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AIM: To evaluate inter-reader agreement between novice and expert radiologists in assessing contrast-enhanced ultrasonography (CEUS) and magnetic resonance imaging (MRI) images for detecting viable tumours with different sizes after conventional transarterial chemoembolisation (cTACE). MATERIALS AND METHODS: This prospective study included patients who had less than five hepatomas and who underwent cTACE. Hepatomas with one or two feeding arteries were selected as target lesions. CEUS and MRI were performed within 1 week after cTACE to evaluate viable tumours. RESULTS: The expert group had higher kappa values in evaluating all tumour sizes via CEUS compared with MRI. The novice group had similar kappa values. In patients with tumours measuring ≤3 cm, the expert group had higher kappa values in reading CEUS compared with MRI images; however, in the novice group, the kappa value was lower in evaluating CEUS compared with MRI images. In patients with tumours measuring >3 cm, the expert and novice groups had good to excellent kappa values. The confidence level of the two groups in reading MRI images was high; however, the novice group had a lower confidence level. CONCLUSION: CEUS is a convenient, cost-effective, and easy to apply imaging tool that can help interventionists perform early detection of viable hepatocellular carcinoma post-TACE. It has a higher inter-rater agreement in interpreting CEUS images compared with MRI images among expert radiologists even when they are extremely familiar with post-cTACE MRI images. In novice radiologists, there may be a learning curve to achieve good consistency in CEUS interpretation.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/irrigação sanguínea , Estudos Prospectivos , Meios de Contraste , Ultrassonografia/métodos , Imageamento por Ressonância MagnéticaRESUMO
Saccharomyces cerevisiae fermentation products are commonly used in dairy cattle ration to improve production efficiency and health. However, whether these benefits will persist during feed-restriction-induced negative energy balance is unknown. The objective of this experiment was to examine the effect of a Saccharomyces cerevisiae fermentation product (NT, NutriTek, Diamond V) on performance, metabolic, inflammatory, and immunological responses to a feed-restriction challenge in mid-lactation dairy cows. Sixty Holstein cows were blocked by parity, days in milk, and milk yield and then randomly assigned to 1 of the 2 supplements: NT or placebo (CTL). The supplements were mixed in total mixed ration before feeding at a rate of 19 g/d per cow. The production phase of the experiment lasted 12 wk. Intake and milk yield were recorded daily, and milk composition was measured weekly. After the production trial, a subset of cows (NT: n = 16; CTL: n = 16) were immediately enrolled in a 5-d feed-restriction challenge with 40% ad libitum intake followed by a 5-d realimentation. Milk yield and composition were measured at each milking from d -2 to 10 relative to feed restriction. Blood samples were collected on d -2, -1, 1, 2, 3, 4, 5, 6, 8, and 10 relative to the initiation of feed restriction to measure circulating metabolites, insulin, cortisol, IL-10, tumor necrosis factor-α, lipopolysaccharide binding protein, and haptoglobin. Immune function assessments, including peripheral mononuclear cell proliferation and functional assays of circulating granulocytes, were performed on d -3 and 4 of the feed restriction. No differences were observed in dry matter intake, milk yield, or concentrations or yield of components except for fat yield. An interaction of parity and treatment was observed for milk fat yield that was lower for CTL than NT in primiparous cows, but no differences were observed among treatments in milk fat yield of multiparous cows. Feed restriction successfully induced negative energy balance and its associated metabolic changes, including reduced concentrations of plasma glucose and increased nonesterified fatty acids and ß-hydroxybutyrate. Cows fed NT had a similar decrease in milk yield but had a more pronounced reduction in plasma glucose concentration and greater ß-hydroxybutyrate concentration during feed restriction than those fed CTL. Feed restriction did not induce evidence of systemic inflammation but did reduce granulocyte functional activity. Compared with CTL, feeding NT improved the reactive oxygen species production by granulocytes after stimulation by extracellular antigens. In conclusion, feeding NT increased milk fat production of first-lactation cows but did not affect overall productive performance. However, supplementation with NT improved induced granulocyte oxidative burst. This may explain the greater glucose utilization by cows fed NT rather than CTL during feed restriction.
