Aim: Augmented Renal Clearance (ARC) is a common phenomenon among critically ill patients and create sub-therapeutic concentrations of antibiotics, due to an increase in renal clearance of them. We evaluated the Pharmacokinetic and Pharmacodynamic (PK/PD) properties of recommended doses of meropenem in critically ill patients with ARC. Methods: Adult critically ill patients with confirmed ARC, based on 12-hour Creatinine Clearance (CrCl) (≥130 ml/min/1.73 m2), who received standard doses of meropenem enrolled. Two blood samples were gathered from each participant, at the steady-state time, to determination of peak and trough concentrations. Serum concentrations of meropenem were measured by High-Performance Liquid Chromatography (HPLC) with Ultra-Violet (UV) detector. Results: From eighteen paired samples (peak and trough concentrations) that were obtained from 16 critically ill patients, peak concentrations were significantly lower in group 1 (received meropenem 1g every 8 hours) than group 2 (received meropenem 2g every 8 hours) (mean ±SD, 5.95 ±3.39 µg/mL vs. 11.93± 4.18 µg/mL, respectively, p= 0.005). Trough concentration were sub-threshold (< 2 µg/mL) in 10 patients of group 1 (83.3%) and 3 patients of group 2 (50%). ft > MIC ≥ 50% was achieved in 83.3% of patients in both groups whereas 16.6% of patients of group 1 and 33.3% of patients of group 2 had ft> MIC= 100%. Conclusion: ARC is an essential cause of sub-therapeutic concentrations of meropenem in critically ill patients, and higher than the recommended doses of meropenem administered as an intermittent infusion may be necessary to achieve the PD targets and improve efficacy.

OBJECTIVE: To demonstrate that delayed cord clamping (DCC) is safe in mothers with confirmed SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS: Prospective, observational study involving epidemiological information from 403 pregnant women with SARS-CoV-2 between March 1st and May 31st, 2020. Data were collected from 70 centers that participate in the Spanish Registry of COVID-19. MAIN OUTCOMES AND MEASURES: The rate of perinatal transmission of SARS-CoV-2 and development of COVID-19 disease in neonates at day 14 of the delivery. RESULTS: The Early cord clamping (ECC) group consisted of 231 infants (57.3%), whereas the DCC group consisted of 172 infants (42.7%). A total of 5 positive cases (1.7% of total tests performed) were identified with the nasopharyngeal PCR tests, 2 from the ECC group (1.7%) and 3 from the DCC group (3.6%). No significant differences between groups were found regarding neonatal tests for COVID-19. No confirmed cases of vertical transmission were detected. The percentage of mothers who made skin-to-skin contact within the first 24 hours after delivery was significantly higher in the DCC group (84.3% versus 45.9%). Breastfeeding in the immediate postpartum period was also significantly higher in the DCC group (77.3% versus 50.2%). CONCLUSIONS: The results of our study have been similar to early cord clamping practices, no skin-to-skin contact, and suppression or delay of breastfeeding. FUNDING: This study was fully funded with public funds from the Institute of Health Carlos III and co-financed with FEDER funds. KEYWORDS: COVID-19, umbilical cord clamping, skin-to-skin, breastfeeding, vertical transmission, safety.

Background and aim of the study The single- and double-patch repairs are the most commonly used techniques for the surgical management of partial anomalous pulmonary venous connection associated with sinus venosus atrial septal defect. The aim of this study was to retrospectively compare early and long-term surgical outcomes in pediatric and adult patients, focusing in particular on the occurrence of postoperative rhythm disturbances. Methods 115 patients (male: 63, 54.8%) underwent surgical repair for partial anomalous pulmonary venous connection with sinus venosus atrial septal defect. 80 patients (70.4%) underwent surgical repair in pediatric age (<16 years old), while 35 (29.6%) patients were operated in adulthood. 49 patients (42.6%) underwent single-patch repair and 65 patients (56.5%) underwent double-patch repair. In only one patient the Warden procedure was performed (0,9%). Median follow-up time was 52 months (IQ 15.1-113). Results The type of surgical technique didn’t affect the overall incidence of all rhythm disturbances (41% in single patch group and 35% in double patch groups, p=0.5). At long-term follow-up, ectopic atrial rhythm, as expression of sinoatrial node disturbance, was however significantly more frequent in the pediatric population (32% pediatric group and 8% adult group, p=0.02). Conclusions The higher incidence of ectopic atrial rhythm in children is probably related to the closer relationship of the sinus node to the superior cavo-atrial incision, which makes iatrogenic traumatism more likely to occur. Surgical techniques that avoid any manipulation on the superior cavo-atrial junction should therefore be preferred for children undergoing partial anomalous pulmonary venous connection repair.

