Depression in the house: The effects of household air pollution from solid fuel use among the middle-aged and older population in China.
Although the adverse health effects of ambient air pollution are well documented, evidence on the depression effects of household air pollution (HAP) are scarce. We investigated the effects of HAP exposure from the use of solid fuel on depression using a nationally representative dataset of middle-aged and older population in China. By employing the propensity score matching method, we first matched the type of household fuel based on background information, including demographic characteristics, lifestyles, health status, and household economic levels. Based on the matched data, we conducted OLS and logistic regressions with cluster standard error at community level to examine the effects of household solid fuel use on depression and adjusted for potential confounders. Heterogeneous effects for vulnerable population were also considered. We found a significantly higher Center for Epidemiologic Studies Depression Scale (CES-D) score and depression risk among current household solid fuel users. After matching and adjusting for potential confounders, current solid fuel users had a higher CES-D score of 0.59 (95% confidence interval [CI]: 0.31, 0.89) than clean fuel users. The OR of depression risk were 1.26 (95% CI: 1.14, 1.41). Solid fuel users had the highest CES-D scores (β = 0.99, 95% CI: 0.62, 1.36) and depression risk (OR = 1.49, 95% CI: 1.30, 1.73) for over five years. These associations were generally higher in females, participants aged 65 years and older, with a BMI ≥ 25, with low education, with low household economic levels, and those suffer from chronic diseases, including diabetes, chronic lung diseases, and cardiovascular diseases. Exposure to HAP from solid fuel combustion was linked with strong depression outcomes. Findings suggested a need to strengthen public health efforts, such as controlling the social, health, and economic costs of depression by taking the physical environment, including HAP exposure, into account.


Unique Lewis and Bronsted acidic sites texture in the selective production of tetrahydropyran and oxepanefrom1,5-pentanediol and 1,6-hexanediol over sustainable red brick clay catalyst.
Activated red brick (ARB) clay material proved superb catalyst for selective conversion of 1,5-pentanediol (1,5-PDO) to tetrahydropyran (THP) and 1,6-hexanediol (1,6-HDO) to oxepane (OP) via dehydration under vapor phase conditions in a continuous flow reactor. As per scanning electron microscopy (SEM), SEM-EDX and X-ray fluorescence (XRF) techniques, ARB clay catalyst majorly possessed silica (quartz), and iron oxide (hematite) species, and synergistic texture contributed to the catalytic efficiency for prolonged time-on-stream (TOS). The combination of active Lewis and Bronsted acidic sites with weak to mild acidic nature in the ARB clay obviously facilitates the dehydration reaction with high selectivity, tetrahydropyran (82%) and oxepane (89%). ARB clay displayed superior catalytic properties in the dehydration of alcohols compared with activities of commercial silica and α-Fe2O3 as catalysts. Commercial silica and α-Fe2O3 catalysts possessing the Lewis acidic sites only did not facilitate synchronous dehydration mechanism.


Dimension Tuning of All-Inorganic Ag-Based Metal Halides by Solvent Engineering.
Dimension growth of metal halides is important for its properties and applications. However, such dimension control of the metal halides is rarely reported in the literature and the growth mechanism is not clear yet. A minute difference of solvent properties can tremendously alter the process of nucleation and growth of crystals. Herein, an intriguing phenomenon of dimension tuning for Ag-based metal halides is reported. The 1D Cs2 AgCl3 crystals can be obtained in pure DMF while the 2D CsAgCl2 crystals are obtained in pure DMSO. Both exhibit bright yellow emission, which are derived from self-trapping excitons (STEs). The photoluminescence quantum yield (PLQY) of Cs2 AgCl3 (1D) and CsAgCl2 (2D) are 28.46 % and 20.61 %, respectively. In order to understand the mechanism of the dimension change, additional solvents (N,N-dimethylacetamide, DMAC, 1,3-Dimethyl-Tetrahydropyrimidin-2(1H)-one, DMPU) are also selected to process the precursor for crystal growth. By comparing the functional group, dielectric constant, and donor number among the four solvents, we find the donor number plays the predominant role in nucleation process for Cs2 AgCl3 and CsAgCl2 . This research reveals the relationship between coordination ability of the solvent and the dimension of metal halides.


Free fatty acid suppositories are as effective as docusate sodium and sorbitol enemas in treating constipation in children.
A well-documented, clinically proven per rectum treatment for childhood constipation is needed. This phase two clinical trial evaluated the efficacy of suppositories containing free fatty acids (FFA) compared with Klyx docusate sodium and sorbitol enemas. A randomised, controlled, single-blind study was undertaken on 77 children aged between one and 17 who presented to an emergency department in Iceland and were diagnosed with constipation. In stage one, 23 patients were randomised to receive lower dose FFA suppositories or Klyx (n = 33). In stage two, 21 different patients were randomised to receive higher dose suppositories and compared with the same Klyx control subjects. The suppositories were effective at bowel emptying in 39% of the group who received the lower FFA doses and 81% of the group receiving higher doses, compared with 88% in the Klyx control group. Symptom relief was obtained in 30% of the group receiving the lower doses and 71% of the group receiving the higher doses, compared with 73% in the control group. The higher dose FFA suppositories were as effective as the Klyx enemas with regard to bowel emptying and symptom relief and might provide an important and less invasive alternative for childhood constipation.


A procedure for electro-elution of DNA from agarose gels.
A simple device is described for efficient and reproducible electro-elution of DNA resolved in agarose gels. DNA (greater than 1 micrograms) is recovered with consistent yields of over 70% into preset elution volumes of 100 to 500 microliters.


Acceptance, satisfaction and cost of an integrative anthroposophic program for pediatric respiratory diseases in a Swiss teaching hospital: An implementation report.
For the pilot phase of an integrative pediatric program, we defined inpatient treatment algorithms for bronchiolitis, asthma and pneumonia, using medications and nursing techniques from anthroposophic medicine (AM). Parents could choose AM treatment as add-on to conventional care. To evaluate the 18-month pilot phase, parents of AM users were asked to complete the Client Satisfaction Questionnaire (CSQ-8) and a questionnaire on the AM treatment. Staff feedback was obtained through an open-ended questionnaire. Economic data for project set-up, medications and insurance reimbursements were collected. A total of 351 children with bronchiolitis, asthma and pneumonia were hospitalized. Of these, 137 children (39%) received AM treatment, with use increasing over time. 52 parents completed the questionnaire. Mean CSQ-8 score was 29.77 (95% CI 29.04-30.5) which is high in literature comparison. 96% of parents were mostly or very satisfied with AM; 96% considered AM as somewhat or very helpful for their child; 94% considered they learnt skills to better care for their child. The staff questionnaire revealed positive points about enlarged care offer, closer contact with the child, more relaxed children and greater role for parents; weak points included insufficient knowledge of AM and additional nursing time needed. Cost for staff training and medications were nearly compensated by AM related insurance reimbursements. Introduction of anthroposophic treatments were well-accepted and led to high parent satisfaction. Additional insurance reimbursements outweighed costs. The program has now been expanded into a center for integrative pediatrics.


[The clinical analysis of with 106 cases aortic dissection].
To explore the risk factors clinical appearance and examination methods of aortic dissection (AD). The clinical data of 106 AD patients admitted from the January, 2001 to July, 2004 were retrospectively reviewed. The symptoms and physical signs of the 106 AD patients were diverse. Chest pain was a common initial symptoms but some patients initial symptoms were atypical. The origins of AD was in ascending aorta when patients had clinical appearance mimicking myocardial infarction, and in descending aorta when patients had pain involving shoulders, dorsum, waist, abdomen or lower limbs. Hypertension was the most important cause of AD. The combination use of echocardiography, CT and MRI may help to make rapid diagnosis. The symptoms and physical signs of AD were diverse. Clinical symptom had some relationship with the origin of AD, the form of AD and hypertension had obvious relations. An obvious correlation exited between the occurrence of AD and hypertension.


Retracted: A Multi-RNN Research Topic Prediction Model Based on Spatial Attention and Semantic Consistency-Based Scientific Influence Modeling.
[This retracts the article DOI: 10.1155/2021/1766743.].


[Evaluation of pyralgin usefulness in premedication of patients before stomatological treatment].
Pyralgin (metamizole sodium) usefulness was tested in premedication of 90 patients subjected to processing of hard tooth tissues by grinding or drilling. The results of the study demonstrated that about 2/3 of the patients failed to observe any difference in the painfulness of the procedure with and without premedication with Pyralgin. In 1/3 of the patients Pyralgin reduced pain, improved wellbeing and raised the emotional status during the procedure. This effect might be regarded as a placebo result.


Inefficiency of emotion regulation as vulnerability marker for bipolar disorder: evidence from healthy individuals with hypomanic personality.
Emotion regulation deficits are a key characteristic of bipolar disorder (BD). In the present study, we asked if deficits in emotion regulation are also a vulnerability marker for BD. To this end, we investigated a healthy group of participants at high-risk for developing BD, defined on the basis of a hypomanic personality trait. We examined the neural correlates of two emotion regulation strategies, reappraisal and distraction. Twenty-two individuals with higher risk for BD and twenty-four controls were investigated in a functional magnetic resonance imaging paradigm. Participants were presented with negative, positive and neutral pictures and were either required to passively view the images, to down-regulate the emotional response by reappraising the pictures' content, or to perform a distracting arithmetic task. High-risk individuals showed increased emotional reactivity to negative stimuli, indicated by heightened amygdala activation during passive viewing. High-risk participants were also less successful in down-regulating amygdala activity using reappraisal of negative stimuli. During distraction from positive stimuli, high-risk individuals showed heightened task-related activity in the inferior parietal cortex, suggesting increased distractibility by task-irrelevant positive background stimuli. There were no differences in habitual emotion regulation as assessed by a self-report questionnaire. Generalizability of the present results is limited by the age- and education-homogenous sample and the small sample size. This is the first study to report neural correlates of increased emotional reactivity and deficient emotion regulation in healthy individuals at risk for BD. These findings suggest inefficient emotion regulation through reappraisal and distraction in individuals with high hypomanic personality who are supposed to be at higher risk to develop bipolar disorder.


