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Tuberculosis (TB) elimination requires interrupting transmission of Mycobacterium tuberculosis. We used a multidisciplinary approach to describe TB transmission in 2 sociodemographically distinct districts in Botswana (Kopanyo Study). During August 2012-March 2016, all patients who had TB were enrolled, their sputum samples were cultured, and M. tuberculosis isolates were genotyped by using 24-locus mycobacterial interspersed repetitive units-variable number of tandem repeats. Of 5,515 TB patients, 4,331 (79%) were enrolled. Annualized TB incidence varied by geography (range 66-1,140 TB patients/100,000 persons). A total of 1,796 patient isolates had valid genotyping results and residential geocoordinates; 780 (41%) patients were involved in a localized TB transmission event. Residence in areas with a high burden of TB, age <24 years, being a current smoker, and unemployment were factors associated with localized transmission events. Patients with known HIV-positive status had lower odds of being involved in localized transmission.
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Mycobacterium tuberculosis , Tuberculose , Adulto , Botsuana , Estudos Epidemiológicos , Genótipo , Humanos , Repetições Minissatélites , Epidemiologia Molecular , Mycobacterium tuberculosis/genética , Adulto JovemRESUMO
Heavy metal pollution is a serious problem in wetland ecosystems, and the toxicity of heavy metals affects microorganisms, thus influencing the biogeochemical process of nitrogen (N). To investigate the effects of heavy metal cadmium (Cd) pollution on N mineralization in urban constructed wetland soils of the Pearl River Delta, a 40-day aerobic incubation experiment was conducted under three Cd addition treatments [no Cd addition (control), low Cd addition (LCA) and high Cd addition (HCA)]. The results showed that compared with the control, the LCA treatment enhanced the soil N mineralization rate (RM), while the HCA treatment inhibited RM, with the average RM values in the control treatment of 0.40 mg kg-1 day-1, LCA treatments (0.66 mg kg-1 day-1), and HCA treatments (0.21 mg kg-1 day-1). The average ammonification rate values in the LCA treatments (- 3.15 to 2.25 mg kg-1 day-1) were higher than those in the HCA treatments (- 2.39 to 0.74 mg kg-1 day-1) and the control treatment (- 0.68 to 0.90 mg kg-1 day-1) (P < 0.05). However, the nitrification values in the HCA treatments (- 0.37 to 3.36 mg kg-1 day-1) were higher than those in the LCA treatments (0.42-1.93 mg kg-1 day-1) and the control treatment (0.20-1.45 mg kg-1 day-1) (P < 0.05). The net N mineralization accumulation generally increased over the entire incubation time in different Cd addition treatments. The percentage of NH4+-N to total inorganic N showed a decrease, while an increase was observed for NO3--N over the incubation time. The urease activities were significantly inhibited in the LCA and HCA treatments and showed a "decreasing before increasing" trend. The abundance of ammonia oxidizing archaea (AOA) was higher in the two Cd addition treatments than the control treatment, and higher in the LCA treatments than in the HCA treatment. AOA was the dominant microorganism in the ammonia oxidation process of N mineralization in constructed wetland soils. The findings of this work indicate that Cd addition has a profound effect on the balance of N mineralization and may further impact the plant productivity and water quality of constructed wetlands.
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Cádmio/química , Nitrogênio/química , Solo/química , Áreas Alagadas , China , Ecossistema , Minerais/química , RiosRESUMO
Reconciliation is an essential procedure for continuous-variable quantum key distribution (CV-QKD). As the most commonly used reconciliation protocol in short-distance CV-QKD, the slice error correction (SEC) allows a system to distill more than 1 bit from each pulse. However, the quantization efficiency is greatly affected by the noisy channel with a low signal-to-noise ratio (SNR), which usually limits the secure distance to about 30 km. In this paper, an improved SEC protocol, named Rotated-SEC (RSEC), is proposed through performing a random orthogonal rotation on the raw data before quantization, and deducing a new estimator for the quantized sequences. Moreover, the RSEC protocol is implemented with polar codes. The experimental results show that the proposed protocol can reach up to a quantization efficiency of about 99%, and maintain at around 96% even at the relatively low SNRs (0.5,1), which theoretically extends the secure distance to about 45 km. When implemented with the polar codes with a block length of 16 Mb, the RSEC achieved a reconciliation efficiency of above 95%, which outperforms all previous SEC schemes. In terms of finite-size effects, we achieved a secret key rate of 7.83×10-3 bits/pulse at a distance of 33.93 km (the corresponding SNR value is 1). These results indicate that the proposed protocol significantly improves the performance of SEC and is a competitive reconciliation scheme for the CV-QKD system.