Foliar water uptake (FWU) may be a significant way for trees to obtain water; however, studies are lacking on FWU. To determine whether FWU occurs in Platycladus orientalis growing in seasonally arid areas, the process of FWU under soil water content (SWC) of 3.9–6.5%, 6.5–9.1%, 9.1–15.6%, 15.6–20.8%, and 20.8–26.0% and different precipitation gradients (1/mm, 5 mm/h, 10 mm/h, and 15 mm/h) was studied using precipitation with labeled isotopes in simulated rainfall experiments with indoor potted plants. The results showed that FWU occurred in each treatment if the SWC ≤ 21.9% no matter the amount of precipitation. The absorption rate of rainfall by leaves increased with the increase of rainfall intensity, but decreased with the increase of SWC. The greatest rates of FWU were 2.77% and 9.52% of rainfall intensity of 1 mm/h and 15 mm/h, respectively, in the 3.9–6.5% treatment. The precipitation absorbed by the leaves of P. orientalis can be transported to xylem or root system along the water potential gradient of leaves–branches–roots. The precipitation with reverse migration in branches and roots increased with the increase of the water potential gradient of leaves–branches–roots. This study provided insight into water use patterns and water migration within trees.

To the Editor: Bronchial asthma is characterized by restricted airflow due to chronic airway inflammation, and frequent lower respiratory viral infections in early life are a significant risk factor for development of the disease. Previous studies demonstrated that anti-viral interferon (IFN) production, including of IFN-α, IFN-β and IFN-λ, by leukocytes and bronchial epithelial cells can be impaired in asthma patients.1 An epidemiological study found that allergic sensitization precedes wheeze during asthma development in children, suggesting that Type 2 (T2) conditions play a key role in the impaired anti-viral IFN production. Furthermore, a prospective cohort study showed that, regardless of the type of virus, each successive lower respiratory viral infection with wheeze increases the risk of asthma by about 1.5 fold.2 However, we still don’t have a full understanding of the precise mechanism(s) of how respiratory viral infections under T2 conditions lead to development of asthma.A meta-analysis of large-scale genome-wide association studies revealed that both IL-33 and its receptor, IL-33 receptor(IL-33R ; also known as ST2 ), are closely associated with asthma development.3 Indeed, IL-33 expression was reportedly increased in rhinovirus-infected bronchial epithelial cells and correlated significantly with the disease severity of asthma.4 This suggests that virus-induced IL-33 in the airway may be fundamentally involved in the mechanistic links between viral infection and development and/or exacerbation of asthma. In addition, impairment of anti-viral IFN production was reported to cause necrosis—but not apoptosis—of the virus-infected epithelium,5 which results in release of bioactive IL-33.MicroRNAs (miRNAs) are small, non-coding RNA molecules (containing about 22 nucleotides) that are found in diverse organisms. miRNAs regulate expression of a broad spectrum of target genes through RNA silencing and/or post-transcriptional regulation. Among them, microRNA-29a (miR-29a) was induced by respiratory syncytial virus (RSV) infection in a human lung adenocarcinoma cell line, A549, and suppressed expression of IFN (α, β and ω) receptor 1 (IFNAR1).6 Furthermore, miR-29a regulated the expression of soluble ST2 (sST2), a decoy receptor for IL-33, in human tenocytes.7 Based on those earlier findings, we focused on miR-29 in the present study. We hypothesized that T2 cytokine induces miR-29 expression in bronchial epithelial cells, leading to suppression of both sST2 release and IFNAR1 expression by epithelial cells, and culminating in asthma development and/or exacerbation.Based on that hypothesis, we first examined whether T2 cytokine and inflammatory cytokine induced sST2 production in a human bronchial epithelial cell line, BEAS-2B. The detailed methods are described in Supporting Information. Specific ELISA showed that IL-4 and TNF-α synergistically induced sST2 release from BEAS-2B, in a dose-dependent