Plasma Amyloid-ß Homeostasis Is Associated with Body Mass Index and Weight Loss in People with Overweight and Obesity.

BACKGROUND: Obesity is linked to a higher incidence of Alzheimer's disease (AD). Studies show that plasma amyloid-ß (Aß) dyshomeostasis, particularly low 42/40 ratio indicates a heightened risk for developing AD. However, the relationship between body mass index (BMI) and circulating plasma Aß has not been extensively studied. OBJECTIVE: We hypothesized that people with a high BMI have altered plasma Aß homeostasis compared with people with a lower BMI. We also tested whether reducing BMI by calorie-restriction could normalize plasma concentrations of Aß. METHODS: Plasma concentrations of Aß40, Aß42, and Aß42/40 ratio were measured in 106 participants with BMIs classified as lean, overweight, or obese. From this cohort, twelve participants with overweight or obese BMIs entered a 12-week calorie-restriction weight loss program. We then tested whether decreasing BMI affected plasma Aß concentrations. RESULTS: Plasma Aß42/40 ratio was 17.54% lower in participants with an obese BMI compared to lean participants (p < 0.0001), and 11.76% lower compared to participants with an overweight BMI (p < 0.0001). The weight loss regimen decreased BMI by an average of 4.02% (p = 0.0005) and was associated with a 6.5% decrease in plasma Aß40 (p = 0.0425). However, weight loss showed negligible correlations with plasma Aß40, Aß42, and Aß42/40 ratio. CONCLUSION: Obesity is associated with aberrant plasma Aß homeostasis which may be associated with an increased risk for AD. Weight loss appears to lower Aß40, but large-scale longitudinal studies in addition to molecular studies are required to elucidate the underlying mechanisms of how obesity and weight loss influence plasma Aß homeostasis.

Is type 2 diabetes associated dementia a microvascular early-Alzheimer's phenotype induced by aberrations in the peripheral metabolism of lipoprotein-amyloid?

There is increasing evidence of a positive association of type 2 diabetes with Alzheimer's disease (AD), the most prevalent form of dementia. Suggested pathways include cerebral vascular dysfunction; central insulin resistance, or exaggerated brain abundance of potentially cytotoxic amyloid-ß (Aß), a hallmark feature of AD. However, contemporary studies find that Aß is secreted in the periphery by lipogenic organs and secreted as nascent triglyceride-rich lipoproteins (TRL's). Pre-clinical models show that exaggerated abundance in blood of TRL-Aß compromises blood-brain barrier (BBB) integrity, resulting in extravasation of the TRL-Aß moiety to brain parenchyme, neurovascular inflammation and neuronal degeneration concomitant with cognitive decline. Inhibiting secretion of TRL-Aß by peripheral lipogenic organs attenuates the early-AD phenotype indicated in animal models, consistent with causality. Poorly controlled type 2 diabetes commonly features hypertriglyceridemia because of exaggerated TRL secretion and reduced rates of catabolism. Alzheimer's in diabetes may therefore be a consequence of heightened abundance in blood of lipoprotein-Aß and accelerated breakdown of the BBB. This review reconciles the prevailing dogma of amyloid associated cytotoxicity as a primary risk factor in late-onset AD, with substantial evidence of a microvascular axis for dementia-in-diabetes. Consideration of potentially relevant pharmacotherapies to treat insulin resistance, dyslipidaemia and by extension plasma amyloidemia in type 2 diabetes are discussed.

Sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid.

