With its broad antimicrobial spectrum and non-specific mode of action via membrane disruption, any resistance to octenidine (OCT) seems unlikely and has not been observed in clinical settings so far. In this study, we aimed to investigate the efficacy of OCT against Escherichia coli and mutants lacking specific lipid head groups which, due to altered membrane properties, might be the root cause for resistance development of membrane-active compounds. Furthermore, we aimed to test its efficacy under different experimental conditions including different solvents for OCT, bacterial concentration and methods for analysis. Our primary goal was to estimate how many OCT molecules are needed to kill one bacterium. We performed susceptibility assays by observing bacterial growth behavior, using a Bioscreen in an analogous manner for every condition. The growth curves were recorded for 20 h at 420–580 nm in presence of different OCT concentrations and were used to assess the inhibitory concentrations (IC100%) for OCT. Bacterial concentrations given in cell numbers were determined, followed by Bioscreen measurement by manual colony counting on agar plates and QUANTOMTM cell staining. This indicated a significant variance between both methods, which influenced IC100% of OCT, especially when used at low doses. The binding capacity of OCT to E. coli was investigated by measuring UV-absorbance of OCT exposed to bacteria and a common thermodynamic framework based on Bioscreen measurements. Results showed that OCT’s antimicrobial activity in E. coli is not affected by changes at the membrane level but strongly dependent on experimental settings in respect to solvents and applied bacterial counts. More OCT was required when the active was dissolved in phosphate or Hepes buffers instead of water and when higher bacterial concentration was used. Furthermore, binding studies revealed that 107–108 OCT molecules bind to bacteria, which is necessary for the saturation of the bacterial surface to initiate the killing cascade. Our results clearly demonstrate that in vitro data, depending on the applied materials and the methods for determination of IC100%, can easily be misinterpreted as reduced bacterial susceptibility towards OCT.

The human papillomavirus (HPV) is a non-enveloped double-stranded DNA virus capable of infecting skin and mucosa epithelial cells. Commonly, HPV infection is associated with sexually transmitted diseases and is considered the leading cause of cervical cancer and other carcinomas of the anogenital tract. However, several studies reported their involvement in cancers of non-sexual regions, including colorectal, head and neck, and breast cancers. There are several studies from the Middle East and North Africa (MENA) regions on the potential association between high-risk HPVs and cancer; nevertheless, there are limited studies that address the significance of HPV vaccination as a potential guard against these cancers. In the current review, we present a comprehensive description of the current HPV-associated cancers prevalence rates in the MENA region, demonstrating their steady increase with time, especially in African regions. Moreover, we discuss the potential impact of vaccination against HPV infections and its outcome on human health in this region.

Background: Iron deficiency (ID) and anemia in patients with Inflammatory Bowel Disease (IBD) are associated with a reduced quality of life. We assessed the prevalence of ID and anemia in Dutch outpatients with IBD and compared routine ID(A) management among medical professionals to the European Crohn’s and Colitis Organisation (ECCO) treatment guidelines. Methods: Between January and November 2021, consecutive adult outpatients with IBD were included in this study across 16 Dutch hospitals. Clinical and biochemical data were extracted from medical records. Additionally, medical professionals filled out questionnaires regarding routine ID(A) management. Results: In total, 2197 patients (1271 Crohn’s Disease, 849 Ulcerative Colitis, and 77 IBD-unclassified) were included. Iron parameters were available in 59.3% of cases. The overall prevalence of anemia, ID, and IDA was: 18.0%, 43.4%, and 12.2%, respectively. The prevalence of all three conditions did not differ between IBD subtypes. ID(A) was observed more frequently in patients with biochemically active IBD than in quiescent IBD (ID: 70.8% versus 23.9%; p < 0.001). Contrary to the guidelines, most respondents prescribed standard doses of intravenous or oral iron regardless of biochemical parameters or inflammation. Lastly, 25% of respondents reported not treating non-anemic ID. Conclusions: One in five patients with IBD suffers from anemia that—despite inconsistently measured iron parameters—is primarily caused by ID. Most medical professionals treat IDA with oral iron or standard doses of intravenous iron regardless of biochemical inflammation; however, non-anemic ID is often overlooked. Raising awareness about the management of ID(A) is needed to optimize and personalize routine care.

Background and objectives: the aim of this study was to analyse the utilisation of proton pump inhibitors (PPIs) during a 12-year period and to show the characteristics and patterns of their prescribing. Materials and methods: firstly, in the pharmacoepidemiological analyses the ATC/DDD methodology was used to assess the utilisation of PPIs in the Republic of Srpska. The annual PPI utilisation was expressed as a number of DDD/1000 inhabitants/year. Secondly, the cross-sectional surveys were used to reveal the characteristics of PPIs prescribing and medicines use, namely the dose, duration and indication, and possible adverse reactions. For the purposes of the surveys, the adapted version of questionnaires related to physicians’ and patients’ perspectives of medicines prescribing and use were performed. Results: the utilisation of medicines for alimentary tract and metabolism (group A/ATC classification) increased by almost threefold in a 12-year period, which was consistent with the total medicine utilisation. Pantoprazole was the most prescribed medicine among the PPIs. With the exclusion of PPIs in the therapy of Helicobacter pylori eradication, more than half of family physicians prescribed PPIs with antibiotics, and only 53/239 physicians, noticed some adverse reactions of PPIs in their patients. Most of the patients knew how to use PPIs and were taking these medicines in recommended daily doses, but approximately 45% of them were using PPIs for a long period of time (>6 months). Conclusions: the overuse of PPIs is a major concern due to potential serious adverse reactions, especially in elderly patients and in a case of prolonged exposure.

