Pathophysiology Of Syndrome Research Articles

Urinary interleukin 13 level in steroid sensitive and resistant nephrotic syndrome: a cross-sectional single center study

Nephrotic syndrome, the most common glomerular disease in pediatric population, is classified into two groups of steroid sensitive (SSNS) and resistant (SSRS). There is growing evidence on the role of T cells cytokines, including interleukin-13, in pathophysiology of nephrotic syndrome and steroid response. This study was a cross-sectional study conducted at Children’s Medical Center Hospital in order to explore the relationship between urinary IL-13 levels and responsiveness to corticosteroid treatment. All children (1 to 15 years) referred from January 2021 to January 2022 diagnosed with nephrotic syndrome were included. Urine samples were collected during the initial phase or relapse of nephrotic syndrome, before the initiation of steroid or alternative treatments. Interleukin-13 levels in the urine were measured using the ELISA method. In this study, 83 cases of nephrotic syndrome were enrolled, of whom 30 (36.1%) were girls and 53 (63.9%) were boys. Out of the 83 cases, 63 (75.9%) were identified as SSNS and 20 (24.1%) as SRNS. There was no significant difference between the urinary interleukin-13 levels between SSNS and SRNS groups (P-value: 0.84). Sex (P-value: 0.598) and age (P-value: 0.704) also had no association with interleukin-13 levels. Further studies in larger population are recommended to better assess the potential of this biomarker to predict response to treatment. .

Elevated Posterior Insula Glutamate in Patients with Sickle Cell Disease

Sickle cell disease (SCD) is an inherited hemolytic disorder accompanied by chronic pain and recurrent acute painful episodes known as vaso-occlusive crises (VOCs). Increased Glx (glutamate+glutamine) and lowered insula GABA concentration has been reported in the insula of patients with fibromyalgia, a nociplastic chronic pain condition, and may affect the pathophysiology of pain-related syndromes. Therefore, proton magnetic resonance spectroscopy (1H-MRS) was conducted to measure levels of Glx and other brain metabolites using a single voxel (size: 2×3×3 cm3) in the right posterior insula cortex (PIC) in 17 individuals with SCD and 17 ethnicity-, age- and sex-matched healthy controls (HCs). The frequency of VOCs in the preceding 12 months was recorded. The concentration of Glx (p=0.019) and the ratio of Glx to tCr (total creatine, p=0.035) in the PIC were significantly higher in patients with SCD as compared to matched HCs (n=17). Secondary analyses with the unpaired full sample of 24 SCD also showed a significantly higher level of Glx/tCr than HCs (n=19), with a positive correlation between the level of Glx/tCr and the number of VOCs (p=0.034, r=0.476), as well as a negative correlation between Glx and sensory sensitivity assessed by tonic pressure pain in gastrocnemius area of the non-dominant leg (p=0.040, r=-0.462). The unpaired full sample additionally revealed a significant difference in sensory sensitivity (p=0.050). Altered metabolites such as GABA and myoinositol were also observed between SCD and HCs. These results suggest that elevated excitatory neurotransmission in the insula might contribute to nociplastic pain in SCD. PerspectiveOur work highlighted the innovative finding of elevated levels of the excitatory neurotransmitter glutamate with glutamine in patients with SCD compared to healthy controls. The trend of positive relationship between Glx/tCr and the frequency of VOCs suggests that an excitatory brain neurotransmitter imbalance may be involved in VOCs.

Tardive Syndromes: A Challenging Multitude of Maladies.

"Tardive syndrome" is an umbrella term for a group of drug-induced movement disorders associated with the prolonged use of mainly dopamine receptor blockers and also other medications. Early recognition followed by gradual withdrawal of the incriminating drug may lead to reversal, although not in all patients. Tardive syndromes are usually mixed movement disorders, with specific phenotypes, which may lead to severe disability. The pathophysiology remains incompletely understood. Treatment ranges from medical options, particularly dopamine-depleting agents and chemodenervation (botulinum toxin), to surgical options (deep brain stimulation and lesioning surgeries). Most studies that focused on treatment are limited by small patient numbers. Unfortunately, tardive syndromes often remain under-recognized in clinical practice. This article reviews the historical aspects, epidemiology and risk factors, pathophysiology, diagnostic criteria, clinical phenotypes, and management of tardive syndromes.