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With the increasing intensity of global human activities, the ecosystem function, which is supported by the microbial community, will be dramatically changed and impaired. To investigate microbial resistance and resilience of microbial communities to human activities, we chose two typical types of human disturbances, urbanization, and reclamation under the higher intensity of human activities than the global average level. We examined microbial traits, including the abundance, diversity, phylogeny, and co-occurrence interactions in soil microbial communities, together with the nitrification activities observed in the subtropical coastal ecosystem of the Pearl River Estuary and in soil microcosm experiments. Microbial communities were less resistant to the environmental changes caused by urbanization than to those caused by reclamation, which was significantly reflected in the nitrogen and/or carbon-related patterns. However, most of the microbial traits could be recovered almost to the original level without significant differences in the microcosm after 40 days of incubation. The co-occurrence interactions between nitrifiers and other microbial communities were dramatically changed and could not be completely recovered, but this change did not affect their nitrification activities for balancing the ammonium in the soil to the original level during the recovery stage, suggesting that the interactions between microbial communities might have fewer effects on their activities than previously thought. This study quantitatively demonstrated that microbial communities as a whole can recover to a status similar to the original state in a short time after the removal of stress at a large ecosystem scale even under the higher intensity of human activities than global average level in coastal ecosystems, which implied a strong recovery capacity of soil microbial community even after intense human disturbance.
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OBJECTIVE: To analyze the genotype of a patient suspected for thalassemia through a series of experiments. METHODS: Conventional methods for detecting common thalassemia mutations was used in conjunction with multiplex ligation-dependent probe amplification (MLPA) in order to determine the genotype of the patient. Corresponding primers were designed for developing a Gap-PCR system for detecting rare type mutations. RESULTS: The patient was identified as a homozygote for Chinese Gγ(Aγδß)0-thal deletion, with clinical manifestations tending to be intermediate or severe based on the hematological characteristics. A Gap-PCR system has been developed for detecting the above mutation with accuracy and rapidity. CONCLUSION: The Chinese Gγ(Aγδß)0-thal is prevalent in southern China, and caution should be taken to avoid misdiagnosis. The Gap-PCR system for detecting Chinese Gγ(Aγδß)0-thal is suitable for extended applications for its simplicity and rapidity.
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Talassemia/genética , Povo Asiático , China , Homozigoto , Humanos , Deleção de SequênciaRESUMO
Thalassemia is the most common monogenic disease, with the highest incidence in Guangxi Zhuang Autonomous Region, People's Republic of China (PRC). The blood test result was not consistent with α-globin gene testing in one of the patients during daily screening. It was confirmed that there were multiple mutations at the α2-globin gene polyadenylation (polyA) signal site: HBA2: c.*64(T>C), HBA2: c.*68(A>C), HBA2: c.*71(G>A), HBA2: c.*74(C>A), HBA2: c.*82(G>A), HBA2: c.*92(A>G) and HBA2: c.*98(T>C) and compound - -SEA/αα by sequencing of the HBA1 and HBA2 genes of the proband and core family members. After that, we found a further two cases of unrelated patients with this type of mutation. The mutation is not an accidental phenomenon, and likely to occur with a considerable incidence in Guangxi Zhuang Autonomous Region, PRC. We analyzed the hematological manifestations of this type of thalassemia and showed that it was a Hb H (ß4) disease caused by rare mutations. We suggest that it is essential to pay attention to this mutation during future clinical diagnoses and genetic counseling of patients.
