Surveillance genome sequencing reveals multiple SARS-CoV-2 variants circulating in central Texas, USA, with a predominance of delta variant and review of vaccine breakthrough cases.

As surges in the COVID-19 pandemic have continued worldwide, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has mutated, spawning several new variants, and impacting, to various degrees, transmission, disease severity, diagnostics, therapeutics, and natural and vaccine-induced immunity. Baylor Scott & White Health has implemented, along with laboratory diagnosis, SARS-CoV-2 sequencing to identify variants in its geographical service area. We analyzed virus sequencing results of specimens collected across Central Texas and found dramatic changes in variant distribution in the first half of 2021. The alpha variant (B 1.1.7) became predominant at week 13 and continued dominance until week 25. A growth rate of 1.20 (R2 = 0.92) for the first 15 weeks was noted and this growth gradually declined to -0.55 (R2 = 0.99) for the final 13 weeks. Currently, B.1.1.7 is being displaced with B.1.617.2 at a 0.58 growth rate (R2 = 0.97). We also investigated vaccine breakthrough cases (VBCs) within our healthcare system and present clinical data on 28 symptomatic patients.

Improved Rates of Same-day Discharge in Patients Undergoing Surgery for Endometrial Cancer Following the COVID-19 Pandemic.

STUDY OBJECTIVE: To determine the effect of the coronavirus disease 2019 (COVID-19) pandemic on the rate of same-day discharge (SDD) after minimally invasive surgery for endometrial cancer. DESIGN: Retrospective cohort. SETTING: Teaching hospital. PATIENTS: A total of 166 patients underwent a minimally invasive surgery procedure for the indication of endometrial cancer at a large academic institution from September 1, 2019, to October 1, 2020-80 patients before the implementation of the COVID-19 restrictions and 86 patients after. INTERVENTIONS: COVID-19 pandemic with visitor restrictions and hospital policy changes placed on March 17, 2020. MEASUREMENTS AND MAIN RESULTS: SDD rate was increased by 18% after the start of the COVID-19 pandemic (40% vs 58%, p = .02). There were no differences between the 2 groups with regard to operative time (p = .07), estimated blood loss (p = .21), uterine weight (p = .12), age (p = .06), body mass index (p = .42), or surgery start time (p = .15). In a multivariable logistic regression model, subjects in the COVID-19 group had 3.08 times (95% confidence interval, 1.40-6.74; p = .01) higher odds of SDD than those in the pre-COVID-19 group. There was no difference in 30-day readmission rates (7.5% vs 5.8%, p = .66). CONCLUSION: There was a significant increase in the SDD of patients with endometrial cancer since the start of the COVID-19 pandemic. The pandemic has strained hospital resources and motivated patients and physicians to avoid hospitalization. This shows that with proper motivation, an increase in SDD rates is possible without an increase in complications or rehospitalization.

Radiological Prevalence of Popliteal Artery Entrapment in Individuals With Anterior Leg Compartment Chronic Exertional Compartment Syndrome.

OBJECTIVE: Determine the radiological prevalence of popliteal artery entrapment (PAE) in subjects with anterior leg compartment chronic exertional compartment syndrome (CECS). DESIGN: Retrospective review. SETTING: Tertiary care center. PATIENTS: Of 71 patients diagnosed with anterior leg compartment CECS using an in-scanner exercise-based magnetic resonance imaging (MRI), 64 also completed Fast Imaging Employing Steady-State Acquisition (FIESTA) imaging. INTERVENTIONS: Electronic health records of patients diagnosed with anterior leg compartment CECS using an in-scanner exercise-based MRI between 2009 and 2018 were reviewed. MAIN OUTCOME MEASURES: Demographics, symptom laterality, and results of vascular work-up. RESULTS: Magnetic resonance imaging was positive for PAE in 33 of 64 (51.6%). Vascular evaluation was performed in 30 of 33 (90.9%). Of these 30, ankle-brachial indices (ABIs) with PAE maneuvers were performed in 29 (96.7%) and positive in 25 (86.2%). Pre-exercise and post-exercise ABIs were performed in 29 (96.7%) and abnormal in 20 (69.0%). Thirteen arterial duplex ultrasounds were performed; 10 were consistent with PAE (76.9%). An MR angiogram was performed in 8 (26.7%) and consistent with PAE in all. One computed tomography angiogram (3.3%) was completed and was normal. Overall, one or more tests were positive for PAE in all 30 with vascular evaluation. CONCLUSIONS: The radiological prevalence of PAE and anterior leg CECS was 51.6%. All subjects with vascular studies (90.9%) had one or more tests confirming radiological PAE. These findings suggest that the coexistence of PAE and CECS is common, and the PAE protocol used has a high correlation with vascular studies.

