It is common for Wilms tumor to invade the inferior vena cava and right atrium, but a massive pulmonary embolism is rare. This case reports describes an 8-year-old male patient who presented to an outpatient clinic with mild pain and abdominal mass. A left renal mass with extension of an inferior vena cava thrombus was seen on abdominal CT, suggesting a Wilms tumor. An exploratory laparotomy biopsy was scheduled, but not completed because the patient's health suddenly deteriorated, and he died despite high-quality cardiopulmonary resuscitation. A massive pulmonary embolism was found to cause a sudden and fatal cardiac arrest.

Objective: To evaluate the accuracy, sensitivity, specificity, and predictive value of preoperative core needle biopsy (CNB) assessment of histological characteristics in primary cervical cancer. Setting: Retrospective cohort study. Population: Women older than 18 with primary cervical cancer enrolled in the prospective Leipzig School MMR study and had CNBs taken before their operation. Methods: We reviewed 318 cases of cervical carcinoma with available pathology reports from preoperative CNB assessment and from final postoperative evaluation of the hysterectomy specimen. Setting the postoperative comprehensive pathological evaluation as reference, we analysed CNB assessment of histological tumor characteristics. In addition, we performed multivariable logistic regression to identify factors influencing the accuracy in identifying lymphovascular space invasion (LVSI) and tumor grade. Main outcome measures: Accuracy, sensitivity, specificity, and predictive values of CNB assessment of histological tumor characteristics and the variables influencing these. Results: CNB was highly accurate in discriminating histological subtype. Sensitivity and specificity were 98.8% and 89% for squamous cell carcinoma (SCC), 92.9% and 96.6% for adenocarcinoma (AC), 33.3% and 100% in adenosquamous carcinoma respectively. Neuroendocrine carcinoma was always recognized correctly. The accuracy of the prediction of lymphovascular space invasion (LVSI) was 61.9% and was positively influenced by tumor size in preoperative MRI and negatively influenced by strong peritumoral inflammation. High tumor grade was diagnosed accurately in 73.9% of cases and was influenced by histological tumor type. Conclusions: CNB is an accurate sampling technique for histological classification of cervical cancer and represents a reasonable alternative to other biopsy techniques. Funding: “Stiftung gynäkologische Onkologie” (non-profit-organization).

This paper aims to uncover fairly interesting optical soliton solutions in (2+1)-dimensions. The fractional temporal Kundu-Mukherjee-Naskar (KMN) equation is reviewed as a governing model. Local M-derivative along with the unified approach is used to acquire these soliton solutions. The predicted solutions are yielded with the constraint conditions and highlighted by their graphical portrayal. Lastly, the inuence of a local fractional parameter upon predicted solutions are depicted through 2D and 3D graphs.

Daphnia magna belongs to the Cladocera order and plays an important role in the water ecosystem. With the intensification of water pollution, the wild population of D. magna has declined rapidly in recent years, and insufficient molecular markers have limited effective research and conservation of this species. In our research, 26 novel microsatellite (SSR) markers were developed in an artificially domesticated of D. magna and 12 wild population of D. magna using restriction site-associated DNA sequencing (RAD-seq). The results showed that the observed heterozygosity (Ho) and expected heterozygosity (He) ranged from 0.083 to 0.999 and 0.085 to 0.862, respectively. The PIC ranged from 0.368 to 0.805. These results indicate that the developed SSR marker is highly polymorphic. Nei’s genetic identity (H) ranged from 0.0926 to 0.3462, with a mean of 0.2233. Shannon’s Information index (I) ranged from 0.1333 to 0.4799, with an average of 0.3073; Shanxi province had the highest value and Hunan province had the lowest. Genetic distance and Nei’s genetic identity analysis, NJ tree diagram analysis, and PCoA analysis were conducted on populations of Daphnia magna from different regions. An analysis of population genetic structure divided the test D. magna samples into two major groups. There was no absolute correlation between the gene distribution of D. magna and its geographic origin. These results indicate that the genetic diversity of D. magna is rich, and the genetic structure of D. magna differs considerably in different regions. These research results and the newly developed polymorphic SSR markers for D. magna are of great significance in terms of the genetic breeding of D. magna, identification of wild and artificially domesticated species and conservation genetics research.

