Extracellular Fluid Research Articles

Subclinical myocardial involvement in a cohort of patients with antisynthetase syndrome.

There is an increasing interest in knowing whether patients with antisynthetase syndrome (ASSD) may have silent myocardial interstitial involvement. Mapping techniques in cardiac magnetic resonance (CMR) can detect subclinical myocardial involvement. The purpose of this study was to identify alterations in multiparametric CMR in ASSD patients without overt cardiac involvement. Patients diagnosed with ASSD underwent a CMR along with the standard clinical workup, investigation of specific and associated myositis antibodies, and high-resolution chest CT. The CMR protocol includes routine morphologic, functional, and late gadolinium enhancement sequences in standard cardiac planes, as well as native T1 and T2 mapping sequences and extracellular volume (ECV) calculation. Twenty-five patients were included in this study (56% women; median age 56.3 years). Three patients were considered in the acute phase at the time of inclusion. Eight patients (32%) showed pathological findings in CMR (6 stable disease, 2 acute phase). Elevated T1, T2 and ECV mapping values were found in 20% (5/25), 17% (4/25) and 24% (6/25) of the group, respectively. Two patients in the acute phase had increased values of both T2 and ECV. Subclinical myocardial involvement in ASSD is not rare (32%) although its clinical significance is uncertain. Myocardial oedema (T2) was the most frequent finding, followed by increased T1 and/or ECV values likely signalling interstitial fibrosis. Of note, patients in the acute phase showed elevated T2 values.

TIM3 Checkpoint Inhibition Fails to Prolong Survival in Ovarian Cancer-Bearing Mice.

Immune checkpoint inhibitor (ICI) therapy has proven revolutionary in the treatment of some cancers. However, ovarian cancer remains unresponsive to current leading ICIs, such as anti-PD1 or anti-PD-L1. In this article, we explored the potential of an upcoming checkpoint molecule, T-cell immunoglobulin and mucin domain 3 (TIM3), for the treatment of ovarian cancer using a syngeneic orthotopic mouse model (ID8-fLuc). Besides therapeutic efficacy, we focused on exploring immune changes in tumor tissue and peritoneal fluid. Our results showed no improvement in survival in ovarian cancer-bearing mice after anti-TIM3 treatment when used as monotherapy nor when combined with anti-PD1 or standard-of-care chemotherapy (carboplatin/paclitaxel). This was reflected in the unaltered immune infiltration in treated mice compared to control mice. Altering the order of drug administration within the combination treatment altered the survival results, but did not result in a survival benefit over chemotherapy alone. These findings highlight the need for further preclinical studies to find beneficial treatment schemes and combination therapies for ovarian cancer.

Retrospective study of acid-base disturbances in patients with chronic kidney disease

Background. Impaired kidney function has a negative effect on the body’s acid-base status (ABS). However, a violation of ABS can worsen the course of chronic kidney disease (CKD). Therefore, during the examination and treatment of patients with CKD, it is necessary to take into account the ABS. The purpose of the study: to conduct a retrospective analysis of the dynamics of ABS indicators in patients with stage 1–5 CKD who sought outpatient medical care in a medical institution in Kyiv. Materials and methods. A retrospective, randomized, cohort study was performed of 53 medical records of patients (form 025/o) who sought outpatient medical care at the Professor Dmytro Ivanov Nephrological Clinic LLC with a diagnosis of stage 1–5 CKD from February 2022 to February 2023. Participants were examined for ABS indicators three times. They were divided into 2 groups: group 1 (n = 31) — stage 1–3 CKD and group 2 (n = 22) — stage 4–5 CKD. An analysis of ABS indicators was carried out in dyna­mics. Results. Results of multiple linear regression for patients with stage 1–5 CKD (n = 53) showed that there was a strong significant effect between potassium (K+) and glomerular filtration rate (GFR) (F(1, 13) = 10.59, p = 0.006, R2 = 0.45, R2 adj = 0.41). The results of multiple linear regression of indicators in patients with stage 1–3 CKD (group 1) demonstrated a weak insignificant influence between lactate and GFR (F(1, 15) = 1.11, p = 0.310, R2 = 0.07, R2 adj = 0.01). The results of multiple linear regression of indicators in patients with stage 4–5 CKD (group 2) showed that there is a very strong combined insignificant influence between the hydrogen index, partial pressure of carbon dioxide, partial pressure of oxygen, bicarbonate concentration, base excess of extracellular fluid, K+, total carbon dioxide, anion gap with K concentration included in the equation, base excess, lactate and GFR (F(10, –3) = 0.3, p = 58.099, R2 = –65.23, R2 adj = 155.53). Conclusions. When studying ABS in patients with stage 1–5 CKD, a correlation was found between K+ and GFR using the multiple linear regression tool. In the first group, the relationship between lactate and GFR, in the second one, all predictors had a relationship with GFR.

