Vertebral body collapse after spine stereotactic body radiation therapy: a single-center institutional experience.

BACKGROUND: Spine stereotactic body radiation therapy (SBRT) for the treatment of metastatic disease is increasingly utilized owing to improved pain and local control over conventional regimens. Vertebral body collapse (VBC) is an important toxicity following spine SBRT. We investigated our institutional experience with spine SBRT as it relates to VBC and spinal instability neoplastic score (SINS). PATIENTS AND METHODS: Records of 83 patients with 100 spinal lesions treated with SBRT between 2007 and 2022 were reviewed. Clinical information was abstracted from the medical record. The primary endpoint was post-treatment VBC. Logistic univariate analysis was performed to identify clinical factors associated with VBC. RESULTS: Median dose and number of fractions used was 24 Gy and 3 fractions, respectively. There were 10 spine segments that developed VBC (10%) after spine SBRT. Median time to VBC was 2.4 months. Of the 11 spine segments that underwent kyphoplasty prior to SBRT, none developed subsequent VBC. No factors were associated with VBC on univariate analysis. CONCLUSIONS: The rate of vertebral body collapse following spine SBRT is low. Prophylactic kyphoplasty may provide protection against VBC and should be considered for patients at high risk for fracture.

Fillable Magnetic Microrobots for Drug Delivery to Cardiac Tissues In Vitro.

Many cardiac diseases, such as arrhythmia or cardiogenic shock, cause irregular beating patterns that must be regulated to prevent disease progression toward heart failure. Treatments can include invasive surgery or high systemic drug dosages, which lack precision, localization, and control. Drug delivery systems (DDSs) that can deliver cargo to the cardiac injury site could address these unmet clinical challenges. Here, a microrobotic DDS that can be mobilized to specific sites via magnetic control is presented. This DDS incorporates an internal chamber that can protect drug cargo. Furthermore, the DDS contains a tunable thermosensitive sealing layer that gradually degrades upon exposure to body temperature, enabling prolonged drug release. Once loaded with the small molecule drug norepinephrine, this microrobotic DDS modulated beating frequency in induced pluripotent stem-cell derived cardiomyocytes (iPSC-CMs) in a dose-dependent manner, thus simulating drug delivery to cardiac cells in vitro. The DDS also navigates several maze-like structures seeded with cardiomyocytes to demonstrate precise locomotion under a rotating low-intensity magnetic field and on-site drug delivery. This work demonstrates the utility of a magnetically actuating DDS for precise, localized, and controlled drug delivery which is of interest for a myriad of future opportunities such as in treating cardiac diseases.

Musculoskeletal Pitfalls on Molecular Imaging Studies of Oncologic Patients: How to Stay Out of Trouble.

An increasing amount of molecular imaging studies are ordered each year for an oncologic population that continues to expand and increase in age. The importance of these studies in dictating further care for oncologic patients underscores the necessity of differentiating benign from malignant findings, particularly for a population in whom incidental findings are common. The aim of this review is to provide pictorial examples of benign musculoskeletal pathologies which may be found on molecular imaging and which may be mistaken for malignant processes. Imaging examples are provided in the form of radiographs, bone scintigraphy, computed tomography, and fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scans. Special attention is paid to specific features that help narrow the differential diagnosis and distinguish benign from malignant processes, with the goal of avoiding unnecessary invasive procedures.

The Puzzle of Marijuana Use and Forced Vital Capacity.

In study after study, marijuana use has been found to be associated with increased forced vital capacity (FVC). This is puzzling, because marijuana is commonly consumed by inhalation of its smoke, and smoke exposure of any kind is not generally considered a cause of increased FVC. Although this observation was first made decades ago, a satisfactory explanation remains elusive. In this review we survey the evidence supporting the relationship between marijuana use and increased FVC, discuss potential threats to validity when inferring causation, and, presupposing a possible causal relationship, pose two key questions. First, what are possible physiologic or pathophysiologic mechanisms by which marijuana use might increase FVC? Second, why might this effect be consistently observed with marijuana use but not with tobacco use? Explanations for the first question include lung and chest growth and remodeling from strenuous marijuana smoke inhalation and reductions in lung elastic recoil from marijuana smoke exposure. Explanations for the second include differences between marijuana and tobacco in smoke composition and patterns of consumption, such as smoking topography. Finally, the possibility that smoke, whether from marijuana or tobacco, might have nonmonotonic effects on FVC depending on the degree of exposure is explored. In synthesizing a curated breadth of epidemiologic and physiologic science, we leverage a perplexing observation to generate potential insights and avenues for further research into the biological effects of smoke, from marijuana or otherwise, on the respiratory system.