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Hemoglobina H/genética , Mutação , Poli A/genética , Poliadenilação , alfa-Globinas/genética , Talassemia alfa/diagnóstico , Talassemia alfa/genética , Adulto , Alelos , Códon , Índices de Eritrócitos , Feminino , Frequência do Gene , Genótipo , Humanos , Análise de Sequência de DNARESUMO
Gene therapy that targets the ROCK2 gene has yielded promising results in the treatment of AD. Our previous study indicated that PEG-PEI/siROCK2 could effectively suppress ROCK2 mRNA expression and showed a promising prospect for the treatment of Alzheimer's disease. However, the ability of PEG-PEI/siROCK2 to reduce Aß-induced cytotoxicity is unknown. To investigate the effect of PEG-PEI/siROCK2 against Aß42-induced neurotoxicity, primary cultured cortical neurons were pretreated with PEG-PEI/siROCK2 for 24 h and then treated with 5 µM Aß42 for 24 h. We found that PEG-PEI/siROCK2 increased the cell viability and reduced the number of apoptotic cells induced by Aß42, as measured using an MTT assay and Annexin V/PI staining. A further study revealed that PEG-PEI/siROCK2 can activate p-Akt, and treatment with the PI3K inhibitor LY294002 attenuated the neuroprotective effects. These results suggest that PEG-PEI/siROCK2 prevents Aß42-induced neurotoxicity and that the activation of PI3K/Akt pathway is involved in neuroprotection. Taken together, these findings shed light on the role of PEG-PEI/siROCK2 as a potential therapeutic agent for AD.
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Doença de Alzheimer/terapia , Peptídeos beta-Amiloides/toxicidade , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Fragmentos de Peptídeos/toxicidade , Polietilenoglicóis/química , Polietilenoimina/análogos & derivados , RNA Interferente Pequeno/administração & dosagem , Quinases Associadas a rho/antagonistas & inibidores , Doença de Alzheimer/genética , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Portadores de Fármacos/química , Embrião de Mamíferos , Técnicas de Transferência de Genes , Terapia Genética/métodos , Humanos , Camundongos , Terapia de Alvo Molecular/métodos , Neurônios/citologia , Neurônios/fisiologia , Fármacos Neuroprotetores/farmacologia , Polietilenoimina/química , Cultura Primária de Células , RNA Interferente Pequeno/farmacologia , Quinases Associadas a rho/genéticaRESUMO
BACKGROUND: The prevalence of chronic kidney disease as measured by biomarkers is increasing, but the recognition for this condition remains low in the USA. Little is known about the awareness of kidney disease at the state level. METHODS: Data from 490,302 adults aged 18 years or older in all 50 states as well as the District of Columbia who participated in the 2011 Behavioral Risk Factor Surveillance System were analyzed. Kidney disease diagnosis, a measure of individual awareness, was ascertained by participants' self-report in the telephone survey. Prevalence ratios of self-reported kidney disease in subpopulations were estimated and tested using log-linear regression analyses with a robust variance estimator. RESULTS: The unadjusted prevalence of self-reported kidney disease was estimated to be 2.5%. After adjustment for age and all other selected covariates, Hispanics had a higher prevalence than non-Hispanic whites (adjusted prevalence ratio 1.2, 95% CI 1.0-1.4). Persons who were unemployed (adjusted prevalence ratio 1.4, 95% CI 1.2-1.5) had a higher prevalence than those who were employed. Persons who had hypertension (adjusted prevalence ratio 1.9, 95% CI 1.7-2.1), diabetes (adjusted prevalence ratio 1.7, 95% CI 1.5-1.8), cardiovascular disease (coronary heart disease, myocardial infarction or stroke; adjusted prevalence ratio 1.5, 95% CI 1.4-1.6) or cancer (adjusted prevalence ratio 1.5, 95% CI 1.3-1.6) had a higher prevalence of self-reported kidney disease than those without these conditions. CONCLUSION: The overall awareness of kidney disease was low in the general population. Efforts are needed to promote the awareness and early detection of kidney disease in public health services and clinical practice.