Knowledge and risky behaviors of Kabul city butchers regarding Crimean-Congo hemorrhagic fever

Abstract Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonotic disease with high morbidity and case fatality rates (CFR) in humans, especially among the high-risk groups, including butchers. Therefore, a cross-sectional study was conducted in Kabul City to determine the knowledge gaps and risky behaviors of Kabul City’s butchers about CCHF. Data were collected from 123 butchers by structured interview using a pre-designed questionnaire. The finding of the present study revealed that of the total CCHF cases in the butchers, their family members, and co-workers, 37.9% died. Nearly half of the butchers (45.0%) experienced splashing of animal blood on their faces, while 70.1% of them had cut their hands with a knife during their occupation life. In addition, 27.0% of the respondents held the knife in their mouth while dressing the animal carcasses, and 27.3% of the butchers consumed raw liver. Hand washing and PPE application were practiced by 94.3% and 22.8% of the respondents, respectively. About 92% of the respondents had heard about CCHF, and 67.4% of the participants had good knowledge about CCHF. The knowledge level of the respondents (poor or good) was statistically related to their age, history of blood splash in the face and eyes of the butchers, holding work knives in the mouth, blowing the skin of animals, hand washing with soap and water, and slaughter places ( p < 0.05). A medium correlation between education and total knowledge of the butchers was observed (r = 0.3; p < 0.05). It is necessary to change such high-risk behaviors by continually coordinating awareness campaigns through mass media, workshops, and informative leaflet distribution to improve knowledge. One Health impact statement CCHF is a multifaceted zoonotic disease where tick bites, direct contact with the tissue, secretions, and body fluids of the infected animals and humans, and consumption of raw milk, meat, and liver of infected animals are the main transmission methods of the disease to humans. Although livestock including cattle, sheep, goats, camels, and ostrich are the main reservoirs of the virus, they are infected in subclinical form, and humans are the only hosts where fatal clinical disease develops. Since the CCHF virus circulates in nature between tick-vertebrates-ticks, the only method that can effectively control and prevent the disease in humans is by using a targeted One Health approach between the human, veterinary, and environmental health sectors. Meanwhile, it has been proven that public awareness campaigns through the use of mass media, community leaders, and integrated workshops are the most effective tools to prevent the transmission of the CCHF virus from infected animals and ticks to humans.

Co-Culture Models: Key Players in In Vitro Neurotoxicity, Neurodegeneration and BBB Modeling Studies.

The biological barriers existing in the human body separate the blood circulation from the interstitial fluid in tissues. The blood-brain barrier (BBB) isolates the central nervous system from the bloodstream, presenting a dual role: the protection of the human brain against potentially toxic/harmful substances coming from the blood, while providing nutrients to the brain and removing metabolites. In terms of architectural features, the presence of junctional proteins (that restrict the paracellular transport) and the existence of efflux transporters at the BBB are the two major in vivo characteristics that increase the difficulty in creating an ideal in vitro model for drug permeability studies and neurotoxicity assessments. The purpose of this work is to provide an up-to-date literature review on the current in vitro models used for BBB studies, focusing on the characteristics, advantages, and disadvantages of both primary cultures and immortalized cell lines. An accurate analysis of the more recent and emerging techniques implemented to optimize the in vitro models is also provided, based on the need of recreating as closely as possible the BBB microenvironment. In fact, the acceptance that the BBB phenotype is much more than endothelial cells in a monolayer has led to the shift from single-cell to multicellular models. Thus, in vitro co-culture models have narrowed the gap between recreating as faithfully as possible the human BBB phenotype. This is relevant for permeability and neurotoxicity assays, and for studies related to neurodegenerative diseases. Several studies with these purposes will be also presented and discussed.