Granulopoietic differentiation in long-term bone marrow cultures from children with congenital neutropenia.
The capacity of granulopoietic precursor cells (CFU-GM) to differentiate in vitro was evaluated in five children with congenital neutropenia using short-term colony assays and long-term marrow cultures. In all five children, methylcellulose assays revealed normal numbers of CFU-GM, which displayed an appropriate response to various sources of GM-CSF and differentiated up to the polymorphonuclear leukocyte state (PMN). In contrast, neutrophil PMN were not observed in long-term bone marrow cultures from three patients, despite a normal production of CFU-GM, myeloblasts, and promyelocytes during the 5-6 week culture period. Thus, in these patients, the characteristic "block" in granulocytic maturation observed in vivo was reproduced in vitro in long-term cultures. Granulocytic differentiation proceeded normally in long-term cultures from the two other patients, thus indicating heterogeneity in the expression of the defect. These results might indicate abnormal interactions between stromal and hematopoietic cells in long-term marrow cultures from some patients with congenital neutropenia. Furthermore, our results showed some correlation between the granulocytic defect in vitro and the clinical outcome in vivo.


Cerebral infarction in patients with transient ischemic attacks.
Cranial computed tomography of 284 patients with transient ischemic attacks (TIAs) and without previous stroke was evaluated. The sample population included patients with carotid and/or vertebrobasilar TIAs. Computed tomography revealed cerebral infarction in 34 patients, including 5 with multiple infarctions. The lesion location was consistent with TIA symptoms in 16 patients. In another 16 patients, however, the lesion location did not correspond to the TIA symptoms; these lesions were attributed to previous silent infarctions. Two patients with multiple infarctions had both symptomatic and asymptomatic lesions. Age and carotid stenosis were each significantly related to an increased chance of detecting cerebral infarction (either symptomatic or asymptomatic). No significant relationship between race, gender, hypertension, diabetes, cardiac disease, or smoking and the incidence of infarction was found by either univariate or multivariate analyses.


Cochlear-motor, transduction and signal-transfer tinnitus: models for three types of cochlear tinnitus.
The present paper reviews possible molecular and cellular mechanisms in the cochlea that might contribute to tinnitus. They constitute a part of a highly integrated network in cochlear sound processing and are divided for easier understanding into three different models, i.e. active motor tinnitus, transduction tinnitus and signal-transfer tinnitus. Some of the steps of the pathophysiological models can even be pharmacologically influenced (as exemplified by experimental applications of lidocaine, calcium channel blocker, benzodiazepine, glutamate and atropine). This provides a rationale for the efficient suppression of tinnitus in some patients by these drugs. The most evident problem of all models in tinnitus, including the ones proposed in this paper, is the lack of objective verification by measurement. Thus, the well-defined clinical situation of each patient is hardly attributable to one of the models suggested. In addition, adequate therapy--perhaps one of the drugs considered--still cannot be based upon a reliable clinical finding.


Necrotizing herpetic retinopathy in an immune-compromised pediatric patient with minimal signs of inflammation: case report.
To report a case of necrotizing herpetic retinopathy(NHR) in an immuno-compromised pediatric patient. An 11-year-old boy presented with a minimal ocular foreign-body sensation and peripheral visual-field defect, as well as mild upper respiratory symptoms. He had undergone the Fontan operation for a ventricular septal defect and single ventricle during infancy, and had been taking oral steroids for 1 year immediately prior to his presentation to treat protein-losing enteropathy. Initially, a case of either cytomegalovirus (CMV) retinitis or acute retinal necrosis (ARN) was suspected, and an intravenous course of ganciclovir and acyclovir was therefore initiated. During treatment, varicella-zoster virus (VZV) was detected in the anterior chamber, and ARN was confirmed when both serum and aqueous humor were found by polymerase chain reaction (PCR) to be positive for VZV DNA. A peripheral retinal break and detachment developed after medical treatment, and a vitrectomy was performed. Typically, ARN is found in both healthy individuals and subclinically immuno-compromised patients of any age. CMV retinitis is somewhat more typical for immuno-compromised patients. Herein, we report a case of NHR in a pediatric patient with poor general condition and showing minimal signs of inflammation.


Mapping of RXRB to human chromosome 6p21.3.
Retinoid X Receptor beta (RXRB) is a member of the retinoid X receptor (RXR) family of nuclear receptors which are involved in mediating the effects of retinoic acid (RA). We have confirmed the localization of RXRB to chromosome 6 and we have mapped the gene to chromosome 6p21.3-p21.1 by PCR amplification of 5' untranslated sequence in panels of rodent-human somatic cell hybrids and to 6p21.3 by fluorescent in situ hybridization.


Pterional surgery of meningiomas of the tuberculum sellae and planum sphenoidale: surgical results with special consideration of ophthalmological and endocrinological outcomes.
The authors reviewed 47 cases of suprasellar meningiomas with special attention to ophthalmological and endocrinological outcomes. All patients underwent surgery performed via a unilateral pterional approach between January 1983 and January 1998. Ophthalmological and endocrinological examinations were performed before the operation as well as 1 week and 3 months postoperatively. A special scoring system was adopted to quantify the extent of ophthalmological disturbances. Complete tumor resection was possible in all but one patient. There were no fatalities and the rate of visual improvement was 80%. The best prognoses were found in patients younger than 50 years and in patients in whom the duration of symptoms was less than 1 year. Before surgery, tumor-related endocrine disturbances were present in only three women who suffered from secondary hypogonadism; two of these patients recovered after surgery. Postoperatively, no patient needed replacement therapy for pituitary dysfunction. The overall tumor recurrence rate was 2.1% (one of 47 cases). For patients in whom long-term (> 5 years) follow-up data were available, the recurrence rate was 4.2% (one of 24 cases). In this series, complete resection of suprasellar meningiomas was possible through a unilateral pterional craniotomy and was associated with a low morbidity rate and no deaths.


Variation in the expression levels of predictive chemotherapy biomarkers in histological subtypes of lung adenocarcinoma: an immunohistochemical study of tissue samples.
Lung adenocarcinoma is often composed of a complex and heterogeneous mixture of histological subtypes. Invasive adenocarcinomas are now classified by their predominant pattern, using the comprehensive histological subtyping of the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), and the European Respiratory Society (ERS) classifications. This study aimed to determine whether the expression levels of predictive chemotherapy biomarkers are associated with the histological subtypes proposed by the IASLC/ATS/ERS classification. We reviewed data on representative tissue samples from 27 patients who received surgical resection and the expression of excision repair cross complementation group 1 (ERCC1), class III β-tubulin, thymidylate synthase (TS), ribonucleotide reductase M1 (RRM1), and c-Met were examined using immunostaining on tumor tissue slides. We assessed immunohistochemical H-scores, as calculated from the intensity and distribution of intratumor expression, according to the IASLC/ATS/ERS histological subtype. The expression levels of predictive chemotherapy biomarkers varied according to histological subtype. The H-scores of TS and class III β-tubulin expression levels were higher in solid-type components than they were in lepidic-type components Tumors with solid predominant histology tended to recur earlier than non-solid predominant tumors. However, none of the H-scores in histologically predominant tissues was significantly associated with staging or overall survival. Immunohistochemical H-scores of the predictive chemotherapy biomarkers were strongly associated with histological subtype. The presence of a solid subtype, which was associated with poor outcomes, might be assessed by measuring these biomarkers in mixed subtype adenocarcinomas.


Laparoscopic Heller myotomy and Dor fundoplication for esophageal achalasia. How I do it.
The advent and the success of minimally invasive surgery have changed the treatment algorithm for esophageal achalasia. Today, a laparoscopic Heller myotomy and partial fundoplication is considered the treatment of choice for this disease. This article describes the technique of laparoscopic Heller myotomy and Dor fundoplication.


Italian Validation of AAS-R: Assessing Psychometric Properties of Adult Attachment Scale-Revised in the Italian Context.
The Adult Attachment Scale-Revised (Collins and Read in J Person Soc Psychol 58(4):644, 1990. https://doi.org/10.1037/0022-3522.214.171.1244) measures the dimensions of the attachment style of adults through the degree to which the individual feels comfortable in intimacy and closeness with the partner (Close), with dependence on the partner (Depend) and worrying about being rejected or unloved (Anxiety). Dimensions measured by the AAS can capture the core of the structure that determines adults' differences in attachment styles. This study aimed to evaluate the factorial structure of the AAS-R among a sample of Italian adults. The Italian translation of AAS-R was administered to the sample of 1546 Italian adults (M = 27.4; SD 9.35). Exploratory factor analysis and confirmatory factor analysis were performed to examine the validity of the Italian version of the AAS-R measure. The present study showed that the Italian version of the AAS-R has a clear factorial structure and good psychometric properties. Clinical and research implications were discussed.


Estimation of ZYKR1 in human urine and plasma utilizing LC-MS/MS positive electrospray ionization; a kappa opioid receptor (KOR) agonist.
ZYKR1, a short chain novel peptide with selective kappa opioid receptor agonist activity used as analgesics for the treatment of pain management. A sensitive and selective LC-MS/MS assay was developed and validated for estimation of ZYKR1 in human urine and plasma. ZY17258, an analogue compound was used as an internal standard. ZYKR1 was quantified using a selective reaction monitoring in electrospray ionization positive mode. The chromatographic separation was performed using mobile phase consisted of 0.05% v/v formic acid in water and methanol in gradient elution by analytical column Kinetex C8, 100 A°, 5 µm, 100 × 4.6 mm with 8.0 min analytical run time. Solid Phase extraction technique was used for purification of ZYKR1 and IS from human urine and plasma. The calibration curves were linear over range of 0.300 ng/mL to 300 ng/mL and 0.500 ng/mL to 500 ng/mL for human urine and plasma, respectively. No matrix effect and no significant carryover were observed. The extraction recovery was consistent and ranged from about 85% to 93% in human urine and in plasma respectively. Inter-day and intra-day accuracy (bias, %) and precision (CV, %) was -11.11 to 5.91 % and -2.25 to 6.65 % in human urine and -2.74 to 7.17 % and 2.24 to 15.18 % in plasma respectively were well within the acceptance criteria. Both the assays were devoid of endogenous matrix interference and commonly used concomitant drug interference. The validated assays were used for estimation of ZYKR1 from clinical pharmacokinetic study sample bioanalysis in healthy human subjects.


Bachelor of nursing students' experiences of a longitudinal team training intervention and the use of teamwork skills in clinical practice-A qualitative descriptive study.
To describe nursing students' experiences of a TeamSTEPPS® longitudinal team training program and the application of teamwork skills in clinical practice. A descriptive qualitative design. Overall, 22 nursing students participated in six online focus group interviews after attending a TeamSTEPPS® team training program from their first semester. The data were audio-recorded, transcribed and analysed using inductive content analysis and reported following the COREQ guidelines. The focus group interviews took place in the students' fifth's semester. The main category "Learning teamwork is not an event; it's a journey" emerged from 3 generic categories and 12 subcategories. The participants reported that grasping the relevance of team training and the use of teamwork skills takes time. Utilizing these skills improved their awareness of being a team member and facilitated learning. Team training raised the participants' awareness of teamwork as an essential component of being a professional nurse. Additionally, understanding the complexity of teamwork takes time.


