Outcomes of Arterial Bypass for Posterior Circulation Atherosclerosis: A Case Series.

BACKGROUND: Extracranial-intracranial bypass is an effective treatment option for moyamoya disease and in well-selected cases of anterior circulation intracranial atherosclerotic disease; however, the effectiveness of bypass is less evident in posterior circulation atherosclerosis. Updated surgical techniques and clinical guidelines necessitate modern appraisal of arterial bypass for symptomatic patients with posterior circulation atherosclerotic disease who are refractory to medical management. OBJECTIVE: To evaluate the complications, graft patency, and postoperative outcomes of arterial bypass for posterior circulation intracranial atherosclerotic disease. METHODS: Perioperative records of consecutive bypass patients were retrospectively evaluated to determine the clinical course and surgical outcomes. RESULTS: Arterial bypass was performed in 8 cases with a median age of 62 years. All 8 patients underwent direct bypass with an autologous occipital artery donor vessel. Recipient vessel selection varied on a case-by-case basis, with the superior cerebellar artery used in 4 cases, the posterior inferior cerebellar artery in 3 cases, and the anterior inferior cerebellar artery in 1 case. There were no significant intraoperative or postoperative complications. Postoperatively, all 8 patients displayed clinical improvement of their preoperative symptoms, with a significant decrease of 2.5 points on the modified Rankin Scale (P < .001). Postoperative imaging confirmed full graft patency in 7 patients and partial patency in 1 patient. CONCLUSION: Excellent postoperative outcomes and no major complications after posterior circulation arterial bypass for intracranial atherosclerotic disease highlight the utility of this intervention for the treatment of medically refractory or symptomatic posterior circulation intracranial atherosclerotic disease. Larger studies may be valuable to validate these findings.

Improved Outcomes with Concurrent Instrumentation and Fusion of the Sacroiliac Joint in Patients with Long Lumbosacral Constructs.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: Spinal fusion, specifically constructs connected to pelvic bones, has been consistently reported as a predisposing factor to sacroiliac joint (SIJ) pain. The aim of this study is to compare SIJ outcomes in patients with constructs to the pelvis following instrumentation vs instrumentation plus fusion of the SIJ. METHODS: Data of study subjects was extracted from a prospectively maintained database as well as retrospectively collected from records at a tertiary academic medical center in the United States between 2018 and 2020. RESULTS: A cohort of 103 patients was divided into 2 groups: 65 in Group 1 [S2AI screw without fusion device] and 38 in Group 2 [S2AI screw with fusion device]. None of the patients in Group 2 developed postoperative SIJ pain compared to 44.6% in Group 1. Sacroiliac joint fusion occurred in all Group 2 but none of Group 1 patients. The postoperative Visual Analogue Scale (VAS) for lower extremity (LE) pain (.8 vs .5; P = .03) and postoperative Oswestry Disability Index (ODI) (18.7 vs 14.2; P < .01) were significantly higher in Group 1. The rate of distal junctional break, failure, and/or kyphosis (DJBFK) and time to DJBFK were not significantly different between the two groups, and the rate of DJBFK did not change in the presence of multiple covariates. CONCLUSION: The SIJs carry the heavy load of long lumbosacral fusion constructs extending to the pelvis. Simultaneous SIJ instrumentation and fusion decreases the risk of disability, prevents the development of postoperative SIJ pain, and may also protect the S2AI screw from loosening and failure.

Transcarotid artery revascularization (TCAR) stenting or angioplasty for intracranial carotid artery stenosis: Case series and novel application.

