Rational, aims and objectives: This study aimed to assess knowledge, attitude and practice (KAP) of using insulin pen in diabetes and determine the related factors to the KAP, adverse drug reactions (ADRs) and glycemic control status. Methods: In our descriptive study, 148 patients with diabetes were interviewed by 16-item questions on knowledge and 8 questions on attitude, and were asked to present the insulin pen injection technique with a sample insulin pen. Results: Proportions of patient having a good knowledge, positive attitude, and good practice were 45.9%, 78.4%, and 44.6%, respectively. The three most incorrect steps were skipping to prime pen needle (90.9%), not removing the used needle from the pen after using (87.8), and not holding for specific count time before withdrawal of pen needle from skin (50.7%). Patients having duration of insulin one year or more had better knowledge (p=0.025), more positive attitude (p=0.017), and better practice of insulin (p=0.042). Patients using insulin combined with oral diabetic medications or having history of using insulin vials had more positive attitude of insulin role (0.038). Frequency of having good knowledge was statistically significantly higher in participants who received counseling from health professionals previously (p=0.001). The study also found a positive correlation between good knowledge of patients and good practical skills (p<0.001). Patients with poor practice of insulin were more likely to have ADRs at the injection sites (p = 0.013). The worse knowledge of patients was significant related to the higher risk of hypoglycemia (p=0.001). KAP levels did not correlate with glycemic control status. Conclusions: Positive attitude in patients was recorded at a significant rate; however, knowledge and practice needs improvement. This study was helpful to shape the patient education and target specific patients for education.

Personalized health monitoring and prediction have become essential for improving health- care delivery, especially with the growing prevalence of chronic diseases and an aging population. Deep learning (DL) has emerged as a promising approach for developing personalized health mon- itoring systems that can predict health outcomes accurately and efficiently. With the increasing availability of personal health data, DL-based methods have emerged as a promising approach to improve healthcare delivery by providing accurate and timely predictions of health outcomes. This article provides a comprehensive review of the recent developments in the application of DL for personalized health monitoring and prediction. It summarizes various DL architectures and their applications for personalized health monitoring, including wearable devices, electronic health records, and social media data. Furthermore, the article also explores the challenges and future directions for the application of DL in personalized health monitoring. valuable insights into the potential of DL for personalized health monitoring and prediction.

The stability of plant biomass production in the face of environmental change is fundamental for maintaining terrestrial ecosystem functioning, as plant biomass is the ultimate source of energy for nearly all life forms. However, most studies have focused on the stabilizing effect of plant diversity, neglecting the effect of soil biodiversity, the largest reservoirs of biodiversity on Earth. Here we investigated the effects of plant and soil biodiversity on the temporal stability of biomass production under varying simulated precipitation in grassland microcosms. Soil biodiversity loss reduced temporal stability by suppressing asynchronous responses of plant functional groups. Greater plant diversity, especially in terms of functional diversity, promoted temporal stability, but this effect was independent of soil biodiversity loss. Moreover, multitrophic biodiversity, plant and soil biodiversity combined, was positively associated with temporal stability. Our study highlights the importance of maintaining the biodiversity of multiple trophic levels for sustainable biomass production.

G protein-coupled receptors modulate a plethora of physiological processes and mediate the effects of one-third of FDA-approved drugs. Notably, depending on which ligand has activated a particular receptor, it can engage different intracellular transducers. This paradigm of ligand-dependent ‘biased signaling’ dictates a need to advance beyond the level of receptors to consider the combined ligand-receptor pair in order to understand physiological signaling. Bias signaling also has the potential to improve medicines by reducing adverse effects. However, this is challenged by inconsistent interpretation of results and lack of commonly agreed guidelines. Here, we present recommended terminology and guidelines to conduct, report and quantify bias in a comparable and reproducible fashion. We expect these recommendations will facilitate a common understanding of experiments and findings across basic receptor research and drug discovery, while the area and the analytical methods to measure bias are still evolving, especially in complex cellular, tissue and organismal systems.

