Food-Derived Peptides as Promising Neuroprotective Agents: Mechanism and Therapeutic Potential.

Many food-derived peptides have the potential to improve brain health and slow down neurodegeneration. Peptides are produced by the enzymatic hydrolysis of proteins from different food sources. These peptides have been shown to be involved in antioxidant and anti-inflammatory activity, neuro-transmission modulation, and gene expression regulation. Although few peptides directly affect chromatin remodeling and histone alterations, others indirectly affect the neuroprotection process by interfering with epigenetic changes. Fish-derived peptides have shown neuroprotective properties that reduce oxidative stress and improve motor dysfunction in Parkinson's disease models. Peptides from milk and eggs have been found to have anti-inflammatory properties that reduce inflammation and improve cognitive function in Alzheimer's disease models. These peptides are potential therapeutics for neurodegenerative diseases, but more study is required to assess their efficacy and the underlying neuroprotective benefits. Consequently, this review concentrated on each mechanism of action used by food-derived peptides that have neuroprotective advantages and applications in treating neurodegenerative diseases. This article highlights various pathways, such as inflammatory pathways, major oxidant pathways, apoptotic pathways, neurotransmitter modulation, and gene regulation through which food-derived peptides interact at the cellular level.

Technical Feasibility and Clinical Efficacy of Iliac Vein Stent Placement in Adolescents and Young Adults with May-Thurner Syndrome.

PURPOSE: To report technical feasibility and clinical efficacy of iliac vein stent placement in adolescent patients with May-Thurner Syndrome (MTS). MATERIALS AND METHODS: Single-institution retrospective review of the medical record between 2014 and 2021 found 63 symptomatic patients (F = 40/63; mean age 16.1 years, 12-20 years) who underwent left common iliac vein (LCIV) stent placement for treatment of LCIV compression from an overriding right common iliac artery, or equivalent (n = 1, left IVC). 32/63 (50.7%) patients presented with non-thrombotic iliac vein lesions (NIVL). 31/63 (49.2%) patients presented with deep vein thrombosis of the lower extremity and required catheter-directed thrombolysis after stent placement (tMTS). Outcomes include technically successful stent placement with resolution of anatomic compression and symptom improvement. Stent patency was monitored with Kaplan-Meier analysis at 3, 6, 12, 24, and 36 months. Anticoagulation and antiplatelet (AC/AP) regimens were reported. RESULTS: Technical success rate was 98.4%. 74 bare-metal self-expanding stents were placed in 63 patients. Primary patency at 12, and 24-months was 93.5%, and 88.9% for the NIVL group and 84.4% and 84.4% for the tMTS group for the same period. Overall patency for the same time intervals was 100%, and 95.4% for the NIVL group and 96.9%, and 96.9% for the tMTS group. Procedural complication rate was 3.2% (2/63) with no thrombolysis-related bleeding complications. Clinical success was achieved in 30/32 (93.8%) and 29/31 (93.5%) patients with tMTS and NIVL groups, respectively. CONCLUSION: CIV stent placement in the setting of tMTS and NIVL is technically feasible and clinically efficacious in young patients with excellent patency rates and a favorable safety profile.

AI Alone Will Not Reduce the Administrative Burden of Health Care.

This Viewpoint considers AI's limits in solving the medical billing quagmire and argues that standardizing health insurance claim forms and simplifying billing must occur before AI can shoulder the load.

Dynamic and functional linkage between von Willebrand factor and ADAMTS-13 with aging: an Atherosclerosis Risk in Community study.

BACKGROUND: von Willebrand factor (VWF) is a multimeric glycoprotein critically involved in hemostasis, thrombosis, and inflammation. VWF function is regulated by its antigen levels, multimeric structures, and the state of enzymatic cleavage. Population studies in the past have focused almost exclusively on VWF antigen levels in cross-sectional study designs. OBJECTIVE: To identify subjects in the Atherosclerosis Risk in Community study who had persistently low and high VWF antigen over 10 years and to quantify longitudinal changes in the biological activities and cleavage of VWF in these subjects. METHODS: We measured VWF antigen, propeptide, adhesive activities, and cleavage by ADAMTS-13 quantified using a mass spectrometry method that detected the cleaved VWF peptide EQAPNLVY, as well as coagulation factor VIII activity. RESULTS: We determined the mean subject-specific increase in VWF to be 22.0 International Units (IU)/dL over 10 years, with 95% between -0.3 and 59.7 IU/dL. This aging-related increase was also detected in VWF propeptide levels, ristocetin cofactor activity, and VWF binding to collagen. We identified 4.1% and 25.0% of subjects as having persistently low (<50 IU/dL) and high (>200 IU/dL) VWF antigen, respectively. Subjects with persistently low VWF had enhanced ristocetin cofactor activity, whereas those with persistently high VWF had elevated levels of ADAMTS-13, resulting in a comparable rate of VWF cleavage between the 2 groups. CONCLUSIONS: These results provide new information about the effects of aging on VWF antigens and adhesive activity and identify a functional coordination between VWF and the rate of its cleavage by ADAMTS-13.

