Variation In Disease Severity Research Articles

ITRAQ‐based proteomic analysis reveals myeloperoxidase (MPO) as a diagnostic and prognostic biomarker of cognitive decline in Parkinson’s disease

AbstractBackgroundParkinson’s disease (PD) is the second most common progressive neurodegenerative disorder and is characterized by loss of dopaminergic neurons, leading to debilitating motor, cognitive, and behavioral symptoms. At present, there are no biological markers for antemortem PD diagnosis.MethodsTo identify potential blood biomarkers of PD, Isobaric Tags for Relative and Absolute Quantitation (iTRAQ)‐based mass spectrometry (MS) was performed to characterize alterations of serum proteins amongst PD patients of varying disease severity according to their Hoehn and Yahr (HY) stages. Sera of mild PD (HY 1.5‐2.0, n = 10), severe PD (HY 3.0‐4.0, n = 10) patients and healthy controls (n = 10) were enriched and subjected to 2D LC‐MS/MS for proteomic analysis. Candidate protein biomarkers were identified based on the relative abundance of the identified tryptic peptides, and were validated using ELISA in a validation set consisting of 103 early PD and 48 healthy controls (HC). Association with clinical outcomes were analyzed at cross‐sectional and longitudinal timepoints.ResultsA total of 96 proteins in the mild PD group and 78 proteins in the severe PD group were found to differ significantly between PD patients and healthy controls. Thirteen proteins were common between the mild PD and severe PD groups and were chosen for further analysis. These dysregulated proteins represent a diversity of biological processes, including innate immune response, complement activation, cytoskeleton reorganization and response to oxidative stress. Of which, myeloperoxidase showed higher serum levels in mild and severe PD. In the validation PD cohort, higher MPO was significantly associated with worse executive function over 4 years.ConclusionUsing an unbiased proteomic approach, we identified serum MPO (a marker of oxidative stress) as a promising biomarker for PD. Our results suggest that MPO could also potentially be an early marker for cognitive decline in PD. Further studies with larger cohorts are needed to validate these findings.

Assessment of trec and krec levels in COVID-19 patients with varying disease severity

According to the WHO data, the number of infected people exceeded 765.2 million people during the COVID-19 pandemic. The severity of patient’s condition is determined by immune system hyperactivation. Activation of T- and B-lymphocyte subsets plays a prominent role in the control of infectious process. A content of small circular DNA molecules — T-cell receptor excision circles (TREC — T-cell receptor excision circles) and B-cell (“kappa”) excision rings (KREC — Kappa-deleting recombination excision circles) — in the peripheral blood can be used as a marker of the functionally active T and B cells maturation. The purpose of this work is to quantify peripheral blood TREC and KREC level in patients with the new coronavirus infection COVID-19 of varying severity.Materials and methods.The material consisted of 1028 blood samples from patients with a confirmed diagnosis of COVID-19, as well as 717 blood samples from apparently healthy volunteers. The content of TREC and KREC DNA fragments in the total DNA fraction was assessed by quantitative Real-time PCR using the “TREC/KREC-AMP PS” test system (St. Petersburg Pasteur Institute, Russia). Blood cell phenotyping was carried out using flow cytometry.Results.TREC/KREC levels were significantly reduced in COVID-19 patients (p 0.0001 at 95% CI). A significant direct correlation was established between the levels of peripheral blood TREC molecules and level of CD45+CD3+CD19–T cells (r = 0.59, p 0.0001), as well as between KREC level and count of CD45+CD3–CD19+B cells (r = 0.66, p 0.0001). The level of TREC molecules in patients with severe vs. moderate infection was significantly reduced in patients aged 30–39 years old (p = 0.0404) and 40–49 years old (p = 0.0356). The negative correlation between severity of COVID-19 clinical manifestations and TREC level in the blood of patients in 30–49 year age group indicates about an opportunity of using this analyte as a diagnostic and prognostic laboratory marker of patient’s condition. A simple PCR analysis algorithm makes it relevant to use the described method for assessing a state of immunity in coronavirus patients in the context of systemic negative impact of the SARS-CoV-2 virus on human organism.