Does proximal versus distal injury location of the medial ulnar collateral ligament of the elbow differentially impact elbow stability? An ultrasound-guided and robot-assisted biomechanical study.

BACKGROUND: The location (proximal vs. distal) of elbow medial ulnar collateral ligament (MUCL) tears impacts clinical outcomes of nonoperative treatment. The purposes of our study were to (1) determine whether selective releases of the MUCL could be performed under ultrasound (US) guidance without disrupting overlying soft tissues, (2) assess the difference in medial elbow stability for proximal and distal releases of the MUCL using stress US and a robotic testing device, and (3) elucidate the flexion angle that resulted in the greatest amount of medial elbow laxity after MUCL injury. METHODS: Sixteen paired, fresh-frozen elbow specimens were used. Valgus laxity was evaluated with both US and robotic-assisted measurements before and after selective MUCL releases. A percutaneous US-guided technique was used to perform proximal MUCL releases in 8 elbows and to perform distal MUCL releases in their matched pairs. The robot was used to determine the elbow flexion angle at which the maximum valgus displacement occurred for both proximally and distally released specimens. Open dissection was then performed to assess the accuracy of the percutaneous releases. RESULTS: Percutaneous US-guided releases were successfully performed in 15 of 16 specimens. The proximal release resulted in greater valgus angle displacement (11° ± 2°) than the distal release (8° ± 2°) between flexion angles of 30° and 70° (P < .0001 at 30°, P < .0001 at 40°, P = .001 at 50°, P = .005 at 60°, and P = .020 at 70°). Valgus displacement between release locations did not reach the level of statistical significance between 80° and 120° (P = .051 at 80°, P = .131 at 90°, P = .245 at 100°, P = .400 at 110°, and P = .532 at 120°). When we compared the values for the mean increase in US delta gap (stressed - supported state) from before to after MUCL release, the proximally released elbows had larger increases than the distally released elbows (5.0 mm proximal vs. 3.7 mm distal, P = .032). After MUCL release, maximum mean valgus displacement occurred at 49° of flexion. CONCLUSIONS: US-guided selective releases of the MUCL can be performed reliably without violating the overlying musculature. Valgus instability is not of greater magnitude for distal releases when compared with proximal releases. This findings suggests there must be alternative factors to explain the difference in clinical prognosis between distal and proximal tears. The observed flexion angle for maximum valgus laxity could have important implications for elbow positioning during US or fluoroscopic stress examination, as well as surgical repair or reconstruction of the MUCL.

Anti-neuroinflammatory effects of a food-grade phenolic-enriched maple syrup extract in a mouse model of Alzheimer's disease.

Objectives: Alzheimer's disease (AD) is a growing global health crisis exacerbated by increasing life span and an aging demographic. Convergent lines of evidence, including genome-wide association studies, strongly implicate neuroinflammation in the pathogenesis of AD. Several dietary agents, including phenolic-rich foods, show promise for the prevention and/or management of AD, which in large part, has been attributed to their anti-inflammatory effects. We previously reported that a food-grade phenolic-enriched maple syrup extract (MSX) inhibited neuroinflammation in vitro but whether these effects are translatable in vivo remain unknown. Herein, we assessed MSX's ability to attenuate early neuroinflammation in a transgenic mouse model of AD.Methods: The effects of MSX on AD-related neuroinflammation was evaluated by orally administering MSX (100 and 200 mg/kg/day for 30 days) to the 3xTg-AD mouse model of AD. The expression of inflammatory markers in mouse brains were analyzed with LC-MS/MS with SWATH acquisition.Results: 3xTg-AD mice dosed orally with MSX have decreased expression of several inflammatory proteins, including, most notably, the AD risk-associated protein 'triggering receptor expressed on myeloid cells-2' (TREM2), and stimulator of interferon genes TMEM173, and suppressor of cytokine signaling-6 (SOCS6). However, this decrease in inflammation did not coincide with a decrease in pathogenic amyloid generation or lipid peroxidation.Discussion: These data demonstrate that oral administration of this maple syrup derived natural product reduces key neuroinflammatory indices of AD in the 3xTg-AD model of AD. Therefore, further studies to investigate MSX's potential as a dietary intervention strategy for AD prevention and/or management are warranted.

