Newly research associate the severity of Covid-19 with obesity and the rise in prothrombotic markers like D-Dimers. As Covid-19 is considered an immunothrombotic disease, the potential benefits of estrogen-free contraceptives like drospirenone are discussed. Adding estrogens in contraception my rise the cardiovascular risk in Covid-19 and Long Covid patients.

Nodular posterior scleritis needs to be differentiated from other simulating intraocular pathology to prevent misguided treatment. Multimodal imaging aids in the diagnosis of this rare entity. We report a case of nodular posterior scleritis managed with corticosteroid therapy with complete resolution.

A 71-year-old man with gallbladder adenocarcinoma and no history of dyslipidemia presented with serum triglyceride level of 912 mg/dL after two months of starting Capecitabine. The lipemia due to elevated triglyceride also led to hemolysis, causing analytical interference to other biochemical tests and complete blood count.

Background: Parotidectomy is commonly performed as an inpatient procedure due to drain insertion. However recent evidence suggests that drainless outpatient parotidectomy is a safe option with comparable postoperative complication and hospital readmission rates to inpatient parotidectomies. Objective: Patient satisfaction on outpatient parotidectomy is unclear and this study aims to report patients’ perspective and satisfaction on drainless outpatient parotidectomy. Design, participants and outcome measures: Anonymous Core questionnaire for the assessment of Patient Satisfaction’ (COPS) for general Day care (COPS-D) questionnaire survey was completed by patients who underwent drainless same day parotidectomy at Ninewells Hospital, Dundee from June 2018 to October 2020. Patient satisfaction on different aspects of their outpatient parotidectomy journey (e.g. pre-admission, admission on ward, in-theatre experience, nursing care, pain control and overall satisfaction) were scored using a five-point Likert scale. Results: A total of 31 drainless outpatient parotidectomies were performed and 28 patients completed the patient satisfaction survey. The majority of patients were highly satisfied (i.e. scored 5/5) with their preadmission visit (79.5%), admission on the ward (84.5%), operating room experience (96.4%), nursing care (83.9%), medical care (87.5%), information received (75.0%), autonomy (79.8%) and discharge and after care (61.9%). Despite preferring drainless parotidectomy, 16/28 (57.1%) patients either stayed for less than 23 hours or preferred to stay overnight in the hospital for non-surgical reasons. Conclusion: Outpatient parotidectomy is well received by patients and the majority preferred drainless parotidectomy over inpatient parotidectomy with drains. Careful consideration should be given when selecting patients for day case parotidectomy.

Extended exposure to low pO2 has multiple effects on signaling cascades. Despite multiple exploratory studies, specific studies elucidating the response of lung and plasma proteome in context of surviving low pO2 exposures are lacking. In this study, we simulated low pO2(PB=40 kPa; 7620 m) exposure in male Sprague-Dawley (SD) rats for 3, 7 and 14 days. Redox stress assays and proteomics were performed using lung and plasma followed by protein network analyses. We observed that redox homeostasis was achieved after day 3 of exposure. Lung proteome revealed cytoskeletal processes were the most significant with STAT3 acting as upstream regulator. Plasma proteome revealed a focus on lipid metabolism derived inflammatory processes. Overall, during prolonged low pO2 exposure, particularly those involving slowly decreasing pressures, redox homeostasis is achieved but energy metabolism is perturbed and this leads to an immune/inflammatory signaling impetus after 3rd day of exposure. We found that an interplay of lung cytoskeletal elements, systemic energy metabolism and inflammatory proteins aid in achieving redox homeostasis and surviving extended low pO2 exposures. Qualitative perturbations to cytoskeletal stability and innate immunity/inflammation were also observed during extended low pO2 exposure in humans exposed to 14,000 ft for 7, 14 and 21 days.

Atrial, sinoatrial node and atrioventricular node disease with preserved conductivity results in tachy-bradycardia syndrome.(1) Tachy-bradycardia syndrome has been reported in fetuses with the missense variant p.(Gly482Arg) in HCN4 gene.(2) Atrial ectopics and junction ectopic tachycardia were reported in fetuses with autoimmune atrioventricular block.(3,4) An unusual dominant involvement of sinoatrial node in a fetus presenting with tachy-bradycardia syndrome of Anti-SSA/SSB-Positive mother.

In this article, we introduce a new concept of quantum integrals which is called $^{\kappa_{2}}T_{q}$-integral. Then we prove several properties of this concept of quantum integrals. Moreover, we present several Hermite-Hadamard type inequalities for $^{\kappa_{2}}T_{q}$-integral by utilizing differentiable convex functions. The results presented in this article are unification and generalization of the comparable results in the literature.