BACKGROUND: Cannabidiol (CBD) confers therapeutic effects in some neurological disorders via modulation of inflammatory, oxidative and cell-signalling pathways. However, CBD is lipophilic and highly photooxidative with low oral bioavailability in plasma and brain. In this study, we aimed to design and test a CBD microencapsulation method as a drug delivery strategy to improve the absorption of CBD. Additionally, we evaluated the brain uptake of CBD capsules when administered alongside capsules containing a permeation-modifying bile acid, deoxycholic acid (DCA). METHODS: Microcapsules containing either CBD or DCA were formed using the ionic gelation method with 1.5% sodium alginate formulations and 100 mM calcium chloride. C57BL/6J wild type mice randomly assigned to three treatment groups (3-4 mice per group) were administered CBD in the following preparations: 1) CBD capsules, 2) CBD capsules + DCA capsules and 3) naked CBD oil (control). To assess the short-term bioavailability of CBD, plasma and brain samples were collected at 0.3, 1 and 3 hours post administration and CBD levels were analysed with liquid chromatography mass spectrometer. RESULTS: We produced spherical capsules at 400 ± 50 µm in size. The CBD capsules were calculated to have a drug loading of 2% and an encapsulation efficiency of 23%. Mice that received CBD capsules + DCA capsules showed a 40% and 47% increase in CBD plasma concentration compared to mice on CBD capsules and naked CBD oil, respectively. Furthermore, the CBD capsules + DCA capsules group showed a 48% and 25% increase in CBD brain concentration compared to mice on CBD capsules and naked CBD oil, respectively. In mice treated with CBD capsules + DCA capsules, the brain CBD concentration peaked at 0.3 hours with a 300% increased availability compared to CBD capsules and naked CBD oil groups, which peaked at 1 hour after administration. CONCLUSIONS: The microencapsulation method combined with a permeation enhancer, DCA increased the short-term bioavailability of CBD in plasma and brain.

Pigment Epithelium-Derived Factor and Sex Hormone-Responsive Cancers.

Oestrogens and androgens play important roles in normal and cancerous tissue and have been shown to negatively regulate pigment epithelium-derived factor (PEDF) expression in sex hormone-responsive tumours. PEDF suppresses tumour growth and its downregulation by oestrogen is implicated in tumorigenesis, metastasis, and progression. PEDF expression is reduced in cancerous tissue of the prostate, breast, ovary, and endometrium compared to their normal tissue counterparts, with a link between PEDF downregulation and sex hormone signalling observed in pre-clinical studies. PEDF reduces growth and metastasis of tumour cells by promoting apoptosis, inhibiting angiogenesis, increasing adhesion, and reducing migration. PEDF may also prevent treatment resistance in some cancers by downregulating oestrogen receptor signalling. By interacting with components of the tumour microenvironment, PEDF counteracts the proliferative and immunosuppressive effects of oestrogens, to ultimately reduce tumorigenesis and metastasis. In this review, we focus on sex hormone regulation of PEDF's anti-tumour action in sex hormone-responsive tumours.

Pigment epithelium-derived factor regulation of neuronal and stem cell fate.

Pigment epithelium-derived factor (PEDF) is an endogenous human glycoprotein first identified as a neurotrophic factor in retinal pigmented epithelium cells. PEDF has since been shown to play a central role in mediating cellular protection against oxidative stress, by promoting cell survival, reducing inflammation, and inhibiting pathological angiogenesis in a range of cell types and tissues. PEDF is a well-established neurotrophic factor which supports neurogenesis and provides neuroprotection in response to cellular stress, with numerous studies demonstrating the ability of PEDF to promote neuronal survival and growth following injury. PEDF is an essential component of the stem cell microenvironment and bone extracellular matrix, where it regulates the differentiation of osteoblast precursor cells to promote normal bone development. Accumulating evidence indicates that PEDF maintains stem cell populations and promotes neuronal growth and bone formation by directing cell fate and regulating cell cycle progression. The ability of PEDF to promote neurogenesis, osteogenesis, and stemness indicates therapeutic potential in diseases characterised by tissue degeneration. In this review, we provide a current summary of the role of PEDF in regulating cellular survival and differentiation in bone, the central nervous system, and other stem cell niches, and highlight the emerging potential of PEDF as a regenerative therapeutic agent.

Cytomegalovirus burden improves a predictive model identifying measures of vascular risk in renal transplant recipients and healthy adults.