A modeling analysis of whole body potassium regulation on a high-potassium diet: proximal tubule and tubuloglomerular feedback effects.

Potassium (K+) is an essential electrolyte that plays a key role in many physiological processes, including mineralcorticoid action, systemic blood-pressure regulation, and hormone secretion and action. Indeed, maintaining K+ balance is critical for normal cell function, as too high or too low K+ levels can have serious and potentially deadly health consequences. K+ homeostasis is achieved by an intricate balance between the intracellular and extracellular fluid as well as balance between K+ intake and excretion. This is achieved via the coordinated actions of regulatory mechanisms such as the gastrointestinal feedforward effect, insulin and aldosterone upregulation of Na+-K+-ATPase uptake, and hormone and electrolyte impacts on renal K+ handling. We recently developed a mathematical model of whole body K+ regulation to unravel the individual impacts of these regulatory mechanisms. In this study, we extend our mathematical model to incorporate recent experimental findings that showed decreased fractional proximal tubule reabsorption under a high-K+ diet. We conducted model simulations and sensitivity analyses to investigate how these renal alterations impact whole body K+ regulation. Model predictions quantify the sensitivity of K+ regulation to various levels of proximal tubule K+ reabsorption adaptation and tubuloglomerular feedback. Our results suggest that the reduced proximal tubule K+ reabsorption under a high-K+ diet could achieve K+ balance in isolation, but the resulting tubuloglomerular feedback reduces filtration rate and thus K+ excretion.NEW & NOTEWORTHY Potassium homeostasis is maintained in the body by a complex system of regulatory mechanisms. This system, when healthy, maintains a small extracellular potassium concentration, despite large fluctuations of dietary potassium. The complexities of the system make this problem well suited for investigation with mathematical modeling. In this study, we extend our mathematical model to consider recent experimental results on renal potassium handling on a high potassium diet and investigate the impacts from a whole body perspective.

Modulation of infectious Salmon Anaemia virus infection by clathrin-mediated endocytosis and macropinocytosis inhibitors

Infectious salmon anaemia virus (ISAV) is a pathogen that causes disease and large mortality in farm-raised Salmo salar L., being considered as a major problem in the salmon industry. However, despite its relevance, there are still numerous knowledge gaps on virus entry and early stages of infection. Previous studies suggested that virus entry into cells occurs via endocytosis, with no description of specific mechanisms. However, it remains unknown if the endocytosis induced by ISAV is a clathrin-dependent or clathrin-independent process. This study aimed to identify cellular mechanisms allowing ISAV entry into Atlantic Salmon head kidney (ASK) cells. Our results showed that ISAV can be found in coated pits and membrane ruffles, the latter being induced by a rearrangement of actin filaments promoted by ISAV infection. Additionally, it was determined that ISAV stimulate the uptake of extracellular fluid in a multiplicity of infection (MOI)-dependent manner. When the clathrin-mediated endocytic pathway was pharmacologically inhibited, ISAV infection was significantly reduced but not entirely inhibited. Similarly, when the Na+/H+ exchanger (NHE), a key component of macropinocytosis, was inhibited, ISAV infection was negatively affected. Our results suggest that ISAV enters cells via both clathrin-mediated endocytosis and most likely macropinocytosis.

Measuring the Levels of Iron, Sodium, Potassium and Chloride in Male Humans with Male Hormone Imbalance

The main hormone in men, testosterone, controls sex differentiation, spermatogenesis, male sex characteristics, and fertility. Low testosterone in men affects several organ systems. Low testosterone affects men's health in physiological ways that affect mood, bone density, muscle mass and strength, and cognitive function. The history, physical examination, clinical symptoms, and testosterone levels are used to make a differential diagnosis. A deficit in iron, commonly brought on by blood loss or other illnesses, results in iron deficiency anemia. The extracellular and intracellular fluids include electrolytes. The main cation and anion in the extracellular fluid are sodium and chloride, respectively. Potassium is the main cation in the intracellular fluid. Electrolytes are essential for preserving homeostasis.