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Glicemia , Saccharomyces cerevisiae , Gravidez , Feminino , Bovinos , Animais , Fermentação , Saccharomyces cerevisiae/metabolismo , Ácido 3-Hidroxibutírico , Glicemia/metabolismo , Dieta/veterinária , Lactação/fisiologia , Leite/química , Ração Animal/análiseRESUMO
To examine the effects of evaporative cooling on systemic and mammary inflammation of lactating dairy cows, 30 multiparous Holstein cows (parity = 2.4, 156 d in milk) were randomly assigned to 1 of 2 treatments: cooling (CL) with fans and misters or not (NC). The experiment was divided into a 10-d baseline when all cows were cooled, followed by a 36-d environmental challenge when cooling was terminated for NC cows. The onset of environmental challenge was considered as d 1. Temperature-humidity index averaged 78.4 during the environmental challenge. Milk yield and dry matter intake (DMI) were recorded daily. Blood and milk samples were collected from a subset of cows (n = 9/treatment) on d -3, 1, 3, 7, 14, and 28 of the experiment to measure cortisol, interleukin 10 (IL10), tumor necrosis factor-α (TNF-α), haptoglobin, and lipopolysaccharide binding protein (LBP). Mammary biopsies were collected from a second subset of cows (n = 6/treatment) on d -9, 2, 10, and 36 to analyze gene expression of cytokines and haptoglobin. A subset of cows (n = 7/treatment) who were not subjected to mammary biopsy collection received a bolus of lipopolysaccharides (LPS) in the left rear quarter on d 30 of the experiment. Blood was sampled from cows and milk samples from the LPS-infused quarter were collected at -4, 0, 3, 6, 12, 24, 48, and 96 h relative to infusion, for analyses of inflammatory products. Deprivation of cooling decreased milk yield and DMI. Compared with CL cows, plasma cortisol concentration of NC cows was higher on d 1 but lower on d 28 of the experiment (cooling × time). Deprivation of cooling did not affect circulating TNF-α, IL10, haptoglobin, or LBP. Compared with CL cows, NC cows tended to have higher milk IL10 concentrations but did not show effects in TNF-α, haptoglobin, or LBP. No differences were observed in mammary tissue gene expression of TNF-α, IL10, and haptoglobin. Milk yield declined after LPS infusion but was not affected by treatment. Compared with CL cows, NC cows had greater milk somatic cell count following intramammary LPS infusion. Non-cooled cows had lower circulating TNF-α and IL10 concentrations and tended to have lower circulating haptoglobin concentrations than CL cows. Milk IL10 and TNF-⺠concentrations were higher 3 h after LPS infusion for NC cows compared with CL cows. Additionally, NC cows tended to have higher milk haptoglobin concentration after LPS infusion than CL cows. In conclusion, deprivation of evaporative cooling had minimal effects on lactating cows' basal inflammatory status, but upregulated mammary inflammatory responses after intramammary LPS infusion.
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OBJECTIVES: Osteoarthritis (OA) is a common degenerative joint disease, and total knee replacement (TKR) is a successful surgical intervention for knee OA treatment. However, the risks of mortality and major cardiovascular events (MACEs) in patients receiving TKR remain unclear. This study investigated the risks of mortality and MACEs in knee OA patients who received TKR. METHODS: For this population-based cohort study, the Longitudinal Health Insurance Database 2000 was used. Two million individuals with knee OA defined by ICD-9-CM codes who received physical therapy between 1999 and 2017 were selected. For propensity score matching (PSM), we considered the year of knee OA diagnosis, demographics, comorbidities, co-medications, and knee OA-related hyaluronic acid or physical therapy at baseline. After PSM, regression analyses were performed to assess the association of mortality or MACEs with TKR and non-TKR individuals. RESULTS: We identified patients (n = 189,708) with a new diagnosis of knee OA between 2000 and 2017. In total, 10,314 propensity-score-paired TKR and non-TKR individuals were selected. The PSM cohort algorithm revealed that the risk of mortality or MACEs was lower in the TKR group (adjusted hazard ratio: 0.791; 95% confidence interval: 0.755-0.830) than in the non-TKR group. CONCLUSIONS: Patients with knee OA who received TKR had decreased risks of mortality and MACEs than those who did not receive TKR. Moreover, the TKR group received a reduced dosage of nonsteroidal anti-inflammatory drugs at the 1-year follow-up.
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Artroplastia do Joelho/métodos , Cardiopatias/mortalidade , Cardiopatias/prevenção & controle , Osteoartrite do Joelho/cirurgia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The measurement of two-particle angular correlation functions in high-multiplicity e^{+}e^{-} collisions at sqrt[s]=10.52 GeV is reported. In this study, the 89.5 fb^{-1} of hadronic e^{+}e^{-} annihilation data collected by the Belle detector at KEKB are used. Two-particle angular correlation functions are measured in the full relative azimuthal angle (ΔÏ) and three units of pseudorapidity (Δη), defined by either the electron beam axis or the event-shape thrust axis, and are studied as a function of charged-particle multiplicity. The measurement in the thrust axis analysis, with mostly outgoing quark pairs determining the reference axis, is sensitive to the region of additional soft gluon emissions. No significant anisotropic collective behavior is observed with either coordinate analyses. Near-side jet correlations appear to be absent in the thrust axis analysis. The measurements are compared to predictions from various event generators and are expected to provide new constraints to the phenomenological models in the low-energy regime.