Aim: In this study, we aimed to define the predictive role of liver function tests at admission to the hospital in outcomes of hospitalized patients with COVID-19. Material and Method: In this multicentric retrospective study, a total of 269 adult patients (≥18 years of age) with confirmed COVID-19 who were hospitalized for the treatment were enrolled. Demographic features, complete medical history, and laboratory findings of the study participants at admission were obtained from the medical records. Patients were grouped regarding their ICU requirements during their hospitalization periods. Results: Among all 269 participants, 106 were hospitalized in the intensive care unit (ICU) and 66 died. The patients hospitalized in ICU were older than patients hospitalized in wards (p=0.001) and expired patients were older than alive patients (p=0.001). Age, elevated serum D-dimer, creatinine, and gamma-glutamyl transferase (GGT) levels at admission were independent factors predicting ICU hospitalization and mortality in COVID-19 patients. Conclusion: In conclusion, in hospitalized patients with COVID-19, laboratory data on admission, including serum, creatinine, GGT and d-dimer levels have an important predictive role for the ICU requirement and mortality. Since these tests are readily available in all hospitals and inexpensive, some predictive formulas may be calculated with these parameters at admission, to define the patients requiring intensive care.

Background: Homologous and heterologous SARS-CoV-2 vaccinations yield different spike protein-directed humoral and cellular immune responses. This study aimed to explore their currently unknown interdependencies. Methods: COV-ADAPT is a prospective, observational cohort study of 417 healthcare workers who received vaccination with homologous ChAdOx1 nCoV-19, homologous BNT162b2 or with heterologous ChAdOx1 nCoV-19/BNT162b2. We assessed humoral (anti-spike-RBD-IgG, neutralizing antibodies, avidity) and cellular (spike-induced T cell interferon‑γ release) immune responses in blood samples up to 2 weeks before (T1) and 2 to 12 weeks following secondary immunization (T2). Results: Initial vaccination with ChAdOx1 nCoV-19 resulted in lower anti-spike-RBD-IgG compared to BNT162b2 (70±114 vs. 226±279 BAU/ml, p<0.01) at T1. Booster vaccination with BNT162b2 proved superior to ChAdOx1 nCoV-19 at T2 (anti-spike-RBD-IgG: ChAdOx1 nCoV-19/BNT162b2 2387±1627 and homologous BNT162b2 3202±2184 vs. homologous ChAdOx1 nCoV-19 413±461 BAU/ml, both p<0.001; spike-induced T cell interferon-γ release: ChAdOx1 nCoV-19/BNT162b2 5069±6733 and homologous BNT162b2 4880±7570 vs. homologous ChAdOx1 nCoV-19 1152±2243 mIU/ml, both p<0.001). No significant differences were detected between BNT162b2-boostered groups at T2. For ChAdOx1 nCoV-19, no booster effect on T cell activation could be observed. We found associations between anti-spike-RBD-IgG levels (ChAdOx1 nCoV-19/BNT162b2 and homologous BNT162b2) and T cell responses (homologous ChAdOx1 nCoV-19 and ChAdOx1 nCoV-19/BNT162b2) from T1 to T2. Additionally, anti-spike-RBD-IgG and T cell response were linked at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2. Conclusions: Interdependencies between humoral and cellular immune responses differ between common SARS-CoV-2 vaccination regimes. T cell activation is unlikely to compensate for poor humoral responses. 

Objective To explore and describe what women who have given birth in Norway emphasise as important aspects of care during childbirth. Design The study is based on data from the Babies Born Better survey, version 2, a mixed-method online survey. Setting The maternity care system in Norway. Study population Women who gave birth in Norway between 2013 and 2018. Method Descriptive statistics were used to describe sample characteristics and to compare data from the B3 survey with national data from the MBRN, using SPSS® software (version 20). The open-ended questions were analysed with an inductive thematic analysis, using NVIVO 12® software. Main outcome measures Themes developed from two open-ended questions. Results The final sample included 8,401 women. There were no important differences between the sample population and the national population with respect to maternal age, marital status, parity, mode of birth and place of birth, except for the proportion of planned homebirths. Four themes and one overarching theme were identified; Compassionate and Respectful Care, A Family Focus, Continuity and Consistency, and Sense of Security, and the overarching theme Coherence in Childbearing. Conclusions Socio-cultural and psychological aspects of care are significant for women in childbirth, alongside physical and clinical factors. Caring for the woman implies caring for her partner and having a baby is about ‘becoming a family or expanding the family’. Childbirth is a continuous experience in women’s lives and continuity and consistency are important for women to maintain and promote a coherent experience.