manner (Figure 1A). Next, to examine the effects of miR-29 overexpression or inhibition on that cytokine-induced sST2 release, BEAS-2B cells were first transfected with miR-29 mimics or inhibitors for 24 hours and then stimulated with a combination of IL-4 and TNF-α for 48 hours.The human miR-29 family consists of three mature members, i.e., miR-29a, miR-29b, and miR-29c. These miR-29s are encoded by the miR-29a/b-1 cluster on chromosome 7q32.3 and the miR-29c/b-2 cluster on chromosome 1q32.2, respectively (Figure 1B).8 The three family members share an identical seed sequence (Figure 1B), and their functional properties are thought to be similar. We examined the effects of miR-29a and miR-29b in this study. ELISA of the culture supernatants showed that inhibition of miR-29a or miR-29b significantly enhanced cytokine-induced sST2 release (Figure 1C). In contrast, overexpression of miR-29a or miR-29b almost completely inhibited that release, indicating that these miR-29s regulate sST2 release from bronchial epithelial cells under T2 conditions. Of note, neither inhibition nor overexpression of miR-29a or miR-29b had any effects on the protein levels of the ST2 receptor in the BEAS-2B cells (Figure 1D, upper panel). These results suggest that T2 cytokine-induced miR-29 plays a critical role in IL-33-dependent allergic inflammation through regulation of sST2 release from bronchial epithelial cells.Furthermore, transfection of either miR-29a or miR-29b inhibitors significantly enhanced IFNAR1 protein expression in the BEAS-2B cells (Figure 1D, middle panel), which is consistent with earlier findings for miR-29a in A549 cells.6 Conversely, transfection of miR-29 mimics resulted in reduced IFNAR1 expression in BEAS-2B cells, suggesting that overproduction of miR-29s in bronchial epithelial cells may lead to suppression of antiviral responses by IFNs. Thus, we found that miR-29s simultaneously regulate the expression of both sST2 and IFNAR1 in bronchial epithelial cells. Our findings suggest the possibility that T2 cytokine-induced miR-29s in airway epithelial cells are key players in the development and/or exacerbation of asthma triggered by respiratory viral infections through both decreasing IFN-regulated antiviral activities and exacerbating IL-33-dependent allergic inflammation.miRNAs are released from cells into the extracellular environment via exosomes, which can then fuse with target cells. This process can deliver various proteins and nucleic acids, including miRNAs, into even distant target/receiving cells.9 We, therefore, examined whether exosomes similarly export miR-29s from bronchial epithelial cells. BEAS-2B cells were stimulated with a combination of IL-4 and TNF-α for 48 hours, and exosomal fractions were collected from the culture supernatants. Although qPCR detected both miR-29a and miR-29b in the exosomes even without that T2 cytokine stimulation (control), both of their copy numbers were significantly increased by that stimulation (Figure 2A). Furthermore, Western blot analysis also found that expression of CD81, an exosome marker, was enhanced by the cytokine stimulation (Figure 2B). These results suggest that T2 cytokine-stimulated epithelial cells release more exosomes containing more miR-29s than unstimulated cells.This study has several limitations. First, no functional experiments were performed in this study to confirm the effects of the changes in sST2 release or IFNAR1 expression. In addition, we did not measure the expression levels of miR-29s in clinical samples.Figure S1 summarizes our findings as a schematic illustration of bronchial epithelial cells. Based on those findings, we hypothesize that elevated nasal, bronchial and/or exosomal levels of miR-29s in infancy may be useful biomarker(s) for predicting later development of asthma, and further studies are needed. Our data suggest a new perspective that miRNAs are crucially involved in the association between viral infection and asthma development. We believe that our research has great significance in pointing to a novel direction for further studies and the existence of a new key player, i.e., miRNAs, in the relationship between viral infections and asthma development.

