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Devastating presentation of mild COVID-19 infection: Dilated Cardiomyopathy, multiple...
RADHAPRIYA YALAMANCHI
Madhan Murugan

RADHAPRIYA YALAMANCHI

and 3 more

October 12, 2020
Coronavirus disease (COVID-19) is a novel disease with multi-system involvement, but majority of patients have pulmonary and cardiovascular involvement in the acute stages. The cardiovascular impact of acute COVID-19 is well recognized ranging from myocarditis arrhythmias, thrombotic occlusion of coronary arteries, spontaneous coronary artery dissection and micro-thrombi in small coronary vessels on autopsy findings. We report a case of young male who recovered from probable mild covid-19 infection presenting few weeks later with devastating cardiovascular involvement with severe left ventricular (LV) impairment due to non-ischemic cardiomyopathy, multiple LV thrombi and embolic stroke.
Dislodged Amplatzer septal occluder in right ventricle, interesting echocardiographic...
Shokoufeh Hajsadeghi
Pegah Joghataie

Shokoufeh Hajsadeghi

and 2 more

October 12, 2020
There are surgical and percutaneous interventional strategies to treat ASD, each with its own advantages and inevitable drawbacks too. Here, we described a case of large size secundum type ASD (30 mm x 31 mm) that first underwent percutaneous closure with ASD Amplatzer device number 33. The day after the procedure, although the patient was asymptomatic, on follow-up echocardiography, it was found that the device was embolized into the right ventricle within Moderator Bands. Hence, the cardiac surgery was performed.
Novel Genetic Characterization of Porcine Epidemic Diarrhoea Virus Strains Circulatin...
Shengnan Chen
Guangzhi Yan

Shengnan Chen

and 10 more

October 12, 2020
In recent years, the emergence and high prevalence of porcine epidemic diarrhoea virus (PEDV) in piglets has been observed in various regions of Guangdong Province. In this study, novel genetic features of the PEDV S1 gene were detected in fifty-five PEDV samples from eleven different pig farms collected from 2018 to 2019 in eight cities in Guangdong Province, China. More than 98.2% (54/55) of the samples tested positive with a PEDV antigen assay. The S1 gene of 11 samples was sequenced. Analysis results showed that the four novel PEDV isolates were 99.9%~100% identical to each other and clustered to a separate clade in the G2a subtype, sharing 90.4–98.8% and 87.7–97.7% identities at the nucleotide and amino acid levels, respectively, with 57 strains from GenBank. It is worth noting that the novel PEDV strains contained nine novel amino acid substitutions (L299I, V312A, Q319P, N/D360A, S558L, S566K, K593R, Y612H and S773F) in the S1 protein compared to the sequences of widely used vaccine strains (CV777 and AJ1102 strains) and other variant PEDV strains (G2 group strains). Furthermore, the amino acid substitutions were in the COE region of the important S protein neutralization epitope. In this study, we detected novel PEDV epidemic strains in Guangdong Province, which had the highest identity (98.7-98.8% nucleotide level, 96.6-97.2% amino acid level) with the BJ2011-1 strain and differed greatly from vaccine strains. Compared to vaccine strains, there are 91 (CV777) or 27 (AJ1102) amino acid changes in the neutralization epitope of the S1 protein, and whether amino acid substitutions affect the immune efficacy of the vaccine should be verified in further studies.
High diversity of genes encoding tetracycline resistance in the microbiota of broiler...
Antonietta Di Francesco
Daniela Salvatore