As a typical Internet of Things application, network traffic prediction (NTP) plays a decisive role in congestion control, resource allocation, and anomaly detection. The trend of network traffic is different at different scales, so multiscale is an important characteristic of network traffic. In addition, the network traffic is nonlinear on each scale and dependent between scales. The existing NTP methods cannot comprehensively consider these characteristics, which limits their performance. In view of the characteristics of network traffic, such as multiscale, nonlinearity, and scale dependence, this article proposes a new multiscale NTP method based on a deep echo-state network (ESN). First, a multiscale parallel layered structure based on deep ESN is designed to fully consider the influence of each scale on the prediction result and then reduce the prediction error. Second, a feature extraction algorithm is proposed to improve the nonlinear approximation ability by extracting more abundant dynamic features with multiple reservoirs. Third, an NTP model based on scale dependence is proposed to reduce the influence from partial scale missing and then improve the prediction accuracy. Finally, simulation results demonstrate that compared with the state-of-the-art NTP methods, the proposed method significantly improves the prediction performance of network traffic with a slight increase in running time.

Introduction Left ventricular thrombus (LVT) is a common complication in patients with systolic heart failure and can cause thromboembolic consequences including stroke. In order to determine the characteristics of LV thrombus among heart failure patients with reduced ejection fraction (HFrEF), the present study was undertaken. Methods and Materials This was retrospective cross-sectional study conducted from referral tertiary hospital in a year period. A total of 810 transthoracic echocardiograms were carried out in our center from January 2021 to December 2021. Forty participants had met the inclusion criteria of the study. Results About 75% of the population was male and the mean age at diagnosis was 51 years (SD: 15). Ischemic cardiomyopathy and dilated cardiomyopathy (DCMP) found to be the most underlying cause of LVT represented (57.5% and 42.5% respectively). Hypertension, hypothyroidism, and atrial fibrillation were found to be the commonest associated risk factors of LVT, 45%, 12.5%, and 30% respectively. Simpson’s Biplane’s approach yielded a mean LVEF of 25.25 ± 6.97. 60% of the patients had a LVEF of ≤25%. The mean LV end-diastolic and end-systolic diameters were 59.2 ± 9.4 mm and 51 ± 8.3mm respectively. Warfarin was administered to 19 (47.5), Rivaroxaban to 8 (20), and Dabigatran to 10 (25). The most prevalent anticoagulant among the individuals in our study was warfarin. A stroke complication was found in 8 patients (20%), two of them were hemorrhagic stroke and they were on dabigatran. A Peripheral Arterial Disease (PAD) affected 6 of the patients (15%). One of those with PAD had also ischemic stroke. Conclusion This study determines that Ischemic and Dilated cardiomyopathy were the most common cause of left ventricular thrombosis among HFrEF patients in Somalia.

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia leading to a five-fold increased risk of stroke. Timely detection of AF is important for the initiation of appropriate therapy and the prevention of adverse outcomes such as AF-related stroke. The aim of this pilot study was to assess the use of a photoplethysmography (PPG)-deriving smartphone application (app) for early detection of AF and initiation of appropriate treatment to avoid AF-related complications such as stroke 1,2 . Patients and Methods: Participants were instructed to perform heart rhythm measurements twice daily and when experiencing symptoms for 7 days using a PPG-deriving smartphone application. All participants with possible AF based on the results of the

Background Adoptive T cell therapy as a treatment for solid tumours is gaining increasing interest. Cancer neoantigens as targets for such therapy is also gaining recognition. Personalised tumour trained lymphocytes (pTTL) is a novel autologous T cell therapy targeting patient-specific neoantigens. A phase I/ II First in Human (FIH) clinical trial of pTTL in Stage IV colorectal cancer (CRC) patients will be initiated in the near future. Methods pTTL is produced through in vitro expansion of T cells derived from regional lymph nodes (RLNs). The T cells derived from RLNs, nodes in anatomical proximity of the tumour, contain a pool of naive and antigen-experienced T cells enriched for tumour-antigen specificity. This enriched population is stimulated during pTTL production with an array of neoantigen epitopes individually designed using PIOR ® , an in house-developed software for neoantigen detec-tion and selection. Selected neoantigens are linked to paramag-netic particles using EpiTCer ® technology. The resulting EpiTCer ® particles are used to stimulate the RLN T cells via phagocytosis and presentation of the neoantigen epitopes by antigen-presenting cells. This process is HLA-independent. Each pTTL product is unique due to the personalised nature of cellular and molecular players (cancer characteristics, immune cell properties and neoantigens are specific to one single individual).