From control to remission: Empowering change in type 2 diabetes care

Madam, Pakistan currently ranks third globally in terms of its diabetic population, with approximately 33 million diagnosed cases of Type 2 Diabetes Mellitus (T2DM). Additionally, there are 11 million individuals living with impaired glucose tolerance and 8.9 million people in Pakistan are unaware that they have diabetes1. Poor dietary habits and sedentary lifestyles are the major factors contributing to Pakistan's high prevalence of diabetes2. Metformin is commonly prescribed as the leading therapeutic choice for type 2 diabetes, either as a standalone treatment or combined with insulin or other glucose-lowering therapies3. However, despite adherence to guidelines-based practices, a significant number of individuals fail to achieve remission in T2DM which has led to the exploration of alternative approaches. The DiRECT trial, which primarily involved ethnically white participants, aimed to reverse the diagnosis of T2DM and restore normal metabolic features through a weight-loss protocol. Within 12 months, nearly 50% of the participants achieved remission to a non-diabetic state and discontinued antidiabetic medications. The trial also highlighted the significant role of visceral fat in the development and remission of T2DM 4. However, the trial's lack of South Asian participants and the well-documented variations in disease severity and average body fat levels between South Asians and other populations raised concerns about its relevance to this particular group. To address this, the STANDby trial was conducted which showed that the remission rates observed in UK-based South Asians were similar to those in white cohorts5. These trials have demonstrated the possibility of achieving T2DM remission, particularly within the first six years following diagnosis. Given these findings, we propose that implementing this weight management program in Pakistan could be a suitable alternative to the current guidelines. This program effectively targets the key factors contributing to the high prevalence of diabetes in the country and emphasizes the importance of facilitating the remission of T2DM rather than just disease control. By addressing dietary habits, promoting physical activity, and targeting visceral fat reduction, this protocol can potentially bring about significant improvements in T2DM outcomes in Pakistan.

Development and content validation of a sunlight exposure diary in patients with erythropoietic protoporphyria

BackgroundErythropoietic protoporphyria is a rare, inherited disorder presenting in early childhood with severe, painful phototoxicity. EPP has significant impacts on health-related quality of life, though there is variable disease severity. Accurately capturing how much time individuals with EPP can spend outdoors before they develop symptoms is critical to understanding HRQoL and measuring therapeutic response. Therefore, the goal of this study was to develop a comprehensive and content valid sun exposure diary to assess the efficacy of new therapies in individuals with EPP.MethodsQualitative interviews were conducted with adult and adolescent EPP participants, as well as five clinical experts, to obtain their input on the content of an existing sun exposure diary. Revisions to the diary were made based on evidence generated in cognitive debriefing interviews analyzed in eight consecutive groups of EPP participant.ResultsInterviews were conducted with 17 adults and 6 adolescents with EPP. The average age of adults was 40 years and of adolescents was 14 years. Clinical experts thought the original diary needed clarification on the description of symptoms, how time outdoors was captured, and the distinction between direct vs. indirect sunlight. Participants with EPP also noted these items needed revision, and that the distinction between prodromal symptoms and full reaction symptoms should be clarified. In the final diary version, participants with EPP found most items to be clear and easy to complete/think about. Seventy-six percent of participants (13/17) asked thought the diary was easy to complete. The remainder thought the majority of the diary was easy to complete with the exception of select questions.ConclusionsEvaluating a new treatment for EPP requires accurately capturing time in sunlight and symptoms in this unique disorder. The newly developed sun exposure diary is content valid and can be used to assess important aspects of symptoms and daily life and therefore evaluate clinically meaningful therapeutic response.

Longitudinal Analysis of Antibody Response Following SARS-CoV-2 Infection Depending on Disease Severity: A Prospective Cohort Study.

Severe coronavirus disease 19 (COVID-19) is characterized by a dysregulated inflammatory response, with humoral immunity playing a central role in the disease course. The objective of this study was to assess the immune response and the effects of vaccination in recovered individuals with variable disease severity up to one year following natural infection. A prospective cohort study was conducted including patients with laboratory-confirmed COVID-19. Disease severity was classified as mild, moderate, and severe based on clinical presentation and outcomes. Anti-RBD (receptor binding domain) and neutralizing antibodies were evaluated at multiple timepoints during the first year after COVID-19 diagnosis. A total of 106 patients were included; of them, 28 were diagnosed with mild, 38 with moderate, and 40 with severe disease. At least one vaccine dose was administered in 58 individuals during the follow-up. Participants with mild disease presented significantly lower anti-RBD and neutralizing antibodies compared to those with moderate and severe disease up to the 3rd and 6th months after the infection, respectively. After adjusting for covariates, in the third month, severe COVID-19 was associated with significantly higher anti-RBD (β: 563.09; 95% confidence intervals (CI): 257.02 to 869.17) and neutralizing (β: 21.47; 95% CI: 12.04 to 30.90) antibodies. Among vaccinated individuals, at the 12th month, a history of moderate disease was associated with significantly higher anti-RBD levels (β: 5615.19; 95% CI: 657.92 to 10,572.46). Severe COVID-19 is associated with higher anti-RBD and neutralizing antibodies up to 6 months after the infection. Vaccination of recovered patients is associated with a remarkable augmentation of antibody titers up to one year after COVID-19 diagnosis, regardless of disease severity.

