 1st January 2009 and 31st December 2013 was conducted. Demographic, clinical and biochemical data were analyzed. We identified a high prevalence of 13.3% of LLAs amongst Australian patients with ESRF on dialysis at our center. The associated risk factors were the presence of diabetes (OR 1.67 [1.49-1.88] p < 0.001), history of foot ulceration (OR 81 [18.20-360.48] p < 0.001), peripheral arterial disease (OR 31.29 [9.02-108.56] p < 0.001), peripheral neuropathy (OR 31.29 [9.02-108.56] p < 0.001), foot deformity (OR 23.62 [5.82-95.93] p < 0.001), retinopathy (OR 6.08 [2.64-14.02] p < 0.001), dyslipidemia (OR 4.6 [1.05-20.05] p= 0.049) and indigenous background (OR 3.39 [1.38-8.33] p= 0.01). 75% of the amputees had aboriginal heritage. We also identified higher HbA1c and CRP levels as well as low serum albumin, hemoglobin and vitamin D levels to have a strong association with LLAs (p < 0.05). There is high prevalence of LLAs amongst Australian indigenous patients with diabetes on dialysis in North Queensland. Other strongly associated risk factors include history of foot ulceration, foot deformity and peripheral neuropathy as well as high HbA1c levels and low serum albumin levels.


2-Hydroxymelatonin promotes the resistance of rice plant to multiple simultaneous abiotic stresses (combined cold and drought).
We investigated the physiological roles of 2-hydroxymelatonin (2-OHMel) in rice seedlings. When they were challenged with simultaneous multiple abiotic stressors, such as a combination of cold and drought, those pretreated with 2-OHMel were resistant, whereas no tolerance was observed in seedlings treated with either melatonin or water (control). The tolerance phenotype was associated with the induction of several transporter proteins, including the proton transporter (UCP1), potassium transporter (HKT1), and water channel protein (PIP2;1). Treatment with 2-OHMel increased the content of the osmoprotectant proline and maintained mitochondrial structure when plants were subjected to a combination of cold and drought stress. We screened the corresponding transcription factors (TFs) for 2-OHMel-mediated resistance to the combined stressors through analysis of large numbers of cold- and drought-related TFs. Two TFs, Myb4 and AP37, were only induced by 2-OHMel treatment. Transgenic rice lines overexpressing rice Myb4 were not resistant to the combined stressors; however, the expression of UCP1, HKT1, and PIP2;1 transcripts was slightly enhanced. These data show that 2-OHMel alleviates the effects of simultaneous abiotic stressors via the actions of multiple TFs, including Myb4 and AP37.


Efficient functional neutralization of lethal peptide toxins in vivo by oligonucleotides.
Medical means to save the life of human patients affected by drug abuse, envenomation or critical poisoning are currently limited. While the compounds at risks are most often well identified, particularly for bioterrorism, chemical intervention to counteract the toxic effects of the ingested/injected compound(s) is restricted to the use of antibodies. Herein, we illustrate that DNA aptamers, targeted to block the pharmacophore of a poisonous compound, represent a fast-acting and reliable method of neutralization in vivo that possesses efficient and long-lasting life-saving properties. For this proof of concept, we used one putative bioweapon, αC-conotoxin PrXA, a marine snail ultrafast-killing paralytic toxin, to identify peptide-binding DNA aptamers. We illustrate that they can efficiently neutralize the toxin-induced (i) displacement of [125I]-α-bungarotoxin binding onto nicotinic receptors, (ii) inhibition of diaphragm muscle contraction, and (iii) lethality in mice. Our results demonstrate the preclinical value of DNA aptamers as fast-acting, safe and cheap antidotes to lethal toxins at risk of misuse in bioterrorism and offer hope for an alternative method than donor sera to treat cases of envenomation.


Further study of fibrinogen degradation products in bladder cancer detection.
A new, rapid immunoassay kit for assaying fibrinogen degradation products (FDP) was studied in 56 patients with cancer of the bladder and in 48 control patients. The specificity of the kit was demonstrated with a small number of false positive results. In bladder cancer patients with low-stage, small superficial tumors, FDP was positive in 32.2 per cent. The combination of urinary cytologic examination with FDP increased the accuracy of the positive results to 80 per cent. The rapid FDP test supplements the urinary cytology in the follow-up and detection of early bladder cancer.


A new capacity of gut microbiota: Fermentation of engineered inorganic carbon nanomaterials into endogenous organic metabolites.
Carbon-based nanomaterials (CNMs) have recently been found in humans raising a great concern over their adverse roles in the hosts. However, our knowledge of the in vivo behavior and fate of CNMs, especially their biological processes elicited by the gut microbiota, remains poor. Here, we uncovered the integration of CNMs (single-walled carbon nanotubes and graphene oxide) into the endogenous carbon flow through degradation and fermentation, mediated by the gut microbiota of mice using isotope tracing and gene sequencing. As a newly available carbon source for the gut microbiota, microbial fermentation leads to the incorporation of inorganic carbon from the CNMs into organic butyrate through the pyruvate pathway. Furthermore, the butyrate-producing bacteria are identified to show a preference for the CNMs as their favorable source, and excessive butyrate derived from microbial CNMs fermentation further impacts on the function (proliferation and differentiation) of intestinal stem cells in mouse and intestinal organoid models. Collectively, our results unlock the unknown fermentation processes of CNMs in the gut of hosts and underscore an urgent need for assessing the transformation of CNMs and their health risk via the gut-centric physiological and anatomical pathways.


