The comment by Sánchez-Tójar et al. (2020, Ecol Lett) questioned the methodology, transparency, and conclusion of our study (Yin et al. 2019, Ecol Lett, 22, 1976). The comment has overlooked important evolutionary assumptions in their reanalysis, and the issues raised were in fact dealt with through the peer-review process. Far from being biased, the key conclusion of our meta-analysis still stands; transgenerational effects are largely adaptive.

A series of rigid triphenylamine (TPA) dyes have been designed with the donor (D)-π-acceptor (A) architecture. To screen the acceptor moities, we have design that’s A1 and A2. The design sensitizer to evaluate the parameters such as geometries, electronic structures, and optical properties, along with dipole moment, polarizability and first-order hyperpolarizability were calculated using density functional theory (DFT) and time-dependent DFT (TD-DFT). Photo physical properties like wavelength of maximum absorption (λmax), oscillator strength (f), light harvesting efficiency (LHE) and dipole moment ( ) have been analyzed. Based on the results A2 acceptor moities having good photo physical properties, so this A2 based dyes having good sensitizer for dye sensitized solar cells application.

In order to explore the influence of isotope effect and ligand modification on the quantum yield of OLED, three classes Pt(II) complexes with 2,2’-bipyridine ligand have been investigated by using density functional theory (DFT) and time-dependent density functional theory (TD-DFT). The explored Pt(II) complexes, class 1 included Pt(RC≡CBpyC≡CR)(C≡CBpy)2, (R = trimethylsilyl，1a or H, 1b, C≡CBpyC≡C = 5,5-bis(ethynyl)-2,2-bipyridine, C≡CBpy corresponds to bipyridineacetylene) and Pt(Bpy)(C≡CBpy)2 (Bpy = bipyridine, 1c); class 2, Pt(Bpy)(C≡CPy)2 (C≡CPy = pyridineacetylene, 2a) , Pt(Bpy)(C≡CPh)2 (C≡CPh =phenylethynyl, 2b), Pt(dbBpy)(C≡CPh)2(dbBpy = 4,4’-di-tert-butyl-2,2’-bipyridine, 2c); and class 3, Pt(Bpy)(Tda) (Tda = tolan-2,2’-diacetylide, 3a), Pt(dbBpy)(Tda) (3b), Pt(3,3’,4,4’-OH-Bpy)(Tda) (3c). The calculation results reveal that the heavy isotope effect effectively reduces the overall vibration frequency of these complexes, and in turn decreases the non-radiative decay rate κnr, which lead to the promotion of phosphorescent quantum yield ϕem. Theoretical studies also reveal the influence of ligand modification on the phosphorescence quantum yields of OLED, and a new Pt(II) complex 3c was designed based on the theoretical study.

Abstract Aim: This study was conducted to investigate the role of the miR-210/Caspase8ap2 pathway in apoptosis and autophagy in hypoxic myocardial cells. Methods: The miR-control, miR-210 mimic and miR-210 inhibitor were transfected into rat myocardial H9C2 cells. The transfection efficiency of exogenous miR-210 was determined by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). H9C2 cells were then treated with CoCl2 for 24, 48 and 72 h to generate a myocardial injury model. The apoptosis of H9C2 cells was assessed by flow cytometry. Additionally, a western blot assay was used to determine the expression of the autophagy-associated proteins light chain 3 (LC3), p62 and Beclin-1, and apoptosis-associated proteins Caspase8ap2, cleaved caspase 8 and cleaved caspase 3. Results: We determined that a 48 h hypoxia treatment duration in H9C2 cardiomyocytes induced myocardial injury. Additionally, the overexpression of miR-210 significantly inhibited cell apoptosis. MiR-210 suppressed autophagy by upregulating p62 and downregulating LC3II/I in hypoxic H9C2 cells. Since Caspase8ap2 was a putative target of miR-210, miR-210 mediated apoptosis and autophagy of H9C2 cells via suppressing Caspase8ap2. Furthermore, the expression of caspase 8, caspase 3 and Beclin-1 were decreased in response to miR-210. Conclusion: miR-210 exhibits anti-apoptosis and anti-autophagy effects, which alleviate myocardial injury in response to hypoxia. Keywords: miR-210; Caspase8ap2; myocardial injury; hypoxia; apoptosis; autophagy