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Conhecimentos, Atitudes e Prática em Saúde , Nefropatias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prevalência , Fatores de Risco , Autorrelato , Estados Unidos/epidemiologia , Adulto JovemRESUMO
PURPOSE: A plenty of studies have demonstrated that the Rho/ROCK pathway is involved in the neuronal loss and inhibition of axonal regeneration observed in Alzheimer's disease (AD). Therefore, we conducted this study to evaluate whether intracranial injection of PEG-PEI/ROCK II siRNA (PPRS) would improve the cognitive impairments in a senescence-accelerated mouse (SAM) model of AD. MATERIALS AND METHODS: Five male senescence-resistant inbred strain (SAMR1) mice and 15 male senescence-accelerated mouse prone-8 (SAMP8) strain mice were divided into the following three groups:PPRS group, PEG-PEI/ ROCK II-Scramble (PPRScr) siRNA group, and normal group (SAMR1). Total volumes of 2.3 µl of nanoparticles or saline were intracranially injected under the guidance of a stereotaxic apparatus. The injections were performed every three days and lasted for two weeks. Four weeks after injection, the Morris water maze (MWM) was used to evaluate the spatial learning and memory functions of the mice. Choline acetyltransferase (ChAT) activity was detected by immunohistochemistry. RESULTS: Mice in the PPRS-treated group exhibited decreases in escape latencies over the three successive days of navigating the test and crossing the target quadrant during the spatial probe test more frequently than did the mice in the PPRScr-treated group. Analyses of ChAT activity revealed that greater numbers of ChAT-positive cells were present in the hippocampal regions of the PPRS-treated mice than in the PPRScr group. CONCLUSIONS: Intracranial injection of PPRS improved the cognitive impairments of SAM mice, and this improvement may have been mediated by enhancement of ChAT activity in the hippocampus.
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Antipsicóticos/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/metabolismo , Polietilenoglicóis/uso terapêutico , Polietilenoimina/análogos & derivados , RNA Interferente Pequeno/uso terapêutico , Quinases Associadas a rho/metabolismo , Envelhecimento/genética , Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Análise de Variância , Animais , Colina O-Acetiltransferase/metabolismo , Transtornos Cognitivos/etiologia , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Deficiências da Aprendizagem/tratamento farmacológico , Deficiências da Aprendizagem/etiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Camundongos , Polietilenoglicóis/metabolismo , Polietilenoglicóis/farmacologia , Polietilenoimina/metabolismo , Polietilenoimina/farmacologia , Polietilenoimina/uso terapêutico , RNA Interferente Pequeno/farmacologiaRESUMO
AIM: CD(+)(4)CD(+)(25) Treg cells are of critical importance for maintenance of tolerance. The purpose of the this study was to observe the number of CD(+)(4)CD(+)(25) Treg cells in the patients with thrombotic thrombocytopenic purpura (TTP) associated with systemic lupus erythematosus (SLE), and to study pathogenesis of TTP with SLE. METHODS: Seven patients with TTP associated with SLE and seven healthy volunteers were studied. The CD(+)(4)CD(+)(25) Treg cells were examined by flow cytometry. Clinical and laboratory data, such as urinary protein, serum creatinine, endothelial markers and immunologic serologics, were obtained from each patient and healthy volunteer. Glomerular injury was assessed by histopathology. Serum IL-2, IL-4, IL-6 and anti-endothelial cell antibody were analyzed by ELISA and anti-ADAMTS13 antibody were detected by Western blotting. RESULTS: CD(+)(4)CD(+)(25) Treg cells significantly decreased in TTP with SLE patients compared with controls (p < 0.05). CD(+)(4)CD(+)(25) Treg cells are negatively correlated with blood urea nitrogen, serum uric acid, supernatant IL-4, and proteinuria, and positively with estimated glomerular filtration rate (eGFR) in TTP with SLE patients. [Formula: see text] Treg cells gradually decreased as the severity of renal histology increased. Serum IL-2, IL-6, supernatant IL-4, anti-endothelial cell antibody, and anti-ADAMTS13 antibody significantly increased in TTP with SLE patients compared to those of the control groups (all p < 0.05). In contrast, serum levels of C3 were significantly decreased in TTP with SLE patients compared to those of the control groups (p < 0.05). CONCLUSIONS: CD(+)(4)CD(+)(25) Treg cells are not only lower in TTP with SLE patients, but also are correlated with disease severity in TTP with SLE patients.CD(+)(4)CD(+)(25)Treg cells may play an important role in the pathogenesis of TTP with SLE.
