Characterization of the ABC methionine transporter from Neisseria meningitidis reveals that MetQ is a lipoprotein

NmMetQ is a substrate binding protein (SBP) from Neisseria meningitidis that has been identified as a surface-exposed candidate antigen for meningococcal vaccines. However, this location for NmMetQ challenges the prevailing view that SBPs in Gram-negative bacteria are localized to the periplasmic space to promote interaction with their cognate ABC transporter embedded in the bacterial inner membrane. To address the roles of NmMetQ, we characterized NmMetQ with and without its cognate ABC transporter (NmMetNI). Here, we show that NmMetQ is a lipoprotein (lipo-NmMetQ) that binds multiple methionine analogs and stimulates the ATPase activity of NmMetNI. Using single-particle electron cryo-microscopy, we determined the structures of NmMetNI in the absence and presence of lipo-NmMetQ. Based on our data, we propose that NmMetQ tethers to membranes via a lipid anchor and has dual function/topology, playing a role in NmMetNI-mediated transport at the inner-membrane in addition to moonlighting functions on the bacterial surface

Choroidal neovascularization secondary to tuberculosis: Presentation and management☆

Purpose While there are many known etiologies of choroidal neovascularization (CNV), tuberculosis is not a well-known causative agent. In this case series, we highlight CNV occurring secondary to tuberculous chorioretinitis, its presentation, and its management. Observations We retrospectively reviewed the charts and imaging of four patients who presented with presumed tuberculous chorioretinitis and CNV. Three of these patients had signs of intraocular inflammation and were also found to have active macular CNV. The one remaining patient had chorioretinal scars from prior posterior uveitis and previously treated macular CNV membranes. The three patients with active disease were started on anti-tuberculosis medications and oral corticosteroids, and they also received intravitreal anti-vascular endothelial growth factor (VEGF) injections as needed for the CNV. There was a significant improvement in the clinical course of all three patients with active disease—the intraocular inflammation subsided, and CNV recurrences were mitigated. Upon completion of systemic treatment, all patients have remained quiescent. Conclusions and importance Our findings demonstrate that CNV may occur in the course of tuberculous chorioretinitis with marked loss of vision, and management with anti-tuberculosis medications, oral corticosteroids, and intravitreal anti-VEGF injections results in notable improvement in their clinical course

Micronutrient Adequacy in Preschool Children Attending Family Child Care Homes

Limited data is available on the micronutrient intake and adequacy in preschool children enrolled in family child care homes (FCCH). The goal of this paper is to describe the micronutrient adequacy relative to age-specific recommendations of preschool-aged children (aged 2–5 years) attending FCCH in Rhode Island (RI). Dietary data among younger preschoolers (aged 2–3 years), n = 245) and older preschoolers (aged 4–5 years), n = 121) in 118 RI FCCH (N = 366 children) were analyzed. Nutrient adequacy was assessed as the amount of nutrient per 1000 kcal of the diet that would meet the Institute of Medicine nutrient requirements (critical nutrient density), and it was compared to the observed nutrient densities of the children. The sodium:potassium ratio was also calculated. For most micronutrients, the observed density met or exceeded the recommendation, meaning the children’s intake was adequate. However, a high proportion of children had nutrient densities under the recommendation for vitamins D, E, K, and potassium (86.1%, 89.1%, 70.8%, and 99.2% of children, respectively). The mean vitamin B12, potassium, and zinc densities were statistically higher in younger vs. older preschoolers (p \u3c 0.05 for all). Low densities in calcium and vitamins K and B5 were more frequent in older children vs. younger children (p \u3c 0.05). In addition, older preschoolers had a higher sodium:potassium ratio than younger children (p \u3c 0.05). The micronutrient intake density was adequate for most nutrients. However, intake of some nutrients was of concern. Further attention to training and compliance in FCCH may improve the diet quality of those cared for in these settings

Epigenetics in radiotherapy: Where are we heading?

Radiotherapy is an important component of anti-cancer treatment. However, not all cancer patients respond to radiotherapy, and with current knowledge clinicians are unable to predict which patients are at high risk of recurrence after radiotherapy. There is therefore an urgent need for biomarkers to guide clinical decision-making. Although the importance of epigenetic alterations is widely accepted, their application as biomarkers in radiotherapy has not been studied extensively. In addition, it has been suggested that radiotherapy itself introduces epigenetic alterations. As epigenetic alterations can potentially be reversed by drug treatment, they are interesting candidate targets for anticancer therapy or radiotherapy sensitizers. The application of demethylating drugs or histone deacetylase inhibitors to sensitize patients for radiotherapy has been studied in vitro, in vivo as well as in clinical trials with promising results. This review describes the current knowledge on epigenetics in radiotherapy

Tobacco smoking, polymorphisms in carcinogen metabolism enzyme genes, and risk of localized and advanced prostate cancer: results from the California Collaborative Prostate Cancer Study

