Background and objectives

Although renin-angiotensin-aldosterone system inhibition (RAASi) is a cornerstone in the treatment of children with CKD, it is sometimes discontinued when kidney function declines. We studied the reasons of RAASi discontinuation and associations between RAASi discontinuation and important risk markers of CKD progression and on eGFR decline in the Cardiovascular Comorbidity in Children with CKD study.

Background:

The negative effect of adverse childhood experiences (ACEs) on physical and mental health has led to calls for routine screening for ACEs in primary care settings. We aimed to examine the association between maternal ACEs and children’s behaviour problems (externalizing and internalizing) at age 5 in the context of other known predictors.

Background:

Previous studies examining potential sex and gender bias in the Canadian Resident Matching Service (CaRMS) match have had conflicting results. We examined the results of the CaRMS match over the period 2013–2019 to determine the potential association between applicants’ gender and the outcome of matching to their first-choice discipline.

Background:

Historically, some chiropractors have been critical of vaccination, and this has been the subject of recent media attention in Canada. We explored the association between media attention and public dissemination of vaccination information on Canadian chiropractors’ websites.

At about 6300 km, Chang Jiang or Long River (长江) is the longest river in Asia and third longest in the world. It is the longest in the world to flow entirely within one country and plays a large role in the history, culture, and economy of China. For thousands of years, the river has been used for water, irrigation, sanitation, transportation, industry, boundary-marking, and war. Passing through 10 provinces, it commences its flow from the Tanggula Mountains (唐古拉山) in ethnic Tibetan Qinghai (青海) Province in northwest China and ends at the East China Sea in Shanghai (上海). Along the middle reaches of the river, between the western upstream Baidi City (白帝城) of Chongqing (重庆) Municipality and Yichang (宜昌) city of Hubei (湖北) Province downstream, the river passes through 3 adjacent gorges, known as the Three Gorges (三峡): Qutang, Wuxia, and Xiling gorge (瞿塘, 巫峡, 西陵峡) cutting through the Wu Mountains (巫山). Spanning a distance of about 120 km, these gorges are noted for their natural beauty: unusual-looking mountain peaks ranging from 800 m to 2000 m, precipitous valleys, dense forest, and spectacular landscape. Many ancient government officials, scholars, poets, and painters visited the Three Gorges and left their impressions and praises in writings. Archeological discoveries in recent years have shown for the first time that the Three Gorges area should be recognized as the birthplace of Chinese civilization.

Quinolones, such as the antimalarial atovaquone, are inhibitors of the malarial mitochondrial cytochrome bc₁ complex, a target critical to the survival of both liver- and blood-stage parasites, making these drugs useful as both prophylaxis and treatment. Recently, several derivatives of endochin have been optimized to produce novel quinolones that are active in vitro and in animal models. While these quinolones exhibit potent ex vivo activity against Plasmodium falciparum and Plasmodium vivax, their activity against the zoonotic agent Plasmodium knowlesi is unknown. We screened several of these novel endochin-like quinolones (ELQs) for their activity against P. knowlesi in vitro and compared this with their activity against P. falciparum tested under identical conditions. We demonstrated that ELQs are potent against P. knowlesi (50% effective concentration, <117 nM) and equally effective against P. falciparum. We then screened selected quinolones and partner drugs using a longer exposure (2.5 life cycles) and found that proguanil is 10-fold less potent against P. knowlesi than P. falciparum, while the quinolones demonstrate similar potency. Finally, we used isobologram analysis to compare combinations of the ELQs with either proguanil or atovaquone. We show that all quinolone combinations with proguanil are synergistic against P. falciparum. However, against P. knowlesi, no evidence of synergy between proguanil and the quinolones was found. Importantly, the combination of the novel quinolone ELQ-300 with atovaquone was synergistic against both species. Our data identify potentially important species differences in proguanil susceptibility and in the interaction of proguanil with quinolones and support the ongoing development of novel quinolones as potent antimalarials that target multiple species.

