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This study investigated the burden of illness associated with 440 cases of Salmonella enterica serotype Typhimurium infection identified in Canada between December 1999 and November 2000. We categorized case subjects' infections by definitive phage type 104 (DT104) and antimicrobial-resistance patterns. These variables were then investigated as risk factors for hospitalization. Hospitalization was more likely to occur among case subjects whose infections were resistant to at least ampicillin, chloramphenicol and/or kanamycin, streptomycin, sulphamethoxazole, and tetracycline (R-type AK/CSSuT; odds ratio [OR], 2.3; P=.003), compared with case subjects with AK/CSSuT-susceptible infections, and among case subjects with non-DT104 R-type AKSSuT infections (OR, 3.6; P=.005), compared with case subjects with non-DT104 AKSSuT-susceptible infections. In contrast, hospitalization rates did not differ between case subjects with DT104 infections and case subjects with non-DT104 infections or between case subjects with DT104 R-type ACSSuT infections and case subjects with DT104 ACSSuT-susceptible infections. We estimated that 57% of the hospitalizations among AK/CSSuT case subjects and 72% of the hospitalizations among non-DT104 AKSSuT case subjects were attributable to the resistance patterns of the infections. Copyright © 2005 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Labral tears and acromioclavicular joint abnormalities were differentiated on physical examination using a new diagnostic test. The standing patient forward flexed the arm to 90 degrees with the elbow in full extension and then adducted the arm 10 degrees to 15 degrees medial to the sagittal plane of the body and internally rotated it so that the thumb pointed downward. The examiner, standing behind the patient, applied a uniform downward force to the arm. With the arm in the same position, the palm was then fully supinated and the maneuver was repeated. The test was considered positive if pain was elicited during the first maneuver, and was reduced or eliminated with the second. Pain localized to the acromioclavicular joint or 'on top' was diagnostic of acromioclavicular joint abnormality, whereas pain or painful clicking described as 'inside' the shoulder was considered indicative of labral abnormality. A prospective study was performed on 318 patients to determine the sensitivity, specificity, and positive and negative predictive values of the test. Fifty-three of 56 patients whose preoperative examinations indicated a labral tear had confirmed labral tears that were repaired at surgery. Fifty-five of 62 patients who had pain in the acromioclavicular joint and whose preoperative examinations indicated abnormalities in the joint had positive clinical, operative, or radiographic evidence of acromioclavicular injury. There were no false-negative results in either group. [ABSTRACT FROM AUTHOR]

Fecal samples from 335 dairy farm residents and 1458 cattle on 80 farms were tested for Vero cytotoxin (VT)-producing Escherichia coli (VTEC). Residents were also tested for antibodies to VT1 and O157 lipopolysaccharide (LPS). Residents and cattle on farms with VTEC-positive persons or E. coli O157:H7-positive cattle were retested. Twenty-one persons (6.3%) on 16 farms (20.8%) and 46% of cattle on 100% of the farms had VTEC in fecal samples. Human VTEC isolates included E. coli O157:H7 and 8 other serotypes, 4 of which were present in cattle on the same farms. More persons had antibodies to VT1 (41%) than to O157 LPS (12.5%). Seropositivity to O157 LPS was associated with isolation of E. coli O157:H7 on the farm (P = .022). Human VTEC infection was negatively associated with age (P < .05) and was not associated with clinical illness. Many dairy farm residents experience subclinical immunizing VTEC infections at a young age, which frequently involve non-O157 VTEC found in cattle. [ABSTRACT FROM AUTHOR]

The potential for delayed evacuation of injured Service members from austere environments highlights the need to develop solutions that can stabilize a wound and enable mobility during these prolonged casualty care (PCC) scenarios. Lower extremity fractures have traditionally been treated by immobilization (splinting) followed by air evacuation - a paradigm not practical in PCC scenarios. In the civilian sector, treatment of extremity injuries sustained during remote recreational activities have similar challenges, particularly when adverse weather or terrain precludes early ground or air rescue. This review examines currently available fracture treatment solutions to include splinting, orthotic devices, and biological interventions and evaluates their feasibility: 1) for prolonged use in austere environments and 2) to enable patient mobilization. This review returned three common types of splints to include: a simple box splint, pneumatic splints, and traction splints. None of these splinting techniques allowed for ambulation. However, fixed facility-based orthotic interventions that include weight-bearing features may be combined with common splinting techniques to improve mobility. Biologically-focused technologies to stabilize a long bone fracture are still in their infancy. Integrating design features across these technologies could generate advanced treatments which would enable mobility, thus maximizing survivability until patient evacuation is feasible., (2023.)