Abstract 14112: Reproductive Risk Factors and Pulmonary Arterial Hypertension in Women

Introduction: Pulmonary arterial hypertension (PAH) is a devastating disease that affects women more often than men. The female predominance has increased over time; recent U.S. cohorts demonstrate a female:male ratio of nearly 4:1. The role of women-specific risk, such as reproductive exposures, is poorly understood in the pathophysiology of PAH. Hypothesis/Goals: We hypothesize that reproductive exposures influence the development and/or severity of PAH in women. We sought to investigate the role of reproductive factors and contribution of exogenous estrogen exposures to PAH onset and severity. Methods: Using reproductive history/exposure questionnaires from 390 women with PAH, enrolled in both the PAH Biobank and United States Pulmonary Hypertension Scientific Registry, we conducted linear regression analyses to assess the association between individual disease severity variables, as well as REVEAL Lite 2.0 scores, and patient reported reproductive variables as the predictors (Table 1). We adjusted for potential confounders including age, race, BMI, and PAH sub-group (idiopathic, heritable, or associated). Results: We found that younger menopause age, less than or equal to 40 years old, associates with a lower cardiac index (CI) at diagnosis [β -0.57, p 0.02]. The association persisted when controlling for use of hormone replacement therapy (HRT). There was a trend toward lower CI in those with menopause age of 41 to 50 years old, but not statistically significant [p 0.10]. Ever use of HRT was associated with a higher pulmonary vascular resistance [β 1.6, p 0.05] and lower CI [β -0.28, p 0.01] at diagnosis. Conclusion: Premature menopause (age less than 40 years) and ever use of HRT associate with worse hemodynamics at diagnosis in women with PAH, including lower cardiac index. Further investigations into reproductive exposures may offer an opportunity for more comprehensive risk factor screening and modification by physicians treating PAH patients.

Dietary Behaviors and Social Determinants of Health Among Adults Living with Sickle Cell Disease

Background: Social determinants of health (SDoH) may impact outcomes in sickle cell disease (SCD), and recent literature reports that particular SDoH, such as food insecurity and housing insecurity, may impact diet choices for individuals with SCD. Notably, health outcomes in SCD are linked to diet choices through increased protein and caloric needs, and through nutrients, such as polyphenols, omega fatty acids and micronutrients, which are involved in SCD pathophysiology. The connection between SDoH and diet quality may occur through multiple pathways including access to food, affordability, chronic pain and psychosocial factors at the individual and family level. Importantly, the impact of this connection may relate to outcomes such as pain frequency, hospitalizations, and SCD pathophysiologic biomarkers, such as inflammation. Study Design and Methods: The Diet and SCD Study (NCT: 05170412) is an observational mixed-methods study initiated in 2021 at the National Institutes of Health Clinical Center (NIH CC) in Bethesda MD with a target sample of 75 adults living with SCD in the United States. The purpose of the study is to evaluate associations between SDoH (food insecurity, neighborhood food access, education, employment, healthcare access), dietary intake, and population health related outcomes among adults living with SCD. Study inclusion criteria consists of adults (≥18 years of age) residing within the United States at the time of screening who have a confirmed diagnosis of sickle cell disease with any genotype, and are not hospitalized at the time of enrollment. To ensure participation from adults in diverse regions of the United States, the study has a hybrid design of in-person and telehealth procedures. In-person protocol visits are conducted at the NIH CC. The CC clinical visit includes a clinical assessment, anthropometric measurements, phlebotomy, as well as monitored/proctored electronic surveys that collect SDoH and disease severity variables. The telehealth protocol visit includes a virtual clinical assessment, phlebotomy at a local laboratory center, as well as the same monitored/proctored electronic surveys completed by CC clinical visit participants. A dietary behavior semi-structured interview is conducted at both the CC clinical visit and telehealth protocol visit to garner participants' personal stories related to food choices and diet. Laboratory variables include SCD disease specific markers, amino acid levels, and measurement of inflammatory cytokine markers. All participants undergo two unannounced phone-administered 24-hour dietary recall interviews with trained NIH nutrition staff to measure recent dietary intake. Data from 24-hour recall interviews are used to determine fluid, caloric, macro and micronutrient, and polyphenol intake. Usual dietary intake of foods of potentially related to SCD pathophysiology (cruciferous vegetables and thiocyanate-rich foods) is measured through self-administered electronic 12-month food frequency questionnaires. Primary objectives are to evaluate social determinants of health related to food security and access relevant to disease severity among adults living with sickle cell disease in the U.S. Secondary outcomes are to evaluate the association of dietary quality, specific dietary nutrient intake and serum levels, including amino acids and polyphenols, with disease severity. Tertiary outcomes include evaluating inflammatory and glucometabolic biomarkers with measures of social determinants of health. When completed, the Diet and SCD study will provide important information on the associations between SDoH, dietary quality, inflammatory biomarkers and disease severity for adults living with SCD and provide initial data for future cohort and intervention studies.