Hemodynamic effects of the novel selective cAMP-phosphodiesterase III inhibitor R 80122 in anesthetized patients with moderate left ventricular dysfunction before coronary artery bypass grafting.
To investigate the hemodynamic effects and safety of R 80122, a novel selective phosphodiesterase (PDE) III inhibitor, and its solvent hydroxypropyl-beta-cyclodextrin. Prospective, randomized study. Operating theater of a university hospital in the Netherlands. Twelve patients with impaired left ventricular function scheduled for coronary artery bypass grafting after induction of anesthesia were included. R 80122 (n = 6) or its solvent (n = 6) was administered using the same infusion regimen. A bolus of 0.1 mL/kg (= 0.1 mg/kg R 80122) was infused over 10 minutes followed by a maintenance infusion of 5 microliters/kg/min (5 micrograms/kg/min R 80122) over 20 minutes. Compared with the solvent, patients receiving R 80122 did not show any significant changes in heart rate, arterial blood pressure, or pulmonary artery pressures. However, R 80122 produced a marked increase (P < 0.05) in cardiac output (thermodilution) and echocardiographically obtained percentage area reduction. No arrhythmias or ischemic episodes occurred during the infusion period. The plasma half-life of R 80122 was 10.6 +/- 1.9 minutes. R 80122 appears to be a potent positive inotropic agent in these patients. Its use is not associated with marked vasodilation, it is devoid of positive chronotropic effects, and it can be administered safely in patients with impaired left ventricular function.


Lysosomal alterations during coronary atherosclerosis in the pigeon: correlative cytochemical and three-dimensional HVEM/IVEM observations.
Lysosomal changes have been implicated as one of the major factors contributing to the progression and complications of atherosclerosis, and recently foam cell formation has been correlated with increases in several acid hydrolases. To explore at the subcellular level relationships among lesion progression, cellular lipid accumulation, and lysosomal change, atherosclerotic lesions from hypercholesterolemic White Carneau pigeons have been studied through combined ultrastructural cytochemistry and stereo (three-dimensional) high-voltage electron microscopy. Lysosomal enzyme activity in the prelesion intima and in foam cells of early lesions was in discrete lysosomes of macrophage foam cells. Foam cell lipid at the early stages was primarily (72%) in cytoplasmic droplets, which formed a three-dimensional network with the small (0.25-0.8 microM in diameter), reaction-positive lysosomes suspended at the vertices of a cytoplasmic lattice that delineated individual lipid pools. Concomitant with lesion progression and increasing complexity, foam cell lysosome number, size, and complexity increased. The complexity was characterized by lysosome lipid accumulation (60% of cell lipid) and the fusion of lysosomes to form multilobulated organelles in which the acid phosphatase reaction product typically was circumferential to the lysosomal lipid core. The involvement of lysosomes climaxed in the more advanced region of lesions with foam cells in which the bulk of cytoplasmic volume was occupied by large (15-20 microM in diameter), multicompartmental, lipid-containing lysosomes. It is suggested that this progressive involvement of lysosomes is responsible for cell and tissue necroses characteristic of advanced lesions.


Operationalizing the Chronic Care Model with Goal-Oriented Care.
The Chronic Care Model has guided quality improvement in health care for almost 20 years, using a patient-centered, disease management approach to systems and care teams. To further advance efforts in person-centered care, we propose strengthening the Chronic Care Model with the goal-oriented care approach. Goal-oriented care is person-centered in that it places the focus on what matters most to each person over the course of their life. The person's goals inform care decisions, which are arrived at collaboratively between clinicians and the person. In this paper, we build on each of the elements of the Chronic Care Model with person-centered, goal-oriented care and provide clinical examples on how to operationalize this approach. We discuss how this adapted approach can support our health care systems, in particular in the context of growing multi-morbidity.


Patchouli alcohol isolated from Pogostemon cablin mediates endothelium-independent vasorelaxation by blockade of Ca2+ channels in rat isolated thoracic aorta.
The aerial parts of Pogostemon cablin (Blanco) Benth. for the treatment of cardiodynia have been documented in Mingyi Bielu of late Han Dynasty, in addition to that the Ca2+ antagonized activities of P. cablin and its critically pharmacological ingredient patchouli alcohol (PA) were reported previously. To investigate the relaxant effects of PA on rat isolated thoracic aortas and further explore its potential mechanisms of actions. The aortas with endothelium and without endothelium were prepared and suspended in the organ bath for isometric tension recordings. The responses to accumulative concentrations of PA in endothelium-intact (E + ) aortas with basal tension and in different treated aortas pre-contracted with potassium chloride (KCl) or phenylephrine (PHE) were observed; the effects of L-NAME and indomethacin in aortas with intact endothelium, and of L-NAME, propranolol, tetraethtylamine (TEA), 4-aminopyridine (4-AP), barium chloride (BaCl2), glyburide in aortas with endothelial denudation on PA-produced vasorelaxation were assessed; the influences of PA on extracellular Ca2+ influx and intracellular Ca2+ release were measured in Ca2+-free medium. Finally, the abilities of PA to inhibit KCl- and PHE-induced contractions were compared to that of verapamil in E- aortas. PA produced vasorelaxant effects in KCl- and PHE-precontracted E + aortas in a concentration-dependent manner, which had no statistically different from that in KCl- and PHE-precontracted E- aortas. PA (10 μM) significantly reduced KCl-induced contractions while PHE-induced contractions were significantly reduced by 100 μM of PA instead of 10 μM and 30 μM in aortas with endothelium. Pre-incubation of E + aortas with L-NAME as well as indomethacin and of E- aortas with L-NAME, propranolol, TEA, 4-AP, BaCl2 and glyburide had no obvious effects on vasorelaxation of PA. In endothelium-removed aortas around Ca2+-free solution, PA remarkably lowered the contractions stimulated with Ca2+ and PHE, and application of ruthenium red and heparin further enhanced the abilities of PA to reduce PHE-caused contractions. In aortas without endothelium, 100 μM of PA markedly attenuated KCl-induced contractions but not affect PHE-induced contractions. Verapamil at the equal dose markedly attenuated KCl- and PHE-induced contractions, and the inhibitory effects on KCl-induced contractions were more forceful than that on PHE-induced contractions. In combined usage, the inhibitory effects on the contractions elicited by KCl were evidently weaker than that of verapamil alone and indifferently stronger than that of PA alone, and the inhibitory effects on the contractions elicited by PHE were evidently weaker than that of single verapamil but stronger than that of single PA. PA may act as a Ca2+ antagonist to exert an intensively vasorelaxant effects through endothelium-independent pathway, and its mechanisms underlying the vasoactivities seem to be associated with the blockade of extracellular Ca2+ influx through VDCCs and ROCCs in vascular smooth muscle cells (VSMCs) membrane and intracellular Ca2+ releases through IP3R- and RYR-mediated Ca2+ channels in sarcolemma.