Cytomegalovirus (CMV) has been implicated in vascular pathologies and may warrant inclusion in cardiovascular predictive algorithms. We addressed this in healthy older adults and renal transplant recipients (RTR) as they retain a high burden of CMV. RTR (n = 45) stable more than 2 years after transplantation and 58 age-matched healthy adults were assessed. Plasma inflammatory biomarkers (soluble isoform of the interferon-ß receptor [sIFNAR2], soluble tumour necrosis factorreceptor-1 [sTNFR1], soluble cluster of differentiation 14 [sCD14], C reactive protein, P-selectin, intracellular cell adhesion molecule-1, vascular cell adhesion molecule-1), and measures of CMV burden (antibodies, saliva CMV DNA, and interferon γ responses to CMV) were assessed in 2014 and evaluated in 2017 as predictors of vascular health-defined using flow-mediated dilatation (FMD), pulse wave velocity (PWV), and augmentation indices (Aix@ 75). Linear regression models adjusted for age, sex, and body mass index (BMI) were optimized to identify risk factors. In 2017, RTR had inferior vascular health marked by impaired FMD and PWV. Detectable CMV DNA (P = .02) was associated with impaired FMD, whilst CMV glycoprotein B (gB) antibody attenuated this effect (P = .03) (adjusted R2 = .42). In healthy adults, the optimal model for predicting FMD (R2 =.22) incorporated high P-selectin (P = .03) and low ICAM-1 (P = .03) levels with no significant impact of CMV. Elevated sIFNAR2 (P = .04) and gB antibody (P = .06) levels predicted increasing Aix@ 75 (poor vascular health) in healthy adults (R2 = .4), whilst optimal models for RTR (R2 = .37) linked low sIFNAR2 and CMV IE-1 antibody levels with lower Aix@ 75 (better vascular health). CMV IE-1 antibody was also protective in relation to PWV in healthy adults (R2 = .55). Overall, measures of active CMV replication were more predictive of impaired FMD in RTR than standard biomarkers, but increased CMV gB antibodies may be protective.

Implementation and effect of concussion education in collegiate women's ice hockey.

Objective: This study aimed to determine whether collegiate women's ice hockey players are receiving pre-season concussion education and evaluate the nature and delivery of this education. Secondarily, we aimed to assess whether players who recall receiving this education have greater knowledge about concussion or are more likely to have reported suspected concussions than their peers.Methods: An anonymous survey was completed by 459 NCAA women's ice hockey players. Players self-reported receipt of pre-season concussion education, year in school, division of competition, player position, and average length of ice hockey career. Players also completed scales assessing concussion knowledge, attitudes and prior reporting behavior for suspected concussions.Results: 65.3% of athletes affirmed that they received pre-season concussion education. Lecture by an athletic trainer was the most common modality. There were no differences in concussion knowledge or attitudes by concussion education status, NCAA division of competition, or year in school. Players with higher knowledge scores were more likely than their peers to have experienced a suspected concussion and to have not reported it (p = 0.056).Conclusions: Not all NCAA women's ice hockey players are receiving (or recall receiving) mandated concussion education from their institution. The inverse association between concussion knowledge and concussion reporting behavior, while not statistically significant, is concerning and warrants further study. More work is needed to develop educational materials about concussion that are acceptable and memorable to this population, and that help increase concussion care-seeking behaviors.

The Influence of Mentors in Orthopedic Surgery.

The importance of mentorship in medicine has been established. However, little is known regarding the influence of mentors in orthopedic surgery. This study sought to (1) determine the prevalence of mentoring relationships in orthopedic surgery, (2) assess the influence of mentors in specialty and subspecialty selection, and (3) evaluate the importance of gender in orthopedic mentoring relationships. An electronic survey was distributed to 358 orthopedic surgeons at academic residency programs. Participants were asked to report mentoring relationships and their attitudes toward mentors, including gender preferences. A total of 117 (95 males and 22 females) surveys were returned. The majority of respondents (66.7%, n=78) had at least one mentor in their career, and the majority of respondents (66.7%, n=52) were satisfied with their mentoring experience. Residency was the most common time to have a mentor, and 73.3% (n=44) of respondents indicated their mentor was influential in determining their subspecialty. Although only 50% of respondents indicated they had a mentor in medical school, 84.2% (n=32) believed their mentor was influential in selecting an orthopedic surgery residency. The majority (79.4%, n=62) of respondents did not have a preference on the gender of their mentor. Many orthopedic surgeons have a mentor at some point in their career who influenced their specialty or subspecialty decision. Mentoring experiences are less prevalent in medical school, and female medical students may lack accessibility to mentoring opportunities. Future efforts should focus on opportunities that connect medical students to orthopedic surgery faculty to further diversify the field and close the gender gap. [Orthopedics. 2020; 43(1):e37-e42.].

Sex-Based Differences in Patient-Reported Outcomes After Arthroscopic Rotator Cuff Repair.

