Postmenopausal Hormone Therapy Was Associated With Later Age of Onset Among Glaucoma Cases.

Purpose: Hormonal therapy (HT) has been suggested to lower the risk of developing glaucoma. Our goal was to investigate the association between HT use and the onset of glaucoma diagnosis in postmenopausal women. Methods: This retrospective case-only study included female veterans with open-angle glaucoma from VA records between 2000 to 2019. Propensity score matching was used to match HT (n = 1926) users to untreated (n = 1026) women on multiple covariates (e.g., age of menopause, BMI, blood pressure, antihypertensive medications, and a co-morbidity index). A simple linear regression was used to evaluate the impact of HT duration on the age of glaucoma diagnosis, and multivariate linear regression analysis was used to determine which factors contributed to the age at diagnosis of glaucoma. Results: We found a linear relationship between the age at diagnosis of glaucoma and menopause in women with (r = 0.54) and without HT (r = 0.57) use. HT users tended to have a later diagnosis of glaucoma. Our multivariate analysis found that 0-2 years, 2-5 years, and >5 years of HT use were associated with a 2.20 [confidence interval (CI), 1.64, 2.76], 3.74 [CI, 3.02, 4.46], and 4.51 [CI, 3.84, 5.18] years later diagnosis of glaucoma. An interaction (-0.009 [-0.015, -0.003]) was observed between HT duration and age of menopause diagnosis, with the impact of HT decreasing for later menopause ages. Conclusions: Longer duration of HT use was associated with a later diagnosis of glaucoma in postmenopausal women in this case-only analysis. The impact of HT may be modulated by menopausal age, although further study is needed. The findings support a protective role of estrogen in glaucoma pathogenesis.

Association of Age of Menopause and Glaucoma Diagnosis in Female Veterans.

Purpose: Age of menopause has been associated with the risk of developing glaucoma; however, it is unclear if the onset of menopause is directly associated with the development of glaucoma. Our objective was to determine if there is an association between the age at diagnosis of menopause and glaucoma. Methods: This retrospective, case-only analysis was performed using the Veterans Affairs (VA) Corporate Data Warehouse of female veterans from 2000 to 2019. Women with both menopause and glaucoma diagnoses were matched based on covariates. The two matched cohorts were early menopause-early comparative (EM-EC; n = 1075) and late menopause-late comparative (LM-LC; n = 1050) women. We used a Pearson correlation to examine the linear relationship between age at diagnosis of menopause and glaucoma. Afterward, we used a multivariate linear regression model with age at diagnosis of glaucoma serving as the outcome variable to account for the covariates. Results: We found that EM women developed glaucoma 6.0 years (interquartile range [IQR], 5.1-6.5) earlier than the EC group (P < 0.001), and LM women developed glaucoma an average of 5.2 years (IQR, 4.8-5.7) later than the LC group (P < 0.001). There was a modest linear relationship between the age of menopause and glaucoma diagnoses in the EM-EC (r = 0.40) and LM-LC (r = 0.46) cohorts. In our multivariate analysis, age at diagnosis of menopause was the largest factor related to age at diagnosis of glaucoma while accounting for our covariates. Our models predicted a 0.67-year delay in age at diagnosis of glaucoma with each additional premenopausal year. Conclusions: This case-only analysis elucidates a temporal association between menopause and glaucoma, highlighting the need to characterize the role of menopause in the onset of glaucoma for women.

Impaired neurocirculatory control in chronic kidney disease: New evidence for blunted sympathetic baroreflex and reduced sympathetic transduction.