The Gerbode defect is a special type of ventricle septum defect causing a communication between the left ventricle and right atrium. In this article, we present a rare case of 2-year-old congenital Gerbode defect. The location of this defect was special, just at the interventricular septum between the tricuspid and mitral valve. She underwent the closure of the defect with an autologous pericardial patch in station of mild hypothermic cardiopulmonary bypass.

Background: Patients with cardiovascular disease are more susceptible to coronavirus disease 2019 (COVID-19) and have worse outcomes when infected. This study reports the largest and most comprehensive echocardiographic evaluation of patients with severe COVID-19 at a quaternary care hospital in the second most affected state in the US, New Jersey. Methods: Clinical, biochemical and echocardiographic features of consecutive patients with severe COVID-19 undergoing echocardiography were studied. Clinical outcome data including length of stay, requirement of mechanical ventilation and in-hospital mortality were collected. Results: 987 patients with confirmed COVID-19 infection were treated at our institution of which 146 consecutive patients (15%) underwent echocardiographic evaluation. Median age was 63 years ;37% were females, 21% had known CAD and 20% had CKD. 57% of patients required mechanical ventilation and 50% required vasopressors . 31% of patients died during the index hospitalization. There was a high prevalence of echocardiographic abnormalities including right ventricular dilation (33%) or dysfunction (21%), left ventricular dysfunction (20%), and pericardial effusion (13%). Multiple biomarkers including troponin T, pro BNP, dimer and CRP were strongly associated with echocardiographic abnormalities and in-hospital mortality. On Cox regression analysis, age (HR 1.04/year) and CAD (HR 2.4) were independent predictors of mortality. Conclusions: Severe COVID-19 infection is accompanied by a significant burden of echocardiographic abnormalities that are strongly correlated with higher degrees of inflammation and biomarker elevation. Additional investigation is warranted in assessing the role of a biomarker-guided approach for early cardiac surveillance using echocardiography in further risk stratifying patients and tailoring adjunctive therapy.

Background Although genome-wide association studies (GWAS) represent the most powerful approach for identifying genes that influence asthma, no studies have established the genetic susceptibility to asthma in the Korean population. To identify genetic variants associated with adult Korean asthmatics and compare them with the significant single nucleotide polymorphisms (SNPs) of UK asthmatics from UK Biobank. Methods Asthmatic patients were defined as having asthma if they were diagnosed by a doctor or taking medications for asthma. Controls were defined as having no asthma and chronic obstructive pulmonary disease. We performed the quality controls, genotype imputation, GWAS, and PrediXcan analysis. In GWAS, P value < 5×10-8 is considered significant. We compared significant SNPs between Korean asthmatics and UK asthmatics. Results A total of 1,386 asthmatic patients and 5,205 controls were analyzed. The SNP rs1770, located near human leukocyte antigen (HLA)-DQB1, was the most significant SNP (P=4.5×10-10). In comparison with 24 SNPs in GWAS of UK asthmatics, 6 SNPs were significant with the same odds ratio direction, including signals related to type 2 inflammation (e.g., IL1RL1, TSLP, and GATA3) and mucus plugging (e.g., MUC5AC). HLA-DQA1 showed an opposite odds ratio direction. HLA-DQB1 gene demonstrated significant imputed mRNA expression levels for lung tissue and whole blood. Conclusions The SNP rs1770 of HLA-DQB1 was the most significant SNP in Korean asthmatics. There were similarities and discrepancies in genetic variants between Korean and UK asthmatics. The GWAS of Korean asthmatics should be replicated and compared with those of GWAS of other ethnicities.

