Markers Of Syndrome Research Articles

Biological markers of bronchiolitis obliterans syndrome in recipients of allogeneic hematopoietic stem cell transplantation

Bronchiolitis obliterans syndrome (BOS) is a rare non-infectious pulmonary complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) or lung transplantation. Early diagnosis of BOS requires new approaches including the search for biological markers of pulmonary damage after allo-HSCT. The aim of this work is to review literary data on biological markers of BOS. Conclusion. Literary data on biomarkers of BOS in allo-HSCT recipients are limited. Further research is needed.

Course of brain damage following malignant hypertension.

Malignant hypertension (MHT) crisis triggers widespread microvascular damage, particularly in the brain. Despite recent MRI evidence highlighting acute cerebral injuries during MHT crises, follow-up data remain scarce. This study seeks to fill this gap by exploring how brain MRI markers evolve following acute MHT crisis management. We conducted a retrospective analysis of brain MRI data from MHT patients admitted to Bordeaux University Hospital between 2008 and 2022. Eligible patients had at least one follow-up MRI. Analysis blinded to clinical data was performed to identify markers of posterior reversible encephalopathy syndrome (PRES), acute stroke, cerebral hemorrhage, and microangiopathy. Out of 149 patients, 47 had follow-up MRIs. Most were male (72.3%) with a mean age of 48.2 ± 10.8 years. The median interval between initial and follow-up MRI was 228 days. Follow-up MRIs revealed new strokes in 10.6% of patients, cerebral hemorrhages in 4.3%, and no cases of PRES. Additionally, more patients exhibited chronic lacunar infarcts and/or microbleeds, with overall Fazekas scores remaining stable in 66.0%, improving in 31.9%, and worsening in 2.1%. Subgroup analyses based on blood pressure control or follow-up duration showed no significant differences in MRI markers. This study sheds light on the risk of new cerebrovascular events and the dynamic changes in brain MRI markers following acute MHT crisis management. Understanding these changes could lead to improved diagnosis, personalized treatment strategies, and proactive patient care for individuals with MHT.

Modeling the pre-symptomatic stage of hemi-parkinsonian state in animals (rodents and monkeys)

The behavioral and functional states preceding the onset specific parkinsonian symptoms were studied at an early (pre-symptomatic) stage of hemi-parkinsonian syndrome development in rodents and monkeys. The pre-symptomatic stage of the hemi-parkinsonian syndrome was determined in rodents (mice and rats) treated by chronic administration of low doses of rotenone toxin. The consecutive steps of neuropathological traits development in rodents included the cognitive impairment at the 1st-2nd week of exposure to rotenone, minor movement disorders at the 3st-4nd week before the onset of severe motor dysfunction as well as some biochemical indicators. The latencies and amplitudes of visually guided saccades (VGS) while conditioned instrumental task performing were studied in nonhuman primates (Macaca mulatta) chronically treated with low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The elongation of VGS latencies and the decline of their accuracy were revealed with development of MPTP-induces syndrome but conditioned instrumental performance was not affected. The negative behavioral effects manifested in animals at the pre-symptomatic stage of toxins induced disease both in the rotenone model in rodents and in MPTP model in monkeys suggesting them as early markers of a hemi-parkinsonian syndrome.

Investigating metabolic syndrome markers and body mass index changes in patients with acne vulgaris treated with isotretinoin: A prospective study.