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OBJECTIVE: Systemic sclerosis (SSc) is a systemic autoimmune disease affecting multiple organs, including the kidneys. There is a lack of long-term renal prognosis studies on patients with SSc. The aim of this study was to assess the risk of end-stage renal disease (ESRD) in patients with SSc. METHOD: We designed a prospective cohort study based on the National Health Insurance Research Database of Taiwan. Patients with SSc and a non-SSc control group were selected from 1 January 2000 to 31 December 2013. The SSc cohort and control group were matched on the propensity score in a 1:2 ratio. The primary outcome was development of ESRD. Cox proportional hazard regression was performed to assess the effects of SSc on ESRD. RESULTS: After propensity score matching, we enrolled 2012 patients in the SSc group and 4024 patients in the control group. During a mean follow-up of 6.5 years, 86 individuals [SSc group, n = 41 (2.04%); control group, n = 45 (1.12%)] had developed ESRD. The risk of ESRD in the SSc group was approximately two times higher than that in the control group [hazard ratio (HR) = 2.12, 95% confidence interval (CI) 1.39-3.24]. Subgroup analysis revealed that the higher risk of ESRD was predominantly in males (HR = 4.14, 95% CI 1.97-8.71) and the younger population (HR = 7.09, 95% CI 2.31-21.80). CONCLUSION: There was a significantly higher risk of ESRD among SSc patients than among the general population, with males and younger generations being the most vulnerable groups.
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Falência Renal Crônica , Escleroderma Sistêmico , Humanos , Incidência , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/epidemiologia , Taiwan/epidemiologiaRESUMO
The objective of this study was to examine the effects of evaporative cooling and dietary supplemental Zn source on heat shock responses and mammary gland development of lactating dairy cows during summer. Seventy-two multiparous lactating Holstein cows were randomly assigned to 1 of 4 treatments in a 2 × 2 factorial arrangement. Cows were either cooled (CL) or not cooled (NC) and fed diets supplemented with 75 mg of Zn/kg of dry matter (DM) from Zn hydroxychloride (IOZ) or 35 mg of Zn/kg of DM from Zn hydroxychloride plus 40 mg of Zn/kg of DM from Zn-Met complex (ZMC). The 168-d trial included a 12-wk baseline phase when all cows were cooled and fed respective dietary treatments, and a subsequent 12-wk environmental challenge phase when NC cows were deprived of evaporative cooling. Plasma was collected from a subset of cows (n = 24) at 1, 3, 5, 12, 26, 41, 54, 68, 81 d of the environmental challenge to measure heat shock protein (HSP) 70 concentration. Mammary biopsies were collected from another subset of cows (n = 30) at enrollment (baseline samples) and at d 7 and 56 of the environmental challenge to analyze gene expression related to heat shock response, apoptosis and anti-oxidative enzymes, and to examine apoptosis and cell proliferation using immunohistochemistry. Supplemental Zn source did not affect milk yield but NC cows produced less milk than CL cows. Supplemental Zn source had no effect on mammary gene expression of HSP27, 70, and 90 or plasma concentrations of HSP70. The NC cows had greater mammary gene expression of HSP than CL cows. Circulating HSP70 of NC cows gradually increased and was higher at 81 d of environmental challenge compared with CL cows. Relative to IOZ, ZMC cows tended to have lower total mammary cell proliferation but greater mammary apoptosis. There was a tendency of greater TNFRSF1A mRNA expression for ZMC compared with IOZ cows, which may suggest upregulated extrinsic apoptosis. At d 7 of environmental challenge, NC cows had numerically higher mammary apoptosis than CL cows although not statistically significant. The NC cows tended to have greater mRNA expression of CAT and SOD3 regardless of time, and had greater mRNA expression of GPX1 at d 56 and FAS at d 7 of the environmental challenge than CL cows. Relative to CL cows, mammary cell proliferation rate was higher for NC cows at d 56 of the environmental challenge. In conclusion, dietary source of supplemental Zn has substantial effect on mammary cell turnover in lactating dairy cows, and prolonged exposure to heat stress increases mammary cell proliferation.