Dataset on sustainable construction practices of foreign and indigenous construction firms.
This dataset conducted a comparative analysis of sustainable construction practices of foreign and indigenous construction firms in Lagos state, Nigeria using a structured questionnaire survey. The dataset contains the level of awareness and consistency of practice of sustainable development on construction projects between the foreign and indigenous construction firms and the impact of implementing sustainable development practices. Descriptive analysis such as frequencies, percentage and mean score were used to present the quantitative data in form of tables. Further analysis of the dataset highlight the practices of indigenous and foreign construction firms in sustainable development which can be beneficial to stakeholders in environmental protection and mitigating climate change issues.


Baseline correction methods to deal with artifacts in femtosecond transient absorption spectroscopy.
In femtosecond transient absorption spectroscopy, artifact contributions are usually observed at ultra-short time scale. These complex signals are very challenging because of their nature, related to ultrafast phenomena, and because they strongly distort the structure of the spectrokinetic data. The purpose of this work is to evaluate the potential of baseline correction methods for femtosecond transient absorption spectroscopy data pre-processing. Indeed, artifacts removal should ideally be performed before multivariate data analysis. The work is thus mainly focused on two different approaches which are filtering by discrete wavelet transform, on the one hand, and smoothing by asymmetric least squares, on the other hand. The results obtained both on simulated data and on femtosecond pump-probe spectroscopy data are discussed. It can be concluded that asymmetric least squares smoothing procedure turns out to perform satisfactory for artifacts removal. Indeed, only mild discrepancies are observed in the transient spectra and, most important, good recovery of the kinetics is obtained at ultra-short time scale.


Sex differences in the association between birth weight and total cholesterol. A meta-analysis.
Determine whether a sex difference exists in the association between birth weight and total cholesterol later in life. Meta-analysis of within-study differences in regression coefficients of cholesterol on birth weight. A total of 34 regression coefficients from 30 studies were included in the analyses; these provided data on 33,650 males and 23,129 females. There was evidence that the inverse association between birth weight and total cholesterol was stronger in males compared to females. The pooled within-study difference in age-adjusted regression coefficients was -0.03 mmol/l (-0.06, -0.01), p = 0.02 and the pooled within-study difference in age and body mass index adjusted regression coefficients was -0.04 mmol/l (-0.07, -0.02), p = 0.002. There was no evidence of heterogeneity in these meta-analyses (both p values > 0.6). These results provide some evidence for a sex difference in the birth weight-total cholesterol association. This is consistent with studies of fetal growth which suggest that birth size reflects different biological processes for females and males. However, other very large studies are required to confirm this finding.


From research to practice: the effects of the jointly sponsored dissemination of an arthritis self-care nursing intervention.
Various educational programs have been developed and found to be effective in the self-management of arthritis. This study reexamined the effectiveness of one such program, "Bone Up On Arthritis" (BUOA), when the program was delivered by a community-based service organization to a sample of persons (N = 154) who differed widely in disease type and demographic characteristics. Arthritis Foundation staff implemented BUOA at four national sites; data were collected and analyzed by University of Michigan nurse researchers. Investigators found improved scores on all outcome measures (self-care behavior, helplessness, pain, dysfunction, and depression). These findings suggest that "Bone Up" is an effective nursing intervention in multiple organizational and community environments and for diverse patient populations.


Primary Site of Coxsackievirus B Replication in the Small Intestines: No Proof of Peyer's Patches Involvement.
Enterovirus (EV) infections are associated with a broad range of diseases. Since the first experimental infection of primates with poliovirus (PV), tonsils and the Peyer's patches (PPs) have been believed to be the primary replication sites of EVs. Our aim was to localize different viral markers in the small intestines (SI) of coxsackievirus B (CVB) orally and intraperitoneally (i.p.) infected mice. Transverse sections of SIs of both infected and control male outbred mice were collected at different intervals post-infection (p.i) and analyzed for presence of interferon-alpha (IFN-α) and viral protein VP1 by immunohistochemistry and in situ hybridization (ISH). Fluorescent marker, eGFP, was identified in cryosections of mice infected with eGFP-CVB3. In the infected SIs, we observed enlarged germinating centers (GCs) in the PPs; IFN-α was detected in the PPs and mucosal layer of the SIs. However, VP1, viral RNA and the eGFP were absent in the GCs of PPs at all stages of infection irrespective of the virus strains used. Virus was present in the epithelial cells but not in GCs of the PPs of the murine SIs. Our results do not support the hypothesis of EV replication in the PP especially in the GCs.


Development of a next-generation automated DICOM processing system in a PACS-less research environment.
The use of clinical imaging modalities within the pharmaceutical research space provides value and challenges. Typical clinical settings will utilize a Picture Archive and Communication System (PACS) to transmit and manage Digital Imaging and Communications in Medicine (DICOM) images generated by clinical imaging systems. However, a PACS is complex and provides many features that are not required within a research setting, making it difficult to generate a business case and determine the return on investment. We have developed a next-generation DICOM processing system using open-source software, commodity server hardware such as Apple Xserve®, high-performance network-attached storage (NAS), and in-house-developed preprocessing programs. DICOM-transmitted files are arranged in a flat file folder hierarchy easily accessible via our downstream analysis tools and a standard file browser. This next-generation system had a minimal construction cost due to the reuse of all the components from our first-generation system with the addition of a second server for a few thousand dollars. Performance metrics were gathered and the system was found to be highly scalable, performed significantly better than the first-generation system, is modular, has satisfactory image integrity, and is easier to maintain than the first-generation system. The resulting system is also portable across platforms and utilizes minimal hardware resources, allowing for easier upgrades and migration to smaller form factors at the hardware end-of-life. This system has been in production successfully for 8 months and services five clinical instruments and three pre-clinical instruments. This system has provided us with the necessary DICOM C-Store functionality, eliminating the need for a clinical PACS for day-to-day image processing.


Artemisinin-piperaquine versus artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Grande Comore island: an open-label, non-randomised controlled trial.
Malaria significantly rebounded in 2018 in the Comoros; this created an urgent need to conduct clinical trials to investigate the effectiveness of artemisinin and its derivatives. An open-label, non-randomised controlled trial of artemisinin-piperaquine (AP) and artemether-lumefantrine (AL) was conducted in Grande Comore island from June 2019 to January 2020. A total of 238 uncomplicated falciparum malaria cases were enrolled and divided 1:1 into two treatments. The primary endpoint was the 42-day adequate clinical and parasitological responses (ACPR). Secondary endpoints were parasitaemia and fever clearance at day 3, gametocytes and tolerability. The 42-day ACPR before and after PCR correction were 91.43% (95% CI 83.93-95.76%) and 98.06% (95% CI 92.48-99.66%) for AP treatment, respectively, and 96.00% (95% CI 88.17-98.14%) and 98.97% (95% CI 93.58-99.95%) for AL treatment, respectively. Complete clearance of the parasitaemia and fever for both groups was detected on day 3. Gametocytes disappeared on day 21 in the AP group and on day 2 in AL group. Specifically, the adverse reactions were mild in both groups. It was found that AP and AL maintained their high efficacy and tolerance in the Comoros. Nonetheless, asymptomatic malaria infections bring new challenges to malaria control.


Impulses and pressure waves cause excitement and conduction in the nervous system.
It is general accepted, that nerval excitement and conduction is caused by voltage changes. However, the influx of fluid into an elastical tube releases impulses or pressure waves. Therefore an influx of ion currents, respectively fluid motions into the elastic neuronal cells and fibres also induce impulses. This motion of charge carriers are measured by voltage devices as oscillations or action potentials, but the voltage changes may be an epiphenomenon of the (mechanical) impulses. Impulse waves can have a high speed. As stiffer or inelastic a tube wall, the greater is the speed of the impulse. Myelin sheaths cause a significant stiffening of the nerve fibre wall and myelinated fibres have a conduction velocity up to 120 m/s. The influx of fluid at the nodes of Ranvier intensifies periodically the impulse wave in the nerve fibres. The authors suggest that also the muscle end-plate acts as a conductor of axonal impulses to the inner of the muscle fibres and that the exocytosis of acetylcholine into the synaptic cleft may be an amplifier of the axonal impulse. It is discussed that intracellular actin filaments may also influence motions at the neuronal membrane. Many sensory nerve cells are excited due to exogenous or endogenous mechanical impulses. It may plausible that such impulses are conducted directly to the sensory nerve cell bodies in the dorsal root ganglia without the transformation in electric energy. Excitation conduction happens without noteworthy energy consumption because the flow of ion currents through the membranes takes place equivalent to the concentration gradient. Impulse waves cause short extensions of the lipid membranes of the cell- and fibres walls and therefore they can induce opening and closing of the included ion channels. This mechanism acts to "voltage gated" and "ligand-gated" channels likewise. The concept of neuronal impulses can be helpful to the understanding of other points of neurophysiology or neuronal diseases. This includes e.g., the brain concussion and pathohistological findings in Alzheimer dementia. To verify the concept of (mechanical) impulses in the nervous system it is necessary to carry out biophysical or mechanical investigations in very small dimensions and the authors hope to give for this a sufficient stimulus.


Membranous nephropathy after allogeneic stem cell transplantation: report of 2 cases.
Nephrotic syndrome (NS) is a rare complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The cases of 2 patients who developed NS after receiving allo-HSCT for chronic myelogenous leukemia and acute lymphoblastic leukemia are described. In both cases, renal biopsy revealed membranous nephropathy (MN), and the patients achieved remission after treatment with prednisolone. Previously reported cases and our experience suggest that most NS patients show MN in histologic tests after allo-HSCT and that its development is related to graft-versus-host disease. Early treatment with steroids seems effective for resolving symptoms of NS and improving renal function.