Assessing afebrile malaria and bed-net use in a high-burden region of India: Findings from multiple rounds of mass screening.

A key obstacle in the fight against malaria is afebrile malaria. It remains undiagnosed and, therefore, is invisible to the health system. Apart from being a serious illness, it contributes to increased transmission. Existing studies in India have not adequately reported afebrile malaria and its determinants, including the use of long-lasting insecticide-treated nets (LLINs). This study used six waves of mass screening, which were conducted by the state government in the high-malaria-burden region of Chhattisgarh, a state in India, in 2020, 2021, and 2022. Each round of data collection included more than 15000 individuals. Descriptive statistics were used to analyse key indicators of malaria prevalence and LLIN use. Multivariate analyses were performed to identify the determinants of afebrile malaria and LLIN use. Malaria prevalence in the afebrile population varied from 0.6% to 1.4% across the different waves of mass screening. In comparison, malaria positivity among febrile individuals was greater than 33% in each wave. Afebrile malaria contributed to 19.6% to 47.2% of the overall malaria burden in the region. Indigenous communities (scheduled tribes) were more susceptible to malaria, including afebrile malaria. Individuals using LLINs were less likely to be affected by afebrile malaria. Overall, 77% of the individuals used LLINs in early monsoon season, and in winter the rate was lower at 55%. LLIN use was significantly associated with the number of LLINs the households received from the government. Although fever continues to be a primary symptom of malaria, afebrile malaria remains a significant contributor to the malaria burden in the region. The free distribution of LLINs should be expanded to include high-burden populations. Global policies must include strategies for surveillance and control of afebrile malaria in high-burden areas.

Role of Mitanin community health workers in improving complementary feeding practices under scaled-up home-based care of young children in a rural region of India.

BACKGROUND: A large proportion of young children in developing countries receive inadequate feeding and face frequent infections. Global research has established the need for improving feeding practices and management of child illnesses. Interventions involving home visits by community health workers (CHWs) for caregiver education have been attempted in many countries. Indian government rolled out an intervention called home-based care of young children (HBYC) in 2018 but no studies exist of its scaled-up implementation. The current study was aimed at assessing the coverage of HBYC in Chhattisgarh state where it has been implemented through 67,000 rural CHWs known as Mitanins. METHODS: This cross-sectional study was based on a primary household survey. Households with children in 7-36 months age were eligible for survey. A multi-stage sample of 2646 households was covered. Descriptive analyses were performed and key indicators were reported with 95% confidence intervals. To find out the association between caregiver practices and receiving advice from the CHWs, multivariate regression models were applied. RESULTS: Overall, 85.1% children in 7-36 months age received at least one home visit from a CHW within the preceding three months. Complementary feeding had been initiated for 67% of children at six months age and the rate was 87% at eight months age. Around one-third of the children were fed less than three times a day. Around 41% households added oil in child's food the preceding day. CHWs were contacted in 73%, 69% and 61% cases of diarrhea, fever and respiratory infections respectively in children. Among those contacting a CHW for diarrhea, 88% received oral rehydration. The adjusted models showed that receiving advice from CHWs was significantly associated with timely initiation of complementary feeding, increasing the frequency of feeding, increasing diet diversity, addition of oil, weighing and consumption of food received from government's supplementary nutrition programme. CONCLUSIONS: Along with improving food security of households, covering a large share of young children population with quality home visits under scaled-up CHW programmes can be the key to achieving improvements in complementary feeding and child care practices in developing countries.

Predicting Delayed Shock in Multisystem Inflammatory Disease in Children: A Multicenter Analysis From the New York City Tri-State Region.