Type 2 diabetes mellitus (T2DM) and depression are significant public health and socioeconomic issues. They commonly co-occur, with T2DM occurring in 11.3% of the US population, while depression has a prevalence of about 9%, with higher rates among youths. Approximately 31% of patients with T2DM suffer from depressive symptoms, with 11.4% having major depressive disorders, which is twice as high as the prevalence of depression in patients without T2DM. Additionally, over 80% of people with T2DM are overweight or obese. This review describes how T2DM and depression can enhance one another, using the same molecular pathways, by synergistically altering the brain's structure and function and reducing the reward obtained from eating. In this article, we reviewed the evidence that eating, especially high-caloric foods, stimulates the limbic system, initiating Reward Deficiency Syndrome. Analogous to other addictive behaviors, neurochemical changes in those with depression and/or T2DM are thought to cause individuals to increase their food intake to obtain the same reward leading to binge eating, weight gain and obesity. Treating the symptoms of T2DM, such as lowering HbA1c, without addressing the underlying pathways has little chance of eliminating the disease. Targeting the immune system, stress circuit, melatonin, and other alterations may be more effective., Competing Interests: The 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., (Copyright © 2023 Wilson, Epstein, Lopez, Brown, Lutfy and Friedman.)

Background: Persons with lower limb trauma are at high risk for falls. Although there is a wide range of measures used to assess stability and fall-risk that include performance measures, temporal-spatial gait parameters, and nonlinear dynamic stability calculations, these measures are typically derived from fall-prone populations, such as older adults. Thus, it is unclear if these commonly used fall-risk indicators are effective at evaluating fall-risk in a younger, higher-functioning population of Service members with lower limb trauma., Methods: Twenty-one Service members with lower limb trauma completed a battery of fall-risk assessments that included performance measures (e.g., four-square-step-test), and gait parameters (e.g., step width, step length, step time) and dynamic stability measures (e.g., local divergence exponents) during 10 min of treadmill walking. Participants also reported the number of stumbles and falls over the previous 4 weeks. Negative Binomial and Quasibinomial Regressions were used to evaluate the strength of associations between fall-risk indicators and self-reported falls., Finding: Participants reported on average stumbling 6(4) times and falling 2(3) times in the previous 4 weeks. At least one fall was reported by 62% of the participants. None of the fall-risk indicators were significantly associated with fall prevalence in this population of Service members with lower limb trauma (p > 0.1)., Interpretation: Despite the high number of reported falls in this young active population, none of the fall-risk indicators investigated effectively captured and quantified the fall-risk. Further research is needed to identify appropriate fall-risk assessments for young, high-functioning individuals with lower limb trauma., Competing Interests: Declaration of Competing Interest The University of Illinois-Chicago owns a patent on some of the technology referenced in this study. Consequently, there may be an institutional conflict of interest. One of the authors (MDG) is an inventor but has no conflicts of interest to declare regarding the present study. The authors have no other conflicts to disclose., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Predicting malignant transformation (MT) in oral epithelial dysplasia (OED) is challenging. The higher rate of MT reported in nonsmokers suggests an endogenous etiology in oncogenesis. We hypothesize that loss of FANCD2 and associated proteins could influence genomic instability and MT in the absence of environmental carcinogens., Study Design: Longitudinal archival samples were obtained from 40 individuals with OED: from diagnosis to the most recent review in 23 patients with stable OED or until excision of the squamous cell carcinoma in 17 patients with unstable OED undergoing MT. Histopathological reassessment, immunohistochemistry for FANCD2, and Western blotting for phosphorylation/monoubiquitylation status of ATR, CHK1, FANCD2, and FANCG were undertaken on each tissue sample., Results: Decreased expression of FANCD2 was observed in the diagnostic biopsies of OED lesions that later underwent MT. Combining the FANCD2 expression scores with histologic grading more accurately predicted MT (P = .005) than histology alone, and it correctly predicted MT in 10 of 17 initial biopsies. Significantly reduced expression of total FANCD2, pFANCD2, pATR, pCHK-1, and pFANCG was observed in unstable OED., Conclusions: There is preliminary evidence that defects in the DNA damage sensing/signaling/repair cascade are associated with MT in