BACKGROUND: Chronic kidney disease (CKD) is characterized by over-activation of the sympathetic nervous system (SNS) that increases cardiovascular risk. Whether sympathetic baroreflex sensitivity (sBRS) is impaired or intact in CKD remains under-studied and controversial. Furthermore, the downstream effect of SNS activation on blood pressure transduction has not been previously examined in CKD. We tested the hypothesis that sBRS is attenuated, while sympathetic transduction is augmented in CKD. METHODS: In 18 sedentary patients with CKD stages III-IV (eGFR: 40±14 ml/min) and 13 age-matched controls (eGFR: 95±10 ml/min), beat-to-beat blood pressure (BP; finger photoplethysmography), heart rate (electrocardiography) and muscle sympathetic nerve activity (MSNA; microneurography) were recorded at rest for 10-min. Weighted linear regression analysis between MSNA burst incidence and diastolic BP was used to determine the spontaneous sBRS. Sympathetic-BP transduction was quantified using signal averaging, whereby the BP response to each MSNA burst was tracked over 15 cardiac cycles and averaged to derive the peak change in BP. RESULTS: Compared with controls, CKD patients had an attenuated sBRS [CKD: -1.34±0.59 versus CON: -2.91±1.09 bursts (100 heartbeats)-1 mmHg-1; P=0.001]. |sBRS| was significantly associated with eGFR (r=0.69, P<0.001). CKD patients had attenuated sympathetic-BP transduction compared to controls (0.75±0.7 vs. 1.60±0.8 mmHg; P=0.010). Resting MSNA was negatively associated with sympathetic transduction (r=-0.57, P=0.002). CONCLUSION: CKD patients exhibit impaired sBRS that may contribute to SNS overactivation and cardiovascular risk in this patient population. In addition, CKD patients had an attenuated sympathetic transduction that may counteract the vascular effects of SNS overactivation.

Distinct developmental reprogramming footprint of macrophages during acute kidney injury across species.

Acute kidney injury (AKI) is a common finding in hospitalized patients, particularly those who are critically ill. The development of AKI is associated with several adverse outcomes including mortality, morbidity, progression to chronic kidney disease, and an increase in healthcare expenditure. Despite the well-established negative impact of AKI and rigorous efforts to better define, identify, and implement targeted therapies, the overall approach to the treatment of AKI continues to principally encompass supportive measures. This enduring challenge is primarily due to the heterogeneous nature of insults that activate many independent and overlapping molecular pathways. Consequently, it is evident that the identification of common mechanisms that mediate the pathogenesis of AKI, independent of etiology and engaged pathophysiological pathways, is of paramount importance and could lead to the identification of novel therapeutic targets. To better distinguish the commonly modulated mechanisms of AKI, we explored the transcriptional characteristics of human kidney biopsies from patients with acute tubular necrosis (ATN), and acute interstitial nephritis (AIN) using a NanoString inflammation panel. Subsequently, we used publicly available single-cell transcriptional resources to better interpret the generated transcriptional findings. Our findings identify robust acute kidney injury (AKI-induced) developmental reprogramming of macrophages (MΦ) with the expansion of C1Q+, CD163+ MΦ that is independent of the etiology of AKI and conserved across mouse and human species. These results would expand the current understanding of the pathophysiology of AKI and potentially offer novel targets for additional studies to enhance the translational transition of AKI research.NEW & NOTEWORTHY Our findings identify robust acute kidney injury (AKI)-induced developmental reprogramming of macrophages (MΦ) with the expansion of C1Q+, CD163+ MΦ that is independent of the etiology of AKI and conserved across mouse and human species.

A Randomized, Sham-Controlled Trial of Cranial Electrical Stimulation for Fibromyalgia Pain and Physical Function, Using Brain Imaging Biomarkers.

Fibromyalgia is a chronic pain syndrome that presents with a constellation of broad symptoms, including decreased physical function, fatigue, cognitive disturbances, and other somatic complaints. Available therapies are often insufficient in treating symptoms, with inadequate pain control commonly leading to opioid usage for attempted management. Cranial electrical stimulation (CES) is a promising non-pharmacologic treatment option for pain conditions that uses pulsed electrical current stimulation to modify brain function via transcutaneous electrodes. These neural mechanisms and the applications of CES in fibromyalgia symptom relief require further exploration. A total of 50 participants from the Atlanta Veterans Affairs Healthcare System (VAHCS) diagnosed with fibromyalgia were enrolled and then block-randomized into either a placebo plus standard therapy or active CES plus standard therapy group. Baseline assessments were obtained prior to the start of treatment. Both interventions occurred over 12 weeks, and participants were assessed at 6 weeks and 12 weeks after treatment initiation. The primary outcome investigated whether pain and functional improvements occur with the application of CES. Additionally, baseline and follow-up resting state functional connectivity magnetic resonance imaging (rs-fcMRI) were obtained at the 6-week and 12-week time points to assess for clinical applications of neural connectivity biomarkers and the underlying neural associations related to treatment effects. This is a randomized, placebo-controlled trial to determine the efficacy of CES for improving pain and function in fibromyalgia and further develop rs-fcMRI as a clinical tool to assess the neural correlates and mechanisms of chronic pain and analgesic response.