BACKGROUND: Carotid artery stenting is associated with a higher rate of stroke compared to carotid endarterectomy (CEA). This is likely due to procedural emboli resulting from plaque disruption. The transcarotid artery revascularization (TCAR) method aims to reduce the stroke rate by flow-reversal. TCAR, which has yet to be utilized for intracranial atherosclerotic disease (ICAD), may be particularly valuable given the lack of surgical treatment options for intracranial arterial stenosis. OBJECTIVE: Presented here are five cases of angioplasty or stenting that demonstrate the feasibility of TCAR for intracranial Internal Carotid Artery (ICA) stenosis treatment. METHODS: Five cases were reviewed retrospectively and summarized using PROCESS and CARE guidelines. RESULTS: All patients who underwent intervention between the petrous and ophthalmic segment of the ICA had no new neurologic deficit nor detected embolic stroke. One patient experienced an asymptomatic 5 mm hemorrhage on postoperative routine Computed Tomography (CT) head imaging. CONCLUSIONS: This highlights a new method for treating intracranial ICA stenosis with a potentially reduced stroke risk. Given the historically higher stroke rates for cervical ICA stenting compared to carotid artery endarterectomy, this method may improve the previously higher stroke rates in endovascular carotid artery treatment, compared to CEA. Although this series is small, it illustrates a novel use for a rising technique that should be further evaluated in a larger study to validate its efficacy as a new treatment modality for surgically inaccessible intracranial disease.

Robotic Arm-Protected Microsurgical Pericallosal and Middle Cerebral Artery Aneurysm Clipping: A Technical Note and Case Series.

BACKGROUND: Managing intraoperative aneurysm rupture (IAR) during intracranial aneurysm clipping can be challenging given the excessive hemorrhage and limited field of view under the microscope for visualizing the proximal artery and safe temporary clipping. OBJECTIVE: To describe the first known use of robotic arm for safeguarding IAR in microsurgical aneurysm clipping. METHODS: A robotic arm was used to safeguard 3 microsurgical clipping cases (1 pericallosal and 2 middle cerebral artery) performed by a single surgeon. The device was installed onto the side rail of the operating table along with the clip applier attachment. After dissecting the cerebral artery segment proximal to the aneurysm, a temporary aneurysm clip was loaded and established at the appropriate segment before dissecting distally toward the aneurysm. RESULTS: Setup for the robotic arm and temporary clip was simple, quick, precise, and without any unforeseen accommodations needed in all 3 instances. The temporary clip acted as an emergency gate and could be deployed either manually or remotely through a controller. IAR occurred in case 1, and the robotic-assisted temporary clip deployment achieved immediate hemostasis without complications. This method bypassed the need for significant suctioning, packing, and further exploration for safe temporary clipping. Case 2 and 3 demonstrated the feasibility for middle cerebral artery protection and ease of intraoperative readjustment. CONCLUSION: This technical note highlights the feasibility and relative ease of using a robotic arm as a safeguard device, and it enables on-demand control of proximal blood flow and may enhance the safety of microsurgical aneurysm procedures.

Inflammatory gut as a pathologic and therapeutic target in Parkinson's disease.

Parkinson's disease (PD) remains a significant unmet clinical need. Gut dysbiosis stands as a PD pathologic source and therapeutic target. Here, we assessed the role of the gut-brain axis in PD pathology and treatment. Adult transgenic (Tg) α-synuclein-overexpressing mice served as subjects and were randomly assigned to either transplantation of vehicle or human umbilical cord blood-derived stem cells and plasma. Behavioral and immunohistochemical assays evaluated the functional outcomes following transplantation. Tg mice displayed typical motor and gut motility deficits, elevated α-synuclein levels, and dopaminergic depletion, accompanied by gut dysbiosis characterized by upregulation of microbiota and cytokines associated with inflammation in the gut and the brain. In contrast, transplanted Tg mice displayed amelioration of motor deficits, improved sparing of nigral dopaminergic neurons, and downregulation of α-synuclein and inflammatory-relevant microbiota and cytokines in both gut and brain. Parallel in vitro studies revealed that cultured dopaminergic SH-SY5Y cells exposed to homogenates of Tg mouse-derived dysbiotic gut exhibited significantly reduced cell viability and elevated inflammatory signals compared to wild-type mouse-derived gut homogenates. Moreover, treatment with human umbilical cord blood-derived stem cells and plasma improved cell viability and decreased inflammation in dysbiotic gut-exposed SH-SY5Y cells. Intravenous transplantation of human umbilical cord blood-derived stem/progenitor cells and plasma reduced inflammatory microbiota and cytokine, and dampened α-synuclein overload in the gut and the brain of adult α-synuclein-overexpressing Tg mice. Our findings advance the gut-brain axis as a key pathological origin, as well as a robust therapeutic target for PD.