BACKGROUND: Rotator cuff repair is one of the most common surgical procedures performed on the shoulder. Previous studies have indicated that pain and disability can vary significantly between patients with similarly appearing rotator cuff tears on diagnostic imaging. Prior literature has compared functional outcomes between operative and nonoperative treatments as well as variability in surgical techniques. However, few studies have examined postoperative outcomes based on patient factors such as sex. PURPOSE: To compare patient-reported outcomes after rotator cuff repair between men and women. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 283 patients (153 male, 130 female) who underwent primary arthroscopic rotator cuff repair were included in this study; of those, 275 patients (97.2%) completed 1-year follow-up. Patient-reported pain visual analog scale (VAS), Veterans RAND 12-item Health Survey (VR-12 mental and physical components), American Shoulder and Elbow Surgeons (ASES), and Single Assessment Numeric Evaluation (SANE) scores were collected preoperatively and at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year postoperatively using an electronic outcomes system. RESULTS: Women reported higher VAS pain scores when compared with men preoperatively (P < .01) and at 2 weeks (P < .01), 6 weeks (P < .01), and 3 months (P = .02) postoperatively. Additionally, women experienced a greater overall change in the mean VAS score preoperatively when compared with 1 year postoperatively (P < .01). The use of narcotic pain medication 2 weeks after surgery was greater in women (P = .032). Women had significantly lower preoperative VR-12 mental scores (P = .03) and experienced a greater increase in the mean VR-12 mental score preoperatively when compared with 1 year postoperatively (P < .01). Men had higher ASES scores preoperatively (P < .01) and at 3 months postoperatively (P < .01). Women experienced a greater overall change in the ASES score preoperatively when compared with 1 year postoperatively (P < .01). CONCLUSION: Women reported greater pain and decreased shoulder function compared with men during the initial 3 months after arthroscopic rotator cuff repair. There were no sex-based differences in patient-reported outcomes at 1-year follow-up. The results of this study indicate that there are sex-related differences in the early postoperative recovery of patients undergoing rotator cuff repair, contributing to postoperative expectations for both clinicians and patients alike.

The role of pigment epithelium-derived factor in protecting against cellular stress.

Since its discovery as a neurotrophic factor in retinal pigmented epithelium cells in the late 1980s, there has been an increase in understanding of the role that pigment epithelium-derived factor (PEDF) plays in cellular functions. PEDF plays an important role in mediating cellular protection during exposure to oxidative stress and inflammation by preventing stress-induced angiogenesis and apoptosis. PEDF acts to reduce oxidative stress by promoting mitochondrial stability and by regulating the expression of enzymes involved in ROS accumulation and clearance. PEDF protects against the negative effects of oxidative stress by regulating cell survival pathways and the expression of inflammatory and proangiogenic mediators. PEDF-mediated cellular protection may be of clinical importance in diseases characterised by oxidative stress, chronic inflammation and pathological neovascularization, indicating that targeting PEDF may be a potential focus for therapeutic interventions in chronic diseases. In this review, we provide a historical perspective on the discoveries of PEDF interactions and functions, and discuss recent in vitro, in vivo and clinical findings to provide a current summary of the important protective effects following cellular exposure to stress stimuli and future clinical potential of PEDF.

Prevalence and Anatomical Distribution of Bone Stress Injuries in the Elite Para Athlete.

Bone stress injury is a common overuse injury in athletes. Risk factors for bone stress injury in athletes include the female athlete triad (triad); this has not been evaluated in para athletes. The aim of this study was to identify risk factors, prevalence, and anatomical distribution of bone stress injury in para athletes. A cross-sectional online survey on health characteristics and previous fractures including bone stress injury was completed by para athletes training for the 2016 or 2018 Paralympic Games. Two hundred sixty para athletes completed the survey (659 invited, response rate = 40%). Half reported previous fracture, and bone stress injury was reported in 9.2% of all athletes. Twenty-four athletes (11 men and 13 women) sustained one or more bone stress injury, including 13 athletes with two bone stress injuries. No risk factors of the triad, disability type, or duration of disability were associated with bone stress injury. Injuries were most common in the metatarsals (n = 8) and hand/wrist (n = 7). In an elite para athlete population, locations for bone stress injury included both the upper and lower limbs. Clinically, para athletes presenting with pain localized to bone require further workup to evaluate for bone stress injury particularly for pain in both upper and lower limbs. Further research is required to identify risk factors for bone stress injury in para athletes.