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Resposta ao Choque Térmico , Lactação , Animais , Bovinos , Dieta/veterinária , Suplementos Nutricionais , Feminino , Leite , ZincoRESUMO
AIMS: To study the association between number and positions of mutations with MICs of fluoroquinolone non-susceptible Haemophilus influenzae. METHODS AND RESULTS: More than 40% of 48 H. influenzae isolated from nursing home residents were not susceptible to fluoroquinolone. Amino acid changes in the quinolone resistance determining regions, and correlation with MICs and inhibition zone diameters were analysed. All isolates with reduced susceptibility to fluoroquinolones (MIC ≥0·125 µg ml-1 ) had at least one mutation in gyrA at position 84 and were resistant to nalidixic acid. Compared to isolates with reduced susceptibility, resistant isolates were associated with mutations in gyrA at positions 88 and 134, and in parC at position 88 (P < 0·001). Inhibition zone diameter for nalidixic acid disk ≥23 mm may detect susceptible isolates. CONCLUSIONS: Reduced susceptibility to fluoroquinolones was associated with mutations at position 84 in gyrA. A further increase in fluoroquinolone MIC was associated with mutations in gyrA at positions 88 and 134, and parC at position 88. SIGNIFICANCE AND IMPACT OF THE STUDY: Due to limited resistant H. influenzae strains, prior studies on association between positions of mutations and fluoroquinolone MICs were inconclusive. The comparison of mutations between isolates with susceptibility, reduced susceptibility and high resistance supported the importance of the present study.
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Anti-Infecciosos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Fluoroquinolonas/farmacologia , Haemophilus influenzae/efeitos dos fármacos , DNA Girase/genética , DNA Topoisomerase IV/genética , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/genética , Haemophilus influenzae/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Mutação , Casas de Saúde , TaiwanRESUMO
AIM: After extended left colectomy, traditional colorectal anastomosis is often not feasible because of insufficient length of the remaining colon to perform a tension-free anastomosis. Total colectomy with ileorectal anastomosis could be an alternative but this can lead to unsatisfactory quality of life. Trans-mesenteric colorectal anastomosis or inverted right colonic transposition (the so-called Deloyers procedure) are two possible solutions for creating a tension-free colorectal anastomosis after extended left colectomy. Few studies have reported their results of these two techniques and mostly via laparotomy. The aim of this study was to describe the trans-mesenteric colorectal anastomosis and the inverted right colonic transposition procedure via a laparoscopic approach and report the outcome in a series of 13 consecutive patients. METHOD: This was retrospective chart review of laparoscopic colorectal surgery with trans-mesenteric colorectal anastomosis or the inverted right colonic transposition procedure from January 2015 up to 2019. An accompanying video demonstrates these two techniques. RESULTS: Thirteen consecutive patients underwent either a laparoscopic trans-mesenteric colorectal anastomosis (n = 9) or an inverted right colonic transposition procedure (n = 4). One patient had intra-operative presacral bleeding that was stopped successfully without conversion. Two patients had a postoperative intra-abdominal abscess, but no anastomotic complications were recorded. The median number of bowel movements per day after 6 months was 2 (range 2-5). CONCLUSIONS: Trans-mesenteric colorectal anastomosis or the inverted right colonic transposition procedure is feasible laparoscopically. The now well-established classical advantages of the laparoscopic approach are associated with good functional outcome after these procedures.
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Neoplasias Colorretais , Laparoscopia , Anastomose Cirúrgica , Colectomia , Neoplasias Colorretais/cirurgia , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Estudos Retrospectivos , Resultado do TratamentoRESUMO
AIM: To evaluate contrast medium delivery protocols for the optimal enhancement profile of the aorta with both a reduced dose of radiation and contrast medium, called double-low computed tomography (CT) angiography (DLCTA). MATERIALS AND METHODS: DLCTA was performed with 70 kVp and 200 mg iodine/kg in 205 patients following four protocols, namely slow rate (n=52), short duration (n=52), low concentration (n=50), and combined method (n=51), in comparison with a conventional group (120 kVp, 400 mg iodine/kg, n=51). The quantitative measurement of aortic attenuation, homogeneity, and subjective scores were evaluated. RESULTS: Overall, in the four DLCTA groups, the radiation dose was reduced by 62%, and the iodine dose was reduced by 50%. Among the four DLCTA groups, the signal to noise ratio (SNR) and contrast to noise ratio (CNR) of the thoracic aorta were similar, but a significant difference was noted in the abdominal aorta. The short-duration group had the highest peak enhancement, least homogeneity, and worst subjective scores. Good contrast enhancement and good homogeneity were significantly more frequent in the slow-rate (86.6% and 90.4%, respectively) and low-concentration groups (78% and 96.0%, respectively). Subjective scores exhibited a trend of higher scores in the low-concentration group and lower scores in the slow-rate group (p=0.071). CONCLUSION: DLCTA with 70 kVp and 200 mg iodine/kg is feasible for whole-aortic CT angiography. The low-concentration protocol is recommended owing to its most consistent optimal aortic enhancement profile. Alternatively, the slow-rate protocol can be considered for patients with limited venous access.