Inflammation is a complex pathophysiological process associated with atherosclerosis, cancers, diabetes, osteoporosis, rheumatoid arthritis, cardiovascular and autoimmune diseases. In this review, we represent an overview of microbial-derived compounds, and nanomaterial with anti-inflammatory activity and compare their efficiency, mode actions, and limitations. This paper aims to provide an insight on possible approaches to expand the chemical space of anti-inflammatory drugs. The micro-based approach through the discovery of new anti-inflammatory compounds from microorganisms and nano-based approach through the augmentation by nanomaterials are among the main suggested natural and chemical resources to provide new anti-inflammation drugs in the future. Furthermore, some nanomaterials by improving the anti-inflammatory properties of commercial drugs or microbial compounds through enhancing their solubility, decreasing unfavorable effects, donating excellent targeting, allowing a lower dosage, and providing substitute less-invasive delivery routes, have shown their indirect anti-inflammatory activity. Additionally, the efficiency of existing drugs can also be modulated by using new synergistic anti-inflammatory compounds from microorganisms or modification/augmentation by nanomaterials. This will aid in designing new nano and bio-based medications for the prevention and treatment of numerous inflammation related-debilitating diseases.

Background Asthma in children is a heterogeneous disease manifested by various phenotypes and endotypes. The level of disease control as well as the effectiveness of anti-inflammatory treatment is variable and inadequate in a significant portion of patients. Objectives By applying machine learning algorithms, we aimed to predict treatment success in a pediatric asthma cohort and to identify key variables for understanding underlying mechanisms. Methods We predicted treatment outcomes in children with mild to severe asthma (N=365), according to changes in asthma control, lung function (FEV1, MEF50) and FENO values after 6 months of controller medication use, using RandomForest and AdaBoost classifiers. Results The highest prediction power is achieved for control- and, to lower extend, for FENO-related treatment outcomes. The most predictive variables for asthma control are related to asthma severity and total IgE, which was also predictive for FENO-based outcomes. MEF50-related treatment outcomes were better predicted than FEV1-based response and one of the best predictive variables for this response was hsCRP. Conclusions Our results suggest that asthma control- and FENO-based outcomes can be more accurately predicted using machine learning than FEV1 and MEF50. This supports the symptom control-based asthma management approach and its complementary FENO-guided tool in children. T2-high asthma seemed to respond best to anti-inflammatory treatment. The prediction of MEF50-based treatment outcomes emphasizes the role of the distal airways in childhood asthma. The results of this study in predicting treatment success will help to enable treatment optimization and to implement the concept of precision medicine in pediatric asthma treatment.

To the Editor, A COVID-19 epidemic started in China and then disseminated to other Asian countries before becoming a pandemic. It appears that the pandemic has so far resulted in proportionately fewer deaths in China and most Eastern Asian countries. Many reasons can explain this picture.1 One of them is the type of diet in the low mortality countries. 2This paper is the sixth of a series attempting to understand the role of diet in the differences of COVID-19 death rates between and within countries with the aim to identify potential preventive measures against COVID-19. The concept paper 2 was followed by two ecological studies comparing death rates in European countries and the consumption of vegetables or fermented foods. 3,4 We then proposed that sulforaphane from cruciferous vegetables1 and lactobacilli from fermented foods (submitted) were possibly involved in the reduction of insulin resistance in COVID-19.It is noteworthy that fermented foods are largely used in Asia.5,6 It is therefore important to check whether some commonly eaten fermented foods in these countries may explain geographic differences in COVID-19. Kimchi will be used as a model of fermented cabbage.