Inhibiting thrombin improves motor function and decreases oxidative stress in the LRRK2 transgenic Drosophila melanogaster model of Parkinson's disease.

Parkinson's disease (PD) is a complex neurodegenerative disease characterized by the presence of tremors, loss of dopaminergic neurons and accumulation of α-synuclein. While there is no single direct cause of PD, genetic mutations, exposure to pesticides, diet and traumatic brain injury have been identified as risk factors. Increasing evidence suggests that oxidative stress and neuroinflammation contribute to the pathogenesis of neuronal injury in neurodegenerative diseases such as PD and Alzheimer's disease (AD). We have previously documented that the multifunctional inflammatory mediator thrombin contributes to oxidative stress and neuroinflammation in AD. Here, for the first time, we explore the role of thrombin in a transgenic PD model, the LRRK2 mutant Drosophila melanogaster. Transgenic flies were treated with the direct thrombin inhibitor dabigatran for 7 days and locomotor activity and indices of oxidative stress evaluated. Our data show that dabigatran treatment significantly (p < 0.05) improved climbing activity, a measurement of locomotor ability, in male but had no effect on locomotor performance in female flies. Dabigatran treatment had no effect on tyrosine hydroxylase levels. Analysis of oxidative stress in male flies showed that dabigatran was able to significantly (p < 0.01) lower reactive oxygen species levels. Furthermore, Western blot analysis showed that the pro-oxidant proteins iNOS and NOX4 are elevated in LRRK2 male flies compared to wildtype and that treatment with dabigatran reduced expression of these proteins. Our results indicate that dabigatran treatment could improve motor function in PD by reducing oxidative stress. These data suggest that targeting thrombin may improve oxidative stress related pathologies in PD.

Equol, a Blood-Brain Barrier Permeable Gut Microbial Metabolite of Dietary Isoflavone Daidzein, Exhibits Neuroprotective Effects against Neurotoxins Induced Toxicity in Human Neuroblastoma SH-SY5Y Cells and Caenorhabditis elegans.

Emerging data support that plant food based isoflavones have ameliorating effects on a variety of neurodegenerative diseases including Parkinson's disease (PD). Our previous investigation revealed that dietary isoflavones including genistein (GEN), daidzein (DAI), and equol (EQL; a gut microbial metabolite of DAI) showed promising blood-brain barrier permeability and anti-neuroinflammatory activity in murine microglial BV2 cells. However, the neuroprotective effects of EQL against neurotoxins induced toxicity in PD related models remains unclear. Herein, EQL, along with GEN and DAI, were evaluated for their cytoprotective effect in a non-contact co-culture model with LPS-BV2-conditioned media and human neuroblastoma SH-SY5Y cells. In addition, their neuroprotective effects against PD related neurotoxins including 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+) induced cytotoxicity were evaluated in SH-SY5Y cells. Furthermore, EQL was evaluated for its neuroprotective effects against MPP+ induced neurotoxicity using in vivo PD model including Caenorhabditis elegans lifespan assay. DAI (10 µM) and EQL (10 and 20 µM) showed cytoprotective effects by decreasing LPS-BV2-conditioned media induced cytotoxicity in SH-SY5Y cells by 29.2, 32.4 and 27.2%, respectively. EQL (10 and 20 µM) also showed neuroprotective effects by decreasing 6-OHDA and MPP+ induced cytotoxicity in SH-SY5Y cells by 30.6-34.5 and 17.9-18.9%, respectively. Additionally, data from the in vivo assay supported EQL's neuroprotective effect as it increases survival of C. elegans exposed to MPP+ from 72 to 108 h. Our findings support a growing body of evidence of the neuroprotective effects of dietary isoflavones and further studies are warranted to elucidate their mechanisms of action.