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Doenças da Aorta/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Meios de Contraste/administração & dosagem , Iohexol/administração & dosagem , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagens de Fantasmas , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador , Razão Sinal-RuídoRESUMO
Purpose: The study examined postoperative cognitive dysfunction in premenopausal and postmenopausal women undergoing surgery with general anesthesia.Methods: This cross-sectional observational study enrolled 30 premenopausal and 28 postmenopausal patients (age 40-60 years) who did not receive hormone replacement therapy, hysterectomy, or oophorectomy. Patients with no menstrual periods for at least 1 year were defined as postmenopausal. The Tablet-based Symbol Digit Modalities Test (T-SDMT) and the Computerized-Digit Vigilance Test (C-DVT) were conducted prior to surgery and on postoperative days (POD) 1 and 7.Results: Postmenopausal patients had a significantly higher T-SDMT reaction time than premenopausal patients preoperatively and on POD 7. Menopausal groups differed in T-SDMT and C-DVT scores preoperatively and postoperatively, but the difference was no longer significant after adjustment for age. Postmenopausal patients had a significantly higher C-DVT hit-reaction time than premenopausal patients on POD 1 and POD 7. On POD 7, 0% of premenopausal and 10.7% of postmenopausal patients had a worse T-SDMT hit-reaction time than at baseline. Pearson's correlation analysis showed that baseline T-SDMT was significantly correlated with age and postmenopausal years; C-DVT was correlated with menopausal duration.Conclusions: By POD 7, menopause status has no noticeable effect on cognitive function in middle-aged women undergoing general surgery.
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Anestesia Geral/efeitos adversos , Pós-Menopausa , Complicações Cognitivas Pós-Operatórias/etiologia , Pré-Menopausa , Adulto , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Although the Sensititre Yeast-One (SYO) and Etest methods are widely utilized, interpretive criteria are not available for triazole susceptibility testing of Candida or Aspergillus species. We collected fluconazole, itraconazole, posaconazole, and voriconazole SYO and Etest MICs from 39 laboratories representing all continents for (method/agent-dependent) 11,171 Candida albicans, 215 C. dubliniensis, 4,418 C. glabrata species complex, 157 C.guilliermondii (Meyerozyma guilliermondii), 676 C. krusei (Pichia kudriavzevii), 298 C.lusitaniae (Clavispora lusitaniae), 911 C.parapsilosissensu stricto, 3,691 C.parapsilosis species complex, 36 C.metapsilosis, 110 C.orthopsilosis, 1,854 C.tropicalis, 244 Saccharomyces cerevisiae, 1,409 Aspergillus fumigatus, 389 A.flavus, 130 A.nidulans, 233 A.niger, and 302 A.terreus complex isolates. SYO/Etest MICs for 282 confirmed non-wild-type (non-WT) isolates were included: ERG11 (C. albicans), ERG11 and MRR1 (C. parapsilosis), cyp51A (A. fumigatus), and CDR2 and CDR1 overexpression (C. albicans and C. glabrata, respectively). Interlaboratory modal agreement was superior by SYO for yeast species and by the Etest for Aspergillus spp. Distributions fulfilling CLSI criteria for epidemiological cutoff value (ECV) definition were pooled, and we proposed SYO ECVs for S. cerevisiae and 9 yeast and 3 Aspergillus species and Etest ECVs for 5 yeast and 4 Aspergillus species. The posaconazole SYO ECV of 0.06 µg/ml for C. albicans and the Etest itraconazole ECV of 2 µg/ml for A. fumigatus were the best predictors of non-WT isolates. These findings support the need for method-dependent ECVs, as, overall, the SYO appears to perform better for susceptibility testing of yeast species and the Etest appears to perform better for susceptibility testing of Aspergillus spp. Further evaluations should be conducted with more Candida mutants.
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Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Candida/efeitos dos fármacos , Triazóis/farmacologia , Aspergilose/tratamento farmacológico , Aspergilose/epidemiologia , Aspergilose/microbiologia , Aspergillus/classificação , Aspergillus/isolamento & purificação , Candida/classificação , Candida/isolamento & purificação , Candidíase/tratamento farmacológico , Candidíase/epidemiologia , Candidíase/microbiologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Farmacorresistência Fúngica , Fluconazol/farmacologia , Humanos , Hospedeiro Imunocomprometido , Itraconazol/farmacologia , Voriconazol/farmacologiaRESUMO
The study of monozygotic twins discordant for attention deficit hyperactivity disorder can elucidate mechanisms that contribute to the disorder, which affects ~7% of children. First, using in vivo neuroanatomic imaging on 14 pairs of monozygotic twins (mean age 9.7, s.d. 1.9 years), we found that discordance for the disorder is mirrored by differing dimensions of deep brain structures (the striatum and cerebellum), but not the cerebral cortex. Next, using whole-blood DNA from the same twins, we found a significant enrichment of epigenetic differences in genes expressed in these 'discordant' brain structures. Specifically, there is differential methylation of probes lying in the shore and shelf and enhancer regions of striatal and cerebellar genes. Notably, gene sets pertaining to the cerebral cortex (which did not differ in volume between affected and unaffected twins) were not enriched by differentially methylated probes. Genotypic differences between the twin pairs-such as copy number and rare, single-nucleotide variants-did not contribute to phenotypic discordance. Pathway analyses of the genes implicated by the most differentially methylated probes implicated γ-aminobutyric acid (GABA), dopamine and serotonin neurotransmitter systems. The study illustrates how neuroimaging can help guide the search for epigenomic mechanisms in neurodevelopmental disorders.