Comparison of arterial storage conditions for delayed arterial ring testing.

Objective: Arterial ring testing is the gold standard for measuring arterial function. Increased arterial tone through arterial contraction and impaired endothelial relaxation (endothelial dysfunction) are key metrics of impaired arterial health in peripheral arterial disease (PAD). To allow for comparative testing of arteries during standard laboratory hours, storage buffers and conditions have been used to extend the functional life of arteries. Various storage conditions have been compared, but there has not been a robust comparison or validation in human arteries. The objective of this work is to optimize storage of arterial segments for endothelial cell (EC) testing in a murine model and to test EC function in human PAD arteries. We hypothesized that certain storage conditions would be superior to others. Methods: Healthy murine aortas were harvested from 10- to 14-week-old C57/Bl6J male and female mice and compared under different storage protocols (24 hours) to immediate arterial testing. The storage conditions tested were: Opti-MEM (37°C or 4°C), Krebs-HEPES with 1.8 mmol/L or 2.5 mmol/L calcium (4°C), or Wisconsin (WI) solution at 4°C. Vascular function was evaluated by isometric force testing. Endothelium-dependent and -independent relaxation were measured after precontraction with addition of methacholine or sodium nitroprusside, respectively. Arterial contraction was stimulated with potassium chloride or phenylephrine. Analysis of variance was used to determine significance compared with immediate testing with P < .05. Under institutional review board approval, 28 PAD arteries were collected at amputation and underwent vascular function testing as described. Disturbed flow conditions were determined by indirect (upstream occlusion) flow to the harvested tibial arteries. Stable flow arteries had in-line flow. Arterial calcification was quantified manually as present or not present. Results: We found that 4°C WI and 37°C Opti-MEM best preserved endothelium-dependent relaxation and performed similarly to immediately testing aortas (termed fresh for freshly tested) (P > .95). Other storage conditions were inferior to freshly tested aortas (P < .05). Vascular smooth muscle function was tested by endothelial-independent relaxation and contractility. All storage conditions preserved endothelial-independent relaxation and contractility similar to freshly tested arteries. However, 4°C WI and 37°C Opti-MEM storage conditions most closely approximated the maximum force of contraction of freshly tested arteries in response to potassium chloride (P > .39). For human arterial testing, 28 tibial arteries were tested for relaxation and contraction with 16 arteries with peripheral artery occlusive disease (PAD with disturbed flow) and 12 without peripheral artery occlusive disease (PAD with stable flow), of which 14 were calcified and 14 were noncalcified. Endothelial-dependent relaxation data was measurable in 9 arteries and arterial contraction data was measurable in 14 arteries. When comparing flow conditions, arteries exposed to disturbed flow (n = 4) had significantly less relaxation (2% vs 59%; P = .03) compared with stable flow conditions (n = 5). In contrast, presence the (n = 6) or absence of calcification (n = 3) did not impact arterial relaxation. Arterial contraction was not different between groups in either comparison by flow (n = 9 disturbed; n = 5 stable) or calcification (n = 6 present; n = 8 absent). Conclusions: In healthy murine aortas, arterial storage for 24 hours in 4°C WI or 37°C Opti-MEM both preserved endothelium-dependent relaxation and maximum force of contraction. In human PAD arteries stored in 4° WI, flow conditions before arterial harvest, but not arterial calcification, led to differences in arterial relaxation in human PAD arteries. Arterial contractility was more robust (11/28 arteries) compared with arterial relaxation (7/28 arteries), but was not significantly different under flow or calcification parameters. This work defines ideal storage conditions for arterial ring testing and identifies that EC dysfunction from disturbed flow may persist in delayed ex vivo arterial testing.

