The immune evasion roles of Staphylococcus aureus protein A and impact on vaccine development.

While Staphylococcus aureus (S. aureus) bacteria are part of the human commensal flora, opportunistic invasion following breach of the epithelial layers can lead to a wide array of infection syndromes at both local and distant sites. Despite ubiquitous exposure from early infancy, the life-long risk of opportunistic infection is facilitated by a broad repertoire of S. aureus virulence proteins. These proteins play a key role in inhibiting development of a long-term protective immune response by mechanisms ranging from dysregulation of the complement cascade to the disruption of leukocyte migration. In this review we describe the recent progress made in dissecting S. aureus immune evasion, focusing on the role of the superantigen, staphylococcal protein A (SpA). Evasion of the normal human immune response drives the ability of S. aureus to cause infection, often recurrently, and is also thought to be a major hindrance in the development of effective vaccination strategies. Understanding the role of S. aureus virulence protein and determining methods overcoming or subverting these mechanisms could lead to much-needed breakthroughs in vaccine and monoclonal antibody development.

Treatment Updates for Pain Management and Opioid Use Disorder.

The medical community has proposed several clinical recommendations to promote patient safety and health amid the opioid overdose public health crisis. For a frontline practicing physician, distilling the evidence and implementing the latest guidelines may prove challenging. This article aims to highlight pertinent updates and clinical care pearls as they relate to primary care management of chronic pain and opioid use disorder.

An Unusual cause of Endocarditis.

A man in his 20s attended the emergency department with three days of fever, headache, reduced appetite and a sore throat. COVID-19 point-of-care test was negative. Blood cultures grew a gram-negative coccobacillus, Neisseria elongata Following an episode of confusion, MRI head revealed septic emboli. Prolapse of the mitral valve with regurgitation was noted on echocardiography. Infection was found to have originated from multiple dental caries and treatment required a combination of dental extraction, prolonged antibiotic therapy and surgery for mitral valve repair.N. elongata is part of the normal oropharyngeal flora but is also a rare cause of endocarditis. There are no established treatment guidelines for endocarditis of this aetiology. N. elongata endocarditis may present atypically, with a murmur only developing several days later. 'Classical' stigmata should not be relied on to make a diagnosis. N. elongata predominantly affects the left side of the heart and predisposes to embolic events.

Glioblastoma and primary central nervous system lymphoma: differentiation using MRI derived first-order texture analysis - a machine learning study.

OBJECTIVES: To evaluate the diagnostic performance of multiple machine learning classifier models derived from first-order histogram texture parameters extracted from T1-weighted contrast-enhanced images in differentiating glioblastoma and primary central nervous system lymphoma. METHODS: Retrospective study with 97 glioblastoma and 46 primary central nervous system lymphoma patients. Thirty-six different combinations of classifier models and feature selection techniques were evaluated. Five-fold nested cross-validation was performed. Model performance was assessed for whole tumour and largest single slice using receiver operating characteristic curve. RESULTS: The cross-validated model performance was relatively similar for the top performing models for both whole tumour and largest single slice (area under the curve 0.909-0.924). However, there was a considerable difference between the worst performing model (logistic regression with full feature set, area under the curve 0.737) and the highest performing model for whole tumour (least absolute shrinkage and selection operator model with correlation filter, area under the curve 0.924). For single slice, the multilayer perceptron model with correlation filter had the highest performance (area under the curve 0.914). No significant difference was seen between the diagnostic performance of the top performing model for both whole tumour and largest single slice. CONCLUSIONS: T1 contrast-enhanced derived first-order texture analysis can differentiate between glioblastoma and primary central nervous system lymphoma with good diagnostic performance. The machine learning performance can vary significantly depending on the model and feature selection methods. Largest single slice and whole tumour analysis show comparable diagnostic performance.

Survival prediction in glioblastoma on post-contrast magnetic resonance imaging using filtration based first-order texture analysis: Comparison of multiple machine learning models.