Modern Appraisal of Patency and Complications in Cerebral Bypass Surgery: A Single Institution Experience.

BACKGROUND: Cerebral bypass is a valuable surgical technique in well-selected patient populations. Updated clinical guidelines and improved surgical techniques warrant a contemporary reevaluation of the complications and patency to inform clinical practice and enhance postoperative patient care. OBJECTIVE: To assess the complication rates and postoperative graft patency for the 3 most common indications for bypass surgery: moyamoya disease, intracranial atherosclerosis, and intracranial aneurysms. METHODS: Perioperative notes of 175 consecutive bypass patients at a single institution were retrospectively identified to evaluate the clinical course and complications of surgery. RESULTS: The rate of total postoperative complications between moyamoya disease (9 of 98, 9.2%), intracranial atherosclerotic disease (7 of 57, 12.3%), and intracranial aneurysm (4 of 20, 20%) was not statistically different (P = .33). Immediate postoperative bypass patency was significantly higher in moyamoya disease (90 of 96, 93.8%) and intracranial atherosclerotic disease (48 of 51, 94.1%) than in intracranial aneurysm (13 of 18, 72.2%; P = .02). Intravenous heparin administration during bypass suturing was negatively associated with immediate postoperative patency (87% heparin patency vs 99% no heparin patency; P = .02). Double-barrel bypass trended toward an increased risk of wound healing complications (2 of 13, 15.4%) compared with the single-barrel bypass technique (4 of 156, 2.6%; P = .07). CONCLUSION: Cerebral bypass surgery remains an excellent surgical treatment for moyamoya disease, intracranial atherosclerosis, and intracranial aneurysms. This study suggests bypass is safer in moyamoya disease and intracranial atherosclerosis. Additional studies to clarify the risk of single-barrel vs double-barrel bypass and intraoperative heparin-stratified complications may be beneficial.

RNA Binding Motif 5 Gene Deletion Modulates Cell Signaling in a Sex-Dependent Manner but Not Hippocampal Cell Death.

RNA-binding motif 5 (RBM5) is a pro-death tumor suppressor gene in cancer cells. It remains to be determined if it is neurotoxic in the brain or rather if it plays a fundamentally different role in the central nervous system (CNS). Brain-specific RBM5 knockout (KO) mice were given a controlled cortical impact (CCI) traumatic brain injury (TBI). Markers of acute cellular damage and repair were measured in hippocampal homogenates 48 h post-CCI. Hippocampal CA1/CA3 cell counts were assessed 7 days post-CCI to determine if early changes in injury markers were associated with histological outcome. No genotype-dependent differences were found in the levels of apoptotic markers (caspase 3, caspase 6, and caspase 9). However, KO females had a paradoxical increase in markers of pro-death calpain activation (145/150-spectrin and breakdown products [SBDP]) and in DNA repair/survival markers. (pH2A.x and pCREB). CCI-injured male KOs had a significant increase in phosphorylated calcium/calmodulin-dependent protein kinase II (pCaMKII). Despite sex/genotype-dependent differences in KOs in the levels of acute cell signaling targets involved in cell death pathways, 7 day hippocampal neuronal survival did not differ from that of wild types (WTs). Similarly, no differences in astrogliosis were observed. Finally, gene analysis revealed increased estrogen receptor α (ERα) levels in the KO hippocampus in females and may suggest a novel mechanism to explain sex-dimorphic effects on cell signaling. In summary, RBM5 inhibition did not affect hippocampal survival after a TBI in vivo but did modify targets involved in neural signal transduction/Ca2+ signaling pathways. Findings here support the view that RBM5 may serve a purpose in the CNS that is dissimilar from its traditional pro-death role in cancer.

Prevention of Neurological Deficit With Intraoperative Neuromonitoring During Anterior Lumbar Interbody Fusion.

