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Maintaining an effective testing program is critical to the success and credibility of the anti-doping movement. However, a low detection ratio compared to the assumed real prevalence of sport doping has led some to question and criticize the effectiveness of the current testing system. In this perspective article, we review the results of the global testing program, discuss the purpose of testing, and compare benefits and limitations of performance indicators commonly used to evaluate testing efforts. We suggest that an effective testing program should distinguish between preventive testing and testing aimed at detecting the use of prohibited substances and prohibited methods. In case of preventive testing, the volume of the test program in terms of number of samples, tests and analyses is likely to be positively related to the extent of the deterrent effect achieved. However, there is a lack of literature on how the deterrent effect works in the practical context of doping testing. If the primary goal is to detect doping, the testing must be risk- and intelligence-based, and quality in test planning is more important than quantity in sample collection. The detection ratio can be a useful tool for evaluating the effectiveness of doping testing, but for the calculation one should take into account the number of athletes tested and not just the number of collected samples, as the former would provide a more precise measure of the tests' ability to detect doping among athletes. [ABSTRACT FROM AUTHOR]

Maintaining an effective testing program is critical to the success and credibility of the anti-doping movement. However, a low detection ratio compared to the assumed real prevalence of sport doping has led some to question and criticize the effectiveness of the current testing system. In this perspective article, we review the results of the global testing program, discuss the purpose of testing, and compare benefits and limitations of performance indicators commonly used to evaluate testing efforts. We suggest that an effective testing program should distinguish between preventive testing and testing aimed at detecting the use of prohibited substances and prohibited methods. In case of preventive testing, the volume of the test program in terms of number of samples, tests and analyses is likely to be positively related to the extent of the deterrent effect achieved. However, there is a lack of literature on how the deterrent effect works in the practical context of doping testing. If the primary goal is to detect doping, the testing must be risk- and intelligence-based, and quality in test planning is more important than quantity in sample collection. The detection ratio can be a useful tool for evaluating the effectiveness of doping testing, but for the calculation one should take into account the number of athletes tested and not just the number of collected samples, as the former would provide a more precise measure of the tests’ ability to detect doping among athletes.

The COVID-19 pandemic led to supply chain disruptions causing a severe shortage of infant formula. The shortage impacted parents of infants with cow's milk protein allergy (CMPA) who rely on specialized formulas. However, research on parent perspectives during formula shortages is limited. We aimed to understand the factors guiding parents' decisions when transitioning to alternative amino acid formula (AAF) or extensively hydrolyzed formula (eHF) during the national formula shortage. We conducted a survey using the ZSMoments platform and found that before the shortage, parents valued safety (83%), tolerability (78%), and reputability (78%) as primary factors in selecting eHFs and AAFs. Post-shortage, formula tolerability (86%), assurance (84%), and safety (80%) gained more importance. Among those switching eHF (n = 54), health care provider recommendations (81%), reputability (78%), taste (78%), and tolerability (78%) were rated as “extremely important.” Among those switching AAF (n = 26), top factors included tolerability (77%), assurance (73%), safety (73%), cost-effectiveness (73%), and formula trustworthiness (73%). These data suggest that parents carefully weigh various factors when managing their child's CMPA and transitioning to different AAF or eHF options.