Rationale. Evidence-based practice (EBP) can improve health care in underprivileged countries. Bolivia’s EBP movement is nascent and the factors contributing to better implementation in nursing are unknown. Aim. To explore Bolivian nurses’ readiness to engage in EBP while highlighting the facilitators and barriers for pursuing EBP. Method. International collaborators used a sequential explanatory mixed methods study. First, general trends were disclosed via a survey of 170 nurses in La Paz, Bolivia, holding at least a baccalaureate regarding their perceived beliefs about EBP. The survey identified facilitators and barriers for implementing EBP in acute and ambulatory settings. Second, qualitative data was gathered via a focus group of nine nurses with the purpose of enhancing the survey findings. Results. The survey results showed that nurses believe that engaging in EBP can improve their clinical practice. However, the nurses’ research behaviors were found to be infrequent. Lack of support from the nurses’ clinics and hospitals and from non-nursing professionals were identified as barriers for engaging in EBP. The qualitative results revealed underlying limitations to nurses’ clinical practice, including “feeling undervalued.” Conclusions. There is a dearth of EBP knowledge among Bolivian nurses stemming from a lack of preparation in EBP environments, including EBP training opportunities. This situation affects nurses’ professional dimensions of relational work, power, and collaboration. Collaborative research among educators, professional nursing societies, and local and international organizations could provide initiatives for implementing EBP, based on local health profiles. Key words: international collaboration, evidence-based practice, nurse-multidisciplinary relationship, barriers to EBP.

Background: The doctor-patient relationship in China is getting worse in the recent years. The aim of our study is to evaluate the effect of evidence-based medicine (EBM) on the communication between residents and patients and the doctor-patient relationship. Methods: The residents were evaluated before learning process. Then the residents in the experimental group were asked to answer a list of questions they may encounter during communication with patients before interacting with patients. Residents in the control group received traditional empirical education. Each resident was graded by a questionnaire filled by patients and senior doctors. The final test was given in the form of standardized-patient (SP) test, and the resident is graded by the SP and the examiner with the same questionnaire. Results: After studying, grades in all types of disease significantly improved in group B. Both after study and in the final test, group B performed much better than group A in all kinds of diseases. Conclusion: This is the first study to explore whether the doctor-patient relationship can be improved by EBM utilized in residents’ daily communication with patients. Based on our results, the new method can benefit the residents in their long-term professional work, and can relieve the tension of relationship between doctors and patients in China.

ABSTRACT Rationale, aims and objectives The primary aim of the study was to understand the mindset of doctors and pharmacists, as they embark upon prescribing in a polypharmacy and multi-morbidity context during routine practice at a hospital acute admissions unit. The study also aimed to evaluate to what extent attitudes, embedded within real-life decision-making scenarios, relate to existing theory and models of prescribing decisions. Methods Anonymised case studies were identified from the medical notes of patients aged 65 and over with conditions likely to be associated with multi-morbidity, medication issues and polypharmacy: namely: fall, urinary tract infection, confusion or lower respiratory tract infection. A total of 39 doctors based on the acute medical admissions unit and 9 pharmacists were recruited to one of three focus groups. Patient case-studies provided the context for discussion from which verbatim transcripts were thematically analysed using an interpretative, qualitative approach. Sub-themes were matched to Murshid and Mohaidin’s proposed model of physician prescribing decisions. Results Seven principal themes were identified that were associated with prescribing decisions on the acute medical unit, namely, ‘patient characteristics’, ‘drug characteristics’, ‘pharmacist factors’, ‘trustworthiness’, ’reliability of medication history, ‘competing pressures and priorities’ and ‘responsibilities of prescribers’. Conclusion Prescribing decisions on the acute medical admissions unit were influenced by a variety of factors, some of which have already been acknowledged within existing theories and models. The findings provisionally offer new insights, which, subject to confirmation by further research, bring to light three attitudinal characteristics that may impact negatively upon the quality of prescribing decisions. These include, first, how perceived poor reliability of medication history may result in information gaps that compromise prescribing decisions; second, how competing pressures and priorities restrict doctors’ aptitude to conduct a review of medication and finally, how doctors may rationalise the assignment of medication review to the GP.

Thrombotic microangiopathies (TMAs) are a group of rare disorders that can be considered life threatening. The hallmark of this disease is a microangiopathic hemolytic anemia with an associated thrombocytopenia which could be congenital or acquired. Acquired vitamin B12 deficiency is overlooked in developed countries but can mimic a TMA. We report the case of 17-year-old male with malabsorption of vitamin B12 with development of pseudo-TMA. When faced with a clinical presentation of a TMA in a child or an adolescent patient, physicians must be aware of the possibility of vitamin B12 deficiency especially in patients at risk for malabsorption.

