Thrombotic microangiopathy associated with calcineurin inhibitor induction doses in patients with a kidney transplant.

We present a case of a 23-year-old male who developed thrombotic microangiopathy associated with the induction dose of tacrolimus. Get an early diagnosis and give timely treatment of thrombotic microangiopathy is essential to improve the prognosis of the kidney transplant.

Phenotypes of Mineral Bone Disorder in Chronic Kidney Disease in a Dialysis Population.

BACKGROUND: Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is associated with clinical outcomes. It is necessary to identify the phenotype to make clinical decisions that optimize resources and follow-up. OBJECTIVE: To determine the frequency of the CKD-MBD phenotype in dialysis patients and the associated factors. METHODS: Cross-sectional study in 440 patients, evaluated for CKD-MBD. Phenotypes show frequency of high, low or on target levels of PTH, vitamin D and phosphorus. The most common phenotype was used for comparisons. RESULTS: Age was 37.5 ± 15.8 years, 53% male, 28% were diabetic, 60% on peritoneal dialysis (PD), dialysis vintage was 12.0 months (IQR 3.0-34.3). High PTH was 58%, low vitamin D 82%, high phosphorus 39%, low calcium 50%, and vascular calcification 55%. The combination of high PTH and low vitamin D and high on-target phosphorus was 39%. Those with high PTH and low vitamin D were more likely to use PD (71 vs 51%; p <0.0001), had higher lipids: total cholesterol (159 vs. 152; p = 0.002) and triglycerides (137 vs. 123; p = 0.02), higher potassium (4.7 ± 0.7 vs. 4.9 ± 0.9 mg/dL; p = 0.04), and higher serum creatinine (11.9 ± 4.4 vs. 10.6 ± 3.7 mg/dL; p = 0.01). Predictors of the most common phenotypes were PD use, total cholesterol, and serum creatinine. CONCLUSIONS: More than one third (38%) of our sample of patients had high PTH and low vitamin D with either high or normal phosphorus. Patients with these phenotypes more frequently used PD, had higher lipids and low potassium. PD use, total cholesterol and serum creatinine were significantly associated with these phenotypes.

Standardisation facilitates reliable interpretation of ETCO2 during manual cardiopulmonary resuscitation.

BACKGROUND: Interpretation of end-tidal CO2 (ETCO2) during manual cardiopulmonary resuscitation (CPR) is affected by variations in ventilation and chest compressions. This study investigates the impact of standardising ETCO2 to constant ventilation rate (VR) and compression depth (CD) on absolute values and trends. METHODS: Retrospective study of out-of-hospital cardiac arrest cases with manual CPR, including defibrillator and clinical data. ETCO2, VR and CD values were averaged by minute. ETCO2 was standardised to 10 vpm and 50 mm. We compared standardised (ETs) and measured (ETm) values and trends during resuscitation. RESULTS: Of 1,036 cases, 287 met the inclusion criteria. VR was mostly lower than recommended, 8.8 vpm, and highly variable within and among patients. CD was mostly within guidelines, 49.8 mm, and less varied. ETs was lower than ETm by 7.3 mmHg. ETs emphasized differences by sex (22.4 females vs. 25.6 mmHg males), initial rhythm (29.1 shockable vs. 22.7 mmHg not), intubation type (25.6 supraglottic vs. 22.4 mmHg endotracheal) and return of spontaneous circulation (ROSC) achieved (34.5 mmHg) vs. not (20.1 mmHg). Trends were different between non-ROSC and ROSC patients before ROSC (-0.3 vs. + 0.2 mmHg/min), and between sustained and rearrest after ROSC (-0.7 vs. -2.1 mmHg/min). Peak ETs was higher for sustained than for rearrest (53.0 vs. 42.5 mmHg). CONCLUSION: Standardising ETCO2 eliminates effects of VR and CD variations during manual CPR and facilitates comparison of values and trends among and within patients. Its clinical application for guidance of resuscitation warrants further investigation.

PKC-α is involved in the signaling of phagocytosis induced by two snake venom secretory PLA2S in macrophages.