Mustn1 is a smooth muscle cell-secreted microprotein that modulates skeletal muscle extracellular matrix composition

ObjectiveSkeletal muscle plasticity and remodeling are critical for adapting tissue function to use, disuse, and regeneration. The aim of this study was to identify genes and molecular pathways that regulate the transition from atrophy to compensatory hypertrophy or recovery from injury. Here, we have used a mouse model of hindlimb unloading and reloading, which causes skeletal muscle atrophy, and compensatory regeneration and hypertrophy, respectively. MethodsWe analyzed mouse skeletal muscle at the transition from hindlimb unloading to reloading for changes in transcriptome and extracellular fluid proteome. We then used qRT-PCR, immunohistochemistry, and bulk and single-cell RNA sequencing data to determine Mustn1 gene and protein expression, including changes in gene expression in mouse and human skeletal muscle with different challenges such as exercise and muscle injury. We generated Mustn1-deficient genetic mouse models and characterized them in vivo and ex vivo with regard to muscle function and whole-body metabolism. We isolated smooth muscle cells and functionally characterized them, and performed transcriptomics and proteomics analysis of skeletal muscle and aorta of Mustn1-deficient mice. ResultsWe show that Mustn1 (Musculoskeletal embryonic nuclear protein 1, also known as Mustang) is highly expressed in skeletal muscle during the early stages of hindlimb reloading. Mustn1 expression is transiently elevated in mouse and human skeletal muscle in response to intense exercise, resistance exercise, or injury. We find that Mustn1 expression is highest in smooth muscle-rich tissues, followed by skeletal muscle fibers. Muscle from heterozygous Mustn1-deficient mice exhibit differences in gene expression related to extracellular matrix and cell adhesion, compared to wild-type littermates. Mustn1-deficient mice have normal muscle and aorta function and whole-body glucose metabolism. We show that Mustn1 is secreted from smooth muscle cells, and that it is present in arterioles of the muscle microvasculature and in muscle extracellular fluid, particularly during the hindlimb reloading phase. Proteomics analysis of muscle from Mustn1-deficient mice confirms differences in extracellular matrix composition, and female mice display higher collagen content after chemically induced muscle injury compared to wild-type littermates. ConclusionsWe show that, in addition to its previously reported intracellular localization, Mustn1 is a microprotein secreted from smooth muscle cells into the muscle extracellular space. We explore its role in muscle ECM deposition and remodeling in homeostasis and upon muscle injury. The role of Mustn1 in fibrosis and immune infiltration upon muscle injury and dystrophies remains to be investigated, as does its potential for therapeutic interventions.

Cardiopulmonary Exercise Testing in Evaluating Transthyretin Amyloidosis.

Cardiopulmonary exercise testing (CPET) has an established role in the assessment of patients with heart failure. However, data are lacking in patients with transthyretin (ATTR) amyloidosis. To use CPET to characterize the spectrum of functional phenotypes in patients with ATTR amyloidosis and assess their association with the cardiac amyloid burden as well as the association between CPET parameters and prognosis. This single-center study evaluated patients diagnosed with ATTR amyloidosis from May 2019 to September 2022 who underwent CPET at the National Amyloidosis Centre. Of 1045 patients approached, 506 were included and completed the study. Patients were excluded if they had an absolute contraindication to CPET or declined participation. The mean (SD) follow-up period was 22.4 (11.6) months. Comparison of CPET parameters across disease phenotypes (ATTR with cardiomyopathy [ATTR-CM], polyneuropathy, or both [ATTR-mixed]), differences in CPET parameters based on degree of amyloid infiltration (as measured by cardiovascular magnetic resonance [CMR] with extracellular volume mapping), and association between CPET parameters and prognosis. Among the 506 patients with ATTR amyloidosis included in this study, the mean (SD) age was 73.5 (10.2) years, and 457 participants (90.3%) were male. Impairment in functional capacity was highly prevalent. Functional impairment in ATTR-CM and ATTR-mixed phenotypes (peak mean [SD] oxygen consumption [VO2], 14.5 [4.3] mL/kg/min and 15.7 [6.2] mL/kg/min, respectively) was observed alongside impairment in the oxygen pulse, with ventilatory efficiency highest in ATTR-CM (mean [SD] ventilatory efficiency/volume of carbon dioxide expired slope, 38.1 [8.6]). Chronotropic incompetence and exercise oscillatory ventilation (EOV) were highly prevalent across all phenotypes, with both the prevalence and severity being higher than in heart failure from different etiologies. Worsening of amyloid burden on CMR was associated with decline in multiple CPET parameters, although chronotropic response and EOV remained abnormal irrespective of amyloid burden. On multivariable Cox regression analysis, peak VO2 and peak systolic blood pressure (SBP) were independently associated with prognosis (peak VO2: hazard ratio, 0.89 [95% CI, 0.81-0.99; P = .03]; peak SBP: hazard ratio, 0.98 [95% CI, 0.97-0.99; P < .001]). In this study, ATTR amyloidosis was characterized by distinct patterns of functional impairment between all disease phenotypes. A high prevalence of chronotropic incompetence, EOV, and ventilatory inefficiency were characteristic of this population. CPET parameters were associated with amyloid burden by CMR and with peak VO2, and SBP, which have been shown to be independent predictors of mortality. These findings suggest that CPET may be useful in characterizing distinct patterns of functional impairment across the spectrum of amyloid infiltration and predicting outcomes, and potentially offers a more comprehensive method of evaluating functional capacity for future prospective studies.