目的 评估起始使用氨基酸配方(amino acid formula, AAF)和深度水解配方(extensively hydrolyzed formula, eHF)治疗牛奶蛋白过敏(cow's milk allergy, CMA)患儿的经济性, 为患儿家庭在疾病膳食管理过程中 优选性价比高的配方粉, 同时也为临床医生选择处方提供相应的经济学证据。方法以我国2岁以下CMA患儿为 研究对象, 构建决策树模拟其临床路径, 并进行成本效果分析。模型从患者视角出发, 评估患儿在治疗CMA过程 中的直接医疗成本和2岁前建立牛奶蛋白耐受所需要的时间(效果指标)。从成本和效果2个方面综合对比评估起 始使用AAF或eHF对CMA患儿疾病膳食管理的经济性。结果 起始使用AAF替代喂养的CMA患儿获得牛奶蛋 白耐受所需时间平均为7.15个月(其中轻中度CMA患儿平均需要6.41个月, 重度CMA患儿平均需要10.11个月)。 患儿2岁前配方粉饮食替代喂养的诊疗及家庭护理等总成本平均为23 455元。起始使用eHF替代喂养的CMA患 儿获得牛奶蛋白耐受所需时间平均为10.50个月(其中轻中度CMA患儿平均需要9.58个月, 重度CMA患儿平均 需要14.13个月)。起始使用eHF的总平均成本高于AAF,无乳糖eHF的总成本平均为30 592元, 略低于含乳糖 eHF的31 337元。与起始使用eHF替代喂养相比, 使用AAF替代喂养不管是对轻中度还是重度CMA患儿都具有 绝对的经济学优势, 且重度CMA患儿获益更大。在考虑模型参数的各种不确定性后, AAF仍有92.0%以上的概 率为优选的CMA管理配方。结论相较于eHF,起始使用AAF替代喂养对于我国CMA患儿治疗具有绝对的经济 学优势, 是一种性价比较高的治疗方案. [ABSTRACT FROM AUTHOR]

Enteroaggregative Escherichia coli (EAEC) is an important cause of diarrhea in children and adults worldwide. This pathotype is phenotypically characterized by the aggregative-adherence (AA) pattern in HEp-2 cells and genetically associated to the presence of the aatA gene. EAEC pathogenesis relies in different virulence factors. At least, three types of adhesins have been specifically associated with EAEC strains: the five variants of the aggregative adherence fimbriae (AAF), the aggregative forming pilus (AFP) and more recently, a fibrilar adhesin named CS22. Our study aimed to evaluate the presence of AAF, AFP and CS22-related genes among 110 EAEC strains collected from feces of children with diarrhea. The presence of aggR (EAEC virulence regulator) and genes related to AAFs (aggA, aafA, agg3A, agg4A, agg5A and agg3/4C), AFP (afpA1 and afpR) and CS22 (cseA) was detected by PCR, and the adherence patterns were evaluated on HeLa cells. aggR-positive strains comprised 83.6% of the collection; among them, 80.4% carried at least one AAF-related gene and presented the AA pattern. aggA was the most frequent AAF-related gene (28.4% of aggR+ strains). cseA was detected among aggR+ (16.3%) and aggR- strains (22.2%); non-adherent strains or strains presenting AA pattern were observed in both groups. afpR and afpA1 were exclusively detected among aggR- strains (77.8%), most of which (71.4%) also presented AA pattern. Our results indicate that AAF- and AFP-related genes may contribute to identify EAEC strains, while the presence of cseA and its importance as an EAEC virulence factor and genotypic marker needs to be further evaluated. [ABSTRACT FROM AUTHOR]

Whereas the O104:H4 enterohemorrhagic Escherichia coli (EHEC) outbreak strain from 2011 expresses aggregative adherence fimbriae of subtype I (AAF/I), its close relative, the O104:H4 enteroaggregative Escherichia coli (EAEC) strain 55989, encodes AAF of subtype III. Tight adherence mediated by AAF/I in combination with Shiga toxin 2 production has been suggested to result in the outbreak strain’s exceptional pathogenicity. Furthermore, the O104:H4 outbreak strain adheres significantly better to cultured epithelial cells than archetypal EAEC strains expressing different AAF subtypes. To test whether AAF/I expression is associated with the different virulence phenotypes of the outbreak strain, we heterologously expressed AAF subtypes I, III, IV, and V in an AAF-negative EAEC 55989 mutant and compared AAF-mediated phenotypes, incl. autoaggregation, biofilm formation, as well as bacterial adherence to HEp-2 cells. We observed that the expression of all four AAF subtypes promoted bacterial autoaggregation, though with different kinetics. Disturbance of AAF interaction on the bacterial surface via addition of α-AAF antibodies impeded autoaggregation. Biofilm formation was enhanced upon heterologous expression of AAF variants and inversely correlated with the autoaggregation phenotype. Co-cultivation of bacteria expressing different AAF subtypes resulted in mixed bacterial aggregates. Interestingly, bacteria expressing AAF/I formed the largest bacterial clusters on HEp-2 cells, indicating a stronger host cell adherence similar to the EHEC O104:H4 outbreak strain. Our findings show that, compared to the closely related O104:H4 EAEC strain 55989, not only the acquisition of the Shiga toxin phage, but also the acquisition of the AAF/I subtype might have contributed to the increased EHEC O104:H4 pathogenicity.