Keratocystoma: A Distinctive Salivary Gland Neoplasm Characterized by RUNX2 Rearrangements.

Keratocystoma is a rare salivary gland lesion that has been reported primarily in children and young adults. Because of a scarcity of reported cases, very little is known about it, including its molecular underpinnings, biological potential, and histologic spectrum. Purported to be a benign neoplasm, keratocystoma bears a striking histologic resemblance to benign lesions like metaplastic Warthin tumor on one end of the spectrum and squamous cell carcinoma on the other end. This overlap can cause diagnostic confusion, and it raises questions about the boundaries and definition of keratocystoma as an entity. This study seeks to utilize molecular tools to evaluate the pathogenesis of keratocystoma as well as its relationship with its histologic mimics. On the basis of targeted RNA sequencing (RNA-seq) results on a sentinel case, RUNX2 break-apart fluorescence in situ hybridization (FISH) was successfully performed on 4 cases diagnosed as keratocystoma, as well as 13 cases originally diagnosed as tumors that morphologically resemble keratocystoma: 6 primary squamous cell carcinomas, 3 metaplastic/dysplastic Warthin tumors, 2 atypical squamous cysts, 1 proliferating trichilemmal tumor, and 1 cystadenoma. RNA-seq and/or reverse transcriptase-PCR were attempted on all FISH-positive cases. Seven cases were positive for RUNX2 rearrangement, including 3 of 4 tumors originally called keratocystoma, 2 of 2 called atypical squamous cyst, 1 of 1 called proliferating trichilemmal tumor, and 1 of 6 called squamous cell carcinoma. RNA-seq and/or reverse transcriptase-PCR identified IRF2BP2::RUNX2 in 6 of 7 cases; for the remaining case, the partner remains unknown. The cases positive for RUNX2 rearrangement arose in the parotid glands of 4 females and 3 males, ranging from 8 to 63 years old (mean, 25.4 years; median, 15 years). The RUNX2 -rearranged cases had a consistent histologic appearance: variably sized cysts lined by keratinizing squamous epithelium, plus scattered irregular squamous nests, with essentially no cellular atypia or mitotic activity. The background was fibrotic, often with patchy chronic inflammation and/or giant cell reaction. One case originally called squamous cell carcinoma was virtually identical to the other cases, except for a single focus of small nerve invasion. The FISH-negative case that was originally called keratocystoma had focal cuboidal and mucinous epithelium, which was not found in any FISH-positive cases. The tumors with RUNX2 rearrangement were all treated with surgery only, and for the 5 patients with follow-up, there were no recurrences or metastases (1 to 120 months), even for the case with perineural invasion. Our findings solidify that keratocystoma is a cystic neoplastic entity, one which appears to consistently harbor RUNX2 rearrangements, particularly IRF2BP2::RUNX2 . Having a diagnostic genetic marker now allows for a complete understanding of this rare tumor. They arise in the parotid gland and affect a wide age range. Keratocystoma has a consistent morphologic appearance, which includes large squamous-lined cysts that mimic benign processes like metaplastic Warthin tumor and also small, irregular nests that mimic squamous cell carcinoma. Indeed, RUNX2 analysis has considerable promise for resolving these differential diagnoses. Given that one RUNX2 -rearranged tumor had focal perineural invasion, it is unclear whether that finding is within the spectrum of keratocystoma or whether it could represent malignant transformation. Most important, all RUNX2 -rearranged cases behaved in a benign manner.

In situ production and secretion of proteins endow therapeutic benefit against psoriasiform dermatitis and melanoma.

