Resumo Fundamento Existem informações conflitantes sobre se a ultrassonografia pulmonar avaliada por linhas B tem valor prognóstico em pacientes com insuficiência cardíaca (ICa). Objetivos Avaliar o valor prognóstico da ultrassonografia pulmonar avaliada por linhas B em pacientes com ICa. Métodos Quatro bases de dados (PubMed, EMBASE, Cochrane Library e Scopus) foram sistematicamente pesquisadas para identificar artigos relevantes. Reunimos a razão de risco (RR) e o intervalo de confiança de 95% (IC) de estudos elegíveis e realizamos análises de heterogeneidade, avaliação de qualidade e viés de publicação. Os dados foram agrupados usando um modelo de efeitos fixos ou de efeito aleatório. Um valor de p <0,05 foi considerado para indicar significância estatística. Resultados Nove estudos envolvendo 1.212 participantes foram incluídos na revisão sistemática. As linhas B > 15 e > 30 na alta hospitalar foram significativamente associadas ao aumento do risco de desfecho combinado de mortalidade por todas as causas ou hospitalização por ICa (RR, 3,37, IC de 95%, 1,52-7,47; p = 0,003; RR, 4,01, IC de 95%, 2,29-7,01; p <0,001, respectivamente). O ponto de corte da linha B > 30 na alta foi significativamente associado ao aumento do risco de hospitalização por ICa (RR, 9,01, IC de 95%, 2,80-28,93; p <0,001). Além disso, o ponto de corte da linha B > 3 aumentou significativamente o risco de desfecho combinado de mortalidade por todas as causas ou hospitalização por ICa em pacientes ambulatoriais com ICa (RR, 3,21, IC de 95%, 2,09-4,93; I2 = 10%; p <0,00001). Conclusão As linhas B podem predizer mortalidade por todas as causas e hospitalizações por ICa em pacientes com ICa. Outros grandes ensaios clínicos randomizados são necessários para explorar se lidar com as linhas B melhoraria o prognóstico nos ambientes clínicos. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Abstract Background There is conflicting information about whether lung ultrasound assessed by B-lines has prognostic value in patients with heart failure (HF). Objectives To evaluate the prognostic value of lung ultrasound assessed by B-lines in HF patients. Methods Four databases (PubMed, EMBASE, Cochrane Library, and Scopus) were systematically searched to identify relevant articles. We pooled the hazard ratio (HR) and 95% confidence interval (CI) from eligible studies and carried out heterogeneity, quality assessment, and publication bias analyses. Data were pooled using a fixed-effects or random-effect model. A p value < 0.05 was considered to indicate statistical significance. Results Nine studies involving 1,212 participants were included in the systematic review. B-lines > 15 and > 30 at discharge were significantly associated with increased risk of combined outcomes of all-cause mortality or HF hospitalization (HR, 3.37, 95% CI, 1.52-7.47; p = 0.003; HR, 4.01, 95% CI, 2.29-7.01; p < 0.001, respectively). A B-line > 30 cutoff at discharge was significantly associated with increased risk of HF hospitalization (HR, 9.01, 95% CI, 2.80-28.93; p < 0.001). Moreover, a B-line > 3 cutoff significantly increased the risk for combined outcomes of all-cause mortality or HF hospitalization in HF outpatients (HR, 3.21, 95% CI, 2.09-4.93; I2 = 10%; p < 0.00001). Conclusion B-lines could predict all-cause mortality and HF hospitalizations in patients with HF. Further large randomized controlled trials are needed to explore whether dealing with B-lines would improve the prognosis in clinical settings.

Abstract Hereditary multiple exostoses (HME) is a rare skeletal disorder characterized by the formation of multiple benign cartilage-capped tumors, usually in the metaphyseal region of the long bones. Over 70% of HME cases arise from monoallelic mutations in either of the two genes encoding the heparan sulfate (HS) synthesis enzymes, ext1 and ext2. To identify more HME-associated mutations, genomic DNA from members of five independent consanguineous families with HME was sequenced with whole exome sequencing (WES). A novel heterozygous splice site mutation (c.1173+2T>A) in ext2 was detected in all three affected members of family V. Further study showed that the novel mutation caused exon 7 of ext2 mRNA to be skipped during splicing and caused a frameshift after the codon for Arg360, which results in the appearance of new 43 codons, followed by a termination codon. Although the resulting truncated protein was still localized to the Golgi, similar to the full-length EXT2, its HS synthesis activity decreased by 40%. In this study, a novel splice site mutation in ext2 was identified and suggested to be a pathogenic mutation of HME, which may expand the genetic etiology spectrum of HME and may be helpful for clinical genetic counseling and prenatal diagnosis.