Screening of Piglets for Signs of Inflammation and Necrosis as Early Life Indicators of Animal Health and Welfare Hazards

Ensuring animal health and well-being requires animal-based measures for early and direct intervention at the point of care. Insight into the pathophysiology of Swine Inflammation and Necrosis Syndrome (SINS) has led to a non-invasive, clinical scoring system that can be used in daily practice. This provides information on the cause of observed lesions for direct intervention in affected herds. The aim of the current study was to re-evaluate the practicality of the SINS scoring system under field conditions. In addition, this is the first study to provide insight into the prevalence of SINS on Dutch farms. This study involved the scoring of 5958 piglets from 20 visits on 13 farms randomly selected by a veterinary practice in the Netherlands. The results showed that up to 64.1% of the piglets had visible inflammatory alterations in different body parts within the first seven days of life. Sow rectal temperature, signs of coprostasis and water intake during pregnancy were significantly (p ≤ 0.05) correlated with the prevalence of SINS in piglets. In conclusion, the SINS scoring system is an easy-to-use, non-invasive diagnostic tool that summarises animal-based observations at the point of care, providing a valuable communication tool between farmers, nutritionists and veterinarians in their efforts to improve animal health and welfare.

The patient-specific mouse model with Foxg1 frameshift mutation provides insights into the pathophysiology of FOXG1 syndrome.

Single allelic mutations in the forebrain-specific transcription factor gene FOXG1 lead to FOXG1 syndrome (FS). To decipher the disease mechanisms of FS, which vary depending on FOXG1 mutation types, patient-specific animal models are critical. Here, we report the first patient-specific FS mouse model, Q84Pfs heterozygous (Q84Pfs-Het) mice, which emulates one of the most predominant FS variants. Remarkably, Q84Pfs-Het mice recapitulate various human FS phenotypes across cellular, brain structural, and behavioral levels, such as microcephaly, corpus callosum agenesis, movement disorders, repetitive behaviors, and anxiety. Q84Pfs-Het cortex showed dysregulations of genes controlling cell proliferation, neuronal projection and migration, synaptic assembly, and synaptic vesicle transport. Interestingly, the FS-causing Q84Pfs allele produced the N-terminal fragment of FOXG1, denoted as Q84Pfs protein, in Q84Pfs-Het mouse brains. Q84Pfs fragment forms intracellular speckles, interacts with FOXG1 full-length protein, and triggers the sequestration of FOXG1 to distinct subcellular domains. Q84Pfs protein also promotes the radial glial cell identity and suppresses neuronal migration in the cortex. Together, our study uncovered the role of the FOXG1 fragment derived from FS-causing FOXG1 variants and identified the genes involved in FS-like cellular and behavioral phenotypes, providing essential insights into the pathophysiology of FS.

The role of 1-Deoxysphingolipids and Polyamines in the pathogenesis of placental syndrome

BackgroundPlacental syndrome, mainly composed of preeclampsia and fetal growth restriction, has an impact on the health of mother and baby dyads. While impaired placentation is central to their pathophysiology, the underlying molecular mechanisms remain incompletely understood. This study investigates the association between placental syndrome and metabolic alterations in 1-deoxysphingolipids (1-deoxySLs) and polyamines, along with their regulatory enzymes.MethodsThis prospective case-control study involved 26 healthy pregnant women and 17 with placental syndrome. Blood samples were collected from maternal, uterine venous, and umbilical cord veins. Levels of 1-deoxySL, spermine, and spermidine, as well as related enzymes of polyamine metabolism such as ornithine decarboxylase (ODC), spermidine/spermine N1-acetyltransferase (SSAT), polyamine oxidase (PAO), and spermine oxidase (SMO), were measured using the techniques of LC-MS and ELISA, respectively.ResultsWomen with placental syndrome had significantly higher levels of 1-deoxySL, spermine, and spermidine in all blood samples compared to the healthy pregnancy group. Additionally, ODC and SSAT levels were reduced significantly in the placental syndrome group, while PAO and SMO levels showed no significant differences. Strong positive correlations were found between the studied enzymes and biomolecules in healthy pregnancies, which were notably weaker in the placental syndrome group.ConclusionThis study demonstrates significantly altered levels of 1-deoxySL and polyamines, with corresponding enzyme activity changes, in placental syndrome compared to healthy pregnancies. The disrupted correlations between these biomolecules suggest alterations in their metabolic pathways and potential utility as biomarkers. Further mechanistic studies are warranted to elucidate their role in placental syndrome pathophysiology.