Application of image overlapping in percutaneous nephrolithotomy.
To investigate the application of ultrasound and CT image overlap in percutaneous nephrolithotomy (PCNL). A total of 140 patients with complicated kidney stones requiring PCNL were prospectively enrolled, from January 2020 to December 2022. These patients were randomly divided into 2 groups, with 70 patients each in the research group and the control group. All participants underwent dual-source, non-contrast CT scan of both kidneys and pelvis before surgery. Preoperative three-dimensional CT reconstruction and simulated puncture were performed in patients from the research group. The best puncture path was determined through ultrasound and CT image overlap. Puncture guided by regular CT and ultrasound was conducted in patients from the control group. Differences in the surgical outcomes between the two groups were compared. Compared to the control group, the research group had higher stone clearance rate in stage I PCNL, success rate of one-time puncture, less percutaneous channels, less reduction of hemoglobin and shorter procedure time. Complications in stage I PCNL were comparable in the two groups, and there was no significant change in the final stone clearance rates between the two groups. An optimal puncture channel can be chosen using ultrasound and CT image overlap. PCNL can be achieved with precise puncturing, thus achieving coincidence between imaging and anatomy and reducing the amount of blood loss during stage I of PCNL. It also shortens the procedure time and improves stone clearance rate of PCNL.


Amphiphilic Polymer Capped Perovskite Compositing with Nano Zr-MOF for Nanozyme-Involved Biomimetic Cascade Catalysis.
CsPbX3 perovskite nanocrystal (NC) is considered as an excellent optical material and is widely applied in optoelectronics. However, its poor water stability impedes its study in enzyme-like activity, and further inhibits its application in biomimetic cascade catalysis. Herein, for the first time, the oxidase-like and ascorbate oxidase-like activities of an amphiphilic polymer capped CsPbX3 are demonstrated, and its catalytic mechanism is further explored. Furthermore, an all-nanozyme cascade system (multifunctional CsPbBr3 @Zr-metal organic framework (Zr-MOF) and Prussian blue as oxidase-like and peroxidase-like nanozyme) is constructed with a portable paper-based device for realizing the dual-mode (ratiometric fluorescence and colorimetric) detection of ascorbic acid in a point-of-care (POC) fashion. This is the first report on the utilization of all-inorganic CsPbX3 perovskite NC in biomimetic cascade catalysis, which opens a new avenue for POC clinical disease diagnosis.


Life-stage-dependent sensitivity of the cyclopoid copepod Mesocyclops leuckarti to triphenyltin.
The effects of triphenyltin (TPT) on non-target aquatic groups like copepods have not yet been studied in detail. Recently, Mesocyclops leuckarti was suggested as a representative species for freshwater cyclopoid copepods to study the effects of plant protection products. We conducted 96h acute toxicity tests in the laboratory to study the effects of TPT on the different life stages of M. leuckarti. We used the recently proposed General Unified Threshold model of Survival (GUTS) to mechanistically describe the underlying toxicokinetic and toxicodynamic process for the nauplii, copepodites and adults (males and females) of M. leuckarti. Experimental results showed that nauplii were significantly more sensitive to TPT compared to the other stages. Also, the 96h LC50 values were much lower than the 48h LC50 values, suggesting that standard acute toxicity test durations for aquatic invertebrates may underestimate toxic effects with respect to compounds like TPT which have a slow mechanism of action. The GUTS analysis, which mechanistically described the toxicity of TPT to the different life stages of M. leuckarti, suggested that the differences in sensitivity were a consequence of a lower threshold of effects in the nauplii compared to a higher threshold in the later stages. This study shows the potential of using the GUTS to understand how toxic compounds interact with different life-stages. Further experiments to provide a more detailed understanding of toxicokinetics of TPT in copepods could be useful.


[External respiration, gas exchange and blood acid-base status in dogs with hyperthermia].
Experiments on dogs have shown that hyperthermia intensifies respiration, increases oxygen consumption, induces pronounced discrepancy of the alveolar ventilation to carbon dioxide elimination, severe hypocapnia and decompensated respiratory alkalosis.


Real-world outcomes of first-line chemotherapy for unresectable stage III and IV bladder cancer.
For many malignancies, considerable divergence between the efficacy found in clinical trials and effectiveness in routine practice have been reported (efficacy-effectiveness gap). The purpose of this study was to evaluate the efficacy-effectiveness gap in palliative first-line (1L) chemotherapy treatment (CTx) for urothelial carcinoma of the bladder. From seven Dutch teaching hospitals, all patients diagnosed with unresectable stage III (cT2-4aN1-3M0) and IV (cT4b and/or cM1) disease, who received 1L-CTx (for both primary as recurrent disease after radical cystectomy) between 2008 and 2016, were captured. Results were compared with data from seven randomised trials that investigated 1L gemcitabine + cisplatin (GemCis) and/or gemcitabine + carboplatin (GemCarbo). Of the 835 included patients, 191 received 1L-CTx. Median overall survival (mOS) of GemCis patients (N = 88) was 10.4 months [95% CI 7.9-13.0], which was shorter compared to clinical trial findings (range mOS: 12.7-14.3 months) despite comparable clinical characteristics. The mOS of GemCarbo patients (N = 92) was 9.3 months [95% CI 7.5-11.1]. Patients who received GemCarbo had worse prognostic characteristics (higher age, impaired renal function and worse performance status (all P-values < 0.001)) compared to GemCis patients, but were equal in occurrence of dose reductions (24.4% vs. 29.5%, P-value = 0.453), early termination (55.7% vs. 54.1%, P-value = 0.839), clinical best response (P-value = 0.733), and toxicity (68.1% vs. 63.3%, P-value = 0.743). In multivariable regression, GemCis was not superior to GemCarbo (HR 0.90 [95% CI 0.55-1.47], P-value = 0.674). There seems to be an efficacy-effectiveness gap in 1L GemCis treatment, despite patients having similar baseline characteristics. Early termination of treatment occurred more often and dose reduction less often compared to clinical trials, hinting towards abandonment of treatment in case of adverse events. Patients treated with 1L GemCis did not have superior survival compared to GemCarbo patients, even though GemCarbo patients had worse baseline characteristics.


Magnetic resonance imaging in spinal emergency.
We studied the diagnostic value of MRI in spinal emergency. One hundred patients were analyzed retrospectively and the MR-findings were compared with operative results or autopsy whenever available. The advantages of MRI compared to CT and conventional myelography are discussed. The limitations of MRI are addressed and the important features of appropriate diagnostic procedure are outlined with special attention to neurosurgical requirements.


Administration of potassium iodide to normal volunteers does not increase killing of Sporothrix schenckii by their neutrophils or monocytes.
The mechanism by which iodide cures sporotrichosis was postulated to be an improvement in phagocyte-mediated killing of the causal fungus, Sporothrix schenckii. We found that both neutrophils and monocytes could readily kill the fungus and that killing could be blocked by adding inhibitors of oxidative metabolism. Iodide, administered to four volunteers for 1 week, raised their serum iodide level 213-fold but failed to improve killing of S. schenckii by their neutrophils or monocytes in a killing assay in vitro. Furthermore addition of iodide directly to neutrophils at concentrations as high as 100 microM did not augment killing. The mechanism by which iodide acts remains obscure.


Revisiting UV/sulfite exposed to air: A redox process for reductive dechlorination and oxidative mineralization.
2,4-Dichlorophenol (2,4-DCP) widely exists in many industrial wastewaters and is considered a priority pollutant due to its high toxicity. In this work, we proposed a UV/sulfite process without aeration for high-efficiency dechlorination and enhanced mineralization. The UV/sulfite system significantly improved the removal of 2,4-DCP (93.33 % in 60 min) and dechlorination rate (85.13 % in 60 min) compared with UV alone and sulfite alone, and the synergistic factor was 6.59. The UV/sulfite system without aeration improved the mineralization rate (49.80 %) compared with the nitrogen aeration system. UV/sulfite was a reduction-oxidation coupled process and was more suitable for neutral and alkaline conditions. Reducing species (hydrated electrons and H•) made 2,4-DCP dechlorinate to form dechlorination products such as p-chlorophenol (4-CP), o-chlorophenol (2-CP), and phenol, which were further mineralized by oxidized species (SO4•-). UV/sulfite remained highly efficient in the presence of coexisting ions and under different water quality conditions. This process was also suitable for removing a wide range of chlorinated organic compounds. The UV/sulfite process without aeration can achieve high dechlorination and enhanced mineralization with simple operation and low cost (1.78 $·m-3 order-1), which has a broad and cost-effective application prospect in removing refractory halogenated organic pollutants.


Atypical Presentation and Treatment Response in a Child with Familial Hypercholesterolemia Having a Novel LDLR Mutation.
Familial hypercholesterolemia (FH) is an autosomal codominantly inherited disease. The severity of clinical presentation depends on the zygosity of the mutations in the LDLR, APOB, or PCSK9 genes. The homozygous form (HoFH) is associated with high mortality rate by third decade of life, while individuals with HeFH begin to suffer from premature cardiovascular disease in fourth or fifth decade of life. Statin drugs have helped to improve the biochemical profile and life expectancy in HeFH, while they are only minimally effective in HoFH. LDL apheresis remains an effective treatment option in HoFH, though limited by its availability and affordability issues. We present the case that highlights a few novel aspects of clinical and genetic heterogeneity in FH, wherein a child presented with features of both HeFH and HoFH. His clinical picture was that of HoFH; however he responded well clinically and biochemically to pharmacologic treatment only. DNA sequencing showed a novel heterozygous rare splicing variant in the LDLR gene in addition to a relatively high polygenic trait score comprised of LDL-C raising alleles from common polymorphic sites. Interestingly his normolipemic mother showed the same heterozygous mutation. Thus this novel splicing variant in LDLR showed nonclassical co-segregation with the disease phenotype and was associated with a high polygenic trait score comprised of common LDL-C raising polymorphic alleles in the affected proband. Thus it indicates the phenotypic heterogeneity of FH and suggests that secondary causes, such as polygenic factors and possibly as yet undetermined genetic or environmental factors, can exacerbate the metabolic phenotype in an individual who is genotypically heterozygous for FH.