Enteroaggregative Escherichia coli (EAEC) is an important cause of diarrhea in children and adults worldwide. This pathotype is phenotypically characterized by the aggregative-adherence (AA) pattern in HEp-2 cells and genetically associated to the presence of the aatA gene. EAEC pathogenesis relies in different virulence factors. At least, three types of adhesins have been specifically associated with EAEC strains: the five variants of the aggregative adherence fimbriae (AAF), the aggregative forming pilus (AFP) and more recently, a fibrilar adhesin named CS22. Our study aimed to evaluate the presence of AAF, AFP and CS22-related genes among 110 EAEC strains collected from feces of children with diarrhea. The presence of aggR (EAEC virulence regulator) and genes related to AAFs (aggA, aafA, agg3A, agg4A, agg5A and agg3/4C), AFP (afpA1 and afpR) and CS22 (cseA) was detected by PCR, and the adherence patterns were evaluated on HeLa cells. aggR-positive strains comprised 83.6% of the collection; among them, 80.4% carried at least one AAF-related gene and presented the AA pattern. aggA was the most frequent AAF-related gene (28.4% of aggR+ strains). cseA was detected among aggR+ (16.3%) and aggR- strains (22.2%); non-adherent strains or strains presenting AA pattern were observed in both groups. afpR and afpA1 were exclusively detected among aggR- strains (77.8%), most of which (71.4%) also presented AA pattern. Our results indicate that AAF- and AFP-related genes may contribute to identify EAEC strains, while the presence of cseA and its importance as an EAEC virulence factor and genotypic marker needs to be further evaluated.

Whereas the O104:H4 enterohemorrhagic Escherichia coli (EHEC) outbreak strain from 2011 expresses aggregative adherence fimbriae of subtype I (AAF/I), its close relative, the O104:H4 enteroaggregative Escherichia coli (EAEC) strain 55989, encodes AAF of subtype III. Tight adherence mediated by AAF/I in combination with Shiga toxin 2 production has been suggested to result in the outbreak strain's exceptional pathogenicity. Furthermore, the O104:H4 outbreak strain adheres significantly better to cultured epithelial cells than archetypal EAEC strains expressing different AAF subtypes. To test whether AAF/I expression is associated with the different virulence phenotypes of the outbreak strain, we heterologously expressed AAF subtypes I, III, IV, and V in an AAF-negative EAEC 55989 mutant and compared AAF-mediated phenotypes, incl. autoaggregation, biofilm formation, as well as bacterial adherence to HEp-2 cells. We observed that the expression of all four AAF subtypes promoted bacterial autoaggregation, though with different kinetics. Disturbance of AAF interaction on the bacterial surface via addition of α-AAF antibodies impeded autoaggregation. Biofilm formation was enhanced upon heterologous expression of AAF variants and inversely correlated with the autoaggregation phenotype. Co-cultivation of bacteria expressing different AAF subtypes resulted in mixed bacterial aggregates. Interestingly, bacteria expressing AAF/I formed the largest bacterial clusters on HEp-2 cells, indicating a stronger host cell adherence similar to the EHEC O104:H4 outbreak strain. Our findings show that, compared to the closely related O104:H4 EAEC strain 55989, not only the acquisition of the Shiga toxin phage, but also the acquisition of the AAF/I subtype might have contributed to the increased EHEC O104:H4 pathogenicity. [ABSTRACT FROM AUTHOR]