Genetic medicines have the potential to treat various diseases; however, certain ailments including inflammatory diseases and cancer would benefit from control over extracellular localization of therapeutic proteins. A critical gap therefore remains the need to develop and incorporate methodologies that allow for posttranslational control over expression dynamics, localization, and stability of nucleic acid-generated protein therapeutics. To address this, we explored how the body's endogenous machinery controls protein localization through signal peptides (SPs), including how these motifs could be incorporated modularly into therapeutics. SPs serve as a virtual zip code for mRNA transcripts that direct the cell where to send completed proteins within the cell and the body. Utilizing this signaling biology, we incorporated secretory SP sequences upstream of mRNA transcripts coding for reporter, natural, and therapeutic proteins to induce secretion of the proteins into systemic circulation. SP sequences generated secretion of various engineered proteins into the bloodstream following intravenous, intramuscular, and subcutaneous SP mRNA delivery by lipid, polymer, and ionizable phospholipid delivery carriers. SP-engineered etanercept/TNF-α inhibitor proteins demonstrated therapeutic efficacy in an imiquimod-induced psoriasis model by reducing hyperkeratosis and inflammation. An SP-engineered anti-PD-L1 construct mediated mRNA encoded proteins with longer serum half-lives that reduced tumor burden and extended survival in MC38 and B16F10 cancer models. The modular nature of SP platform should enable intracellular and extracellular localization control of various functional proteins for diverse therapeutic applications.

The 'faulty male' hypothesis for sex-biased mutation and disease.

Biological differences between males and females lead to many differences in physiology, disease, and overall health. One of the most prominent disparities is in the number of germline mutations passed to offspring: human males transmit three times as many mutations as do females. While the classic explanation for this pattern invokes differences in post-puberty germline replication between the sexes, recent whole-genome evidence in humans and other mammals has cast doubt on this mechanism. Here, we review recent work that is inconsistent with a replication-driven model of male-biased mutation, and propose an alternative, 'faulty male' hypothesis. This model proposes that males are less able to repair and/or protect DNA from damage compared to females. Importantly, we suggest that this new model for male-biased mutation may also help to explain several pronounced differences between the sexes in cancer, aging, and DNA repair. Although the detailed contributions of genetic, epigenetic, and hormonal influences of biological sex on mutation remain to be fully understood, a reconsideration of the mechanisms underlying these differences will lead to a deeper understanding of evolution and disease.

Intratendinous Calcified Chondroid Mesenchymal Neoplasm: A Case Report.

Introduction: We present a case report concerning calcified chondroid mesenchymal neoplasms (CCMN), a novel category of tumors that exhibit chondroid formation and contain fibronectin 1-receptor tyrosine kinase fusions. Case Report: Our report focuses on a 73-year-old female patient who presented with pain in her right hip and gluteal region. Initially, the condition was misdiagnosed as calcific tendinitis based on X-ray imaging. However, a subsequent magnetic resonance imaging (MRI) revealed a solid lobulated mass originating from the right hamstring tendon origin, exhibiting heterogeneously hypointense T1-weighted signal, heterogeneously isointense proton density fat-suppressed signal, and heterogeneous contrast-enhancement compared to skeletal muscle. Further, investigation through computed tomography (CT) demonstrated intratumoral calcifications accompanied by erosive changes in the adjacent right ischial tuberosity. Histologic examination of a CT-guided biopsy confirmed the presence of large calcium pyrophosphate crystal deposits, along with benign chondroid tissue, thus supporting the diagnosis of CCMN. Notably, there is considerable overlap in the imaging characteristics of CCMN and the more commonly encountered calcific tendinitis (calcium hydroxyapatite depositional disease). Contrast-enhanced MRI findings play a crucial role in distinguishing between these two conditions. Conclusion: To the best of our knowledge, this is the first documented report describing the imaging features of CCMN across multiple modalities, including radiography, CT, and MRI.

GLUT3 promotes macrophage signaling and function via RAS-mediated endocytosis in atopic dermatitis and wound healing.

