Do chromium-resistant bacterial symbionts of hyperaccumulator Callitriche cophocarpa support their host in phytobial remediation of water?

Callitriche cophocarpa Sendtn. is a macrophyte widely distributed in aquatic systems of the temperate climate zone and a known hyperaccumulator of chromium. Ten pure symbiotic bacterial isolates of C. cophocarpa were obtained and identified. Three of the isolates showed the highest resistance to Cr(VI): Microbacterium sp. (Ct1), Aeromonas sp. (Ct3) and Acinetobacter sp. (Ct6). Acinetobacter sp. (Ct6) was able to survive up to a concentration of 104 mg/L (2 mM). The isolates were also able to effectively detoxify Cr(VI) by reducing it to Cr(III). We tested whether inoculation of plants with a consortium consisting of Ct1, Ct3 and Ct6 affects: (1) the phytoextraction of chromium from leachates, (2) the physiological state of plants after Cr(VI) treatment. The solutions were landfill leachates and contained 10.7 mg/L of Cr(VI) - an amount 530 times exceeding the legal limits. We influenced the plants with Cr in two steps, each lasting for 10 days, first using mature shoots and then apical ones. The highest Cr content concomitant with the highest bioconcentration factor (BCF) were found in the inoculated plants: 1274 and 119 mg/kg dry mass (d.m.), respectively. The physiological status of the plants was assessed by biometric tests and advanced chlorophyll fluorescence analyses. The photosynthetic activity of mature shoots was influenced by Cr(VI) more negatively than that of young apical shoots. The inoculation with the bacterial consortium significantly reduced the negative effect of Cr(VI) on mature organs. In some cases the inoculated mature plants exhibited photosynthetic activity that was even higher than in the control plants. The results unequivocally show a beneficial effect of C. cophocarpa inoculation with the tested isolates resulting in a significant improvement of the phytoremediation properties of this aquatic chromium hyperaccumulator.

Impaired Expression of the Salvador Homolog-1 Gene Is Associated with the Development and Progression of Colorectal Cancer.

Salvador homolog-1 (SAV1) is a component of the Hippo pathway that regulates tissue growth and homeostasis by affecting diverse cell processes, including apoptosis, cell division, and differentiation. The aberrant expression of Hippo pathway components has been observed in various human cancers. This study aimed to examine the expression level of the SAV1 gene in colorectal cancer (CRC) and its prognostic value and associations with tumor progression. We obtained matched pairs of tumor tissue and non-cancerous mucosa of the large intestine from 94 CRC patients as well as 40 colon biopsies of healthy subjects collected during screening colonoscopy. The tissue samples and CRC cell lines were quantified for SAV1 mRNA levels using the quantitative polymerase chain reaction method, while SAV1 protein expression was estimated in the paired tissues of CRC patients using immunohistochemistry. The average level of SAV1 mRNA was decreased in 93.6% of the tumor tissues compared to the corresponding non-cancerous tissues and biopsies of healthy colon mucosa. A downregulated expression of SAV1 mRNA was also noted in the CRC cell lines. Although the average SAV1 immunoreactivity was increased in the CRC samples compared to the non-cancerous tissues, a decreased immunoreactivity of the SAV1 protein in the tumor specimens was associated with lymph node involvement and higher TNM disease stage and histological grade. The results of our study suggest that the impaired expression of SAV1 is involved in CRC progression.

WNT4 Gene and Protein Expression in Endometrial Cancer and Its Significance.