Early detection of myocardial involvement by non-contrast T1ρ mapping of cardiac magnetic resonance in type 2 diabetes mellitus.

This study aims to determine the effectiveness of T1ρ in detecting myocardial fibrosis in type 2 diabetes mellitus (T2DM) patients by comparing with native T1 and extracellular volume (ECV) fraction. T2DM patients (n = 35) and healthy controls (n = 30) underwent cardiac magnetic resonance. ECV, T1ρ, native T1, and global longitudinal strain (GLS) values were assessed. Diagnostic performance was analyzed using receiver operating curves. The global ECV and T1ρ of T2DM group (ECV = 32.1 ± 3.2%, T1ρ = 51.6 ± 3.8 msec) were significantly higher than those of controls (ECV = 26.2 ± 1.6%, T1ρ = 46.8 ± 2.0 msec) (all P < 0.001), whether there was no significant difference in native T1 between T2DM and controls (P = 0.264). The GLS decreased significantly in T2DM patients compared with controls (-16.5 ± 2.4% vs. -18.3 ± 2.6%, P = 0.015). The T1ρ and native T1 were associated with ECV (Pearson's r = 0.50 and 0.25, respectively, both P < 0.001); the native T1, T1ρ, and ECV were associated with hemoglobin A1c (Pearson's r = 0.41, 0.52, and 0.61, respectively, all P < 0.05); and the ECV was associated with diabetes duration (Pearson's r = 0.41, P = 0.016). The AUC of ECV, T1ρ, GLS, and native T1 were 0.869, 0.810, 0.659, and 0.524, respectively. In T2DM patients, T1ρ may be a new non-contrast cardiac magnetic resonance technique for identifying myocardial diffuse fibrosis, and T1ρ may be more sensitive than native T1 in the detection of myocardial diffuse fibrosis.

Global longitudinal strain and plasma biomarkers for prognosis in heart failure complicated by diabetes: a prospective observational study

BackgroundHeart failure (HF) and diabetes are associated with increased incidence and worse prognosis of each other. The prognostic value of global longitudinal strain (GLS) measured by cardiovascular magnetic resonance (CMR) has not been established in HF patients with diabetes.MethodsIn this prospective, observational study, consecutive patients (n = 315) with HF underwent CMR at 3T, including GLS, late gadolinium enhancement (LGE), native T1, and extracellular volume fraction (ECV) mapping. Plasma biomarker concentrations were measured including: N-terminal pro B-type natriuretic peptide(NT-proBNP), high-sensitivity troponin T(hs-TnT), growth differentiation factor 15(GDF-15), soluble ST2(sST2), and galectin 3(Gal-3). The primary outcome was a composite of all-cause mortality or HF hospitalisation.ResultsCompared to those without diabetes (n = 156), the diabetes group (n = 159) had a higher LGE prevalence (76 vs. 60%, p < 0.05), higher T1 (1285±42 vs. 1269±42ms, p < 0.001), and higher ECV (30.5±3.5 vs. 28.8±4.1%, p < 0.001). The diabetes group had higher NT-pro-BNP, hs-TnT, GDF-15, sST2, and Gal-3. Diabetes conferred worse prognosis (hazard ratio (HR) 2.33 [95% confidence interval (CI) 1.43–3.79], p < 0.001). In multivariable Cox regression analysis including clinical markers and plasma biomarkers, sST2 alone remained independently associated with the primary outcome (HR per 1 ng/mL 1.04 [95% CI 1.02–1.07], p = 0.001). In multivariable Cox regression models in the diabetes group, both GLS and sST2 remained prognostic (GLS: HR 1.12 [95% CI 1.03–1.21], p = 0.01; sST2: HR per 1 ng/mL 1.03 [95% CI 1.00-1.06], p = 0.02).ConclusionsCompared to HF patients without diabetes, those with diabetes have worse plasma and CMR markers of fibrosis and a more adverse prognosis. GLS by CMR is a powerful and independent prognostic marker in HF patients with diabetes.