Multimodal Imaging Analyses of Brain Hippocampal Formation Reveal Reduced Cu and Lipid Content and Increased Lactate Content in Non-Insulin-Dependent Diabetic Mice.

Non-insulin-dependent diabetes mellitus (NIDDM) is reported to increase the risk of cognitive impairment and dementia. However, the underlying mechanisms are not fully understood. While the brain homeostasis of metals and lipids is pivotal to maintaining energy metabolism and redox homeostasis for healthy brain function, no studies have reported hippocampal metal and biochemical changes in NIDDM. Therefore, we here utilized direct spectroscopic imaging to reveal the elemental distribution within the hippocampal subregions of an established murine model of NIDDM, db/db mice. In 26-week-old insulin resistant db/db mice, X-ray fluorescence microscopy revealed that the Cu content within the dentate gyrus and CA3 was significantly greater than that of the age-matched nondiabetic control mice. In addition, Fourier transform infrared (FTIR) spectroscopy analysis indicated a significant increase in the abundance of lactate within the corpus callosum (CC), dentate gyrus, CA1, and CA3 regions of diabetic db/db mice compared to that of the control, indicating altered energy metabolism. FTIR analysis also showed a significant decrease in the level of lipid methylene and ester within the CC of db/db mice. Furthermore, immunomicroscopy analyses demonstrated the increase in the level of glial fibrillary acidic protein expression and peri-vascular extravasation of IgG, indicating astrogliosis and blood-brain barrier dysfunction, respectively. These data suggest that astrogliosis-induced alterations in the supply of Cu, lipids, and energy substrates may be involved in the mechanisms of NIDDM-associated cognitive decline.

A high burden of cytomegalovirus marks poor vascular health in transplant recipients more clearly than in the general population.

OBJECTIVES: Meta-analyses have now confirmed that persistent infections with cytomegalovirus (CMV) can accelerate the onset of diseases of ageing, notably cardiovascular pathologies. We address the circumstances in which the association may be strong enough to warrant intervention to reduce the viral burden. RESULTS: We compare markers of the burden of CMV with established indices of vascular pathology in healthy adults (n = 82) and in renal transplant recipients (RTR; n = 81). Levels of all inflammatory and vascular biomarkers and CMV antibodies were higher in RTR, and flow-mediated dilation (FMD) values were lower indicating inferior endothelial function. In multivariable regression models without adjustment for estimated glomerular filtration rate (eGFR), CMV antibody levels, age and gender were independently associated with FMD in RTR, whilst only CRP associated with FMD in healthy adults. After adjustment for eGFR, associations between CMV antibody and FMD in RTR were reduced. METHODS: Carotid intima-media thickness, FMD, eGFR and plasma levels of CMV antibodies (reactive with a lysate, CMV IE-1 or CMV gB), ICAM-1, VCAM-1, P-selectin, sIFNαR2, sTNFR1, sCD14 and CRP were determined. CONCLUSION: Levels of CMV antibody predict declining endothelial health in RTR and not in healthy adults, presumably by reflecting a high burden of CMV. The levels of CMV antibodies were a poor reflection of plasma biomarkers thought to reflect 'inflammaging' or vascular damage.

Blood-brain barrier disturbances in diabetes-associated dementia: Therapeutic potential for cannabinoids.

Type-2 diabetes (T2D) increases the risk of dementia by ˜5-fold, however the mechanisms by which T2D increases dementia risk remain unclear. Evidence suggests that the heightened inflammation and oxidative stress in T2D may lead to disruption of the blood-brain barrier (BBB), which precedes premature cognitive decline. Studies show that vascular-targeted anti-inflammatory treatments protect the BBB by attenuating neuroinflammation, and in some studies attenuate cognitive decline. Yet, this potential pathway is understudied in T2D-associated cognitive impairment. In recent years, therapeutic potential of cannabinoids has gained much interest. The two major cannabinoids, cannabidiol and tetrahydrocannabinol, exert anti-inflammatory and vascular protective effects, however few studies report their potential for reversing BBB dysfunction, particularly in T2D. Therefore, in this review, we summarize the current findings on the role of BBB dysfunction in T2D-associated dementia and consider the potential therapeutic use of cannabinoids as a protectant of cerebrovascular BBB protection.