BACKGROUND: The inappropriate action of WNT4 and estrogens affects uterine homeostasis and function, and may lead to endometrial cancer (EC). OBJECTIVE: The aim was to evaluate the alterations of WNT4 gene expression and WNT4 protein immunoreactivity (Ir) in EC, considering tumor characteristics, the clinicopathological association and estrogen dependence. METHODS: WNT4 mRNA levels were compared between benign (control) endometrium (n = 8) and endometroid EC (EEC) and non-endometroid EC (non-EEC) samples (n = 28) using the real-time PCR technique. The WNT4-Ir and ERα-Ir were evaluated by immunohistochemistry (IHC). WNT4 mRNA gene and WNT4-Ir were correlated with clinicopathological and blood morphological parameters. Overall survival (OS) was assessed. The bioanalysis was utilized to study WNT4 expression in large patient cohort (n = 549). RESULTS: WNT4 gene expression was decreased in EC samples (specifically in EEC but not in non-EEC) compared to the control. The WNT4 gene expression was also decreased in EC samples categorized by the tumor characteristics. There was no statistical difference in WNT4-Ir or ERα-Ir between the control and EC. There was no correlation between OS and WNT4 gene expression and WNT4-Ir. Bioanalysis showed that WNT4 and ESR1 gene expression alterations tended to be mutually exclusive. An alteration in WNT4 expression was found in different histological tumor types in a large group of EC patients. CONCLUSIONS: There is a great need to evaluate the molecular background of EC. Our study suggests that the WNT4 gene has the potential to be a marker of functional estrogen signaling in EEC.

Improving community-based COPD care in general practice in Poland - a cluster randomized controlled trial.

INTRODUCTION AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. The aim of the study was to evaluate the impact of intervention on exacerbations of COPD in elderly patients compared to those receiving usual care. MATERIAL AND METHODS: A 12 month, multicentre, three-arm, pragmatic, cluster randomized controlled trial was performed (CRCT). The 97 largest PHC clinics with at least 46 COPD registered patients in the Lódz Province, in central Poland. In total, 27,534 COPD patients aged 65 and over were identified from the National Health Fund (NFZ) electronic health records. A checklist of selected, recommended COPD interventions sent to GPs once or twice by post and shown on their desk in their clinics, in the intervention arms. RESULTS: A primary outcome was the difference in exacerbations or deaths between the 3 arms at 12 months. The amounts of specific short- and long-acting drugs purchased by patients were also assessed as secondary outcomes. Only 0.44% (122 of 27 534) COPD patients demonstrated exacerbations after the one-year study period. No statistically significant associations were found between interventions and exacerbations (p=0.1568, Chi-Square) or deaths (p=0.8128, Chi-Square) at 12 months. CONCLUSIONS: As this study coincided with the pandemic period, the results should be interpreted with care. The intervention had no association with exacerbations. Future research on interventions aimed at improving chronic illness care are needed.

Disease-Specific Quality Indicators for Outpatient Antibiotic Prescribing for Respiratory Infections (ESAC Quality Indicators) Applied to Point Prevalence Audit Surveys in General Practices in 13 European Countries.

Up to 80% of antibiotics are prescribed in the community. An assessment of prescribing by indication will help to identify areas where improvement can be made. A point prevalence audit study (PPAS) of consecutive respiratory tract infection (RTI) consultations in general practices in 13 European countries was conducted in January-February 2020 (PPAS-1) and again in 2022 (PPAS-4). The European Surveillance of Antibiotic Consumption quality indicators (ESAC-QI) were calculated to identify where improvements can be made. A total of 3618 consultations were recorded for PPAS-1 and 2655 in PPAS-4. Bacterial aetiology was suspected in 26% (PPAS-1) and 12% (PPAS-4), and an antibiotic was prescribed in 30% (PPAS-1) and 16% (PPAS-4) of consultations. The percentage of adult patients with bronchitis who receive an antibiotic should, according to the ESAC-QI, not exceed 30%, which was not met by participating practices in any country except Denmark and Spain. For patients (≥1) with acute upper RTI, less than 20% should be prescribed an antibiotic, which was achieved by general practices in most countries, except Ireland (both PPAS), Croatia (PPAS-1), and Greece (PPAS-4) where prescribing for acute or chronic sinusitis (0-20%) was also exceeded. For pneumonia in adults, prescribing is acceptable for 90-100%, and this is lower in most countries. Prescribing for tonsillitis (≥1) exceeded the ESAC-QI (0-20%) in all countries and was 69% (PPAS-1) and 75% (PPAS-4). In conclusion, ESAC-QI applied to PPAS outcomes allows us to evaluate appropriate antibiotic prescribing by indication and benchmark general practices and countries.