OBJECTIVE: Magnetic resonance texture analysis (MRTA) is a relatively new technique that can be a valuable addition to clinical and imaging parameters in predicting prognosis. In the present study, we investigated the efficacy of MRTA for glioblastoma survival using T1 contrast-enhanced (CE) images for texture analysis. METHODS: We evaluated the diagnostic performance of multiple machine learning models based on first-order histogram statistical parameters derived from T1-weighted CE images in the survival stratification of glioblastoma multiforme (GBM). Retrospective evaluation of 85 patients with GBM was performed. Thirty-six first-order texture parameters at six spatial scale filters (SSF) were extracted on the T1 CE axial images for the whole tumor using commercially available research software. Several machine learning classification models (in four broad categories: linear, penalized linear, non-linear, and ensemble classifiers) were evaluated to assess the survival prediction performance using optimal features. Principal component analysis was used prior to fitting the linear classifiers in order to reduce the dimensionality of the feature inputs. Fivefold cross-validation was used to partition the data iteratively into training and testing sets. The area under the receiver operating characteristic curve (AUC) was used to assess the diagnostic performance. RESULTS: The neural network model was the highest performing model with the highest observed AUC (0.811) and cross-validated AUC (0.71). The most important variable was the age at diagnosis, with mean and mean of positive pixels (MPP) for SSF = 0 being the second and third most important, followed by skewness for SSF = 0 and SSF = 4. CONCLUSIONS: First-order texture features, when combined with age at presentation, show good accuracy in predicting GBM survival.

Repeat Head CT for Neurologically Stable Patients With Mild Traumatic Subarachnoid Hemorrhage During Interfacility Transfer and Follow-Up Does Not Alter Patient Care [Formula: see text].

PURPOSE: To evaluate the impact of repeat head computed tomography (CT) during (1) interfacility transfer and (2) inpatient and/or outpatient follow-up on management, cost-effectiveness, and radiation dose in neurologically stable patients with mild traumatic subarachnoid hemorrhage (tSAH). MATERIAL AND METHODS: This is a single-center retrospective study evaluating patients with mild tSAH presenting between January 2017 and July 2019. A total of 101 and 140 patients met the eligibility criteria for the first and second subgroups, respectively. Common inclusion criteria were isolated mild tSAH, Glasgow Coma Scale between 13 and 15, and neurological stability. Additional inclusion criteria for the first subgroup were availability of brain imaging at the outside institution prior to transfer and the second subgroup was the availability of follow-up imaging. RESULTS: In the first subgroup, 76.20% of patients had stable SAH, 18.80% had reduced SAH, while 5% had an interval increase in SAH. None required any surgical intervention. Additional per-patient mean radiation exposure was 1.77 ± 0.26 mSv. In the second subgroup, all 140 patients had complete resolution of tSAH. One patient had a new tiny subdural hemorrhage, which subsequently resolved on follow-up. The additional mean radiation exposure was 2.47 ± 1.29 mSv. A total of 256 avoidable CT scans were performed resulting in excess health care costs of about US$531 696. CONCLUSION: In neurologically stable isolated tSAH patients, repeat brain imaging during interfacility transfer and inpatient and/or outpatient follow-up do not alter patient management despite increased health care costs and radiation burden.

Presurgical detection of brain invasion status in meningiomas based on first-order histogram based texture analysis of contrast enhanced imaging.

OBJECTIVE: Invasion of brain parenchyma by meningioma can be a critical factor in surgical planning. The aim of this study was to determine the diagnostic utility of first-order texture parameters derived from both whole tumor and single largest slice of T1-contrast enhanced (T1-CE) images in differentiating meningiomas with and without brain invasion based on histopathology demonstration. METHODS: T1-CE images of a total of 56 cases of grade II meningiomas with brain invasion (BI) and 52 meningiomas (37 grade I and 15 grade II) with no brain invasion (NBI) were analyzed. Filtration-based first-order histogram derived texture parameters were calculated both for whole tumor volume and largest axial cross-section. Random forest models were constructed both for whole tumor volume and largest axial cross-section individually and were assessed using a 5-fold cross validation with 100 repeats. RESULTS: In detection of brain invasion, random forest model based on whole tumor segmentation had an AUC of 0.988 (95 % CI 0.976-1.00) with a cross validated value of 0.74 (95 % CI 0.45-0.96). For differentiation of grade I meningiomas from grade II meningiomas with brain invasion, the AUC was 0.999 (95 % CI 0.995-1.00) and 0.81 (95 % CI 0.61-0.99) in the training and validation cohorts, respectively. Similarly, when using only the single largest slice, the cross-validated AUC to distinguish BI versus NBI and BI versus grade I meningiomas was 0.67 (95 % CI 0.47, 0.92 and 0.78 (95 % CI 0.52, 0.95) respectively. CONCLUSION: Radiomics based feature analysis applied on routine MRI post-contrast images may be helpful to predict presence of brain invasion in meningioma, possibly with better performance when comparing BI versus grade I meningiomas.

Mycetoma in Timor-Leste and first report of nocardiosis.