Background: Drains are used post-parotidectomy to reduce seroma and haematoma formation. Tissue derived thrombin sealant can enable a drainless procedure, allowing for an earlier discharge, less discomfort and a more cost-efficient method. We aimed to assess whether tissue sealant improves wound-related outcomes in parotidectomy. Method: A systematic literature review was performed using a standardised published methodology and custom database search strategy. A fixed-effect meta-analysis of the combined complications was conducted. Results: Thirteen studies were identified relating to parotidectomies using tissue sealants. Our analysis showed a statistically significant reduction in the complication rates with tissue sealant use, including haematoma and seroma (Odds Ratio 0.59 [0.36, 0.95], 95% CI, I2 =23%, P =0.03). Conclusion: The use of drains post-parotidectomy is superseded by tissue sealant due to the shorter admission time and the lower risk of post-operative complications.

Photovoltaic properties of the natural dyes of chlorophylls consist of Chl a, Chl b, Chl c2, Chl d, Phe a, Phe y and Mg-Phe a, were studied in the gas phases. The extension of the π-conjugated system, the substitution of the central Mg2+ and proper functional groups in the chlorophyll structures can amplify the charge transfer and photovoltaic performance. Chl a shows more favorable dynamics of charge transfer than other studied chlorophylls. Chl d, Phe a, Phe y and Mg-Phe a, have a greater rate of the exciton dissociation in comparison with Chl a, Chl b, and Chl c2 originated from a lower electronic chemical hardness, a lower exciton binding energy, and a bigger electron-hole radius. As a result, better efficiencies of the light-harvesting and energy conversion of the chlorophylls mainly appear in the Soret band. Finally, based on the energy conversion efficiency, Chl a, Phe a, and Mg-Phe a, are proposed as the best candidates for using in the dye-sensitized solar cells.

Background: The SARS-CoV-2 was first reported in December 2019 in Wuhan, China and has been declared a pandemic in March 2020. COVID-19 has caused unprecedented and lasting biopsychosocial effects worldwide. All healthcare professionals have faced life threatening risks by attending their daily jobs. The daily emergence of advice and guidelines was necessary to ensure the safety of patients and staff. To this effect, all elective services came to a halt to preserve hospitals’ capacity for dealing with the sickest. This retrospective, descriptive review aims to assess the volume and timing of the advice released specifically relevant to the UK Otolaryngologist. Methods: The search included online advice published in English by international, national and ENT-specific organisations between the 1st of January to the 31st of May. The date, title, source, type of advice and link to the advice was recorded in Excel. The resources were analysed per week of publication. A separate search for peer-reviewed publications was conducted using PubMed Central and Cochrane databases. Findings: 175 covid-19 related guidance’s were identified. 52/175 (29.7%) articles were published by international organisations. 56/175 (32%) were produced by national organisations and 67/175 (38.28%) were produced by ENT specific organisations. The peak guidance production took place in the third and fourth week of March (16/03/2020- 29/03/2020) with 72/175 publications. Of these, 27/72 came from the international category, 17/72 from national bodies and 28/72 from ENT-specific organisations. 13,863 total publications relating to COVID-19 were found using PubMed and Cochrane search strategies; 76% were relevant to ENT surgeons. Conclusion: The challenges faced by the Otolaryngologist relate to the unprecedented, sudden and daily changes to clinical practice. Multiple bodies interpreted the guidance giving an opportunity for confusion and delays in treatments for patients. Implementing a system with clear lines of communication and dissemination of information will improve our response in future pandemic events whilst maintaining a commercial awareness to better use the human and financial resources of an already financially-restricted NHS.