Acne vulgaris is a common inflammatory skin disease that occurs during puberty, affecting approximately 85% of young adults and may persist into adulthood. The pathophysiology of acne is multifactorial, involving hormonal, inflammatory, and immune mechanisms. Isotretinoin is widely used for treating severe cystic acne or recurrent acne. This medication is considered a pharmacological option that significantly reduces sebum secretion, leading to a reduction in the size of sebaceous glands. It also induces a lack of differentiation in sebaceous cysts, resulting in a decrease in lipid accumulation. This research is a prospective study. Patient contact details were obtained directly from those visiting the dermatology clinic, and they were monitored for a duration of 3 months. Essential data was gathered through patient examinations and inquiries at the clinic, including the prescription of tests prior to initiating isotretinoin treatment. Furthermore, follow-up tests and examinations were performed within the initial and third months post-treatment commencement. Sixty-two patients participated in the study, selected through non-probability (convenience) sampling. The therapeutic dose taken by patients was 20 mg of isotretinoin daily (n = 49) or every other day (n = 13). Among the participants, six patients experienced a decrease of 3 units or more in HDL levels, while 16 patients saw an increase of 3 units or more in LDL levels, 3 months after beginning the treatment. Additionally, the triglyceride (TG) levels increased by 9 units or more in six individuals, and the blood sugar (BS) levels increased by 5 units or more in nine individuals, 3 months after treatment initiation. Moreover, one person's waist circumference increased by 1.5 cm 3 months after treatment began. The average weight of the individuals at the end of the treatment rose from 60.74 kg to 61.12 kg. However, this weight increase was not statistically significant. (p > 0.05). In general, the results of our study show that the use of oral isotretinoin as a treatment option for the management of acne vulgaris can be effective when administered at the correct dosage, offering a safe and low-complication option.

Association Between the Triglyceride-Glucose Index and Serum Uric Acid to High-Density Lipoprotein (HDL) Cholesterol Ratio in Type 2 Diabetes Mellitus in Gabes City, Tunisia.

Background Type 2 diabetes mellitus (T2DM) is a significant risk factor for cardiovascular diseases (CVD). The triglyceride-glucoseindex (TyGi) is a novel biomarker for insulin resistance, strongly linked to CVD. Elevated serum uric acid levels and the uric acid to high-density lipoproteincholesterol ratio (UHR) are emerging as markers of metabolic syndrome and cardiovascular risk in T2DM. This study aimed to explore the association between the TyGiand UHR in T2DM patients. Objectives The aim of this study is to compare metabolic parameters in T2DM patients and assess the association between the TyGiand serum UHR. Methodology A cross-sectional case-control study was conducted at the University Hospital of Gabes, Gabes City, Tunisia with 50 T2DM patients and 50 gender-matched healthy controls. Inclusion criteria included adults aged 30-75 years with a confirmed diagnosis of T2DM on stable medication for at least three months. Exclusion criteria included other types of diabetes, significant liver or kidney disease, recent cardiovascular events, endocrine disorders, and substance abuse. Metabolic and biochemical parameters, including fasting blood sugar, postprandial blood sugar, glycosylated hemoglobin, lipid profile, and renal function, were measured. The TyGiand serum UHR were calculated and analyzed for correlations. Results T2DM patients exhibited significantly higher fasting blood sugar, postprandial blood sugar, glycosylated hemoglobin, TyGi, and serum UHR compared to controls, indicating impaired glycemic control and adverse lipid profiles. The UHR showed a positive correlation with a strong negative correlation with HDL and a positive correlation with uric acid levels. The linear regression analysis indicated a weak positive trend between the TyGi and serum UHR, although not statistically significant. Conclusion This study underscores the importance of the TyGiand serum UHRas biomarkers for evaluating metabolic and cardiovascular risk in T2DM. Further research is needed to explore their combined utility in clinical practice for early detection and management of cardiovascular complications in diabetic patients.

Neurological-related proteomic profiling in plasma of children with metabolic healthy and unhealthy overweight/obesity.

Children with overweight/obesity (OW/OB) exhibit poor cardiometabolic health, yet mechanisms influencing brain health remain unclear. We examined the differences in neurological-related circulating proteins in plasma among children with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) and the association with metabolic syndrome markers. In this cross-sectional study, we included 84 Caucasian children (39% girls), aged 10.1 ± 1.1 years, from the ActiveBrains project (NCT02295072). A ninety-two-protein targeted approach using Olink's® technology was used. We identified distinct concentrations of CD38, LAIR2, MANF and NRP2 proteins in MHO compared with MUO. Moreover, individual metabolic syndrome (MS) markers were linked to nine proteins (CD38, CPM, EDA2R, IL12, JAMB, KYNU, LAYN, MSR1 and SMOC2) in children with OW/OB. These proteins play crucial roles in diverse biological processes (e.g., angiogenesis, cholesterol transport, nicotinamide adenine dinucleotide (NAD+) catalysis and maintenance of blood-brain barrier) related to brain health. Our proteomics study suggests that cardiometabolic health (represented by MHO/MUO or individual MS markers) is associated with the concentration in plasma of several proteins involved in brain health. Larger-scale studies are needed to contrast/confirm these findings, with CD38 standing out as a particularly noteworthy and robust discovery.