Total choline intake and working memory performance in adults with phenylketonuria.

BACKGROUND: Despite early diagnosis and compliance with phenylalanine (Phe)-restricted diets, many individuals with phenylketonuria (PKU) still exhibit neurological changes and experience deficits in working memory and other executive functions. Suboptimal choline intake may contribute to these impairments, but this relationship has not been previously investigated in PKU. The objective of this study was to determine if choline intake is correlated with working memory performance, and if this relationship is modified by diagnosis and metabolic control. METHODS: This was a cross-sectional study that included 40 adults with PKU and 40 demographically matched healthy adults. Web-based neurocognitive tests were used to assess working memory performance and 3-day dietary records were collected to evaluate nutrient intake. Recent and historical blood Phe concentrations were collected as measures of metabolic control. RESULTS: Working memory performance was 0.32 z-scores (95% CI 0.06, 0.58) lower, on average, in participants with PKU compared to participants without PKU, and this difference was not modified by total choline intake (F[1,75] = 0.85, p = 0.36). However, in a subgroup with complete historical blood Phe data, increased total choline intake was related to improved working memory outcomes among participants with well controlled PKU (Phe = 360 µmol/L) after adjusting for intellectual ability and mid-childhood Phe concentrations (average change in working memory per 100 mg change in choline = 0.11; 95% CI 0.02, 0.20; p = 0.02). There also was a trend, albeit nonsignificant (p = 0.10), for this association to be attenuated with increased Phe concentrations. CONCLUSIONS: Clinical monitoring of choline intake is essential for all individuals with PKU but may have important implications for working memory functioning among patients with good metabolic control. Results from this study should be confirmed in a larger controlled trial in people living with PKU.

Association of Health Care Utilization and Access to Care With Vascular Assessment Before Major Lower Extremity Amputation Among US Veterans.

Importance: Patient-level characteristics alone do not account for variation in care among US veterans with peripheral artery disease (PAD). Presently, the extent to which health care utilization and regional practice variation are associated with veterans receiving vascular assessment prior to major lower extremity amputation (LEA) is unknown. Objective: To assess whether demographics, comorbidities, distance to primary care, the number of ambulatory clinic visits (primary and medical specialty care), and geographic region are associated with receipt of vascular assessment prior to LEA. Design, Setting, and Participants: This national cohort study used US Department of Veterans Affairs' Corporate Data Warehouse data from March 1, 2010, to February 28, 2020, for veterans aged 18 or older who underwent major LEA and who received care at Veterans Affairs facilities. Exposures: The number of ambulatory clinic visits (primary and medical specialty care) in the year prior to LEA, geographic region of residence, and distance to primary care. Main Outcomes and Measures: The main outcome was receipt of a vascular assessment (vascular imaging study or revascularization procedure) in the year prior to LEA. Results: Among 19 396 veterans, the mean (SD) age was 66.78 (10.20) years and 98.5% were male. In the year prior to LEA, 8.0% had no primary care visits and 30.1% did not have a vascular assessment. Compared with veterans with 4 to 11 primary care clinic visits, those with fewer visits were less likely to receive vascular assessment in the year prior to LEA (1-3 visits: adjusted odds ratio [aOR], 0.90; 95% CI, 0.82-0.99). Compared with veterans who lived less than 13 miles from the closest primary care facility, those who lived 13 miles or more from the facility were less likely to receive vascular assessment (aOR, 0.88; 95% CI, 0.80-0.95). Veterans who resided in the Midwest were most likely to undergo vascular assessment in the year prior to LEA than were those living in other regions. Conclusions and Relevance: In this cohort study, health care utilization, distance to primary care, and geographic region were associated with intensity of PAD treatment before LEA, suggesting that some veterans may be at greater risk of suboptimal PAD care practices. Development of clinical programs, such as remote patient monitoring and management, may represent potential opportunities to improve limb preservation rates and the overall quality of vascular care for veterans.