Objective: To evaluate the risk of lymph node metastasis and figure out necessity of lymphadenectomy in grade 3 endometroid endometrial cancer (EEC) patients. Methods: From 2009 to 2019, 3751 endometrial cancer (EC) patients were diagnosed at Gynecology Hospital of Fudan University, 1235 EEC patients were enrolled in multivariable analysis. 381 patients had survival analysis attributed to sufficient follow-up information. Kaplan-Meier curve and logrank test were used to analyze the survival rate. Results: Among 1235 EEC patients, multivariate analysis showed lymph-vascular invasion (LVSI), adnexal involvement (AI), cervical stroma involvement (CSI) were independent risk factors of lymph node metastasis (LNM) in grade 3 (G3) cohort (OR=3.45, 5.83, 8.93; 95% CI 1.12-10.64, 1.52-22.35, 2.85-28.00 respectively). LNM rates increased from 3.3% to 75% for EEC G3 cohort with the increase of risk factors from one to three. There were no differences between G3 and grade 1&2 (G1&2) in overall survival or progression free survival. Similarly, no survival advantage was found for EEC G3 patients at early stage with different plans of adjuvant treatment. Conclusion: When EEC G3 patients combine with one or more risk factors including LVSI, AI and CSI, lymphadenectomy is recommended. For those with only one factor of G3, it is recommended to evaluate the status of lymph nodes by considering other methods such as sentinel lymph node biopsy technology to avoid overtreatment. Survival analysis showed no difference in EEC G3 cohort compared with G1&2. Also, different plans of adjuvant treatment had no impact on overall survival for EEC G3 patients.

Background: Rectovaginal fistula is a major complication of surgery for deep endometriosis. Objective: To assess whether placement of a biological mesh (Permacol) between the vaginal and rectal sutures reduces the rate of rectovaginal fistula, in patients with deep rectovaginal endometriosis. Study Design: Retrospective, comparative study enrolling patients with vaginal infiltration > 3cm diameter and rectal involvement in two centers. They benefited from complete excision of rectovaginal endometriotic nodules, with or without a biological mesh placed between the vaginal and rectal sutures. Rectovaginal fistula rate was compared between the two groups. Results: 209 patients were enrolled: 42 patients underwent interposition of biological mesh (cases) and 167 did not (controls). 92% of cases and 86.2% of controls had rectal infiltration greater than 3cm in diameter. Cases underwent rectal disc excision more frequently (64.3% vs. 49.1%) and had a lower distance between the rectal stapled line and the anal verge (4.4+/-1.4 cm vs. 6+/-2.9cm). Rectovaginal fistulae occurred in 4 cases (9.5%) and 12 controls (7.2%). Logistic regression analyses revealed no difference in the rate of rectovaginal fistula following the use of mesh (adj OR 0.61, 95%CI 0.2-2.3). A distance < 7cm between the rectal stapled line and the anal verge was found to be an independent risk factor for the development of rectovaginal fistulae (adj OR 16.4, 95%CI 1.8-147). Conclusions: Placement of a biological mesh between the vagina and rectal sutures has no impact on the rate of postoperative rectovaginal fistula formation following excision of deep infiltrating rectovaginal endometriosis.

The clinical rationale of Sacubitril/valsartan for therapeutic treatment in Sars-CoV-2

Background: Borderline ovarian tumors (BOTs) although rare, have shown an increase in the incidence worldwide. Although the survival rate is high, the recurrence rate is estimated to be between 5% and 34%. The objective of this study was to identify risk factors for recurrence of BOTs. Methods: This retrospective multicenter study included 493 patients treated surgically for BOT between January 2001 and December 2018. Results: Thirty-seven patients showed recurrence (group R, 7.5%), while 456 did not (group NR, 92.5%). With an average follow-up of 30.5 months (1-276), the overall recurrence rate was 7.5%. Recurrence rates for the BOT and invasive types were 5.7% (n=28) and 1.4% (n=7), respectively. The mean time to recurrence was 44.1 (3-251) months. Univariate analysis showed that age at diagnosis, type of surgical procedure, histological type, and FIGO stage were factors influencing recurrence. Multivariate analysis showed that the risk factors for recurrence of BOT were conservative treatment (OR=7 [95% CI 3.01-16.23]; p<0.05) and advanced FIGO stage (OR=5.86 [95% CI 2.21-15.5]; p<0.05). Conclusion: To the best of our knowledge, this multicenter study was one of the largest studies on the risk factors for BOT recurrence. Conservative treatment and advanced FIGO stage were identified as risk factors for BOT recurrence. These results reinforce the need for restaging of patients who did not have an optimal initial surgical staging so as not to avoid missing a tumor in the advanced stage. Referral to a surgical oncology center is suggested to optimize overall patient management.