Peste des petits ruminants (PPR) is an acute, highly contagious, world organization for animal health (OIE) notifiable and economically important transboundary viral disease of sheep and goats and caused by PPR virus (PPRV), which belongs to the genus Morbillivirus of the family Paramyxoviridae. The disease is endemic across Asia, the Middle East and African regions and is considered to be a major obstacle to the development of sustainable agriculture across the developing world due to huge burden for the economy and development of the affected countries and has recently been targeted by the OIE and the Food and Agriculture Organization (FAO) for eradication with the aim of global elimination of the disease by 2030. In this review, the regional epidemiology of PPR outbreaks and associated risk factors with special reference to the PPR-affected countries in South， Central and East Asia is comprehensively discussed.

Background: Chimeric antigen receptor (CAR) T cell therapy of pediatric sarcomas is challenged by the paucity of targetable cell surface antigens. A candidate target in osteosarcoma (OS) is the ganglioside GD2, but heterogeneous expression limits its value. We aimed to identify mechanisms that upregulate GD2 expression in OS. Methods: Surface expression of GD2 in OS cell lines was assessed by flow cytometry. Transcription and translation of genes encoding for enzymes involved in GD2 synthesis were studied by quantitative real-time PCR and by using a construct containing the 5’ untranslated region (5’UTR) of the GD3 synthase-mRNA. An in vitro cytotoxicity assay was used to study the sensitivity of OS cells to targeting by GD2-specific CAR T cells. Results: GD2 surface expression varies both among and within individual OS cell lines. Pharmacological approaches, including inhibition of the histone methyltransferase Enhancer of Zeste Homolog 2 (EZH2) and modulation of the protein kinase C (PKC), failed to increase GD2 expression. Instead, cell confluency was associated with higher GD2 expression levels both in monolayer cultures and in tumor spheroids and with increased sensitivity to in vitro cytolysis by GD2-specific CAR T cells. Confluency-dependent upregulation of GD2 expression in OS cells is mediated by increased de novo biosynthesis through a yet unknown mechanism. Conclusions: Expression of GD2 in OS is highly variable and associated with increasing cell confluency in vitro. Strategies for selective upregulation of GD2 are needed to enable effective therapeutic targeting of this antigen in OS.

Aims: The aim of the study was to investigate the effect of pre-pregnancy body mass index on weight gain during pregnancy. Methods and Material: This retrospective study was conducted on family medicine units in Turkey between March 2018 to September 2018. Pregnant files of the last 5 years were scanned and a questionnaire with 40 questions was filled. Results: 1061 pregnants from 72 provinces included in the study. Net weight difference during pregnancy was significantly higher in cesarean patients, in civil servants and in those with first pregnancy (p <0.05). Net weight difference was found to be significantly lower in those without education compared to other groups (p <0.05). Conclusions: Consequently, In conclusion, pre-pregnancy BMI and individual weight gain during pregnancy should be planned. Thus, many complications that may develop in mother and baby can be prevented. In this regard, benefiting from family medicine units that can reach all segments of the society and monitor pregnant women can increase their success rates. Key-words: Pregnancy, body mass index, gestational weight gain Key Messages: What’s already known about this topic? • According to various studies, nearly half of today’s pregnant women are overweight or obese • The body weight of the mother before pregnancy and the weight gained during pregnancy have an effect on pregnancy results. What does this article add? • Lifestyle changes required for ideal BMI should be planned in pre-pregnancy counseling. To achieve this, teams of family physicians, dieticians and individual sports trainers should be formed. • Those in the high risk group (eg, first pregnancy, uneducated and civil servant) should be monitored more frequently in terms of weight gain during pregnancy. • Personal and social information should be provided to correct false information that taking iron and multivitamin support during pregnancy causes weight gain.

With the improvement of medical consumption level, patients have more and more demand for the prediction of treatment costs. However, the prediction accuracy of existing research methods is low when the amount of data is small. In order to solve this problem, a weighted lasso regression method is proposed to predict the treatment cost based on the electronic medical record. Firstly, a set of transformation method of text-based medical record data is established, and the missing values are supplemented according to the clustering distance to realize the data representation of medical records. Then, in view of the low prediction accuracy of the traditional regression model, the lasso regression model with local weighting is established by introducing the data feature weight into lasso regression method. Finally, the model is verified by the medical record data provided by the hospital, and the results show that the model has higher prediction accuracy.