The Synergistic Enhancement of Anti-Metabolic Diseases Function of Morus alba with the Combination of Cha (Camellia sinensis)

Background: Functional foods play an important role in the prevention and ameliora-tion of metabolic syndromes leading to type 2 diabetes. Plant resources that have anti-metabolic syndromes activity, such as Morus alba L. and Cha [Camellia sinensis L.], have been used in functional foods against diabetes. Since Morus and Cha have different mechanisms of action against metabolic syndromes, such as prevention of sugar uptake and lipidosis, respectively, and the combination of both resources will be a reliable approach for developing more efficient functional food against type 2 diabetes because certain synergism is expected in their functions. Methods: Male Wister Rats were fed the high fat-high sucrose [HFHS] diet for 12 weeks, with and without supplementation of Morus and Cha alone and their combination, and the effect of their supplementation on the markers of the metabolic syndrome such as obesity, lipidosis, and fatty liver formation, were examined. Results: Several metabolic syndrome markers, including body weight gain, lipid deposit, and fatty liver formation, were more significantly prevented by the diet supplemented with Morus and Cha combination compared to Morus or Cha given separately . Conclusion: Appropriate formulation of food resources with different functional mechanisms is a promising strategy for developing effective dietary treatment of type 2 diabetes that is a typical Mibyou.

Integrated analysis of gut microbiome and its metabolites in ACE2-knockout and ACE2-overexpressed mice.

Aberrant activation of the classic renin-angiotensin system (RAS) and intestinal micro dysbiosis adversely affect insulin resistance (IR), dyslipidemia, and other metabolic syndrome markers. However, the action of angiotensin-converting enzyme 2 (ACE2) and gut health in systemic homeostasis vary, and their interaction is not completely understood. We adopted a combinatory approach of metabolomics and fecal 16S rRNA analysis to investigate gut microbiota and metabolite in two different mouse models, ACE2 knockout (ACE2 KO) mice and the ACE2-overexpressing obese mice. 16S rRNA gene sequencing revealed that ACE2 influences microbial community composition and function, and ACE2 KO mice had increased Deferribacteres, Alcaligenaceae, Parasutterella, Catenibacterium, and Anaerotruncus, with decreased short-chain fatty acid (SCFA)-producing bacteria (Marvinbryantia and Alistipes). In contrast, ACE2-overexpressed mice exhibited increased anti-inflammatory probiotic (Oscillospiraceae, Marinifilaceae, and Bifidobacteriaceae) and SCFA-producing microbes (Rikenellaceae, Muribaculaceae, Ruminococcaceae, Odoribacter, and Alistipes) and decreased Firmicutes/Bacteroidetes, Lactobacillaceae, Erysipelotrichaceae, and Lachnospiraceae. Metabolome analysis indicated differential metabolites in ACE2 KO and ACE2-overexpression mice, especially the glucolipid metabolism-related compounds. Furthermore, correlation analysis between gut microbiota and metabolites showed a dynamic mutual influence affecting host health. Our study confirms for the first time a significant association between ACE2 status and gut microbiome and metabolome profiles, providing a novel mechanism for the positive effect of ACE2 on energy homeostasis.

Mitochondrial Biomarkers and Metabolic Syndrome in Bipolar Disorder

The object of this study is test whether mitochondrial blood-based biomarkers are associated with markers of metabolic syndrome in bipolar disorder, hypothesizing higher lactate but unchanged cell-free circulating mitochondrial DNA levels in bipolar disorder patients with metabolic syndrome. In a cohort study, primary testing from the FondaMental Advanced Centers of Expertise for bipolar disorder (FACE-BD) was conducted, including 837 stable bipolar disorder patients. The I-GIVE validation cohort consists of 237 participants: stable and acute bipolar patients, non-psychiatric controls, and acute schizophrenia patients. Multivariable regression analyses show significant lactate association with triglycerides, fasting glucose and systolic and diastolic blood pressure. Significantly higher levels of lactate were associated with presence of metabolic syndrome after adjusting for potential confounding factors. Mitochondrial-targeted metabolomics identified distinct metabolite profiles in patients with lactate presence and metabolic syndrome, differing from those without lactate changes but with metabolic syndrome. Circulating cell-free mitochondrial DNA was not associated with metabolic syndrome. This thorough analysis mitochondrial biomarkers indicate the associations with lactate and metabolic syndrome, while showing the mitochondrial metabolites can further stratify metabolic profiles in patients with BD. This study is relevant to improve the identification and stratification of bipolar patients with metabolic syndrome and provide potential personalized-therapeutic opportunities.