Background and Purpose: Patients with community acquired pneumonia (CAP) may suffer from myocardial injury, which is associated with increased risk of major adverse cardiovascular events (MACE). Corticosteroids are often prescribed to CAP patients, but the relationship between their use, myocardial injury and outcomes in these patients is unknown. Experimental Approach: 541 CAP patients were recruited (334 males; mean age: 71.9±16.2 years). High-sensitivity troponin T (hs-cTnT) was measured at admission, during the hospital stay and at discharge. MACE occurrence was registered during a long-term follow-up. Key Results: Overall, 318 patients (59%) showed hs-cTnT elevation > 99th percentile (>0.014 µg/L). Patients with hs-cTnT elevation were older, more likely to be former smokers, and with a higher prevalence of cardiovascular comorbidities. In a median follow-up of 22.7 months, a multivariable Cox proportional hazard regression analysis showed age, heart failure and the increasing quintiles of hs-cTnT (HR: 2.16; 95% CI: 1.82-2.58; p<0.001) predicted MACE. In-hospital corticosteroid use was found in 137 (25%) patients. Among patients with hs-cTnT >0.014 µg/L at admission, 102 patients (31%) were on corticosteroids and showed lower intra-hospital hs-cTnT increase compared to untreated ones (p=0.003). Among patients with hs-cTnT >0.014 µg/L, corticosteroid-treated patients showed a lower incidence of MACE than untreated ones [29% (27/99) vs. 43% (92/213); p value =0.042]; no effect of corticosteroids on MACE was observed in CAP patients with normal troponin. Conclusion and Implications: The study provides evidence that corticosteroid use is associated with lower increase of hs-cTnT and incidence of MACE in CAP patients.

People with diabetes represent a population at greater risk of infection and complications from Sars-Cov-2 (COVID-19), Diabetes represents one of the most important comorbidities related to the severity of viral infection causing an increased risk of serious complications such as severe acute respiratory syndrome and multi-organ dysfunction associated with a hyperinflammatory state. Glycemic normalization in patients with diabetes must be managed in the best possible way even during COVID-19 infection to avoid serious complications. However, for some antidiabetic agents such as DPP-4 inhibitors (gliptins) there is evidence of efficacy against COVID-19 extra pancreatic glycemic normalization. The objective of this article is to provide an overview of current evidence on the potential therapeutic benefits of gliptins to combat Sars-Cov-2 infection.

Background: We described the QTc interval prolongation and related adverse cardiac events during the administration of hydroxychloroquine (HCQ) and its combinations for treatment of COVID-19. Methods: The hospitalized patients who were infected with SARS-CoV-2 and received HCQ with initial and follow up ECGs from March 10th to May 30th were included. The critical QTc prolongation was accepted as QTc >500 ms if QRS<120ms and >550 ms if QRS >120 ms or ∆QTc levels >60 ms when compared with the initial ECG. Primary outcomes were critical QTc prolongation, ventricular tachyarrhythmia, and sudden cardiac arrest. Results: Out of 336 hospitalized patients with suspected or confirmed COVID-19, 297 received HCQ, and 94 met the inclusion criteria, and 66 cases were included in final analysis. The mean baseline QTc was 444.5 (sd= 39.5) ms. In total, 63% of the patients’ QTc levels increased under HCQ treatment and critical QTc prolongation occurred in 8 cases (12%) all of whom were male. The male gender (p=0.033), DM (p=0.035) and oseltamivir use (p=0.047) were significantly associated with critical QTc prolongation. In multivariate analysis, DM (OR:5.8, %95 Cl:1.11-30.32, p:0.037), and concomitant use of oseltamivir (OR:5.3, %95 Cl:1,02-28, p:0.047) were found to be associated with critical QTc prolongation. Conclusion: Critical QTc prolongation was detected in 12% of the patients. The DM and concomitant oseltamivir use were associated with critical QTc prolongation. The use of concurrent drugs that have potential to enhance QTc interval should be kept in mind and special attention should be paid for ECG monitoring.