Eating disorder recovery in men: A pilot study.

OBJECTIVE: This pilot study examined the validity of a comprehensive definition of recovery (physical, behavioral, and cognitive recovery indices) for the first time in men. METHOD: Men with an eating disorder history were recruited from former patients at eating disorder centers, university campuses, and fitness centers/gyms. At baseline and a 12-month follow-up, data were collected via online surveys, diagnostic interviews, and measured weight and height from men with an eating disorder history (n = 36) and men with no eating disorder history (n = 27). RESULTS: Of the men with an eating disorder history, 15 met criteria for an eating disorder, 7 met criteria for partial recovery, and 5 for full recovery. Men who met criteria for full recovery did not differ significantly from men with no eating disorder history and had significantly lower levels of broad eating pathology, thinness and restricting expectancies, body shame, difficulties in stopping thoughts about body, food, or exercise, and male body attitudes related to muscularity and body fat than men with an eating disorder. Men meeting criteria for full recovery had higher levels of body acceptance and intuitive eating than men who met criteria for partial recovery or an eating disorder. In terms of predictive validity, of those fully recovered at baseline, 60% also met full recovery criteria at follow-up. DISCUSSION: Preliminary findings suggest that a comprehensive definition of recovery applies to men. Although research with larger samples is needed, this research provides some optimism for the potential of recovery in men.

Evaluation of Polyphenol Anthocyanin-Enriched Extracts of Blackberry, Black Raspberry, Blueberry, Cranberry, Red Raspberry, and Strawberry for Free Radical Scavenging, Reactive Carbonyl Species Trapping, Anti-Glycation, Anti-ß-Amyloid Aggregation, and Microglial Neuroprotective Effects.

Glycation is associated with several neurodegenerative disorders, including Alzheimer's disease (AD), where it potentiates the aggregation and toxicity of proteins such as ß-amyloid (Aß). Published studies support the anti-glycation and neuroprotective effects of several polyphenol-rich fruits, including berries, which are rich in anthocyanins. Herein, blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts were evaluated for: (1) total phenolic and anthocyanins contents, (2) free radical (DPPH) scavenging and reactive carbonyl species (methylglyoxal; MGO) trapping, (3) anti-glycation (using BSA-fructose and BSA-MGO models), (4) anti-Aß aggregation (using thermal- and MGO-induced fibrillation models), and, (5) murine microglia (BV-2) neuroprotective properties. Berry crude extracts (CE) were fractionated to yield anthocyanins-free (ACF) and anthocyanins-enriched (ACE) extracts. The berry ACEs (at 100 µg/mL) showed superior free radical scavenging, reactive carbonyl species trapping, and anti-glycation effects compared to their respective ACFs. The berry ACEs (at 100 µg/mL) inhibited both thermal- and MGO-induced Aß fibrillation. In addition, the berry ACEs (at 20 µg/mL) reduced H2O2-induced reactive oxygen species production, and lipopolysaccharide-induced nitric oxide species in BV-2 microglia as well as decreased H2O2-induced cytotoxicity and caspase-3/7 activity in BV-2 microglia. The free radical scavenging, reactive carbonyl trapping, anti-glycation, anti-Aß fibrillation, and microglial neuroprotective effects of these berry extracts warrant further in vivo studies to evaluate their potential neuroprotective effects against AD.

The Role of Ultrasound in the Diagnosis and Treatment of Meniscal Injuries.