Cardiometabolic biomarker patterns associated with cardiac MRI defined fibrosis and microvascular dysfunction in patients with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a complex disease process influenced by metabolic disorders, systemic inflammation, myocardial fibrosis, and microvascular dysfunction. The goal of our study is to identify potential relationships between plasma biomarkers and cardiac magnetic resonance (CMR) imaging markers in patients with HFpEF. Nineteen subjects with HFpEF and 15 age-matched healthy controls were enrolled and underwent multiparametric CMR and plasma biomarker analysis using the Olink® Cardiometabolic Panel (Olink Proteomics, Uppsala, Sweden). Partial least squares discriminant analysis (PLS-DA) was used to characterize CMR and biomarker variables that differentiate the subject groups into two principal components. Orthogonal projection to latent structures by partial least squares (OPLS) analysis was used to identify biomarker patterns that correlate with myocardial perfusion reserve (MPR) and extracellular volume (ECV) mapping. A PLS-DA could differentiate between HFpEF and normal controls with two significant components explaining 79% (Q2 = 0.47) of the differences. For OPLS, there were 7 biomarkers that significantly correlated with ECV (R2 = 0.85, Q = 0.53) and 6 biomarkers that significantly correlated with MPR (R2 = 0.92, Q2 = 0.32). Only 1 biomarker significantly correlated with both ECV and MPR. Patients with HFpEF have unique imaging and biomarker patterns that suggest mechanisms associated with metabolic disease, inflammation, fibrosis and microvascular dysfunction.

A case of Duchenne muscular dystrophy recovered from prolonged ischemic kidney injury which emerged with a normal creatinine level.

Duchenne muscular dystrophy (DMD) is an inherited disease characterized by progressive degeneration of the skeletal muscles. Renal dysfunction in patients with DMD has recently become more apparent as life expectancy has increased owing to advances in respiratory devices and heart failure therapies. A 23-year-old man with DMD who required nasal tube feeding was referred to our hospital with a 4-month history of renal dysfunction and anemia. The patient's serum creatinine (sCr) level was within the normal range (0.84mg/dL), but his serum cystatin C level and estimated glomerular filtration rate calculated by cystatin C (5.90mg/L and 7.5mL/min/1.73m2, respectively) indicated severe renal impairment. A urinalysis revealed elevated levels of protein and tubular markers. The patient's hemoglobin and erythropoietin levels indicated renal anemia. Hypotension, a collapsed inferior vena cava, and a poor tube feeding episode suggested that the kidney injury was due to renal ischemia, which progressed to tubulointerstitial kidney injury, an intrinsic kidney injury. The angiotensin-converting enzyme inhibitors and beta-blockers were discontinued, and extracellular fluid was infused. Thereafter, the patient's renal function recovered. Subsequently, the patient's urinary findings and anemia improved. Although advances in cardioprotective agents are expected to improve the prognosis of patients with DMD, it is important to consider that the number of patients with kidney injury due to renal ischemia may increase and that it is difficult to evaluate renal function using sCr level in patients with DMD because of decreased skeletal muscle mass.

Morphofunctional Alteration of Mesenteric Lymph Nodes in the Inflammation of the Abdominal Cavity.