The facilitative GLUT1 and GLUT3 hexose transporters are expressed abundantly in macrophages, but whether they have distinct functions remains unclear. We confirmed that GLUT1 expression increased after M1 polarization stimuli and found that GLUT3 expression increased after M2 stimulation in macrophages. Conditional deletion of Glut3 (LysM-Cre Glut3fl/fl) impaired M2 polarization of bone marrow-derived macrophages. Alternatively activated macrophages from the skin of patients with atopic dermatitis showed increased GLUT3 expression, and a calcipotriol-induced model of atopic dermatitis was rescued in LysM-Cre Glut3fl/fl mice. M2-like macrophages expressed GLUT3 in human wound tissues as assessed by transcriptomics and costaining, and GLUT3 expression was significantly decreased in nonhealing, compared with healing, diabetic foot ulcers. In an excisional wound healing model, LysM-Cre Glut3fl/fl mice showed significantly impaired M2 macrophage polarization and delayed wound healing. GLUT3 promoted IL-4/STAT6 signaling, independently of its glucose transport activity. Unlike plasma membrane-localized GLUT1, GLUT3 was localized primarily to endosomes and was required for the efficient endocytosis of IL-4Rα subunits. GLUT3 interacted directly with GTP-bound RAS in vitro and in vivo through its intracytoplasmic loop domain, and this interaction was required for efficient STAT6 activation and M2 polarization. PAK activation and macropinocytosis were also impaired without GLUT3, suggesting broader roles for GLUT3 in the regulation of endocytosis. Thus, GLUT3 is required for efficient alternative macrophage polarization and function, through a glucose transport-independent, RAS-mediated role in the regulation of endocytosis and IL-4/STAT6 activation.

Precision Medicine: Disease Subtyping and Tailored Treatment.

The genomics-based concept of precision medicine began to emerge following the completion of the Human Genome Project. In contrast to evidence-based medicine, precision medicine will allow doctors and scientists to tailor the treatment of different subpopulations of patients who differ in their susceptibility to specific diseases or responsiveness to specific therapies. The current precision medicine model was proposed to precisely classify patients into subgroups sharing a common biological basis of diseases for more effective tailored treatment to achieve improved outcomes. Precision medicine has become a term that symbolizes the new age of medicine. In this review, we examine the history, development, and future perspective of precision medicine. We also discuss the concepts, principles, tools, and applications of precision medicine and related fields. In our view, for precision medicine to work, two essential objectives need to be achieved. First, diseases need to be classified into various subtypes. Second, targeted therapies must be available for each specific disease subtype. Therefore, we focused this review on the progress in meeting these two objectives.

Left-Sided Sensorineural Hearing Loss and Facial Weakness in a 35-Year-Old Patient: A Diagnostic Challenge and Case Report.

We present the case of a 35-year-old patient who presented with a three-month history of left-sided sensorineural hearing loss and left-sided facial weakness. Initial imaging suggested a schwannoma, and the patient underwent ten treatments of intra-tympanic steroid injections and antibiotics, and was scheduled for surgery. However, the planned schwannoma removal surgery with gamma-knife was aborted due to the absence of the previously identified mass on the pre-procedure MRI. Subsequent imaging revealed continued enhancement of the left internal auditory canal (IAC), leading to considerations of lymphoma, sarcoidosis, IgG4 disease, or other inflammatory condition. The patient's symptoms have significantly improved since and are currently being conservatively managed and monitored. However, the patient continues to show persistent findings on MRI. This case highlights the diagnostic challenges faced in identifying the underlying etiology of this patient and emphasizes the need for further investigations and multidisciplinary management in patients with similar presentations.

Effect of a dedicated PI-QUAL curriculum on the assessment of prostate MRI quality.

PURPOSE: The Prostate Imaging Quality (PI-QUAL) score is a metric to evaluate the diagnostic quality of multiparametric magnetic resonance imaging (MRI) of the prostate. This study evaluated the impact of a prostate MRI quality training lecture on the participant's ability to assess prostate MRI image quality. METHODS: Eighteen in-training-radiologists of varying experience in reviewing diagnostic prostate MRI assessed the image quality of ten examinations. Then, they attended a dedicated lecture on MRI quality assessment using the PI-QUAL score. After the lecture, the same participants evaluated the image quality of a new set of ten scans applying the PI-QUAL score. Results were assessed using receiver operating characteristic (ROC) analysis. The reference standard was the PI-QUAL score assessed by a fellowship trained abdominal radiologist with experience in reading prostate MRI. RESULTS: There was a significant improvement in the average area under the curve (AUC) for assessment of prostate MRI image quality from baseline (0.82; [0.576 - 0.888]) to post teaching (1.0; [0.954-1]), with an improvement of 0.18 (p < 0.03). When ROC curves were computed for different cohorts stratified based on year of training, difference ranged from 0.48 for second year residents to 0.32 for fourth year residents (p < 0.001-0.01). For abdominal imaging fellows, the pre-teaching AUC was 0.9 [0.557-1] and post teaching AUC was 1 [0.957-1], a difference of 0.1 (p = 0.20). CONCLUSIONS: A dedicated lecture on PI-QUAL improved the ability of radiologists-in-training to assess prostate MRI image quality, with variable impact depending on year of training.