Phagocytosis, an essential process for host defense, requires the coordination of a variety of signaling reactions. MT-II, an enzymatically inactive Lys49 phospholipase A2 (PLA2) homolog, and MT-III, a catalytically-active Asp49 PLA2, are known to activate phagocytosis in macrophages. In this study, the signaling pathways mediating phagocytosis, focusing on protein kinases, were investigated. Macrophages from male Swiss mice peritoneum were obtained 96 h after intraperitoneal thioglycolate injection. Phagocytosis was evaluated using non-opsonized zymosan particles in the presence or absence of specific inhibitors, as well as PKC and PKC-α localization by confocal microscopy. Moreover, protein kinase C (PKC) activity was assessed by γP32 ATP in macrophages stimulated by both PLA2s. Data showed that both sPLA2s increased phagocytosis. Cytochalasin D, staurosporine/H7, wortmannin, and herbimycin, inhibitors of actin polymerization, PKC, phosphoinositide 3-kinase (PI3K), and protein tyrosine kinase (PTK), respectively, significantly reduced phagocytosis induced by both PLA2s. PKC activity was increased in macrophages stimulated by both PLA2s. Actin polymerization and talin were evidenced by immunofluorescence and talin was recruited 5 min after both PLA2s stimulation. PKC and PKC-α localization within the cell were increased after 60 min of MT-II and MT-III stimulation. These data suggest that the effect of both PLA2s depends on actin cytoskeleton rearrangements and the activation of PKC, PI3K, and PTK signaling events required for phagocytosis.

A Visual Approach for Inducing Dolichoectasia in Mice to Model Large Vessel-Mediated Cerebrovascular Dysfunction.

The blood-brain (BBB) is a crucial system that regulates selective brain circulation with the periphery, as an example, allowing necessary nutrients to enter and expel excessive amino acids or toxins from the brain. To model how the BBB can be compromised in diseases like vascular dementia (VaD) or Alzheimer's disease (AD), researchers developed novel methods to model vessel dilatation. A compromised BBB in these disease states can be detrimental and result in the dysregulation of the BBB leading to untoward and pathological consequences impacting brain function. We were able to modify an existing technique that enabled us to inject directly into the Cisterna magna (CM) to induce dilatation of blood vessels using elastase, and disrupt the tight junctions (TJ) of the BBB. With this method, we were able to see various metrics of success over previous techniques, including consistent blood vessel dilatation, reduced mortality or improved recovery, and improving the fill/opacifying agent, a silicone rubber compound, delivery for labeling blood vessels for dilatation analysis. This modified minimally invasive method has had promising results, with a 19%-32% increase in sustained dilatation of large blood vessels in mice from 2 weeks to 3 months post-injection. This improvement contrasts with previous studies, which showed increased dilatation only at the 2 week mark. Additional data suggests sustained expansion even after 9.5 months. This increase was confirmed by comparing the diameter of blood vessels of the elastase and the vehicle-injected group. Overall, this technique is valuable for studying pathological disorders that affect the central nervous system (CNS) using animal models.

Epidemiologic Features of Recovery From SARS-CoV-2 Infection.

Importance: Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden. Objective: To determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days. Design, Setting, and Participants: For this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health-funded cohorts that have enrolled and followed participants since 1971. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection. Exposure: Preinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires. Main Outcomes and Measures: Probability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days. Results: Of 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P < .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections. Conclusions and Relevance: In this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.

Association of estimated pulse wave velocity with cognitive function in a multiethnic diverse population: The Northern Manhattan Study.