Whole blood transcriptomic signature of Cushing's syndrome.

Cushing's syndrome is characterized by high morbidity and mortality with high interindividual variability. Easily measurable biomarkers, in addition to the hormone assays currently used for diagnosis, could reflect the individual biological impact of glucocorticoids. The aim of this study is to identify such biomarkers through the analysis of whole blood transcriptome. Whole blood transcriptome was evaluated in 57 samples from patients with overt Cushing's syndrome, mild Cushing's syndrome, eucortisolism, and adrenal insufficiency. Samples were randomly split into a training cohort to set up a Cushing's transcriptomic signature and a validation cohort to assess this signature. Total RNA was obtained from whole blood samples and sequenced on a NovaSeq 6000 System (Illumina). Both unsupervised (principal component analysis) and supervised (Limma) methods were used to explore the transcriptome profile. Ridge regression was used to build a Cushing's transcriptome predictor. The transcriptomic profile discriminated samples with overt Cushing's syndrome. Genes mostly associated with overt Cushing's syndrome were enriched in pathways related to immunity, particularly neutrophil activation. A prediction model of 1500 genes built on the training cohort demonstrated its discriminating value in the validation cohort (accuracy .82) and remained significant in a multivariate model including the neutrophil proportion (P = .002). Expression of FKBP5, a single gene both overexpressed in Cushing's syndrome and implied in the glucocorticoid receptor signaling, could also predict Cushing's syndrome (accuracy .76). Whole blood transcriptome reflects the circulating levels of glucocorticoids. FKBP5 expression could be a nonhormonal marker of Cushing's syndrome.

BIOCHEMICAL IMBALANCE IN ISCHEMIC HEART DAMAGE COMBINED WITH STEATOHEPATOSIS

The development of steatohepatosis in most cases is the primary process and consequence of the metabolic syndrome. This disease has a long asymptomatic course. The connection of steatohepatosis with the development and progression of coronary heart disease occurs when steatohepatosis is associated with metabolic syndrome and obesity. Patients with steatohepatosis usually have signs of metabolic syndrome: arterial hypertension, abdominal obesity, impaired glucose tolerance, atherogenic dyslipidemia, which are considered risk factors for cardiovascular diseases. Biochemical parameters were determined in coronary artery disease complicated by steatohepatosis. 101 people were examined. When examining the serum level of brain natriuretic peptide in patients with ischemic heart disease in combination with steatohepatosis, a higher level was found than in uncomplicated coronary heart disease, which indicates a deeper violation of the functional state of the myocardium in ischemic heart disease in combination with steatohepatosis. When examining the cytolytic syndrome markers LDH, AST and ALT, a probable increase in their activity is observed. The detected activation of LDH is associated with damage, tissue necrosis, which is observed in the case of damage to the myocardium and hepatocytes in the examined groups, which indicates an inflammatory type of pathogenesis. Apparently, activation of transaminases is associated with cytolytic syndrome in myocardial damage and increased energy expenditure of hepatocytes in fatty hepatosis. Signs of impaired glucose tolerance were found in the examined subjects: the fasting glucose level and the postprandial glucose level probably exceeded normal values, the HbA1c level was 1.5 times higher than the control in myocardial ischemia, and 1.7 times higher in coronary heart disease and steatohepatosis (p< 0.05). Disruption of hormonal regulation of carbohydrate metabolism was detected in both examined groups. An elevated level of total cholesterol and dyslipoproteinemia were also found in both groups of examined patients, however, the most pronounced changes are observed in the case of complications of steatohepatosis. The obtained results indicate complex disorders of lipid metabolism in myocardial ischemia and ischemic heart damage in combination with steatohepatosis, which confirms the development of metabolic syndrome.