Development and validation of a LC-MS/MS method for the determination of isoeugenol in finfish.
A simple, rapid, selective and sensitive LC-MS/MS method was developed and validated for the determination of isoeugenol in finfish using an off-line dansylation derivatization step to enhance signal intensity. The sample was extracted with 10mL acetone using a tissue homogenizer, followed by derivatization with dansyl chloride and analysis by liquid chromatography tandem mass spectrometry. The method detection limit ranged from 0.2 to 0.7ngg-1 in six fish species. The limit of quantification was 2.5ngg-1 in each species. Recoveries of isoeugenol at three different levels (5, 10 and 20ngg-1) over two different days ranged from 91.2% to 108.0%. Precision (%RSDR) values determined at 10ngg-1 were 4.3%, 8.0%, 5.3%, 5.1%, 2.6% and 8.0% for tilapia, catfish, trout, salmon, hybrid striped bass and yellow perch, respectively. Studies of linearity in the range 2.5-40ngg-1 produced determination coefficients (R2) above 0.997 for all matrices.


Comparative study of non-invasive force and stress inference methods in tissue.
In the course of animal development, the shape of tissue emerges in part from mechanical and biochemical interactions between cells. Measuring stress in tissue is essential for studying morphogenesis and its physical constraints. For that purpose, a possible new approach is force inference (up to a single prefactor) from cell shapes and connectivity. It is non-invasive and can provide space-time maps of stress in a whole tissue, unlike existing methods. To validate this approach, three force-inference methods, which differ in their approach of treating indefiniteness in an inverse problem between cell shapes and forces, were compared. Tests using two artificial and two experimental data sets consistently indicate that our Bayesian force inference, by which cell-junction tensions and cell pressures are simultaneously estimated, performs best in terms of accuracy and robustness. Moreover, by measuring the stress anisotropy and relaxation, we cross-validated the force inference and the global annular ablation of tissue, each of which relies on different prefactors. A practical choice of force-inference methods in different systems of interest is discussed.


Cerebral dysfunction following infantile dietary chloride deficiency.
Twenty-two children who were chloride-depleted in infancy due to a chloride-deficient diet and who had resultant hypochloremic alkalosis were analyzed in regard to their signs and symptoms, metabolic studies, and growth parameters. Deceleration of weight, linear growth, and head growth occurred in most, and persistent growth failure occurred in some. The majority had cognitive deficits at follow-up. Comparison with growth parameters in a chronically malnourished group of children who had a variety of disorders revealed a similar degree of deceleration of weight (p = 0.50) and height (p = 0.70), but more severe deceleration of head growth (p = 0.01). Comparison with follow-up cognitive deficits reported in the United States medical literature in children with similar severity of nutritional deprivation indicates that the chloride-depleted infants had more frequent and more severe cognitive deficits (p = 0.09). Cognitive deficits have been documented in U. S. children who are nutritionally deprived only when disorders causing concomitant chloride depletion are responsible for the malnutrition.


Persistence of the neutralizing antibody response after SARS-CoV-2 infection.
Neutralizing antibodies are among the factors used to measure an individual's immune status for the control of infectious diseases. We aimed to confirm the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody levels in patients who had recovered from coronavirus disease 2019 (COVID-19). Plasma donors in South Korea who had completely recovered from SARS-CoV-2 infection had follow-up testing to determine the persistence of neutralizing antibodies using a plaque-reduction neutralization test and ELISA. Of the 111 participants-aged 20-29 years, 37/111 (33.3%); 30-39 years, 17/111 (15.3%); 40-49 years, 23/111 (20.7%); 50-59 years, 21/111 (18.9%); 60-65 years, 13/111 (11.7%); male, 43/111 (38.7%); female, 68/111 (61.3%)-66.1% still had neutralizing antibodies approximately 9 months (range 255-302 days) after confirmation of the diagnosis. In this study we analysed the titre of neutralizing antibodies associated with predicting immune status in individuals with natural infection. Information about the persistence and change in levels of neutralizing antibodies against SARS-CoV-2 can be utilized to provide evidence for developing vaccination schedules for individuals with previous infection.


Advances in cardiac biomarkers.
The diagnostic and prognostic roles of new and established cardiac biomarkers are continually changing. This update article discusses clinical diagnosis as a framework for directing biomarker testing. Markers are reviewed in the settings of acute coronary syndromes, decompensated heart failure, and noncardiac clinical scenarios.