3 Ethnoracial Differences in Anchor Agreement and MCID Estimation in Alzheimer’s Disease

Objective:Alzheimer’s disease (AD) clinical trials lack diverse representation, limiting their generalizability. In addition, the clinical meaningfulness of observed changes during treatment may vary as a function of participant characteristics. Defining meaningful change in AD within diverse ethnoracial groups is therefore greatly needed. Meaningful change in AD trials can be assessed by three different anchors: participants, informants, or clinicians. Previous research has suggested that estimations of the minimal clinically important difference (MCID) vary by disease severity, choice of anchor, and anchor agreement. These relationships have been studied primarily within non-Hispanic white (NHW) samples. This project evaluates anchor-based MCID within and across the three most prevalent ethnoracial groups in the United States, non-Hispanic White (NHW), Hispanic/Latino (H/L), and Black/African-American (B/AA).Participants and Methods:Data from the National Alzheimer’s Coordinating Center Uniform Dataset (NACC UDS) were used to investigate MCID within older adults (ages 50+) diagnosed as cognitively normal or cognitively impaired due to suspected AD. Data were taken from all versions of the UDS and consisted of all available participants with two consecutive annual visits. The identified sample (N=22,043) is approximately 83.6% NHW, 4.7% H/L, and 11.7% B/AA. Participant, informant, and clinician anchor variables were utilized to compare proportions of anchor agreement within and across ethnoracial groups. MCID on the Mini-Mental State Exam (MMSE) was estimated within each ethnoracial group and compared across the independent variables of anchor agreement and disease severity (cognitively normal (CN), mild cognitive impairment (MCI), and dementia) in 2x3 ANOVAs.Results:Participant age (M = 71.56, SD = 9.03) did not significantly differ across ethnoracial groups; years of education significantly differed across groups, p < .001, with NHW (M=15.83 SD=3.05), H/L (M=12.49, SD=5.01), and B/AA (M=14.42, SD=3.22). Across all three anchors (participant, informant, clinician), unanimous agreement about the presence or absence of a decline in functioning was present in about 75.1% of the full sample. To further explore agreement differences across groups, anchor agreement was classified into a 3-level variable: 1) agreement that the participant remained stable over time, 2) agreement that the participant declined, and 3) disagreement. The proportion of each level within each ethnoracial group was significantly different, (x2(4, n = 22,043) = 179.16, p < .001, phi = .09, NHW (34.5% agreement-stable, 41.4% agreement-declined, 24.1% disagreement), H/L (30.5%, 42.6%, 26.9%, respectively), and B/AA (42.2%, 28.1%, 29.7%, respectively). MCID estimates on the MMSE followed similar trends within each ethnoracial group. There was a significant main effect of disease severity, such that MCID estimates increased in magnitude with increasing disease severity. There were no significant main effects of anchor agreement for any ethnoracial group. Within the NHW sample only, an interaction effect between diagnostic severity and anchor agreement was significant (p = .007).Conclusions:Across ethnoracial groups, MCID estimates on the MMSE are reliably influenced by the severity of disease. However, the benefit of anchor-based MCID estimates may vary by ethnoracial group with respect to both anchor choice and use of anchor agreement. The origins of anchor disagreement and perceived stability in functioning warrant further exploration.

Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits

Phenotypic heterogeneity in monogenic neurodevelopmental disorders can arise from differential severity of variants underlying disease, but how distinct alleles drive variable disease presentation is not well understood. Here, we investigate missense mutations in DNA methyltransferase 3A (DNMT3A), a DNA methyltransferase associated with overgrowth, intellectual disability, and autism, to uncover molecular correlates of phenotypic heterogeneity. We generate a Dnmt3aP900L/+ mouse mimicking a mutation with mild to moderate severity and compare phenotypic and epigenomic effects with a severe R878H mutation. P900L mutants exhibit core growth and behavioral phenotypes shared across models but show subtle epigenomic changes, while R878H mutants display extensive disruptions. We identify mutation-specific dysregulated genes that may contribute to variable disease severity. Shared transcriptomic disruption identified across mutations overlaps dysregulation observed in other developmental disorder models and likely drives common phenotypes. Together, our findings define central drivers of DNMT3A disorders and illustrate how variable epigenomic disruption contributes to phenotypic heterogeneity in neurodevelopmental disease.

A New Test Method for Biochemical Analysis of Plasmalogens in Dried Blood Spots and Erythrocytes From Patients With Peroxisomal Disorders.

Measurement of plasmalogens is useful for the biochemical diagnosis of rhizomelic chondrodysplasia punctata (RCDP) and is also informative for Zellweger spectrum disorders (ZSD). We have developed a test method for the simultaneous quantitation of C16:0, C18:0, and C18:1 plasmalogen species and their corresponding fatty acids in dried blood spots (DBS) and erythrocytes (RBC) by using capillary gas chromatography-mass spectrometry (GC-MS). Normal reference ranges for measured markers and 10 calculated ratios were established by the analysis of 720 and 473 unaffected DBS and RBC samples, respectively. Determination of preliminary disease ranges was made by using 45 samples from 43 unique patients: RCDP type 1 (DBS: 1 mild, 17 severe; RBC: 1 mild, 6 severe), RCDP type 2 (DBS: 2 mild, 1 severe; RBC: 2 severe), RCDP type 3 (DBS: 1 severe), RCDP type 4 (RBC: 2 severe), and ZSD (DBS: 3 severe; RBC: 2 mild, 7 severe). Postanalytical interpretive tools in Collaborative Laboratory Integrated Reports (CLIR) were used to generate an integrated score and a likelihood of disease. In conjunction with a review of clinical phenotype, phytanic acid, and very long-chain fatty acid test results, the CLIR analysis allowed for differentiation between RCDP and ZSD. Data will continue to be gathered to improve CLIR analysis as more samples from affected patients with variable disease severity are analyzed. The addition of DBS analysis of plasmalogens may allow for at-home specimen collection and second-tier testing for newborn screening programs. This article is protected by copyright. All rights reserved.

Severe Thrombocytopenia Due to Bone Marrow Failure in Children With Dyskeratosis Congenita Does Not Respond to Eltrombopag Treatment: Case Series.

Dyskeratosis congenita is a rare inherited disease with classic cutaneous symptoms, sometimes accompanied with more severe extracutaneous manifestations such as bone marrow failure, which can be lethal. Eltrombopag is an orally available thrombopoietin receptor agonist in clinical use for increasing platelet levels in patients with immune thrombocytopenia and aplastic anemia. Here, 3 pediatric patients with dyskeratosis congenita are presented with varying disease severity, in which off-label eltrombopag treatment had no clinical effect on bone marrow failure. This, in addition to the negative results in a previous case report, supports the preclusion of eltrombopag use in dyskeratosis congenita.

Expression Pattern of Cholesterol 25-Hydroxylase and Serum Level of 25-Hydroxycholesterol and Relevant Inflammatory Cytokines in Patients with Varying Disease Severity of COVID-19.