Assessing serum c reactive protein/albumin ratio and leukocyte count as biochemical markers of polycystic ovary syndrome

Assessing serum c reactive protein/albumin ratio and leukocyte count as biochemical markers of polycystic ovary syndrome

Evidence of phenotypes and dissociative diagnostic markers for demonic possession syndrome

ObjectiveAccording to clinical models of personality, patients with dissociative identity disorder (DID) who have experienced demonic possession (psychiatric possession syndrome or PPS) may present two profiles: the schizo-paranoid profile (characteristic of psychotic spectrum disorder or PSD) and the hysteroid-histrionic profile (characteristic of affective disorders). The present study aimed to examine the clinical and statistical evidence of these phenotypic personality structures in patients with PPS and DID (with and without PSD). MethodsThe design of this investigation was based on structural equation modeling. A total of 303 patients were diagnosed with DID without psychosis and 306 were diagnosed with DID with PSD; the diagnosis was made by clinical professionals who collaborated on this research and conducted the assessment tests. All patients completed clinical questionnaires on their personality structures, and dissociation level was also measured. The physician-psychiatrist assessed each patient using the Psychiatric Possession Syndrome Checklist (PPS-C), a new hetero-applied questionnaire on the symptomatic intensity of PPS. ResultsThe results led to the conclusion that both personality structures were 65 %–66 % predictive of possession syndrome. Dissociative symptoms attributable to DID modulated the PPS variance by 21 % to 26 %. Validity evidence has been obtained for the combined phenotypic personality model that integrates DID and PSD structures. ConclusionsWe discuss the psychopathological and therapeutic implications of the analysis on the dissociative mechanisms involved in each personality phenotype. We also provide a graphical summary of the PPS symptoms, organized into a normalized distribution, which may prove useful for professional practice. Additionally, we present potential clinical scores from the PPS-C.

Study of senile astheny markers against the background of acute inflammatory process in elderly and senile patients in emergency abdominal surgery

The aim of our work was to determine the influence of the acute inflammatory process on the diagnostic value of markers of senile asthenia in emergency abdominal surgery. Material and methods. The basis of the work included 92 (100.0 %) patients, the average age in the entire group was 72.0 ± 2.3 years. All patients were divided into three groups: group A – 32 (34.8 %) patients with acute surgical pathology and confirmed senile asthenia syndrome. The group included 15 (16.3 %) patients with acute cholecystitis and 17 (18.5 %) with perforation of a gastric or duodenal ulcer. Group B included 30 (32.6 %) people with acute surgical pathology, which was statistically comparable in terms of the number of surgical diagnoses to group A, but without asthenia. To determine the reliability of the inflammatory process influence on markers of senile asthenia, we formed group C – 30 (32.6 %) patients without acute surgical pathology, but with the syndrome of senile asthenia. Based on the literature analysis, we selected markers of malnutrition syndrome: total protein, albumin and cholesterol levels, and the marker of sarcopenia – somatotropic hormone. Results. Based on the comparison of the obtained results, we found a decrease in the level of total protein in groups A and C, which was not significantly different, p = 0.2519, U = 372.0. Whereas when comparing groups, A and B, a significant decrease was found in the group of patients with asthenia (A) – p = 0.0009, U = 224.0. The same data were obtained when comparing the level of albumin; in groups A and C the level of albumin was reduced but did not differ significantly between groups – p = 0.1932, U = 361.5, whereas comparing groups with senile asthenia syndrome (group A) and without it (group B), a significant difference was found – p = 0.0072, U = 268.0. When determining the cholesterol level, we did not find a significant difference between the groups with asthenia (A and C) – p = 0.0614, U = 323.0, as well as between the groups with asthenia and without asthenia with acute inflammation (A and B) – p = 0.01646. It was determined that the level of somatotropic hormone in the groups with asthenia (A and C) was equally low – p = 0.9646, U = 466.5, while when comparing the group with and without asthenia (A and B), a significant decrease in this hormone was found in group A – p = 0.0030, U = 248.5. Conclusions. The absence of acute inflammatory process influence on the diagnostic value of the studied markers of senile asthenia in the groups was determined. When comparing the results between group A (acute surgical pathology + senile asthenia syndrome) and group B (acute surgical pathology without senile asthenia syndrome), a significant decrease in the level of total protein, albumin, and somatotropic hormone was revealed, p = 0.0009, p = 0.0072 and p = 0.0030, respectively, while when comparing groups with asthenia (A and C) no significant difference was found, p = 0.2519, p = 0.1932 and p = 0.9646. The level of total cholesterol cannot be used as a marker for the diagnosis of senile asthenia in emergency abdominal surgery, as there are a significant number of factors that directly affect the results of the diagnosis. Comparison of the results of the groups with asthenia and without asthenia on the background of acute inflammatory process (A and B) showed no significant difference, p = 0.1646. The same negative results were obtained when evaluating groups with asthenia (A and C) – p = 0.0614.