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: While intraoperative neuromonitoring (IONM) has been increasingly used in spine surgery to have a real-time evaluation of the neurological injury, we aim here to assess its utility during anterior lumbar interbody fusion (ALIF) and its association with postoperative neurological deficit. SUMMARY OF BACKGROUND DATA: ALIF is a beneficial surgical approach for patients with degenerative disease of the lower lumbar spine who would benefit from increased lordosis and restoration of neuroforaminal height. One risk of ALIF is iatrogenic nerve root injury. IONM may be useful in preventing this injury. MATERIALS AND METHODS: We performed a retrospective cohort study of 111 consecutive patients who underwent ALIF at a tertiary care academic center by 6 spine surgeons. We aimed to describe the association between IONM, postoperative weakness, and factors that predispose our center to using IONM. RESULTS: The 111 patients had a median age of 62 years [interquartile range (IQR): 53-69 y]. Neuromonitoring was used in 67 patients (60.3%) and not used in 44 patients. Seven neuromonitoring patients had IONM changes during the surgery. Three of these patients' surgeries featured intraoperative adjustments to reduce iatrogenic neural injury. The IONM cohort underwent significantly more complex procedures [5 levels (IQR: 3-7) vs. 2 levels (IQR: 2-5), P=0.001]. There was no difference in rates of new or worsened postoperative weakness (IONM: 20.6%, non-IONM: 20.5%). CONCLUSIONS: We demonstrate evidence of the potential benefits of IONM for patients undergoing ALIF. Intraoperative changes in neuromonitoring signals resulted in surgical adjustments that likely prevented neurological deficits postoperatively. IONM was protective so that more complex surgeries did not have a higher rate of postoperative weakness.

Mesenchymal Stem Cell-Induced Anti-Neuroinflammation Against Traumatic Brain Injury.

Traumatic brain injury (TBI) is a pervasive and damaging form of acquired brain injury (ABI). Acute, subacute, and chronic cell death processes, as a result of TBI, contribute to the disease progression and exacerbate outcomes. Extended neuroinflammation can worsen secondary degradation of brain function and structure. Mesenchymal stem cell transplantation has surfaced as a viable approach as a TBI therapeutic due to its immunomodulatory and regenerative features. This article examines the role of inflammation and cell death in ABI as well as the effectiveness of bone marrow-derived mesenchymal stem/stromal cell (BM-MSC) transplants as a treatment for TBI. Furthermore, we analyze new studies featuring transplanted BM-MSCs as a neurorestorative and anti-inflammatory therapy for TBI patients. Although clinical trials support BM-MSC transplants as a viable TBI treatment due to their promising regenerative characteristics, further investigation is imperative to uncover innovative brain repair pathways associated with cell-based therapy as stand-alone or as combination treatments.

Stem Cells for Aging-Related Disorders.

This review captures recent advances in biological and translational research on stem cells. In particular, we discuss new discoveries and concepts regarding stem cell treatment of aging-related disorders. A myriad of stem cell sources exists, from hematopoietic to mesenchymal and neural cell lineages. We examine current applications of exogenous adult bone marrow-derived stem cells as an effective and safe transplantable cell source, as well as the use of electrical stimulation to promote endogenous neurogenesis for Parkinson's disease. We also explore the potential of transplanting exogenous umbilical cord blood cells and mobilizing host resident stem cells in vascular dementia and aging. In addition, we assess the ability of small molecules to recruit resident stem cells in Alzheimer's disease. Finally, we evaluate mechanisms of action recently implicated in stem cell therapy, such as the role of long non-coding RNAs, G-protein coupled receptor 5, and NeuroD1. Our goal is to provide a synopsis of recent milestones regarding the application of stem cells in aging.

Vascular tortuosity in endovascular mechanical thrombectomy.