Mycetoma is a neglected tropical disease with an unknown global burden. Although considered endemic to South-east Asia, it has not previously been reported from Timor-Lest. We describe two cases in Timor-Leste, highlighting the challenges surrounding microbiological diagnosis and management shared by many low to middle-income countries. As characteristically described, both patients lived rurally and presented late with marked soft tissue involvement and multiple draining sinuses following a prolonged period of high morbidity. Nocardia brasiliensis, a beadedbranched, modified acid-fast, gram-positive bacilli, was isolated and confirmed by molecular testing in the first case. The causative organism in the second case could not be confirmed due to limited microbiological capabilities. Due to limited local laboratory capabilities, Nocardia spp. infection cannot be routinely confirmed in Timor- Leste. However, the microbiology laboratory is essential for the successful diagnosis and management of Mycetoma. In both cases, medical therapy alone resulted in cure and favorable outcomes, although supply of antibiotic remains an ongoing resource issue.

Spontaneous methicillin-sensitive Staphylococcus aureus spondylodiscitis-Short course antibiotic therapy may be adequate: Evidence from a single centre cohort.

Spontaneous methicillin-sensitive Staphylococcus aureus spondylodiscitis is increasing in prevalence and there appears to be little consensus on the optimum management of this condition. This paper analyses antimicrobial therapy and associated outcomes over a seven-year period at a large UK hospital trust. A retrospective search strategy identified 55 patients; notes were available for 39. Patients were treated with a median 12 weeks of antibiotics (IQR 7), with 6 weeks intravenous (IQR 3) and 9 weeks oral therapy (IQR 6). 23 different treatment regimens were utilised. 33/36 (92%) patients for whom outcomes were available were cured or improved at latest follow-up. This study reports a wide variation in antibiotic prescribing at a single centre. Outcomes were generally positive regardless of total duration of therapy and proportion of intravenous therapy. These findings highlight the need for multi-centre prospective randomised controlled trials to determine the most clinically effective and low-risk treatment strategy.

Assessing the performance of the four question abbreviated mental test in the acute geriatric setting.

BACKGROUND: NCognitive impairment is common amongst acute geriatric hospital admissions but detection is often poor and this is associated with worse outcomes. The four-question abbreviated mental test (AMT4) has previously been promoted nationally in the acute setting as a succinct assessment tool. However, a recent national dementia Commissioning for Quality and Innovation (CQUIN) goal recommends a single screening question followed by the tenquestion abbreviated mental test (AMT10). We aimed to evaluate the negative predictive value of the AMT4 within the acute setting by comparing it to three other validated tools. METHOD: We identified 100 acute medical admissions (>60 years old) with a negative AMT4 and administered the AMT10, six-item cognitive impairment test (6CIT) and confusion assessment method (CAM) within 24 hours of admission. RESULTS: Forty-six percent of the participants scored positively on at least one of the additional tests despite a negative AMT4. Forty-four patients had a positive 6CIT, 23 had a positive AMT10 and six had a positive CAM. Using the 6CIT as a diagnostic standard, tests of short-term memory had the greatest sensitivity and specificity for cognitive impairment. CONCLUSION: Nearly half of the participants had signs of cognitive impairment despite a negative AMT4. Consequently, there is a risk of under diagnosis with potentially serious consequences for morbidity and mortality. Tests of shortterm memory were strongly associated with cognitive impairment. We propose the addition of such a test in order to increase the sensitivity of the AMT4 without compromising its brevity and utility in the acute setting.

Correlates of relationship, psychological, and sexual behavioral factors for HIV risk among Indian women.

The rate of HIV/AIDS among women in India is expected to rise yet few studies have examined factors related to HIV risk among Indian women. The objective of this prospective, cross-sectional study was to characterize similarities and differences in the relationships, psychological well-being, and sexual behaviors among Indian women (N=459). Both HIV positive (N=216) and negative (N=243) women from urban and rural areas in India were included in this study. Chi-square, analysis of variance, and logistic regression analyses revealed that in both geographic groups, HIV-positive women were significantly more likely to report marital dissatisfaction, a history of forced sex, domestic violence, depressive symptoms and husband's extra marital sex when compared to the HIV-negative women. Findings also indicate that specific factors related to the quality of the marital relationship such as domestic violence, martial dysfunction, and depressive symptoms may be related to HIV-related risks for women. Implications for future research and culturally relevant interventions are discussed.

Correlates and predictors of HIV risk among inner-city African American female teenagers.