Acute respiratory distress syndrome (ARDS) is a disabling and potentially lethal syndrome requiring prompt recognition and urgent interventions to prevent morbidity and mortality[1]. Although constipation is not generally recognized as a cause for ARDS or usually listed within the differential diagnosis, there have been case reports describing such an association[2,3]. We present the case of a patient with history of intermittent constipation presenting with progressive abdominal pain and an acute abdomen that required emergent surgical fecal decompaction. This was followed by hypoxemic respiratory distress leading to respiratory failure in the setting of severe constipation and aspirated feculent material. To our knowledge, this is the first published case report describing aspirated feculent material in a child with respiratory failure due to ARDS.

Thermobifida fusca cutinase ( TfC ) is a carboxylesterase (CE) that degrades the environmental pollutant, polyethylene terephthalate (PET). TfC also acts upon PET’s degradation intermediates (DIs), such as oligoethylene terephthalate (OET), and bis-/mono-hydroxyethyl terephthalate (BHET/MHET), to convert these into terephthalic acid (TPA), the terminal product of PET degradation. We examined TfC’s surface, compared it to that of other CEs, and performed molecular docking and MD simulations with an OET, 2HE-(MHET) 3, to understand interactions between TfC’s surface and the OET, at TfC’s active site as well as vicinal regions. We mutated 17 residues on TfC’s surface, mostly individually, but sometimes using pairs of mutations, to see how these modulate TfC’s activity. Most mutants/variants showed a decrease in activity against solid PET. Some killed activity completely. However, three mutations (L90F, F209I and F249R), made using a background mutation (G62A) already reported to improve activity by almost ~2.0-fold, yielded increases in activity that were between ~1.3- and ~2.0-fold higher than that of G62A TfC (which we found to display a ~1.7-fold increase in activity over TfC, in our own experiments). TfC variants, G62A/F249R, and G62A/F209I, exhibit the highest activities yet observed in any TfC mutants/variants, against PET, and BHET, respectively.

Background and Purpose: Individualized assessment of the activity of cytochrome P450 2D6 (CYP2D6), a highly variable drug-metabolizing enzyme, is performed through phenotyping during which a probe drug is administered to measure the enzyme’s activity. In order to avoid any iatrogenic harm (allergic drug reaction, dosing error) related to the probe drug, the development of non-invasive tools for real-time phenotyping of CYP2D6 could significantly contribute to the expansion of precision medicine in clinical practice. This study focuses on the identification of endogenous markers of the CYP2D6 enzyme in human biofluids using a liquid chromatography (LC)-high-resolution mass spectrometry (HRMS)-based metabolomics approach. Experimental Approach: Data from a control session were compared to data from an inhibition session. Before the latter, healthy volunteers (extensive and ultrarapid metabolizers) received a daily dose of paroxetine 20 mg over seven days. CYP2D6 genotyping and phenotyping, using single oral dose of dextromethorphan 5 mg, were also performed in all participants. Key Results: In CYP2D6 extensive and ultrarapid metabolizers (n = 37), mean relative intensities of five features were significantly reduced during the inhibition session compared to the control session (fold changes ≤ 0.67, FDR-adjusted P < 0.0001). Furthermore, mean relative intensities of these candidates were significantly higher in the CYP2D6 extensive-ultrarapid metabolizer group (n = 37) compared to the poor metabolizer group (n = 6) (fold changes ≤ 0.67, P < 0.0001). Conclusion and Implications: The applied untargeted metabolomics strategy was able to identify five CYP2D6 endogenous metabolites, a promising discovery for non-invasive phenotyping and personalised medicine.