Obesity is a modifiable risk factor in breast cancer patients and is predictive of disease outcomes in early‐onset breast cancer survivors. The purpose of this review is to summarize the current evidence in the association between early‐onset breast cancer and obesity, specifically in African‐American women. Reviewing the molecular mechanisms and social determinants of disease in this population can provide a foundation for future interventions in prevention, detection, and treatment aiming at improving outcomes for young breast cancer patients. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic led to supply chain disruptions causing a severe shortage of infant formula. The shortage impacted parents of infants with cow's milk protein allergy (CMPA) who rely on specialized formulas. However, research on parent perspectives during formula shortages is limited. We aimed to understand the factors guiding parents' decisions when transitioning to alternative amino acid formula (AAF) or extensively hydrolyzed formula (eHF) during the national formula shortage. We conducted a survey using the ZSMoments platform and found that before the shortage, parents valued safety (83%), tolerability (78%), and reputability (78%) as primary factors in selecting eHFs and AAFs. Post-shortage, formula tolerability (86%), assurance (84%), and safety (80%) gained more importance. Among those switching eHF ( n  = 54), health care provider recommendations (81%), reputability (78%), taste (78%), and tolerability (78%) were rated as "extremely important." Among those switching AAF ( n  = 26), top factors included tolerability (77%), assurance (73%), safety (73%), cost-effectiveness (73%), and formula trustworthiness (73%). These data suggest that parents carefully weigh various factors when managing their child's CMPA and transitioning to different AAF or eHF options., Competing Interests: MW has served as a consultant for Reckitt. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Fabbrini, Farrar, Brown, Oliveros, Florio, Beacker, Lamos, Baran and Wilsey.)

The development of an aorta-atrial fistula secondary to mechanical aortic valve infective endocarditis, is a rare, serious complication. The fistula is an aberrant intra-cardiac shunt that occurs between the aorta and either the left or right atrium. An aorta-atrial fistula can be congenital or acquired. In the case of infective endocarditis, the infection’s expansion beyond the valvular structure, may result in an aorto-cavitary fistula (ACF or AAF) with an estimated incidence of 1-2% (1). No clinical trials have been conducted for the best approach of management for this condition. Therefore, treatment strategies are applied to a case-by-case basis by expert opinion. Patients develop symptoms of heart failure secondary to AAF complications. The underlying cause of AAF needs to be identified with the use of imaging studies, to determine the approach of optimal treatment (2). We are reporting a case of a 32-year-old male with a history of repaired congenital heart disease, who developed mechanical aortic valve infective endocarditis from intravenous drug use with subsequent development of an aorta-atrial fistula.

We consider the multihop power line communication (PLC) networks of one source, two repeaters, and one destination. In the previous scheme, when the repeaters receive the retransmission data from the source, they use the traditional distributed space-time block code (DSTBC) with all decode-and-forward (DAF) elements to transmit the data, and they do not consider the incorrect decoding. The original contribution is that we propose a novel DSTBC scheme with embedded adaptive DAF/amplify-and-forward (AAF) elements for data retransmission in multihop PLC networks with existing opportunistic listening (OL) protocols. The new scheme has two types (instead of only one type as in the previous scheme), and, in the second type, the coding matrix for data retransmission can use either all DAF elements or hybrid AAF/DAF elements depending on the correctness of OL results. The advantage is to avoid a loss of diversity because of incorrectly received data at the relays. The effectiveness of the proposed scheme is shown in the simulation results. For the impulsive noise parameter δ = 0.8 and worst case background noise (narrowband interference and colored noise) at bit error rate 10−3, our proposed system has 1 dB gain over the previous scheme with the traditional DSTBC with all DAF elements. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Enteroaggregative Escherichia coli (EAEC) bears remarkable capacity to adhere the host intestinal mucosal surface and results in acute or persistent childhood diarrhea worldwide. In this study, an attempt has been made to inhibit EAEC cell adherence in-vitro using synthetic peptides. E. coli isolates (n = 54) were isolated from the stool samples of clinically diagnosed pediatric diarrheal patients. 92.8% isolates showed different types of aggregative adherence patterns with HEp-2 cells. AAF-II (Aggregative Adherence Fimbriae-II) EAEC exhibited the maximum ability to form biofilm and intracellular survival. Peptides were designed against the high antigenic epitopic regions of AAF-II adhesin of EAEC O42 using prediction algorithms like BcePred and ProPred software to block the EAEC cell adhesion in-vitro . Peptides P2 (DITITPATNRDVNV) and P3 (MRIKAWGEANHGQL) demonstrated higher inhibition of EAEC cell adhesion than P1 (GMQGSITPAIPLRPG). Interestingly, increasing the pre-incubation time of the peptides with HEp-2 cells from 1 h to 2 h showed the maximum inhibition. The data suggested the potential role of P2 and P3 peptides in successfully blocking the binding of AAF-II EAEC with HEp-2 cell receptors. Hence, the peptides may be efficacious in designing new chemotherapeutic for the management of EAEC mediated diarrhea. [ABSTRACT FROM AUTHOR]