A NOVEL GENETIC ALGORITHM APPROACH TO THE MAXIMUM INDEPENDENT SET PROBLEM

A 7-year-old boy was diagnosed with RUNX1-RUNX1T1-positive acute myeloid leukemia. Although he achieved complete remission (CR) after conventional chemotherapy, he experienced relapse 6 months after completing initial treatment. The cytoplasm of myeloblasts examined at relapse contained pink giant granules. These myeloperoxidase-positive granules were considered to be pseudo-Chediak-Higashi (PCH) granules. Meanwhile, blasts had acquired genetic alterations such as hypotetraploidy with RUNX1-RUNX1T1 and C-MYC amplification, and a KIT N822K mutation. The patient underwent cord blood transplantation and maintains a second CR. A previous report suggests that C-MYC amplification might be associated with PCH granule formation, and our case supports this hypothesis.

Although many therapies have been proposed, there is no evidence of any effective treatment for COVID-19 to date. Currently, the main therapies being used to treat the critically patients with COVID-19 are antiviral drugs, chloroquine/hydroxychloroquine and respiratory therapy. Pharmacokinetics (PK) and pharmacodynamics (PD) play an important role in different clinical situations, and are keys to balance the effect (reduction of SARS-CoV-2 virus and symptom improvement) and toxicity (adverse effects). Critically ill patients always have altered PK and PD due to multiple factors such as hypoproteinemia, organ dysfunction, and organ support treatment including continuous renal replacement therapy (CRRT), and extracorporeal membrane oxygenation (ECMO). Here we provide an overview of the effects of the clinical treatments for critically COVID-19 patients and the pathological state of patients on pharmacokinetics and pharmacodynamics parameters of therapeutic drugs in detail. However, current evidence is insufficient to speculate the changes of drug concentration of antimicrobials, therapeutic drug monitoring (TDM) is a useful tool used in severe patients since many suspected factors were exist to influence the clinical responses and adverse drug reactions of drugs.

Objectives: To propose new causal structures to clarify the structures and mechanisms of measurement bias (MB). Methods: We propose a new structure for measuring one singleton variable firstly, and then extend it into clarifying the effect between an exposure and an outcome, aided by the Directed Acyclic Graphs (DAGs). Results: The MB for one singleton variable arises in the selection of an imperfect I/O device-like measurement system only. For effect estimation, however, extra source of MB arises from any redundant association between a measured exposure and a measured outcome. The misclassification will be bidirectionally differential for a common outcome, unidirectionally differential for a causal relation, and non-differential for a common cause or an independence, between the measured exposure and the measured outcome. The measured exposure can actually affect the measured outcome, or vice versa. Reverse causality is a concept defined at the level of measurement. Conclusions: Measurement extends the causality from real world to human thinking. MB has two origins: an imperfect measurement system and any redundant association at the measurement level. Our new DAGs have clarified the structures and mechanisms of MB.

Fucoxanthin is a xanthophyll carotenoid with high market value. Currently, seaweeds are the primary feedstock for fucoxanthin industrial production. However, marine microalgae reach 5 to 10 times higher concentrations (2.24 to 26.6 mg g-1 DW), and are considered a promising source. In this work, two marine microalgae were produced at industrial scale to evaluate biomass and fucoxanthin production; Phaeodactylum tricornutum for autumn/winter and Tisochrysis lutea for spring/summer. Both strains were grown in 15 m3 tubular flow-through photobioreactors, for 170 consecutive days, in semi-continuous cultivation regime. The average volumetric biomass productivities of P. tricornutum and T. lutea were 0.11 and 0.09 g DW L-1 day-1. P. tricornutum reached higher maximum biomass concentration (2.87 g DW L-1) than T. lutea (1.47 g DW L-1). This is the first work in literature reporting a long-term industrial production of T. lutea. P. tricornutum fucoxanthin content ranged between 0.2 and 0.7 % DW, while T. lutea between 0.2 and 0.6 % DW. The fucoxanthin content was correlated with the irradiation (MJ m-2) and the biomass concentration in the photobioreactor (g L-1). Overall, this work shows possible scenarios for fucoxanthin production from microalgae, increasing the window to supply the industry with steady production throughout the year.

