Project description:Lytic enzymes, or lysins for short, break down peptidoglycan and interrupt the continuity of the cell wall, which, in turn, causes osmotic lysis of the bacterium. Their ability to destroy bacteria from within makes them promising antimicrobial agents that can be used as alternatives or supplements to antibiotics. In this paper, we briefly summarize basic terms and concepts used to describe lysin sequences and delineate major lysin groups. More importantly, we describe the domain repertoire found in lysins and critically review bioinformatic tools or databases which are used in studies of these enzymes (with particular emphasis on the repositories of Hidden Markov models). Finally, we present a novel comprehensive, meticulously curated set of lysin-related family and domain models, sort them into clusters that reflect major families, and demonstrate that the selected models can be used to efficiently search for new lysins.
Project description:A 37-year-old man presented with heart failure caused by severe aortic regurgitation (AR). He had a history of being involved in a traffic accident 3 months earlier. Imaging tests at admission detected no abnormalities in the aortic valve or aortic wall; however, the left coronary cusp prolapsed slightly on transthoracic echocardiography. He underwent aortic valve replacement because of uncontrolled heart failure and severe AR. Intraoperatively, the intima of the aortic wall just above the commissure of the left and right coronary cusps was torn to the short axial direction. Local aortic tear was the final diagnosis for the subacute AR. <Learning objective: Acute or subacute aortic regurgitation (AR) is comparatively rare, and it is sometimes difficult to clinically recognize. The tear in the aortic wall just above the commissure caused by a traffic accident led to the gradual progression of AR, and the diagnosis of the cause of AR was difficult despite using transesophageal echocardiography and contrast-enhanced computed tomography. We should recognize that the detection of subacute AR caused by a local aortic tear can be challenging.>.
Project description:Background and purposeSome retrospective studies have found that the aneurysm wall enhancement on high-resolution MR vessel wall postgadolinium T1WI has the potential to distinguish unstable aneurysms. This study aimed to identify hemodynamic characteristics that differ between the enhanced and nonenhanced areas of the aneurysm wall on high-resolution MR vessel wall postgadolinium T1WI.Materials and methodsTOF-MRA and high-resolution MR vessel wall T1WI of 25 patients were fused to localize the enhanced area of the aneurysm wall. Using computational fluid dynamics, we studied the aneurysm models. Mean static pressure, mean wall shear stress, and oscillatory shear index were compared between the enhanced and nonenhanced areas.ResultsThe aneurysmal enhanced area had lower wall shear stress (P < .05) and a lower oscillatory shear index (P = .021) than the nonenhanced area. In addition, the whole aneurysm had lower wall shear stress (P < .05) and a higher oscillatory shear index (P = .007) than the parent artery.ConclusionsThis study suggests that there are hemodynamic differences between the enhanced and nonenhanced areas of the aneurysm wall on high-resolution MR vessel wall postgadolinium T1WI.
Project description:Eccentric saccular aneurysms result from a focal weakness of the arterial wall that may be due to a focal tear or a partial disruption of the arterial wall. Saccular morphology itself is often used as a factor for immediate intervention, because the risk of rupture is higher than that of the common fusiform aneurysms. We present a case of a 72-year-old female patient with a huge saccular aneurysm of the infrarenal aorta. In this case report, we discuss the algorithm that can be used for the differential diagnosis of any saccular shape aneurysm and that the main parameter that needs to be clarified before the endovascular treatment of any saccular aneurysm is the presence or absence of infection of the arterial wall.
Project description:Since the advent of penicillin, humans have known about and explored the phenomenon of bacterial inhibition via antibiotics. However, with changes in the global environment and the abuse of antibiotics, resistance mechanisms have been selected in bacteria, presenting huge threats and challenges to the global medical and health system. Thus, the study and development of new antimicrobials is of unprecedented urgency and difficulty. Bacteria surround themselves with a cell wall to maintain cell rigidity and protect against environmental insults. Humans have taken advantage of antibiotics to target the bacterial cell wall, yielding some of the most widely used antibiotics to date. The cell wall is essential for bacterial growth and virulence but is absent from humans, remaining a high-priority target for antibiotic screening throughout the antibiotic era. Here, we review the extensively studied targets, i.e., MurA, MurB, MurC, MurD, MurE, MurF, Alr, Ddl, MurI, MurG, lipid A, and BamA in the cell wall, starting from the very beginning to the latest developments to elucidate antimicrobial screening. Furthermore, recent advances, including MraY and MsbA in peptidoglycan and lipopolysaccharide, and tagO, LtaS, LspA, Lgt, Lnt, Tol-Pal, MntC, and OspA in teichoic acid and lipoprotein, have also been profoundly discussed. The review further highlights that the application of new methods such as macromolecular labeling, compound libraries construction, and structure-based drug design will inspire researchers to screen ideal antibiotics.