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Linfócitos T CD4-Positivos/imunologia , Subunidade alfa de Receptor de Interleucina-2 , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Púrpura Trombocitopênica Trombótica/complicações , Púrpura Trombocitopênica Trombótica/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Autoanticorpos , Feminino , Humanos , Interleucina-6 , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Trombótica/sangueRESUMO
The intensification of market competition makes refined operation management become the focus of attention of major manufacturers. As an important branch of artificial intelligence (AI), machine learning (ML) plays a key role in it, and has its application prospect in various systems. Based on this situation, this paper takes vending machines as the research object. On the one hand, the product classification model of vending machine is constructed based on decision tree algorithm. On the other hand, based on neural network (NN), the sales forecast model of vending machines is built. Finally, based on the above research, the theoretical framework of decision support system (DSS) for vending machines is constructed. The research shows that: (1) The accuracy of C4.5 algorithm can reach 87 % at the highest and 68 % at the lowest. The accuracy of the improved C4.5 algorithm can reach 87 % at the highest and 67 % at the lowest, with little difference between them. (2) The maximum running time of the improved C4.5 algorithm is about 5500 ms, and the minimum is close to 1 ms. In addition, the running time of all seven datasets is better than that of the unmodified algorithm. (3) When the back propagation neural network (BPNN) is used to forecast the sales of vending machines, the curve of the predicted data basically coincides with the curve of the actual data, which shows that its accuracy is high. This paper aims to build a convenient and secure DSS by taking vending machines as an example. In addition, this paper also uses reinforcement learning to optimize the research methods of this paper. It can further optimize the performance and efficiency of vending machines and provide better service experience for customers. Meanwhile, the use of reinforcement learning can make the whole system more intelligent and adaptive to better cope with the changing market environment.
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OBJECTIVE: To investigate the association between a low oocyte maturity ratio from in vitro fertilization cycle and blastocyst euploidy. METHODS: A total of 563 preimplantation genetic testing (PGT) cycles (PGT cycles with chromosomal structural rearrangements were excluded) were performed between January 2021 and November 2022 at our center (average oocyte maturity rate: 86.4% ± 14.6%). Among them, 93 PGT cycles were classified into the low oocyte maturity rate group (group A, < mean - 1 standard deviation [SD]), and 186 PGT cycles were grouped into the average oocyte maturity rate group (group B, mean ± 1 SD). Group B was 2:1 matched with group A. Embryological, blastocyst ploidy, and clinical outcomes were compared between the two groups. RESULTS: The oocyte maturity (metaphase II [MII oocytes]), MII oocyte rate, and two pronuclei (2PN) rates were significantly lower in group A than in group B (5.2 ± 3.0 vs. 8.9 ± 5.0, P = 0.000; 61.6% vs. 93.0%, P = 0.000; 78.7% vs. 84.8%, P = 0.002, respectively). In group A, 106 of 236 blastocysts (44.9%) that underwent PGT for aneuploidy were euploid, which was not significantly different from the rate in group B (336/729, 46.1%, P = 0.753). However, euploid blastocysts were obtained only in 55 cycles in group A (55/93, 59.1%), which was lower than the rate in group B (145/186, 78.0%, P = 0.001). The clinical pregnancy rate in group B (73.9%) was higher than that in group A (58.0%) (P = 0.040). CONCLUSION: Our results suggest that a low oocyte maturity ratio is not associated with blastocyst euploidy but is associated with fewer cycles with euploid blastocysts for transfer, lower 2PN rates, and lower clinical pregnancy rates.
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BACKGROUND/AIM: CD4+CD25+ regulatory T (Treg) cells are of critical importance for maintenance of tolerance. We showed that the number of CD4+CD25+ Treg cells was significantly lower in tonsils of patients with IgA nephropathy (IgAN); however, the function of tonsillar CD4+CD25+ Treg cells in IgAN has not been reported. The aim of this study was to investigate the effect of tonsillar CD4+CD25+ Treg cells of IgAN patients on experimental IgAN in rats. METHODS: Tonsillar CD4+CD25+ Treg cells were isolated by magnetic beads. A total of 2 × 10(6) CD4+CD25+ Treg cells were transferred into rats that were previously orally immunized over a period of 14 weeks and subsequently received an injection of BSA into the tail vein on 3 consecutive days. Urine protein and erythrocytes were measured. Glomerular injury was assessed by histopathology. Plasminogen activator inhibitor type 1 (PAI-1), interleukin (IL)-6 and transforming growth factor (TGF)-ß1 in mesangial cells of rats were examined by reverse transcription PCR. Serum IgA and C3 and supernatants of IL-2, IL-4 and IL-6 in splenic cells were analysed by ELISA. Transferred tonsillar CD4+CD25+ Treg cells were tracked by reverse transcription PCR and flow cytometry. RESULTS: IgA deposition in the mesangial region and the glomerular planar area and the number of cells, levels of serum IgA and supernatant IL-2, IL-4 and IL-6 in splenic cells and PAI-1, IL-6 and TGF-ß1 expression in renal mesangial cells of rats that received CD4+CD25+ Treg cells from IgAN patients were significantly higher than in rats that received CD4+CD25+ Treg cells from the control group, although they were dramatically lower compared with rats treated without CD4+CD25+ Treg cells. Transferred tonsillar CD4+CD25+ Treg cells migrated predominantly to secondary lymphoid organs but not to the kidneys. CONCLUSION: Dysfunction of tonsillar CD4+CD25+ Treg cells may be an important cause of IgAN progression.