Cholesterol 25-hydroxylase (CH25H) and its product 25-hydroxycholesterol (25HC) showed antiviral effects against various viruses in vitro. CH25H expression is regulated in mice by pro-inflammatory cytokine interferons (IFNs) in mice but data on its possible correlation with IFNs in humans are still unclear. We examined gene expression of CH25H, IFN-α, and IFN-β and serum levels of 25HC in Iranian patients with mild and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Fifty intensive care unit (ICU) patients and outpatients with SARS-CoV-2 and 25 healthy controls were studied. Gene expression of CH25H and relevant inflammatory cytokines was quantified in peripheral blood mononuclear cells by real-time polymerase chain reaction. The expression of CH25H and serum levels of 25HC were significantly higher in ICU patients with SARS-CoV-2. Notably, IFN-α levels increased in healthy controls. However, compared to healthy controls, IFN-β was considerably higher in outpatients. Finally, statistical analysis shows that no correlation was found between CH25H and IFN-α expression; nevertheless, a lower correlation was found with IFN-β. The data revealed that CH25H and 25HC levels increase after SARS-CoV-2 infection. In other words, decreased levels of those factors in severe patients compared with mild patients may indicate the importance of their function in controlling the progression of the disease.

Optimizing Fungicide Sprays to Tackle Powdery Mildew (Uncinula necator) At The Right Time For healthy grapes production

Introduction: Powdery mildew, caused by the fungus Uncinula necator, is a prevalent and harmful disease affecting grapevines, resulting in decreased fruit set and yield. This study aimed to evaluate the effectiveness of various fungicides and spray timings in managing U. necator in grape vineyards. Methods: A field trial was conducted in Pishin, Balochistan in 2020, employing a randomized complete block design with two factors: four fungicides (control, protective fungicide-Bordeaux mixture, curative fungicide-Elite 45 wp, systemic fungicide-Quintec) and four spray timings (dormant spray, bud break, one week before bloom, and berry formation). Results: The findings revealed significant variations in disease severity (PDI) among leaves, inflorescence, and bunches across different fungicides, spray timings, and their interactions. Application of the protective fungicide one week before bloom proved highly effective in preventing U. necator infection, resulting in the lowest PDI values for leaves (0.44%), inflorescence (0.67%), and bunches (0.0%). Curative fungicides sprayed at bloom stage also reduced PDI for inflorescence (2.17%) and bunches (3.56%). Systemic fungicides applied during berry formation exhibited lower PDI for inflorescence (6.44%) and bunches (4.0%) compared to other fungicides. The highest grape production (27.10 t ha-1) was achieved with the protective fungicide sprayed at bloom stage, followed by the curative fungicide at bloom stage (25.87 t ha-1). The negative and highly significant relationship (R2=0.809) between PDI of leaves and grape yield indicated that higher disease severity led to decreased yield. Conclusion: In conclusion, a protective fungicide spray before bloom, followed by a systemic fungicide spray at berry formation, effectively controls U. necator and ensures healthier and higher grape yields.

A - 95 State of the Science Systematic Review of the Neuropsychology of Solid Organ Transplantation.

Organ failure is associated with cognitive dysfunction; however, the acute and longitudinal effects of different types of organ failure and transplantation on cognition have yet to be fully elucidated. This systematic review aimed to identify evidence for key neurocognitive profiles by organ type among pre- and post-transplant patients and identify health and behavior factors that may influence cognition in transplant populations. PubMed, EMBASE, and PsychInfo database systemic searches were performed. The primary inclusion criteria were adult patients, peer-reviewed articles, full-organ transplant, and neuropsychological test results. Screening and data extraction were performed independently by two authors following PRISMA criteria. A total of 737 abstracts were screened, 237 full-text articles were reviewed for relevance in the second-level screening process, and a total of 125 articles were thoroughly reviewed and included. The number of studies by organ type included the following: liver (62), kidney (30), cardiac (17), lung (12), and multi-organ (4). Available research reported diffuse impairments in liver and cardiac transplant candidates, more circumscribed deficits (i.e., attention, executive functioning, and memory) in kidney transplant candidates, and few cognitive impairments among lung transplant candidates. Post-transplant research showed notable improvement across all organ recipients. Results appear to be impacted by disease severity and demographic variables, with older age more often associated with worse cognitive performance over time. Results highlight the several literature gaps that can be improved with further transplant neuropsychology research.

Association of ethnicity and time to surgery among patients with chronic rhinosinusitis.