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Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/genética , Epigênese Genética/genética , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Encéfalo/anatomia & histologia , Encéfalo/fisiopatologia , Cerebelo/diagnóstico por imagem , Cerebelo/fisiologia , Criança , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/fisiopatologia , Metilação de DNA , Doenças em Gêmeos/genética , Epigenômica , Feminino , Genótipo , Humanos , Masculino , Transtornos do Neurodesenvolvimento/genética , Fenótipo , Gêmeos Monozigóticos/genética , Gêmeos Monozigóticos/psicologiaRESUMO
Estimating epidemiological cutoff endpoints (ECVs/ECOFFS) may be hindered by the overlap of MICs for mutant and nonmutant strains (strains harboring or not harboring mutations, respectively). Posaconazole MIC distributions for the Aspergillus fumigatus species complex were collected from 26 laboratories (in Australia, Canada, Europe, India, South and North America, and Taiwan) and published studies. Distributions that fulfilled CLSI criteria were pooled and ECVs were estimated. The sensitivity of three ECV analytical techniques (the ECOFFinder, normalized resistance interpretation [NRI], derivatization methods) to the inclusion of MICs for mutants was examined for three susceptibility testing methods (the CLSI, EUCAST, and Etest methods). The totals of posaconazole MICs for nonmutant isolates (isolates with no known cyp51A mutations) and mutant A. fumigatus isolates were as follows: by the CLSI method, 2,223 and 274, respectively; by the EUCAST method, 556 and 52, respectively; and by Etest, 1,365 and 29, respectively. MICs for 381 isolates with unknown mutational status were also evaluated with the Sensititre YeastOne system (SYO). We observed an overlap in posaconazole MICs among nonmutants and cyp51A mutants. At the commonly chosen percentage of the modeled wild-type population (97.5%), almost all ECVs remained the same when the MICs for nonmutant and mutant distributions were merged: ECOFFinder ECVs, 0.5 µg/ml for the CLSI method and 0.25 µg/ml for the EUCAST method and Etest; NRI ECVs, 0.5 µg/ml for all three methods. However, the ECOFFinder ECV for 95% of the nonmutant population by the CLSI method was 0.25 µg/ml. The tentative ECOFFinder ECV with SYO was 0.06 µg/ml (data from 3/8 laboratories). Derivatization ECVs with or without mutant inclusion were either 0.25 µg/ml (CLSI, EUCAST, Etest) or 0.06 µg/ml (SYO). It appears that ECV analytical techniques may not be vulnerable to overlap between presumptive wild-type isolates and cyp51A mutants when up to 11.6% of the estimated wild-type population includes mutants.
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Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Mutação/genética , Triazóis/farmacologia , Farmacorresistência Fúngica/genética , Testes de Sensibilidade Microbiana , Voriconazol/farmacologiaRESUMO
HBsAg decline during nucleos(t)ide analogue therapy in chronic hepatitis B with lower pretherapy ALT is usually small and slow. This study aimed to investigate why ~10% of such patients showed "rapid HBsAg decline" ≥0.5 log10 IU/mL by month 6 of therapy. Patients with persistent pretherapy ALT <5X ULN who had qHBsAg at baseline, months 6 and 12 of entecavir or tenofovir therapy were studied. "On-treatment ALT elevation" was defined as >10% increase above baseline to >2X ULN during first 6 months of therapy. Of the 256 patients treated, 51 experienced transient "on-treatment ALT elevation" [group A], including 30 (11.7%) with ALT elevation to 2-5X ULN [group A-1] and 21 (8.2%) flared to >5X ULN [group A-2]. The magnitude of qHBsAg decline and rate of "rapid HBsAg decline" by month 6 was significantly greater and more frequent in group A (-0.446 vs -0.042 log10 IU/mL; 45.1 vs 8.8%, respectively, P = 0.000) than in the remaining 205 patients without on-treatment ALT elevation (group B), being greatest in patients with hepatitis flare (group A-2: -0.559 log10 IU/mL and 57.1%, respectively). In patients with therapy ≥2 years, patients with "on-treatment ALT elevation" also showed significantly greater annual HBsAg decline, more frequent to <100 IU/mL and 4 times higher HBsAg seroclearance rate. "On-treatment ALT elevation," especially flare >5X ULN, during entecavir therapy or tenofovir therapy may enhance/accelerate HBsAg decline, suggesting the effect of immune restoration upon potent viral suppression.