Characterization of Choline Nutriture among Adults and Children with Phenylketonuria.

Choline is an essential nutrient for brain development and function that is attained through high-protein foods, which are limited in the phenylalanine-restricted diet of people with phenylketonuria (PKU). This study compared choline consumption among individuals with PKU to a reference sample from the National Health and Nutrition Examination Survey (NHANES), and identified treatment and diet-related factors that may modulate choline needs. Participants were individuals with PKU (n = 120, 4-61 years) managed with dietary therapy alone (n = 49), sapropterin dihydrochloride for ≥1 year (n = 38), or pegvaliase for ≥1 year with no medical food (n = 33). NHANES participants were not pregnant or nursing and came from the 2015-2018 cycles (n = 10,681, 4-70 years). Dietary intake data were used to estimate total usual intake distributions for choline, and mean probability of adequacy (MPA) was calculated as a summary index of nutrient adequacy for four methyl-donor/co-factor nutrients that impact choline utilization (folate, vitamin B12, vitamin B6, and methionine). Only 10.8% (SE: 2.98) of the total PKU sample (14.7% [SE: 4.03] of children; 6.8% [SE: 2.89] of adults) achieved the adequate intake (AI) for choline, while 12.2% (SE:0.79) of the NHANES sample met the recommended level. Adults receiving pegvaliase were the most likely to exceed the AI for choline (14.82% [SE: 4.48]), while adults who were on diet therapy alone were the least likely (5.59% [SE: 2.95]). Without fortified medical foods, individuals on diet therapy and sapropterin would not be able to achieve the AI, and MPA for other methyl donor/co-factor nutrients would be reduced. More frequent monitoring of choline intake and increased choline fortification of medical foods could benefit this population.

An in vivo model of glioblastoma radiation resistance identifies long noncoding RNAs and targetable kinases.

Key molecular regulators of acquired radiation resistance in recurrent glioblastoma (GBM) are largely unknown, with a dearth of accurate preclinical models. To address this, we generated 8 GBM patient-derived xenograft (PDX) models of acquired radiation therapy-selected (RTS) resistance compared with same-patient, treatment-naive (radiation-sensitive, unselected; RTU) PDXs. These likely unique models mimic the longitudinal evolution of patient recurrent tumors following serial radiation therapy. Indeed, while whole-exome sequencing showed retention of major genomic alterations in the RTS lines, we did detect a chromosome 12q14 amplification that was associated with clinical GBM recurrence in 2 RTS models. A potentially novel bioinformatics pipeline was applied to analyze phenotypic, transcriptomic, and kinomic alterations, which identified long noncoding RNAs (lncRNAs) and targetable, PDX-specific kinases. We observed differential transcriptional enrichment of DNA damage repair pathways in our RTS models, which correlated with several lncRNAs. Global kinomic profiling separated RTU and RTS models, but pairwise analyses indicated that there are multiple molecular routes to acquired radiation resistance. RTS model-specific kinases were identified and targeted with clinically relevant small molecule inhibitors. This cohort of in vivo RTS patient-derived models will enable future preclinical therapeutic testing to help overcome the treatment resistance seen in patients with GBM.

Rapid Antiretroviral Therapy Program: Development and Evaluation at a Veterans Affairs Medical Center in the Southern United States.