The world has been under terror of another morbid viral pandemic which is a virus belongs to the corona virus family as SARS-COV2 (Severe acute respiratory syndrome-corona virus) related to previously existing SARS-COV (Severe acute respiratory syndrome) and MERS-COV (Middle East respiratory syndrome). It is considered to be zoonotic in origin as it is transmitted from animals to human. It presents crown like morphology with spike like protein which adheres to the surfaces of the body mainly in respiratory system. Mild symptoms like fever, dry cough, and body pain, loss of smell and taste, headache, shortness of breath appear on exposure to virus leading to major symptoms damaged lungs and drop in oxygen saturation. Pharmacological drug trials and various nutritional therapies are being used to prevent the symptoms of the infection. Researchers are developing proper vaccination to cure the infection.

Langerhans Cell Histiocytosis (LCH) is characterized by activating variants of the MAPK pathway. Inhibition of the MAPK pathway with trametinib (MEK inhibitor) has been shown to induce responses in LCH patients. Two adolescent males with LCH driven by BRAF p.N486_P490del have received trametinib for >1 year with no reactivation in one and partial response in another (including stable lung disease). A third male with neonatal LCH and MAP2K1 p.K57_G61del had a complete response to trametinib with no active disease after 22 months. All patients continue on trametinib monotherapy with tolerable skin and CPK toxicity.

Background: Mucositis is a common side effect of cancer therapies and transplant conditioning regimens. Management of mucositis involves multiple approaches from oral hygiene, anti-inflammatory, anti-apoptotic, cytoprotective and antioxidant agents, to cryo-, physical therapy, and growth factors. There is room for novel, affordable treatment options or improvement of currently available therapies. Vitamin D (Vit D) has been shown to regulate mucosa- resident cell populations such as Th17 or innate lymphoid cells and critical mucosal cytokine IL-22, however their therapeutic potential has not been put to test in preclinical mouse models. In this study, we aimed to test the therapeutic potential of Vit D injections and IL-22 overexpression in a murine model of chemotherapy-induced mucositis. Methods: Balb/c mice were given daily intraperitoneal injections of Vit D. Another group received IL-22 plasmid via hydrodynamic gene delivery. Mucositis was induced by methotrexate. Weight loss, intestinal histopathology and IL-22, IL-17A and GM-CSF protein levels in intestinal tissue were measured. Intestinal Il23, Ifng, Tnfa and Il10 gene expression were analyzed by real-time qPCR. Intestinal lamina propria B cell, neutrophil and total innate lymphoid cells were quantified. Results: Daily Vit D injections significantly ameliorated intestinal inflammation and elevated intestinal IL-22 levels compared with control groups. Temporal overexpression of IL-22 by hydrodynamic gene delivery slightly increased intestinal IL-22 but failed to confer significant protection from mucositis. Conclusion: To our knowledge, this is the first experimental demonstration in animal model of mucositis that Vit D and IL-22 supplementation may be beneficial and warrants further trials in human patients.

Background and Purpose Glycyrrhizic acid (GA) is a major triterpene glycoside isolated from liquorice root that has been shown to inhibit osteoclastogenesis. However, there have been no reports regarding the effect of GA on osteogenic differentiation. Therefore, this study was performed to explore the effects and mechanism of action of GA on osteogenesis. Experimental Approach A CCK-8 array was used to assess cell viability. The osteogenic capability was investigated by real-time quantitative PCR, western blotting and immunofluorescence analyses. ALP staining and ARS were used to evaluate ALP activity and mineralisation, respectively. GA-GelMA hydrogels were designed to verify the therapeutic effects of GA in vivo by radiographic analysis and histological evaluation. Key Results Our results show that GA had no significant influence on the viability or proliferation of human bone mesenchymal stem cells (hBMSCs). GA promoted osteogenic differentiation and enhanced calcium deposition. Furthermore, levels of active β-catenin protein increased after treatment w ith GA. Wnt/catenin signalling inhibitor partially reversed the effects of GA on osteogenic differentiation. In a mouse femoral fracture model, GA-GelMA hydrogels accelerated bone healing. Conclusion and Implications Our results show that GA promotes the osteogenic differentiation of hBMSCs by modulating the Wnt/β-catenin signalling pathway. GA-GelMA hydrogels promoted bone fracture healing. GA has potential as a cost-effective treatment of bone defects.