Abstract Aim: To compare the effectiveness and safety of two high-intensity atorvastatin doses (40mg vs. 80mg) among acute coronary syndrome (ACS) patients. Methods: This retrospective observational cohort study using real-world data included patients admitted with ACS to the Heart Hospital in Qatar between January 1, 2017 and December 31, 2018. The primary endpoint was a composite of cardiovascular disease (CVD)-associated death, non-fatal ACS, and non-fatal stroke. Cox proportional hazard regression analysis was used to determine the association between the two high-intensity atorvastatin dosing regimens and the primary outcome at 1 month and 12 months post-discharge. Results: Of the 626 patients included in the analyses, 475 (75.9%) received atorvastatin 40mg, while 151 (24.1%) received atorvastatin 80mg following ACS. Most of the patients were Asian (73%), male (97%) with a mean age of 50 years, and presented with ST-elevation myocardial infarction (60%). The incidence of the primary effectiveness outcome did not differ between the atorvastatin 40mg and 80mg groups at 1 month (0.8% vs. 1.3%; aHR= 0.59, 95% CI 0.04-8.13, p= 0.690) and at 12 months (3.2% vs. 4%; aHR= 0.57, 95% CI 0.18-1.80, p= 0.340). Similarly, the use of the two doses of atorvastatin resulted in comparable safety outcomes, including liver toxicity, myopathy, and rhabdomyolysis with an event rate of < 1% in both groups. Conclusion: The use of atorvastatin 40mg in comparison to atorvastatin 80mg in patients with ACS resulted in similar cardiovascular effectiveness and safety outcomes.

AbstractIn pair-living mammals, genetic monogamy is extremely rare. One possible reason is that in socially monogamous animals, mate choice can be severely constrained, generating a risk of inbreeding or incompatibility between partners. To escape these constraints and minimize inbreeding, individuals might engage in extra-pair copulations. Alternatively, inbreeding can be avoided by natal dispersal. However, little is known about the interactions between mating system, mate choice and dispersal in pair-living mammals. Here we show that coppery titi monkeys (Plecturocebus cupreus), are mostly genetically monogamous, as parentage analyses indicated no cases of extra-pair paternity. We did not find evidence for relatedness- or heterozygosity-based mate choice. Despite the lack of evidence for active inbreeding avoidance via mate choice, mating partners were on average not related. We further found that dispersal was opportunistic, with both sexes dispersing over varying distances. Our findings indicate that even opportunistic dispersal, as long as it is not constrained, can generate sufficient genetic diversity to prevent inbreeding. This, in turn, can render both active inbreeding avoidance via mate choice and extra-pair copulations unnecessary, thus helping to maintain genetic monogamy.Key wordsGenetic monogamy, mate choice, dispersal, titi monkeys, Plecturocebus

