1,148 research outputs found

    Differentiation Between Women With Vulvovaginal Symptoms Who are Positive or Negative for Candida Species by Culture

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    Objective: To investigate whether clinical criteria could differentiate between women with vulvovaginitis who were culture positive or negative for vaginal Candida species. Methods: Vulvovaginal specimens were obtained from 501 women with a vaginal discharge and/or pruritis. Clinical information and wet mount microscopy findings were obtained. All specimens were sent to a central laboratory for species identification. Results: A positive culture for Candida species was obtained from 364 (72.7%) of the specimens. C. albicans was identified in 86.4% of the positive cultures, followed by C. glabrata in 4.5%, C. parapsilosis in 3.9%, C. tropicalis in 2.7% and other Candida species in 1.4%.Women with a positive Candida culture had an increased utilization of oral contraceptives (26.1% vs. 16.8%, p = 0.02) and antibiotics (8.2% vs. 0.7%, p = 0.001), and were more likely to be pregnant (9.1% vs. 3.6%, p = 0.04) than the culture-negative women. Dyspareunia was more frequent in women without Candida (38.0% vs. 28.3%, p = 0.03) while vaginal erythema (p = 0.01) was more common in women with a positive Candida culture. Conclusions: Although quantitative differences were observed, the presence of vaginal Candida vulvovaginitis cannot be definitively identified by clinical criteria

    How Prosecutors and Defense Attorneys Differ in Their Use of Neuroscience Evidence

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    Much of the public debate surrounding the intersection of neuroscience and criminal law is based on assumptions about how prosecutors and defense attorneys differ in their use of neuroscience evidence. For example, according to some commentators, the defense’s use of neuroscience evidence will abdicate criminals of all responsibility for their offenses. In contrast, the prosecution’s use of that same evidence will unfairly punish the most vulnerable defendants as unfixable future dangers to society. This “double- edged sword” view of neuroscience evidence is important for flagging concerns about the law’s construction of criminal responsibility and punishment: it demonstrates that the same information about the defendant can either be mitigating or aggravating depending on who is raising it. Yet empirical assessments of legal decisions reveal a far more nuanced reality, showing that public beliefs about the impact of neuroscience on the criminal law can often be wrong. This Article takes an evidence-based and multidisciplinary approach to examining how courts respond to neuroscience evidence in capital cases when the defense presents it to argue that the defendant’s mental state at the time of the crime was below the given legal requisite due to some neurologic or cognitive deficiency

    Unravelling the genetics of non-random fertilization associated with gametic incompatibility

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    In the dairy industry, mate allocation is dependent on the producer’s breeding goals and the parents’ breeding values. The probability of pregnancy differs among sire-dam combinations, and the compatibility of a pair may vary due to the combination of gametic haplotypes. Under the hypothesis that incomplete incompatibility would reduce the odds of fertilization, and complete incompatibility would lead to a non-fertilizing or lethal combination, deviation from Mendelian inheritance expectations would be observed for incompatible pairs. By adding an interaction to a transmission ratio distortion (TRD) model, which detects departure from the Mendelian expectations, genomic regions linked to gametic incompatibility can be identified. This study aimed to determine the genetic background of gametic incompatibility in Holstein cattle. A total of 283,817 genotyped Holstein trios were used in a TRD analysis, resulting in 422 significant regions, which contained 2075 positional genes further investigated for network, overrepresentation, and guilt-by-association analyses. The identified biological pathways were associated with immunology and cellular communication and a total of 16 functional candidate genes were identified. Further investigation of gametic incompatibility will provide opportunities to improve mate allocation for the dairy cattle industry

    The segregation of different submicroscopic imbalances underlying the clinical variability associated with a familial karyotypically balanced translocation