Endovascular mechanical thrombectomy effectively removes occlusive thrombi from the arterial lumen; however, there is little literature supporting the relevance of vascular geometry on surgical outcomes. Critical vessel characteristics including the degree of angulation and tortuosity influence the ability to advance stent retriever devices toward the site of occlusion. Therefore, it is crucial to evaluate the impact of carotid artery catheter pathway accessibility on the thrombectomy outcomes in acute ischemic stroke (AIS) patients. Traditional imaging modalities generate incomplete pictures of the vascular tortuosity and are prone to clinical judgment errors. Recent three-dimensional computed tomography angiography image analysis techniques circumvent these limitations to calculate accurate tortuosity and angulation measurements. These novel images facilitate classifying common anatomical variant patients into groups that may be treated with specially designed catheter devices. Importantly, this image analysis method reveals significant angulation in the common carotid artery and extracranial internal carotid artery that correlates with delays in reaching the occlusion site. Increased age, which is associated with increased risk of stroke, also increases the incidence of severe tortuosity. The semi-automated measurements technique also demonstrate that full 360° arterial loops are present in nearly 3% of catheter pathways and that the overall degree of angulation differs bilaterally. In this review, we examine the utility of this novel image analysis procedure and evaluate the recent literature relevant to neuroendovascular thrombectomy in AIS patients. Three literature databases - PubMed, Embase, and Web of Science were queried for original articles investigating both preclinical and clinical thrombectomy applications.

Correlates Between Physical Activity and Sunburn Prevalence Among a Nationally Representative Sample of US High School Students, 2015-2017.

BACKGROUND: Physical activity is associated with greater odds of sunburn in adults, increasing harmful sun exposure and skin cancer risk. The authors sought to investigate parallel associations between sunburn and physical activity among US high school students. METHODS: The authors examined pooled cross-sectional data from the 2015 and 2017 Youth Risk Behavior Survey. A nationally representative sample of 21,894 US high school students who responded to the sunburn question was included. RESULTS: Prevalence of sunburn was 56.6% between 2015 and 2017. Sunburn prevalence was higher in physically active students (88.3%; 95% confidence interval [CI], 86.7%-90.0%; P < .0001) and student athletes (63.0%; 95% CI, 59.4%-66.7%; P < .0001). Among male students who were vigorously physically active (≥5 d) or on ≥3 teams, the odds of sunburn were 2.33 (95% CI, 1.81-3.00; P < .0001) and 2.52 (95% CI, 1.96-3.23; P < .0001), respectively. Among female students who were vigorously physically active (≥5 d) or on ≥3 teams, the odds of sunburn were 1.65 (95% CI, 1.36-2.02; P < .0001) and 2.92 (95% CI, 2.07-4.13; P < .0001), respectively. CONCLUSIONS: Many US high school students are affected by sunburn, and the odds of sunburn are elevated during physical activity and team sports participation. Efforts are needed to improve sun safety regulations, education, and resources for youth during school and physical activity.

Pituitary Adenylate Cyclase-Activating Polypeptide: A Potent Therapeutic Agent in Oxidative Stress.

Stroke is a life-threatening condition that is characterized by secondary cell death processes that occur after the initial disruption of blood flow to the brain. The inability of endogenous repair mechanisms to sufficiently support functional recovery in stroke patients and the inadequate treatment options available are cause for concern. The pathology behind oxidative stress in stroke is of particular interest due to its detrimental effects on the brain. The oxidative stress caused by ischemic stroke overwhelms the neutralization capacity of the body's endogenous antioxidant system, which leads to an overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and eventually results in cell death. The overproduction of ROS compromises the functional and structural integrity of brain tissue. Therefore, it is essential to investigate the mechanisms involved in oxidative stress to help obtain adequate treatment options for stroke. Here, we focus on the latest preclinical research that details the mechanisms behind secondary cell death processes that cause many central nervous system (CNS) disorders, as well as research that relates to how the neuroprotective molecular mechanisms of pituitary adenylate cyclase-activating polypeptides (PACAPs) could make these molecules an ideal candidate for the treatment of stroke.

Teflon versus Ivalon in Microvascular Decompression for Trigeminal Neuralgia: A 2-Center 10-Year Comparison.