Aim: Multiple papers have reported the development of new-onset arthralgias with vedolizumab (VDZ) for the treatment of inflammatory bowel disease (IBD). Other studies have shown that VDZ may help in preexisting enteropathic spondyloarthropathy. We sought to probe this issue by conducting a systematic review. Methods: Embase, Medline, Cochrane Central, and Web of Science were searched up to June 29, 2020 for randomized controlled trials evaluating vedolizumab treatment in patients with IBD in which development of arthralgias was noted. Risk of bias and quality were assessed using Cochrane’s collaboration tool and the GRADE system, respectively. PROSPERO registration number: CRD42020197101. Results: Four hundred sixty-one discrete articles were retrieved. Five studies (n=2,899) met inclusion criteria. Comparing the risk of arthralgia in patients treated with VDZ and placebo yielded odds ratio’s which ranged between 1.01 (95% confidence interval (CI) 0.61-1.65) and 10.20 (95% CI: 0.53-195.78). While each study noted an increased incidence of arthralgias in patients receiving VDZ, none proved statistically significant. Studies were heterogeneous in disease populations, VDZ dosage, time-points for evaluation, and data points collected. Post-hoc analyses suggested an increased risk of arthralgias in patients with prior TNF inhibitor use. Conclusion: The included studies showed a trend toward increased arthralgias in patients with IBD who received VDZ. However, our study lacked any statistically significant findings to identify a clear link. More research is needed to substratify which patients develop arthralgias when treated with VDZ in order to better understand whether heightened risk can be predicted prior to treatment initiation.

Chinese hamster ovary (CHO) cell is the predominant cell factory to produce biopharmaceuticals such as immunoglobulin G (IgG), but in CHO cells lactate accumulation and cell death compromise IgG production while fucosylation mitigates the antibody-dependent cellular cytotoxicity (ADCC) of IgG. To tackle these problems, we harnessed a burgeoning gene silencing system, CRISPR-Cas13d, to effectively suppress the endogenous genes governing lactate production (LDHA), fucosylation (GFT) and cell death (DDIT3), hence repressing lactate accumulation and core fucosylation. We further exploited the Sleeping Beauty system to integrate the CRISPR-Cas13d module co-targeting these 3 genes and generated a CHO cell platform for IgG production. The new platform exhibited simultaneous knockdown of LDHA, GFT and DDIT3, accumulated less lactate, had prolonged longevity, produced more IgG with less fucosylation and stronger ADCC efficacy. These data collectively warrant the potentials of CRISPR-Cas13d for CHO cell engineering and improving antibody production with regard to quantity and quality.

Objective: This systematic review and meta-analysis was aimed to evaluate the therapeutic benefits and safety of tocilizumab (TCZ) in treating severe coronavirus disease 2019 (COVID-19) and associated health complications. Methods: The electronic search was performed using PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials (RCTs) and Google scholar databases to identify the randomized control trials. Mortality, incidences of ICU admission, need of mechanical ventilation (MV), length of stay in the hospital (LOS) and length of stay in the ICU (LOS-ICU) and the incidences of super-infection, bacteraemia, fugleman, pneumonia and pulmonary thrombosis were evaluated as the primary outcomes. The comparison will be between TCZ versus standard of care (SOC)/placebo. Results: Based on the inclusion criteria there were 24 retrospective studies involving 5686 subjects were included. The outcomes of the meta-analysis have revealed that the TCZ has reduced the mortality (Mantel-Haenszel (M-H), random effects risk difference (RE-RD) of -0.11 (-0.18 to -0.04), at 95% CI, p = 0.001, I2 = 88%) and increased the incidences of super-infections (M-H, RE-Risk ratio (RR) of 1.49 (1.13 to 1.96) at 95% CI, p=0.004, I2 = 47%). However, there is no significant difference in ICU admissions rate, need of MV, LOS, LOS-ICU, and incidences of pulmonary thrombosis compared to SOC/control. Conclusion: Based on the outcomes of the meta-analysis we can conclude that administration of TCZ would reduce the risk of mortality, and however there is no much difference observed between the TCZ and SOC/control groups in other parameters.