PURPOSE OF REVIEW: This review evaluates the current understanding of the role of ultrasound in the diagnosis and treatment of meniscal disorders. RECENT FINDINGS: Ultrasound (US) demonstrates similar sensitivity and specificity when compared to magnetic resonance imaging in the evaluation of meniscal injuries when compared to arthroscopy. Meniscal extrusion (ME) under US can be a reliable metric to evaluate for meniscal root tears in knees with and without osteoarthritis (OA). Sonographic ME is associated with development of OA in knees without OA. US following allograft meniscal transplant may be useful in predicting graft failure. US findings can be used to screen for discoid menisci and may demonstrate snapping of a type 3 discoid lateral meniscus. Shear wave elastography for meniscal injuries is in its infancy; however, increased meniscal stiffness may be seen with meniscal degeneration. Perimeniscal corticosteroid injections may provide short term relief from meniscal symptoms, and intrameniscal platelet-rich plasma injections appear to be safe and effective up to three years. Ultrasound-assisted meniscal surgery may increase the safety of all inside repairs near the lateral root and may assist in assessing meniscal reduction following root repair. Diagnostic US can demonstrate with high accuracy a variety of meniscal pathologies and can be considered a screening tool. Newer technologies such as shear wave elastography may allow us to evaluate characteristics of meniscal tissue that is not possible on conventional imaging. US-guided (USG) treatment of meniscal injuries is possible and may be preferable to surgery for the initial treatment of degenerative meniscal lesions. USG or US-assisted meniscal surgery is in its infancy.

Celosiadines A and B, unusual guanidine alkaloids from Iresine diffusa.

Two unusual di-isopentenyl guanidine alkaloids, named celosiadines A (1) and B (2), were isolated from Iresine diffusa aerial parts. The structures of the compounds were elucidated from extensive spectroscopic analyses including HRMS, NMR and ECD. Celosiadines A and B showed favorable binding affinity to the androgen receptor (AR) in silico and were cytotoxic towards AR-sensitive (LNCaP) but not AR-insensitive (PC3) human prostate cancer cells in vitro.

Prevalence and mechanisms of somatic deletions in single human neurons during normal aging and in DNA repair disorders.

Replication errors and various genotoxins cause DNA double-strand breaks (DSBs) where error-prone repair creates genomic mutations, most frequently focal deletions, and defective repair may lead to neurodegeneration. Despite its pathophysiological importance, the extent to which faulty DSB repair alters the genome, and the mechanisms by which mutations arise, have not been systematically examined reflecting ineffective methods. Here, we develop PhaseDel, a computational method to detect focal deletions and characterize underlying mechanisms in single-cell whole genome sequences (scWGS). We analyzed high-coverage scWGS of 107 single neurons from 18 neurotypical individuals of various ages, and found that somatic deletions increased with age and in highly expressed genes in human brain. Our analysis of 50 single neurons from DNA repair-deficient diseases with progressive neurodegeneration (Cockayne syndrome, Xeroderma pigmentosum, and Ataxia telangiectasia) reveals elevated somatic deletions compared to age-matched controls. Distinctive mechanistic signatures and transcriptional associations suggest roles for somatic deletions in neurodegeneration.

Outcomes of Acute Inpatient Rehabilitation After Ventricular Assist Device Placement.

OBJECTIVE: The aim of the study was to compare outcomes of inpatient rehabilitation after ventricular assist device placement with outcomes for other cardiac diagnoses. DESIGN: This was a retrospective review of the electronic health records of 265 patients admitted to inpatient rehabilitation: 166 patients were admitted after ventricular assist device placement and 99 were admitted for other cardiac disease. Data collected included functional independence measure score on admission and discharge, dates of admission and discharge, and disposition. RESULTS: Patients admitted after ventricular assist device placement had a mean functional independence measure gain of 25.7 and length of stay of 8.7 days. Patients admitted for other cardiac diagnoses had a mean functional independence measure gain of 25.9 and length of stay of 9.4 days. These differences were not statistically significant. Change in functional independence measure from admission to discharge was statistically significant within each group (P < 0.001). Most patients were discharged home, and the proportions who returned to acute care or home were not different between groups. CONCLUSIONS: Both the ventricular assist device and nonventricular assist device groups had significant and equivalent improvements in functional outcomes after inpatient rehabilitation. This study found that ventricular assist device patients benefit from inpatient rehabilitation with similar disposition rates as patients with other cardiac diagnoses. Inpatient rehabilitation is the appropriate setting for this group. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Describe the role of rehabilitation in the care of individuals after ventricular assist device (VAD) placement; (2) Compare the outcomes of inpatient rehabilitation for individuals after VAD placement to those admitted for other cardiac reasons; and (3) Recognize potential complications that may occur during the course of a VAD patient's inpatient rehabilitation stay. LEVEL: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Short-term treatment with dabigatran alters protein expression patterns in a late-stage tau-based Alzheimer's disease mouse model.

