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BackgroundPrevious studies show an increasing incidence of gram-negative organisms in surgical site infections after spine surgery. This study is looking for the association of the post-operative prophylactic use of Bactrim and the gram-negative surgical site infection after lumbar spine surgery.MethodsPatients who underwent lumbar spine surgery between August 2010 and December 2019 at the institution were retrospectively reviewed.ResultsThere were 11 infections out of 511 cases where no oral antibiotics were given (2.2%). There were 2 infections out of 84 cases where Bactrim was given (2.4%). This was not statistically significant (P=0.89). The organisms cultured from the no oral antibiotic group were 8 cases of methicillin sensitive Staphylococcus aureus (MSSA), 1 case of E. coli, 1 case of Pseudomonas aeruginosa, 1 case of MRSA. The organisms cultured from the Bactrim group were 1 case of MRSA, and 1 case of combined Citrobacter freundii and methicillin sensitive Staphylococcus aureus (MSSA).ConclusionThere was no statistically significant difference in SSIs when Bactrim was given for two weeks after surgery. However, two subjects who developed infection from the Bactrim group were paradoxically affected by gram-negative and antibiotic resistant organisms. So, clinicians should be judicious in their use of oral antibiotics after spine surgery. Level of Evidence: III.

IntroductionAlzheimer's disease (AD) is the most common form of dementia. Beta-secretase (BACE) inhibitors have been proposed as potential therapeutic interventions; however, initiating treatment once disease has significantly progressed has failed to effectively stop or treat disease. Whether BACE inhibition may have efficacy when administered prophylactically in the early stages of AD has been under-investigated. The present studies aimed to evaluate prophylactic treatment of the BACE inhibitor verubecestat in an AD mouse model using the National Institute on Aging (NIA) resources of the Model Organism Development for Late-Onset Alzheimer's Disease (MODEL-AD) Preclinical Testing Core (PTC) Drug Screening Pipeline.Methods5XFAD mice were administered verubecestat ad libitum in chow from 3 to 6 months of age, prior to the onset of significant disease pathology. Following treatment (6 months of age), in vivo imaging was conducted with 18F-florbetapir (AV-45/Amyvid) (18F-AV45) and 18-FDG (fluorodeoxyglucose)-PET (positron emission tomography)/MRI (magnetic resonance imaging), brain and plasma amyloid beta (Aβ) were measured, and the clinical and behavioral characteristics of the mice were assessed and correlated with the pharmacokinetic data.ResultsProphylactic verubecestat treatment resulted in dose- and region-dependent attenuations of 18F-AV45 uptake in male and female 5XFAD mice. Plasma Aβ40 and Aβ42 were also dose-dependently attenuated with treatment. Across the dose range evaluated, side effects including coat color changes and motor alterations were reported, in the absence of cognitive improvement or changes in 18F-FDG uptake.DiscussionProphylactic treatment with verubecestat resulted in attenuated amyloid plaque deposition when treatment was initiated prior to significant pathology in 5XFAD mice. At the same dose range effective at attenuating Aβ levels, verubecestat produced side effects in the absence of improvements in cognitive function. Taken together these data demonstrate the rigorous translational approaches of the MODEL-AD PTC for interrogating potential therapeutics and provide insight into the limitations of verubecestat as a prophylactic intervention for early-stage AD.

Much of the literature on nonmarriage uses autonomy and choice as central values. This article explores the conscriptive side of family law, where choice is irrelevant. For example, genetic parents can often be conscripted into legal parentage, and no parent can 'divorce' their adult children. These rules arguably represent substantive normative judgments about what it means to be a 'parent.' To be sure, the state does not have a good track record when it asserts its right to define 'family.' But substantive normative judgments about what a 'family' is, and what membership in a 'family' entails, do not have to be tools for oppression and exclusion. This article explores ways that they could support progressive projects like imposing support obligations on former cohabitants and current co-parents. Each of these reforms needs a defense that is not solely grounded in autonomy and choice. One such defense is that certain relationships constitute a 'family' and members of a 'family' have obligations toward one another, regardless of choice. comments, I would like to thank the participants at the 2022 Nonmarriage Roundtable at Washington University School of Law., INTRODUCTION Much of the literature on nonmarriage uses autonomy and choice as central values. (1) Scholars argue that the state should respect the choices of people to form families. (2) [...]

When most people think about the water coming from their kitchen faucets, they seldom consider where the water originates and how transporting it to their homes has environmental impacts. Utilities that supply water know the complexity of their systems, but from their position as a "utility," they view their job as supplying safe water to their customers, not necessarily stewarding the environment. Consequently, when building large projects like dams, canals, and tunnels, utilities regard environmental disruption as a necessary byproduct of serving growing cities with water. Representations of these projects often replicate the "man conquering nature" frame, praising these engineering marvels for their defiance of nature. Denver Water, the utility that serves almost 1.5 million people on the arid eastern slope of the Colorado Rockies, has produced films describing its complex system since the early 20th century, and these films reveal an evolution of values from dominating nature to actively stewarding the environment. This paper reports on a grounded theory analysis of films produced by Denver Water between 1933 and 2018 examining how the films frame human relationships to the natural environment. The results reveal that the films increasingly express stewardship ideals over those of domination, with recent public communication actively advocating for environmental causes. The paper concludes by suggesting that we can learn important lessons from Denver Water about ethical organizational action for environmental stewardship.