This paper provides data regarding the ratios of the functional structures of lymph nodes after inflammation in the abdominal organs. Lymph systems, including lymph nodes, function as filters of tissues and tissue fluids and are places of origin and lymphocyte production for normal physiological functions. They display specific morphological and functional responses in reaction to endogenous and exogenous substances. The morphological pattern of the mesenteric lymph node in experimental rat groups reflects a decrease in its immune function due to the processes of inflammation in the abdominal cavity. These processes work together with the associated organs and their involvement in the abdominal lymph nodes, in which there are discharges of the structure of the paracortical zone under conditions of reduced lymphogenic processes, according to the decrease in the size of the paracortex and the ratios of lymphoid nodes with and without germinal centers. Histological and morphometric analyses show changes in the mesenteric lymph node. These analyses are characterized by changes in the cortical and medullary substances, while the proportion of the cortical structure decreases. We also noted an increase in the number of macrophages in the lymphoid nodes and cerebral sinus, as well as a decrease in the number of mature plasmocytes, the paracortex, and the pulp strands. These changes indicate immunosuppressive effects on the lymph node. Under the conditions of inflammation, the formation of a mixed immune response occurs.

Diffuse myocardial fibrosis is uncommon in people with perinatally acquired human immunodeficiency virus infection

BackgroundCardiovascular disease (CVD) remains a leading cause of death in people living with HIV. Myocardial fibrosis is well-described in HIV infection acquired in adulthood. We evaluate the burden of fibrosis by cardiac magnetic resonance in people with perinatal HIV infection.MethodsIndividuals with perinatally acquired HIV (pnHIV) diagnosed before 10 years-old and on antiretroviral treatment for ≥ 6 months were matched with uninfected controls. Patients with significant cardiometabolic co-morbidities and pregnancy were excluded. Diffuse fibrosis was assessed by cardiac magnetic resonance (CMR) with native T1 mapping for calculation of extracellular volume fraction (ECV). Viability was assessed with late gadolinium enhancement. The normality of fibrosis was assessed using the Komogrov-Smirnov test. Fibrosis between the groups was analyzed using a Mann-Whitney U test, as the data was not normally distributed. Statistical significance was defined as a p-valve < 0.05.ResultsFourteen adults with pnHIV group and 26 controls (71% female and 86% Black race) were assessed. The average (± standard deviation) age in the study group was 29 (± 4.3) years-old. All pnHIV had been on ART for decades. Demographic data, CMR functional/volumetric data, and pre-contrast T1 mapping values were similar between groups. Diastolic function was normal in 50% of pnHIV patients and indeterminate in most of the remainder (42%). There was no statistically significant difference in ECV between groups; p = 0.24.ConclusionPerinatally-acquired HIV was not associated with diffuse myocardial fibrosis. Larger prospective studies with serial examinations are needed to determine whether pnHIV patients develop abnormal structure or function more often than unaffected controls.

Profile of serum microRNAs in heart failure with reduced and preserved ejection fraction: Correlation with myocardial remodeling

Background and aimsCardiomyocyte hypertrophy and interstitial fibrosis are key components of myocardial remodeling in Heart Failure (HF) with preserved (HFpEF) or reduced ejection fraction (HFrEF). MicroRNAs (miRNAs) are non-coding, evolutionarily conserved RNA molecules that may offer novel insights into myocardial remodeling. This study aimed to characterize miRNA expression in HFpEF (LVEF ≥ 45%) and HFrEF (LVEF < 45%) and its association with myocardial remodeling. MethodsProspectively enrolled symptomatic HF patients (HFpEF:n = 36; HFrEF:n = 31) and controls (n = 23) underwent cardiac magnetic resonance imaging with T1-mapping and circulating miRNA expression (OpenArray system). Results13 of 188 miRNAs were differentially expressed between HF groups (11 downregulated in HFpEF). Myocardial extracellular volume (ECV) was increased in both HF groups (HFpEF 30 ± 5%; HFrEF 30 ± 3%; controls 26 ± 2%, p < 0.001). miR-128a-3p, linked to cardiac hypertrophy, fibrosis, and dysfunction, correlated positively with ECV in HFpEF (r = 0.60, p = 0.01) and negatively in HFrEF (r = −0.51, p = 0.04). miR-423-5p overexpression, previously associated HF mortality, was inversely associated with LVEF (r = − 0.29, p = 0.04) and intracellular water lifetime (τic) (r = −0.45, p < 0.05) in both HF groups, and with NT-proBNP in HFpEF (r = −0.63, p < 0.01). ConclusionsmiRNA expression profiles differed between HF phenotypes. The differential expression and association of miR-128a-3p with ECV may reflect the distinct vascular, interstitial, and cellular etiologies of HF phenotypes.