Enteroaggregative Escherichia coli (EAEC) is an important diarrhoeal pathogen causing diseases in multiple epidemiological and clinical settings. In developing countries like India, diarrhoeal diseases are one of the major killers among paediatric population and oddly, few studies are available from Indian paediatric population on the variability of EAEC virulence genes. In this study, we examined the distribution of plasmid and chromosomal-encoded virulence determinants in EAEC isolates, and analysed cytokines response generated against EAEC with specific aggregative adherence fimbriae (AAF) type in duodenal biopsies using in vitro organ culture (IVOC) mimicking in vivo conditions. Different virulence marker combinations among strains were reflected as a function of specific adhesins signifying EAEC heterogeneity. fis gene emerged as an important genetic marker apart from aggA and aap. Further, EAEC infection in IVOC showed upregulation of IL-8, IL-1ß, IL-6, TNF-α and TLR-5 expression. EAEC with AAFII induced significant TLR-5 and IL-8 response, conceivably owing to more pathogenicity markers. This study sheds light on the pattern of EAEC pathotypes prevalent in North Indian paediatric population and highlights the presence of unique virulence combinations in pathogenic strains. Thus, evident diversity in EAEC virulence and multifaceted bacteria-host crosstalk can provide useful insights for the strategic management of diarrhoeal diseases in India, where diarrhoeal outbreaks are more frequent. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Thyroid nodules frequently require ultrasound and Fine Needle Aspiration Cytology (FNAC) evaluation. However, FNA cytology does not allow differentiation between follicular adenoma and carcinoma on Bethesda type IV lesions. This situation leads to many unnecessary surgical procedures because it is not possible to assure the benignity of the lesions, even when most of the specimens correspond to adenomas or even other benign lesions. The objective is this study is to establish if there are any US characteristics that would help us to predict the risk of malignancy of nodules with a pathological diagnosis of follicular neoplasm in order to achieve a more conservative management for non-suspicious nodules., Material and Methods: We studied 61 nodules in 61 patients (51 women and 10 men) that underwent thyroid surgery and had histopathological results of either follicular adenoma or carcinoma. Different US characteristics of the nodules were analysed (composition, echogenicity, margin, calcification status, the presence of halo and overall observer suspicion of malignancy) and were correlated with the histopathological analysis., Results: We have found a statistically significant association between the presence of calcifications, ill-defined borders and overall observer suspicion or impression (defined by well-known suspicious for malignancy ultrasonographic features, such as calcification, poorly defined margin, and a markedly hypoechoic solid nodule; and benign ultrasonographic features, such as predominantly cystic echogenic composition and the presence of a perinodular hypoechogenic halo) with follicular carcinoma. However all those features have shown low sensitivities in the present study (30%, 30% and 50%, respectively). On the other hand, the absence of halo sign has shown a sensitivity of 100% and a negative predictive value (NPV) of 100% in our study., Conclusions: The presence of calcifications, ill-defined borders and the overall impression or suspicion of malignancy associate with a higher risk for follicular carcinoma in Bethesda type IV thyroid nodules but their absence do not allow to predict benignity in these nodules. Inversely, when a halo sign lesion is observed, benign follicular neoplasm should be considered., (Copyright © 2020 SERAM. Published by Elsevier España, S.L.U. All rights reserved.)