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Glomerulonefrite por IGA/imunologia , Tolerância Imunológica , Tonsila Palatina/imunologia , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Animais , Complemento C3/metabolismo , Modelos Animais de Doenças , Feminino , Glomerulonefrite por IGA/metabolismo , Glomerulonefrite por IGA/patologia , Humanos , Masculino , Tonsila Palatina/patologia , Ratos , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/transplante , Adulto JovemRESUMO
X-Linked Alport Syndrome (XLAS) is an X-linked, dominant, hereditary nephropathy mainly caused by mutations in the COL4A5 gene, found on chromosome Xq22. In this study, we reported a pedigree with XLAS caused by a COL4A5 mutation. This family gave birth to a boy with XLAS who developed hematuria and proteinuria at the age of 1 year. We used next-generation sequencing (NGS) to identify mutations in the proband and his parents and confirmed the results using Sanger sequencing. This testing showed there was a single nucleotide missense variation, c.3659G>A (p.Gly1220Asp) (NM_033380.3), in the COL4A5 gene. To prevent the inheritance of the syndrome, we used eight embryos for trophoblast biopsy after assisted reproductive technology treatment, and whole genome amplification (WGA) was performed using multiple annealing and looping-based amplification cycles (MALBAC). Embryos were subjected to Preimplantation Genetic Testing (PGT) procedures, including Sanger sequencing, NGS-based single nucleotide polymorphism (SNP) haplotype linkage analysis, and chromosomal copy number variation (CNV) analysis. The results showed that three embryos (E1, E2, and E4) were free of CNV and genetic variation in the COL4A5 gene. Embryo E1 (4AA) was transferred after consideration of the embryo growth rate, morphology, and PGT results. Prenatal diagnosis in the second trimester showed that the fetus had a normal karyotype and did not carry the COL4A5 mutation (c.3659G>A). Ultimately, a healthy boy was born and did not carry the pathogenic COL4A5 mutation, which indicated that PGT prevented the intergenerational transmission of the causative mutation of XLAS.
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BACKGROUND: Biallelic loss-of-function variants in WWOX cause WWOX-related epileptic encephalopathy (WOREE syndrome), which has been reported in 60 affected individuals to date. In this study, we report on an affected individual with WOREE syndrome who presented with early-onset refractory seizures and global neurodevelopmental delay and died at the age of two and a half years. METHODS: We present clinical and molecular findings in the affected individual, including biallelic pathogenic variants in the WWOX gene. We employed different molecular approaches, such as whole exome sequencing, quantitative real-time polymerase chain reaction (qPCR), and whole-genome sequencing, to identify the genetic variants. The breakpoints were determined through gap PCR and Sanger sequencing. RESULT: Whole exome sequencing revealed homozygous exon 6 deletion in the WWOX gene in the proband. Quantitative real-time PCR confirmed that the parents were heterozygous carriers of exon 6 deletion. However, using whole-genome sequencing, we identified three larger deletions (maternal allele with exon 6-8 deletion and paternal allele with two deletions in proximity one in intron 5 and the other in exon 6) involving the WWOX gene in the proband, with deletion sizes of 13,261 bp, 53,904 bp, and 177,200 bp. The exact breakpoints were confirmed through gap PCR and Sanger sequencing. We found that the proband inherited the discontinuous deletion of intron 5 and exon 6 from the father, and the exons 6-8 deletion from the mother using gap PCR. CONCLUSION: Our findings extend the variant spectrum of WOREE syndrome and support the critical role of the WWOX gene in neural development.