Early HIV viral suppression (VS) improves individual health outcomes and decreases onward transmission. We designed an outpatient clinic protocol to rapidly initiate antiretroviral therapy (ART) in a large Veterans Health Administration (VA) HIV clinic. A pre-post evaluation was performed using a retrospective cohort study design for new diagnoses of HIV infection from January 2012 to February 2020. Time-to-event analyses were performed using the Cox proportional hazards model with the intervention group as the main exposure adjusted for integrase inhibitor usage, baseline viral load, age, gender, and race. Most of the patients were men (historical control: 94.8%, n = 55; Rapid Start: 94.8%, n = 55) and Black or African American persons (historical control: 87.9%, n = 51; Rapid Start: 82.8%, n = 48). More patients initiated treatment with an integrase inhibitor-based regimen in the Rapid Start group (98.3%, n = 57) compared with the historical control group (39.7%, n = 23). Compared with controls, the Rapid Start patients were significantly more likely to achieve VS at any given time during the study period (hazard ratio 2.65; p < 0.001). Median days (interquartile range) from diagnosis to VS decreased from 180.5 (102.5-338.5) to 62 (40-105) (p < 0.001), first appointment to VS decreased from 123 (68.5-237.5) to 45 (28-82) (p < 0.001), referral to first visit decreased from 20 (10-43) to 1 (0-3) (p < 0.001), and from first visit to ART dispense date decreased from 27.5 (3-50) to 0 (0-0) (p = 0.01). Prioritizing immediate ART initiation can compress the HIV care continuum from diagnosis to linkage to VS. Implementation of the Rapid Start Protocol should be considered at all VA facilities providing HIV care.

Use of oral anti-diabetic drugs and risk of hospital and intensive care unit admissions for infections.

BACKGROUND: Sepsis is one of the leading causes of hospital mortality, and diabetes is a risk factor for the development of infections. Although strong evidence has shown an association between metformin and reduced risk of infections, the risk of developing infections with newer classes of oral anti-diabetic drugs (OADs) has been less certain. Our study aims to examine the association between outpatient OAD use and hospital admissions for infections. METHODS: The study cohort included 1.39 million adults with diabetes utilizing the Veterans Health Affairs Corporate Data Warehouse. Multivariate logistic regression was used to estimate the effect of each drug class on hospital admission for infection while adjusting for covariates. RESULTS: After adjusting for covariates, those who took metformin during the study period had 3.3% lower odds of hospital admission for infection compared to those who were never on metformin (OR 0.97, 95% CI 0.95-0.98). OADs that were associated with a statistically significant increased odds of being admitted included meglitinides (OR 1.22, 95% CI 1.07-1.38), SGLT2 inhibitors (OR 1.16, 95% CI 1.08-1.24), alpha-glucosidase inhibitors (OR 1.09, 95% CI 1.04-1.15), and DPP4 inhibitors (OR 1.04, 95% CI 1.01-1.06). CONCLUSIONS: Metformin was associated with lower odds of hospital admission for infection while meglitinides, SGLT2 inhibitors, alpha-glucosidase inhibitors, and DPP4 inhibitors were associated with higher odds of admission for infection.

COVID-19-associated venous thromboembolism portends worse survival.

Patients with coronavirus disease 2019 (COVID-19) seem to be at high risk for venous thromboembolism (VTE) development, but there is a paucity of data exploring both the natural history of COVID-19-associated VTE and the risk for poor outcomes after VTE development. This investigation aims to explore the relationship between COVID-19-associated VTE development and mortality. A prospectively maintained registry of patients older than 18 years admitted for COVID-19-related illnesses within an academic health care network between March and September 2020 was reviewed. Codes from the tenth revision of the International Classification of Diseases for VTE were collected. The charts of those patients with a code for VTE were manually reviewed to confirm VTE diagnosis. There were 2,552 patients admitted with COVID-19-related illnesses. One hundred and twenty-six patients (4.9%) developed a VTE. A disproportionate percentage of patients of Black race developed a VTE (70.9% VTE v 57.8% non-VTE; P = .012). A higher proportion of patients with VTE expired during their index hospitalization (22.8% VTE v 8.4% non-VTE; P < .001). On multivariable logistic regression analysis, VTE was independently associated with mortality (odds ratio = 3.17; 95% confidence interval, 1.9-5.2; P < .001). Hispanic/Latinx ethnicity was associated with decreased mortality (odds ratio = 0.45; 95% confidence interval, 0.21-1.00; P = .049). Hospitalized patients of Black race with COVID-19 were more prone to VTE development, and patients with COVID-19 who developed in-hospital VTE had roughly nearly threefold higher odds of mortality. Further emphasis should be placed on optimizing COVID-19 anticoagulation protocols to reduce mortality in this high-risk cohort.