The rising rates of antibiotic resistance increasingly compromise empirical treatment. Knowing the antibiotic susceptibility of a pathogen’s close genetic relative(s) may improve empirical antibiotic selection. Using genomic and phenotypic data for Escherichia coli isolates from three separate clinically derived databases, we evaluated multiple genomic methods and statistical models for predicting antibiotic susceptibility, focusing on potentially rapidly available information, such as lineage or genetic distance from archived isolates. We applied these methods to derive and validate the prediction of antibiotic susceptibility to common antibiotics. We evaluated 968 separate episodes of suspected and confirmed infection with Escherichia coli from three geographically and temporally separated databases in Ontario, Canada, from 2010 to 2018. Across all approaches, model performance (area under the curve [AUC]) ranges for predicting antibiotic susceptibility were the greatest for ciprofloxacin (AUC, 0.76 to 0.97) and the lowest for trimethoprim-sulfamethoxazole (AUC, 0.51 to 0.80). When a model predicted that an isolate was susceptible, the resulting (posttest) probabilities of susceptibility were sufficient to warrant empirical therapy for most antibiotics (mean, 92%). An approach combining multiple models could permit the use of narrower-spectrum oral agents in 2 out of every 3 patients while maintaining high treatment adequacy (~90%). Methods based on genetic relatedness to archived samples of E. coli could be used to predict antibiotic resistance and improve antibiotic selection.

Imipenem-relebactam (I-R) is a recently developed carbapenem–beta-lactamase inhibitor combination agent that can overcome carbapenem resistance, which has now emerged in Escherichia coli, including sequence type 131 (ST131) and its fluoroquinolone-resistant H30R subclone, the leading cause of extraintestinal E. coli infections globally. To clarify the likely utility of I-R for carbapenem-resistant (CR) E. coli infections in the United States, we characterized 203 recent CR clinical E. coli isolates from across the United States (years 2002 to 2017) for phylogroup, clonal group (including ST131, H30R, and the CTX-M-15-associated H30Rx subset within H30R), relevant beta-lactamase genes, and broth microdilution MICs for I-R and 11 comparator agents. Overall, I-R was highly active (89% susceptible), more so than all comparators except tigecycline and colistin (both 99% susceptible). I-R’s activity varied significantly in relation to phylogroup, clonal background, resistance genotype, and region. It was greatest among phylogroup B2, ST131-H30R, H30Rx, Klebsiella pneumoniae carbapenemase (KPC)-positive, and northeast U.S. isolates and lowest among phylogroup C, New Delhi metallo-β-lactamase (NDM)-positive, and southeast U.S. isolates. Relebactam improved imipenem’s activity against CR isolates within each phylogroup—especially groups A, B1, and B2—and particularly against isolates containing KPC. I-R remained substantially active against isolates coresistant to comparator agents, albeit somewhat less so than against the corresponding susceptible isolates. These findings suggest that I-R should be useful for treating most CR E. coli infections in the United States, largely independent of coresistance, although this likely will vary in relation to the local prevalence of specific E. coli lineages and carbapenem resistance mechanisms.

The effects of multiple-dose administration of tenofovir disoproxil fumarate (TDF) on the pharmacokinetics of morinidazole (MOR) were compared in healthy subjects. MOR exposure was similar, with an area under the curve from 0 h to infinity (AUC_0-) treatment ratio for MOR+TDF/MOR of 1.01 (90% confidence interval, 0.97 to 1.06). No relevant differences were observed regarding plasma exposure of metabolites. Renal clearances of MOR and its metabolites were not affected by TDF. No unexpected safety or tolerability issues were observed.

In this study, the plasmid content of clinical and commensal strains was analyzed and compared. The replicon profile was similar in both populations, except for L, M, A/C, and N (detected only in clinical strains) and HI1 (only in commensal strains). Although I1 and F were the most frequent replicons, only IncI1, sequence type 12 (ST12) was associated with bla_CMY-2 in both populations. In contrast, the widespread resistant IncF plasmids were not linked to a single epidemic plasmid.