Objectives: This study aimed to ascertain current practices prevalent among medical students using electroacoustic devices. We also aimed to determine pattern and frequency of hearing loss among medical students. Design: Cross-sectional Participants: Students of 3rd year and 4th year MBBS at Jinnah Sindh Medical University, Karachi, Pakistan were included. Data collection dated from December 2019 till February 2020 using convenience sampling technique. Setting: Students were invited to ENT OPD, Jinnah Postgraduate Medical Centre, Karachi. Through a structured proforma, we recorded practices regarding electroacoustic devices. We investigated hearing of medical students by tuning fork tests and Pure Tone Audiometry. Main Outcome Measures: Using SPSS software version 23 we applied Chi square test, Pearson correlation and independent t test at 95% CI and p=<0.05 as significance level. Results: A total of 221 students fulfilled inclusion criteria. 96.4%(n=213) regularly used electroacoustic devices. Students mostly used insert type earphones connected with a smartphone. More than 30% of medical students demonstrated low frequency (0.25-0.5kHz) sensorineural hearing loss (SNHL). Pearson correlation yielded strong positive correlation with hearing loss and years of exposure(p=<0.001). Male students used electroacoustic devices more frequently than female students(p=0.01). However, we did not observe significant difference between their mean thresholds. Conclusion: Acoustic trauma has been conventionally described to affect higher frequencies. We found low frequency SNHL among majority of students. This indicates that specific type of acoustic trauma can affect particular frequencies on audiogram. KEY WORDS: Low frequency hearing loss, medical students, Pure Tone Audiometry, personal listening devices, hearing thresholds, noise induced hearing loss, sensorineural hearing loss

Heavy metals M (Cr (III), Ni (II), Cu (II), Zn (II)) in nickel plating wastewater were recovered by complexation-ultrafiltration (C-UF) with the complexant PMA. The important factors pH and PMA/M mass ratio (P/M) on metals rejections were investigated, and all rejections could reach to 98% at pH 6.0 and P/M 8. Besides, the shear rate () distribution on the membrane surface was analyzed by CFD revealed that  increased along the radius.The criticl shear rates (c) of PMA-M complexes were calculated to judge the shear stability of different complexes,and c of PMA-Cr, PMA-Ni, PMA-Cu and PMA-Zn complexes were 1.14×105, 1.48×105, 2.07×105 and 1.21×104 s-1 ,respectively. Furthermore, the pairwise separation coefficients of metals were calculated, and the maximum of βZn/Cr, βCr/Ni and βNi/Cu are 95.5, 42.0 and 47.3. The high selective separation of heavy metals and PMA were achieved by shear induced orderly dissociation coupling with ultrafiltration（SIOD-UF）.

Background: With the widespread use of hematopoietic stem cell transplantation (HSCT), long-term complications have come to the fore. The aim of this study is to determine the prevalence and risk factors of chronic kidney disease (CKD) developing in the long term in patients who underwent allogeneic HSCT in childhood and also to investigate the superiority of eGFR formulas. Methods: The present study evaluated CKD in patients undergoing allogeneic HSCT. We analyzed the 94 children who received allogeneic HSCT at the Ege University in İzmir between 2019 August and 2019 November. The patients were evaluated at least 2 years after transplantation. CKD was defined as a glomerular filtration rate (GFR)<90 mL/min/1.73 m2, using eGFR equations which are based on serum creatinine (SCr), cystatin C (CysC), and SCr plus CysC. Results: In our study, 9 (9.4%) according to Bedside Schwartz, 59 (76.6%) according to CKiD-eGFR-CysC and 20 (26%) patients according to CKiD-eGFR-SCr-CysC equation were evaluated as CKD. In cases evaluated as CKD according to CysC, early development of acute kidney injury (AKI), posttransplant cytomegalovirus (CMV) reactivation and being >10 years old during transplantation were found to be associated with the development of CKD. Conclusion: We may be delayed in detecting CKD by calculating SCr-based formulas in HSCT cases, which is a patient group where early diagnosis and treatment of CKD is very important.