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Antivirais/administração & dosagem , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Exacerbação dos Sintomas , Adulto , Idoso , Feminino , Guanina/administração & dosagem , Guanina/análogos & derivados , Hepatite B Crônica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tenofovir/administração & dosagem , Fatores de TempoRESUMO
In this study, we evaluated the long-term antifungal effectiveness of 3 types of interior building materials (gypsum board [GB], cement board [CB], and softwood plywood [S-PW]) impregnated with thermally reduced silver nanoparticles supported by titanium dioxide (AgNPs/TiO2 ) under 95% relative humidity for 4 weeks. AgNPs/TiO2 was synthesized at 2 thermal reduction temperatures (TRTs, 120 and 200°C) with 2 different AgNP weight percentages (2 and 5 wt%). Four different silver-loading levels (SLLs, 0.025, 0.05, and 0.5 µg/cm2 and the critical concentration required to inhibit fungal growth on agar plates) and 3 fungal species (Aspergillus niger, Penicillium spinulosum, and Stachybotrys chartarum) were used in the experiments. Higher temperature reduced more ionic Ag+ to metallic Ag0 and increased the dispersion of Ag on TiO2 surface. The 200°C thermally reduced AgNPs/TiO2 demonstrated excellent antifungal efficiency: Mold growth was almost completely inhibited for 28 days at the low SLL of 0.5 µg/cm2 . Additionally, AgNPs/TiO2 exhibited higher antifungal activity on GB and CB than on S-PW. The stepwise regression results indicated that the TRT of AgNPs/TiO2 (ß = -0.739 to -0.51), the SLL (ß = -0.477 to -0.269), and the Ag0 level in the AgNPs (ß = -0.379 to -0.136) were the major factors influencing antifungal activity and TRT might be the most significant one.
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Antifúngicos , Materiais de Construção/microbiologia , Fungos/crescimento & desenvolvimento , Nanopartículas Metálicas , Prata , Temperatura AltaRESUMO
Amniotic fluid is a rich source of multipotent mesenchymal stem cells (MSCs). Amniotic fluid stem cells (AFSCs) have become a new source of stem cells; they have low immunogenicity and are easily harvested. For this reason, they may be useful in clinical tissue engineering. Moreover, AFSCs have anti-inflammatory properties and can repair tissues. This study evaluated the utility of AFSC injection to treat bilateral ovarian dystrophy in Holstein-Friesian cows. Bovine AFSCs (BAFSCs) were collected at slaughter from Holstein-Friesian cows during the third or fourth month of pregnancy and cultured in vitro. The BAFSCs began to show a fibroblast-like morphology. They were positive for ß-integrin, CD44, CD73, CD106 and Oct4 and negative for CD34 and CD45. After induction, the cells differentiated into mesodermal lineages. Bilateral ovarian dystrophy was confirmed by ultrasonography in 16 lactating cows. The subsequent experiment lasted 15 weeks. Serum was collected weekly to analyse progesterone concentrations, and weekly ultrasonography recorded ovarian changes. Each cow was equipped with an automatic heat detection system to facilitate oestrus observation and breeding records. The progesterone concentration of two cows in the treatment group (25%) significantly increased during weeks 10-15. On ultrasonography, the treatment group demonstrated mature follicles after BAFSCs injection, and foetuses were visualized approximately 40 days after artificial insemination (AI). Oestrus rates in the control and treatment groups were 0% (0/8) and 50% (4/8), respectively; pregnancy rates were 0% (0/8) and 25% (2/8), respectively. Calves were successfully delivered in both cases of pregnancy. These results show that BAFSCs can alleviate bovine ovarian dystrophy and restore fertility.
Assuntos
Líquido Amniótico/citologia , Doenças dos Bovinos/terapia , Transplante de Células-Tronco Mesenquimais , Doenças Ovarianas/veterinária , Animais , Bovinos , Diferenciação Celular , Células Cultivadas , Clima , Feminino , Fertilidade , Inseminação Artificial/veterinária , Células-Tronco Multipotentes/transplante , Doenças Ovarianas/terapia , Gravidez , Progesterona/sangueRESUMO
BACKGROUND/OBJECTIVES: We aim to (1) examine the influence of long-term adiposity status/short-term adiposity changes on asthma with high or low fractional exhaled nitric oxide (FeNO), and (2) to determine the differences in long-term adiposity status/short-term adiposity changes on atopy, airway inflammation and pulmonary function. SUBJECTS/METHODS: We recruited 2450 fourth- to sixth-grade children from the nationwide Taiwan Children Health Study. Data regarding various adiposity indicators, atopic status, pulmonary function tests and asthma outcomes were collected annually. New-onset asthma was stratified by airway inflammation status using FeNO. The generalized estimating equation was used for analyzing longitudinal relationships between long-term adiposity status/short-term adiposity changes and new-onset asthma. Individual adiposity growth slopes were obtained using a hierarchical linear model to establish the relationships between short-term adiposity changes and asthma among children with high airway inflammation. RESULTS: We found long-term adiposity status predicted childhood asthma with low FeNO, whereas short-term adiposity changes may increase risks of childhood asthma with high FeNO. Long-term adiposity status reduced pulmonary function, whereas short-term adiposity increase were associated with atopic diseases and airway inflammation. CONCLUSIONS: Obesity-induced asthma could be mediated by high or low airway inflammation, depending on the velocity of increase in adiposity. Rapid adiposity growth may increase risks of childhood asthma and airway inflammation.