Background and Purpose GABAA-α5 subunit-containing receptors have been shown to play a key modulatory role in cognition and represent a promising drug target for cognitive dysfunction, as well as other disorders. We describe the preclinical and clinical profile of basmisanil, a potent and highly selective negative allosteric modulator (NAM) of GABAA α5 receptors. Experimental Approach In vitro assays assessed binding and functional selectivity. In vivo occupancy studies measured target engagement. Effects on cognition were tested in rats (Morris water maze) and non-human primates (NHP; object retrieval) and potential side effects (anxiety and proconvulsant) were tested in rats. In healthy volunteers, target engagement and modulation of neuronal network activity were assessed using PET and EEG. Key Results Basmisanil bound to recombinant human GABAA-α5 receptors with 5 nM affinity and more than 90-fold selectivity versus α1, α2, and α3 subunit-containing receptors. Basmisanil inhibited GABA-induced currents at GABAA-α5 yet had little or no effect at the other receptor subtypes. In vivo, basmisanil demonstrated dose-dependent target engagement in rats. Basmisanil attenuated diazepam-induced spatial learning impairment in rats and improved executive function in NHPs. At these efficacious plasma concentrations, basmisanil had no anxiogenic and proconvulsant effects. In healthy volunteers, PET showed target engagement and established the plasma exposure to receptor occupancy relationship. Basmisanil modulated brain function reflected in characteristic changes of EEG spectral power. There were no serious adverse events. Conclusion and Implications Basmisanil is a highly potent and selective GABAA α5 receptor NAM with good safety and tolerability allowing for clinical testing in multiple brain disorders.

Background and objectives Several large scale cohort studies suggest that BCG vaccination in early childhood may reduce the risk of allergic disease, but the consequences remain controversial. The objective of this study was to investigate the associations between early childhood BCG vaccination and the risk of developing allergic disease. Methods Eligible studies published on PubMed, EMBASE and Cochrane Central Register of Controlled Trials were systematically sourced from inception to April 2020. Large-scale cohort or cross-sectional studies with 100 participants or more, focusing on the association between BCG vaccine and allergic disease including eczema, asthma and, rhinitis were included. An assessment was undertaken by two independent investigators looking at methods, interventions, outcomes, and study quality. Odds Ratio (OR) with 95% confidence interval (CI) were calculated. Results Our study included 13 large-scale studies involving a total of 260,029 participants. Our quantitative analysis found that administering BCG vaccine in early childhood significantly reduced the risk of developing asthma (OR 0.74, 95%CI 0.61 to 0.91), but there was no association between early childhood BCG vaccination and the risk of developing eczema (OR 0.87, 95%CI 0.68 to 1.11) or rhinitis. (OR 1.03, 95%CI 0.87 to 1.22). The effect of BCG vaccination with asthma was evident especially in European countries (OR 0.59, 95%CI 0.40 to 0.88) and American countries (OR 0.90, 95%CI 0.82 to 0.98) Conclusions Use of BCG vaccination in early childhood may be associated with a reduced risk of allergic disease, especially in European and American countries.

Background: In order to involve patients in collaborative decisions (SDM), they need to know the treatment options and determine the patient’s preferences from the doctors. This process is a must to be evaluated in the Republic of Moldova. Objective: The study’s aim was to evaluate Shared Decision Making in adult strabismus care from both patients’ and physicians’ perspectives. Material and methods: A prospective, transversal study was conducted. Sixty nine adult strabismus patients and their attending physician were asked to fill out the SDM-9 and SDM-9-DOC questionnaires related to their perception of SDM during the entire period of strabismus treatment. After treatment, patients were asked to describe their satisfaction level. Results: All the participants completed the questionnaire (mean age  =  29.7  ±  6.9 years, 49.3% female and 50.7% male). The mean SDM-Q-9 score among the patients was 78.42% (IQR = 75.6–82.2%). The mean SDM-Q-Doc score was 86.7% (IQR 84.4–88.9%). The SDM-Q-Doc values were consistently higher than the SDM-Q-9 values (average difference of 6.7%). Female and yang patients reported a lower SDM score. Pearson correlation test revealed a positive significant correlation between both SDM-Q-9 score and patient satisfaction t (69)= .28, p .02. Conclusions: Our research pointed out blanks in assessing patient information needs as the main obstacles to SDM. Doctors are more confident in their belief that the information provided as well as deliberations and the shared decision process are performed at a high level compared to patients’ expectations. These findings can serve as a springboard to further improve communication and SDM between patients and physicians, thereby raising patient satisfaction.