BS-80K: The first large open-access dataset of bone scan images.
Radionuclide bone scanning is one of the most common tools in the inspection of bone metastasis. Conventionally, the analysis of bone scan image is derived from manual diagnosing. However, this task requires extensive subjective diagnostic experience and is extremely time-consuming. To this end, a series of studies concerning computer-aided diagnosis via machine learning tools have been proposed. Although some inspiring progress has been achieved, the implemented bone scan image datasets in these research areas are generally too small, private or non-general, which limits their practical significance and impedes the follow-up research. To address this issue, we present a large, publicly available and general dataset consisting of 82544 bone scan images associated with 3247 patients from West China Hospital, named BS-80K. In BS-80K, each patient provides two whole bone scan images corresponding to the anterior view (ANT) and the posterior view (POST). For each view, there are 13 region-wise slices of the body parts susceptible to bone metastasis. Based on an authorized original labeling criterion, labels annotated by experienced specialists are offered with the images. Moreover, within each whole body image, multiple bounding boxes containing suspectable hot spots and their annotations are supplied as well. All images in BS-80K have been de-identified to protect patients' privacy. Based on 6 popular deep learning models for classification and object detection, we provide the benchmark for a number of computer-aided medical tasks, including general bone metastasis prediction and object detection for whole body images, and specific bone metastasis prediction for different body parts. According to extensive experiments, the adopted classification models achieve remarkable results in accuracy and specificity (around 95%) on most metastasis prediction tasks, which are approximate to the average ability of corresponding specialists. As for the object detection task, the best average precision of the adopted models reaches 0.2484 and the lowest is 0.1334. Through the comparison of metastasis prediction performance between the benchmark and related work, we observe that the widely used models trained by BS-80K achieve significantly better results than the elaborately designed models trained by smaller datasets. This indicates that with the large amount of data, BS-80K has great potential to galvanize the research about computer-aided analysis on bone scan image. To the best of our knowledge, BS-80K is the first large publicly available dataset of bone scanning, which favors a wide range of research on computer-aided bone metastasis diagnosis. The full dataset is now available at https://drive.google.com/drive/folders/1DOBkLXgQeREQjF-nQIGNBBzPCb5s7RNu?usp=sharing.


Large-scale mutational analysis for the annotation of the mouse genome.
After sequencing the human and mouse genomes, the annotation of these sequences with biological functions is an important challenge in genomic research. A major tool to analyse gene function on the organismal level is the analysis of mutant phenotypes. Because of its genetic and physiological similarity to man, the mouse has become the model organism of choice for the study of genetic diseases. In addition, there is at the moment no other vertebrate for which versatile techniques to manipulate the genome are as well developed. Several mouse mutagenesis projects have provided the proof-of-principle that a systematic and comprehensive mutagenesis of every gene in the mammalian genome will be feasible. An exhaustive functional annotation of the mammalian genome can only be achieved in a combination of phenotype- and gene-driven approaches in large- and small-scale academic and private projects. Major challenges will be to develop standardised phenotyping protocols for the clinical and pathological characterisation of mouse mutants, the improvement of mutation detection methods and the dissemination of resources and data. Beyond gene annotation, it will be necessary to understand how gene functions are integrated into the complex network of regulatory interactions in the cell.


Are there differences between officers and ratings on merchant vessels concerning effort-reward imbalance: a cross-sectional maritime field study.
Today, measures to economise in the operation of ships can cause either an effort-reward imbalance or health impairments. The goal of this study was to assess the risk of effort-reward imbalance including overcommitment among officers and ratings on merchant vessels during their assignments and to evaluate lifestyle factors of seafarers as well as the health-promoting conditions on board. A study sample of 308 male seafarers was examined during a total of 20 sea voyages on German container ships (participation rate 91.9%). Only 11 seafarers were identified as having an increased health risk of an effort-reward imbalance (ER ratio > 1). Officers tended to have a higher risk of an elevated ratio than ratings (4.4% vs. 3.1%) and also showed a significantly higher risk of an ER ratio above the median (58.8% vs. 41.8%; p = 0.022). Compared to land-based populations, the average overcommitment score of seafarers was high (17.9)-particularly among officers (20.3 vs. 16.5; p = 0.031). This corresponded to an elevated risk of overcommitment among officers compared to ratings (OR 2.14; 95% CI 1.78-2.37). This elevated risk remained significant after adjustment for age (OR 2.11; 95% CI 1.76-2.35) and job-related stressors. Although an elevated risk of effort-reward imbalance was only observed in few seafarers, this study revealed a high prevalence of overcommitment particularly among officers. In the course of time, overcommitment can lead to mental exhaustion. Therefore, shipboard health-promoting conditions need to be optimised.


Korean Maize Hybrids Present Significant Diversity in Fatty Acid Composition: An Investigation to Identify PUFA-Rich Hybrids for a Healthy Diet.
Precise information on the content and composition of nutritionally essential metabolites in food crops is a prerequisite for dietary recommendations and nutrient-dense food formulations. In the present study, the fatty acid profile of 21 Korean maize hybrids was analyzed by gas chromatography (GC)-mass spectrometry (MS). In the studied hybrids, linoleic acid (LA; C18:2n6c) was dominant (38.0-58.9%), followed by oleic (OA; C18:1n9c) (23.5-45.3%), palmitic (C16:0) (10.8-17.3%), and stearic acids (C18:0) (1.84-3.86%). Among all the quantified fatty acids, the highest variation was recorded for LA and OA. The highest amount of LA (58.9%), the lowest amount of OA (23.5%), and the highest polyunsaturated fatty acids (PUFAs)/monounsaturated fatty acids (MUFAs) ratio of 2.47 were recorded in the Shingwang hybrid. The highest PUFAs/saturated fatty acids (SFAs) ratio of 4.04 was recorded in the Ahndaok hybrid due to the high content of LA (57.8%) and low amount of SFA. Similarly, the highest PUFAs + MUFAs/SFAs ratio of 6.38 was recorded in the Pyeonggangok hybrid as a result of the high OA (34.6%) and LA (51.4%) contents, along with the lowest amount of SFAs. Considering the high levels of health-beneficial MUFAs and PUFAs and low levels of undesirable SFAs, the maize hybrids Pyeonggangok, Ahndaok, and Shingwang can be used in the preparation of a healthy PUFA-rich diet.


Theoretical study on the degradation mechanism, kinetics and toxicity for aqueous ozonation reaction of furan derivatives.
The compounds including furan-2,5-dicarboxylic acid (FDCA), 2-methyl-3-furoic acid (MFA), and 2-furoic acid (FA), containing Furan ring are considered to be possessing high ozone reactivity, although in depth studies of their ozonation processes have not been carried out yet. Hence, mechanism, kinetics and toxicity by quantum chemical, and their structure activity relationship are being investigated in this study. Studies of reaction mechanisms revealed that during the ozonolysis of three furan derivatives containing C=C double bond, furan ring opening occurs. At temperature (298 K) and pressure of 1 atm, the degradations rates of 2.22 × 103 M-1 s-1 (FDCA), 5.81 × 106 M-1 s-1 (MFA) and 1.22 × 105 M-1 s-1 (FA) suggested that the reactivity order is: MFA > FA > FDCA. In the presence of water, oxygen and ozone, the Criegee intermediates (CIs) as the primary products of ozonation would produce lower molecule weight of aldehydes and carboxylic acids by undergoing degradation pathways. The aquatic toxicity reveals that three furan derivatives play green chemicals roles. Significantly, most of the degradation products are least harmful to organisms residing in the hydrosphere. The mutagenicity and developmental toxicity of FDCA is minimum as compared to FA and MFA, which shows the applicability of FDCA in a wider and broader field. Results of this study reveal its importance in the industrial sector and degradation experiments.


[Treatment of lung lesions by stereotactic body radiation therapy after computed tomography guided placement of a Visicoil(®) marker: initial experience].
To describe the technique of stereotactic body radiation therapy (SBRT) of lung lesions after the computed tomography (CT) guided placement of an internal fiducial marker and to assess the results, complications and secondary effects of these procedures. A series of 39 lesions (8 primary and 31 metastases) in 25 patients treated using this procedure were analysed. A CT-guided percutaneous transthoracic puncture was performed for placing the internal marker in the lesion or near to it. The procedure did not require sedation. The marker serves as a guide for the treatment of the lesion using SBRT with respiratory synchronism, which allows the movement of the tumour to be controlled and to decrease the radiation volume, giving high doses with precision to the tumour, and minimal to the surrounding healthy tissue. The only complication of the percutaneous fiducial placement was a pneumothorax in 6 (24%) patients. A pleural drain had to be placed in 3 patients. Local control was achieved in 96.7% of the lesions. The radiation produced a grade 1 asthenia in 1 patient, a grade 2 pneumonitis in one patient and a grade 1 pneumonitis in the remainder. The CT-guided placement of internal markers in lung lesions is a safe technique that may be performed as ambulatory procedure. SBRT with respiratory synchronism allows the dose to the tumour to be increased, and reduces the volume of healthy lung treated, with few secondary effects.


Quiet Time Improves the Patient Experience.
A quiet environment promotes rest and healing but is often challenging to provide in a busy acute care setting. Improving quiet in the hospital for designated hours improves patient satisfaction. Such efforts have typically been the primary responsibility of the nursing staff. Two medical units with consistently low Hospital Consumer Assessment of Health Care Providers and Systems (HCAHPS) "always quiet" scores were chosen for this study. A multidisciplinary team used Lean methods and the Model for Improvement to test interventions for quiet time (QT) and used HCAHPS "always quiet" scores as the primary outcome measure. The team instituted nighttime and afternoon QT supported by rounding and scripting, dimming lights, lowering staff voices, offering a sleep menu at night, and replacing noisy wheels. Quiet scores improved on both units after 11 months. Noise in hospitals is often beyond the scope of nurse-driven improvement; however, a QT protocol led by nurses, developed by multiple stakeholders, and focused on changing expectations for quiet can lead to measurable improvements in patient perception of quiet.


Prospective comparison of cell cultures and nucleic acid amplification tests for laboratory diagnosis of Chlamydia trachomatis Infections.
Specimens submitted in M5 medium for cell culture detection of Chlamydia trachomatis were tested by nucleic acid amplification testing (NAAT) and in cell cultures. Of 35 (genital) and 26 (nongenital) specimens positive for C. trachomatis, 21 and 14 specimens, respectively, were detected exclusively by NAAT. NAAT is significantly (P<0.0001) more sensitive than cell culture and should be considered the new "gold standard" for the laboratory diagnosis of C. trachomatis infections.