Antonietta Di Francesco

and 8 more

October 12, 2020
Tetracycline resistance is still considered one of the most abundant antibiotic resistances among pathogenic and commensal microorganisms. The aim of this study was to evaluate the prevalence of tet genes encoding tetracycline resistance in broiler chickens in Tunisia, by PCR. Individual cloacal swabs from 195 broiler chickens were collected at two slaughterhouses in the governorate of Ben Arous (Grand Tunis, Tunisia). Chickens were from 7 farms and belonged to 13 lots consisting of 15 animals randomly selected. Individual whole genomic DNA was extracted and tested for 14 tet genes. All the lots examined were positive for at least 9 tet genes, with an average number of 11 tet genes per lot. Of the 195 animals tested, 194 (99%) were positive for one or more tet genes. Tet(L), tet(M) and tet(O) genes were found in 98% of the samples, followed by tet(A) in 90.2%, tet(K) in 88.7% and tet(Q) in 80%. These results confirm the antimicrobial resistance impact in the Tunisian’s poultry sector and suggest the urgent need to establish a robust national antimicrobial resistance monitoring plan.
A rare neoplasm in the right atrium
Xingzhi Huang
Jia Hu

Xingzhi Huang

and 3 more

October 12, 2020
Primary neoplasm of the atrium are usually thrombus or the cardiac myxomas. Cardiac hemangiomas are rare primary cardiac neoplasms. The natural evolution is uncertain due to various manifestation over time. Transthoracic echocardiography (TTE) can clearly display the location and size and clarify the impact of its relationship with myocardium, valves, and hemodynamics. We present the case of a female patient who with a complete medical history of right atrium cardiac hemangioma accidentally.
MDT to HIM
Zhiping Yang
daiming fan

Zhiping Yang

and 1 more

October 12, 2020
This is a comment article on MDT, not a original article.
A rapid and cost-effective multiplex ARMS-PCR method for the simultaneous genotyping...
Md. Tanvir Islam
A. S. M. Alam

Md. Tanvir Islam

and 9 more

October 12, 2020
Tracing the globally circulating SARS-CoV-2 mutants is essential for the outbreak alerts and far-reaching epidemiological surveillance. The available technique to identify the phylogenetic clades through high-throughput sequencing is costly, time-consuming, and labor-intensive that hinders viral genotyping in low-income countries. Here, we propose a rapid, simple, and cost-effective amplification-refractory mutation system (ARMS)-based multiplex reverse-transcriptase PCR assay to identify six distinct phylogenetic clades: S, L, V, G, GH, and GR. This approach is applied on 24 COVID-19 positive samples as confirmed by CDC approved real-time PCR assay for SARS-CoV-2. Our multiplex PCR is designed in a mutually exclusive way to identify V-S and G-GH-GR clade variants separately. The pentaplex assay included all five variants and the quadruplex comprised of the triplex variants alongside either V or S clade mutations that created two separate subsets. The procedure was optimized in the primer concentration (0.2-0.6 µM) and annealing temperature (56-60°C) of PCR using a 3-5 ng/µl cDNA template synthesized upon random- and oligo(dT)-primer based reverse transcription. The different primer concentrations for the triplex and quadruplex adjusted to different strengths ensured an even amplification with a maximum resolution of all targeted amplicons. The targeted Sanger sequencing further confirmed the presence of the clade-featured mutations with another set of our designed primers. This multiplex ARMS-PCR assay is a sample, cost-effective, and convenient that can successfully discriminate against the circulating phylogenetic clades of SARS-CoV-2.
Otorhinolaryngology in the COVID-19 era: Are there significant differences between ho...
Anasuya Guha
Jan Plzak

Anasuya Guha

and 3 more

October 12, 2020
Objectives The COVID-19 disease had an incredible impact on both hospital-based and private practices in the field of otorhinolaryngology and head and neck surgery. Practical issues faced by both types of practice were not well addressed in most studies. A national study was designed to address these issues. Design Prospective questionnaire-based study Setting Online google questionnaire sent to members of the Czech Society of Otorhinolaryngology and Head and Neck Surgery Participants All doctors practicing Otorhinolaryngology in Czech Republic with access to online link to questionnaire between 15th April and 26th April 2020. Main outcome measures Primary aims of the study was to evaluate any significant differences between the two types of practice in the field of Otorhinolaryngology. We formulated null hypotheses stating there were no statistical differences in the preparation and availability of personal protective equipment amongst both practices a month after the first cases of COVID-19 in Czech Republic. Statistical analyses including the Mann-Whitney U test were performed to test the hypotheses. Results Analysis and results were based on completion of the entire questionnaire by the doctors. There were no statistically significant differences between both the practices, however individual analyses of both the practices showed a different outcome. Conclusion Despite our statistical results, it was observed that private practices faced more deficits and were more financially vulnerable. They were also other issues reported by both practices that could compromise the care of patients, functioning of workplaces and support of doctors.
Clinical implication of endometriosis in the surgical management of early ovarian can...
Myong Cheol Lim
Sang-Soo Seo