Objective: To characterize office and operating room hysteroscopy in women 70 years of age or older. Design: This was a retrospective chart analysis. Setting: A single tertiary-care medical center. Population: All women aged 70 years of age or older who underwent a hysteroscopy procedure between March 2011 and August 2018. Methods: All hysteroscopic interventions performed during the study period were reviewed. All patients had at least one gynecological examination that included an ultrasound study prior to the hysteroscopy. Main outcome measures: Primary outcomes included procedure success and histopathological findings. Secondary outcomes included short-term complications of the procedure. Results: The data of 577 patients were analyzed. The median age at the time of the procedure was 76 years. 225 office hysteroscopy procedures and 405 operating room procedures were included. Of the 236 patients with PMB, 73(30.9%) were diagnosed as having malignancy compared to 25 (7.3%) of the 341 patients with no PMB (p < .001, odds ratio (OR) = 5.66; confidence interval (CI) 3.46-9.26). The office procedure was successful in 194 (87%) patients. 53 patients required a second hysteroscopy, which revealed 12 cases of premalignant or malignant lesions. The volume of procedures in the office increased 16 times during the study period. Conclusions: Office hysteroscopy for women over the age of 70 is safe, feasible, and reliable for diagnosis of endometrial malignancy. Failed hysteroscopy and a moderate-to-high index of suspicion for malignancy indicates the need for a repeat hysteroscopy. The diagnostic yield using the office procedure has increased over time.

Objective: To assess whether positive flow cytometry quantification of fetal red blood cells is associated with adverse outcomes in cases of mild trauma during pregnancy. Design: A retrospective computerized database cohort. Population: Pregnant women with viable gestation involved in trauma who underwent flow cytometry. Flow cytometry was considered positive (≥0.03/≥30 ml). Methods: A univariate analysis was followed by a multivariate analysis. Main outcome measures: Composite adverse maternal and neonatal outcome was defined as one or more of the following: intrauterine fetal death, placental abruption, pre-term birth < 37 weeks of gestation, immediate premature rupture of the membranes, and immediate delivery following trauma. Results: During the study 1023 women met inclusion and exclusion criteria. Among the cohort, 119 women (11.6%) had positive flow cytometry (≥0.03/≥30 ml) with median result of 0.03 [0.03-0.04], while 904 women (88.4%) had negative flow cytometry test result (≤0.03/≤30 ml) with median result of 0.01 [0.01-0.02]. Composite adverse outcome occurred in 8% of the women, with no difference in the groups with vs. without positive flow cytometry (4.2% vs. 8.5%; p=0.1). Positive flow cytometry was not associated with any adverse maternal or neonatal outcome. This was confirmed on a multivariate analysis. Conclusions: Flow cytometry result is not related to adverse maternal and fetal/neonatal outcome of women involved in minor trauma during pregnancy. We suggest that flow cytometry should not be routinely assessed in pregnant women involved in minor trauma.

Background.Endovascular aortic aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) is increasingly used and become the standard treatment option for AAA. The aim of the current study was to evaluate the outcomes and predictors of survival of endovascular treatment of AAA at the short and medium-term. Methods.A total of 222 patients having endovascular AAA repair between January 2013 and December 2019 by the same surgical team were included in the study. Patient demographics, perioperative and follow-up data including mortality,complications and need for secondary intervention were collected.Primary endpoint was all-cause mortality.Kaplan-Meier analysis was conducted for survival and Cox regression models were assessed for predictors of survival. Results. Median age was 70 years with male predominance(202 patients,91%). Thirty-day mortality was 1.8%. Median follow-up to the primary endpoint was 20 months(range,1 to 80 months). Survival rates at one, three and five years were 93.5%,81.4% and 62.2% respectively. Freedom from secondary intervention rates were 95.5% at one year,88.7% at three years and 82.1% at five years. Cox proportional hazard models showed that preoperative creatinine levels ≥1.8 mg/dl(hazard ratio (HR) 2.68, 95%CI1.21-6.42, p=0.027), hemoglobin levels <10 gr/dl (HR 3.38 95%CI 1.16-9.90,p=0.026), ejection fraction < 30% (HR 5.67,95%CI1.29-24.86,p=0.021)and AAA diamete≥6.0 cm(HR 2.20,95%CI1.01-4.81,p=0.049)were independently associated with mid-term survival. Conclusion.EVAR is a safe procedure with low postoperative morbidity and mortality. This study confirms that the mid-term survival and results are favorable.However, the analyzed factors in this study that predict reduced survival(high preoperative creatinine,ow hemoglobin,low ejection fraction and larger aneurysms) should be judged when planning EVAR.