OBJECTIVES: Patients with multisystem inflammatory disease in children (MIS-C) are at risk of developing shock. Our objectives were to determine independent predictors associated with development of delayed shock (≥3 hours from emergency department [ED] arrival) in patients with MIS-C and to derive a model predicting those at low risk for delayed shock. METHODS: We conducted a retrospective cross-sectional study of 22 pediatric EDs in the New York City tri-state area. We included patients meeting World Health Organization criteria for MIS-C and presented April 1 to June 30, 2020. Our main outcomes were to determine the association between clinical and laboratory factors to the development of delayed shock and to derive a laboratory-based prediction model based on identified independent predictors. RESULTS: Of 248 children with MIS-C, 87 (35%) had shock and 58 (66%) had delayed shock. A C-reactive protein (CRP) level greater than 20 mg/dL (adjusted odds ratio [aOR], 5.3; 95% confidence interval [CI], 2.4-12.1), lymphocyte percent less than 11% (aOR, 3.8; 95% CI, 1.7-8.6), and platelet count less than 220,000/uL (aOR, 4.2; 95% CI, 1.8-9.8) were independently associated with delayed shock. A prediction model including a CRP level less than 6 mg/dL, lymphocyte percent more than 20%, and platelet count more than 260,000/uL, categorized patients with MIS-C at low risk of developing delayed shock (sensitivity 93% [95% CI, 66-100], specificity 38% [95% CI, 22-55]). CONCLUSIONS: Serum CRP, lymphocyte percent, and platelet count differentiated children at higher and lower risk for developing delayed shock. Use of these data can stratify the risk of progression to shock in patients with MIS-C, providing situational awareness and helping guide their level of care.

Pediatric Croup Due to Omicron Infection Is More Severe Than Non-COVID Croup.

OBJECTIVE: Croup due to infection with the omicron variant of COVID is an emerging clinical entity, but distinguishing features of omicron croup have not yet been characterized. We designed a study to compare the clinical features of croup patients presenting to the pediatric emergency department pre-COVID pandemic with COVID-positive croup patients who presented during the initial omicron surge. METHODS: This was a retrospective observational cohort study of children 0 to 18 years old who presented to our urban, tertiary care pediatric emergency department with symptoms of croup. The study compared a cohort of croup patients who presented in the year before the onset of the COVID pandemic to a cohort of COVID-positive croup patients who presented during the initial omicron surge. The primary outcomes included illness severity and treatments required in the emergency department. The secondary outcome was hospital admission rate. RESULTS: There were 499 patients enrolled in the study, 88 in the omicron croup cohort and 411 in the classic croup cohort. Compared with the classic croup patients, omicron croup patients were more likely to present with stridor at rest (45.4% vs 31.4%; odds ratio [OR], 1.82; confidence interval [CI], 1.14-2.91) and hypoxia (3.4% vs 0.5%; OR, 7.22; CI, 1.19-43.86). Omicron croup patients required repeat dosing of inhaled epinephrine in the emergency department more often (20.4% vs 6.8%; OR, 3.51; CI, 1.85-6.70), and they were more likely to require respiratory support (9.1% vs 1.0%; OR, 10.18; CI, 2.99-34.60). Admission rates were significantly higher for omicron croup patients than for classic croup patients (22.7% vs 3.9%; OR, 7.26; CI, 3.58-14.71), and omicron croup patients required intensive care more frequently (5.7% vs 1.5%; OR, 4.07; CI, 1.21-13.64). CONCLUSIONS: Pediatric patients with omicron croup develop more severe disease than do children with classic croup. They are more likely to require additional emergency department treatments and hospital admission than patients with croup before the COVID pandemic.

Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) is an uncommon but emerging syndrome related to SARS-CoV-2 infection. While the presentation of MIS-C is generally delayed after exposure to the virus that causes coronavirus 2019, both MIS-C and Kawasaki disease (KD) share similar clinical features. Multisystem inflammatory syndrome in children poses a diagnostic and therapeutic challenge given the lack of definitive diagnostic tests and a paucity of evidence regarding treatment modalities. We review the clinical presentation, diagnostic evaluations, and management of MIS-C and compare its clinical features to those of KD.

A designated trauma social worker improves coordination of patient care by coordinating ancillary consults.

Trauma patients face unique challenges that require coordination by social workers knowledgeable in the intricacies of trauma patient psychosocial support which is often achieved by obtaining ancillary consultations. The impact of employing a designated trauma social worker (DTSW) in the utilization of these consults has not been described. A retrospective review was conducted of trauma patients admitted to an academic, urban Level 1 trauma center. The pre-intervention cohort (n = 272) corresponded to patients admitted before the presence of a DTSW (01/2013 to 06/2013), while the post-intervention cohort (n = 282) corresponded to patients admitted afterward (09/2015 to 01/2016). Data collection included demographics, injury profile, and types of interdisciplinary or therapy consultations. Post-intervention patients were found to be older and admitted with more injuries. Supportive care, physical therapy and occupational therapy consultations were more likely to be obtained in the post-intervention cohort. Hospital length of stay remained unchanged. This study suggests that the implementation of a DTSW significantly facilitates the utilization of interdisciplinary consultations. Length of stay remains unchanged, suggesting that a DTSW helps to coordinate care in a timely manner without increasing the hospital stay. DTSW implementation may be considered in trauma centers where one does not currently exist.