Understanding the structure of messenger RNA (mRNA) lipid nanoparticles, and specifically the microenvironment of the mRNA molecules within these entities, is fundamental to advancing their biomedical potential. Here, we show that a permeating cationic dye, thionine, can serve as a cryogenic electron microscopy contrasting agent by binding selectively to encapsulated mRNA without disturbing lipid nanoparticle morphology. Cryo-electron microscopy images identify the mRNA location, revealing that mRNA may exist within solvent-filled cavities or may be substantially lipid associated.

STEFAN GEORGE The homosexual imaginary PETER MORGAN 208pp. Legenda. 85 [pounds sterling]. When I was a student in Trier I was given a poem by Stefan George (1868-1933) about the [...]

The aim of this work is to determine the effect of upper‐body high intensity interval training (HIIT) on cardiometabolic risks in individuals with chronic paraplegia. Twenty‐seven individuals (14 females, 13 males, mean ± SD age: 46 ± 9 years) with chronic paraplegia (spinal cord injury between T2 and L5 >1‐year post‐injury) took part in a randomized controlled trial and were included in the final analysis. Participants in the HIIT group (n = 18) performed ∼30 min of arm crank exercise (60 s intervals at 80%–90% peak heart rate) four times per week, for 6 weeks. Participants in the control (CON) group (n = 9) were asked to maintain their habitual diet and physical activity patterns over the study period. Outcome measures were taken at baseline and follow‐up. The primary outcome measures were fasting insulin, peak power output (PPO) and peak aerobic capacity (V̇O2peak${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$). Secondary outcome measures included body composition, postprandial glycaemic control, fasting blood lipids, inflammatory biomarkers and resting blood pressure. Differences between groups were assessed by ANCOVA, using baseline values as a covariate. PPO was higher in the HIIT (101 W, 97–106) compared to the CON (90 W, 83–96) group at follow‐up (P = 0.006). There were no differences in fasting insulin (P = 0.415) or relative V̇O2peak${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ (P = 0.417). Postprandial Matsuda insulin sensitivity index (ISIMatsuda) was higher in the HIIT (5.42, 4.69–6.15) compared to the CON (3.75, 2.46–5.04) group at follow‐up (P = 0.036). Six weeks of upper‐body HIIT increased PPO and ISIMatsuda, with no other beneficial effect on cardiometabolic component risks in persons with chronic paraplegia. Highlights: What is the central question of this study?What is the effect of upper‐body high intensity interval training (HIIT) on cardiometabolic component risks in individuals with chronic paraplegia?What is the main finding and its importance?Six weeks of upper‐body HIIT increased PPO and improved insulin sensitivity, but had no beneficial effect on other cardiometabolic component risks in persons with chronic paraplegia. The large effect size observed for insulin sensitivity may be important in terms of reducing the risk of type‐2 diabetes in this population. [ABSTRACT FROM AUTHOR]

The relationship between popular vernacular Catholicism and the more official liturgical variety has varied over centuries. Following the subjugation of Ireland by the late 17th century, and the institution of anti-Catholic proscriptions, the number of priests available became more restricted. Religious observation subsequently centered on holy days and local sacred sites including healing wells, many of them dedicated to saints. Always central figures in death rituals, women who mourned the dead—"keening women"—were so called because they lamented the dead through a combination of voice and song. We will show how the songs relate to a deep liminal spirituality that existed semi-independently of official Church norms, and how the voice served to establish their position. In the Catholic revival of the late nineteenth century, such forms were ousted by European modes of worship, but persisted at the margins, allowing us insight into their previous vigor. [ABSTRACT FROM AUTHOR]

PURPOSE Over 95% of patients who screen positive on the Patient Health Questionnaire-9 (PHQ-9) suicide risk item do not attempt or die by suicide, which could lead to unnecessary treatment and/or misallocation of limited resources. The present study seeks to determine if suicide risk screening can be meaningfully improved to identify the highest-risk patients. METHODS Patients eligible to receive medical treatment from the US Department of Defense medical system were recruited from 6 military primary care clinics located at 5 military installations around the United States. Patients completed self-report measures including the PHQ-9 and 16 items from the Suicide Cognitions Scale (SCS) during routine primary care clinic visits. Postbaseline suicidal behaviors (suicide attempts, interrupted attempts, and aborted attempts) were assessed by evaluators who were blind to screening results using the Self-Injurious Thoughts and Behaviors Interview. RESULTS Among 2,744 patients, 13 (0.5%) engaged in suicidal behavior in the 30 days after screening and 28 (1.0%) displayed suicidal behavior in the 90 days after screening. Multiple SCS items differentiated patients with suicidal behavior less than 30 days after screening positive for suicide risk. Augmenting the PHQ-9 suicide risk item with SCS items improved the identification of patients who were most likely to have suicidal behavior within a month of screening positive without sacrificing sensitivity. CONCLUSION Among primary care patients who screen positive for suicide risk on the PHQ-9, SCS items improved screening efficiency by identifying those patients who are most likely to engage in suicidal behavior within the next 30 days. Key words: primary health care; mass screening, suicide, INTRODUCTION From 1999 to 2017, the US suicide rate increased by more than 33%. (1) Suicides have increased at an even faster rate among military personnel and veterans. (2) Nearly [...]