Cytosolic free magnesium modulates Na/Ca exchange currents in pig myocytes.
Cardiac Na/Ca exchanger (NCX) protein is up-regulated and intracellular free magnesium ([Mg(2+)](i)) is significantly reduced in experimental heart failure. We asked whether changes in [Mg(2+)](i) in a physiologically relevant range could alter the I(NCX). The nickel-sensitive current was measured in voltage-clamped myocytes (Yorkshire pig; left ventricular) exposed to ramp pulses at 37 degrees C in Tyrode's solution containing ouabain, nifedipine and +/- Ni(2+) (5 mmol/l). The intracellular free [Ca(2+)] and [Mg(2+)] concentrations were set at 50 nmol/l and 1.25 mmol/l (HiMg) or 0.13 mmol/l (LoMg), respectively, through pipette dialysis. Reducing [Mg(2+)](i) resulted in a significant increase in both outward and inward Ni-sensitive current without a shift in the reversal potential. This effect was not due to the inadvertent reduction of intracellular free [ATP] secondary to binding of ATP to Mg(2+); reducing intracellular [ATP] in LoMg cells from 1.35 mmol/l to 0.18 mmol/l did not affect I(NCX). The intracellular free [Ca(2+)] was raised from 50 to 200 nmol/l, resulting in augmented inward and outward current due to calcium activation. HiMg attenuated both inward and outward currents significantly compared to LoMg, suggesting that [Mg(2+)](i) competes with [Ca(2+)](i) at the allosteric regulatory site. Cytosolic free magnesium modulates the I(NCX) over a physiologic range independent of [ATP](i). Reduced [Mg(2+)](i) in heart failure could contribute to altered calcium regulation of the NCX, contributing to the altered heart failure phenotype through enhanced NCX activity.


Visual field effects for processing content and function words.
This study investigated the processing of content and function words when input to the left vs right hemispheres. For both lexical decision and naming there was a larger RVF advantage for function as compared to content words: function words were processed more slowly than content in the LVF, but not in the RVF. These results do not replicate the previous report of Bradley and Garrett, Neuropsychologia 21, 155-159, 1983, and provide some support for the view that function words are less accessible to the right hemisphere. In a second experiment, there was no difference in VF asymmetry when acceptability judgments were required for function vs content word phrases. Grammaticality judgments, of any sort, may be predominantly processed in the left hemisphere.


Diet-hormone interactions: protein/carbohydrate ratio alters reciprocally the plasma levels of testosterone and cortisol and their respective binding globulins in man.
The aim of this study was to determine if a change in protein/carbohydrate ratio influences plasma steroid hormone concentrations. There is little information about the effects of specific dietary components on steroid hormone metabolism in humans. Testosterone concentrations in seven normal men were consistently higher after ten days on a high carbohydrate diet (468 +/- 34 ng/dl, mean +/- S.E.) than during a high protein diet (371 +/- 23 ng/dl, p less than 0.05) and were accompanied by parallel changes in sex hormone binding globulin (32.5 +/- 2.8 nmol/l vs. 23.4 +/- 1.6 nmol/l respectively, p less than 0.01). By contrast, cortisol concentrations were consistently lower during the high carbohydrate diet than during the high protein diet (7.74 +/- 0.71 micrograms/dl vs. 10.6 +/- 0.4 micrograms/dl respectively, p less than 0.05), and there were parallel changes in corticosteroid binding globulin concentrations (635 +/- 60 nmol/l vs. 754 +/- 31 nmol/l respectively, p less than 0.05). The diets were equal in total calories and fat. These consistent and reciprocal changes suggest that the ratio of protein to carbohydrate in the human diet is an important regulatory factor for steroid hormone plasma levels and for liver-derived hormone binding proteins.


Fixing Flexner: Disrupting and Rebuilding Academic Medicine for Women of Color to Lead.
In an effort to address the lack of compositional diversity seen in academic leadership, our generation has an opportunity to rebuild academic medicine in a way that welcomes, values, and supports the development and success of women of color.


Protocol to isolate mature thymic T cell subsets using fluorescence-activated cell sorting for assessing gene expression by RNA-seq and transcription factor binding across the genome by CUT&RUN.
Here, we describe steps to isolate mature thymic T cell subsets, namely CD4 single positive (SP), CD8 SP, and invariant natural killer T (iNKT) cells starting from murine total thymocytes using fluorescence-activated cell sorting. We detail protocols to study gene expression by RNA-seq and assess binding of transcription factors across the genome using CUT&RUN. This approach deciphers the molecular principles that govern T cell lineage specification and function. This protocol works well with limited starting material. For complete details on the use and execution of this protocol, please refer to Äijö et al. (2022).1.


Towards the rational design of ionic liquid matrices for secondary ion mass spectrometry: role of the anion.
The role of the ionic liquid (IL) anion structure on analyte signal enhancements has been systematically investigated in secondary ion mass spectrometry (SIMS) using a variety of samples, including lipids, sterols, polymers, and peptides. Twenty-four ILs were synthesized. The 12 matrix acids were cinnamic acid derivatives. Two bases were employed: 1-methylimidazole and tripropylamine. Three matrices, methylimmidazolium o-coumarate, tripropylammonium o-coumarate, and tripropylammonium 3,4,5-trimethoxycinnamate, were "universal" matrices enhancing all analytes tested. The pKa of the matrix acid does not appear to have a strong effect on analyte ion intensities. Rather, it is observed that a single hydroxyl group on the anion aromatic ring leads to significantly increased molecular ion intensities. No analyte signal enhancements were observed for -CH3, -CF3 and -OCH3 groups present on the aromatic ring. The position of the -OH group on the aromatic ring also alters molecular ion intensity enhancements. As well as the chemical identity and position of substituents, the number of moieties on the aromatic ring may affect the analyte signal enhancements observed. These observations suggest that the activation of the IL anion aromatic ring is important for optimizing analyte signal intensities. The implications for SIMS imaging of complex structures, such as biological samples, are discussed.


Clinical relevance of cardiac arrhythmias generated by afterdepolarizations. Role of M cells in the generation of U waves, triggered activity and torsade de pointes.
Recent findings point to an important heterogeneity in the electrical behavior of cells spanning the ventricular wall as well as important differences in the response of the various cell types to cardioactive drugs and pathophysiologic states. These observations have permitted a fine tuning and, in some cases, a reevaluation of basic concepts of arrhythmia mechanisms. This brief review examines the implications of some of these new findings within the scope of what is already known about early and delayed afterdepolarizations and triggered activity and discusses the possible relevance of these mechanisms to clinical arrhythmias.


Effects of dipyridamole in experimental atherosclerosis. Action on PGI2, platelet aggregation and atherosclerotic plaque formation.
Experimental atherosclerosis in rabbits induced by feeding a standard atherogenic diet for 4 months resulted in an increased sensitivity of platelets to the proaggregatory action of collagen and ADP. Treatment with dipyridamole (3 x 10 mg/day i.m.) for 4 weeks normalized platelet loss in atherosclerotic rabbits and abolished the increased sensitivity to proaggregatory collagen, but not to ADP. Dipyridamole treatment lowered basal as well as PGI2-induced cAMP levels below values seen in platelets from normal rabbits, but the stimulation by PGI2 relative to basal cAMP levels was not affected or even increased by dipyridamole treatment. Dipyridamole did not affect the increased sensitivity of platelets from atherosclerotic rabbits to the antiaggregatory action of PGI2, indicating that dipyridamole decreased absolute cAMP levels, probably due to reduction of the adenine nucleotide pool in platelets without affecting the adenylate cyclase function. Dipyridamole enhanced atherosclerotic plaque formation in arterial walls. Basal as well as PGI2-stimulated cAMP content was lower in homogenates from atherosclerotic than from normal aortic tissue. Dipyridamole-treated animals showed a further decrease in basal as well as PGI2-stimulated cAMP content of the aortic tissue, suggesting that this decrease in cAMP content may be linked to the enhanced proliferative activity seen in artherosclerotic plaque formation.


Does hypoxia play a role in infantile hemangioma?
Infantile hemangioma (IH), the most common tumor of infancy, is characterized by rapid growth during infancy, followed by spontaneous involution over 5-10 years. Certain clinical observations have led to the suggestion that IH is triggered and maintained by hypoxia. We review the literature on the possible role of hypoxia in the etiology of IH, in particular, (1) the role of hypoxia inducible factor-1α (HIF-1α) and its downstream targets including GLUT-1 and VEGF; (2) the pathophysiological link between IH and retinopathy of prematurity; (3) hypoxic events in the early life including placental insufficiency, pre-eclampsia and low birthweight that have the potential to promote hypoxic stress; and (4) the evidence supporting the development of IH independent of HIF-1α. We also discuss these observations in the context of recent evidence of the crucial role of stem cells and the cytokines niche that governs their proliferation and inevitable differentiation, offering novel insights into the biology of IH. We propose that various triggers may simultaneously up-regulate HIF-1α, which is downstream of the renin-angiotensin system, specifically angiotensin II, which promotes production of HIF-1α. These developments shed light to the understanding of this enigmatic condition.


Identification and characterization of specific clones: strategy for confirming the validity of presumptive clones.
It should now be apparent that establishing the identity of a particular recombinant is not a simple procedure. In the absence of unambiguous and internally consistent DNA and protein sequence information, analyses become dependent on a series of characteristics which, together, may be unique to a specific gene and/or gene product. The process of identification is, thus, often more a corroboration of predicted characteristics than absolute proof. It is critical that the process of identification is not simply reduced to the circular arguments generated by reconfirming characteristics used during the initial selection scheme.


Oxi-DIGE: A novel proteomic approach for detecting and quantifying carbonylated proteins.
Proteins are involved in key cellular functions and our health and wellness depends on their quality. Accumulation of oxidatively damaged proteins is a hallmark of deleterious processes such increased oxidative stress, chronic inflammation, ageing and age-related diseases. Thus, quantifying and identifying oxidized proteins is a biomarker of choice for monitoring biological ageing and/or the efficiency of anti-oxidant, ant-inflammatory and anti-ageing therapies. However, the absence of reliable tools for analyses has inhibited its establishment as the gold standard for measuring the efficacy of anti-ageing and age related diseases interventions. Herein, we present a novel proteomics technology, named Oxi-DIGE?, which provides a significant improvement in terms of specificity, reproducibility and statistical support for proteomic analysis of carbonylated proteins. In Oxi-DIGE, protein carbonyls are labelled with fluorescent hydrazide probes that bind specifically to carbonyl groups in proteins. Experimental groups (e.g. control and experimental samples) are labelled with different flurophore-binded hydrazides that fluoresce light at different wavelengths, producing different colour fluorescence. Thus samples from different experimental groups are co-resolved on a single 2D gel. Increased accuracy is provided due to: (i) reduced false positives by using an exogenous synthetic fluorescent tag; (ii) multiplexing, that is the possibility to run multiple samples on the same gel, (iii) the use of an internal standard on each gel which eliminates inter-gel variations and provides an increased statistical confidence. In addition, the resolution of the carbonyl groups is improved, forming distinct spots that can be identified by mass spectrometry. ?Patent Application (M. Baraibar, R. Ladouce., B. Friguet, A method for detecting and/or quantifying carbonylated proteins (WO/2012/175519) filed by UPMC and referring to the technology described in this abstract.