Abstract Purpose. To investigate the mechanisms of macrophage pyroptosis mediated by TLR4/NLRP3/GSDMD signaling pathway in adjuvant arthritis (AA) rats and the role of Paeoniflorin-6′-O-benzene sulfonate (CP-25). Experimental Approach. AA model was induced in Wistar rats via complete Freund’s adjuvant. Normal group, AA model group, CP-25 (50 mg/kg) group and MTX (0.5 mg/kg) group were included in this experiment. The co-expression of TLR4 and NLRP3 and membrane expression of GSDMD and NLRP3 in macrophages were detected by immunofluorescence assay. The expression of TLR4, the ratio of macrophage pyroptosis and M1/2-type macrophages were detected by Flow Cytomery. Cell morphology was observed by scanning electron microscopy. The levels of IL-18 and IL-1β cytokines in plasma and supernatant of cultured macrophage were detected by ELISA. The expression of TLR4, MyD88, NLRP3, Caspase-1, ASC and GSDMD in macrophages was detected by Western Blot. Key Results. Macrophage pyroptosis was found in AA rats; CP-25 has a therapeutical effect on AA rats by improving the joint inflammation and reducing the pathological process of the joints of AA rats; CP-25 can inhibit the pyroptosis of macrophages by down-regulate the expression of TLR4, MyD88, NLRP3, Caspase-1, ASC and GSDMD of macrophages in vivo; CP-25 inhibits LPS and ATP-induced macrophages pyroptosis by inhibiting the activation of TLR4/NLRP3/GSDMD signaling pathway in vitro. Conclusion and Implications. Macrophage pyroptosis was mediated through TLR4/NLRP3/GSDMD signaling pathway, and CP-25 can regulate macrophage pyroptosis by inhibiting TLR4/NLRP3/GSDMD signaling pathway, thereby improving synovitis in AA rats.

Commercial apple production relies on managed honey bees for pollination, and on intensive management for pest control. Previous studies revealed the detrimental effects of these factors on wild bee diversity in agroecosystems, and the pollination services they provide. However, the extent to which honey bee dominance and management interact under field-realistic conditions to shape wild communities has never been investigated. We measured the species richness and functional and phylogenetic diversity of wild bees associated with apple blossoms, in 46 organic and non-organic orchards, and along a climatic gradient across Western Europe and Morocco. Our results consistently show a strong and negative association between honey bee dominance and all diversity indices, regardless of local practices and surrounding landscape cover. Collectively, we show that wild bee diversity decreases with increasing honey bee density, with alternative management practices (i.e., organic) having no significant influence on wild bee communities in commercial apple orchards.

Backgroud: Tyrosine kinase inhibitors (TKIs) has gradually replaced HSCT as the first-line treatment for pediatric patients with chronic-phase Chronic myeloid leukemia (CML-CP). However, there are few reports detailing the long-term effect and safety of TKIs in Chinese children with CML-CP. Procedure: A total of 58 patients (43 children and 15 adolescents) with newly diagnosed CML-CP received imatinib mesylate (IM) as first-line therapy and 2G-TKIs as second-line therapy. The responses and safety to TKI therapy, and the rates of overall survival (OS), progression-free survival (PFS) and event-free survival (EFS) were assessed. Results: After 3 months of IM treatment, 91.4% (53/58) of patients achieved complete hematologic response (CHR). Fifty-one patients received further IM treatment for up to 12 months, and 88.2% (45/51) of them achieved major cytogenetic response (MCyR), with 68.6% (35/51) achieving complete cytogenetic response (CCyR). The cumulative incidence of achieving major molecular response (MMR) was 45.1% (23/51) and 66.0% (31/47) after 12 months and 18 months from initial IM treatment, respectively. Sixteen patients were switched to second-generation TKIs (2G-TKIs), dasatinib (n=8) and nilobinib (n=8), due to lack of response to IM treatment. Among them, 11 patients (68.8%) achieved MMR at a median time of 3.7 months. With a median follow-up duration of 44.8 months, the 9-year overall survival rate (OS) was 81.1%, the 9-year progression-free survival rate (PFS) was 80.5%, and the 9-year event-free survival rate (EFS) was 44.4%. Conclusion: IM as first-line therapy and 2G-TKI as second-line therapy are effective long-term therapeutic measures for children and adolescents in CML-CP.