Blink detection and magnetic force generation for correction of lagophthalmos, with specific regard to implant compatibility testing.

PURPOSE: The overall goal was to restore a normal and synchronous blink in unilateral lagophthalmos. We describe the biocompatibility profiling of a novel ferromagnetic implant used for electromagnetic eyelid force generation. METHODS: A non-contact blink detection system and an electromagnetic stimulation system were designed and tested. A modified Lester-Burch speculum equipped with strain gauge technology was used in blinking force measurement. Samarium-cobalt magnets were prototyped and coated with parylene-C. Biocompatibility testing was performed using NIH/3T3 mouse fibroblast cells with MTT colorimetric assay cytotoxic quantification. OUTCOME MEASURES: Cellular viability and interleukin concentrations. RESULTS: Our system was capable of detecting 95.5 ± 3.6% of blinks in various lighting conditions. Using our force measuring device, the difference between non-paralyzed and paralyzed orbicularis oculi (OO) for normal and forceful blinking closure was 40.4 g and 101.9 g, respectively. A 16.6 × 5.0 × 1.5 mm curved shaped samarium cobalt eyelid implant was successfully developed and showed a reproducible blink at 100 ms with full corneal coverage with external eyelid taping. Compared to gold weights, parylene-C coated samarium cobalt implants showed not only excellent cell viability (82.0 ± 4.9% vs. 88.4 ± 0.9%, respectively, p > .05), but also below detection threshold for pro-inflammatory marker concentrations (interleukin-6 < 2 pg/mL and interleukin-10 < 3 pg/mL). CONCLUSIONS: We demonstrated excellent in-vitro biocompatibility of our parylene-C coated samarium cobalt implants. We believe that our novel approach can improve the quality-of-life of affected individuals and provides new understanding of blinking biomechanics.

Electronic Health Records as Biased Tools or Tools Against Bias: A Conceptual Model.

Policy Points Electronic health records (EHRs) are subject to the implicit bias of their designers, which risks perpetuating and amplifying that bias over time and across users. If left unchecked, the bias in the design of EHRs and the subsequent bias in EHR information will lead to disparities in clinical, organizational, and policy outcomes. Electronic health records can instead be designed to challenge the implicit bias of their users, but that is unlikely to happen unless incentivized through innovative policy. CONTEXT: Health care delivery is now inextricably linked to the use of electronic health records (EHRs), which exert considerable influence over providers, patients, and organizations. METHODS: This article offers a conceptual model showing how the design and subsequent use of EHRs can be subject to bias and can either encode and perpetuate systemic racism or be used to challenge it. Using structuration theory, the model demonstrates how a social structure, like an EHR, creates a cyclical relationship between the environment and people, either advancing or undermining important social values. FINDINGS: The model illustrates how the implicit bias of individuals, both developers and end-user clinical providers, influence the platform and its associated information. Biased information can then lead to inequitable outcomes in clinical care, organizational decisions, and public policy. The biased information also influences subsequent users, amplifying their own implicit biases and potentially compounding the level of bias in the information itself. The conceptual model is used to explain how this concern is fundamentally a matter of quality. Relying on the Donabedian model, it explains how elements of the EHR design (structure), use (process), and the ends for which it is used (outcome) can first be used to evaluate where bias may become embedded in the system itself, but then also identify opportunities to resist and actively challenge bias. CONCLUSIONS: Our conceptual model may be able to redefine and improve the value of technology to health by modifying EHRs to support more equitable data that can be used for better patient care and public policy. For EHRs to do this, further work is needed to develop measures that assess bias in structure, process, and outcome, as well as policies to persuade vendors and health systems to prioritize systemic equity as a core goal of EHRs.

Coverage of home-based newborn care and screening by ASHA community health workers: Findings from a household survey in Chhattisgarh state of India.