Neurodevelopmental Outcomes for Retinopathy of Prematurity: A Taiwan Premature Infant Follow-up Network Database Study.
To evaluate the neurodevelopmental outcomes in premature infants who received intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections to treat retinopathy of prematurity (ROP). Retrospective cohort study. This study was conducted using the database from the Taiwan Premature Infant Follow-up Network. Demographic data, systemic risk factors, ROP status, and neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) were collected. Patients were divided into 4 groups: prematurity without ROP, ROP without treatment, ROP with laser treatment, and ROP with intravitreal anti-VEGF treatment. A generalized estimating equation was used for analyzing repeated measurements of Bayley-III at the corrected ages of 6, 12, and 24 months. A total of 2090 patients with a mean gestational age of 31.2 weeks were included. The Bayley-III composite scores of patients with ROP treated with anti-VEGF were comparable to those of patients with ROP without treatment (cognitive: P = .491; language: P = .201; motor: P = .151) and premature patients without ROP (cognitive: P = .985; language: P = .452; motor: P = .169) after adjusting for confounders. Patients with ROP treated with laser photocoagulation exhibited poorer cognitive composite scores than did those without treatment (P < .001), premature patients without ROP (P < .001), and those treated with anti-VEGF (P < .001), but they had similar language and motor composite scores. Intravitreal anti-VEGF treatment for ROP was not associated with adverse neurodevelopment in premature infants. Further studies are needed to determine whether general anesthesia or sedation used in laser treatment for ROP has significant impacts on neurodevelopmental outcomes.


A SEM-correlation of the anatomy of the vitreous body: making visible the invisible.
The naked human vitreous (sclera, iris and cornea removed) suspended in water does not reveal inner structures. After ink injection into the vitreous, the presence of different compartments and the existence of cisterns becomes evident. A concept of the internal system of cisterns is given on the basis of stereoscopic-lightmicroscopic images. An attempt is made to correlate images of the complete vitreous body, obtained with a stereo-lightmicroscope, with images of segments of cisternal walls produced with a scanning electron-microscope (SEM). A comparison is made between SEM-images of the vitreous bodies of human and rabbit eyes.


Hemosiderin deposition in muscle. Report of three cases.
This report presents the morphological character of iron deposits in muscle biopsies of three patients who have been suffering from secondary hemochromatosis. The granules observed by light microscopy and located either in the cytoplasm of macrophages or inside muscle fibres are illustrated in electron micrographs. In this study, Thiery's technic, which is a specific and very sensitive reaction, has been very useful to confirm by electron microscopy that these granules contain iron. Such a study in muscle appears to be unique. In our experience, accumulation of hemosiderin pigment in muscle does not seem to be specific of any disease but suggests that a hepatic biopsy must be done.


Ethyl 2-cyano-2-{(Z)-2-[2,2-di-cyano-1-(4-methyl-phen-yl)eth-yl]cyclo-hexyl-idene}acetate.
In the title compound, C22H23N3O2, the cyclo-hexane ring adopts a chair conformation. The methyl-phenyl ring is oriented at an angle of 36.2 (1)° with respect to the best plane of cyclo-hexane moiety. In the crystal, mol-ecules associate via C-H⋯N hydrogen bonds, forming a three-dimensional network.


Dermal preservation using the Versajet hydrosurgery system for debridement of paediatric burns.
Loss of dermis is one of the principal factors that contributes to poor scar outcome after severe burn. Dermal loss may be due to the primary injury, surgical management or as a result of infection. Strategies for dermal preservation are therefore important to improve scar quality. We report our early experience using the Versajet hydrosurgery system, to preserve dermal tissues, both directly during surgical debridement and indirectly by reducing infection and optimising the use of biological dressings. In deep partial thickness burns softer necrotic dermis can be removed with the Versajet sparing the underlying tougher viable dermis. In superficial burns the Versajet cleans and removes loose epidermal elements providing an optimal wound surface for the application of biological dressings, even a number of days after injury. Versajet is most useful when the tissue to be removed is softer than that to be left behind.


Replicating predictive serum correlates of greater translocator protein distribution volume in brain.
Greater activation of glia, a key component of neuroinflammation, is an important process to target in neuropsychiatric illnesses. However, the magnitude of gliosis varies across cases so low-cost predictors are needed to stratify subjects for clinical trials. Here, several such blood serum measures were assessed in relation to TSPO VT, an index of translocator protein density, measured with positron emission tomography. Blood serum concentration of several products known to be synthesized by activated microglia (and to some extent astroglia) [prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2α), and tumor necrosis factor alpha (TNFα)], controlled by an index of peripheral inflammation [C-reactive protein (CRP)] and TSPO VT were measured in 3 cohorts: prefrontal cortex TSPO VT of 20 subjects with major depressive episodes (MDEs) from major depressive disorder (MDD); and 56 subjects with treatment resistant MDEs from MDD; and dorsal caudate TSPO VT of 20 subjects with obsessive-compulsive disorder. Ln(PGE2/CRP) and ln(TNFα/CRP) consistently correlated with TSPO VT (R2 = 0.36 to 0.11, p = 0.0030 to p = 0.0076). Assessment of threshold serum values to predict highly elevated TSPO VT, demonstrated that a positive predictive value (PPV) of 80% was possible while retaining 40% of participant samples and that receiver operating curves (ROC) ranged from 75 to 81%. Post-hoc selection of ln(CRP) was more predictive (R2 = 0.23 to 0.39, p = 0.0058 to p = 0.00013; ROC > 80%). Systematic assessment of selected peripheral inflammatory markers is promising for developing low cost predictors of TSPO VT. Marker thresholds with high PPV will improve subject stratification for clinical trials of glial targeting therapeutics.


Stochastic Navier-Stokes Equations on a Thin Spherical Domain.
Incompressible Navier-Stokes equations on a thin spherical domain Q ε along with free boundary conditions under a random forcing are considered. The convergence of the martingale solution of these equations to the martingale solution of the stochastic Navier-Stokes equations on a sphere S 2 as the thickness converges to zero is established.