Background and purpose: Alpha 7 nicotinic acetylcholine receptors (CHRNA7) suppress inflammation through diverse pathways in immune cells, so is potentially involved in a number of inflammatory diseases. However, the detailed mechanisms underlying CHRNA7’s anti-inflammatory effects remain elusive. Experimental approach: The anti-inflammatory effects of CHRNA7 agonists in both murine macrophages (RAW 264.7) and bone marrow-derived macrophages (BMDM) stimulated with LPS were examined. The role of adenylyl cyclase 6 (AC6) in Toll-like Receptor 4 (TLR4) degradation was explored via overexpression and knockdown. A mouse model of chronic obstructive pulmonary disease was used to confirm key findings. Key results: Anti-inflammatory effects of CHRNA7 were largely dependent on AC6 activation, as knockdown of AC6 considerably abnegated the effects of CHRNA7 agonists while AC6 overexpression promoted them. We found that CHRNA7 and AC6 are co-localized in lipid rafts of macrophages and directly interact. Activation of AC6 led to the promotion of TLR4 degradation. Administration of CHRNA7 agonist PNU282987 attenuated pathological and inflammatory end points in a mouse model of chronic obstructive pulmonary disease (COPD). Conclusion and implications: CHRNA7 inhibit inflammation through activating AC6 and promoting degradation of TLR4. The use of CHRNA7 agonists might represent a novel therapeutic approach for treating COPD and likely other inflammatory diseases.

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.

Gout is the best known type of arthritis with a prevalence of 1-3% in the western world [1,2]. Although well understood there is growing evidence of the misdiagnosis of gout from other forms of arthritis. These errors lead to delay in accurate diagnosis and in appropriate care [2]

The effect of COVID-19 is not limited to the respiratory system. Patients who are at risk to develop cardiac arrhythmias might be affected especially when unmasked with fever. A 41-year-old Bangladeshi male patient presented with frequent palpitations and dizziness. His ECG revealed Brugada pattern while being diagnosed with COVID-19.

Objectives: Given that 30-50% of children with Down syndrome have persistent obstructive sleep apnea (OSA) after adenotonsillectomy, we evaluated whether demographic, clinical and polysomnographic factors predicted persistent OSA and OSA severity after adenotonsillectomy. Design: Retrospective study. Setting: Secondary care hospital. Participants: Retrospective review of 32 children with the diagnosis of DS and OSA by polysomnography type 1 who underwent adenotonsillectomy, from January 2010 to December 2018. Main outcome and measure: Non-parametric analysis was used to compare pre and postoperative factors, regression was used to model persistent OSA and OSA severity. Results: Thirty-two children were included (17 male, median age 10.00 ± 8.00 years, median body mass index z-score 0.89 ± 1.25). Overall, adenotonsillectomy resulted in a significant improvement in median obstructive apnea-hypopnea index (oAHI) from 7.5 ± 8.95 to 4.40 ± 4.38 events per hour (p<0.001) and in median OSA-18 score from 85.00 ± 12.00 to 61 ± 37.75 (p<0.001). Persistent OSA was found in 56.25% of the children. Univariate regression suggests that postoperative OSA-18 score predicted persistent OSA after adenotonsillectomy. Preoperative oAHI, preoperative oxygen desaturation rate, pre and postoperative OSA-18 scores correlated with OSA severity after adenotonsillectomy. However, in a multivariate model only the postoperative OSA-18 score was able to predict OSA severity after adenotonsillectomy. Conclusions: Although adenotonsillectomy results in a significant improvement of OSA in children with Down syndrome, more than half of the children had persistent OSA. The postoperative OSA-18 score predicted both persistent OSA and OSA severity after adenotonsillectomy.