Low energy availability, menstrual dysfunction, and impaired bone health: A survey of elite para athletes.

INTRODUCTION: The Female Athlete Triad (Triad) is a syndrome describing three interrelated conditions: low energy availability (LEA), menstrual dysfunction, and low bone mineral density (BMD). Relative Energy Deficiency in Sport (RED-S) expands the Triad to include multiple physiologic consequences of LEA in both sexes. The purpose of this study is to determine the prevalence of factors associated with the Triad/RED-S in an elite para athlete population. METHODS: Athletes were U.S. elite para athletes training to qualify for the 2016 or the 2018 Paralympic Games. Participants completed an online questionnaire characterizing nutrition, menstrual status (in females), bone health, and awareness of the Triad/RED-S. RESULTS: The athletes were 260 elite para athletes (150 male, 110 female). While few reported prior eating disorder (3.1%), 32.4% had elevated Eating Disorder Examination Questionnaire (EDE-Q) pathologic behavior subscale scores. Most athletes (95 male, 65 female) were attempting to change their body composition or weight to improve performance. Forty-four percent of premenopausal females had oligomenorrhea/amenorrhea. Bone stress injury was reported in 9.2% of athletes; of these, 54.5% (n = 12) had low BMD. Less than 10% of athletes reported awareness of the Triad/RED-S. CONCLUSIONS: Factors associated with the Triad/RED-S are present in an elite para athlete population, regardless of sex or sport type. Awareness of the Triad/RED-S in para athletes is low. The consequences of LEA in para athlete populations are poorly understood. However, the high prevalence of factors observed suggests value in advancing screening tools and education efforts to optimize health in this population.

Reporting the Influence of Sex in Research: Trends at AAOS Annual Meetings.

BACKGROUND: Several initiatives have urged the inclusion of sex in data analysis, but few studies have examined the prevalence of sex-specific reporting in musculoskeletal research. This study aims at determining the presence of sex-specific analyses reported in research at American Academy of Orthopaedic Surgeons Annual Meetings. METHODS: Abstracts listed in the American Academy of Orthopaedic Surgeons Annual Meeting programs from 2006 to 2013 were retrospectively reviewed for the presence of research reporting the results of a sex-specific analysis. RESULTS: The number of abstracts reporting a sex-specific analysis increased from 48 (2006) to 117 (2013) but accounts for 5.4% of research presented from 2006 to 2013. Hip and knee arthroplasty literature accounted for 37% of included abstracts. CONCLUSIONS: The reporting of sex-specific analyses has improved over time but accounts for 5.4% of research presented at annual meetings from 2006 to 2013. The inclusion of sex-specific analyses should be required for future research publications to better understand the influence of sex in musculoskeletal medicine.

Probucol prevents blood-brain barrier dysfunction and cognitive decline in mice maintained on pro-diabetic diet.

An emerging body of evidence consistently suggests that compromised blood-brain barrier integrity may be causally associated with cognitive decline induced by type-2 diabetes. Our previous studies demonstrated that selected anti-inflammatory/anti-oxidative agents can preserve the integrity of blood-brain barrier and prevent neuroinflammation in mouse models of dysfunctional blood-brain barrier. Therefore, we have tested whether the previously proven blood-brain barrier protective agent, probucol, can prevent blood-brain barrier breakdown and cognitive decline in a dietary-induced murine model of diabetic insulin resistance. After 6-month chronic ingestion of a diet high in fat and fructose, the mice became insulin resistant. The high-fat and high-fructose-fed mice showed significant cognitive decline assessed by Morris water maze, concomitant with significant elevations in cortical and hippocampal glial acidic fibrillary protein and Fluoro Jade-C staining, indicating heightened neuroinflammation and neurodegeneration, respectively. The integrity of blood-brain barrier in high-fat and high-fructose-fed mice was substantially compromised, and this showed a significant association with heightened neurodegeneration. Co-provision of probucol with high-fat and high-fructose diet completely prevented the cognitive decline and blood-brain barrier dysfunction. Similarly, metformin was able to restore the cognitive function in high-fat and high-fructose-fed mice, while its blood-brain barrier protective effects were modest. These data suggest that probucol may prevent cognitive decline induced by insulin resistance by preserving the integrity of blood-brain barrier, whereas metformin's neuroprotective effects may be mediated through a separate pathway.