Time-Specific Pattern of Iron Deposition in Different Regions in Parkinson's Disease Measured by Quantitative Susceptibility Mapping.

Studies have shown the spatial specificity of cranial iron deposition in different regions in Parkinson's disease (PD). However, the time-specific patterns of iron deposition are not yet clear. The purpose of this study was to investigate the time pattern of iron variations and its clinical relevance in multiple gray matter nuclei in PD using quantitative susceptibility mapping (QSM). Thirty controls and 33 PD patients were enrolled, namely, 11 cases of early stage of PD (ESP) and 22 cases of advanced stage of PD (ASP) according to the Hoehn-Yahr stages. The iron content in the subcortical nuclei covering substantia nigra (SN), red nucleus (RN), head of the caudate nucleus (CN), globus pallidus (GP), and putamen (PT) was measured using QSM, and the clinical symptoms of PD were evaluated by various rating scales. The QSM values in SN, RN, GP, and PT significantly increased in PD patients compared with the controls. Further subgroup comparison with the controls indicated that the iron content in SN and GP (paleostriatum) gradually elevated in the whole disease duration and was related to clinical features. While the iron content in RN and PT (neostriatum) only elevated significantly in ESP patients, further iron deposition was not obvious in ASP patients. Our study confirmed that QSM could be used as a disease biomarker and could be suitable for longitudinal monitoring. However, considering the temporal characteristics of iron deposition in neostriatum, iron deposition in the neostriatum should be paid more attention in the early stage of the disease, even in the preclinical stage, in future research.

Personalized Visual Mapping Assistive Technology to Improve Functional Ability in Persons With Dementia: Feasibility Cohort Study.

BACKGROUND: Mobile health (mHealth) apps using novel visual mapping assistive technology can allow users to develop personalized maps that aid people living with cognitive impairment in the recall of steps needed to independently complete activities of daily living (ADLs), such as bathing, toileting, and dressing. OBJECTIVE: This study aims to determine the feasibility and preliminary impact of an mHealth assistive technology app providing guidance to aid individuals living with cognitive impairment in the recall of steps to independently complete ADLs. METHODS: A total of 14 Veterans (mean age 65 SD 9.5 years; 14/14, 100% male; 10/14, 71.4% Black) and 8 non-Veterans (mean age 78, SD 10.3 years; 5/8, 62.5% male; 8/8, 100% Black) were recruited and enrolled from the Department of Veterans Affairs (VA) and non-VA cognitive care clinics. A visual mapping software program, MapHabit, was used to generate a series of personalized visual map templates focused on ADLs created within the MapHabit app. The visual maps were accessed through a tablet device. A 19-item exit questionnaire was administered to the participants to assess perceived improvement in their functional ability after using the MapHabit system for 3 months. RESULTS: A total of 13 (93%) VA clinic participants and 8 (100%) non-VA clinic participants completed the 3-month study. Baseline cognitive testing indicated impaired to significantly impaired cognitive function. After 3 months of using the MapHabit system, VA clinic participants reported perceived improvement in social engagement (P=.01) and performance of ADLs (P=.05) compared to the baseline, whereas non-VA clinic participants reported improvements in the performance of ADLs (P=.02), mood (P=.04), social engagement (P=.02), and memory (P=.02). All study participants reported they would recommend the MapHabit system to a colleague, and 85% (11/14) of VA and 100% (8/8) of non-VA clinic participants reported a willingness to participate in a future study. CONCLUSIONS: Older VA and non-VA clinic participants with cognitive impairment were willing to use an mHealth app to assist with the completion of ADLs, and they reported positive preliminary effects. A larger study is warranted to assess the efficacy in the setting of a randomized controlled trial.

Opportunity to increase deceased donation for United States veterans.