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Mães , Proteínas Supressoras de Tumor , Feminino , Humanos , Pré-Escolar , Oxidorredutase com Domínios WW/genética , Proteínas Supressoras de Tumor/genética , Síndrome , Reação em Cadeia da Polimerase em Tempo Real , Deleção de GenesRESUMO
Background: This study aimed to perform preimplantation genetic testing (PGT) for a female Coffin-Lowry Syndrome (CLS) patient with a de novo mutation (DNM) in RPS6KA3. It was challenging to establish the haplotype in this family because of the lack of information from affected family members. Hence, we explored a new and reliable strategy for the detection of the DNM in PGT, using Oxford Nanopore Technologies (ONT) and the MARSALA platform. Methods: We performed whole-exome sequencing (WES) on the proband and confirmed the pathogenic mutation by Sanger sequencing. The proband then underwent PGT to prevent the transmission of the pathogenic mutation to her offspring. We diverged from the conventional methods and used long-read sequencing (LRS) on the ONT platform to directly detect the mutation and nearby SNPs, for construction of the haplotype in the preclinical phase of PGT. In the clinical phase of embryo diagnosis, the MARSALA method was used to detect both the SNP-based haplotype and chromosome copy number variations (CNVs), in each blastocyst. Finally, a normal embryo was selected by comparison to the haplotype of the proband and transferred into the uterus. Sanger sequencing and karyotyping were performed by amniocentesis, at 17 weeks of gestation, to confirm the accuracy of PGT. Results: Using WES, we found the novel, heterozygous, pathogenic c.1496delG (p.Gly499Valfs*25) mutation of RPS6KA3 in the proband. The SNP-based haplotype that was linked to the pathogenic mutation site was successfully established in the proband, without the need for other family members to be tested with ONT. Eight blastocysts were biopsied to perform PGT and were assessed with a haplotype linkage analysis (30 SNP sites selected), to give results that were consistent with direct mutation detection using Sanger sequencing. The results of PGT showed that three of the eight blastocysts were normal, without the DNM. Moreover, the patient had a successful pregnancy, after transfer of a normal blastocyst into the uterus, and delivered a healthy baby. Conclusion: The ONT platform, combined with the MARSALA method, can be used to perform PGT for DNM patients without the need for other samples as a reference.
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Using data from the 2008 Behavioral Risk Factor Surveillance System on 281,303 adults aged 18-64 years in the United States, we examined the relationship between HIV risk behaviors and binge drinking of alcoholic beverages and the frequency of binge drinking among a subgroup of 41,073 respondents who were acknowledged binge drinkers (bingers), based on reported drinking behavior in the year preceding survey. Our findings show that the weighted prevalence of HIV risk behaviors (including injection drug use, exchange of sex for money/drugs, and anal sex without a condom) among binge drinkers [corrected] [7.0%, 95% confidence interval (95% CI): 6.4-7.6%] is twice that among nonbingers (2.9%, 95% CI: 2.7-3.0%). The highest prevalence of HIV risk behaviors is among the bingers aged 18-20 years (14%, 95% CI: 11.2-18.2%). After adjusting for covariates, bingers are 1.77 (95% CI: 1.58-2.00) times more likely than nonbingers to report HIV risk behaviors. Risk increases in bingers with the number of episodes. Compared with bingers reporting 1-2 binge episodes in the month proceeding survey, the adjusted odds of reporting HIV risk behaviors among bingers are 1.27 (1.08-1.49), 1.68 (1.35-2.10), 1.67 (1.08-2.57), and 1.70 (1.34-2.16), respectively for bingers with 3-4, 5-6, 7-8, and ≥9 episodes in the same period. Our results suggest that HIV risk behaviors are strongly linked with binge drinking and its frequency. Effective measures to prevent binge drinking are essential to HIV prevention, especially among youth aged 18-20 years.