Sodium alginate capsulation increased brain delivery of probucol and suppressed neuroinflammation and neurodegeneration.

AIM: To enhance the bioavailability and brain uptake of probucol and examine whether it attenuates neuroinflammation and neurodegeneration by utilizing a sodium alginate nanoencapsulation technique. MATERIALS & METHODS: Wild-type mice were given either low-fat standard chow, high-fat (HF) diet to induce neuroinflammation and neurodegeneration, HF diet supplemented with nanocapsuled probucol at a concentration of 0.1% (w/w), HF diet supplemented with noncapsulated probucol at the same concentration of 0.1%, or HF diet supplemented with noncapsulated probucol at higher concentration (1%) for 24 weeks. RESULTS & CONCLUSION: The nanoencapsulation increased the plasma and brain concentration of probucol significantly compared with the mice that was given the same dosage of probucol without capsulation, and significantly suppressed the neuroinflammation and neurodegeneration.

Patient Satisfaction With Nonopioid Pain Management Following Knee Arthroscopic Partial Meniscectomy and/or Chondroplasty.

The purpose of this study was to determine the efficacy of nonopioid pain management following arthroscopic partial meniscectomy and/or chondroplasty and to assess patients' attitudes regarding their need for opioid pain medication following these procedures. Patients who underwent a knee arthroscopy procedure for either partial meniscectomy and/or chondroplasty from July 2016 to January 2017 by a single surgeon at a single institution were included. Medical records were reviewed, and demographics were recorded. Two weeks postoperatively, patients self-reported opioid and nonopioid medication use. Patients were also questioned regarding their perceived need for opioid medication, whether they felt their pain was adequately controlled, and how their pain compared with their preoperative expectations. Thirty-four patients (17 male, 17 female), with a mean age at the time of surgery of 47.79 years (range, 19-68 years), were included. Eighty-two percent (n=28) of the patients reported using nonopioid analgesics for pain control, whereas 18% (n=6) reported using opioids. Of those not using opioids, 96.4% (n=27) reported not feeling the need for opioid medications. Three of 6 patients requiring opioids were unable to take nonsteroidal anti-inflammatory drugs. All 6 patients who took opioids felt that they needed them for adequate pain control. This study provides initial encouragement that it is largely possible to remove opioids from the postoperative pain regimen of knee arthroscopy patients and maintain adequate pain control and patient satisfaction. [Orthopedics. 2018; 41(4):209-214.].

Patient-Reported Outcomes Following Fasciotomy for Chronic Exertional Compartment Syndrome.

BACKGROUND: Lower extremity chronic exertional compartment syndrome (CECS) can negatively affect exercise and activity and may require operative intervention to release the fascia. Few studies have evaluated or compared patient-reported outcomes for bilateral versus single-leg staged fasciotomy and number of compartments released. METHODS: A total of 27 eligible patients who underwent a fasciotomy procedure for CECS at a single institution were identified. A retrospective review of the medical record was performed, and individuals were contacted by phone to collect patient-reported outcomes, including ability to return to desired exercise level, postoperative expectation assessment, European Quality of Life-Five Dimensions, and the Foot and Ankle Ability Measure sports subscale. RESULTS: A total of 21 patients were available for follow-up (average follow-up 36.9 months). The average single numeric assessment evaluation of lower-extremity function in sport was 87.5% in those who underwent a simultaneous bilateral fasciotomy (n = 10), 94% in those who had a staged unilateral fasciotomy (n = 5), and 74% in those who underwent an isolated single-leg fasciotomy. In all, 91% (n = 10) of patients who had all 4 compartments released intra-operatively were able to return to their desired exercise level versus 66.7% (n = 6) of those who did not have all 4 compartments released. CONCLUSION: The patient-reported outcomes of a staged unilateral fasciotomy and simultaneous bilateral fasciotomy for CECS are similar. Those who did not have all 4 compartments released reported worse outcomes. Further research should be conducted on the short-term outcomes and cost-effectiveness of a bilateral versus staged fasciotomy procedure. LEVELS OF EVIDENCE: Level IV: Case series.