Neurological Manifestations of Non-Severe COVID-19-A Multidirectional Approach.

COVID-19 remains a significant clinical issue worldwide, with frequent neurological manifestations. In this study, the authors combine data obtained from the patient's medical history, physical examinations, and additional test results in the pursuit of any clinically relevant connections. Fifty-eight adult patients hospitalized in the Department of Neurology and Infectiology over a five-months period were retrospectively enrolled in this study. On admission, all patients included in this study were classified as mild or moderate COVID-19 cases, according to the World Health Organization (WHO) guidelines. Laboratory tests, Electroencephalography (EEG), and Magnetic Resonance Imaging (MRI) were performed. There was no statistically significant difference in the Neutrophil-Lymphocyte Ratio (NLR), C-reactive protein (CRP), and Interleukin 6 (IL-6) in patients who reported to the hospital within a week from the symptoms' onset and in those who reported later. In total, 49.06% of patients with eligible EEG recordings presented abnormal brain activity, while 27.59% of the study population had COVID-19-associated MRI findings. EEG and MRI abnormality occurrence did not correlate with the incidence of mild neurological symptoms (headache, olfactory, and gustatory disorders) of the SARS-CoV-2 infection. In three patients in this study population, unprovoked generalized epileptic seizures occurred for the first time in their life. Non-severe SARS-CoV-2 infection causes functional and structural abnormalities within the central nervous system. Brain microhemorrhages are frequently present in non-severe COVID-19 patients. There is no significant association between mild neurological symptoms of COVID-19 and additional test abnormalities. The time from SARS-CoV-2 infection's onset to hospital admission does not seem to influence the prognostic value of CRP, IL-6, and NLR in non-severe COVID-19. Mild-to-moderate SARS-CoV-2 infection can be a trigger factor for epilepsy and epileptic seizures.

Effect of a multifaceted antibiotic stewardship intervention to improve antibiotic prescribing for suspected urinary tract infections in frail older adults (ImpresU): pragmatic cluster randomised controlled trial in four European countries.

OBJECTIVE: To evaluate whether antibiotic prescribing for suspected urinary tract infections in frail older adults can be reduced through a multifaceted antibiotic stewardship intervention. DESIGN: Pragmatic, parallel, cluster randomised controlled trial, with a five month baseline period and a seven month follow-up period. SETTING: 38 clusters consisting of one or more general practices (n=43) and older adult care organisations (n=43) in Poland, the Netherlands, Norway, and Sweden, from September 2019 to June 2021. PARTICIPANTS: 1041 frail older adults aged 70 or older (Poland 325, the Netherlands 233, Norway 276, Sweden 207), contributing 411 person years to the follow-up period. INTERVENTION: Healthcare professionals received a multifaceted antibiotic stewardship intervention consisting of a decision tool for appropriate antibiotic use, supported by a toolbox with educational materials. A participatory-action-research approach was used for implementation, with sessions for education, evaluation, and local tailoring of the intervention. The control group provided care as usual. MAIN OUTCOME MEASURES: The primary outcome was the number of antibiotic prescriptions for suspected urinary tract infections per person year. Secondary outcomes included the incidence of complications, all cause hospital referrals, all cause hospital admissions, all cause mortality within 21 days after suspected urinary tract infections, and all cause mortality. RESULTS: The numbers of antibiotic prescriptions for suspected urinary tract infections in the follow-up period were 54 prescriptions in 202 person years (0.27 per person year) in the intervention group and 121 prescriptions in 209 person years (0.58 per person year) in the usual care group. Participants in the intervention group had a lower rate of receiving an antibiotic prescription for a suspected urinary tract infection compared with participants in the usual care group, with a rate ratio of 0.42 (95% confidence interval 0.26 to 0.68). No differences between intervention and control group were observed in the incidence of complications (<0.01 v 0.05 per person year), hospital referrals (<0.01 v 0.05), admissions to hospital (0.01 v 0.05), and mortality (0 v 0.01) within 21 days after suspected urinary tract infections, nor in all cause mortality (0.26 v 0.26). CONCLUSIONS: Implementation of a multifaceted antibiotic stewardship intervention safely reduced antibiotic prescribing for suspected urinary tract infections in frail older adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT03970356.