Background and Objectives: Community health workers known as Accredited Social Health Activists (ASHAs) provide home visits for home-based newborn care (HBNC) in India. The objectives of the study were to assess coverage of HBNC, to assess current practices of newborn care by the care providers and to assess status of screening of sick newborns by ASHAs in rural Chhattisgarh. Methods: The study was a quantitative cross-sectional study. Multi-stage random sampling was applied to draw a representative sample from rural Chhattisgarh. The survey collected primary data of 1928 newborns by interviewing the caregivers. Descriptive statistical analysis using cross tabulations was performed. Confidence intervals at 95% were computed for key indicators. Results: ASHAs were present during 84.3% of the deliveries. 74.1% newborns received the designated six home visits from ASHAs whereas 3.6% newborns did not receive any visits. Coverage of different important messages ranged from 74% to 90%. Around 95% of newborns were screened by ASHAs for signs of sickness. ASHAs identified 12.9% of newborns as sick. Of the identified sick newborns, 48.1% were referred by ASHAs to health facilities, whereas 34.7% were treated directly by ASHAs by using amoxicillin. Early initiation of breastfeeding was reported for 85.4% of newborns and skin-to-skin contact was practiced for 63.6%. Conclusions: ASHAs were able to achieve an adequate coverage of HBNC in rural Chhattisgarh. Uptake of desired newborn care practices by caregivers was found. Identification of sick newborn was also adequate. Further research is recommended to identify factors facilitating the coverage under HBNC.

Perspectives on the Role of APOE4 as a Therapeutic Target for Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease that is coupled with chronic cognitive dysfunction. AD cases are mostly late onset, and genetic risk factors like the Apolipoprotein E (APOE) play a key role in this process. APOE ɛ2, APOE ɛ3, and APOE ɛ4 are three key alleles in the human APOE gene. For late onset, APOE ɛ4 has the most potent risk factor while APOE ɛ2 plays a defensive role. Several studies suggests that APOE ɛ4 causes AD via different processes like neurofibrillary tangle formation by amyloid-ß accumulation, exacerbated neuroinflammation, cerebrovascular disease, and synaptic loss. But the pathway is still unclear that which actions of APOE ɛ4 lead to AD development. Since APOE was found to contribute to many AD pathways, targeting APOE ɛ4 can lead to a hopeful plan of action in development of new drugs to target AD. In this review, we focus on recent studies and perspectives, focusing on APOE ɛ4 as a key molecule in therapeutic strategies.

Bridging the divide between physicians and administrators during COVID-19.

This article describes the tension that the coronavirus disease 2019 (COVID-19) pandemic brought up between administrators and physicians and offers a potential set of solutions to deal with it.

Incidence and Timing of Thrombosis After the Norwood Procedure in the Single-Ventricle Reconstruction Trial.

Background Thrombosis is common in infants undergoing staged surgeries for single-ventricle congenital heart disease. The reported incidence and timing of thrombosis varies widely, making it difficult to understand the burden of thrombosis and develop approaches for prevention. We aimed to determine the timing and cumulative incidence of thrombosis following the stage I Norwood procedure and identify clinical characteristics associated with thrombosis. Methods and Results We analyzed data from the Pediatric Heart Network Single Ventricle Reconstruction trial from 2005 to 2009 and identified infants with first-time thrombotic events. In 549 infants, the cumulative incidence of thrombosis was 21.2% (n=57) from stage I through stage II. Most events occurred during stage I (n=35/57, 65%), with a median time to thrombosis of 15 days. We used a Cox proportional hazards model to estimate the association of clinical variables with thrombosis. After adjusting for baseline variables, boys had a higher hazard of thrombosis (adjusted hazard ratio [HR], 2.69; 95% CI, 1.44-5.05; P=0.002), non-hypoplastic left heart syndrome cardiac anatomy was associated with a higher early hazard of thrombosis (adjusted HR, 3.93; 95% CI, 1.89-8.17; P<0.001), and longer cardiopulmonary bypass time was also associated with thrombosis (per 10-minute increase, adjusted HR, 1.07; 95% CI, 1.01-1.12; P=0.02). Lower oxygen saturation after the Norwood procedure increased the hazard for thrombosis in the unadjusted model (HR, 1.08; 95% CI, 1.02-1.14; P=0.011). Conclusions Thrombosis affects 1 in 5 infants through Stage II discharge, with most events occurring during stage I. Male sex, non-hypoplastic left heart syndrome anatomy, longer cardiopulmonary bypass time, and lower stage I oxygen saturation were associated with thrombosis.

Could COVID-19 become a policy tipping point? a Q&A with Kavita K. Patel, MD, MS.

To mark the 25th anniversary of the journal, each issue in 2020 will include an interview with a health care thought leader. The October issue features a conversation with Kavita K. Patel, MD, MS, nonresident fellow at The Brookings Institution and editorial board member of AJMC®.