Lung Function in Women With and Without Human Immunodeficiency Virus.

BACKGROUND: Prior studies have found that human immunodeficiency virus (HIV) infection is associated with impaired lung function and increased risk of chronic lung disease, but few have included large numbers of women. In this study, we investigate whether HIV infection is associated with differences in lung function in women. METHODS: This was a cross-sectional analysis of participants in the Women's Interagency HIV Study, a racially and ethnically diverse multicenter cohort of women with and without HIV. In 2018-2019, participants at 9 clinical sites were invited to perform spirometry. Single-breath diffusing capacity for carbon monoxide (DLCO) was also measured at selected sites. The primary outcomes were the post-bronchodilator forced expiratory volume in 1 second (FEV1) and DLCO. Multivariable regression modeling was used to analyze the association of HIV infection and lung function outcomes after adjustment for confounding exposures. RESULTS: FEV1 measurements from 1489 women (1062 with HIV, 427 without HIV) and DLCO measurements from 671 women (463 with HIV, 208 without HIV) met standards for quality and reproducibility. There was no significant difference in FEV1 between women with and without HIV. Women with HIV had lower DLCO measurements (adjusted difference, -0.73 mL/min/mm Hg; 95% confidence interval, -1.33 to -.14). Among women with HIV, lower nadir CD4 + cell counts and hepatitis C virus infection were associated with lower DLCO measurements. CONCLUSIONS: HIV was associated with impaired respiratory gas exchange in women. Among women with HIV, lower nadir CD4 + cell counts and hepatitis C infection were associated with decreased respiratory gas exchange.

Clinical application of brain perfusion imaging in detecting stroke mimics: A review.

Stroke mimics constitute a significant proportion of patients with suspected acute ischemic stroke. These conditions may resemble acute ischemic stroke and demonstrate abnormalities on perfusion imaging sequences. The most common stroke mimics include seizure/epilepsy, migraine with aura, brain tumors, functional disorders, infectious encephalopathies, Wernicke's encephalopathy, and metabolic abnormalities. Brain perfusion imaging techniques, particularly computed tomography perfusion and magnetic resonance perfusion, are being widely used in routine clinical practice for treatment selection in patients presenting with large vessel occlusion. At the same time, the utilization of these imaging modalities enables the opportunity to better diagnose patients with stroke mimics in a time-sensitive setting, leading to appropriate management, decision-making, and resource allocation. In this review, we describe patterns of perfusion abnormalities that could discriminate patients with stroke mimics from those with acute ischemic stroke and provide specific case examples to illustrate these perfusion abnormalities. In addition, we discuss the challenges associated with interpretation of perfusion images in stroke-related pathologies. In general, perfusion imaging can provide additional information in some cases-when used in combination with conventional magnetic resonance imaging and computed tomography-and might help in detecting stroke mimics among patients who present with acute onset focal neurological symptoms.

Clinical applications of arterial spin labeling of the intracranial compartment in vascular anomalies-A case-based review.

Arterial spin labeling (ASL) is a magnetic resonance perfusion technique that allows for quantification of cerebral blood flow (CBF) without the use of contrast or radiation. Several applications of ASL have been described in diagnosis of strokes and stroke mimics, intracranial tumors, and other conditions. Various vascular anomalies exhibit specific CBF patterns that correlate with different signal intensities on ASL. In this case-based review, we demonstrate the utility of ASL in diagnosis and surveillance of vascular anomalies in the intracranial compartment.

Cervical fusion for adult patients with atlantoaxial rotatory subluxation.