BACKGROUND: Trigeminal neuralgia features jolts of pain along the distribution of the trigeminal nerve. If patients fail conservative management, microvascular decompression (MVD) is typically the next step in treatment. MVD consists of implanting a separating material, often Teflon, between the nerve and compressive lesions. A review found similar success and complication rates between Teflon and Ivalon, another commonly used material. The aim of this study was to analyze outcomes and complications associated with Teflon and Ivalon in MVD. METHODS: We conducted a 2-center retrospective cohort study of trigeminal neuralgia treated with MVD between 2005 and 2019. Patients with no postoperative follow-up were excluded. Postoperative pain was graded using the Barrow Neurological Institute (BNI) pain intensity score. Relapse was defined as a BNI score of 4-5 during follow-up after initial pain improvement or an initial BNI score of 1-3. RESULTS: The study included 221 MVD procedures in 219 patients. Ivalon was implanted in 121 procedures, and Teflon was implanted in 100 procedures. Multivariate analysis found that implant type had no effect on final BNI score (P = 0.305). Relapse rates were similar at 5- and 10-year follow-up (5-year: Ivalon 10.7%, Teflon 18.0%, P = 0.112; 10-year: Ivalon 11.6%, Teflon 19.0%, P = 0.123). There was no difference in postoperative immediate facial numbness (P = 0.125). Postoperative hearing difficulty was higher in the Ivalon cohort (8.4% vs. 1.0%; P = 0.016). CONCLUSIONS: We found no significant difference in final BNI score or risk of relapse between Ivalon and Teflon. Complications were similar, although Ivalon was more associated with temporary postoperative hearing loss.

Impact of mind-body treatment interventions on quality of life in neurofibromatosis patients: A systematic review and meta-analysis.

Individuals with neurofibromatosis (NF) experience poorer quality of life (QoL), in part contributed by the clinical manifestations of NF, such as functional disability, chronic pain, and altered physical appearance. Mind-body therapies (MBTs) tailored to NF have been developed, and have demonstrated promising potential to improve QoL in this population. We sought to systematically review current evidence on the effectiveness of MBTs in addressing QoL deficits in NF patients. Databases were reviewed between the date of inception and June 2020, using search terms: neurofibromatosis, schwannomatosis, psychotherapy, mind-body, mindfulness, meditation, resiliency, and behavioral therapy. Quality appraisal was assessed using the Cochrane Risk of Bias Tools and National Institutes of Health Study Quality Assessment Tools. We conducted a meta-analysis of mean differences and reported aggregate effect estimates with 95% confidence intervals. A total of 10 articles, including randomized-controlled trials and pre-post studies, were identified. Meta-analytic results of randomized-controlled trial data from six citations demonstrated MBTs were associated with improved physical (MD = 13.63, 95%CI 6.95-20.30, P < .0001, I2 = 24%), psychological (MD = 14.11, 95%CI 6.44-21.78, P = .0003, I2 = 38%), social (MD = 9.63, 95%CI 2.93-16.33, P = .005, I2 = 0%), and environmental QoL (MD = 14.14, 95%CI 8.28-20.00, P < .00001. I2 = 0%) in NF patients. These associations were maintained at 6-months follow-up for physical, psychological, and environmental QoL (P < .05). Our findings suggest that NF-adapted MBT strategies are associated with improving QoL in diverse NF populations, including NF2 patients experiencing deafness and youth NF patients. Providers and caregivers for NF should be aware of the potential benefits of MBT in chronic NF management.

A Museum of Stem Cells Points to Muse Cells as Robust Transplantable Cells for Stroke: Review.

Stem cell-based therapy stands as a robust experimental treatment for ischemic stroke. Stem cells derived from fetal, embryonic, and adult tissues serve as potential sources for transplantable cells in the setting of ischemic stroke. However, the search continues for finding an optimal cell line for clinical use. Muse cells, a distinct subset of mesenchymal stem cells found sporadically in the connective tissue of nearly every organ, may be a suitable candidate due to its safety and accessibility. These cells have been investigated for therapeutic usage in chronic kidney disease, liver disease, acute myocardial infarction, and stroke. Muse cells display the ability to engraft and differentiate into the host neural network unlike many other cell lines which only display bystander immunomodulating effects. Taking advantage of this unique engraftment and differentiation mechanism behind Muse cells' therapeutic effects on the central nervous system, as well as other organ systems, will undoubtedly advance the cells' utility for cell-based regenerative medicine in stroke.

Fighting the War Against COVID-19 via Cell-Based Regenerative Medicine: Lessons Learned from 1918 Spanish Flu and Other Previous Pandemics.