Predictors of disordered eating in a sample of elite Division I college athletes.
The present study sought to investigate the relationship between a number of areas of elite student-athletes' lives and disordered eating. We surveyed 1445 elite Division I athletes at 11 different institutions and in 11 different sports. Hierarchical regression was used to indicate specific areas of the participants' collegiate experience that may be associated with disordered eating attitudes and symptomatology. Results demonstrate that the variables entered into each model predicted between 40.5% and 46.4% of the variance for the restriction of food, body dissatisfaction, and drive for thinness. Categories of variables that generally predicted the most variance for each dependent measure were demographics, athletic involvement, and personality. Of the 11 sports included in the analysis, wrestling and gymnastics demonstrated elevated levels of drive for thinness, food restriction, and purging behavior compared to other athletes. Findings suggest that in elite athletes gender, ethnicity, sport, and self-esteem are associated with several behaviors and attitudes indicative of disordered eating.


Altered cytokine levels in the blood and cerebrospinal fluid of chronic pain patients.
This study replicates and extends prior reports of abnormal cytokine levels in chronic pain patients and has correlated the alterations with pain severity. In addition, there appeared to be a need to directly assess cerebrospinal fluid (CSF) because previous findings on cytokine concentrations in peripheral circulation have been inconsistent. CSF and blood specimens were obtained from 14 patients with distal painful non-diabetic polyneuropathy (DPPN) or post-traumatic neuralgia (PTN). Elevated receptor levels for Tumor Necrosis Factor (sTNFr) were the most distinctive abnormality along with low interleukin-10 (IL-10). sTNFr in CSF and blood, and IL-1ss in CSF, were positively associated with pain intensity, whereas IL-10 in both compartments was inversely correlated with pain symptoms. An imbalance of pro- and anti-inflammatory cytokines appears to be a clinically relevant feature, which may contribute to the maintenance of chronic pain.


The effect of ofloxacin otic drops on the regeneration of human traumatic tympanic membrane perforations.
To investigate the effects of direct application of ofloxacin otic drops on human traumatic tympanic membrane perforations (TMPs). Prospective, sequential allocation, controlled clinical study. Tertiary university hospital. In total, 149 patients with traumatic TMPs were recruited. They were allocated sequentially to two groups: a conservative observation group (n = 75) and a ofloxacin drops-treated group (n = 74). The closure rate, closure time and rate of otorrhoea were compared between the groups at 6 months. In total, 145 patients were analysed. The closure rates of medium perforations between the groups were not significantly different (P = 0.35); however, the ofloxacin drops-treated group had a significantly shorter closure time for medium perforations than the observation group (P < 0.01). Additionally, the ofloxacin drops-treated group showed improvement in the closure rate of large perforations (P = 0.02) and a significantly shorter mean closure time (P < 0.01) than the observation group. However, purulent otorrhoea was not significantly different between the groups (P = 0.37). The present findings indicate that the moist eardrum environment resulting from topical application of ofloxacin drops shortened the closure time and improved the closure rate, but did not affect hearing improvement or increase the rate of middle ear infection of large traumatic TMPs. Thus, although traumatic TMPs tend to heal spontaneously, moist therapy can be considered for traumatic, large TMPs in the clinic.


Deep learning referral suggestion and tumour discrimination using explainable artificial intelligence applied to multiparametric MRI.
An appropriate and fast clinical referral suggestion is important for intra-axial mass-like lesions (IMLLs) in the emergency setting. We aimed to apply an interpretable deep learning (DL) system to multiparametric MRI to obtain clinical referral suggestion for IMLLs, and to validate it in the setting of nontraumatic emergency neuroradiology. A DL system was developed in 747 patients with IMLLs ranging 30 diseases who underwent pre- and post-contrast T1-weighted (T1CE), FLAIR, and diffusion-weighted imaging (DWI). A DL system that segments IMLLs, classifies tumourous conditions, and suggests clinical referral among surgery, systematic work-up, medical treatment, and conservative treatment, was developed. The system was validated in an independent cohort of 130 emergency patients, and performance in referral suggestion and tumour discrimination was compared with that of radiologists using receiver operating characteristics curve, precision-recall curve analysis, and confusion matrices. Multiparametric interpretable visualisation of high-relevance regions from layer-wise relevance propagation overlaid on contrast-enhanced T1WI and DWI was analysed. The DL system provided correct referral suggestions in 94 of 130 patients (72.3%) and performed comparably to radiologists (accuracy 72.6%, McNemar test; p = .942). For distinguishing tumours from non-tumourous conditions, the DL system (AUC, 0.90 and AUPRC, 0.94) performed similarly to human readers (AUC, 0.81~0.92, and AUPRC, 0.88~0.95). Solid portions of tumours showed a high overlap of relevance, but non-tumours did not (Dice coefficient 0.77 vs. 0.33, p < .001), demonstrating the DL's decision. Our DL system could appropriately triage patients using multiparametric MRI and provide interpretability through multiparametric heatmaps, and may thereby aid neuroradiologic diagnoses in emergency settings. Our AI triages patients with raw MRI images to clinical referral pathways in brain intra-axial mass-like lesions. We demonstrate that the decision is based on the relative relevance between contrast-enhanced T1-weighted and diffusion-weighted images, providing explainability across multiparametric MRI data. • A deep learning (DL) system using multiparametric MRI suggested clinical referral to patients with intra-axial mass-like lesions (IMLLs) similar to radiologists (accuracy 72.3% vs. 72.6%). • In the differentiation of tumourous and non-tumourous conditions, the DL system (AUC, 0.90) performed similar with radiologists (AUC, 0.81-0.92). • The DL's decision basis for differentiating tumours from non-tumours can be quantified using multiparametric heatmaps obtained via the layer-wise relevance propagation method.