Is it time to end the use of base deficit for fetal well-being assessment?

Authors have expressed reservations regarding the use of base deficit measured in umbilical artery blood samples to assess fetal well-being during the course of labor and to predict neonatal neurologic morbidity. Despite its integration into clinical practice for more than 50 years, obstetricians and maternal-fetal medicine specialists may not realize that this marker has significant limitations in accurately identifying neonatal metabolic acidosis as a proxy for fetal well-being. In brief, there are 2 large families of base deficit, namely whole blood and extracellular fluid. Both rely on equations that use normal adult acid-base characteristics (pH 7.40 and partial CO2 pressure of 40 mm Hg) that overlook the specificity of the normal in utero acid-base status of pH 7.27 and partial CO2 pressure of 54 mm Hg. In addition, it ignores the unique characteristic of the in utero fetal response to acute hypoxia. The dependence on placental circulation for CO2 elimination may lead to extremely high values (up to 130 to 150 mm Hg) during hypoxic events, a phenomenon that is absent in adults with acute metabolic acidosis who can hyperventilate. The dispute over if to include a correction for high partial CO2 pressure in the bicarbonate estimation, as presented in the Great Trans-Atlantic Debates, remains unresolved. The key constants computed for adult acid-base physiology in the current base deficit algorithms, without accounting for the impact of high partial CO2 pressure or other fetal characteristics of buffering capacity (eg, differences in body water content composition, plasma protein, and hemoglobin attributes), may lead to an overestimation of metabolic acidosis, especially in newborns who are experiencing hypercarbia during the early stages of the hypoxic response. These unrecognized limitations impact the base deficit results and may mislead clinicians on fetal well-being assessments when discussing the management of fetal heart rate monitoring and neonatal outcomes. Based on our arguments, we believe that it is prudent to consider an alternative to base deficit for drawing conclusions regarding fetal well-being during the course of birth management. We propose a marker specifically related to the newborn acid-base physiology--the neonatal eucapnic pH correction. This marker can be added to arterial cord blood gas analysis, and we have described how to interpret it as a marker of neonatal metabolic acidosis.

Nuchal Translucency and Congenital Heart Defects.

Nuchal translucency comprises a temporary accumulation of fluid in the subcutaneous tissue on the back of a fetus's neck, which accompanies the crown-rump length and is observed through an ultrasound performed between 11 and 13 weeks + 6 days gestation. Nuchal translucency is considered to be above normal when values are higher than the 95th/99th percentile or equal to or higher than 2.5/3.5 mm. The first connection between increased nuchal translucency and the presence of congenital heart defects is described in the study of Hyett et al., who observed that they are directly proportional. Since that time, several studies have been conducted to understand if nuchal translucency measurements can be used for congenital heart defect screening in euploid fetuses. However, there is great variability in the estimated nuchal translucency cutoff values for congenital heart defect detection. The purpose of this review was to understand how increased nuchal translucency values and congenital heart defects are related and to identify which of these defects are more frequently associated with an increase in these values.

A Novel Likely Pathogenic Variant in NOTCH1 Associated With Primary Lymphedema

Lymphedema is a chronic condition characterized by the accumulation of lymphatic fluid in interstitial and fibro-adipose tissues. Primary lymphedema that arises from intrinsic defects in the lymphatic system is a rare form of lymphedema with a variable age of onset and heterogeneous presentation. Although a number of genetic variants have been identified and matched to corresponding phenotypes, a genetic cause for lymphedema is found in less than 30% of individuals with primary lymphedema. Recently, Michelini et al proposed NOTCH1 as a candidate gene for primary lymphedema, having identified missense variants in NOTCH1 in 7 of 235 patients with primary lymphedema for whom no causative gene had previously been identified. We report the case of a young female who developed bilateral primary lower limb lymphedema and on genetic testing was found to have a previously unreported heterozygous frameshift variant in the NOTCH1 gene predicting loss of function.