The human population is in the midst of battling a rapidly-spreading virus- Severe Acute Respiratory Syndrome Coronavirus 2, responsible for Coronavirus disease 2019 or COVID-19. Despite the resurgences in positive cases after reopening businesses in May, the country is seeing a shift in mindset surrounding the pandemic as people have been eagerly trickling out from federally-mandated quarantine into restaurants, bars, and gyms across America. History can teach us about the past, and today's pandemic is no exception. Without a vaccine available, three lessons from the 1918 Spanish flu pandemic may arm us in our fight against COVID-19. First, those who survived the first wave developed immunity to the second wave, highlighting the potential of passive immunity-based treatments like convalescent plasma and cell-based therapy. Second, the long-term consequences of COVID-19 are unknown. Slow-progressive cases of the Spanish flu have been linked to bacterial pneumonia and neurological disorders later in life, emphasizing the need to reduce COVID-19 transmission. Third, the Spanish flu killed approximately 17 to 50 million people, and the lack of human response, overcrowding, and poor hygiene were key in promoting the spread and high mortality. Human behavior is the most important strategy for preventing the virus spread and we must adhere to proper precautions. This review will cover our current understanding of the pathology and treatment for COVID-19 and highlight similarities between past pandemics. By revisiting history, we hope to emphasize the importance of human behavior and innovative therapies as we wait for the development of a vaccine. Graphical Abstract.

Stem Cells as Drug-like Biologics for Mitochondrial Repair in Stroke.

Stroke is a devastating condition characterized by widespread cell death after disruption of blood flow to the brain. The poor regenerative capacity of neural cells limits substantial recovery and prolongs disruptive sequelae. Current therapeutic options are limited and do not adequately address the underlying mitochondrial dysfunction caused by the stroke. These same mitochondrial impairments that result from acute cerebral ischemia are also present in retinal ischemia. In both cases, sufficient mitochondrial activity is necessary for cell survival, and while astrocytes are able to transfer mitochondria to damaged tissues to rescue them, they do not have the capacity to completely repair damaged tissues. Therefore, it is essential to investigate this mitochondrial transfer pathway as a target of future therapeutic strategies. In this review, we examine the current literature pertinent to mitochondrial repair in stroke, with an emphasis on stem cells as a source of healthy mitochondria. Stem cells are a compelling cell type to study in this context, as their ability to mitigate stroke-induced damage through non-mitochondrial mechanisms is well established. Thus, we will focus on the latest preclinical research relevant to mitochondria-based mechanisms in the treatment of cerebral and retinal ischemia and consider which stem cells are ideally suited for this purpose.

Subcutaneous Fat Fibrosis Links Obesity to Insulin Resistance in Chinese Americans.

Objective: Type 2 diabetes presents at a lower body mass index (BMI) in Chinese individuals than in white individuals. We sought to determine the role of subcutaneous adipose tissue (SCAT)-intrinsic factors, vs BMI or adiposity per se, in the vulnerability of Chinese individuals to obesity-associated impairment of insulin sensitivity. Research Design and Methods: Thirty-two Chinese and 30 white men and women from a cohort in the San Francisco Bay Area underwent anthropometric measurements, body composition (dual-energy X-ray absorptiometry) analyses, and measurement of fasting plasma glucose and insulin. Forty-eight also provided abdominal SCAT samples for transcriptional and biochemical analyses of tissue fibrosis. Results: BMI correlated with total body fat in white (r = 0.74, P < 0.001) but not Chinese individuals, whereas BMI correlated with visceral adipose tissue (VAT) accrual in both ethnicities (r = 0.88 and 0.81, respectively; P < 0.01). Insulin resistance (homeostatic model assessment of insulin resistance) worsened with VAT mass, but not total body fat, in Chinese subjects (r = 0.63, P < 0.01), whereas it worsened with both in white individuals. By contrast, SCAT mRNA levels of genes encoding profibrotic proteins rose remarkably along with both BMI and VAT mass in Chinese but not white subjects. Similarly, SCAT levels of hydroxyproline, an indicator of tissue collagen content that correlated with increasing VAT mass, were higher in Chinese vs white subjects, particularly in the setting of relative insulin resistance. Conclusions: Our findings dissociate BMI from adiposity in Chinese individuals and instead highlight SCAT fibrosis as a process linked to visceral adiposity and insulin resistance in this group.