OED. Loss of expression of FANCD2 protein in association with a higher histologic grade of dysplasia offered better prediction of MT than clinicopathologic parameters alone., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Introduction: Lower extremity injury is common in the military and can lead to instability, pain, and decreased function. Military service also places high physical demands on service members (SMs). Standard treatment interventions often fail to align with these unique demands. Thus, the goal of the study was to evaluate the effectiveness of a military-specific virtual reality-based rehabilitation (VR) intervention supplemental to standard care (SC) in improving military performance in SMs with lower extremity injuries., Materials and Methods: As part of an institutional review board-approved randomized control trial, SMs receiving care at an advanced rehabilitation center were randomized to receive either SC or VR in addition to SC (VR+SC). Participants were evaluated before treatment and ∼3 weeks later using a previously developed and validated military-specific assessment. Perceived improvement in physical function was measured using a Global Rating of Change (GROC) questionnaire. A repeated measures ANOVA was used to evaluate the effects of adding VR on the military-specific assessment measures. Linear regression was used to determine the relationship between perceived improvement, measured improvement, and VR volume., Results: The VR+SC group was able to traverse a greater distance in the assessment following the VR intervention. There was no significant difference in GROC between groups. For the VR+SC group, change in distance completed was not correlated with GROC, but GROC was correlated with VR volume., Conclusion: VR improved the distance that participants were able to traverse in the assessment. However, the VR+SC group demonstrated a disconnect between their perceived functional improvement as measured by the GROC and functional improvement as measured by the change in the distance completed. Rather, the perceived improvement appears to be more correlated with the volume of VR received. The way in which the treatment progression is structured and communicated may influence how patients perceive their change in physical function., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: The link between cannabis use and erectile dysfunction remains unclear. Moreover, the effect of cannabis in tandem with current Western dietary habits is an area in male sexual health that has yet to be explored. This study seeks to investigate the impact of diet and cannabis on penile health in an animal model., Aim: To determine the effects of diet and oral cannabis extract on fibrosis and oxidative stress within the corpora cavernosa of mice., Methods: This is a pilot animal study in which groups of 2-month old C57BL/6J male mice were fed a normal chow diet (NCD) or high-fat diet (HFD) daily and treated with or without either MJ or THC extract for 2 months. After euthanization, mouse penises were isolated and processed for immunohistochemical studies to determine: (i) smooth muscle cell to collagen content, (ii) myofibroblast proliferation, and (iii) anti-oxidative activity., Main Outcome Measures: Quantitative assessment of immunohistochemical markers of fibrosis and oxidative stress within the corpora cavernosa of mice fed a high-fat diet in combination with either oral marijuana (MJ) or Δ-9-tetrahydrocannabinol extract (THC)., Results: The combination of HFD with MJ resulted in: (i) a decrease in the smooth/collagen ratio in the corpora cavernosa, (ii) an increase in alpha-smooth muscle actin expression in the tunica albuginea compatible with myofibroblast proliferation, and (iii) a decrease in heme oxygenase 1 expression indicating an increase in oxidative stress. Significant histological changes were not observed in the HFD + THC group., Conclusions: HFD combined with oral MJ extract led to structural alterations in erectile tissue that are associated with accelerated corporal fibrosis. However, the addition of THC to the diet did not exacerbate histological changes within the corpora. Further studies are warranted to elucidate the discrepant effects between MJ and THC in order to optimize the therapeutic potential of cannabis and minimize its adverse effects on penile health. S Nguyen, M Mangubat, S Eleswarapu, et al. The Combination of High-Fat Diet and Oral Marijuana Promotes the Development of Fibrosis in the Mouse Corpora Cavernosa. Sex Med 2021;9:100312., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Bilateral adrenalectomy (BLA) is a treatment option for patients with Cushing's Disease (CD) if transsphenoidal pituitary surgery fails or is not a therapeutic option. For most patients, BLA eliminates endogenous glucocorticoid and mineralocorticoid production, but for a small number of patients, endogenous secretion of adrenal hormones from adrenal tissue continues or recurs, leading to signs and symptoms of hypercortisolism. If adrenal tissue is confined to the adrenal