Project description:PurposeTo improve the signal-to-noise ratio (SNR) and image sharpness for whole brain isotropic 0.5 mm three-dimensional (3D) T1 weighted (T1w) turbo spin echo (TSE) intracranial vessel wall imaging (IVWI) at 3 T.MethodsThe variable flip angle (VFA) method enables useful optimization across scan efficiency, SNR and relaxation induced point spread function (PSF) for TSE imaging. A convolutional neural network (CNN) was developed to retrospectively enhance the acquired TSE image with PSF blurring. The previously developed VFA method to increase SNR at the expense of blur can be combined with the presented PSF correction to yield long echo train length (ETL) scan while the acquired image remains high SNR and sharp. The overall approach can enable an optimized solution for accelerated whole brain high-resolution 3D T1w TSE IVWI. Its performance was evaluated on healthy volunteers and patients.ResultsThe PSF blurred image acquired by a long ETL scan can be enhanced by CNN to restore similar sharpness as a short ETL scan, which outperforms the traditional linear PSF enhancement approach. For accelerated whole brain IVWI on volunteers, the optimized isotropic 0.5 mm 3D T1w TSE sequence with CNN based PSF enhancement provides sufficient flow suppression and improved image quality. Preliminary results on patients further demonstrated its improved delineation for intracranial vessel wall and plaque morphology.ConclusionThe CNN enhanced VFA TSE imaging enables an overall image quality improvement for high-resolution 3D T1w IVWI, and may provide a better tradeoff across scan efficiency, SNR and PSF for 3D TSE acquisitions.
Project description:PurposeThe vessel wall MR imaging (VWI) literature was systematically reviewed to assess the criteria and measurement methods of VWI-related imaging endpoints for symptomatic intracranial plaque in patients with ischemic events.MethodsPubMed, Scopus, Web of Science, EMBASE, and Cochrane databases were searched up to October 2019. Two independent reviewers extracted data from 47 studies. A modified Guideline for Reporting Reliability and Agreement Studies was used to assess completeness of reporting.ResultsThe specific VWI-pulse sequence used to identify plaque was reported in 51% of studies. A VWI-based criterion to define plaque was reported in 38% of studies. A definition for culprit plaque was reported in 40% of studies. Frequently scored qualitative imaging endpoints were plaque quadrant (21%) and enhancement (21%). Frequently measured quantitative imaging endpoints were stenosis (19%), lumen area (15%), and remodeling index (14%). Reproducibility for all endpoints ranged from good to excellent (range: ICCT1 hyperintensity = 0.451 to ICCstenosis = 0.983). However, rater specialty and years of experience varied among studies.ConclusionsInvestigators are using different criteria to identify and measure VWI-imaging endpoints for culprit intracranial plaque. Early awareness of these differences to address methods of acquisition and measurement will help focus research resources and efforts in technique optimization and measurement reproducibility. Consensual definitions to detect plaque will be important to develop automatic lesion detection tools particularly in the era of radiomics.
Project description:Background and purposeThe incidence of wall enhancement of cerebral aneurysms on vessel wall MR imaging has been described as higher in ruptured intracranial aneurysms than in unruptured intracranial aneurysms, but the difference in the degree of enhancement between ruptured and unruptured aneurysms is unknown. We compared the degree of enhancement between ruptured and unruptured intracranial aneurysms by using quantitative MR imaging measures.Materials and methodsWe performed quantitative analyses of circumferential enhancement along the wall of cerebral aneurysms in 28 ruptured and 76 unruptured consecutive cases by using vessel wall MR imaging. A 3D-T1-weighted fast spin-echo sequence was obtained before and after contrast media injection, and the wall enhancement index was calculated. We then compared characteristics between ruptured and unruptured aneurysms.ResultsThe wall enhancement index was significantly higher in ruptured than in unruptured aneurysms (1.70 ± 1.06 versus 0.89 ± 0.88, respectively; P = .0001). The receiver operating characteristic curve analysis found that the most reliable cutoff value of the wall enhancement index to differentiate ruptured from unruptured aneurysms was 0.53 (sensitivity, 0.96; specificity, 0.47). The wall enhancement index remained significant in the multivariate logistic regression analysis (P < .0001).ConclusionsGreater circumferential enhancement along the wall of cerebral aneurysms correlates with the ruptured state. A quantitative evaluation of circumferential enhancement by using vessel wall MR imaging could be useful in differentiating ruptured from unruptured intracranial aneurysms.