The relationship between tobacco smoking and prostate cancer (PCa) remains inconclusive. This study examined the association between tobacco smoking and PCa risk taking into account polymorphisms in carcinogen metabolism enzyme genes as possible effect modifiers (9 polymorphisms and 1 predicted phenotype from metabolism enzyme genes). The study included cases (n = 761 localized; n = 1199 advanced) and controls (n = 1139) from the multiethnic California Collaborative Case–Control Study of Prostate Cancer. Multivariable conditional logistic regression was performed to evaluate the association between tobacco smoking variables and risk of localized and advanced PCa risk. Being a former smoker, regardless of time of quit smoking, was associated with an increased risk of localized PCa (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0–1.6). Among non-Hispanic Whites, ever smoking was associated with an increased risk of localized PCa (OR = 1.5; 95% CI = 1.1–2.1), whereas current smoking was associated with risk of advanced PCa (OR = 1.4; 95% CI = 1.0–1.9). However, no associations were observed between smoking intensity, duration or pack-year variables, and advanced PCa. No statistically significant trends were seen among Hispanics or African-Americans. The relationship between smoking status and PCa risk was modified by the CYP1A2 rs7662551 polymorphism (P-interaction = 0.008). In conclusion, tobacco smoking was associated with risk of PCa, primarily localized disease among non-Hispanic Whites. This association was modified by a genetic variant in CYP1A2, thus supporting a role for tobacco carcinogens in PCa risk

Definition of large bowel obstruction by primary colorectal cancer:A systematic review

Aim: Controversies on therapeutic strategy for large bowel obstruction by primary colorectal cancer mainly concern acute conditions, being essentially different from subacute obstruction. Clearly defining acute obstruction is important for design and interpretation of studies as well as for guidelines and daily practice. This systematic review aimed to evaluate definitions of obstruction by colorectal cancer in prospective studies. Method: A systematic search was performed in PubMed, Embase and the Cochrane Library. Eligibility criteria included randomized or prospective observational design, publication between 2000 and 2019, and the inclusion of patients with an obstruction caused by colorectal cancer. Provided definitions of obstruction were extracted with assessment of common elements. Results: A total of 16 randomized controlled trials (RCTs) and 99 prospective observational studies were included. Obstruction was specified as acute in 28 studies, complete/emergency in five, (sub)acute or similar terms in four and unspecified in 78. Five of 16 RCTs (31%) and 37 of 99 cohort studies (37%) provided a definition. The definitions included any combination of clinical symptoms, physical signs, endoscopic features and radiological imaging findings in 25 studies. The definition was only based on clinical symptoms in 11 and radiological imaging in six studies. Definitions included a radiological component in 100% of evaluable RCTs (5/5) vs. 54% of prospective observational studies (20/37, P = 0.07). Conclusion: In this systematic review, the majority of prospective studies did not define obstruction by colorectal cancer and its urgency, whereas provided definitions varied hugely. Radiological confirmation seems to be an essential component in defining acute obstruction

Clinical Findings in a Multicenter MRI Study of Mild TBI

Background: Uncertainty continues to surround mild traumatic brain injury (mTBI) diagnosis, symptoms, prognosis, and outcome due in part to a lack of objective biomarkers of injury and recovery. As mTBI gains recognition as a serious public health epidemic, there is need to identify risk factors, diagnostic tools, and imaging biomarkers to help guide diagnosis and management. Methods: One hundred and eleven patients (15-50 years old) were enrolled acutely after mTBI and followed with up to four standardized serial assessments over 3 months. Each encounter included a clinical exam, neuropsychological assessment, and magnetic resonance imaging (MRI). Chi-square and linear mixed models were used to assess changes over time and determine potential biomarkers of mTBI severity and outcome. Results: The symptoms most frequently endorsed after mTBI were headache (91%), not feeling right (89%), fatigue (86%), and feeling slowed down (84%). Of the 104 mTBI patients with a processed MRI scan, 28 (27%) subjects had white matter changes which were deemed unrelated to age, and 26 of these findings were deemed unrelated to acute trauma. Of the neuropsychological assessments tested, 5- and 6-Digit Backward Recall, the modified Balance Error Scoring System (BESS), and Immediate 5-Word Recall significantly improved longitudinally in mTBI subjects and differentiated between mTBI subjects and controls. Female sex was found to increase symptom severity scores (SSS) at every time point. Age \u3e/= 25 years was correlated with increased SSS. Subjects aged \u3e/= 25 also did not improve longitudinally on 5-Digit Backward Recall, Immediate 5-Word Recall, or Single-Leg Stance of the BESS, whereas subjects \u3c 25 years improved significantly. Patients who reported personal history of depression, anxiety, or other psychiatric disorder had higher SSS at each time point. Conclusions: The results of this study show that 5- and 6-Digit Backward Recall, the modified BESS, and Immediate 5-Word Recall should be considered useful in demonstrating cognitive and vestibular improvement during the mTBI recovery process. Clinicians should take female sex, older age, and history of psychiatric disorder into account when managing mTBI patients. Further study is necessary to determine the true prevalence of white matter changes in people with mTBI