Initial symptoms and three months follow-up after acute COVID-19 in outpatients: An international prospective cohort study.

BACKGROUND: Most studies on long-term follow-up of patients with COVID-19 focused on hospitalised patients. No prospective study with structured follow-up has been performed in non-hospitalised patients with COVID-19. OBJECTIVES: To assess long-COVID and post-COVID (WHO definition: symptomatic at least 12 weeks), describe lingering symptoms, their impact on daily activities, and general practice visits and explore risk factors for symptom duration in outpatients. METHODS: A prospective study of adult outpatients with confirmed SARS-CoV-2 infection and symptoms consistent with COVID-19 in 11 European countries, recruited during 2020 and 2021 from primary care and the community. Structured follow-up by phone interviews (symptom rating, symptom impact on daily activities and general practice visits) was performed at weeks 2, 4, 8, and 12 by study personnel. Data was analysed descriptively by using correlation matrixes and Cox regression. RESULTS: Of 270 enrolled patients, 52% developed long-COVID and 32% post-COVID-syndrome. When only considering the presence of moderate or (very) severe symptoms at weeks 8 and 12, these percentages were 28% and 18%, respectively. Fatigue was the most often reported symptom during follow-up. The impact of lingering symptoms was most evident in sports and household activities. About half (53%) had at least one general practice contact during follow-up. Obese patients took twice as long to return to usual health (HR: 0.5, 95%CI: 0.3-0.8); no other risk profile could predict lingering symptoms. CONCLUSION: Long-COVID and post-COVID are also common in outpatients. In 32%, it takes more than 12 weeks to return to usual health.

Trifluoromethylated 4,5-Dihydro-1,2,4-triazin-6(1H)-ones via (3+3)-Annulation of Nitrile Imines with α-Amino Esters.

The synthesis of two series of monocyclic and bicyclic trifluoromethylated 4,5-dihydro-1,2,4-triazin-6(1H)-one derivatives based on (3+3)-annulation of methyl esters derived from natural α-amino acids with in situ generated trifluoroacetonitrile imines has been described. The devised protocol is characterized by a wide scope, easily accessible substrates, remarkable functional group tolerance, and high chemical yield. In reactions with chiral starting materials, no racemization at the stereogenic centers was observed and the respective enantiomerically pure products were obtained. Selected functional group interconversions carried out under catalytic hydrogenation and mild PTC oxidation conditions were also demonstrated.

Malignancies in adult kidney transplant candidates and recipients: current status.

Posttransplant malignancies, particularly recurrent and de novo, in solid organs including kidney transplant recipients (KTRs) are a significant complication associated with substantial mortality, largely attributed to the long-term immunosuppression necessary to maintain allograft tolerance. Older age at transplantation and oncogenic virus infection along with pretransplant malignancies are among the main factors contributing to the risk of cancer in this population. As the mean age of transplant candidates rises, the rate of transplant recipients with pretransplant malignancies also increases. The eligibility criteria for transplantation in patients with prior cancer have recently changed. The overall risk of posttransplant malignancies is at least double after transplantation, including KTRs, relative to the general population, and is most pronounced for skin cancers associated with UV radiation and virally mediated tumors. The risk of renal cell carcinoma is specifically increased in the kidney transplant population. The therapy for cancer in transplant patients is associated with risk of higher toxicity, and graft rejection and/or impairment, which poses a unique challenge in its management. Reduction of immunosuppression and the use of mammalian target of rapamycin inhibitors are common after cancer diagnosis, although optimal immunosuppression for transplant recipients with cancer remains undefined. Suboptimal cancer treatment contributing to a worse prognosis has been reported for malignancies in this population. In this article, we focus on the prevalence and outcomes of posttransplant malignancies, cancer therapy including a short overview of immunotherapy, cancer screening and prevention strategies, and immunosuppression as a cancer risk factor. The 2020/2021 recommendations of the Kidney Disease: Improving Global Outcomes and the American Society of Transplantation for transplant candidates with a history of cancer are presented.