Myong Cheol Lim

and 5 more

October 12, 2020
Objective To investigate the surgical effort of endometriosis the in the surgical management of early ovarian cancer. Design: A retrospective study Setting National Cancer Center Population All women who underwent cytoreductive surgery between January 2001 and July 2008 Method: Retrospective medical chart review Main Outcomes Measure Requirement of the rectosigmoid colon and pathological outcome of resected the rectosigmoid colon Results: Of the 37 stage I and 15 stage II ovarian cancer women, twelve cases (23.1%) were serous carcinomas and 40 (76.9%) were non-serous carcinomas (9 mucinous, 11 endometrioid, 14 clear cell, 2 transitional cell, and 4 mixed carcinomas). Co-existence of endometriosis was identified in 28.8% of the patients at adnexa, pelvic peritoneum, and rectum. Resection of the rectosigmoid colon to completely resect all suspicious lesions was required in 15 patients (28.8%). Cancer and endometriosis were identified in 6 (40%) and 5 (33%) patients, respectively. Fibrosis and/or adhesion were identified in 4 (27%) patients. Complications related resection of the rectosigmoid colon such as fistula or leakage were not identified with a median follow up of 50 months. Conclusions: Resection of the rectosigmoid colon with adjacent pelvic peritonectomy is required in approximately one-third of the patients with early ovarian cancer for complete removal of all suspicious metastatic lesions in the pelvis. Cancer invasion, endometriosis, and fibrosis and/or adhesion are the causes to perform resection of the rectosigmoid colon in such patients.
Selection of high-risk individuals for a large niche development based on a scoring c...
Wang Jing
Qiushi Pang

Wang Jing

and 8 more

October 12, 2020
Objective: To develop a risk prediction model to identify the high-risk individuals of large niche formation after cesarean section (CS). Design A retrospective study. Setting Women’s health research in Anhui, China. Population: Women received CS between Jan 2012 to Jun 2017. Methods: Women were arranged to receive uterine scar examination by transvaginal ultrasonography, and those diagnosed with niche were divided into two groups according to whether they suffer from postmenstrual spotting. The cut-off values of depth, RMT (residual myometrium thickness), and depth/AMT (adjacent myometrium thickness) were chosen to define a large niche. Then, all participants were classified into three groups, including a control, a small niche, and a large niche group. The scores of each variable in the prediction model were calculated by dividing the minimum β-coefficient from the multivariate logistic analysis. Main outcome: Primary outcome was a prediction scoring model for large niche formation. Results: In total, 727 women were recruited in this study, and the large niche was defined as more than 0.50 cm in depth, less than 0.21 cm in RMT, more than 0.56 in depth/AMT. The large niche prediction model included eight variables of age at delivery, retroflexed uterine, meconium-stained amniotic fluid, history of CS, B-Lynch suture, operation duration, premature rupture of membranes and cervical dilatation more than 4 cm. The cut-off value of 5 in this score-based model presented sensitivity and specificity as 67.48% and 90.07% respectively. Conclusions: This score-based risk prediction model could present the risk of large niche formation of individuals after CS.
Increasing access to reproductive health services through maternity waiting homes for...
Jody Lori
Michelle Munro-Kramer