Assuntos
Adiposidade , Asma/fisiopatologia , Inflamação/fisiopatologia , Obesidade Infantil/fisiopatologia , Adiposidade/imunologia , Adolescente , Asma/prevenção & controle , Índice de Massa Corporal , Testes Respiratórios , Criança , Comorbidade , Exercício Físico , Expiração , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Inflamação/prevenção & controle , Comunicação Interdisciplinar , Estudos Longitudinais , Masculino , Óxido Nítrico/análise , Obesidade Infantil/complicações , Obesidade Infantil/prevenção & controle , Aptidão Física/fisiologia , Taiwan/epidemiologia , Redução de Peso/fisiologiaRESUMO
Adjuvant pegylated interferon plus ribavirin treatment (PegIFN/RBV) reduces recurrence and prolongs survival in early stage hepatocellular carcinoma (HCC) patients with chronic hepatitis C (CHC) infection receiving resection or ablation. However, the impact of antiviral therapy in intermediate and advanced stage of CHC-HCC patients is uncertain. This study aimed to investigate the impact PegIFN/RBV treatment on recurrence-free interval and survival in patients with HCC receiving transarterial chemoembolization (TACE). From 2010 to 2013, 274 CHC patients from a 1073 patient-based cohort composed of freshly diagnosed HCC and receiving TACE treatment the Chang Gung Memorial Hospital, Linkou Medical Center were recruited. Propensity score matching (PSM) (age, gender, AST to Platelet Ratio Index (APRI), tumour size, tumour number and Child-Turcotte-Pugh score) with the ratio 1:2 for patients with and without PegIFN/RBV treatment was performed. Statistics were performed with SPSS V.20 (IBM, USA). After matching, 153 patients were analysed and 27 patients (17.6%) achieved sustained virologic response (SVR). The 2-year cumulative overall survival rate and recurrence-free survival rate among patients with SVR, non-SVR, and untreated were 85.2% vs 58.3% vs 69.6% (P=.001) and 73.3% vs 53.8% vs 58.5% (P=.013). By Cox regression analysis, non-SVR, untreated, increase CTP score and nonresponder to TACE were independent factors related to mortality. The SVR achieved by PegIFN/RBV treatment markedly improves survival and reduces tumour recurrence in CHC-HCC patients receiving TACE treatment after complete response.
Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Análise de Sobrevida , Resposta Viral Sustentada , Taiwan , Resultado do TratamentoRESUMO
INTRODUCTION & AIMS: Haemophilic arthropathy (HA) is a major complication in patients with haemophilia (PWH), but the study of age-specific prevalence and severity of HA is very limited in Asian countries. MATERIALS & METHODS: This study retrospectively reviewed 146 severe- and moderate-type Taiwanese PWH aged 4-73 years, with roentgenograms of elbows, knees and ankles and calculated Pettersson scores. RESULTS: The prevalence of HA, mean number of HAs per patient and mean Pettersson scores of all the joints were 42.8%, 1.3 and 1.9 points in PWH aged 4-10 years; 64.3%, 1.4 and 4.1 points in PWH aged 11-19 years; 97.1%, 2.9 and 15.6 points in PWH aged 20-29 years; 93.1%, 4.4 and 33.1 points in PWH aged 30-39 years; 100%, 5.1 and 46.1 points in PWH aged 40-49 years and 100%, 5 and 49.6 points in PWH aged ≥50 years, respectively. There was a high prevalence of HA for PWH aged ≥20 years. Among PWH aged <20 years, prevalence of HA was low and mild ankle arthropathy was the most common. Besides, in the four age groups aged <40 years, the prevalence of ankle arthropathy was the highest, followed by elbow arthropathy and then knee arthropathy. CONCLUSIONS: Although severe arthropathy of the six major joints was rare in PWH aged <30 years, it increased rapidly in PWH after 30 years. Analysis of clinical correlates suggested that age, severity of haemophilia, absence of prophylaxis and presence of HCV infection correlated positively with Pettersson scores.