Proteins that regulate the coagulation cascade, including thrombin, are elevated in the brains of Alzheimer's disease (AD) patients. While studies using amyloid-based AD transgenic mouse models have implicated thrombin as a protein of interest, the role of thrombin in tau-based animal models has not been explored. The current study aims to determine how inhibiting thrombin could alter oxidative stress, inflammation, and AD-related proteins in a tau-based mouse model, the Tg4510. Aged Tg4510 mice were treated with the direct thrombin inhibitor dabigatran or vehicle for 7 days, brains collected, and western blot and data-independent proteomics using mass spectrometry with SWATH-MS acquisition performed to evaluate proteins related to oxidative stress, intracellular signaling, inflammation, and AD pathology. Dabigatran reduced iNOS, NOX4, and phosphorylation of tau (S396, S416). Additionally, dabigatran treatment increased expression of several signaling proteins related to cell survival and synaptic function. Increasing evidence supports a chronic procoagulant state in AD, highlighting a possible pathogenic role for thrombin. Our data demonstrate that inhibiting thrombin produces alterations in the expression of proteins involved in oxidative stress, inflammation, and AD-related pathology, suggesting that thrombin-mediated signaling affects multiple AD-related pathways providing a potential future therapeutic target.

Unnarmicin D, an Anti-inflammatory Cyanobacterial Metabolite with δ and µ Opioid Binding Activity Discovered via a Pipeline Approach Designed to Target Neurotherapeutics.

To combat the bottlenecks in drug discovery and development, a pipeline to identify neuropharmacological candidates using in silico, in vitro, and receptor specific assays was devised. The focus of this pipeline was to identify metabolites with the ability to reduce neuroinflammation, due to the implications that chronic neuroinflammation has in chronic pain and neurodegenerative diseases. A library of pure compounds isolated from the cyanobacterium Trichodesmium thiebautii was evaluated using this method. In silico analysis of drug likelihood and in vitro permeability analysis using the parallel artificial membrane permeability assay (PAMPA) highlighted multiple metabolites of interest from the library. Murine BV-2 microglia were used in conjunction with the Griess assay to determine if metabolites could reduce lipopolysaccharide induced neuroinflammation followed by analysis of pro-inflammatory cytokine concentrations in the supernatant of the treated cell cultures. The nontoxic metabolite unnarmicin D was further evaluated due to its moderate permeability in the PAMPA assay, promising ADME data, modulation of all cytokines tested, and prediction as an opioid receptor ligand. Molecular modeling of unnarmicin D to the µ and δ opioid receptors showed strong theoretical binding potential to the µ opioid receptor. In vitro binding assays validated this pipeline showing low micromolar binding affinity for the µ opioid receptor launching the potential for further analysis of unnarmicin D derivatives for the treatment of pain and neuroinflammation related diseases.

The Telemedicine Musculoskeletal Examination.

Telemedicine uses modern telecommunication technology to exchange medical information and provide clinical care to individuals at a distance. Initially intended to improve health care for patients in remote settings, telemedicine now has a broad clinical scope with the general purpose of providing convenient, safe, and time- and cost-efficient care. The coronavirus disease 2019 pandemic has created marked nationwide changes in health care access and delivery. Elective appointments and procedures have been canceled or delayed, and multiple states still have some degree of shelter-in-place orders. Many institutions are now relying more heavily on telehealth services to continue to provide medical care to individuals while also preserving the safety of health care professionals and patients. Telemedicine can also help reduce the surge in health care needs and visits as restrictions are lifted. In recent weeks, there has been a significant amount of information and advice on how to best approach telemedicine visits. Given the frequent presentation of individuals with musculoskeletal complaints to the medical practitioner, it is important to have a framework for the virtual musculoskeletal physical examination. This will be of importance as telemedicine continues to evolve, even after coronavirus disease 2019 restrictions are lifted. This article will provide the medical practitioner performing a virtual musculoskeletal examination with a specific set of guidelines, both written and visual, to enhance the information obtained when evaluating the shoulder, hip, knee, ankle, and cervical and lumbar spine. In addition to photographs, accompanying videos are included to facilitate and demonstrate specific physical examination techniques that the patient can self-perform.