Jody Lori

and 21 more

October 12, 2020
Objective: To report on the effectiveness of a standardized core Maternity Waiting Home (MWH) model to increase facility deliveries and access to reproductive health services among women living farthest from a health facility (>10km) using facility-based data. Design: Quasi-experimental design. Setting: Seven rural districts in Zambia. Population: Women delivering at 40 health facilities between June 2016 to August 2018. Methods: 20 intervention sites and 20 comparison sites were used to test if MWHs increased access to reproductive health services for women living in rural Zambia. The difference-in-differences (DID) methodology was used to examine the effectiveness of the core MWH model on our primary outcomes. Main Outcome Measures: Differences in the change from baseline to endline in the percentage of women who: 1) traveled greater than 10 km for delivery, (2) attended a postnatal visit at 6 days postpartum, and (3) were referred to a higher-level health facility between intervention and comparison group. Results: We detected a significant difference for the percentage of deliveries at intervention facilities with the core MWH model for all women living >10km away (p=0.03), adolescent women (<18 years) living >10km away (p=0.002), and primigravida women living >10km away (p=0.01). There were no significant differences for women attending a postnatal care visit at 6 days postpartum (p=0.07) or for women referred to the next level of care (p=0.29). Conclusion: The core MWH model was successful in reaching women with historically low rates of facility delivery, those living >10km from a healthcare facility, including adolescent women and primigravidas.
Stability Analysis of Discretized Structure Systems Based on the Complex Network with...
Chaoyu Wang
Yinhe Wang

Chaoyu Wang

and 1 more

October 12, 2020
The stability analysis of dynamic continuous structural system (DCSS) has often been investigated by discretizing it into several low-dimensional elements. The integrated results of all elements are employed to describe the whole dynamic behavior of DCSS. In this paper, DCSS is regarded as the complex dynamic network with the discretized elements as the dynamic nodes and the time-varying stiffness as the dynamic link relations between them, by which the DCSS can be regarded to be the large-scale system composed of the node subsystem (NS) and link subsystem (LS). Therefore, the dynamic model of DCSS is proposed as the combination of dynamic equations of NS and LS, in which their state variables are coupled mutually. By using the model, this paper investigates the stability of DCSS. The research results show that the state variables of NS and LS are uniformly ultimately bounded (UUB) associated with the synthesized coupling terms in LS. Finally, the simulation example is utilized to demonstrate the validity of method in this paper.
New families of exact traveling wave solutions to the van der Waals p-system
Muhammad  Bilal
Muhammad  younis

Muhammad Bilal

and 5 more

October 12, 2020
In this article, we successfully construct various kinds of exact traveling wave solutions like, hyperbolic (kink and singular kink-shaped soliton), trigonometric (periodic and singular periodic) as well as rational function solutions for the best known mixed hyperbolic-elliptic system of conservation laws, namely the van der Waals gas system in the viscosity-capillarity regularization version by means of ($\frac{G’}{G^2}$)-expansion and advanced $\mbox{e}^{-\phi(\tau)}$-expansion functions methods. These techniques are very useful and exceptionally helpful in a contrast with other analytical schemes, which show the effectiveness and the simplicity to discuss the exact solutions. 3D and contour figures are sketched in order to understand the physical movement of the gained results under the selections ofunknown parameters.
A testicular and paratesticular localization of Desmoplastic Small Round Cell Tumor:...
Fabricio Romagnol
Maria Teresa Alves

Fabricio Romagnol

and 5 more

October 12, 2020
Desmoplastic Small Round Cell Tumor (DSRCT) is an aggressive neoplasm that classically grows in peritoneal cavity and has poor prognosis. We describe a 13-year old boy with testicular DSRCT, treated with orchiectomy and chemotherapy and is free of disease 96 months after diagnosis. This is the fifth case of primary DSRCT of the testis described in literature. Moreover, we present a literature review of 28 cases of testicular and paratesticular DSRCT and discuss these locations as a prognostic factor.
Transition Navigator Intervention improves transition readiness to adult care and add...
Deepa Manwani
Maya Doyle