Project description:Using the 1957-2011 data from the Wisconsin Longitudinal Study, I integrate the gender relations theory, a life course perspective, and a biosocial stress perspective to explore the effect of women's job authority in 1975 (at age 36) and 1993 (at age 54) on breast cancer incidence up to 2011. Findings indicate that women with the authority to hire, fire, and influence others' pay had a significantly higher risk of a breast cancer diagnosis over the next 30 years compared to housewives and employed women with no job authority. Because job authority conferred the highest risk of breast cancer for women who also spent more hours dealing with people at work in 1975, I suggest that the assertion of job authority by women in the 1970s involved stressful interpersonal experiences, such as social isolation and negative social interactions, that may have increased the risk of breast cancer via prolonged dysregulation of the glucocorticoid system and exposure of breast tissue to the adverse effects of chronically elevated cortisol. This study contributes to sociology by emphasizing gendered biosocial pathways through which women's occupational experiences become embodied and drive forward physiological repercussions.
Project description:ImportanceContradictory differences regarding fertility among adults born very preterm (VP; <32 weeks' gestation) or with very low birth weight (VLBW; <1500 g) have been reported at different ages. Longitudinal investigations of fertility beyond ages 20 to 29 years are lacking.ObjectiveTo assess whether VP and VLBW are associated with lower fertility up to age 35 years.Design, setting, and participantsThis prospective population-based cohort study was conducted in Bavaria, Germany, with participants born between January 1985 and March 1986 who required admission to a children's hospital within the first 10 days after birth. Healthy infants born at term (ie, at least 37 weeks' gestation) in the same hospital and children alive at 6 years were selected as controls. Follow-up occurred repeatedly up to 34 to 35 years. Data were analyzed from July to December 2024.ExposuresGestational age and birth weight.Main outcomes and measuresCumulative incidence of having the first alive child (ie, fertility) was calculated using Kaplan-Meier estimation and the difference between participants born VP or with VLBW and term-born participants was compared with log-rank tests. Univariable and hierarchical multivariable Cox proportional hazards regressions were performed to estimate hazard ratios (HRs) for fertility associated with VP and VLBW adjusting for individual factors. Estimations were compared between early (<30 years) and late (≥30 years) reproductive windows.ResultsA total of 414 participants (212 born VP or with VLBW and 202 term-born) were included (mean [SD] age, 34.67 [0.53] years; 216 [52.2%] female). Cumulative incidence of having the first alive child was lower in participants born VP or with VLBW throughout the follow-up. The association of VP and VLBW with lower fertility was significant during the late (HR, 0.46; 95% CI, 0.31-0.68) but not early (HR, 0.73; 95% CI, 0.47-1.14) reproductive window; this association attenuated after adjusting for neonatal factors (sex and family socioeconomic status) and childhood neurosensory impairment at step 2 (HR, 0.59; 95% CI 0.40-0.88), childhood family factors (eg, parenting) at step 3 (HR, 0.61; 95% CI, 0.40-0.92), and there was no longer an association after adjusting for sociodemographic factors (eg, partnering) at step 4 (HR, 0.78; 95% CI, 0.50-1.20). Partnering (ie, being married or cohabitating with a partner) had the largest magnitude association with fertility across both the early (HR, 7.87; 95% CI, 3.44-18.00) and late (HR, 3.95; 95% CI, 2.47-6.31) reproductive windows.Conclusions and relevanceIn this cohort study of participants born VP or with VLBW and term-born adults, VP and VLBW were associated with overall lower fertility. A major reason was an association of less partnering with lower fertility, suggesting that partnering is key to reproductive success.