Background and Purpose: Many psychotherapeutic drugs, including clozapine, display polypharmacology and act on GABAA receptors. Patients with schizophrenia show alterations in function, structure and molecular composition of the hippocampus, and a recent study demonstrated aberrant levels of hippocampal a5 subunit-containing GABAA receptors. The purpose of this study is to investigate tricyclic compounds in a5 subunit-containing receptor subtypes.Experimental Approach: Functional studies of effects by seven antipsychotic and antidepressant medications were performed in several GABAA receptor subtypes by two‐electrode voltage‐clamp electrophysiology using Xenopus laevis oocytes. Computational structural analysis was employed to design mutated constructs of the a5 subunit, probing a novel binding site. Radioligand displacement data complemented the functional and mutational findings. Key Results: We show that the antipsychotic drugs clozapine and chlorpromazine exert functional inhibition on multiple GABAA receptor subtypes, including a5-containing ones. Based on a chlorpromazine binding site observed in a GABA-gated bacterial homologue, we identified a novel site in a5 GABAA receptor subunits and demonstrate differential usage of this and the orthosteric sites by these ligands.Conclusion and Implications: Despite high molecular and functional similarities among the tested ligands, they reduce GABA currents by differential usage of allosteric and orthosteric sites. The C C C C C C site we describe here is a new potential target for optimizing antipsychotic medications with beneficial polypharmacology. Further studies in defined subtypes are needed to substantiate mechanistic links between the therapeutic effects of clozapine and its action on certain GABAA receptor subtypes.

Smart drainage management to limit summer drought damage in Nordic agriculture under the circular economy conceptSyed Md Touhidul Mustafa 1, *, Kedar Ghag1, Anandharuban Panchanathan2, Bishal Dahal 1, Amirhossein Ahrari1, Toni Liedes 3, Hannu Marttila1, Tamara Avellán1, Mourad Oussalah2, Björn Klöve 1, & Ali Torabi Haghighi11Water, Energy and Environmental Engineering Research Unit, University of Oulu, P.O. Box 4300, FIN90014, Oulu, Finland2Center for Machine Vision and Signal Analysis, University of Oulu, Finland3Intelligent Machines and Systems, University of Oulu, PO Box 4200, 90014 Oulu, Finland

We present a rare case of ectopic pregnancy in a woman using IUD. IUD leads to mild inflammation of uterus, nearby fallopian tube and obstruction in conveyance of ovum. Suspicion of ovarian pregnancy should be considered in a woman using IUD with abdominal pain, vaginal bleeding, positive pregnancy test.

Bladder prolapse is a rare condition in mares and may occur as a result of excessive straining during the parturition or in the postpartum period. We report a case of dystocia associated prolapse and incarceration of the small colon through the external urethral opening into a prolapsed urinary bladder. No previous reports of this condition were found. An 11-year-old Thoroughbred mare was presented to The Equine Hospital at the Jockey Club of Saudi Arabia for evaluation and treatment of dystocia. Prolapse of the urinary bladder was concomitantly diagnosed. Initial assessment deemed replacement of the urinary bladder in the normal position and vaginal delivery not possible. The mare was immediately prepared for caesarean section. The foal was successfully delivered and resuscitated. Detailed assessment of the bladder during the surgery revealed that the small colon had prolapsed through the external urethral opening and was inside the bladder. The urinary bladder was opened. The small colon was replaced into the abdominal cavity; a first surgeon gently replaced the small colon through the external urethral sphincter and a second surgeon retrieved the small colon by gentle traction. The mare recovered uneventfully from general anaesthesia. The mare and the foal were discharged from the hospital seventeen days post-operatively.

Background: The COVID-19 pandemic represents one of the most stressful events of recent times. Among the population, healthcare professionals who treat COVID-19 patients are most likely to develop psychological distress and posttraumatic stress symptoms (PTSS). The present study thus aimed to investigate the psychological impact of the COVID-19 outbreak on Italian healthcare workers. Methods: The responses of 145 healthcare workers (72 medical doctors and 73 nurses) were included in the final dataset. Participants were asked to provide sociodemographic and clinical information, and to complete: 1) quality of life and health-related Visual Analogue Scales, 2) State-Trait Anxiety Inventory-Form Y1, 3) Beck Depression Inventory, and 4) PTSD Checklist for DSM-5. Results: A comparison between healthcare professionals working in COVID-19 wards and other units revealed that the former reported higher levels of both depressive symptoms and PTSS. Moreover, the results of regression analyses showed that in healthcare professionals working with COVID-19 patients, gender and marital status, and gender and age significantly predicted depressive symptoms and PTSS, respectively. Particularly, being female and not in a relationship were found to be associated with higher levels of depressive symptoms, whereas being female and older were found to be related to higher levels of PTSS. Conclusions: The current findings suggest that specific predisposing factors could identify healthcare workers who are at high risk of developing mental health symptoms when faced with COVID-19 patients.