INTRODUCTION: Arterial stiffness is linked to age-related cognitive dysfunction. Estimated pulse wave velocity (ePWV) is associated with cerebrovascular disease. We sought to determine whether ePWV was associated with cognition in a multiethnic population. METHODS: We included 1257 participants enrolled in a Northern Manhattan Study magnetic resonance imaging MRI-cognitive study (mean age 64 ± 8 years, 61% women, 67% Hispanic, 18% non-Hispanic Black, 15% non-Hispanic white) and analyzed cognitive performance at two time points, at enrollment and on an average 5.0 ± 0.6 years later. ePWV was calculated using baseline age and blood pressure. Cognition and cognitive change scores were regressed on ePWV in multivariable linear regression models. RESULTS: In adjusted models, ePWV (mean 11 ± 2 m/s) was significantly associated with cognition (b = -0.100, 95% CI, -0.120, -0.080) and cognitive change over time (b = -0.063, 95% CI, -0.082, -0.045). Effect modification by race and sex was found. DISCUSSION: In this multiethnic population, the associations of ePWV with cognitive performance underline the role of vascular stiffness in age-related cognitive decline. HIGHLIGHTS: ePWV is a modest but independent predictor of cognitive function and cognitive decline among older individuals. After adjustment, the ePWV measure was inversely associated with performance and decline in global cognition, processing speed, episodic memory, executive function, and semantic memory. After adjustment, modification of the association between ePWV and change in episodic memory and executive function by race and ethnicity was suggested by a significant interaction term. The association between ePWV and episodic memory decline was stronger in females.

Patient Attitudes Toward Self- or Partner-, Friend-, or Family-Administered Long-acting Injectable Antiretroviral Therapy: A Mixed-Methods Study Across 3 Urban Human Immunodeficiency Virus Clinics.

Background: Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) offers a novel drug delivery option for persons with human immunodeficiency virus (PWH) but requires administration every 4 or 8 weeks by a medical professional. Methods: To facilitate LAI antiretroviral therapy (ART) scale-up, we evaluated patient interest in alternative administration approaches via a mixed-methods, serial cross-sectional study across 3 US HIV clinics. We surveyed PWH (December 2021 to May 2022) on appeal of self- or partner/friend/family-administered LAI-CAB/RPV; multivariable ordinal logistic regression explored associated characteristics. To contextualize survey results, we thematically analyzed semi-structured interview data collected from PWH (August 2020 to July 2021) on attitudes toward out-of-clinic LAI-ART administration. Results: Among 370 surveyed PWH (median age, 46 years; 26% cisgender female, 59% Black, 56% sexual minority, 34% housing instability), self-administering LAI-CAB/RPV appealed to 67%. PWH who were White (adjusted odds ratio [aOR], 3.30 [95% confidence interval {CI}, 1.42-7.64]), stably housed (aOR, 2.16 [95% CI, 1.30-3.59]), or gay/bisexual (aOR, 1.81 [1.14-2.89]) were more likely to endorse self-administration. Fewer PWH (60%) reported partner/friend/family administration as appealing; adjusted models revealed similar sociodemographic preferences for this outcome. In 72 interviews, PWH noted that acceptability of out-of-clinic LAI-ART administration was qualified by convenience, prior injection experience, and potential fear of self-inflicted pain, dependence on others, and/or HIV disclosure. Conclusions: In a multisite sample of PWH, self- and, to a lesser extent, partner/friend/family-administration of LAI-CAB/RPV appealed to most; however, was less appealing among populations more impacted by health disparities. Innovative LAI-ART delivery options could free up in-clinic resources to focus scale-up among marginalized populations.

Prognostic impact of vasopressor test in transcatheter edge-to-edge repair of secondary mitral regurgitation: The PETIT study.

BACKGROUND: Vasopressor test (VPT) might be useful in patients with functional mitral regurgitation (MR) and left ventricular dysfunction (MITRA-FR-like patients) during transcatheter edge-to-edge repair (TEER). AIMS: We aimed to evaluate the prognostic impact of VPT. METHODS: MR treated with TEER were included in a multicenter prospective registry. VPT was used intraprocedurally in patients with left ventricular dysfunction and/or hypotension. The 1-year echocardiographic and clinical outcomes were compared according to the use of VPT. The primary endpoint was a combination of mortality + heart failure (HF) readmission at 1-year. RESULTS: A total of 1115 patients were included, mean age was 72.8 ± 10.5 years and 30.4% were women. VPT was performed in 128 subjects (11.5%), more often in critically ill patients with biventricular dysfunction. Postprocedurally the VPT group had greater rate of MR ≥ 2+ (46.9% vs. 31.7%, p = 0.003) despite greater number of devices (≥2 clips, 52% vs. 40.6 p = 0.008) and device repositioning or new clip in 12.5%. At 1-year, the primary endpoint occurred more often in the VPT group (27.3% vs. 16.9%, p = 0.002) as well as all-cause mortality (21.9% vs. 8.1%, p ≤ 0.001) but no differences existed in HF readmission rate (14.8% vs. 13.2%, p = 0.610), cardiovascular mortality (4.4% vs. 3.9%, p = 0.713) or residual MR ≥ 2+ (51.1% vs 51.7%, p = 0.371). CONCLUSIONS: Dynamic evaluation of MR during TEER procedure through VPT was performed in patients with worse baseline risk who also presented higher all-cause mortality at 1-year follow-up. However, 1-year residual MR, cardiovascular mortality and HF readmission rate remained comparable suggesting that VPT might help in the management of MITRA-FR-like patients.