Polyphenol Microbial Metabolites Exhibit Gut and Blood⁻Brain Barrier Permeability and Protect Murine Microglia against LPS-Induced Inflammation.

Increasing evidence supports the beneficial effects of polyphenol-rich diets, including the traditional Mediterranean diet, for the management of cardiovascular disease, obesity and neurodegenerative diseases. However, a common concern when discussing the protective effects of polyphenol-rich diets against diseases is whether these compounds are present in systemic circulation in their intact/parent forms in order to exert their beneficial effects in vivo. Here, we explore two common classes of dietary polyphenols, namely isoflavones and lignans, and their gut microbial-derived metabolites for gut and blood-brain barrier predicted permeability, as well as protection against neuroinflammatory stimuli in murine BV-2 microglia. Polyphenol microbial metabolites (PMMs) generally showed greater permeability through artificial gut and blood-brain barriers compared to their parent compounds. The parent polyphenols and their corresponding PMMs were evaluated for protective effects against lipopolysaccharide-induced inflammation in BV-2 microglia. The lignan-derived PMMs, equol and enterolactone, exhibited protective effects against nitric oxide production, as well as against pro-inflammatory cytokines (IL-6 and TNF-α) in BV-2 microglia. Therefore, PMMs may contribute, in large part, to the beneficial effects attributed to polyphenol-rich diets, further supporting the important role of gut microbiota in human health and disease prevention.

Levodopa-Reduced Mucuna pruriens Seed Extract Shows Neuroprotective Effects against Parkinson's Disease in Murine Microglia and Human Neuroblastoma Cells, Caenorhabditis elegans, and Drosophila melanogaster.

Mucuna pruriens (Mucuna) has been prescribed in Ayurveda for various brain ailments including 'kampavata' (tremors) or Parkinson's disease (PD). While Mucuna is a well-known natural source of levodopa (L-dopa), published studies suggest that other bioactive compounds may also be responsible for its anti-PD effects. To investigate this hypothesis, an L-dopa reduced (<0.1%) M. pruriens seeds extract (MPE) was prepared and evaluated for its anti-PD effects in cellular (murine BV-2 microglia and human SH-SY5Y neuroblastoma cells), Caenorhabditis elegans, and Drosophila melanogaster models. In BV-2 cells, MPE (12.5⁻50 µg/mL) reduced hydrogen peroxide-induced cytotoxicity (15.7-18.6%), decreased reactive oxygen species production (29.1-61.6%), and lowered lipopolysaccharide (LPS)-induced nitric oxide species release by 8.9⁻60%. MPE (12.5-50 µg/mL) mitigated SH-SY5Y cell apoptosis by 6.9-40.0% in a non-contact co-culture assay with cell-free supernatants from LPS-treated BV-2 cells. MPE (12.5-50 µg/mL) reduced 6-hydroxydopamine (6-OHDA)-induced cell death of SH-SY5Y cells by 11.85⁻38.5%. Furthermore, MPE (12.5-50 µg/mL) increased median (25%) and maximum survival (47.8%) of C. elegans exposed to the dopaminergic neurotoxin, methyl-4-phenylpyridinium. MPE (40 µg/mL) ameliorated dopaminergic neurotoxin (6-OHDA and rotenone) induced precipitation of innate negative geotaxis behavior of D. melanogaster by 35.3 and 32.8%, respectively. Therefore, MPE contains bioactive compounds, beyond L-dopa, which may impart neuroprotective effects against PD.