Objectives: To investigate whether discharge summaries are accurately coding clinical details of patient admissions and to identify whether such differences lead to a loss of financial income for acute trusts. Design: A cross-sectional study of medical records, discharge summaries and financial outcomes. Participants: A review was conducted of two weeks of discharge summaries and patient notes from the stroke unit, totaling 95 patient episodes. Results: The total number of medical details not coded in discharge summaries was 580, resulting in a loss of income of £17,488.38. Extrapolated over the year, this could have led to a missed income of £454,000 for the stroke department. Sub-group analysis identified that 24% of un-coded details were extra primary diagnoses, 45% secondary diagnoses, 14% social factors, 3% investigations performed, and 14% were specialty team reviews. Conclusions: The impact of the quality of discharge summaries has proven to be huge. A major contributor is unawareness of the correct terminology by both clinical and coding teams. Specific measures to introduce standard diagnoses and coding practices to minimise variability will lead to clearer coding and allow for the trust to be accurately paid for the care performed.

Aim: Covid-19 mortality rate varies according to age and the presence of chronic disease. In this study, demographic characteristics, comorbidities, presenting symptoms, physical examination findings, laboratory findings, and administered drugs of the discharged or deceased patients admitted to our hospital and hospitalized with the COVID-19 diagnosis were compared to investigate the factors that affect mortality Methods: A retrospective study was performed and included COVID-19 pneumonia patients. 390 consecutive discharged or deceased patients, who were hospitalized in our hospital between March 20 and May 20, 2020, after detection of pneumonia and diagnosis of COVID-19, were included in the study. Result: Of the 390 patients included in the study, 352 (90.25%) were discharged after recovery, while 38 (9.75%) were deceased. The average age of all the patients was 49.46±17,86, the average age of the discharged patients was 47.19±16.76, and the average age of the deceased patients was 70.42±13.7. The average age of deceased patients was significantly higher. Of all the patients, 40.8% was PCR positive Conclusion: The present study revealed that the drugs that patients take due to their comorbidities have no effect on the prognosis of the disease and that the presence of comorbidity itself is indicative of the poor prognosis. Taking into account the PCR positivity of 57.9%, even in deceased patients, we believe PCR is inadequate in the diagnosis, and CT is much more valuable in this regard.

In this paper, we propose a model for the dynamics of HIV-1 epidemics under distinct regimes and study the emergence of drug resistance. Our main result shows that the stability analysis for delay differential equation through strum sequence. Under this technique, we arrive at the general conditions on the coefficients of a characteristic equation of degree four, such that it describes an asymptotically stable steady state which becomes unstable as the delay parameter is increased. To apply this technique for analyzing the stability of HIV-1 infection delay model with HARRT regimes. A sensitivity methodology for nonlinear delay systems arising in one class of cellular HIV infection models is presented. Theoretical foundations for a typical sensitivity investigation and illustrative computations are given. Simulations using realistic parameter values are then constructed to illustrate and support our theoretical results. This model provides important insights on how HAART might play a crucial role in the long term behavior of HIV infection

The Corona virus disease 2019 (COVID-19) mainly caused by the novel severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) became a global pandemic by March 2020. Actual there is no strong evidence of weather and COVD-19 spread relation as it is a new virus. This study is mainly focussed on the tropical weather impact on the spatio-temporal spread of COVID-19 during the early stages i.e. March-May 2020 in India, which is a large country where the disease has shown an exponential growth. This study is an attempt to assess the relationship of major environmental parameters like solar radiation, air temperature and humidity with the positive cases of COVID-19 for the period March-May 2020 which is the summer season or pre-monsoon season over India. The time series and significant correlation analysis at daily, weekly scale and the spatial analysis of weather and COVID-19 cases are presented. The results show significant correlation of solar radiation and atmospheric temperature with COVID-19 cases both at daily and weekly scale in India whereas humidity has low correlation in the study period. But the temperature humidity index (THI) a measure of the thermal stress shows positive correlation with the disease spread. These results can be a good input for developing the integrated modelling framework for the COVID-19 forecasting using state of art numerical weather prediction model and disease process modelling.