Object: Hodgkin lymphoma (HL) is one of the pediatric and adult cancers, with treatment of chemotherapy alone or combined with radiotherapy (RT). Considering the complications of RT, we aimed to evaluate the consequences and outcomes of the treatment with and without RT in a retrospective study. Method: We carried a cross-sectional retrospective study by referring and review of records for all patients admitted in Motahari hospital with HL diagnosis from 1995 to 2016. The staging of disease was classified by the Ann Arbor staging system. Results: 35 patients enrolled in our study that 54.3% were female and 45.7% were male patients. The mean age of patients was 10.08±6.38 years. 10 (28.6%) cases classified in stage 1, 13 (37.1%) case in stage 2, 9 (25.7%) cases in stage 3, and 3 (8.6%) cases in stage 4. 30 patients (85.7%) were treated by chemotherapy and 5 (14.3%) patients with chemotherapy and radiation combination. In our study, the overall survival was 97.1% of patients who treated with chemotherapy alone and one patient died due to drug side effects. That is comparable with the result of other studies that treated patients with chemotherapy and radiotherapy. Conclusion: According to our findings chemotherapy without radiotherapy as initial treatment in Hodgkin lymphoma would have similar results of concomitant radiotherapy and chemotherapy, so with consideration of cost and harms of radiation therapy, we suggest a limitation of radiation therapy to patients with resistant disease that do not respond to chemotherapy solo-protocols.

Vasculitis is considered a hidden factor for many pathological conditions, and thus, there is a need to develop a distinctive animal model to aid drug testing. Studies reported that the adjunct use of antigens, ovalbumin, and lipopolysaccharide exaggerates inflammation. However, to date, none has established the effect of Ova and LPS individually or in combination in vasculitis induction. The study aimed to investigate the effect of ovalbumin and lipopolysaccharide on vasculitis induction in rats. The rats were sensitized with Ova and challenged with LPS. The sensitization and challenge in rats have shown a significant increase in circulating inflammatory cells, Erythrocyte Sedimentation Rate (ESR), Inflammatory cytokines (IL-1β, IL-6, and TNF-α), C-reactive protein (CRP), ANCA (Anti-MPO, Anti-PR3), liver function enzymes (AST, ALT), kidney damage markers (BUN, Creatinine) in the serum. MMP-9 level was significantly increased in the temporal, carotid, aorta, iliac, mesentery, and coronary arteries. We also found the disease control group developed hematuria and proteinuria, which was incomparable to the normal control. Furthermore, the histopathology suggested significant neutrophil infiltration with fibrinoid necrosis, indicating vascular injury and hyperplasia, resulting in extracellular matrix degradation. Thus, we conclude that the ovalbumin and lipopolysaccharide, in combination, have developed vasculitis like conditions, which suggest OVA-LPS as a possible new experimental model for vasculitis and could be considered in future therapeutic studies.

Objective: To investigate the subsequent fertility in women with a history of caesarean scar pregnancy Design: Observational study Setting: Tertiary hospital in China Sample: 149 women treated for caesarean scar pregnancy were followed up for five years. Methods: 53 women had unprotected sexual intercourse attempting to become pregnant again, while most women did not even attempt to conceive. Data including clinical parameters and treatment options at the time of diagnosis, and the outcomes in subsequent pregnancy were collected. In addition, a questionnaire about the menstrual cycle after treatment was voluntarily completed by these women. Main Outcome Measures: The outcomes of subsequent fertility from 53 women were analyzed. Results: Of the 53 women, 46 (84%) women had a subsequent pregnancy, while 7 (14%) women did not. There was no difference in clinical parameters in previous caesarean scar pregnancy or treatment options between the two groups. From the questionnaire, there was no difference seen in the length of the menstrual cycle and menses between the two groups. However, a higher number of women with light menstrual bleeding was seen in women without a subsequent pregnancy (67%), compared with women who did (27%). Furthermore, 6 women (13%) who had a subsequent pregnancy experienced missed miscarriage in the first trimester. Conclusion: We reported that 14% of women treated for cesarean scar pregnancy did not have a subsequent pregnancy, after unprotected sexual intercourse. Light menstrual bleeding after treatment may be one of the reasons for this adverse effect. Our findings need to be further investigated.

Abstract BACKGROUND AND PURPOSE The multi-tyrosine kinase inhibitor sunitinib malate is associated with cardiotoxicity through inhibition of 5’adenosine monophosphate protein kinase (AMPK) signalling. Here we demonstrate the cardioprotective properties of metformin limiting the adverse cardiotoxic effect of sunitinib. EXPERIMENTAL APPROACH Heart rate (HR), left ventricular developed pressure (LVDP), coronary flow (CF), infarct size, and phosphorylated-AMPKα levels were measured in the rat Langendorff hearts perfused with 1 µM sunitinib ± 50 µM metformin ± 1 µM human equilibrative nucleoside transporter inhibitor S-(4-Nitrobenzyl)-6-thionosine (NBTI). Isolated cardiac myocytes were incubated with 1 µM sunitinib ± 50 µM metformin ± 1 µM NBTI to determine the live cell population levels. Human hepatoma G2 (HepG2) and promyelocytic leukemia (HL-60) cells were incubated with 0.1-100 µM sunitinib ± 50 µM metformin to determine the cell viability. KEY RESULTS Sunitinib significantly increased the infarct size and decreased the LVDP, while the p-AMPKα level declined. In the cardiac myocytes study, treatment with sunitinib decreased the cell viability. Co-administration of metformin abolished these cardiotoxic effects of sunitinib. Co-administration of NBTI (1 µM) inhibited the cardioprotective effects of metformin. Anti-cancer properties of sunitinib and metformin was recorded using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MTT revealed that co-administration of metformin with sunitinib decreased sunitinib’s antiproliferative properties, evidenced by an increase in EC50 concentration value when compared to sunitinib monotreatment in in-vitro HepG2 and HL60 cell lines. However, metformin co-administration did not inhibit sunitinib’s properties CONCLUSIONS AND IMPLICATIONS This study highlights the novel cardioprotective properties of metformin via AMPK during sunitinib-induced cardiotoxicity.