Alterations in Neurotrophins in Alcohol-Addicted Patients during Alcohol Withdrawal.

Alcohol use disorder (AUD) is related to mental and somatic disorders that result in alcohol withdrawal syndrome (AWS), with 30% of AWS cases leading to life-threatening delirium tremens (DTs). Currently, studies do not support using any one biomarker in DTs. Neurotrophins affect neuromodulation, playing a role in the pathogenesis of AUD, AWS, and DTs. This review aims to summarize experimental and clinical data related to neurotrophins and S100B in neuroplasticity, as well as neurodegeneration in the context of AUD, AWS, and DTs. This work used publications that were selected based on the protocol consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The BDNF level could be a good candidate biomarker for relapse susceptibility, as it is significantly reduced during consumption and gradually increases during abstinence. GDNF influences AUD through its integral role in the function of dopaminergic neurons and ablates the return to alcohol-drinking behavior. NGF protects neurons from ethanol-induced cytotoxic damage and affects recovery from cognitive deficits after brain damage. The NT-3 level is decreased after alcohol exposure and is involved in compensatory mechanisms for cognitive decline in AUD. NT-4 affects oxidative stress, which is associated with chronic alcohol consumption. S100B is used as a biomarker of brain damage, with elevated levels in serum in AUD, and can protect 5-HT neurons from the damage caused by alcohol. BDNF, GDNF, NT-3, NT-4, NGF, and S100B may be valuable markers for withdrawal syndrome. In particular, the most relevant is their association with the development of delirium complications. However, there are few data concerning some neurotrophins in AWS and DTs, suggesting the need for further research.

#512 Two are better than one: a new combination treatment for cystinosis

Abstract Background and Aims Nephropathic cystinosis is a rare, lysosomal storage disorder resulting from mutations in the CTNS gene, encoding a cystine transporter. Disruption of this protein leads to the accumulation of cystine in cells and the formation of crystals that damage tissues and organs. Patients usually present around 6-months of age with failure to thrive, excessive thirst (polydipsia) and urination (polyuria) and Fanconi syndrome (excessive loss of important nutrients in the urine). The kidneys are seriously affected due to proximal tubule dysfunction and if left untreated this can lead to kidney failure by the age of 10. Patients receive the drug-based therapy cysteamine from the time of diagnosis. However, even with prolonged treatment, individuals may still advance to kidney failure, necessitating transplantation. As such, there is an urgent need for alternative treatments. In previous work using stem cell and kidney organoid models, we discovered that a drug combination of cysteamine and the mTOR inhibitor, Everolimus, can correct the cystinotic cell phenotype. To evaluate the therapeutic potential of this therapy in vivo, we generated a cystinotic rat model that faithfully recapitulates the human disease phenotype within 3–6 months as seen by: failure to gain weight, polydipsia and polyuria, cystine accumulation, Fanconi syndrome and kidney dysfunction. Using these Ctns knockout (KO) rats we performed pre-clinical testing to evaluate the therapeutic potential of Cysteamine/Everolimus combination treatment. Method Six-week-old male Ctns KO rats (n = 6) were dosed with either vehicle, Cysteamine-only, Everolimus-only or combination (Cysteamine and Everolimus) delivered via jelly pills for 6 months. Body weights were recorded weekly and blood and urine collected monthly for in-depth chemical analysis of Fanconi syndrome markers. At the end of the study, tissues were harvested for cystine measurements, immunohistochemistry and histology. Results Cysteamine monotreatment was efficacious in ameliorating the disease phenotype while Everolimus alone showed mixed results. However, combination treatment resulted in a superior reduction in tissue cystine levels, polydipsia, polyuria and a superior improvement in Fanconi syndrome markers, gross kidney morphology and histology compared to monotreatments. Specifically, in-depth urine analysis at 6 months showed significantly reduced levels of albumin, total protein and glucose in combination-treated animals compared to cysteamine monotreatment. Furthermore, the kidneys of combination-treated animals showed a greater amount of undamaged proximal renal tubules when compared to vehicle, cysteamine and Everolimus-treated kidneys along with a greater preservation of Lrp2/Megalin. Conclusion Overall the combination treatment resulted in greater preservation and protection of renal structures compared to monotreatments. These results demonstrate the potential of a Cysteamine/Everolimus dual therapy to improve the treatment of cystinosis.