bed, it is considered adrenal remnant tissue , while if it is outside the adrenal bed, it is considered adrenal rest tissue . We retrospectively evaluated morning serum cortisol, nighttime serum cortisol, nighttime salivary cortisol, and 24-h urine free cortisol on at least three occasions in 10 patients suspected of having endogenous cortisol production. Imaging of adrenal remnant tissue was also reviewed. Ten of 51 patients who underwent BLA during this time period had adrenal remnant/rest tissue marked by detectable endogenous glucocorticoid production; 9 of the 10 patients had signs and symptoms of hypercortisolism. Localization and treatment proved difficult. We conclude that the incidence of adrenal remnant/rest tissue in those undergoing BLA following unsuccessful pituitary surgery was 12% although there may have been a selection bias affecting this prevalence. The first indication of remnant tissue occurrence is a reduction in glucocorticoid replacement with symptoms of hypercortisolism. If this occurs, endogenous cortisol production should be tested for by cortisol measurements using a highly specific cortisol assay while the patient is taking dexamethasone or no glucocorticoid replacement. Endocrinologists need to monitor the development of both adrenal remnant tissue and Nelson's syndrome following BLA., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Introduction: Rehabilitation research of wounded service members (SMs) commonly focuses on physical ability to return to duty (RTD) as a measure of successful recovery. However, numerous factors or barriers may influence a SM's ability and/or desire to RTD after lower extremity musculoskeletal trauma. SMs themselves as well as the clinical care team that works with them daily, often for years at a time, both offer unique perspectives on the influential factors that weigh into decisions to RTD. The purpose of this study was to identify the intrinsic and extrinsic factors patients and clinicians recognized as influencing the decision to RTD after severe lower extremity trauma., Materials and Methods: Thirty-two SMs with severe lower extremity trauma (amputation and lower limb salvage) and 30 providers with at least 2 years' experience caring for SMs with similar injuries participated separately in either a SM or provider/clinician focus group. Open-ended questions on factors influencing RTD and other rehabilitation success were discussed. Data analysis consisted of qualitative transcription and participatory active sorting, followed by thematic coding and grouping of qualitative data., Results: Individual (health condition, personal traits, and career consideration), interpersonal (clinician's impact, family influence, and peer influence), health care system (systems of care, transdisciplinary rehabilitation, and innovation availability), and institutional (policy, benefits, and unit/commander) themes emerged amongst SM patients and clinicians. Expected frequently occurring themes common to both groups were the influence of the team and family unit, as well as career trajectory options after a severe injury. An unexpected theme was acknowledgment of and dissatisfaction with the recent dismantling of institutional systems that support wounded SMs. Patients placed less emphasis on severity of injury and greater emphasis on system and policy barriers than did clinicians., Conclusions: Characterization and classification of these clinician and SM-identified factors that influence the decision to RTD after severe lower extremity trauma is expected to improve the efficacy of future rehabilitation efforts and clinical practice guidelines by providing the clinical team the knowledge necessary to recognize modifiable barriers to patient success. A better understanding of factors influencing RTD decision-making may support policies for mitigating RTD barriers, better monitoring of the changing landscape of RTD after lower extremity trauma, improving systems of health care, and/or reducing turnover and facilitating force readiness., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

IκB kinase 2 (IKK2) is well known for its pivotal role as a mediator of the canonical NF-κB pathway, which has important functions in inflammation and immunity, but also in cancer. Here we identify a novel and critical function of IKK2 and its co-factor NEMO in the activation of oncogenic c-Jun N-terminal kinase (JNK) signaling, induced by the latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV). Independent of its kinase activity, the TGFβ-activated kinase 1 (TAK1) mediates LMP1 signaling complex formation, NEMO ubiquitination and subsequent IKK2 activation. The tumor progression locus 2 (TPL2) kinase is induced by LMP1 via IKK2 and transmits JNK activation signals downstream of IKK2. The IKK2-TPL2-JNK axis is specific for LMP1 and differs from TNFα, Interleukin-1 and CD40 signaling. This pathway mediates essential LMP1 survival signals in EBV-transformed human B cells and post-transplant lymphoma, and thus qualifies as a target for treatment of EBV-induced cancer.