Determine factors associated with delayed endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). This is a retrospective cohort study conducted at a tertiary care academic center. Patients were included in the study if they were at least 18 years old and underwent surgery for CRS. Electronic medical records were retrospectively reviewed to collect demographic and clinical data. Patients with CRS secondary to another pathology such as malignancy were excluded. Multiple linear regression was performed to determine factors associated with the number of days between a patient's preoperative consultation and the date of surgery. A total of 103 patients with a mean age of 46.6 ± 16.8 years were included in the analysis; 51.5% of patients were females, 46.6% identified as White, and 29.1% identified as Hispanic. The majority of patients (67.0%) had preferred provider organization health insurance; 43.7% of patients had nasal polyps, 70.9% had a deviated nasal septum, and the mean preoperative Sinonasal Outcomes Test-22 (SNOT-22) score was 41.0 ± 23.8. The mean time to surgery after the final preoperative visit was 71.7 days ± 65.6 days. Hispanic ethnicity was associated with increased time to surgery (p < .05) when controlling for other variables. No other variables were associated with time to surgery on multivariate analysis. Hispanic ethnicity may be an independent predictor of increased time to sinus surgery independent of disease severity and other demographic variables. 2b.

Let's stick together: Infection enhances preferences for social grouping in a songbird species.

Acute infections can alter foraging and movement behaviors relevant to sociality and pathogen spread. However, few studies have directly examined how acute infections caused by directly transmitted pathogens influence host social preferences. While infected hosts often express sickness behaviors (e.g., lethargy) that can reduce social associations with conspecifics, enhanced sociality during infection might be favored in some systems if social grouping improves host survival of infection. Directly assaying social preferences of infected hosts is needed to elucidate potential changes in social preferences that may act as a form of behavioral tolerance (defined as using behavior to minimize fitness costs of infection). We tested how infection alters sociality in juvenile house finches (Haemorhous mexicanus), which are both highly gregarious and particularly susceptible to infection by the bacterial pathogen Mycoplasma gallisepticum (MG). We inoculated 33 wild-caught but captive-held juvenile house finches with MG or media (sham control). At peak infection, birds were given a choice assay to assess preference for associating near a flock versus an empty cage. We then repeated this assay after all birds had recovered from infection. Infected birds were significantly more likely than controls to spend time associating with, and specifically foraging near, the flock. However, after infected birds had recovered from MG infection, there were no significant differences in the amount of time birds in each treatment spent with the flock. These results indicate augmented social preferences during active infection, potentially as a form of behavioral tolerance. Notably, infected birds showed strong social preferences regardless of variation in disease severity or pathogen loads, with 14/19 harboring high loads (5-6 log10 copies of MG) at the time of the assay. Overall, our results show that infection with a directly transmitted pathogen can augment social preferences, with important implications for MG spread in natural populations.

A large‐scale survey reveals agro‐ecological factors influence spatio‐temporal distribution and epidemics of maize leaf blight: Implications for prioritizing sustainable management options

AbstractIntroductionProductivity of maize (Zea mays L.) is predominantly constrained by diseases, weeds, and insect pests. The northern leaf blight (NLB) disease, caused by Exserohilum turcicum, inflicts significant maize yield losses in the tropics and humid tropics, including Ethiopia. A large‐scale field survey was conducted to assess the spatio‐temporal distribution of maize NLB in southern Ethiopia, and to determine the association of maize farming practices and agro‐ecological factors with NLB epidemics during 2016–2019.Materials and MethodsA total of 814 maize farms were assessed in 12 major maize‐producing districts. During the assessment, data related to the disease, crop, farming practices and agro‐ecological factors were collected. The associations of disease severity with independent factors were determined using the ordinal logistic regression model.ResultsThe results showed that all studied districts and zones recorded high (≥85%) NLB prevalence over the 4 years, and the disease continues to be a major threat to maize production. Variable disease severity was recorded across districts/zones during the study periods. The highest (75.45%) mean severity was recorded from Boreda, followed by Konso (75.36%), Bonke (71.61%) and Derashe (71.30%), while Mihirab Abaya (33.25%) and Arba Minch (38.285%) districts recorded the lowest mean severity. In the multiple regression model, zone, altitude, cropping year, land preparation, NPS fertilization, weeding practice, growth stage and cropping system were highly significantly (p &lt; 0.0001) associated with disease severity.ConclusionMaize cultivation at an altitude of ≤1500 m with intermediate to good weeding practices, recommended NPS (51–100 kg ha–1) fertilization, mixed‐ and intercropping systems, sparse plant (≤20 plants m‒2) population, and vegetative to blistering growth stages had significant relationships with low (≤25, 26%–50%) disease severity, and can be considered as management options to reduce NLB pressure and yield losses to sustainably ensure maize production and productivity.