Background: The proportion of the population with allergic diseases has increased rapidly in recent decades. Studies on the prevalence of allergens contribute to the treatment and prevention of allergic diseases. Although many studies have been published on the prevalence of allergens in China, there are limited studies on the geographic distribution of allergens. Objective: The aim of this study was to explore the prevalence patterns of sensitization to allergens among patients with allergic diseases in all the seven geographic regions of mainland China. Methods: A large epidemiological study was conducted on the prevalence patterns of serum allergen-specific IgE (sIgE) sensitization to the four most common food allergens and five aeroallergens among 44156 patients with allergic symptoms from 2015 to 2018. The data were analyzed using the chi-square test, and descriptive statistics, forest plots and geographic heatmaps. Results: First, house dust mites were the allergen with the highest prevalence of sensitization in all seven regions, with the highest in South China (40.79%) and the lowest prevalence in Northeast China (11.21%). The prevalence of allergens varied in different regions and seasons. Second, the prevalence of sensitization was significantly higher among male than female subjects. Third, except for egg whites and milk, which had the highest positive rates in children, sensitization to other allergens tended to be the highest in teenagers and young adults. Conclusions: Our findings could help clinical staff apply effective treatment to unique patient groups and direct researchers to conduct deeper studies on the epidemiology of allergic diseases.

A recently proposed risk stratification of medulloblastomas has shown that Sonic Hedgehog (SHH) subtype with TP53 mutation is the worst prognostic. Here, we describe the case of a 6-year-old boy with clinically very aggressive SHH medulloblastoma like TP53 mutant, but the genetic status of the case was wild type. Copy number analysis showed MYCN amplification, chromosome 17p loss, and chromothripsis, which are known to be strongly associated with TP53-mutated SHH tumors. The presence of both chromosome 17p loss and chromothripsis in SHH medulloblastoma may suggest a p53 pathway dysregulation regardless of the TP53 status, leading to a much worse prognosis.

Background：Wheezing is an important respiratory symptom in the diagnosis of asthma. However, wheezing is common in children and often related to viral infection. This and the lack of reliable biological indicators for asthma create difficulty in diagnosing asthma early in children. Objective: In this study, the levels of CD4+CCR6+CRTh2+ memory Th2 cells in wheezing children with different diagnostic outcomes were investigated to determine correlation with a diagnosis of asthma and to assess their potential clinical value as a biological indicator for this disease. Methods: A prospective study was performed with a cohort of wheezing children aged 3 months to 6 years hospitalized in the Division of Pulmonary Pediatrics at Shanghai Xinhua hospital and Shanghai children’s medical center affiliated to Shanghai Jiao Tong University School of Medicine from July 2017 to March 2018. After inclusion, the level of serum IgE, presence of allergen-specific serum IgE (sIgE) and proportion of circulating CD4+CCR6+CRTh2+ memory Th2 cells were counted. In addition, the patients’ personal and family histories of allergic disease were acquired by questionnaire. The children were followed up annually over 2 years by telephone call with a guardian to record whether the child had been diagnosed with asthma. The accuracy of an increased proportion of CD4+CCR6+CRTh2+ memory Th2 cells as an indicator of asthma was assessed. Results: A total of 43 children completed follow-up. The median of circulating CD4+CCR6+CRTh2+ memory Th2 cells in wheezing children diagnosed with or without asthma was 1.2%(0.8%~2.9%) and 0.6%(0.1%~0.9%), respectively, and was significantly higher in children diagnosed with asthma (P<0.01). The median of circulating CD4+CCR6+CRTh2+ memory Th2 cells in atopic children was also significantly higher in children diagnosed with asthma than in children without asthma, at 1.3%(0.8%~2.9%) and 0.6%(0.3%~1.0%), respectively, (P<0.01). Furthermore, the level of serum IgE was significantly higher in children with asthma (P<0.05). Logistic regression analysis indicated that the level of circulating CD4+CCR6+CRTh2+ memory Th2 cells were independent risk factors for asthma. The area under the receiver operating characteristic curve (ROC) was 0.922. There was no significant difference in the positive rate of memory Th2 cells in the context of allergic rhinitis (AR) or atopic dermatitis (AD) (P>0.05). Conclusion: Our exploratory study found that an increase in the level of circulating CD4+CCR6+CRTh2+ memory Th2 cells could be used as a biological indicator for early diagnosis of asthma, especially in predicting the risk of asthma in atopic children.