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    Abstract\ud \ud Background\ud About 7 % of karyotypically balanced chromosomal rearrangements (BCRs) are associated with congenital anomalies due to gene or regulatory element disruption, and cryptic imbalances on rearranged chromosomes. Rare familial BCRs segregating with clinical features are a powerful source for the identifying of causative genes due to the presence of several affected carriers.\ud \ud \ud Case presentation\ud We report on a karyotypically balanced translocation t(2;22)(p13;q12.2) associated with variable learning disabilities, and craniofacial and hand dysmorphisms, detected in six individuals in a three-generation family. Combined a-CGH, FISH and mate-pair sequencing revealed a ten-break complex rearrangement, also involving chromosome 5. As the consequence of the segregation of the derivative chromosomes der(2), der(5) and der(22), different imbalances were present in affected and clinically normal family members, thus contributing to the clinical variability. A 6.64 Mb duplication of a 5q23.2-23.3 segment was the imbalance common to all affected individuals. Although LMNB1, implicated in adult-onset autosomal dominant leukodystrophy (ADLD) when overexpressed, was among the 18 duplicated genes, none of the adult carriers manifested ADLD, and LMNB1 overexpression was not detected in the two tested individuals, after qRT-PCR. The ectopic location of the extra copy of the LMBN1 gene on chromosome 22 might have negatively impacted its expression. In addition, two individuals presenting with more severe learning disabilities carried a 1.42 Mb 2p14 microdeletion, with three genes (CEP68, RAB1A and ACTR2),which are candidates for the intellectual impairment observed in the previously described 2p14p15 microdeletion syndrome, mapping to the minimal overlapping deleted segment. A 5p15.1 deletion, encompassing 1.47 Mb, also detected in the family, did not segregate with the clinical phenotype.\ud \ud \ud Conclusion\ud The disclosing of the complexity of an apparently simple two-break familial rearrangement illustrates the importance of reconstructing the precise structure of derivative chromosomes for establishing genotype-phenotype correlations.This work was funded by FAPESP - Fundação de Amparo à Pesquisa do Estado\ud de São Paulo (Grants: CEPID-Human Genome and Stem Cell Research Center\ud 2013/08028-1; student fellowships 2011/14293-4 and 2013/01146-9); the Lundbeck\ud Foundation (2013–14290), the UCPH Programme for Interdisciplinary Research\ud (Global Genes, Local Concerns) and The Danish Council for Independent Research\ud - Medical Sciences (4183-00482B). The authors thank Mrs. Maria Raimunda L. S.\ud Pinheiro for technical support

    Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages

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    Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3-16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different from known anti-tubercular drugs

    Differential Impact of the Pinewood Nematode on Pinus Species Under Drought Conditions

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    The pinewood nematode (PWN), Bursaphelenchus xylophilus, responsible for the pine wilt disease (PWD), is a major threat to pine forests worldwide. Since forest mortality due to PWN might be exacerbated by climate, the concerns regarding PWD in the Mediterranean region are further emphasized by the projected scenarios of more drought events and higher temperatures. In this context, it is essential to better understand the pine species vulnerability to PWN under these conditions. To achieve that, physiological responses and wilting symptoms were monitored in artificially inoculated Pinus pinaster (P. pinaster), Pinus pinea (P. pinea), and Pinus radiata (P. radiata) saplings under controlled temperature (25/30°C) and water availability (watered/water stressed). The results obtained showed that the impact of PWN is species-dependent, being infected P. pinaster and P. radiata more prone to physiological and morphological damage than P. pinea. For the more susceptible species (P. pinaster and P. radiata), the presence of the nematode was the main driver of photosynthetic responses, regardless of their temperature or water regime conditions. Nevertheless, water potential was revealed to be highly affected by the synergy of PWN and the studied abiotic conditions, with higher temperatures (P. pinaster) or water limitation (P. radiata) increasing the impact of nematodes on trees' water status. Furthermore, water limitation had an influence on nematodes density and its allocation on trees' structures, with P. pinaster revealing the highest nematode abundance and inner dispersion. In inoculated P. pinea individuals, nematodes' population decreased significantly, emphasizing this species resistance to PWN. Our findings revealed a synergistic impact of PWN infection and stressful environmental conditions, particularly on the water status of P. pinaster and P. radiata, triggering disease symptoms and mortality of these species. Our results suggest that predicted drought conditions might facilitate proliferation and exacerbate the impact of PWN on these two species, through xylem cavitation, leading to strong changes in pine forests of the Mediterranean regions
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