In children requiring lopinavir coformulated with ritonavir in a 4:1 ratio (lopinavir-ritonavir-4:1) and rifampin, adding ritonavir to achieve a 4:4 ratio with lopinavir (LPV/r-4:4) overcomes the drug-drug interaction. Possible drug-drug interactions within this regimen may affect abacavir concentrations, but this has never been studied. Children weighing <15 kg needing rifampin and LPV/r-4:4 were enrolled in a pharmacokinetic study and underwent intensive pharmacokinetic sampling on 3 visits: (i) during the intensive and (ii) continuation phases of antituberculosis treatment with LPV/r-4:4 and (iii) 1 month after antituberculosis treatment completion on LPV/r-4:1. Pharmacometric modeling and simulation were used to compare exposures across weight bands with adult target exposures. Eighty-seven children with a median (interquartile range) age and weight of 19 (4 to 64) months and 8.7 (3.9 to 14.9) kg, respectively, were included in the abacavir analysis. Abacavir pharmacokinetics were best described by a two-compartment model with first-order elimination and transit compartment absorption. After allometric scaling adjusted for the effect of body size, maturation could be identified: clearance was predicted to be fully mature at about 2 years of age and to reach half of this mature value at about 2 months of age. Abacavir bioavailability decreased 36% during treatment with rifampin and LPV/r-4:4 but remained within the median adult recommended exposure, except for children in the 3- to 4.9-kg weight band, in which the exposures were higher. The observed predose morning trough concentrations were higher than the evening values. Though abacavir exposure significantly decreased during concomitant administration of rifampin and LPV/r-4:4, it remained within acceptable ranges. (This study is registered in ClinicalTrials.gov under identifier NCT02348177.)

We characterized 29 bla_CTX-M-27-harboring plasmids of Escherichia coli sequence type 131 (ST131) sublineage C1/H30R isolates from healthy individuals and long-term-care facility (LTCF) residents. Most (27/29) plasmids were of the FIA, FIB, and FII multireplicon type with the same plasmid multilocus sequence typing (pMLST). Several plasmids (7/23) from LTCF residents harbored only bla_CTX-M-27 as the resistance gene; however, their fundamental structures were very similar to those of previously isolated bla_CTX-M-27/F1:A2:B20 plasmids, suggesting their prevalence as a newly arising public health concern.

Unlike replicative senescence, oncogene-induced senescence caused heterochromatin-body formation.

Background:

Relatives of patients with bladder cancer have been shown to be at increased risk for kidney, lung, thyroid, and cervical cancer after correcting for smoking-related behaviors that may concentrate in some families. We demonstrate a novel approach to simultaneously assess risks for multiple cancers to identify distinct multicancer configurations (multiple different cancer types that cluster in relatives) surrounding patients with familial bladder cancer.

BACKGROUND AND PURPOSE:

The massa intermedia is a normal midline transventricular thalamic connection. Massa intermedia aberrations are common in schizophrenia, Chiari II malformation, X-linked hydrocephalus, Cornelia de Lange syndrome, and diencephalic-mesencephalic junction dysplasia, among others. We have noticed that massa intermedia abnormalities often accompany other midline malformations. The massa intermedia has never been formally evaluated in a group of exclusively pediatric patients, to our knowledge. We sought to compare and contrast the prevalence, size, and location of the massa intermedia in pediatric patients with and without congenital midline brain abnormalities.

BACKGROUND AND PURPOSE:

In the medicolegal literature, notching of the corpus callosum has been reported to be associated with fetal alcohol spectrum disorders. Our purpose was to analyze the prevalence of notching of the corpus callosum in a fetal alcohol spectrum disorders group and a healthy population to determine whether notching occurs with increased frequency in the fetal alcohol spectrum disorders population.

Năm 2012 bố tôi mất. Sau đó, tôi có làm giấy tờ sang tên 3 thửa đất lại cho tôi (giấy tờ đất đứng tên bố). Hiện nay, tôi muốn chuyển nhượng 400m2 đất cho người khác nhưng anh chị em trong nhà không đồng ý. Hỏi: Tôi có quyền chuyển nhượng quyền sử dụng đất cho người khác được không?

Mẹ tôi qua đời năm 2010. Khi lập di chúc chia nhà đất cho các con, do già yếu và không biết chữ nên bà đã nhờ người hàng xóm đến nhà để làm chứng cho việc lập di chúc. Vậy di chúc đó có được xem là hợp pháp?