INTRODUCTION: The anemia leads to a worse prognosis in patients with heart failure(HF). There are few data on the impact of anemia on mortality in patients with acute heart failiure(AHF), and the studies available are mainly retrospective and include hospitalized patients. OBJECTIVE. Evaluate the role of anemia in 30-days and one-year mortality in patients with AHF attended in hospital emergency departments(HEDs). METHODS. Multicenter, observational study of prospective cohorts of patients with AHF. Study variables: anemia(hemoglobin<12g/dL in women and <13g/dL in men), 30-days-mortality and at one year, risk factors, comorbidity, functional impairment, basal functional grade for dyspnea, chronic and acute treatment, clinical and analytical data of the episode and patient destination. Statistical analysis: bivariate analysis and survival analyses using Cox regression. RESULTS. A total of 13,454 patients were included, 7662(56.9%) of whom had anemia. Those with anemia were older, had more comorbidity, a worse functional status and New York Heart Association class, greater renal function impairment and more hyponatremia. The mortality was higher in patients with anemia at 30-days and one-year: 7.5% vs. 10.7%(p<0.001) and 21.2% vs. 31.4%(p<0.001), respectively. The crude and adjusted hazard ratios of anemia for 30-days-mortality were: 1.46(confidence interval[CI]95% 1.30-1.64);p<0.001 and 1.20(CI95% 1.05-1.38);p=0.009, respectively, and 1.57(CI95% 1.47-1.68) and 1.30(CI95% 1.20-1.40) for one-year-mortality. The weight of anemia on mortality was different in each follow-up period. CONCLUSIONS. Anemia is an independent predictor of 30-days-mortality and one year in patients with AHF attended in HEDs. It is important to study the etiology of AHF since adequate treatment would reduce mortality.

Background/ Aims Anthropometric characteristics, namely overweight/obesity, height and waist circumference have been associated with various cancer types. The aim of this systematic review and meta-analysis is to evaluate the potential associations between anthropometric characteristics and bladder cancer risk, synthesizing longitudinal cohort studies. Methods Literature search across MEDLINE, EMBASE, Scopus, Google Scholar and Cochrane Central was performed up to December 31, 2019 and data abstraction was performed independently by two authors. Random-effects (DerSimonian-Laird) models were used to estimate pooled relative risks (RR) and 95% confidence intervals (95%CI); subgroup analyses were performed geographical region, mean age, publication year, length of follow-up, sample size, method of BMI estimation and adjustment for smoking. Results A total of 27 studies were included (88,593 bladder cancer cases in a total cohort of 49,647,098 subjects). Increased bladder cancer risk was noted in overweight men (pooled RR=1.12, 95%CI: 1.04-1.21) but not in overweight women. Both obese men (pooled RR=1.14, 95%CI: 1.06-1.22) and women (pooled RR=1.19, 95%CI: 1.02-1.38) showed increased risk. Interestingly, height increase per 5 cm did not seem to affect risk of bladder cancer in men (pooled RR=1.03, 95%CI: 0.99- 1.06) and women (pooled RR=1.02, 95%CI: 0.97-1.06). Larger waist circumference was associated with bladder cancer risk in men (pooled RR=1.18, 95%CI: 1.09-1.26) but not women. Conclusion In conclusion, bladder cancer risk seems to be related with obesity overall and central obesity in men. In contrast to other cancer types, height does not seem to affect risk, but more studies are needed to extract safe conclusions.