A pathway linking pulse pressure to dementia in adults with Down syndrome.

Adults with Down syndrome are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease and is linked to a diagnosis of dementia in adults with Down syndrome via structural imaging markers of cerebrovascular disease and atrophy. The study included participants with Down syndrome from the Alzheimer's Disease - Down Syndrome study (n = 195, age = 50.6 ± 7.2 years, 44% women, 18% diagnosed with dementia). Higher pulse pressure was associated with greater global, parietal and occipital white matter hyperintensity volume but not with enlarged perivascular spaces, microbleeds or infarcts. Using a structural equation model, we found that pulse pressure was associated with greater white matter hyperintensity volume, which in turn was related to increased neurodegeneration, and subsequent dementia diagnosis. Pulse pressure is an important determinant of brain health and clinical outcomes in individuals with Down syndrome despite the low likelihood of frank hypertension.

Green synthesis of zinc oxide nanoparticles from Sida acuta leaf extract for antibacterial and antioxidant applications, and catalytic degradation of dye through the use of convolutional neural network.

This study synthesized zinc oxide nanoparticles (ZnO NPs) using a novel green approach, with Sida acuta leaf extract as a capping and reducing agent to initiate nucleation and structure formation. The innovation of this study lies in demonstrating the originality of utilizing zinc oxide nanoparticles for antibacterial action, antioxidant potential, and catalytic degradation of Congo red dye. This unique approach harnesses eco-friendly methods to initiate nucleation and structure formation. The synthesized nanoparticles' structure and conformation were characterized using UV-vis (λmax = 280 nm), X-ray, atomic force microscopy, SEM, HR-TEM and FTIR. The antibacterial activity of the Nps was tested against Pseudomonas sp, Klebsiella sp, Staphylococcus aureus, and E. coli, demonstrating efficacy. The nanoparticles exhibited unique properties, with a crystallite size of 20 nm (XRD), a surface roughness of 2.5 nm (AFM), and a specific surface area of 60 m2/g (SEM). A Convolutional Neural Network (CNN) was effectively employed to accurately classify and analyze microscopic images of green-synthesized zinc oxide nanoparticles. This research revealed their exceptional antioxidant potential, with an average DPPH scavenging rate of 80% at a concentration of 0.05 mg/mL. Additionally, zeta potential measurements indicated a stable net negative surface charge of approximately -12.2 mV. These quantitative findings highlight the promising applications of green-synthesized ZnO NPs in healthcare, materials science, and environmental remediation. The ZnO nanoparticles exhibited catalytic capabilities for dye degradation, and the degradation rate was determined using UV spectroscopy. Key findings of the study encompass the green synthesis of versatile zinc oxide nanoparticles, demonstrating potent antibacterial action, antioxidant capabilities, and catalytic dye degradation potential. These nanoparticles offer multifaceted solutions with minimal environmental impact, addressing challenges in various fields, from healthcare to environmental remediation.

Validation of bedside manual versus automated measurements of brain arterial diameters from MR angiography.