Prognostic nutrition index affects the prognosis of patients undergoing trimodality therapy for locally advanced non-small cell lung cancer.
Trimodality therapy, comprised of induction chemoradiotherapy (iCRT) followed by surgery, is a highly invasive treatment option for locally advanced non-small cell lung cancers (LA-NSCLCs; defined as a heterogenous disease). We conducted this study to investigate the prognostic nutritional index (PNI) of LA-NSCLC patients undergoing trimodality therapy, which has not been studied in detail before. The subjects of this retrospective study were 127 patients who underwent trimodality therapy between 1999 and 2016. We measured the PNI at three points: before iCRT (pre-iCRT), before the operation, and after the operation. PNIs decreased significantly as treatment progressed. Patients with clinical T3/4 (cT3/4) disease had a significantly lower PNI than those with cT1/2 disease, but the extent of lymph-node metastasis did not affect the PNI at any point. Using the cut-off values of receiver-operating curve analyses, multivariable analyses revealed that a high PNI pre-iCRT correlated significantly with a better survival of LA-NSCLC patients, especially those with cT3/4 disease (hazard ratio 3.84; 95% confidential interval 1.34-12.5, P = 0.012). Measuring the PNI before trimodality therapy is important for predicting the clinical outcome of patients with LA-NSCLC, with differing predictive ability according to the disease extent. Perioperative intensive nutritional intervention must be considered for patients who undergo trimodality therapy for LA-NSCLC.


Environmental fate of sulfonated-PCBs: Soil partitioning properties, bioaccumulation, persistence, and mobility.
Two new classes of PCB metabolites were recently discovered: sulfonated-polychlorinated biphenyls (sulfonated-PCBs) and hydroxy-sulfonated-polychlorinated biphenyls (OH-sulfonated-PCBs). These metabolites, originating from PCB degradation, seem to possess more polar characteristics than their parent compounds. However, no other information, such as their chemical identity (CAS number) or their ecotoxicity or toxicity, is available so far, although more than about one hundred different chemicals were observed in soil samples. In addition, their physico-chemical properties are still uncertain since only estimations are available. Here we show the first evidence on the fate of these new classes of contaminants in the environment, producing results from several experiments, to evaluate sulfonated-PCBs and OH-sulfonated-PCBs soil partition coefficients, degradation in soil after 18 months of rhizoremediation, uptake into plant roots and earthworms, as well as a preliminary analytical method to extract and concentrate these chemicals from water. The results give an overview of the expected environmental fate of these chemicals and open questions for further studies.


Ultrasonographic analysis of facial skin thickness in relation to age, site, sex, and body mass index.
Numerous nonsurgical but invasive cosmetic procedures are performed blindly in the dermis or subcutaneous fat layer of the facial skin. To measure the numerical skin thickness of the facial areas where dermatological procedures are performed by applying ultrasound techniques, and to make it possible to estimate the skin thickness by investigating the influence of several individual constitutional factors such as age, sex, and body mass index (BMI), so that these variables can be applied to estimate skin thickness. Skin thickness was measured at eight different facial points using an ultrasound machine (Affiniti 50; Philips Inc.). Demographic data were gathered using questionnaires. Manual BMI was calculated from the weight and height of each participant, and individual BMI measurements were performed using a body composition analyzer. In terms of whole skin thickness, the thickest point was the mouth corner, and the thinnest point was the lateral forehead. The thickest point in the epidermis was the chin, and the thinnest point was the nasolabial fold. The thickest point in the dermis was the corner of the mouth, and the thinnest was the lateral forehead. Full skin thickness and dermal thickness were mostly lower in females. Skin thickness was not significantly correlated with BMI. The skin thickness at different points on the face was variable, and realistic data about skin thickness can be obtained by in vivo ultrasonographic analysis of the skin.


Personality characteristics of sex offenders: a review.
Research utilizing psychometric instruments to assess personality characteristics of sex offenders is reviewed. A methodological shortcoming of this research is the frequent use of the MMPI. It is argued that this test was originally developed as a measure of types of psychopathology and has not been validated as a personality test. Studies using tests other than the MMPI have seldom controlled for institutionalization and impression management. Further, little attention has been paid to criminal history, making it difficult to conclude that the current offense is representative of past behavior. In the case of child molesting, there has been a failure to specify and/or control for age and sex of victim and degree of force used. Results suggest that men who engage in rape and child molesting are guilt-ridden individuals who inhibit aggression, but these findings are tentative because of the aforementioned methodological problems.


Medial prefrontal cortex neuronal circuits in fear behavior.
The medial prefrontal cortex (mPFC) has emerged as a key structure involved in the modulation of fear behavior over the past few decades. Anatomical, functional and electrophysiological studies have begun to shed light on the precise mechanisms by which different prefrontal regions regulate the expression and inhibition of fear behavior. These studies have established a canonical view of mPFC functions during fear behavior with dorsal regions selectively involved in the expression of fear behavior and ventral regions linked to the inhibition of fear behavior. Although numerous reports support this view, recent data have refined this model and suggested that dorsal prefrontal regions might also play an important role in the encoding of fear behavior itself. The recent development of sophisticated approaches such as large scale neuronal recordings, simultaneous multisite recordings of spiking activity and local field potentials (LFPs) along with optogenetic approaches will facilitate the testing of these new hypotheses in the near future. Here we provide an extensive review of the literature on the role of mPFC in fear behavior and propose further directions to dissect the contribution of specific prefrontal neuronal elements and circuits in the regulation of fear behavior.