Genomic Profiling Identifies Putative Pathogenic Alterations in NSCLC Brain Metastases.

Introduction: Brain metastases (BM) severely affect the prognosis and quality of life of patients with NSCLC. Recently, molecularly targeted agents were found to have promising activity against BM in patients with NSCLC whose primary tumors carry "druggable" mutations. Nevertheless, it remains critical to identify specific pathogenic alterations that drive NSCLC-BM and that can provide novel and more effective therapeutic targets. Methods: To identify potentially targetable pathogenic alterations in NSCLC-BM, we profiled somatic copy number alterations (SCNAs) in 51 matched pairs of primary NSCLC and BM samples from 33 patients with lung adenocarcinoma and 18 patients with lung squamous cell carcinoma. In addition, we performed multiregion copy number profiling on 15 BM samples and whole-exome sequencing on 40 of 51 NSCLC-BM pairs. Results: BM consistently had a higher burden of SCNAs compared with the matched primary tumors, and SCNAs were typically homogeneously distributed within BM, suggesting BM do not undergo extensive evolution once formed. By comparing focal SCNAs in matched NSCLC-BM pairs, we identified putative BM-driving alterations affecting multiple cancer genes, including several potentially targetable alterations in genes such as CDK12, DDR2, ERBB2, and NTRK1, which we validated in an independent cohort of 84 BM samples. Finally, we identified putative pathogenic alterations in multiple cancer genes, including genes involved in epigenome editing and 3D genome organization, such as EP300, CTCF, and STAG2, which we validated by targeted sequencing of an independent cohort of 115 BM samples. Conclusions: Our study represents the most comprehensive genomic characterization of NSCLC-BM available to date, paving the way to functional studies aimed at assessing the potential of the identified pathogenic alterations as clinical biomarkers and targets.

Dexmedetomidine Increases MMP-12 and MBP Concentrations after Coronary Artery Bypass Graft Surgery with Extracorporeal Circulation Anaesthesia without Impacting Cognitive Function: A Randomised Control Trial.

Postoperative neurological deficits remain a concern for patients undergoing cardiac surgeries. Even minor injuries can lead to neurocognitive decline (i.e., postoperative cognitive dysfunction). Dexmedetomidine may be beneficial given its reported neuroprotective effect. We aimed to investigate the effects of dexmedetomidine on brain injury during cardiac surgery anaesthesia. This prospective observational study analysed data for 46 patients who underwent coronary artery bypass graft surgery with extracorporeal circulation between August 2018 and March 2019. The patients were divided into two groups: control (CON) with typical anaesthesia and dexmedetomidine (DEX) with dexmedetomidine infusion. Concentrations of the biomarkers matrix metalloproteinase-12 (MMP-12) and myelin basic protein (MBP) were measured preoperatively and at 24 and 72 h postoperatively. Cognitive evaluations were performed preoperatively, at discharge, and 3 months after discharge using Addenbrooke's Cognitive Examination version III (ACE-III). The primary endpoint was the ACE-III score at discharge. Increased MMP-12 and MBP concentrations were observed in the DEX group 24 and 72 h postoperatively. No significant differences in ACE-III scores were observed between the groups at discharge; however, the values were increased when compared with initial values after 3 months (p = 0.000). The current results indicate that the administration of dexmedetomidine as an adjuvant to anaesthesia can increase MMP-12 and MBP levels without effects on neurocognitive outcomes at discharge and 3 months postoperatively.