BACKGROUND AND PURPOSE: Brain arterial luminal diameters are reliably measured with automated imaging software. Nonautomated imaging software alternatives such as a Picture Archiving Communication System are more common bedside tools used for manual measurement. This study is aimed at validating manual measurements against automated methods. METHODS: We randomly selected 600 participants from the Northern Manhattan Study (NOMAS) and 260 participants from the Atahualpa Project studied with 1.5 Tesla MR angiography. Using the Radiant measuring tool, three independent readers (general practitioner, neurology resident, and vascular neurologist) measured manually the diameter of arterial brain vessels. The same vessels were also measured by LKEB Automated Vessel Analysis (LAVA). We calculated the intraclass correlation coefficient (ICC) of each rater's diameters versus those obtained with LAVA. RESULTS: The ICC between diameters obtained by the general practitioner or the neurology resident compared to LAVA was excellent for both internal carotid arteries (ICA) and Basilar Arteries (BA) (ICC > .80 in all comparisons) in NOMAS. In the Atahualpa Project, ICC between diameters obtained by a vascular neurologist and LAVA was good for both ICA and BA (ICC > .60 in all comparisons). The ICCs for the measurements of the remaining arteries were moderate to poor. CONCLUSION: Results suggest that manual measurements of ICA and BA diameters, but not MCA or ACA, are valid and could be used to identify dilated brain arteries at the bedside and for eventual selection of patients with dolichoectasia into clinical trials.

Bridging personality dimensions and eating symptoms: A transdiagnostic network approach.

OBJECTIVE: Eating disorders (ED) have recently been studied from a network approach, conceptualising them as a complex system of interconnected variables, while highlighting the role of non-ED symptoms and personality dimensions. This study aims to explore the connections between personality and ED symptoms, identify central nodes, and compare the EDs network to a healthy control network. METHODS: We employed network analysis to examine the personality-ED symptom connections in 329 individuals with an ED diagnosis and 192 healthy controls. We estimated a regularised partial correlation network and the indices of centrality and bridge centrality to identify the most influential nodes for each group. Network differences between groups were also examined. RESULTS: Low Self-Directedness and high Harm avoidance emerged as central bridge nodes, displaying the strongest relationship with ED symptoms. Both networks differed in their global connectivity and structure, although no differences were found in bridge centrality and centrality indices. CONCLUSIONS: These findings shed light on the role of personality dimensions, such as Self-Directedness and Harm Avoidance in the maintenance of ED psychopathology, supporting the transdiagnostic conceptualisation of ED. This study advances a deeper understanding of the complex interplay between personality dimensions and ED symptoms, offering potential directions for clinical interventions.

General regulatory factors exert differential effects on nucleosome sliding activity of the ISW1a complex.

BACKGROUND: Chromatin dynamics is deeply involved in processes that require access to DNA, such as transcriptional regulation. Among the factors involved in chromatin dynamics at gene regulatory regions are general regulatory factors (GRFs). These factors contribute to establishment and maintenance of nucleosome-depleted regions (NDRs). These regions are populated by nucleosomes through histone deposition and nucleosome sliding, the latter catalyzed by a number of ATP-dependent chromatin remodeling complexes, including ISW1a. It has been observed that GRFs can act as barriers against nucleosome sliding towards NDRs. However, the relative ability of the different GRFs to hinder sliding activity is currently unknown. RESULTS: Considering this, we performed a comparative analysis for the main GRFs, with focus in their ability to modulate nucleosome sliding mediated by ISW1a. Among the GRFs tested in nucleosome remodeling assays, Rap1 was the only factor displaying the ability to hinder the activity of ISW1a. This effect requires location of the Rap1 cognate sequence on linker that becomes entry DNA in the nucleosome remodeling process. In addition, Rap1 was able to hinder nucleosome assembly in octamer transfer assays. Concurrently, Rap1 displayed the highest affinity for and longest dwell time from its target sequence, compared to the other GRFs tested. Consistently, through bioinformatics analyses of publicly available genome-wide data, we found that nucleosome occupancy and histone deposition in vivo are inversely correlated with the affinity of Rap1 for its target sequences in the genome. CONCLUSIONS: Our findings point to DNA binding affinity, residence time and location at particular translational positions relative to the nucleosome core as the key features of GRFs underlying their roles played in nucleosome sliding and assembly.

Improving in vivo assays in snake venom and antivenom research: A community discussion.