Hormones regulate hepatic gene expressions to maintain metabolic homeostasis. Ectonucleotide pyrophosphatase/phosphodiesterase 1 has been thought to interfere with insulin signaling. To determine its potential role in the regulation of metabolism, we analyzed its gene (Enpp1) expression in the liver of rats experiencing fasting and refeeding cycles, and in primary rat hepatocytes and human hepatoma HepG2 cells treated with insulin and dexamethasone using northern blot and real-time PCR techniques. Hepatic Enpp1 expression was induced by fasting and reduced by refeeding in the rat liver. In primary rat hepatocytes and HepG2 hepatoma cells, insulin reduced Enpp1 mRNA abundance, whereas dexamethasone induced it. Dexamethasone disrupted the insulin-reduced Enpp1 expression in primary hepatocytes. This is in contrast to the responses of the expression of the cytosolic form of phosphoenolpyruvate carboxykinase gene to the same hormones, where insulin reduced it significantly in the process. In addition, the dexamethasone-induced Enpp1 gene expression was attenuated in the presence of 8-Br-cAMP. In conclusion, we demonstrated for the first time that hepatic Enpp1 is regulated in the cycle of fasting and refeeding, a process that might be attributed to insulin-reduced Enpp1 expression. This insulin-reduced Enpp1 expression might play a role in the development of complications in diabetic patients.

Background: Compared to conventional therapies, sacral neuromodulation (SNM) may offer an alternative, non-destructive treatment for SCI patients with bladder dysfunction. Understanding bladder response to SNM treatment for SCI in different phases may yield new insights for innovative use of this promising technique. Materials and Methods: Female Sprague-Dawley rats were used in this study to examine the effects of acute SNM on bladder reflex in complete SCI rats. All rats were anesthetized and set up for continuous saline infusion. Acute SNM treatment was implemented for about 6 hours for each rat. Cystometric parameters, including time between contractions, contraction duration, bladder peak pressure, and number of uninhibited contractions, were analyzed and compared within rats before and after SNM treatment. Results: For the spinally transected rats during early phase (less than two weeks post spinalization), the time between contractions and contraction duration both increased after SNM treatments, yet the increased amplitude was about or less than 20%. For the spinally transected rats with a longer days survival (about two to four weeks post spinalization), the time between contractions and contraction duration substantially increased after SNM treatment and the changes for their average values were more than 90%. For the spinally transected rats with a much longer days survival (more than five weeks post spinalization), the time between contractions and contraction duration increased after SNM treatments, yet the magnitude of changes were less than 30%. Conclusion: The present study suggested that the significant effectiveness of SNM for complete SCI played its role after the spinal shock phase and prior to the development of detrusor overactivity. It indicated that the time point of SNM treatment is necessary to be paid attention.

Major histocompatibility complex class I chain-related A (MICA) is a highly polymorphic gene located within the MHC class I region of the human genome. Expressed as a cell surface glycoprotein, MICA modulates immune surveillance by binding to its cognate receptor on natural killer cells, NKG2D, and its genetic polymorphisms have been recently associated with susceptibility to some infectious diseases. We determined whether MICA polymorphisms were associated with the high rate of Schistosoma parasitic worm infection or severity of disease outcome in the Dongting Lake region of Hunan Province, China. Polymerase chain reaction-sequence specific priming (PCR-SSP) and sequencing-based typing (SBT) were applied for high-resolution allele typing of schistosomiasis cases (N = 103, age range = 36.2-80.5 years, 64 males and 39 females) and healthy controls (N = 141, age range = 28.6-73.3 years, 73 males and 68 females). Fourteen MICA alleles and five short-tandem repeat (STR) alleles were identified among the two populations. Three (MICA*012:01/02, MICA*017 and MICA*027) showed a higher frequency in healthy controls than in schistosomiasis patients, but the difference was not significantly correlated with susceptibility to S. japonicum infection (Pc > 0.05). In contrast, higher MICA*A5 allele frequency was significantly correlated with advanced liver fibrosis (Pc < 0.05). Furthermore, the distribution profile of MICA alleles in this Hunan Han population was significantly different from those published for Korean, Thai, American-Caucasian, and Afro-American populations (P < 0.01), but similar to other Han populations within China (P > 0.05). This study provides the initial evidence that MICA genetic polymorphisms may underlie the severity of liver fibrosis occurring in schistosomiasis patients from the Dongting Lake region.