Deepa Manwani

and 13 more

October 12, 2020
Background Adolescents and young adults (AYA) with Sickle Cell Disease (SCD) experience especially high rates of acute care utilization and increased morbidity, due in part to disease exacerbation and in part to the developmental challenges of adolescence. It is at this very high-risk time that they also face the need to transition their care to adult services, further adding to the heightened morbidity and acute care utilization, if poorly coordinated. Previous research supports the effectiveness of patient navigators to assist those with complex health conditions and healthcare needs, and has also identified the utility of a transition navigator for youth with special health care needs. Methods We developed a protocolized transition navigator intervention that used ecological assessment and motivational interviewing to assess transition readiness, identify goals, and remove barriers to transition, as well as to provide disease and pain management education and skills to AYAs with SCD. We assessed feasibility, acceptability and short-term efficacy in n=60 youth aged 17-20 with SCD. Findings Participation in the TN program was associated with significant improvement in transition readiness, disease knowledge, and confidence in disease and pain management for youth with SCD Conclusion The TN intervention was acceptable to youth with SCD and feasible to implement at an urban academic medical center and addressed most of the barriers to transition identified by the youth. Longer-term assessment is needed to determine if the transition navigator intervention improved successful transfer to and retention in adult care and reduced morbidity and ED reliance over time.
The relationship between the conservation laws and multi-Hamiltonian structures of th...
Jian-bing Zhang
Yingyin Gongye

Jian-bing Zhang

and 2 more

October 12, 2020
By the Lagrangian multiplier and constraint variational derivative, a relationship between conserved quantities and multi-Hamiltonian structures is built. Making using the relation a method is founded to prove the infinite-dimensional Liouville integrability of evolution equations with continuous variables. As the application, the conservation laws of the Kundu equation are firstly obtained. Its conserved quantities are deduced for comparing by Fokas' method different from the method used in the existed literature. The integrability of the equation is proved through taking the conservation laws as a starting point.
Recent and new results on octonionic Bergman and Szeg\”o kernels
Rolf Soeren Krausshar

Rolf Soeren Krausshar

October 12, 2020
Very recently one has started to study Bergman and Szeg\“o kernels in the setting of octonionic monogenic functions. In particular, explicit formulas for the Bergman kernel for the octonionic unit ball and for the octonionic right half-space as well as a formula for the Szeg\”o kernel for the octonionic unit ball have been established. In this paper we extend this line of investigation by developing explicit formulas for the Szeg\“o kernel of strip domains of the form ${\cal{S}} := \{z \in \mathbb{O} \mid 0 < \Re(z) < d\}$ from which we derive by a limit argument considering $d \to \infty$ the Szeg\”o kernel of the octonionic right half-space. Additionally, we set up formulas for the Bergman kernel of such strip domains and relate both kernels with each other. In fact, these kernel functions can be expressed in terms of one-fold periodic octonionic monogenic generalizations of the cosecant function and the cotangent function, respectively.
PREFERENCES FOR DISCLOSING ADVERSE CHILDHOOD EXPERIENCES FOR CHILDREN AND ADULTS WITH...
Wadsworth Williams
Manu Jain

Wadsworth Williams

and 3 more

October 12, 2020
Introduction: The 2017-2018 National Survey of Children’s Health estimates that 30 million (42%) US children have experienced at least one adverse childhood experience (ACE), including abuse, neglect, and household dysfunction. ACEs negatively impact long-term health, and there has been no study of ACEs in cystic fibrosis (CF). We assessed willingness to disclose ACEs experienced by children with CF by surveying their parents and adults with CF. Methods: We anonymously surveyed parents of children with CF and adults with CF at the Northwestern University/ Lurie Children’s CF Center to determine their willingness to disclose ACEs. Results: The survey was completed by 46/157 (29%) parents and 36/105 (34%) adults with CF. Few parents (22%) and adults (17%) were willing to discuss most or all specific ACEs, more were willing to disclose the number of ACEs experienced in a category (57% parents, 47% adults), and the majority were willing to participate in anonymous research about ACEs (76% parents, 67% adults). Most parents (63%) and adults (50%) would prefer to have ACEs screened separately from their CF appointment, and most parents (63%) and adults (56%) wanted to learn more about ACEs from a member of their care team. Conclusions: Participants preferred to disclose the number of categorical ACEs rather than specific ACEs and most were open to participating in anonymous ACEs research. More research is needed before widespread adoption of ACE screening in CF.
A severe case of COVID-19 in an adolescent with PIMS-TS, cardiomyopathy, and pulmonar...
Andreea Panciu
Cristina Neaga