OBJECTIVE DESIGN: For human immunodeficiency virus (HIV)-related prevention initiatives to be most effective, they should be broad-based and incorporate multiple domains of influence. This study tested how several ecodevelopmental domains influenced HIV-risk related attitudes and behaviors in a community sample of African American female teens (N = 242). MAIN OUTCOME MEASURES: Outcome measures were number of partners, frequency of intercourse, number of pregnancies, abstinence/condom use, HIV/AIDS-related attitudes and behaviors, and HIV testing. RESULTS: Structural Equation Modeling revealed many direct paths from ecodvelopmental domains to risky sexual behaviors. The findings include having more partners was associated with parental alcohol-related problems, more drug use, and a younger age at first intercourse. More frequent intercourse was associated with less cultural pride and more drug use. More pregnancies were related to a younger age at first intercourse and parental alcohol problems. HIV testing was associated with having experienced sexual abuse, an older age at first intercourse, and stronger self-efficacy. CONCLUSIONS: Prevention programs that focus on risk reduction could expand their focus beyond sexual behavior to include a broad-range of psychosocial domains that are associated with HIV-risk. The effectiveness of prevention programs should be monitored carefully for appropriateness in different ethnic groups.

Suicidality, depression, and alcohol use among adolescents: a review of empirical findings.

Suicide is a serious health problem as it is currently the third leading cause of death for teenagers between the ages of 15 and 24 years. Depression, which is also a serious problem for adolescents, is the most significant biological and psychological risk factor for teen suicide. Alcohol use remains extremely widespread among today's teenagers and is related to both suicidality and depression. Suicidality refers to the occurrence of suicidal thoughts or suicidal behavior. The consensus in empirical research is that mental disorders and substance abuse are the most important risk factors in both attempted and completed adolescent suicide. Therefore, it is incumbent upon researchers to identify the factors that can lead to their prevention among today's youth. This review compiles the existing literature on suicidality, depression, and alcohol use among adolescents spanning over the past 15 years. Both Problem Behavior Theory and Stress-coping Theory can explain the relationships among suicidality, depression and alcohol use. The prevention of suicidality is critical, especially during the early school years, when it is associated with depression and alcohol use. Suicidality, depression and alcohol use are three phenomenon that noticeably increase in adolescence marking this time period as an ideal opportunity for prevention efforts to commence. Future empirical work is needed that will further assess the impact of adolescent depression and alcohol use on suicidality. In sum, this review of empirical research highlights critical results and limitations, as well as indicates a need for continued efforts in preventing suicidality, depression, and alcohol use among adolescents.

Childhood adversity, poly-substance use, and disordered eating in adolescent Latinas: mediated and indirect paths in a community sample.

OBJECTIVE: Although many studies have identified associations between childhood maltreatment and later substance use and disordered eating, few have examined causal or explanatory pathways, and whether victim characteristics predict the development of one versus the other of these outcomes remains uninvestigated. Furthermore, relatively little childhood maltreatment research has examined Latino samples. To address these gaps, this study examined among Latina adolescents the effects of sexual abuse, physical/emotional abuse, neglect, disconnection from family, and parental alcohol problems on poly-substance use and disordered eating, and whether five individual characteristics explain or differentiate these outcomes. METHOD: Data from a community sample of 361 Latina adolescents were analyzed using structural equation modeling. RESULTS: Physical/emotional abuse predicted poly-substance use and weight concerns, and these associations were mediated by impaired current attachment. Disconnection from family predicted bulimic behaviors, and this association was mediated by dysphoria. One indirect path also emerged: Disconnection from family predicted low social conformity, and low social conformity predicted poly-substance use. Childhood sexual abuse did not uniquely predict any adverse outcome or individual characteristic examined. CONCLUSIONS: Dysphoria and impaired current attachment appear to play important roles in the development of substance use and disordered eating in Latina adolescents when physical/emotional abuse or disconnection from family predicts these outcomes. Dysphoria and low social conformity may differentiate the development of bulimic behaviors and poly-substance use, respectively, when family disconnection predicts these outcomes.

Childhood adversity and poor mothering: consequences of polydrug abuse use as a moderator.

Drug abuse consequences have been typically examined as a direct or main effect on various later outcomes. Drug abuse may also serve as a consequence that alters (moderates) critical developmental trajectories. This study examined the relationship between childhood adversity factors (parent alcohol and drug-related problems, childhood maltreatment) and future parenting practices through an analysis of the moderating effects of polydrug problems. Data from a community sample of mothers was divided into two groups based on the median split level of polydrug problems (alcohol, marijuana, cocaine) that they reported (low, N=123; high, N=114). Confirmatory factor models (CFAs) were developed for the two groups and compared with multiple group analyses (MGAs). Results revealed that mothers who had parents with alcohol or drug-related problems were more likely to become poor parents, if they themselves used drugs and had problems related to drug use.