[Detection of L forms of Vibrio cholerae in the water of open water reservoirs].
L-forms of cholera vibrios were isolated from the river water for the first time. The presence of L-forms in water permitted to suppose that such variants served as one of the forms of cholera causative agent preservation in the external medium.


Molecular urinary sediment analysis in patients with transitional cell bladder carcinoma.
Nowadays urinary cytology methods in early diagnosis of superficial bladder transitional carcinoma (TCC) allow the identification of about 35-50% of tumors. Cytoscopy and biopsy are reliable but invasive. It has been recently shown that allelic abnormalities detected by microsatellite analysis of DNA extracted from urine sediment can be successfully used in TCC. We performed a comparative study between urinary cytology and microsatellite sequence alterations in patients affected by TCC. Fifty-eight patients were recruited for the study. Of these, 45 had cystoscopic diagnosis of TCC, while 7 were without apparent lesions after TUR but presented urinary irritative symptoms after BCG endocavitary administration, and 6 who underwent open surgery for benign prostatic hypertrophy represented the control groups. DNA extraction and PCR analysis were performed by using 13 different primers, while urinary cytology was performed by using an Autocyte Preparation System. Urinary cytology confirmed the presence of TCC in 22% of patients while in 15.5% of them a displastic/inflammatory status was found. Microsatellite analysis allowed the identification of 82% of tumors with a 100% specificity. A high sensitivity was obtained in patients affected by superficial (79%) or G1(80%) tumors. Microsatellite analysis represents a highly sensitive and specific marker in TCC diagnosis and monitoring.


Inhibition of Inflammation-Associated Olfactory Loss by Etanercept in an Inducible Olfactory Inflammation Mouse Model.
To determine the effect of a soluble human tumor necrosis factor alpha (TNF-α) receptor blocker (etanercept) on an inducible olfactory inflammation (IOI) mouse model. An in vivo study using a transgenic mouse model. Research laboratory. To study the impact of chronic inflammation on the olfactory system, a transgenic mouse model of chronic rhinosinusitis-associated olfactory loss was utilized (IOI mouse), expressing TNF-α in a temporally controlled fashion within the olfactory epithelium. In one group of mice (n = 4), etanercept was injected intraperitoneally (100 μg/dose, 3 times/week) concurrent with a 2-week period of TNF-α expression. A second group of mice (n = 2) underwent induction of TNF-α expression for 8 weeks, with etanercept treatment administered during the final 2 weeks of inflammation. Olfactory function was assayed by elecro-olfactogram (EOG), and olfactory tissue was processed for histology and immunohistochemical staining. Each group was compared with an equal-number control group. Compared with nontreated IOI mice, etanercept-treated IOI mice showed significantly improved EOG responses after 2 weeks (P < .001). After 8 weeks of induced inflammation, there was massive loss of olfactory epithelium and no EOG response in nontreated IOI mice. However, in etanercept-treated mice, regeneration of olfactory epithelium was observed. Concomitant administration of etanercept in IOI mice results in interruption of TNF-α-induced olfactory loss and induction of neuroepithelial regeneration. This demonstrates that etanercept has potential utility as a tool for elucidating the role of TNF-α in other olfactory inflammation models.


Mutagenesis of anaerobic cultures of Salmonella typhimurium by nitrosoguanidine, diethyl sulfate and 9-aminoacridine.
Despite a previous report to the contrary, anaerobic cultures of Salmonella typhimurium strain LT2 hisG46 are revertible (although to a slightly reduced extent) by both N-methyl-N'-nitro-N-nitrosoguanidine and diethyl sulfate, while anaerobic cultures of a strain carrying the frameshift hisC3076 marker are fully revertible by 9-aminoacridine.


Adenosine-5'-triphosphate levels in experimental CaNT and Fib/t tumours of varying volume and degree of hypoxia.
The variation of adenosine-5'-triphosphate (ATP) content per unit mass of tumour, versus tumour volume was measured in vivo under normoxic conditions, using CaNT and Fib/t murine tumours grown in CBA and WHT mice respectively. A monotonically decreasing relation was found. Artificially induced tumour hypoxia resulting from 15 min of clamping was accompanied by reduced ATP levels.


Sexually transmitted infection prevalence in a population seeking no-cost contraception.
We used universal screening to determine the prevalence rates of Neisseria gonorrhoeae (GC), Chlamydia trachomatis (CT), and Trichomonas vaginalis (TV) in 9256 women enrolling into a contraceptive study. We offered screening using nucleic acid amplification or culture to all participants enrolling into the Contraceptive CHOICE Project. Demographic characteristics were collected through staff-administered questionnaires. Univariate and multivariable analyses were performed to assess the risk of sexually transmitted infection at baseline and to compare risk profiles of CT and TV. Results were available for 8347 consenting women with satisfactory results; 656 (7.9%) were tested positive for 1 or more infections. Approximately one third of participants were older than 26 years, and half were identified as African American. There were 35 cases of GC for a prevalence of 0.4% (95% confidence interval [CI], 0.3-0.6), 260 cases of CT for a prevalence of 3.1% (95% CI, 2.8-3.5), and 410 cases of TV for a prevalence of 4.9% (95% CI, 4.4-5.4). Black women were more likely to be tested positive (odds ratio, 3.95; 95% CI, 3.08-5.06) compared with white women and accounted for 81.3% of cases. T. vaginalis was more prevalent in black women (8.9%) compared with white women (0.9%). Older age was a risk factor for TV, whereas younger age was associated with CT. Of the 656 positive cases, 106 (16%) were diagnosed in women older than 25 years, falling outside traditional screening guidelines. We found GC, CT, and TV to be more prevalent than current national statistics, with TV being the most prevalent. Current screening recommendations would have missed 16% of infected women.