Detection frequency and duration of circulating antiphospholipid syndrome markers in patients with verified COVID-19

Aim: to develop enzyme-linked immunosorbent tests for assessing the antiphospholipid syndrome (APS) markers and determine prevalence of three antiphospholipid antibody (aPL) types at different COVID-19 stages. Materials and Methods. A comparative longitudinal controlled study was conducted by examining 120 subjects with COVID-19 diagnosis verified by reverse transcription polymerase chain reaction. Donor serum samples collected before November 2019 were used as a control group. The laboratory study included measurement of IgA, IgM and IgG against β2-glycoprotein 1 (β2-GP1), cardiolipin, phosphatidylserine-prothrombin complex (PS-PT) by using domestically produced test systems based on indirect two-step enzyme-linked immunosorbent assay. Results. Validation of the developed experimental tests was carried out in comparison with foreign commercial analogues in accordance with international standards. Alternative antigenic targets for effective diagnosis of antibodies against β2-GP1 were studied. Analyzing rate of aPL in patients at different COVID-19 stages showed that in acute vs. convalescence stage it was higher by 1.3-fold (81.7 and 65.0 %, respectively). The first rank detection place was assigned to IgG against β2-GP1, cardiolipin and PS-PT, the second – IgM against cardiolipin. The profile of the detected antibodies changed at various COVID-19 stages driven by time frame elapsed from the moment of diagnosis. Conclusion. Recombinant constructs are created and analytical conditions are optimized for determining various aPL types. It was shown that along with other viral infections, COVID-19 triggers autoantibody production demonstrating that 54.2 % individuals infected with SARS-CoV-2 were positive at least for one autoantibody type. The majority of such virus-associated aPL are presumably transiently positive.

The Development of Socially Directed Attention: An Functional Magnetic Resonance Imaging Study in Infant Monkeys.

Socially guided visual attention, such as gaze following and joint attention, represents the building block of higher-level social cognition in primates, although their neurodevelopmental processes are still poorly understood. Atypical development of these social skills has served as early marker of autism spectrum disorder and Williams syndrome. In this study, we trace the developmental trajectories of four neural networks underlying visual and attentional social engagement in the translational rhesus monkey model. Resting-state fMRI (rs-fMRI) data and gaze following skills were collected in infant rhesus macaques from birth through 6 months of age. Developmental trajectories from subjects with both resting-state fMRI and eye-tracking data were used to explore brain-behavior relationships. Our findings indicate robust increases in functional connectivity (FC) between primary visual areas (primary visual cortex [V1] - extrastriate area 3 [V3] and V3 - middle temporal area, ventral motion areas middle temporal area - AST, as well as between TE and amygdala (AMY) as infants mature. Significant FC decreases were found in more rostral areas of the pathways, such as areas temporal area occipital part - TE in the ventral object pathway, V3 - lateral intraparietal (LIP) of the dorsal visual attention pathway and V3 - temporo-parietal area of the ventral attention pathway. No changes in FC were found between cortical areas LIP-FEF and temporo-parietal area - Area 12 of the dorsal and ventral attention pathways or between AST-AMY and AMY-insula. Developmental trajectory of gaze following revealed a period of dynamic changes with gradual increases from 1 to 2 months, followed by slight decreases from 3 to 6 months. Exploratory association findings across the 6-month period showed that infants with higher gaze following had lower FC between primary visual areas V1-V3, but higher FC in the dorsal attention areas V3-LIP, both in the right hemisphere. Together, the first 6 months of life in rhesus macaques represent a critical period for the emergence of gaze following skills associated with maturational changes in FC of socially guided attention pathways.