Aims: Gene variants the calcium channels have been associated with Brugada syndrome (BrS). The investigation of the human cellular phenotype and the use of drugs for BrS is still lacking. Methods and results: This study recruited cells from a BrS patient carrying a missense variant (c.425C>T/p.S142F) in CACNB2 with uncertain significance as well as from three healthy persons. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) generated from skin biopsies of healthy persons and the BrS patient (BrS-hiPSC-CMs) as well as CRISPR/Cas9 corrected cells (isogenic control, site-variant corrected) were used. HiPSC-CMs from the BrS patient showed a significantly reduced L-type calcium channel current (ICa-L). The inactivation curve was shifted to a more positive potential and the recovery from inactivation was accelerated. The protein expression of CACNB2 from the BrS-patient was significantly decreased. Moreover, the correction of the CACNB2 site-variant rescued the changes. In addition, the peak sodium current was significantly reduced as compared with the controls consistent with the reduction of the amplitude and upstroke velocity of action potentials in BrS-hiPSC-CMs. Arrhythmia events were more frequently detected in BrS-hiPSC-CMs. In cells without arrhythmic events, carbachol induced the occurrence of arrhythmias with a higher chance in BrS-hiPSC-CMs than in healthy cells. Whereas ajmaline (sodium channel blocker) did not increase arrhythmic events, bisoprolol (beta-blocker) at low concentration and quinidine decreased arrhythmic events. Conclusions: The CACNB2 variant (c.425C>T/p.S142F) causes a loss-of-function of L-type calcium channels and is pathogenic for this type of BrS. Bisoprolol and quinidine may be effective for treating BrS with this variant.

Objectives: This study aims to compare the graft success and hearing results of the palisade and island cartilage graft, with a new wheel-shaped composite cartilage graft for type 1 tympanoplasty. Design: The study was designed retrospectively. Setting: The study was conducted at Katip Celebi University, Ataturk Training and Research Hospital, Otolaryngology-Head & Neck Surgery Clinic. Participants: Only patients with conductive hearing loss and simple pars tensa perforation of the tympanic membrane were included in the study. Main outcome measures: Pure tone average (PTA), air-bone gap gain (ABG), word recognition score (WRS), ABG closure and grafts success were compared between the graft groups. Results: Records of 111 patients were analyzed. The graft success rate was 89.7% for palisade cartilage graft (PCG, n= 39), 86.1% for island cartilage graft (ICG, n=36), and 97.2% for wheel-shaped composite cartilage graft (WsCCG, n= 36) (p=0.244). Average postoperative PTA and ABG values were significantly affected by the cartilage graft type, but WRS was not affected. (p = 0.005, 0.019, 0.306, respectively, One Way-Anova test). Post-Hoc LSD test showed a statistically significant decrease in PTA and ABG averages for WsCCG group compared to the ICG group (p= 0.004; CI%95= 15.1-2.2 dB and p= 0.023; CI%95= 8.2-0.4 dB, respectively). Postoperative PTA and ABG averages for WsCCG and PCG groups were similar (p= 0.069 and p=0.053, respectively). In addition, while there were 2 (5.1%) retractions in the PCG group and 1 (2.7%)in the ICG group, there was no retraction in the WsCCG group. Conclusion: The WsCCG provided comparable results with classical reliable graft techniques (PCG and ICG) and may recommend as a more suitable graft due to hearing results and resistance against retraction.

Objectives: Pulsatile tinnitus (PT) is usually caused by vascular pulsation, its pathogenic mechanism is still unclear. We conducted a retrospective analysis of some patients diagnosed with PT, aiming to provide clinical reference for future studies on PT. Design: Retrospective study. Setting: Single institution. Participants: Surgical treatment of PT in 52 patients. Methods: We counted basic characteristics of all patients, analyzed the prognostic factors and the treatment results, classified the etiology according to the imaging findings. Results: The gender difference was statistically significant in PT（2=44.308, P＜0.001). The analysis results found a correlation between duration of tinnitus and the prognosis of surgery (P<0.05). we found 19 conditions can lead to PT. We reported the first case in the world that the mirror man suffers from PT in our study. Conclusions: Our study suggests that we attribute the cause of PT to the superposition of the degree and number of risk factors over time. The duration of tinnitus is related to prognosis. The hearing loss of PT is mainly low frequency hearing loss. A total of 19 imaging conditions can cause PT were found. PT caused by sigmoid sinus diverticulum had the best surgical effect, while high jugular bulb had the worst. PT in mirror person is reported for the first time, which provides clinical reference for the diagnosis and treatment of PT in mirror person. At the same time, we raised some new questions for the study of PT.