Aortic stenosis (AS) is among the most common valvular heart diseases encountered in the United States. In this review the authors examine differences between racial and ethnic groups in the epidemiology and management of severe AS, explore potential explanations for these findings, and discuss the implications for improving the delivery of care to racially and ethnically diverse populations. Underrepresented racial and ethnic groups experience a paradoxically lower prevalence or incidence of AS relative to white subjects, despite having a higher prevalence of traditional risk factors. Historically, UREGs with severe AS have had lower rates of both surgical and transcatheter aortic valve replacement and experienced more post-surgical complications, including, bleeding, worsening heart failure, and rehospitalization. Last, UREGs with severe AS have an increased risk for morbidity and mortality relative to white patients. To date much of the research on AS has examined black-white differences, so there is a need to understand how other racial and ethnic groups with severe AS are diagnosed and treated, with examination of their resulting outcomes. Overall, racial and ethnic disparities in health care access and care delivery are a public health concern given the changing demographics of the U.S. population. These differences in AS management and outcomes highlight the need for additional research into contributing factors and appropriate interventions to address the lower rates of aortic valve replacement and higher morbidity and mortality among UREGs., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The Epstein-Barr virus (EBV) is one of the predominant tumor viruses in humans, but so far no therapeutic or prophylactic vaccination against this transforming pathogen is available. We demonstrated that heterologous prime-boost vaccination with the nuclear antigen 1 of EBV (EBNA1), either targeted to the DEC205 receptor on DCs or expressed from a recombinant modified vaccinia virus Ankara (MVA) vector, improved priming of antigen-specific CD4+ T cell help. This help supported the expansion and maintenance of EBNA1-specific CD8+ T cells that are most efficiently primed by recombinant adenoviruses that encode EBNA1. These combined CD4+ and CD8+ T cell responses protected against EBNA1-expressing T and B cell lymphomas, including lymphoproliferations that emerged spontaneously after EBNA1 expression. In particular, the heterologous EBNA1-expressing adenovirus, boosted by EBNA1-encoding MVA vaccination, demonstrated protection as a prophylactic and therapeutic treatment for the respective lymphoma challenges. Our study shows that such heterologous prime-boost vaccinations against EBV-associated malignancies as well as symptomatic primary EBV infection should be further explored for clinical development.

First-line treatments for classical Hodgkin lymphoma (HL) include ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and BEACOPP escalated (escalated dose bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone). To further improve overall outcomes, positron emission tomography-driven strategies and ABVD or BEACOPP variants incorporating the antibody-drug conjugate brentuximab vedotin (BV) or anti-PD1 antibodies are under investigation in advanced-stage patients. The present study aimed to elicit preferences for attributes associated with ABVD, BEACOPP escalated and BV-AVD (BV, adriamycin, vinblastine and dacarbazine) among patients and physicians. Cross-sectional online discrete choice experiments were administered to HL patients (n = 381) and haematologists/oncologists (n = 357) in France, Germany and the United Kingdom. Included attributes were progression-free survival (PFS), overall survival (OS), and the risk of neuropathy, lung damage, infertility and hospitalisation due to adverse events. Whereas 5-year PFS and OS were the most important treatment attributes to patients, the relative importance of each attribute and preference weights for each level varied among physicians according to the description of the hypothetical patient for whom treatment was recommended. PFS and OS most strongly influenced physicians' recommendations when considering young female patients who did not want children or young male patients. Infertility was more important to physicians' treatment decision than PFS when considering young women with unknown fertility preferences, whereas hospitalisations due to adverse events played the largest role in treatment decisions for older patients., (© 2018 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Genetics plays a role, to a greater or lesser extent, in all diseases. Variations in our DNA and differences in how that DNA functions (alone or in combinations), alongside the environment (which encompasses lifestyle), contribute to disease processes. This review explores the genetic basis of human disease, including single gene disorders, chromosomal imbalances, epigenetics, cancer and complex disorders, and considers how our understanding and technological advances can be applied to provision of appropriate diagnosis, management and therapy for patients., (© 2018 The Author(s).)