Nucleotide excision repair (NER) is responsible for the removal of a large variety of structurally diverse DNA lesions. Mutations of the involved proteins cause the xeroderma pigmentosum (XP) cancer predisposition syndrome. Although the general mechanism of the NER process is well studied, the function of the XPA protein, which is of central importance for successful NER, has remained enigmatic. It is known, that XPA binds kinked DNA structures and that it interacts also with DNA duplexes containing certain lesions, but the mechanism of interactions is unknown. Here we present two crystal structures of the DNA binding domain (DBD) of the yeast XPA homolog Rad14 bound to DNA with either a cisplatin lesion (1,2-GG) or an acetylaminofluorene adduct (AAF-dG). In the structures, we see that two Rad14 molecules bind to the duplex, which induces DNA melting of the duplex remote from the lesion. Each monomer interrogates the duplex with a β-hairpin, which creates a 13mer duplex recognition motif additionally characterized by a sharp 70° DNA kink at the position of the lesion. Although the 1,2-GG lesion stabilizes the kink due to the covalent fixation of the crosslinked dG bases at a 90° angle, the AAF-dG fully intercalates into the duplex to stabilize the kinked structure. [ABSTRACT FROM AUTHOR]

Abstract: Delayed auditory feedback (DAF) impacts the speech fluency of normally fluent males more than that of normally fluent females. Understanding this gender difference may contribute to our understanding of gender differences in the prevalence of developmental stuttering. To characterize this gender difference in fluent people, DAF-induced dysfluency was measured in 20 male and 21 female young adults during oral reading and conversation tasks. Stutter-like dysfluencies (SLDs), articulation errors, interjections, reading errors, and speech rate were measured for both speech tasks as the participant spoke without feedback, with non-delayed feedback, and with DAF presented with 5 delay intervals (14 conditions total). DAF induced SLDs (but not other dysfluencies) more frequently during conversation than reading, and this effect was significantly greater for males than females (Gender × Task × Feedback interaction). Males also produced significantly more reading errors than females. DAF reduced speaking rate significantly more while reading than conversing (Task × Feedback interaction). DAF significantly decreased the frequency of interjections and increased the frequency of articulation errors; however, no Gender effects on these variables were observed. Although significant order effects indicated improved fluency across trials, covariance analysis suggested that order effects could not explain other results. Educational Objectives: After reading this article, the reader will be able to (1) Discuss developmental stuttering (DS) and gender differences in DS prevalence. (2) Define delayed auditory feedback (DAF). (3) Evaluate the evidence that gender is linked to DAF effects on fluent people. (4) Summarize the results of new research designed to assess sex differences in DAF effects on speech fluency in normally fluent adults. (5) Evaluate the degree to which evidence from the literature indicating that individual differences in attentional control may help us understand gender difference in DAF effects and possibly in DS prevalence as well. [Copyright &y& Elsevier]

Enteroaggregative Escherichia coli (EAEC) are causative agents of diarrhea, being characterized by aggregative adherence to cultured epithelial cells. In this study, phenotypic properties of EAEC were analyzed with respect to AA, hemagglutination, clump and biofilm formation, all of which are mediated by aggregative adherence fimbriae (AAF). The strains were also screened for AAF types, AAF adhesin variants and Dr adhesin by PCR. Of the three known AAF types, AAF/I and AAF/II adhesin variants were identified. An association between the AAF/adhesin genotypes and the subtypes/scores of phenotypic properties was sought and it was observed that strains harboring same adhesins displayed different subtypes/scores and vice versa. [ABSTRACT FROM AUTHOR]

We have computed the total energy as a function of six important torsion angles of the carcinogen N-2-acetylaminofluorene (AAF) bonded to the nitrogen N2 of deoxyguano sine using the semiempirical quantum mechanical method AM1. One global minimum and one local minimum are found separated by a modest barrier. We have computed the normal-mode frequencies of the relevant torsional motions and have determined the rate of conversion between the two minima. [ABSTRACT FROM AUTHOR]