Adolescent predictors of young adult and adult alcohol involvement and dysphoria in a prospective community sample of women.

The adolescent predictors of later alcohol involvement (AI), dysphoria (D), and their shared association (AD) among women have not been adequately established. Three waves of data from an ethnically diverse community sample of women, assessed over 16 years are used to study how various psychosocial factors in adolescence influenced later drinking, depression, and their shared association. Structural equation models revealed that several adolescent ecodevelopmental and social development model variables influenced their later outcome in young adulthood and adulthood. The strongest relation was between adolescent Social Conformity and adult AD (beta = -.46) over a 16-year period, emphasizing the impact of this construct. Numerous other relations were revealed. For instance, less satisfaction with school during adolescence predicted adult AI. Having a good bond to the family in adolescence predicted a lower quantity of alcohol consumed during adulthood. Lower satisfaction with "what you want to be" during adolescence predicted young adult D. Higher levels of adolescent relationship satisfaction and school satisfaction predicted less suicidal ideation as an adult. Prevention interventions focusing on increasing socially conforming attitudes and on strengthening relationships both in and out of the home during adolescence are likely to be effective in reducing aspects of AI, D, and AD for women in the general community.

Child maltreatment, parent alcohol and drug-related problems, polydrug problems, and parenting practices: a test of gender differences and four theoretical perspectives.

The authors tested how adverse childhood experiences (child maltreatment and parent alcohol- and drug-related problems) and adult polydrug use (as a mediator) predict poor parenting in a community sample (237 mothers and 81 fathers). These relationships were framed within several theoretical perspectives, including observational learning, impaired functioning, self-medication, and parentification-pseudomaturity. Structural models revealed that child maltreatment predicted poor parenting practices among mothers. Parent alcohol- and drug-related problems had an indirect detrimental influence on mothers' parenting and practices through self-drug problems. Among fathers, emotional neglect experienced as a child predicted lack of parental warmth more parental neglect, and sexual abuse experienced as a child predicted a rejecting style of parenting.

Childhood experiences and psychosocial influences on HIV risk among adolescent Latinas in southern California.

This study determined how adverse childhood experiences influenced risky sexual behavior in a community sample of Latina adolescents in Los Angeles (N = 904) within a modified ecodevelopmental perspective. Psychosocial, sociocultural, and environmental mediators of the relations between childhood experiences and risky sexual behavior were tested. Many direct and mediated paths were revealed using structural equation modeling. Childhood maltreatment was associated with risk sexual practices, including more partners, less condom use, more frequent intercourse, and less HIV testing. Drug use and general self-efficacy mediated several relationships. Reducing childhood maltreatment reduced HIV risk and improved psychosocial functioning. Many factors tested did not influence HIV risk. Much of what is known about HIV risk among other populations may not apply to young Latina women.

Psychosocial outcomes of alcohol involvement and dysphoria in women: a 16-year prospective community study.

OBJECTIVE: Alcohol involvement, dysphoria, and their combined effects, may have long-term psychosocial consequences. However, because of weaknesses in existing literature, the exact relationships are unclear, as are the relative contributions of either construct or their combined effects to later psychosocial outcomes. This study tests the relationships between these conditions during late adolescence andyoung adulthood as predictors of adult marital, relational and job satisfaction; divorce; perceived opportunity; and job stability. We also test the influence of a change (increase or decrease) in alcohol involvement, dysphoria, or their combined association, on adult psychosocial functioning. METHOD: This study used three waves of data from an ethnically diverse, longitudinal community sample (N = 305 women) assessed over a 16-year span. The measures used have established validity and reliability. RESULTS: Structural equation models revealed that a second-order factor reflecting alcohol involvement and dysphoria during young adulthood was a stronger predictor of psychosocial maladjusument in adulthood than either alcohol involvement or dysphoria alone, predicting decreased satisfaction in multiple psychosocial domains (marriage, relationships and employment). An increase in the shared association between alcohol involvement and dysphoria from late adolescence to young adulthood reduced adult perceived opportunity. CONCLUSIONS: Early intervention is crucial. Clinicians should emphasize the screening for and treatment of alcohol involvement, dysphoria, and their combined effects, in late adolescence and young adulthood. Psychoeducational and treatment efforts to raise awareness of long-term consequences of these conditions are critical.