Eating Behaviours in Sportswomen from the Silesian Training in Different Sports Disciplines.

Eating disorders are characterized by abnormal, unhealthy eating habits, and disordered body image. In severe cases, it can cause serious health consequences, including cardiac problems, osteoporosis, infertility, or missing menstrual periods. In women competitively training sports, the main cause for disordered eating behaviours are factors associated with dissatisfaction with their appearance and body image and a need to reduce body weight. Factors related to dissatisfaction with one's own appearance and body image, a need to reduce body weight, a negative perception of themselves and their bodies, the pressure in sports circles, and stress are predictors for eating disorders. The aim of the study was to compare eating behaviours, body satisfaction, and taking various actions related to body mass reduction among women training competitively in volleyball, athletics, gymnastics, and young women not participating in sports. MATERIAL AND METHODS: The study covered a group of girls and young women from the Silesian, Poland, who represented three sports disciplines (volleyball, athletics, and gymnastics), of which 30 girls were used as a control group (B). The study was conducted using a study questionnaire. RESULTS: The study participants ate regularly and consumed all food groups during a week. The majority of girls from A1 (83.33%), A3 (53.33%), and B (80%) groups expressed their dissatisfaction with their body weight. In the group of gymnasts, a positive correlation was noted between the need to reduce body weight and regular eating (r = 0.449; p = 0.013). In the group of volleyball players, it was demonstrated that the higher the competitive experience and the greater the training load, the more regular their eating was (r = 0.475; p = 0.009). CONCLUSIONS: The importance of a diagnosis of early signs of eating disorders in girls and women as a basic component contributing to FAT development implies that further studies in this area, as well as education of the entire sports circle are necessary.

Fluorinated and Non-Fluorinated 1,4-Diarylpyrazoles via MnO2-Mediated Mechanochemical Deacylative Oxidation of 5-Acylpyrazolines.

A solvent-free two-step synthesis of polyfunctionalized pyrazoles under ball-milling mechanochemical conditions was developed. The protocol comprises (3 + 2)-cycloaddition of in situ generated nitrile imines and chalcones, followed by oxidation of the initially formed 5-acylpyrazolines with activated MnO2. The second step proceeds via an exclusive deacylative pathway, to give a series of 1,4-diarylpyrazoles functionalized with a fluorinated (CF3) or non-fluorinated (Ph, COOEt, Ac) substituent at C(3) of the heterocyclic ring. In contrast, MnO2-mediated oxidation of a model isomeric 4-acylpyrazoline proceeded with low chemoselectivity, leading to fully substituted pyrazole as a major product formed via dehydrogenative aromatization. The presented approach extends the scope of the known methods carried out in organic solvents and enables the preparation of polyfunctionalized pyrazoles, which are of general interest in medicine and material sciences.

Developing a Tool for Auditing the Quality of Antibiotic Dispensing in Community Pharmacies: A Pilot Study.

BACKGROUND: The European Centre for Disease Prevention and Control describes the community pharmacist as the gatekeeper to the quality of antibiotic use. The pharmacist has the responsibility to guard safe and effective antibiotic use; however, little is known about how this is implemented in practice. AIMS: To assess the feasibility of a method to audit the quality of antibiotic dispensing in community pharmacy practice and to explore antibiotic dispensing practices in Greece, Lithuania, Poland, and Spain. METHODS: The Audit Project Odense methodology to audit antibiotic dispensing practice was adapted for use in community pharmacy practice. Community pharmacists registered antibiotic dispensing on a specifically developed registration chart and were asked to provide feedback on the registration method. RESULTS: Altogether, twenty pharmacists were recruited in four countries. They registered a total of 409 dispenses of oral antibiotics. Generally, pharmacists were positive about the feasibility of implementing the registration chart in practice. The frequency of checking for allergies, contraindications and interactions differed largely between the four countries. Pharmacists provided little advice to patients. The pharmacists rarely contacted prescribers. CONCLUSION: This tool seems to make it possible to get a useful picture of antibiotic dispensing patterns in community pharmacies. Dispensing practice does not seem to correspond with EU guidelines according to these preliminary results.