Giardiasis in the Southwest Region of the United States: Causes and Preventive Measures

Giardia is a protozoan parasite of the small intestine, and a leading cause of diarrheal diseases worldwide in a variety of animals, as well as humans. Despite the decrease, Giardiasis remains the most commonly reported intestinal parasitic infection principally in the Southwestern region of the United States. The parasite is typically transmitted by fecal-oral route and may be transmitted by direct intake or indirectly from contaminated food or water. Symptomatic Giardiasis is often treated to reduce the duration of symptoms, to prevent future complications, and to minimize transmission of the parasite to other hosts. The clinical image of Giardiasis is mixed, with high variability in severity of clinical disease which can become chronic or be followed by post-infectious sequelae. At present, treatment options include nitroimidazoles derivatives; especially metronidazole, which has been the mainstay of treatment for decades and is still widely used. The Navajo Nation located in the Southwestern region of the United States has suffered from the scarcity of water expediting Navajo populations to use water resources such as underground water, river streams, lakes and surface water as their main source of accessibility. The lack of adequate domestic and municipal water has led several Navajo families to become ill with waterborne infectious diseases like Giardiasis. More recently, molecular methods have become amateur in diagnosis for testing patient samples as well as water samples for Giardiasis. Through direct immunofluorescent staining and other methods that detect intact organisms have improved the detection of Giardia trophozoites or cysts. An understanding of clinical and molecular variability of organisms is important for effective treatment and the response of remedies that are commonly used. The molecular classification of bacteria and viruses isolated from Indigenous patients might have their own specification that can be correlated with isolates from water samples collected from the same localities. This correlation could help us in source tracking and finding solutions for the communities who are already at risk due to the lack of infrastructure and resources. In this review of literature, the causes and preventive measures of Giardiasis are covered to potentially help understand the importance behind this parasitic disease, more specifically on the Navajo Nation of the Southwest of the US.

Effects of Exercise, Rehabilitation, and Nutritional Approaches on Body Composition and Bone Density in People with Multiple Sclerosis: A Systematic Review and Meta-Analysis.

People with multiple sclerosis (pwMS) are affected by a wide range of disabilities, including a decrease in bone mineral density (BMD) and a worsening of body composition (BC), which negatively impact their quality of life quality. This study aims to analyze the effects of nonpharmacological interventions-in particular, physical activity, nutritional approaches, and rehabilitation-on BC and BMD in pwMS. This systematic review and meta-analysis was performed following the updated version of the PRISMA guidelines. In July 2022, five databases (MEDLINE, Embase, The Cochrane Library, Google Scholar, Web of Science) and gray literature were screened. Relevant articles published between 1 January 1990 and 1 September 2022 in any language were included. Outcomes of interest were anthropometric, BC measures, and BMD. The RoB 2.0 tool was used to assess the risk of bias. After duplicates elimination, 1120 records were screened, and 36 studies were included. A total of 25 articles were focused on physical activity and rehabilitation, 10 on nutrition, and 1 on multimodal intervention. One-third of the studies were judged to be at high risk of bias. The meta-analysis showed a high degree of heterogeneity due to the high variability in disease severity and intervention duration, intensity, frequency, and type. In general, no intervention showed consistent positive effects on BC. However, the most promising interventions seemed to be high-intensity training and ketogenic diets. Only a few studies considered BMD, and the results are inconsistent. Nevertheless, more studies are needed in order to confirm these results.

Developing a Blood Cell-Based Diagnostic Test for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Peripheral Blood Mononuclear Cells.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by debilitating fatigue that profoundly impacts patients' lives. Diagnosis of ME/CFS remains challenging, with most patients relying on self-report, questionnaires, and subjective measures to receive a diagnosis, and many never receiving a clear diagnosis at all. In this study, a single-cell Raman platform and artificial intelligence are utilized to analyze blood cells from 98 human subjects, including 61 ME/CFS patients of varying disease severity and 37 healthy and disease controls. These results demonstrate that Raman profiles of blood cells can distinguish between healthy individuals, disease controls, and ME/CFS patients with high accuracy (91%), and can further differentiate between mild, moderate, and severe ME/CFS patients (84%). Additionally, specific Raman peaks that correlate with ME/CFS phenotypes and have the potential to provide insights into biological changes and support the development of new therapeutics are identified. This study presents a promising approach for aiding in the diagnosis and management of ME/CFS and can be extended to other unexplained chronic diseases such as long COVID and post-treatment Lyme disease syndrome, which share many of the same symptoms as ME/CFS.