Andreea Panciu

and 12 more

October 12, 2020
We report the case of a 14-year-old male patient with no previous history of cardiovascular disease or thromboembolic episodes, admitted to our hospital with a severe form of COVID-19, in the 9th day of disease evolution, with acute respiratory and heart failure symptoms. Chest computer tomography showed bilateral multilobular ground-glass opacities, consolidations, and a sub segmental arterial branch thromboembolism. The echocardiography showed a dilated left ventricle with severely impaired left ventricular function (LVEF=30%) . Blood test showed extremely elevated NT pro-BNP (22 558 ng/L), inflammatory markers and D-dimers. The diagnosis of PIMS-TS, COVID-19 sepsis-related cardiomyopathy and pulmonary thromboembolism was made, with a favourable outcome under supportive treatment. Clinicians should be aware of this severe presentation of COVID-19 in children.
Comparative microbial community analysis of fur seals and salmon aquaculture in Tasma...
Erin D'Agnese
Ryan McLaughlin

Erin D'Agnese

and 5 more

October 12, 2020
In Tasmania, Australia, the farmed Atlantic salmon (Salmo salmar L) industry utilizes marine leases to cultivate stock and faces opportunistic predation pressure from wild Australian fur seals (Arctocephalus pusillus doriferus). Microbial connectivity between aquaculture and wild pinnipeds was explored during this research, to find potential indicators for microbial sharing, identify potential pathogens at this interface, and elucidate potential effects of interactions on the microbiota of wild seals. High-throughput sequencing of the V1-V3 region of the 16S rRNA genes found in the gut microbial communities of 221 fur seals was performed; 41 males caught at fish farms, 50 fresh adult scats from haul-outs near farms, 24 necropsied seals, and controls from Bass strait rookeries including: 56 adult scats and 50 pup swabs. QIIME2 and R software were used for analysis of fur seal microbiomes, and to compare seal microbiomes to previously collected salmon microbiomes. Foraging at farms appears to shift biodiversity in fur seal microbiota; seals foraging at or near farms having greater phylogenetic diversity in their gut microbial communities compared to control seals. Taxonomic analysis showed a greater divergence in Proteobacteria representatives in male seals captured at farms compared to all other groups and identified indicator OTUs which could be used as minimally invasive indicators for interactions at this interface. These indicator OTUs included members of the following taxa: Clostridium sensu stricto I, Psychrobacter, Xanthomonadaceae, Suttonella, Pelomonas, an unclassified Weeksellaceae genus, Edwardsiella hoshinae, Pleisomonas shigelloides, and Cetobacterium ceti. Several potential pathogens were identified to monitor for human and animal health.
Invasive plant has higher resistance to native generalist herbivore than exotic non-i...
Li Chen
Zhen Liu

Li Chen

and 4 more

October 12, 2020
Studies on the effects of invasive plants on native herbivores often only concern about short-term effects, and few studies have focused on the long-term effects of invasive plants on herbivores. We investigated the development of Spodoptera litura to the second generation on the invasive plant Phytolacca americana and the exotic non-invasive plant Phytolacca icosandra, meanwhile, we tested the impacts of the P. americana on the S. litura through laboratory bioassay, oviposition preference and detoxifying enzyme activity analysis. The results show that S. litura have feeding and oviposition preference to P. icosandra, the larval weight and oviposition preference index (OPI) of S. litura feeding on P. icosandra are higher. However, the developmental duration of S. litura on P. icosandra is shorter than that of P. americana; the activities of Acetyl cholinesterase (AchE) and Glutathione-S-transferase (GST) of S. litura feeding on the leaves of the P. americana were higher than those of feeding on artificial diet and P. icosandra. There is no significant difference of activities of AchE and GST between S. litura feeding on artificial diet and P. icosandra. These findings have important implications for the evaluation of the impacts of invasive plant P. americana on native herbivores in the local ecosystem and explain that invasive plant has higher resistance to herbivores and suffer less damage than exotic non-invasive plant in the invaded range.
Flexibility Index of Black-Box Models with Parameter Uncertainty through Derivative-F...
Fei Zhao
Ignacio Grossmann