Pathway-level mutation analysis in primary high-grade serous ovarian cancer and matched brain metastases.

Brain metastases (BMs) in ovarian cancer (OC) are a rare event. BMs occur most frequently in high-grade serous (HGS) OC. The molecular features of BMs in HGSOC are poorly understood. We performed a whole-exome sequencing analysis of ten matched pairs of formalin-fixed paraffin-embedded samples from primary HGSOC and corresponding BMs. Enrichment significance (p value; false discovery rate) was computed using the Reactome, the Kyoto Encyclopedia of Genes and Genomes pathway collections, and the Gene Ontology Biological Processes. Germline DNA damage repair variants were found in seven cases (70%) and involved the BRCA1, BRCA2, ATM, RAD50, ERCC4, RPA1, MLHI, and ATR genes. Somatic mutations of TP53 were found in nine cases (90%) and were the only stable mutations between the primary tumor and BMs. Disturbed pathways in BMs versus primary HGSOC constituted a complex network and included the cell cycle, the degradation of the extracellular matrix, cell junction organization, nucleotide metabolism, lipid metabolism, the immune system, G-protein-coupled receptors, intracellular vesicular transport, and reaction to chemical stimuli (Golgi vesicle transport and olfactory signaling). Pathway analysis approaches allow for a more intuitive interpretation of the data as compared to considering single-gene aberrations and provide an opportunity to identify clinically informative alterations in HGSOC BM.

Optimising the sensing volume of OPM sensors for MEG source reconstruction.

Magnetoencephalography (MEG) based on optically pumped magnetometers (OPMs) has been hailed as the future of electrophysiological recordings from the human brain. In this work, we investigate how the dimensions of the sensing volume (the vapour cell) affect the performance of both a single OPM-MEG sensor and a multi-sensor OPM-MEG system. We consider a realistic noise model that accounts for background brain activity and residual noise. By using source reconstruction metrics such as localization accuracy and time-course reconstruction accuracy, we demonstrate that the best overall sensitivity and reconstruction accuracy are achieved with cells that are significantly longer and wider that those of the majority of current commercial OPM sensors. Our work provides useful tools to optimise the cell dimensions of OPM sensors in a wide range of environments.

Methenamine hippurate to prevent recurrent urinary tract infections in older women: protocol for a randomised, placebo-controlled trial (ImpresU).

INTRODUCTION: Methenamine hippurate is a urinary antiseptic used as preventive treatment for recurrent urinary tract infections (UTIs) in some Scandinavian countries. However, the scientific evidence for the preventive effect and safety for longer-term use is limited. The aim of this study is to assess whether methenamine hippurate can reduce the incidence of UTIs in older women with recurrent UTIs. METHODS AND ANALYSIS: The ImpresU consortium is a collaboration between Norway, Sweden, Poland and the Netherlands. The study is a randomised, controlled, triple-blind phase IV clinical trial. Women ≥70 years with recurrent UTIs are screened for eligibility in a general practice setting. We aim to include 400 women in total, with 100 recruited from each collaborating country. The participants are randomised to treatment with methenamine hippurate 1 g or placebo tablets two times per day for a treatment period of 6 months, followed by a drug-free follow-up period of 6 months. The primary outcome is number of antibiotic treatments for UTIs during the treatment period. The secondary outcomes include number of antibiotic treatments for UTIs during the follow-up period and self-reported symptom of severity and duration of UTI episodes. Differences in complications between the treatment groups are measured as safety outcomes. We also aim to investigate whether strain characteristics or phylogenetic subgroups of Escherichia coli present in the urine culture at inclusion have a modifying effect on the outcomes. ETHICS AND DISSEMINATION: Ethical approvals are obtained in all participating countries. The results will be communicated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04077580); EudraCT: 2018-002235-15.