Gia đình vợ tôi gồm có cha mẹ vợ, 1 ông anh vợ và vợ tôi là hết. Anh vợ tôi mất sớm chỉ để lại một đứa con gái. Cha vợ tôi cũng bệnh mất sau đó một thời gian, cả 2 không để lại di chúc gì cả. Mẹ vợ tôi cùng vợ và cháu nội của bà, 3 người có ra phòng công chứng làm thủ tục phân chia tài sản và bà cho tặng tất cả phần tài sản của bà cho vợ tôi. Sau cùng cả 3 cùng thống nhất tại phòng công chứng là cháu nội được hưởng 1/6 giá trị tài sản đó. Cụ thể tài sản là căn nhà mẹ vợ và vợ tôi đã ở từ trước 75 đến nay. Cháu nội tôi ở nơi khác (Hoa Kỳ). Nay mẹ vợ tôi già yếu vẫn cùng vợ tôi cư ngụ trong căn nhà trên, người cháu về đặt vấn đề phân chia căn nhà đó. Cho tôi hỏi vợ tôi và mẹ vợ tôi có bắt buộc phải phân chia ngay tại thời điểm này theo yêu cầu của người cháu nội đó hay không? Và khi mẹ chúng tôi mất thì vợ tôi có phải phân chia tài sản đó ngay theo như yêu cầu của người cháu hay không? Vì căn nhà mẹ và vợ tôi vẫn ở từ xưa đến giờ và không có tài sản nhà để ở nơi khác. Sau này vợ tôi có còn được ở trong căn nhà đó cho đến khi mua được nhà khác để ở mới bán căn nhà trên rồi mới chia tài sản cho người cháu hay phải bắt buộc chia liền? Xin cám ơn Luật sư.

Tôi và chồng sống chung với nhau từ năm 2002, có hai đứa con nhưng không đăng ký kết hôn. Trước tôi, anh ấy có một người vợ và ba con chung. Tháng 4/2017, chồng tôi mất và có di chúc để lại toàn bộ tài sản cho người vợ trước với ba con của họ. Xin hỏi con tôi không có tên trong di chúc thì có được chia thừa kế hay không?

“Các cụ vẫn bảo, đàn ông có ba việc lớn nhất định phải hoàn thành trong đời mới xứng phận nam nhi, đó là tậu trâu, cưới vợ, làm nhà. Nhưng cũng bởi hai chữ “sĩ diện” muốn xây ngôi nhà hoành tráng mà tôi đã đẩy gia đình lâm vào cảnh nợ nần chồng chất”, anh Tấn chia sẻ.

Sau 5 năm đi làm, chàng trai 9X ở Hà Tĩnh đã mua được một căn hộ chung cư rộng rãi tại Hà Nội với giá gần 2 tỷ đồng từ tiền tiết kiệm.

Mặt tiền của ngôi nhà được thiết kế đẹp sẽ tạo thêm điểm nhấn và nâng tầm vẻ đẹp cho ngôi nhà. Vì vậy, trước khi hoàn thiện, các gia chủ luôn đau đầu cho việc tìm kiếm giải pháp thiết kế, trang trí để giúp cho ngôi nhà của mình có một bộ mặt hoàn hảo nhất.

Chúng ta vẫn thường chú trọng đến cách kết hợp màu sắc không gian nội thất nhưng lại quên mất rằng ngoại thất cũng cần được được phối màu hài hòa, hợp mắt. Khi thiết kế sân vườn, hãy thử chọn vài ba màu sắc mà mình yêu thích và trồng những loại cây mang màu sắc đó nhằm biến vườn nhà trở nên rực rỡ và ấn tượng hơn.

Mùa đông đến, hãy thiết kế ban công nhà bạn trở nên ấm áp hơn để có thể thoải mái ngồi ngắm cảnh từ ban công và tận hưởng bầu không khí trong lành ngay cả khi những cơn gió lạnh đang ùa về.

Đừng vội vứt những chai nhựa, chai thủy tinh, giấy gói quà hay bóng đèn đã cháy đi bởi bạn có thể tái sinh chúng để trồng cây, cắm hoa, bảo quản hạt giống...

Tôi muốn hỏi chi phí cho một phòng trọ 12m2 không có gác là bao nhiêu?