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Consumo de Bebidas Alcoólicas/psicologia , Etanol/intoxicação , Infecções por HIV/epidemiologia , Assunção de Riscos , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estados Unidos/epidemiologia , Adulto JovemRESUMO
INTRODUCTION: Binge drinking (men, ≥ 5 drinks, women, ≥ 4 on an occasion) accounts for more than half of the 79,000 annual deaths due to excessive alcohol use in the United States. The frequency of binge drinking is associated with poor health-related quality of life (HRQOL), but the association between binge drinking intensity and HRQOL is unknown. Our objective was to examine this association. METHODS: We used 2008-2010 Behavioral Risk Factor Surveillance System data and multivariate linear regression models to examine the association between binge drinking intensity (largest number of drinks consumed on any occasion) among US adult binge drinkers and 2 HRQOL indicators: number of physically and mentally unhealthy days. RESULTS: Among binge drinkers, the highest-intensity binge drinkers (women consuming ≥ 7 drinks and men consuming ≥ 8 drinks on any occasion) were more likely to report poor HRQOL than binge drinkers who reported lower levels of intensity (women who consumed 4 drinks and men who consumed 5 drinks on any occasion). On average, female binge drinkers reported more physically and mentally unhealthy days (2.8 d and 5.1 d, respectively) than male binge drinkers (2.5 d and 3.6 d, respectively). After adjustment for confounding factors, women who consumed ≥ 7 drinks on any occasion reported more mentally unhealthy days (6.3 d) than women who consumed 4 drinks (4.6 d). Compared with male binge drinkers across the age groups, female binge drinkers had a significantly higher mean number of mentally unhealthy days. CONCLUSION: Our findings underscore the importance of implementing effective population-level strategies to prevent binge drinking and improve HRQOL.
Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Intoxicação Alcoólica/epidemiologia , Etanol/intoxicação , Qualidade de Vida , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologiaRESUMO
Purpose: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common pathogens of community- and hospital-acquired infections, and its prevalence is increasing globally. Guiyang is the capital city of Guizhou Province, Southwest China; as the transport and tourism centre of Southwest China, Guizhou Province is bordered by Yunnan, Sichuan, Chongqing, and Guangxi Provinces. Although MRSA prevalence is increasing, little is known about its aspects in the area. The purpose of this study was to analyse MRSA molecular characteristics, antimicrobial resistance, and virulence genes in Guiyang. Methods: In total, 209 MRSA isolates from four hospitals (2019-2020) were collected and analysed by antimicrobial susceptibility testing and molecular classification by the MLST, spa, and SCCmec typing methods. Isolate antibiotic resistance rates were detected by a drug susceptibility assays. PCR amplification was used to detect the virulence gene-carrying status. Results: Twenty-four STs, including 4 new STs (ST7346, ST7347, ST7348, and ST7247) and 3 new allelic mutations, were identified based on MLST. The major prevalent ST type and clone complex were ST59 (49.8%) and CC59 (62.7%), respectively. Spa type t437 (42.1%) and SCCmec IV (55.5%) were identified by spa and SCCmec typing methods as the most important types. Drug sensitivity data showed that the multidrug resistance rate was 79.0%. There were significant differences in multidrug resistance rates and virulence gene-carrying rates for seb, hla, hlb, cna and bap between ST59 and non-ST59 types. Conclusion: ST59-SCCmecIV-t437 is a major epidemic clone in Guiyang that should be monitored by local medical and health institutions. The situation differs from other adjacent or middle provinces of China, which may be due to the special geographical location of the region and the trend in antibiotic use or lifestyle. This study provides empirical evidence for local medical and health departments to prevent and control the spread of MRSA.
RESUMO
Dehydration-responsive element binding proteins (DREBs) are an important class of transcription factors related to plant stress tolerance. Ammopiptanthus mongolicus is an evergreen broadleaf shrub endemic to desert areas of northwest China, and it has a very high tolerance to harsh environments. In order to reveal the functions and mechanisms of the AmDREB1F gene from this species in enduring abiotic stresses, we performed subcellular localization test, expression pattern analysis, and stress tolerance evaluation of transgenic Arabidopsis harboring this gene. The protein encoded by AmDREB1F was localized in the nucleus. In laboratory-cultured A. mongolicus seedlings, the expression of AmDREB1F was induced significantly by cold and drought but very slightly by salt and heat stresses, and undetectable upon ABA treatment. In leaves of naturally growing shrubs in the wild, the expression levels of the AmDREB1F gene were much higher during the late autumn, winter and early spring than in other seasons. Moreover, the expression was abundant in roots and immature pods rather than other organs of the shrubs. Constitutive expression of AmDREB1F in Arabidopsis induced the expression of several DREB-regulated stress-responsive genes and improved the tolerance of transgenic lines to drought, high salinity and low temperature as well as oxidative stress. The constitutive expression also caused growth retardation of the transgenics, which could be eliminated by the application of gibberellin 3. Stress-inducible expression of AmDREB1F also enhanced the tolerance of transgenic Arabidopsis to all of the four stresses mentioned above, without affecting its growth and development. These results suggest that AmDREB1F gene may play positive regulatory roles in response to abiotic stresses through the ABA-independent signaling pathways.