Background: Atlantoaxial rotatory subluxation (AARS) is a rare injury of the C1/C2 junction. It is often associated with trauma in adults. Treatment may depend on the duration of symptoms and clinical presentation, but there is no consensus regarding the ideal management of these injuries. Our objective is to ascertain the prevalence of neurological deficit, complications, and outcomes of patients diagnosed with AARS undergoing cervical fusion (CF) versus those treated without CF. Methods: The 2016-2019 National Inpatient Sample (NIS) was queried using International Classification of Diseases, 10th revision (ICD-10) for adult patients with C1/C2 subluxation. Patients undergoing CF were defined through ICD-10 procedure codes. Baseline health and acute illness severity was calculated using the 11-point modified frailty index (mFI-11). Presenting characteristics, treatment complications, and outcomes were evaluated of CF vs. non-CF patients. Results: Of 990 adult patients with AARS, 720 were treated without CF and 270 were treated with CF. CF patients were more often myelopathic. Patients that had undergone CF treatment were negatively associated with having had extensive trauma. Patients undergoing CF experienced significantly longer length of stay (LOS), increased healthcare resource utilization, and decreased inpatient mortality. Sepsis had a negative association with patients that underwent CF treatment while pneumonia had a positive association. Conclusions: Adult patients undergoing CF for AARS demonstrated an increase in healthcare resource utilization but also a significant decrease in mortality. Extent of acute injury appears to have a strong influence on decision making for CF. Further study of decision making for treatment of this rare injury in adults is warranted.

Characteristics of Patients Selected for Surgical Treatment of Spinal Meningioma.

BACKGROUND: Spinal meningiomas are benign extra-axial tumors that can present with neurological deficits. Treatment partly depends on the degree of disability as there is no agreed-upon patient selection algorithm at present. We aimed to elucidate general patient selection patterns in patients undergoing surgery for spinal meningioma. METHODS: Data for patients with spinal tumors admitted between 2016 and 2019 were extracted from the U.S. Nationwide Inpatient Sample. We identified patients with a primary diagnosis of spinal meningioma (using International Classification of Disease, 10th revision codes) and divided them into surgical and nonsurgical treatment groups. Patient characteristics were evaluated for intergroup differences. RESULTS: Of 6395 patients with spinal meningioma, 5845 (91.4%) underwent surgery. Advanced age, nonwhite race, obesity, diabetes mellitus, chronic renal failure, and anticoagulant/antiplatelet use were less prevalent in the surgical group (all P < 0.001). The only positive predictor of surgical treatment was elective admission status (odds ratio, 3.166; P < 0.001); negative predictors were low income, Medicaid insurance, anxiety, obesity, and plegia. Patients with bowel-bladder dysfunction, plegia, or radiculopathy were less likely to undergo surgical treatment. The surgery group was less likely to experience certain complications (deep vein thrombosis, P < 0.001; pulmonary embolism, P = 0.002). Increased total hospital charges were associated with nonwhite race, diabetes, depression, obesity, myelopathy, plegia, and surgery. CONCLUSIONS: Patients treated surgically had a decreased incidence of complications, comorbidities, and Medicaid payer status. A pattern of increased utilization of health care resources and spending was also observed in the surgery group. The results indicate a potentially underserved population of patients with spinal meningioma.

Beth Levine's Legacy: From the Discovery of BECN1 to Therapies. A Mentees' Perspective.

With great sadness, the scientific community received the news of the loss of Beth Levine on 15 June 2020. Dr. Levine was a pioneer in the autophagy field and work in her lab led not only to a better understanding of the molecular mechanisms regulating the pathway, but also its implications in multiple physiological and pathological conditions, including its role in development, host defense, tumorigenesis, aging or metabolism. This review does not aim to provide a comprehensive view of autophagy, but rather an outline of some of the discoveries made by the group of Beth Levine, from the perspective of some of her own mentees, hoping to honor her legacy in science.

The combined effect of physical activity and fruit and vegetable intake on decreasing cognitive decline in older Taiwanese adults.

The factors associated with cognitive decline among older adults include physical activity and fruit and vegetable intake. However, the long-term effects of concomitant physical activity and fruit and vegetable intake are unknown. This 16-year longitudinal study explored the joint effect of mitigating cognitive decline in a cohort of older Taiwanese individuals. Five population-based surveys (Taiwan Longitudinal Survey on Aging [1999-2015]) involving 4440 respondents over 53 years old in 1999 were conducted. Cognitive function was assessed using the Short Portable Mental Status Questionnaire (SPMSQ). The demographic, socioeconomic, health-related, behavioral, and disease status covariates were adjusted in the regression analysis. Trends in cognitive decline were observed over 16 years. The risk of cognitive decline decreased by 63% when high physical activity and high fruit and vegetable intake were combined (odds ratio 0.37; 95% confidence interval 0.23-0.59), indicating a potential combined effect of physical activity and fruit and vegetable intake on mitigating cognitive decline. These personal actions are safe, effective, and economical approaches to health promotion and disease prevention.