The biochemistry and genetics of translesion synthesis (TLS) and, as a consequence, of mutagenesis has recently received much attention in view of the discovery of novel DNA polymerases, most of which belong to the Y family. These distributive and low fidelity enzymes assist the progression of the high fidelity replication complex in the bypass of DNA lesions that normally hinder its progression. The present paper extends our previous observation that in Escherichia coli all three SOS-inducible DNA polymerases (Pol II, IV and V) are involved in TLS and mutagenesis . The genetic control of frameshift mutation pathways induced by N-2-acetylaminofluorene (AAF) adducts or by oxidative lesions induced by methylene blue and visible light is investigated. The data show various examples of mutation pathways with an absolute requirement for a specific combination of DNA polymerases and, in contrast, other examples where two DNA polymerases exhibit functional redundancy within the same pathway. We suggest that cells respond to the challenge of replicating DNA templates potentially containing a large diversity of DNA lesions by using a pool of accessory DNA polymerases with relaxed specificities that assist the high fidelity replicase. [ABSTRACT FROM AUTHOR]

2-Acetylaminofluorene (AAF) inhibited in a dose dependent manner mouse spleen cell blastogenesis in response to phorbol 12-myristate 13-acetate (PMA)/Ionomycin (Io) activation, the T-cell lectin, concanavalin A (Con A), and following stimulation by alloantigens as measured by the mixed lymphocyte response (MRL). AAF also markedly suppressed the T-cell dependent antibody forming cell (AFC) response to sRBC. AAF was most inhibitory on both the sRBC IgM AFC response and Con A stimulated proliferation when added during the first 24 h following initiation of culture. Direct addition of high concentrations of AAF (100 μM) to spleen cell cultures at 48 h following Con A stimulation produced a very modes inhibition (<20%) of T-cell proliferation as compared to 90% when added at the time cultures were initiated. Similarly, AAF (75 and 100 μM) produced a greater than 80% inhibition of the in vitro AFC response when spleen cells were sensitized with antigen in presence of AAF. In contrast, no inhibition of the IgM AFC response was produced when AAF (75μM) was added to spleen cell cultures 48 or 72 h after antigen sensitization. Con A-triggered cell-cycle progression was attenuated at the G stage by the addition of AAF (50 and 100 μM) with no inhibition of S to G/M phase transition. These results suggest that the mechanism of AAF-mediated immune suppression is through a blockade of cell cycle progression from G to S phase. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Thyroid nodules frequently require ultrasound and Fine Needle Aspiration Cytology (FNAC) evaluation. However, FNA cytology does not allow differentiation between follicular adenoma and carcinoma on Bethesda type IV lesions. This situation leads to many unnecessary surgical procedures because it is not possible to assure the benignity of the lesions, even when most of the specimens correspond to adenomas or even other benign lesions. The objective in this study is to establish if there are any US characteristics that would help us to predict the risk of malignancy of nodules with a pathological diagnosis of follicular neoplasm in order to achieve a more conservative management for non-suspicious nodules., Material and Methods: We studied 61 nodules in 61 patients (51 women and 10 men) that underwent thyroid surgery and had histopathological results of either follicular adenoma or carcinoma. Different US characteristics of the nodules were analysed (composition, echogenicity, margin, calcification status, the presence of halo and overall observer suspicion of malignancy) and were correlated with the histopathological analysis., Results: We have found a statistically significant association between the presence of calcifications, ill-defined borders and overall observer suspicion or impression (defined by well-known suspicious for malignancy ultrasonographic features, such as calcification, poorly defined margin, and a markedly hypoechoic solid nodule; and benign ultrasonographic features, such as predominantly cystic echogenic composition and the presence of a perinodular hypoechogenic halo) with follicular carcinoma. However all those features have shown low sensitivities in the present study (30%, 30% and 50%, respectively). On the other hand, the absence of halo sign has shown a sensitivity of 100% and a negative predictive value (NPV) of 100% in our study., Conclusions: The presence of calcifications, ill-defined borders and the overall impression or suspicion of malignancy are associated with a higher risk for follicular carcinoma in Bethesda type IV thyroid nodules but their absence does not allow to predict benignity in these nodules. Inversely, when a halo sign lesion is observed, benign follicular neoplasm should be considered., (Copyright © 2020 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Among persons with obstructive airway disease, the relative contributions of chronic obstructive pulmonary disease (COPD), asthma, and common comorbid conditions to health care utilization and patient-centered outcomes (PCOs) have not been previously reported., Methods: We followed a total of 3,486 persons aged ≥40 years with COPD, asthma, or both at baseline, from the Medical Expenditure Panel Survey (MEPS) cohorts enrolled annually from 2008 through 2012 for 1 year. MEPS is a prospective observational study of US households recording self-reported COPD, asthma, and ten medical conditions: angina, arthritis, cancer, coronary heart disease, cognitive impairment, diabetes, hypertension, lung cancer, myocardial infarction, and stroke/transient ischemic attack. We studied the separate contributions of these conditions to health care utilization (all-cause and respiratory disease hospitalization, any emergency department [ED] visit, and six or more outpatient visits) and PCOs (seven or more days spent in bed due to illness, incident loss of mobility, and incident decline in self-perceived health)., Results: COPD made the largest contributions to all-cause and respiratory disease hospitalization and ED visits, while arthritis made the largest contribution to outpatient health care. Arthritis and COPD, respectively, made the greatest contributions to the PCOs., Conclusion: COPD made the largest and second largest contributions to health care utilization and PCOs among US adults with obstructive airway disease. The twelve medical conditions collectively accounted for between 52% and 61% of the health care utilization outcomes and between 53% and 68% of the PCOs. Cognitive impairment, diabetes, hypertension, and stroke also made significant contributions., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The present study aimed to characterize cerebral morphology in young adult ferrets and its sexual dimorphism using high-field MRI and MRI-based morphometry. Ex vivo short TR/TE (typical T1-weighted parameter setting for conventional MRI) and T2W (long TR/TE) MRI with high spatial resolution at 7-tesla could visualize major subcortical and archicortical structures, i.e., the caudate nucleus, lentiform nucleus, amygdala and hippocampus. In particular, laminar organization of the olfactory bulb was identifiable by short TR/TE-MRI. The primary and secondary sulci observable in the adult ferret were distinguishable on either short TR/TE- or T2W-MRI, and the cortical surface morphology was reproduced well by 3D-rendered images obtained by short TR/TE-MRI. The cerebrum had a significantly lower volume in females than in males, which was attributed to region-specific volume reduction in the cerebral cortex and subcortical white matter in females. A sexual difference was also detected, manifested by an overall reduction in normalized signal ratios of short TR/TE-MRI in all cerebral structures examined in females than in males. On the other hand, an alternating array of higher and lower short TR/TE-MRI intensity transverse zones throughout the cortex, which was reminiscent of the functional cortical areas, was revealed by maximum intensity projection (MIP) in 3D. The normalized signal ratio of short TR/TE-MRI, but not T2W-MRI in the cortex, was negatively correlated with the density of myelin-basic protein immunoreactive fibers (males, r=-0.440; females, r=-0.481). The present results suggest that sexual differences in the adult ferret cerebrum are characterized by reduced volumes of the cerebral cortex and subcortical white matter in females, and by overall reductions in physiochemical characteristics, as obtained by short TR/TE-MRI, in females. It should be noted that short TR/TE-MRI-based MIP delineated functional cortical areas related to myeloarchitecture in 3D. Such an approach makes possible conventional investigation of the functional organization of the cerebral cortex and its abnormalities using high-field MRI., (Copyright © 2013 Elsevier Inc. All rights reserved.)

To compare age-related deterioration of neural responses in each subfield of the auditory cortex in C57BL/6 mice, we evaluated amplitudes of tonal responses in young (5-11 weeks old) and adult (16-23 weeks old) groups using transcranial flavoprotein fluorescence imaging. Cortical responses to 20-kHz amplitude-modulated (AM) sounds, which were mainly found in the anterior auditory field (AAF) and the primary auditory cortex (AI) of the core region, were not markedly different between the two groups. In contrast, cortical responses to direction reversal of slow frequency-modulated (FM) sounds, which were mainly found in the ultrasonic field (UF), were significantly disrupted in the adult group compared with those in the young group. To investigate the mechanisms underlying such age-related deterioration, biotinylated dextran amine (BDA) was injected into UF. The number of retrograde labeled neurons in the dorsal division of the medial geniculate body (MGd) was markedly reduced in the adult group compared with that in the young group. These results strongly suggest that cortical responses to FM direction reversal in UF of adult C57BL/6 mice are mainly deteriorated by loss of non-lemniscal thalamic inputs from MGd to UF due to aging., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)