Recent changes to organ procurement organization (OPO) performance metrics have highlighted the need to identify opportunities to increase organ donation in the United States. Using data from the Organ Procurement and Transplantation Network (OPTN), Scientific Registry of Transplant Recipients (SRTR), and Veteran Health Administration Informatics and Computing Infrastructure Clinical Data Warehouse (VINCI CDW), we sought to describe historical donation performance at Veteran Administration Medical Centers (VAMCs). We found that over the period 2010-2019, there were only 33 donors recovered from the 115 VAMCs with donor potential nationwide. VA donors had similar age-matched organ transplant yields to non-VA donors. Review of VAMC records showed a total of 8474 decedents with causes of death compatible with donation, of whom 5281 had no infectious or neoplastic comorbidities preclusive to donation. Relative to a single state comparison of adult non-VA inpatient deaths, VAMC deaths were 20 times less likely to be characterized as an eligible death by SRTR. The rate of conversion of inpatient donation-consistent deaths without preclusive comorbidities to actual donors at VAMCs was 5.9% that of adult inpatients at non-VA hospitals. Overall, these findings suggest significant opportunities for growth in donation at VAMCs.

Elevated Heme Oxygenase-1 Correlates With Increased Brain Iron Deposition Measured by Quantitative Susceptibility Mapping and Decreased Hemoglobin in Patients With Parkinson's Disease.

Background: Brain iron deposition, low hemoglobin (HGB), and increased heme oxygenase-1 (HO-1) have been implicated in Parkinson's disease (PD). However, the association among them in PD is poorly studied. Objective: To explore the association of the level of HO-1 with brain iron deposition and low level of HGB in PD. Methods: A total of 32 patients with PD and 26 controls were recruited for this study. C57BL/6 male mice were used in generating 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced chronic PD model. The Levels of serum HO-1 and HGB of human subjects and mice were assayed by ELISA, blood routine test, respectively. Quantitative susceptibility mapping (QSM) was used to quantitatively analyze brain iron deposition in human subjects and mice. HO-1 inhibitor (Sn-protoporphyrin, SnPP) was used to suppress the function and expression of HO-1 in PD mice. Correlations between the concentration of serum HO-1 and iron deposition of the region of interests (ROIs), levels of HGB, between the three factors mentioned above, and scores of clinical scales were explored in PD patients. Results: This study revealed significant elevation of the serum HO-1 concentration, iron deposition within bilateral substantial nigra (SN), red nucleus (RN), and putamen (PUT) and decrease of HGB level in PD patients. There was a significantly positive correlation between the serum HO-1 concentration and iron deposition within SN, an inverse correlation between the serum HO-1 concentration and HGB level in PD patients. A significant increase in HO-1 expression of serum and iron deposition in SN was also observed in the PD mouse model, and the SnPP could significantly reduce iron deposition in the SN. Conclusions: The high level of HO-1 may be the common mechanism of iron deposition and low HGB in PD. Therefore, the findings presented in this study indicate that HO-1 correlates with brain iron deposition and anemia in PD.

Familial amyotrophic lateral sclerosis induced by gene mutation of SOD1G142A: a case report.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving both upper and lower motor neurons. The total prevalence of ALS is [2-9]/100,000, with an annual incidence rate of 3/100,000. The disease progresses rapidly and clinically is considered to be progressive degeneration of the upper and lower motor neurons. Although this is a kind of rare disease, the mortality is high once it occurs, which has a great impact on patients and their families. Currently there is no treatment for either the sporadic or familial form. Therefore, it is of great significance to explore the diagnosis and treatment of familial amyotrophic lateral sclerosis (FALS). We report the diagnosis and treatment of a patient with familial ALS caused by mutation of the Cu/Zn superoxide dismutase (SOD1) gene c.425g > C (p.g142a), which is considered rare. We got to know that genetic testing of the patient and his immediate family members assisted in diagnosis and palliative care. Edaravone and Riluzole were used in this case according to the guideline in this case. The progress of the disease was alleviated and the survival experience of patients improved because of this medication administration. The aim of this case report is to provide a reference for the diagnosis and treatment strategy in FALS. What's more, further exploration of treatment using integrated traditional Chinese and Western medicine to delay the disease process has great significance for improved patient outcomes.