To predict and mitigate the effects of climate change on communities and ecosystems, the joint effects ofextreme climatic events on species interactions need to be understood.Using the common ragweed (Ambrosia artemisiifolia L.)—leaf beetle (Ophraella communa) system, we investigated the effects of heat wave and elevated CO2 on common ragweed growth, secondary metabolism, and the consequent impacts on the beetle. The results showed that elevated CO2 and heat wave facilitated A. Artemisiifolia growth; further, A. artemisiifolia accumulated large amounts of defensive secondary metabolites. Being fed on A. artemisiifolia grown under elevated CO2 and heat wave conditions resulted in the poor performance of O. communa (high mortality, long development period, low reproduction). Overall, under elevated CO2, heat wave strengthened the defensive ability of A. artemisiifolia to herbivores. Super adaptability to climatic changes may aggravate invasive plant distribution, posing a challenge to the control of invasive plants in the future.

Generalist species are important for maintaining network structure and function. Previous studies showed that interactions between generalists persist across sites and years. However, the mechanisms for persistence across spatiotemporal scales are not clear. To address this gap, we collected data on plant--pollinator interactions throughout the flowering period for five years across six plots in a subalpine meadow. We hypothesized that tolerance of environmental variation across time and space plays a key role in species' generalization by regulating spatiotemporal overlap with partners. We found that interactions between species with broader temporal and spatial distributions tended to be more generalized such that interactions near the network core were more persistent across years and plots and within seasons. These results further understanding of networks by linking the role of environmental variation in time and space in organizing interactions, marrying niche concepts that emphasize species environmental constraints and their role in the community.

A document by Maurizio Mennini. Click on the document to view its contents.

With urbanization and economic development in China, medical needs in urban areas continue to increase, but the building of public hospitals is, however, restricted by available space. As a result, many hospitals have set up multiple campuses, with associated issues such as lack of experience in running a multicampus model, quality standardization, cost control, and culture conflicts. We have four campuses with successful operations. In this paper, we will share our management and operation experiences, which may provide some insights for other hospital managers.

Objective: To provide the latest evidence on the efficacy and safety of Arbidol (Umifenovir) in COVID-19. Methods: A comprehensive systematic search of the evidence was carried out in PubMed, Cochran library, Embase, and Medrxiv up to October 1, 2020. The Cochrane risk of bias tool and Newcastle-Ottawa Scale checklist were used for assessing the quality of studies. Meta-analysis was performed using RevMan (version 5.3). Results: Fifteen studies were met for the inclusion. No significant difference was observed between Arbidol and control groups in terms of primary outcomes, including negative rate of PCR (NR-PCR) on 7 days (risk ratio [RR] 0.89; P=0.37) and 14 days (RR: 1.10;P=0.17), negative conversion time (NCT) (mean difference [MD]: 0.74; P=0.37), and as well as secondary outcomes (P<0.05). Compared with LPV/r, Arbidol showed a better efficacy in terms of NR-PCR on 14 days (P=0.02). In contrast, NCT in LPV/r was higher (P=0.007). However, not significant difference was found in terms of NR-PCR on 7 days (P=0.05). Adding Arbidol to LPV/r was led to a better efficacy in terms of NR-PCR on 7 days and NCT (P<0.05). Nevertheless, it was not significant reading NR-PCR on 14 days (P=0.99). There is no significant difference Arbidol vs. Interferon /Arbidol and IFN/Arbidol vs. Interferon (P<0.05). Conclusion: Arbidol was not superior to control against COVID-19. Additionally, not major treatment effect was found compared with other therapeutic agents. There are needed well-designed studies with large sample size to establish on efficacy and safety of Arbidol.