On the 26 th January 2023, a free to attend, 'improving in vivo snake venom research: a community discussion' meeting was held virtually. This webinar brought together researchers from around the world to discuss current neutralisation of venom lethality mouse assays that are used globally to assess the efficacy of therapies for snakebite envenoming. The assay's strengths and weaknesses were highlighted, and we discussed what improvements could be made to refine and reduce animal testing, whilst supporting preclinical antivenom and drug discovery for snakebite envenoming. This report summarises the issues highlighted, the discussions held, with additional commentary on key perspectives provided by the authors.

Body Awareness as a Protective Factor against Suicidal Orientations in College Students.

In this study, binary logistic regression and linear regression analyses were used to examine the relationship between interoceptive body awareness and suicidal orientation among Colombian university students. Additionally, the bootstrap technique was employed to resample and estimate the distribution of the data. The results support the idea that greater interoceptive awareness may protect against suicidal orientation by improving emotional regulation. An inverse relationship was found between interoceptive awareness and suicidal ideation. These findings align with previous literature emphasizing the importance of body awareness for emotional well-being. Further longitudinal research is needed to explore this relationship more deeply.

Comparison of the intrageneric neutralization scope of monospecific, bispecific/monogeneric and polyspecific/monogeneric antisera raised in horses immunized with sub-Saharan African snake venoms.

BACKGROUND: Snakebite envenomation inflicts a high burden of mortality and morbidity in sub-Saharan Africa. Antivenoms are the mainstay in the therapy of envenomation, and there is an urgent need to develop antivenoms of broad neutralizing efficacy for this region. The venoms used as immunogens to manufacture snake antivenoms are normally selected considering their medical importance and availability. Additionally, their ability to induce antibody responses with high neutralizing capability should be considered, an issue that involves the immunization scheme and the animal species being immunized. METHODOLOGY/PRINCIPAL FINDINGS: Using the lethality neutralization assay in mice, we compared the intrageneric neutralization scope of antisera generated by immunization of horses with monospecific, bispecific/monogeneric, and polyspecific/monogeneric immunogens formulated with venoms of Bitis spp., Echis spp., Dendroaspis spp., spitting Naja spp. or non-spitting Naja spp. It was found that the antisera raised by all the immunogens were able to neutralize the homologous venoms and, with a single exception, the heterologous congeneric venoms (considering spitting and non-spitting Naja separately). In general, the polyspecific antisera of Bitis spp, Echis spp, and Dendroaspis spp gave the best neutralization profile against venoms of these genera. For spitting Naja venoms, there were no significant differences in the neutralizing ability between monospecific, bispecific and polyspecific antisera. A similar result was obtained in the case of non-spitting Naja venoms, except that polyspecific antiserum was more effective against the venoms of N. melanoleuca and N. nivea as compared to the monospecific antiserum. CONCLUSIONS/SIGNIFICANCE: The use of polyspecific immunogens is the best alternative to produce monogeneric antivenoms with wide neutralizing coverage against venoms of sub-Saharan African snakes of the Bitis, Echis, Naja (non-spitting) and Dendroaspis genera. On the other hand, a monospecific immunogen composed of venom of Naja nigricollis is suitable to produce a monogeneric antivenom with wide neutralizing coverage against venoms of spitting Naja spp. These findings can be used in the design of antivenoms of wide neutralizing scope for sub-Saharan Africa.

Cerebrovascular disease emerges with age and Alzheimer's disease in adults with Down syndrome.

Adults with Down syndrome have a genetic form of Alzheimer's disease (AD) and evidence of cerebrovascular disease across the AD continuum, despite few systemic vascular risk factors. The onset and progression of AD in Down syndrome is highly age-dependent, but it is unknown at what age cerebrovascular disease emerges and what factors influence its severity. In the Alzheimer's Biomarker Consortium-Down Syndrome study (ABC-DS; n = 242; age = 25-72), we estimated the age inflection point at which MRI-based white matter hyperintensities (WMH), enlarged perivascular spaces (PVS), microbleeds, and infarcts emerge in relation to demographic data, risk factors, amyloid and tau, and AD diagnosis. Enlarged PVS and infarcts appear to develop in the early 30s, while microbleeds, WMH, amyloid, and tau emerge in the mid to late 30s. Age-residualized WMH were higher in women, in individuals with dementia, and with lower body mass index. Participants with hypertension and APOE-ε4 had higher age-residualized PVS and microbleeds, respectively. Lifespan trajectories demonstrate a dramatic cerebrovascular profile in adults with Down syndrome that appears to evolve developmentally in parallel with AD pathophysiology approximately two decades prior to dementia symptoms.