Patients' views on early sensory relearning following nerve repair-a Q-methodology study.
Descriptive study. Early sensory relearning where the dynamic capacity of the brain is used has been shown to improve sensory outcome after nerve repair. However, no previous studies have examined how patients experience early sensory relearning. To describe patient's views on early sensory relearning. Statements' scores were analyzed by factor analysis. Thirty-seven consecutive adult patients with median and/or ulnar nerve repair who completed early sensory relearning were included. Three factors were identified, explaining 45% of the variance: (1) "Believe sensory relearning is meaningful, manage to get an illusion of touch and complete the sensory relearning"; (2) "Do not get an illusion of touch easily and need support in their sensory relearning" (3) "Are not motivated, manage to get an illusion of touch but do not complete sensory relearning". Many patients succeed in implementing their sensory relearning. However, a substantial part of the patient population need more support, have difficulties to create illusion of touch, and lack motivation to complete the sensory relearning. To enhance motivation and meaningfulness by relating the training clearly to everyday occupations and to the patient's life situation is a suggested way to proceed. The three unique factors indicate motivation and sense of meaningfulness as key components which should be taken into consideration in developing programs for person-centered early sensory relearning. 3.


Characterization and sequence confirmation of unnatural amino acid containing peptide libraries using electrospray ionization mass spectrometry.
The content of 24 12-membered heptapeptide libraries was investigated using capillary liquid chromatography coupled with an electrospray ionization quadrupole orthogonal acceleration time-of-flight mass spectrometer. Adjustment of the chromatographic parameters led to the separation of most of the components. Extraction of the [M + 2H]2+ ions allowed us to demonstrate the presence of all expected species in the library and to evaluate their relative abundance in the mixture. Rapid sequence confirmation was achieved by subtraction of product ion spectra, a way to eliminate common ions and to simplify the spectra for interpretation. This technique can also easily be applied to other libraries consisting of components with a common core.


Identification of two regulatory binding sites which confer myotube specific expression of the mono-ADP-ribosyltransferase ART1 gene.
Mono-ADP-ribosyltransferase (ART) 1 belongs to a family of mammalian ectoenzymes that catalyze the transfer of ADP-ribose from NAD+ to a target protein. ART1 is predominantly expressed in skeletal and cardiac muscle. It ADP-ribosylates alpha7-integrin which together with beta1-integrin forms a dimer and binds to laminin, a protein of the extracellular matrix involved in cell adhesion. This posttranslational modification leads to an increased laminin binding affinity. Using C2C12 and C3H-10T 1/2 cells as models of myogenesis, we found that ART1 expression was restricted to myotube formation. We identified a fragment spanning the gene 1.3 kb upstream of the transcriptional start site as the functional promoter of the ART1 gene. This region contains an E box and an A/T-rich element, two conserved binding sites for transcription factors found in the promoters of most skeletal muscle specific genes. Mutating the DNA consensus sequence of either the E box or the A/T-rich element resulted in a nearly complete loss of ART1 promoter inducibility, indicating a cooperative role of the transcription factors binding to those sites. Gel mobility shift analyses carried out with nuclear extracts from C2C12 and C3H-10T 1/2 cells revealed binding of myogenin to the E box and MEF-2 to the A/T-rich element, the binding being restricted to C2C12 and C3H-10T 1/2 myotubes. Here we describe the molecular mechanism underlying the regulation of the ART1 gene expression in skeletal muscle cells. The differentiation-dependent upregulation of ART1 mRNA is induced by the binding of myogenin to an E box and of MEF-2 to an A/T-rich element in the proximal promoter region of the ART1 gene. Thus the transcriptional regulation involves molecular mechanisms similar to those used to activate muscle-specific genes.


Is chlorine and sodium levels in the amniotic fluid a new marker for fetal lung maturation and RDS severity?
Amniotic fluid (AF) is a dynamic liquid whose contents vary according to the needs of the fetus. Levels of the amniotic components have been used in numerous studies as potential biomarkers to screen pregnancy-related abnormalities. As a reflection of Na+ and Cl- levels of fetal lung fluid, amniotic fluid's Na+ and Cl- levels can be used as an indicator of lung maturation in the newborn period. This study aimed to investigate whether Na+ and Cl- levels in the amniotic fluid would be a new marker to determine the severity of respiratory distress and pulmonary maturation in the newborn. This prospective cohort study was conducted at Hacettepe University Neonatal Intensive Care Unit. One hundred twenty single infants who were delivered with the cesarean section between January 2015 and March 2016 were included. Na+ and Cl- levels were measured from AF. There were 46 of 120 infants (33.3%) in Group-1 and 74 infants (66.7%) in Group-2. Na + and Cl- levels of the AF of Group-1 were higher than Group 2 and this was statistically significant (p < .001/p: .01, respectively). Na+ and Cl- levels of the AF were significantly higher in infants who needed surfactant (p < .001/p: .001, respectively). Our results showed that Na+ and Cl- levels of the AF can be used as an indicator of infant lung maturation.


[Pesticides].
This review introduces the most important groups of pesticides. The necessary application of pesticides involves advantages as well as risks for man and environment.


Economic Burden of Veno-occlusive Disease in Patients With B-cell Acute Lymphoblastic Leukemia in the United States.
The goal of this study was to evaluate the incidence, inpatient mortality, and economic burden of hepatic veno-occlusive disease (VOD) in adults with B-cell acute lymphoblastic leukemia (ALL) in the United States. Using MarketScan Commercial Claims and Encounters Database and Medicare Supplemental and Coordination of Benefits Database, data for patients with B-cell ALL from April 1, 2009, to October 31, 2016, were extracted by using diagnosis codes. VOD was identified based on clinical criteria and expert opinions. Patients with VOD were followed up from diagnosis of VOD until the earliest occurrence of inpatient death, end of continuous enrollment, end of study period, or for a maximum of 100days. The incidence of VOD and VOD-associated inpatient mortality were calculated. VOD-related health care costs based on paid adjudicated claims were calculated. Of the 2571 adults with B-cell ALL, the overall incidence of VOD was low at 3.4% (88 of 2571). Of these patients with VOD, 52% (46 of 88) experienced multiorgan failure and were identified as having severe VOD. VOD was only identified in patients having undergone hematopoietic stem cell transplantation (5.4% [88 of 1624]). The inpatient mortality rate of those with any VOD over the 100-day postindex period was 26.1%, and the inpatient mortality was even higher for patients with severe VOD (37.0%). Total mean (SD) medical costs per patient during the 100 days' post-VOD diagnosis were $55,975 ($160,335); mean (SD) costs per patient were ∼4-fold higher for severe ($86,953 [$206,906]) versus nonsevere ($22,047 [$72,847]) VOD. Clinical criteria were used to identify VOD events and thus VOD might be underdiagnosed. The mortality of VOD also might be underestimated because only inpatient deaths are captured in the data. The incidence and mortality of VOD could also be underestimated because we focused on adult patients who might receive reduced-intensity treatment. The economic burden of VOD may be underestimated because the Healthcare Common Procedure Coding System code specific for defibrotide was not available, and thus the cost for defibrotide might not be included. Finally, as the study population consisted of patients with commercial or Medicare supplemental insurance, results may not be generalizable to all patients with VOD in the United States. Although VOD occurred infrequently in adults with B-cell ALL, it was associated with high inpatient mortality and substantial costs. Patients with severe VOD were associated with highest mortality and highest costs. Given the clinical and economic burden associated with VOD, it is important that patients at high risk for VOD be identified and treated to minimize this risk.


International Committee of the Red Cross (ICRC): Cemetery planning, preparation and management during COVID-19: A quick guide to proper documentation and disposition of the dead.
Based on its forensic capacity and experience gained worldwide from the management of the dead in emergencies, including epidemics, the International Committee of the Red Cross has been asked by the authorities and other relevant stakeholders in some of its operational contexts to advise on the planning, preparation and management of cemeteries during COVID19. The management of the dead process includes proper documentation and appropriate disposition, including temporary burials. If there is a sudden and significant increase in the number of deaths, local capacities can quickly become overwhelmed. This guidance, prepared for the COVID19 pandemic, can be applied to any incident involving mass fatalities when the local capacity to provide safe, appropriate and dignified burials is overwhelmed. Specifications on size, spacing, excavation depths, and information about other important considerations are provided. In addition, it provides recommendations on how to correctly map graves while ensuring the traceability and correct management of bodies in a cemetery. Procedures for receiving bodies, as well as measures to ensure the health and safety of relatives and cemetery staff are also covered in this guidance.


Does environmental pollution influence household asset allocation? Evidence from China.
This paper establishes a causal relation between households' decision of asset allocation and environmental pollution based on urban PM2.5 concentration data and a nationally representative survey in China. We find a significantly negative effect of environmental pollution on households' demand for housing assets but an inverted U-shaped effect on the demand for risky assets. The effects are remarkably robust to correcting the endogenous issue and a battery of robustness checks. Social interaction can partly explain such an effect of pollution. Furthermore, we also find that because households with lower economic status are at greater risk of exposure to environmental pollution and lack of economic capabilities, their holdings of financial assets decrease more than that of the households with higher economic status when faced with pollution; however, their holdings of low liquid assets declining less.


Target β-catenin/CD44/Nanog axis in colon cancer cells by certain N'-(2-oxoindolin-3-ylidene)-2-(benzyloxy)benzohydrazides.
Cell surface molecule CD44 plays a major role in regulation of cancer stem cells CSCs on both phenotypic and functional level, however chemical inhibition approach of CD44 to targets CSCs is poorly studied. Herein, we report the discovery of certain N'-(2-oxoindolin-3-ylidene)-2-(benzyloxy)benzohydrazides as a novel inhibitor of CD44. Molecular docking study showed interference of the scaffold of these compounds with β-catenin/TCF-4 complex, building a direct relationship between CD44 inhibition and observed well-fitted binding domain. Compound 11a, most potent member elicits inhibition effect on TCF/LEF reporter activity conformed the involvement of Wnt pathway inhibition as a mechanism of action. Furthermore, the treatment by the mentioned compound leads to inhibition of embryonic transcriptional factor Nanog but not Sox2 or Oct-4 suggested specific targeted effect. Moreover, the cytotoxicity and cell cycle effect of this series seems to be dependent on CD44 expression.