Absent or hypoplastic nasal bone: What to tell the prospective parents?

Absent or hypoplastic nasal bone (AHNB) on first or second-trimester ultrasonography (USG) is an important soft marker of Down syndrome. However, due to its varied incidence in euploid and aneuploid fetuses, there is always a dilemma of whether to go for invasive fetal testing for isolated AHNB. This study aims to assess outcomes specifically within the context of Indian ethnicity women. This was a prospective observational study. All patients who reported with AHNB in the first- or second-trimester USG were included. Genetic counseling was done, and noninvasive and invasive testing was offered. Chromosomal anomalies were meticulously recorded, and pregnancy was monitored. The incidence of AHNB in our study was 1.16% (47/4051). Out of 47 women with AHNB, the isolated condition was seen in 32 (0.78%) cases, while AHNB with structural anomalies was seen in nine cases (0.22%). Thirty-nine women opted for invasive testing. Six out of 47 had aneuploidy (12.7%), while two euploid cases (4.25%) developed nonimmune hydrops. The prevalence of Down syndrome in fetuses with AHNB was 8.5% (4/47) and 0.42% (17/4004) in fetuses with nasal bone present. This difference was statistically significant (p = .001). The results indicate that isolated AHNB cases should be followed by a comprehensive anomaly scan rather than immediately recommending invasive testing. However, invasive testing is required when AHNB is associated with other soft markers or abnormalities. As chromosomal microarray is more sensitive than standard karyotype in detecting chromosomal aberrations, it should be chosen over karyotype.

Diagnostic markers of acute encephalitis syndrome and COVID-associated multisystem inflammatory syndrome in children from Southern India.

Acute encephalitis syndrome (AES) in children poses a significant public health challenge in India. This study aims to explore the utility of host inflammatory mediators and neurofilament (NfL) levels in distinguishing etiologies, assessing disease severity, and predicting outcomes in AES. We assessed 12 mediators in serum (n = 58) and 11 in cerebrospinal fluid (CSF) (n = 42) from 62 children with AES due to scrub typhus, viral etiologies, and COVID-associated multisystem inflammatory syndrome (MIS-C) in Southern India. Additionally, NfL levels in serum (n = 20) and CSF (n = 18) were examined. Clinical data, including Glasgow coma scale (GCS) and Liverpool outcome scores, were recorded. Examining serum and CSF markers in the three AES etiology groups revealed notable distinctions, with scrub typhus differing significantly from viral and MIS-C causes. Viral causes had elevated serum CCL11 and CCL2 compared with scrub typhus, while MIS-C cases showed higher HGF levels than scrub typhus. However, CSF analysis showed a distinct pattern with the scrub typhus group exhibiting elevated levels of IL-1RA, IL-1β, and TNF compared with MIS-C, and lower CCL2 levels compared with the viral group. Modeling the characteristic features, we identified that age ≥3 years with serum CCL11 < 180 pg/mL effectively distinguished scrub typhus from other AES causes. Elevated serum CCL11, HGF, and IL-6:IL-10 ratio were associated with poor outcomes (p = 0.038, 0.005, 0.02). Positive CSF and serum NfL correlation, and negative GCS and serum NfL correlation were observed. Median NfL levels were higher in children with abnormal admission GCS and poor outcomes. Measuring immune mediators and brain injury markers in AES provides valuable diagnostic insights, with the potential to facilitate rapid diagnosis and prognosis. The correlation between CSF and serum NfL, along with distinctive serum cytokine profiles across various etiologies, indicates the adequacy of blood samples alone for assessment and monitoring. The association of elevated levels of CCL11, HGF, and an increased IL-6:IL-10 ratio with adverse outcomes suggests promising avenues for therapeutic exploration, warranting further investigation.