Efficient leukocytes detection and classification in microscopic blood images using convolutional neural network coupled with a dual attention network.

Leukocytes, also called White Blood Cells (WBCs) or leucocytes, are the cells that play a pivotal role in human health and are vital indicators of diseases such as malaria, leukemia, AIDS, and other viral infections. WBCs detection and classification in blood smears offers insights to pathologists, aiding diagnosis across medical conditions. Traditional techniques, including manual counting, detection, classification, and visual inspection of microscopic images by medical professionals, pose challenges due to their labor-intensive nature. However, traditional methods are time consuming and sometimes susceptible to errors. Here, we propose a high-performance convolutional neural network (CNN) coupled with a dual-attention network that efficiently detects and classifies WBCs in microscopic thick smear images. The main aim of this study was to enhance clinical hematology systems and expedite medical diagnostic processes. In the proposed technique, we utilized a deep convolutional generative adversarial network (DCGAN) to overcome the limitations imposed by limited training data and employed a dual attention mechanism to improve accuracy, efficiency, and generalization. The proposed technique achieved overall accuracy rates of 99.83%, 99.35%, and 99.60% for the peripheral blood cell (PBC), leukocyte images for segmentation and classification (LISC), and Raabin-WBC benchmark datasets, respectively. Our proposed approach outperforms state-of-the-art methods in terms of accuracy, highlighting the effectiveness of the strategies employed and their potential to enhance diagnostic capabilities and advance real-world healthcare practices and diagnostic systems.

Metrics of impulsiveness of manual chest compressions for out-of-hospital cardiopulmonary resuscitation.

Aim: Propose new metrics of impulsiveness of manual chest compressions (CCs) that account for shape and duration, separate the characteristics of the compressive part of the CC cycle from those of the recoil part, and are uncorrelated to CC depth and rate. Methods: We conducted a retrospective analysis of adult out-of-hospital cardiac arrest monitor-defibrillator recordings having CPR data. Specifically, episodes of adult patients with ≥ 1000 compressions free of leaning were examined. CCs were obtained from the depth signal of the valid episodes, and we calculated the novel metrics: compression area index (CAI), recoil area index (RAI), compression impulsiveness index (CII) and recoil impulsiveness index (RII). Generalized linear mixed-effects models and Jonckheere-Terpstra trend analyses were employed to measure differences between populations and trends, and the absolute value of Pearson's correlation coefficient |r| was used to report dependence between variables. Statistics are reported as median and interquartile range. Results: We analyzed 982,340 CCs corresponding to 453 episodes, for which we calculated their CAI, RAI and duty cycle (DC). We analyzed the metrics for various populations: age, sex, any ROSC achieved and disposition, and found that CAI was significantly different according to patient disposition and RAI relative to age and sex (p<0.05). None of the metrics was correlated strongly to depth or rate (|r| values of 0.22 or smaller), and all of them varied for CC series corresponding to the same rescuer over the course of resuscitation (ptrend<0.05). However, we observed that the metrics are not balanced, in that for any value of DC, CAI and RAI span almost their entire ranges. Conclusion: The proposed metrics correctly and completely describe manual CC waveforms, improve upon the DC, since they depend on the signal waveform, and provide additional information to current indicators of quality CPR, depth and rate. Furthermore, they allow to differentiate the compressive and recoil parts of the CC cycle, reflecting influence of the rescuer (via CAI or CII) and of the biomechanics of the patient's chest (via RAI or RII). Thus, they have the potential to contribute to better understanding CPR dynamics and, eventually, to enhanced quality of CPR practice as additional indicators of proper manual CC technique.