Fei Zhao

and 3 more

October 11, 2020
The existing methods of flexibility index are mainly based on mixed-integer linear or nonlinear programming methods, making it difficult to readily deal with complex mathematical models. In this article, a novel solution strategy is proposed for finding a reliable upper bound of the flexibility index where the process model is implemented in a black box that can be directly executed by a commercial simulator, and also avoiding the need for calculating derivatives. Then, the flexibility index problem is formulated as a sequence of univariate derivative-free optimization (DFO) models. An external DFO solver based on trust-region methods can be called to solve this model. Finally, after calculating the critical point of the model parameters, the vertex enumeration method and two gradient approximation methods are proposed to evaluate the impact of process parameters and to evaluate the flexibility index. A reaction model is studied to show the efficiency of the proposed algorithm.
Oral paclitaxel with encequidar compared to intravenous paclitaxel in patients with a...
Christopher Jackson
Tak Hung

Christopher Jackson

and 17 more

October 12, 2020
Background and purpose: Paclitaxel is a widely used anti-neoplastic agent but has low oral bioavailability due to gut extrusion by P-glycoprotein (P-gp). Oral paclitaxel could be more convenient, less resource intensive, and more tolerable than intravenous administration. Encequidar (HM30181A) is a novel, minimally absorbed gut specific P-gp inhibitor. We tested whether administration of oral paclitaxel with encequidar (oPac+E) achieved comparable AUC to intravenous paclitaxel (IVP) 80mg/m2. Experimental approach: We conducted a multi-centre randomised crossover study with two treatment periods. Patients (pts) with advanced cancer received either oral paclitaxel 615mg/m2 divided over three days and encequidar 15mg orally one-hour prior, followed by IVP 80mg/m2, or the reverse sequence. PK blood samples were taken up to day 9 for oPac+E and day 5 for IVP. Key Results: 42 pts were enrolled; 35 completed both treatment periods. AUC0-∞was 5033.5 +/- 1401.1 ng.h/mL for oPac+E and 5595.9 +/- 1264.1 ng.h/mL with IVP. The geometric mean ratio (GMR) for AUC was 89.5% (90% CI 83.9-95.5). Mean absolute bioavailability of oPac+E was 12%. PK parameters did not change meaningfully after 4 weeks administration of oPac+E in an extension study. G3 treatment emergent adverse events occurred in 7 (18%) pts with oPac+E and 2 (5%) with IVP. 75% of pts preferred oPac+E over IVP. Conclusion and Implications: GMR for AUC was within the predefined acceptable range of 80%-125% for demonstrating equivalence. oPac+E is tolerable and there is no evidence of P-gp induction with repeat administration. With further study, oPac+E is a candidate to replace IVP.
The heterozygous mutation of c.346-1G>A in SOHLH1 gene is irrelevant to nonobstruc...
LIU Mohan
Yihong Yang

Mohan Liu

and 4 more

October 11, 2020
Nonobstructive azoospermia (NOA) is an important cause of male infertility, and the genetic pathogenesis is still incompletely understood. The previous study reported that heterozygous mutation of c.346-1G>A in SOHLH1 gene was identified in two NOA patients. However, in our research, this heterozygous mutation was confirmed in a Chinese infertile patient who was suffered from teratozoospermia, and intriguingly, a homozygous mutation of c.346-1G>A in SOHLH1 gene was detected in another patient with severe oligozoospermia. Additionally, we correlated the good prognosis of intracytoplasmic sperm injection (ICSI) in the patient carrying the heterozygous mutation of c.346-1G>A in SOHLH1 gene. Thus, we suggested that the heterozygous mutation of c.346-1G>A in SOHLH1 may not be the direct genetic cause for NOA, and this homozygous mutation might impair spermatogenesis and further lead to the reduced sperm count and abnormal sperm morphology, eventually causing male infertility.
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