Application of rapid invisible frequency tagging for brain computer interfaces.

BACKGROUND: Brain-computer interfaces (BCI) based on steady-state visual evoked potentials (SSVEPs/SSVEFs) are among the most commonly used BCI systems. They require participants to covertly attend to visual objects flickering at specified frequencies. The attended location is decoded online by analysing the power of neuronal responses at the flicker frequency. NEW METHOD: We implemented a novel rapid invisible frequency-tagging technique, utilizing a state-of-the-art projector with refresh rates of up to 1440 Hz. We flickered the luminance of visual objects at 56 and 60 Hz, which was invisible to participants but produced strong neuronal responses measurable with magnetoencephalography (MEG). The direction of covert attention, decoded from frequency-tagging responses, was used to control an online BCI PONG game. RESULTS: Our results show that seven out of eight participants were able to play the pong game controlled by the frequency-tagging signal, with average accuracies exceeding 60 %. Importantly, participants were able to modulate the power of the frequency-tagging response within a 1-second interval, while only seven occipital sensors were required to reliably decode the neuronal response. COMPARISON WITH EXISTING METHODS: In contrast to existing SSVEP-based BCI systems, rapid frequency-tagging does not produce a visible flicker. This extends the time-period participants can use it without fatigue, by avoiding distracting visual input. Furthermore, higher frequencies increase the temporal resolution of decoding, resulting in higher communication rates. CONCLUSION: Using rapid invisible frequency-tagging opens new avenues for fundamental research and practical applications. In combination with novel optically pumped magnetometers (OPMs), it could facilitate the development of high-speed and mobile next-generation BCI systems.

Community determinants of COPD exacerbations in elderly patients in Lodz province, Poland: a retrospective observational Big Data cohort study.

OBJECTIVES: To evaluate the prevalence and identify demographic, economic and environmental local community determinants of chronic obstructive pulmonary disease (COPD) exacerbations in elderly in primary care using Big Data approach. DESIGN: Retrospective observational case-control study based on Big Data from the National Health Found, Tax Office and National Statistics Center databases in 2016. SETTING: Primary care clinics in the Lodz province in Poland. PARTICIPANTS: 472 314 patients aged 65 and older in primary care, including 17 240 patients with COPD and 1784 with exacerbations (including deaths). OUTCOME MEASURES: Exacerbations with demographic, economic and environmental local community determinants were retrieved. Conditional logistic regression for matched pairs was used to evaluate the local community determinants of COPD exacerbations among patients with COPD. RESULTS: The overall prevalence of COPD in the population of elderly patients registered in primary healthcare clinic clinics in Lodz province in 2016 was 3.65%, 95% CI (3.60% to 3.70%) and the prevalence of exacerbations was 10.35%, 95% CI (9.89% to 10.80%). The high number of consultations in primary care clinics was associated with higher risk of COPD exacerbations (p=0.0687).High-income patients were less likely to have exacerbations than low-income patients (high vs low OR 0.601, 95% CI (0.385 to 0.939)). The specialisation of the primary care physician did not have an effect on exacerbations (OR 1.076, 95% CI (0.920 to 1.257)). Neither the forest cover per gmina (high vs low OR 0.897, 95% CI (0.605 to 1.331); medium vs low OR 0.925, 95% CI (0.648 to 1.322)), nor location of gmina (urban vs urban-rural OR 1.044; 95% CI (0.673 to 1.620)), (rural vs urban-rural OR 0.897, 95% CI (0.630 to 1.277)) appears to influence COPD exacerbations. CONCLUSIONS: Big Data statistical analysis facilitated the evaluation of the prevalence and determinants of COPD exacerbation in the elderly residents of Lodz province, Poland.Modification of identified local community determinants may potentially decrease the number of exacerbations in elderly patients with COPD.