Preventive Antibiotics and Delayed Cerebral Ischaemia in Patients with Aneurysmal Subarachnoid Haemorrhage Admitted to the Intensive Care Unit.
Delayed cerebral ischemia (DCI) is an important contributor to poor outcome after aneurysmal subarachnoid haemorrhage (aSAH). Development of DCI is multifactorial, and inflammation, with or without infection, is one of the factors independently associated with development of DCI and poor outcome. We thus postulated that preventive antibiotics might be associated with a reduced risk of DCI and subsequent poor outcome in aSAH patients. We performed a retrospective cohort-study in intensive care units (ICU) of three university hospitals in The Netherlands. We included consecutive aSAH patients with minimal ICU stay of 72 h who received either preventive antibiotics (SDD: selective digestive tract decontamination including systemic cefotaxime or SOD: selective oropharyngeal decontamination) or no preventive antibiotics. DCI was defined as a new hypodensity on CT with no other explanation than DCI. Hazard ratio's (HR) for DCI and risk ratio's (RR) for 28-day case-fatality and poor outcome at 3 months were calculated, with adjustment (aHR/aRR) for clinical condition on admission, recurrent bleeding, aneurysm treatment modality and treatment site. Of 459 included patients, 274 received preventive antibiotics (SOD or SDD) and 185 did not. With preventive antibiotics, the aHR for DCI was 1.0 (95% CI 0.6-1.8), the aRR for 28-day case-fatality was 1.1 (95% CI 0.7-1.9) and the aRR for poor functional outcome 1.2 (95% CI 1.0-1.4). Preventive antibiotics were not associated with reduced risk of DCI or poor outcome in aSAH patients in the ICU.


Post-exposure prophylaxis following consented sexual exposure: impact of national recommendations on user profile, drug regimens and estimates of averted HIV infections.
The aim of the study was to describe the characteristics, impact and outreach of post-exposure prophylaxis (PEP) for sexual exposure in Brazil. We used secondary data from the Brazilian Ministry of Health to describe the impact of national guidelines on the frequency of prescription, user profile and antiretroviral regimens. We also estimated the number of potentially averted HIV infections attributable to PEP for consented sexual exposure between 2009 and 2017. A total of 260 457 PEP regimens were prescribed to individuals ≥ 14 years old; 104 613 (40.2%) were prescribed for consented sexual exposure, with an increasing frequency since 2011. Drugs used in PEP regimens underwent significant modifications during the period, reflecting national recommendations. We estimated that there were up to 3138 potentially averted HIV infections attributable to PEP for consented sexual exposure between 2009 and 2017. In the context of a combined HIV prevention strategy, PEP is still an essential tool for individuals for whom other methods are contraindicated or fail to be applied.


Perfusion of the fourth cerebral ventricle with fentanyl induces naloxone-reversible bradycardia, hypotension, and EEG synchronisation in conscious dogs.
Injection of fentanyl into the cisterna magna of the brain leads to hypotension and bradycardia in anesthetised dogs. To determine if this effect is related to the recently discovered opiate receptors fentanyl was perfused in increasing concentrations (2.5-20 microgram/ml) through the cerebro-ventricular system in conscious dogs. Blood pressure was recorded continuously from a punctured exteriorised carotid artery; heart rate was derived from the ECG. Baroreflex activity was tested repeatedly by clamping of both common carotid arteries. Cerebral activity was evaluated from the EEG. Perfusion of the fourth cerebral ventricle resulted in a concentration-related fall in heart rate by 43% and in an inhibition of the reflex response of heart rate to carotid clamping. In contrast, blood pressure fell only moderately by 14% and its reflex response was well maintained. The EEG pattern changed from frequencies in the beta-band (awake control) to gradual synchronisation with delta-activity corresponding to behavioural signs of tranquilisation and sleep-like states. All these effects were reversed by naloxone. No effects were seen when fentanyl was perfused through the lateral ventricles and third ventricle although this yielded similar serum concentration as after perfusion of the fourth ventricle. It is concluded that opiate receptors bordering the fourth cerebral ventricle mediate the cardiovascular and hypnotic action of fentanyl.


Critical current density improvement in CSD-grown high-entropy REBa2Cu3O7-δ films.
High-entropy oxide (HEO) superconductors have been developed since very recently. Different superconductors can be produced in the form of a high-entropy compound, including REBa2Cu3O7-δ (REBCO). However, until now, mainly bulk samples (mostly in polycrystalline form) have been reported. In this work, the first CSD-grown high-entropy (HE) REBCO nanocomposite films were successfully synthesized. In particular, high-quality Gd0.2Dy0.2Y0.2Ho0.2Er0.2Ba2Cu3O7-δ nanocomposite films with 12 mol% BaHfO3 nanoparticles were grown on SrTiO3 substrates. The X-ray diffraction patterns show a near-perfect c-axis oriented grain growth. Both T c and 77 K J sf c, 91.9 K and 3.5 MA cm-2, respectively, are comparable with the values of the single-RE REBCO films. Moreover, at low temperatures, specifically at 30 K, the J c values are larger than those of the single-RE samples. A transmission electron microscopy (TEM) study, including energy-dispersive X-ray spectroscopy (EDXS) measurements, reveals that the different RE3+ ions are distributed homogeneously in the matrix without forming clusters. This distribution causes point-like pinning centres that explain the superior performances of these samples at low temperatures. Although still seen as a proof-of-concept for the feasibility of preparing such films, these results demonstrate that the HE REBCO films are a promising option for the future fabrication of high-performance coated conductors. In the investigated B-T range, however, their J c values are still lower than those of other, medium-entropy REBCO films, which shows that an optimization of the composition of the HE REBCO films is needed to maximize their performance.