Decoupling and understanding the various mass, charge and heat transport phenomena involved in the electrocatalytic transformation of small molecules (i.e. CO2, CO, H2, N2, NH3, O2, CH4) is challenging but it can be readily achieved using dimensionless quantities (i.e. Reynolds, Sherwood, Schmidt, Damköhler, Nusselt, Prandtl, and Peclet Numbers) to simplify the characterization of systems with multiple interacting physical phenomena. Herein we report the development of a gastight rotating cylinder electrode cell with well-defined mass transport characteristics that can be applied to experimentally decouple mass transfer effects from intrinsic kinetics in electrocatalytic systems. The gastight rotating cylinder electrode cell enables the dimensionless analysis of electrocatalytic systems and should enable the rigorous research and development of electrocatalytic technologies.

Monogenean infection of the internal organs is extremely rare when compared to external infections. This study describes mass mortality of Nile tilapia (Oreochromis niloticus L.) originating from co-infection with Enterogyrus spp. and Aeromonas jandaei following transport stress. The first fish deaths occurred on day 1 post-transport, while cumulative mortality reached approximately 90% by day 10 post-stocking. An atypical amount of pale (whitish) faeces floating on the surface of the water as well as typical clinical signs of motile Aeromonas septicemia, were reported. Adult monogeneans and countless eggs of monogeneans were found in the stomachs and the intestines of both moribund and dead fish, respectively. Two strains of A. jandaei were isolated from the kidneys. Scanning electron microscope microphotographs of the stomach revealed the presence of numerous monogeneans penetrating deep into the gastric tissue, and diffuse lesions filled with bacilliform bacteria. This is the first report of co-infection by Enterogyrus spp. and A. jandaei in Nile tilapia and the first report of E. coronatus, E. foratus, and E. malbergi parasitizing tilapia in Brazil. These findings indicate that synergic co-infection by Monogenean stomach parasites (E. coronatus, E. foratus, and E. malbergi) and A. jandaei may induce high mortalities in tilapia following transport stress.

Background: Chronic spontaneous urticaria is well-described in adults, but less so in children. The aim of this study is to describe the demographics, clinical characteristics, comorbidities, and outcomes of children with chronic, spontaneous urticaria. Methods: This retrospective study followed children up to 18 years-old, diagnosed with chronic spontaneous urticaria, between the years 2002-2018 and treated in a tertiary referral allergy and clinical immunology center. Data including demographics, clinical characteristics, comorbidities, treatments and outcomes was extracted from electronic medical records. Results: Records of 380 children coded to have chronic urticaria were reviewed, of which 250 (65.8%) fulfilled the diagnostic criteria for chronic spontaneous urticaria. There were 136 females (54.4%). Mean age at diagnosis was 11.4 years, 122 (48%) were adolescents. The average duration of chronic spontaneous urticaria was 12.25±15.2 months. The urticaria in 208 children )83.2%) resolved within 24 months. Eighty-seven patients (34.8%) had at least one atopic disease. Atopic comorbidities included atopic dermatitis in 17.2%, allergic rhinitis in 16%, asthma in 13.2% and food allergy in 3.2%. Eighteen patients (7.2%) had a concomitant autoimmune disease. Nine (3.6%) had thyroid disease. Conclusions and clinical relevance: Chronic spontaneous urticaria in children is a self-limited disease with favorable prognosis. Atopic diseases are more prevalent in children with chronic spontaneous urticaria than in the general pediatric population; increasing the possibility of a special subgroup of TH2-related chronic urticaria in children.