NREM-related parasomnias in Machado-Joseph disease: clinical and polysomnographic evaluation.
Spinocerebellar ataxias (SCA) are autosomal dominant neurodegenerative disorders that affect the cerebellum and its connections, and have a marked clinical and genetic variability. Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3)--MJD/SCA3--is the most common SCA worldwide. MJD/SCA3 is characterized classically by progressive ataxia and variable other motor and non-motor symptoms. Sleep disorders are common, and include rapid eye movement (REM) sleep behaviour disorder (RBD), restless legs syndrome (RLS), insomnia, excessive daytime sleepiness, excessive fragmentary myoclonus and sleep apnea. This study aims to focus upon determining the presence or not of non-REM (NREM)-related parasomnias in MJD/SCA 3, using data from polysomnography (PSG) and clinical evaluation. Forty-seven patients with clinical and genetic diagnosis of MJD/SCA3 and 47 control subjects were evaluated clinically and by polysomnography. MJD/SCA3 patients had a higher frequency of arousals from slow wave sleep (P < 0.001), parasomnia complaints (confusional arousal/sleep terrors, P = 0.001; RBD, P < 0.001; and nightmares, P < 0.001), REM sleep without atonia (P < 0.001), periodic limb movements of sleep index (PLMSi) (P < 0.001), percentage of N3 sleep (P < 0.001) and percentage of N1 sleep (P < 0.001). These data show that NREM-related parasomnias must be included in the spectrum of sleep disorders in MJD/SCA3 patients.


Conformational analysis of the endogenous mu-opioid agonist endomorphin-1 using NMR spectroscopy and molecular modeling.
Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) is a highly selective and potent agonist of the mu-opioid receptor. To identify structural attributes unique to this opioid peptide and potential sites of recognition, a conformational analysis has been performed using multidimensional NMR and molecular modeling techniques. The spectroscopic results, derived from experiments in both DMSO and water, indicate that endomorphin-1 exists in the cis- and trans-configuration with respect to the Pro-omega bond in approximately 25% and 75% populations, respectively. In DMSO, the cis-configuration adopts a compact sandwich conformation in which the Tyr and Trp aromatic rings pack against the proline ring, whereas the trans-configuration adopts an extended conformation. Although non-random structure was not observed in water, condensed phase molecular dynamics calculations indicate that trans-isomers dominate the population in this higher dielectric medium. Structural comparison of the cis- and trans-configurations with morphine and selective mu-peptide ligands PL-017 and D-TIPP, as well as the delta-selective peptide ligands TIPP (delta-antagonist, mu-agonist) and DPDPE were also performed and suggest the trans-isomer is likely the bioactive form. A hypothesis is proposed to explain mu- and delta-selectivity based on the presence of spatially distinct selectivity pockets among these ligands.


Components required for membrane assembly of newly synthesized K+ channel KcsA.
An Escherichia coli in vitro transcription-translation system was used to study the components involved in the biogenesis of the homotetrameric potassium channel KcsA. We show that a functional signal recognition particle pathway is essential for tetramer formation, probably to direct correct monomer insertion in the membrane. In the absence of YidC or at reduced SecYEG levels, KcsA assembly occurs with lower efficiency. Strikingly, the highest efficiency of tetramerization was observed when transcription-translation was carried out in the presence of pure lipid vesicles, demonstrating that a phospholipid bilayer is the minimal membrane requirement to form the KcsA tetramer. It is concluded that SecYEG and YidC are not required for the formation of tetrameric KcsA in vitro.


Gradients in population fluctuations of Tengmalm's owl Aegolius funereus in Europe.
I studied the importance of geographical location, snow cover and food to the fluctuations in 30 breeding populations of Tengmalm's owl (Aegolius funereu) in Europe. Cyclicity indices were positively related both to latitude and longitude, but within Fennoscandia they were better correlated with snow cover. Population fluctuations increased northward, while food niche breadth and degree of site tenacity decreased northwards.Microtine fluctuations become more pronounced northwards and are more synchronized, while number of alternative prey increases southwards. These factors promote instability in North European and stability in central European owl populations. Furthermore, snow conditions were more important within Fennoscandia, since this small owl cannot hunt voles protected by deep snow. Environmental predictability and diversity of available food for Tengmalm's owl increase southwards in Europe. Thus, the owl is a resident generalist predator of small mammals and birds in central Europe and adopts a partial migration strategy (males being resident and females nomadic) in South and West Finland, changing its habits to nomadic microtine specialist in areas with pronounced vole cycles (in northern Fennoscandia). These changes fit well with the recent suggestion that gradients in density variations of small rodents are related to sustainable numbers of generalist predators.


Chest CT in COVID-19 pneumonia: A review of current knowledge.
The current COVID-19 pandemic has highlighted the essential role of chest computed tomography (CT) examination in patient triage in the emergency departments, allowing them to be referred to "COVID" or "non-COVID" wards. Initial chest CT examination must be performed without intravenous administration of iodinated contrast material, but contrast material administration is required when pulmonary embolism is suspected, which seems to be frequent in severe forms of the disease. Typical CT features consist of bilateral ground-glass opacities with peripheral, posterior and basal predominance. Lung disease extent on CT correlates with clinical severity. Artificial intelligence could assist radiologists for diagnosis and prognosis evaluation.


Pediatric high-field magnetic resonance imaging.
High-field 3 T magnetic resonance (MR) imaging provides greater signal-to-noise ratio (SNR) compared with 1.5 T systems. Various MR imaging clinical applications in children can benefit from improvements resulting from this increased SNR. High-resolution imaging of the brain, arterial spin labeling perfusion imaging, diffusion imaging, MR spectroscopy, and imaging of small anatomic parts are some areas in which these improvements can increase our clinical diagnostic capabilities. However, challenges inherent to 3 T imaging become more relevant in children. The use of 3 T imaging in children has allowed better diagnostic efficacy in neuroimaging, but certain technique modifications may be required for optimal imaging.


Nutrient deficiency stimulates the production of superoxide in the noxious red-tide-forming raphidophyte Chattonella antiqua.
The raphidophyte Chattonella antiqua is a single-celled alga that forms 'red tides' in coastal areas. C. antiqua produces superoxide anions (O2-), the excessive production of which has been associated with fish mortality. It is suggested that putative NADPH oxidase in the outer membrane oxidizes intracellular NADPH to produce O2- and secrete it externally. Earlier studies revealed that photosynthetic electron transport, a major producer of NADPH in photosynthetic organisms, is involved in the production of O2- in C. antiqua but the details of the O2- production mechanism have yet to be elucidated. Since nutrient deficiency adversely affects the formation of blooms of C. antiqua, in this study, we examined the effects of nutrient deficiency on O2- production in C. antiqua. When cells were grown under nitrogen (N)- or phosphorus (P)-deficient conditions, the production of O2- was stimulated. In particular, the extracellular levels of O2- under N- or P-deficient conditions were high during the dark period when photosynthetic activities in terms of actual quantum efficiency and photochemical quenching were low. The extracellular levels of O2- under the nutrient-deficient conditions were unaffected by the presence of 3-(3,4-dichlorophenyl)-1,1‑dimethylurea (DCMU), an inhibitor of photosynthetic electron transport, but decreased when the nutrients were present. Furthermore, the intracellular ratio of NADPH to NADP+ under N- or P-deficient conditions was higher than that under nutrient-replete conditions. These observations suggest that another metabolic pathway, independent of photosynthesis, provides NADPH for the production of O2- under nutrient deficiency.


Measurement of Accurate Interfluorine Distances in Crystalline Organic Solids: A High-Frequency Magic Angle Spinning NMR Approach.
Long-range interatomic distance restraints are critical for the determination of molecular structures by NMR spectroscopy, both in solution and in the solid state. Fluorine is a powerful NMR probe in a wide variety of contexts, owing to its favorable magnetic properties, ease of incorporation into biological molecules, and ubiquitous use in synthetic organic molecules designed for diverse applications. Because of the large gyromagnetic ratio of the 100% naturally abundant 19F isotope, interfluorine distances as long as 20 Å are accessible in magic-angle spinning (MAS) dipolar recoupling experiments. Herein, we present an approach for the determination of accurate interfluorine distances in multispin systems, using the finite pulse radio frequency driven recoupling (fpRFDR) at high MAS frequencies of 40-60 kHz. We use a series of crystalline "molecular ruler" solids, difluorobenzoic acids and 7F-L-tryptophan, for which the intra- and intermolecular interfluorine distances are known. We describe the optimal experimental conditions for accurate distance determinations, including the choice of a phase cycle, the relative advantages of selective inversion one-dimensional versus two-dimensional correlation experiments, and the appropriate numerical simulation protocols. An optimal strategy for the analysis of RFDR exchange curves in organic solids with extended spin interaction networks is presented, which, even in the absence of crystal structures, can be potentially incorporated into NMR structure determination.


Role of serum cytokine profile in ulcerative colitis assessment.
Several cytokines are overexpressed in the colonic mucosa of patients with ulcerative colitis (UC). The measurement of these parameters in plasma could be useful in diagnosis and disease assessment. In all, 67 UC patients and 21 healthy controls were enrolled. At inclusion, clinical, endoscopic, and histological disease activity were assessed using the Ulcerative Colitis Activity Index (UCAI) and the Baron and Geboes scales, respectively. Serum cytokine concentrations were analyzed with a multiplex system (Bio-Plex pro, Bio-Rad) measuring interleukin (IL)-1-β, IL-2, IL-6, IL-8, IL-10, IL-13, IL-17, interferon-gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α). Multiple logistic regression was used to design a serum cytokines profile. In the UC group the disease activity was moderate to severe based on clinical evaluation in 35 patients (52.2%), by endoscopic appearance in 45 (67.2%), and in 53 patients (81.6%) using histology. With respect to controls, the multivariate analysis identified that UC patients had higher IL-8 (odds ratio [OR] = 1.37; P = 0.002) and IL-10 concentrations (OR = 3.88; P = 0.012) with lower levels of IFN-γ (OR = 0.95; P = 0.002). The model had an accuracy of 77.3%, which increased to 94.6% when only newly diagnosed patients were considered. Patients with moderate to severe disease according to their clinical score showed a higher concentration of IL-8 (OR = 1.16; P = 0.012) and IL-10 (OR = 1.76; P = 0.039) with lower levels of IL-17 (OR = 0.97; P = 0.021). The IL-8 serum concentration was also related to endoscopic and histological severity (OR = 1.10; P = 0.026 and OR = 1.33, P = 0.017, respectively). A serum cytokine profile may be an auxiliary tool for the diagnosis and severity assessment of UC. IL-8 seems to be a reliable biomarker, closely related to disease activity.