Improving general practitioners’ approaches to functional somatic syndromes: a pilot training program with a focus on compassion and communication

BackgroundFunctional somatic syndromes are common in primary care and represent a challenge for general practitioners (GPs), with a risk of deterioration in the doctor-patient relationship, and of compassion fatigue on the part of the physician. Little is known about how to teach better management of these symptoms.MethodsThe aim of our scientific team was to develop a training session about functional somatic syndromes for GPs, with the objective to improve the therapeutic attitude of the participants. The first session of the training was constructed as a pilot session, followed by a qualitative study to complete content validation. The educational framework of the training session is multimodal and includes theory on the pathophysiology of functional somatic syndromes, communication skills, and introspective learning including an introduction to compassion meditation. 20 physicians attended the pilot training session. 10 of them participated in the qualitative study. The qualitative study consisted of five individual semi-structured interviews and one focus group of five persons, investigating the impact of the training session on the clinical practices, as perceived by the participants. The interviews were analysed through an inductive method inspired by Malterud’s systematic text condensation strategy.ResultsWe identified three main themes in the responses of the participants: (1) the crucial issue of putting a name to chronic psychosomatic suffering; (2) the importance of self-compassion for physicians; (3) changes in therapeutic attitude fostering a reconciliation between “self” and “care”. Participants expressed a need for more regular meetings of this type. The opportunity to share their negative feelings about therapeutic relationship within a peer group, with compassionate supervision of the trainers, seemed to play an important role in the improvement of their self-compassionConclusionA multimodal teaching session seems to help the physicians to feel more comfortable and competent when treating patients with functional somatic syndromes. Including compassion meditation in the teaching seems a promising tool to prevent compassion fatigue.

Ndufs4 knockout mice with isolated complex I deficiency engage a futile adaptive brain response

Paediatric Leigh syndrome (LS) is an early-onset and fatal neurodegenerative disorder lacking treatment options. LS is frequently caused by mutations in the NDUFS4 gene, encoding an accessory subunit of mitochondrial complex I (CI), the first complex of the oxidative phosphorylation (OXPHOS) system. Whole-body Ndufs4 knockout (KO) mice (WB-KO mice) are widely used to study isolated CI deficiency, LS pathology and interventions. These animals develop a brain-specific phenotype via an incompletely understood pathomechanism. Here we performed a quantitative analysis of the sub-brain proteome in six-weeks old WB-KO mice vs. wildtype mice. Brain regions comprised of a brain slice (BrSl), cerebellum (CB), cerebral cortex (CC), hippocampus (HC), inferior colliculus (IC), and superior colliculus (SC). Proteome analysis demonstrated similarities between CC/HC, and between IC/SC, whereas BrSl and CB differed from these two groups and each other. All brain regions displayed greatly reduced levels of two CI structural subunits (NDUFS4, NDUFA12) and an increased level of the CI assembly factor NDUFAF2. The level of CI-Q module subunits was significantly more reduced in IC/SC than in BrSl/CB/CC/HC, whereas other OXPHOS complex levels were not reduced. Gene ontology and pathway analysis demonstrated specific and common proteome changes between brain regions.Across brain regions, upregulation of cold-shock-associated proteins, mitochondrial fatty acid (FA) oxidation and synthesis (mtFAS) were the most prominent. FA-related pathways were predominantly upregulated in CB and HC. Based upon these results, we argue that stimulation of these pathways is futile and pro-pathological and discuss alternative strategies for therapeutic intervention in LS. SignificanceThe Ndufs4 knockout mouse model is currently the most relevant and most widely used animal model to study the brain-linked pathophysiology of human Leigh Syndrome (LS) and intervention strategies. We demonstrate that the Ndufs4 knockout brain engages futile and pro-pathological responses. These responses explain both negative and positive outcomes of intervention studies in Leigh Syndrome mice and patients, thereby guiding novel intervention opportunities.

Obesity and Polycystic Ovary Syndrome.

The core pathophysiology of polycystic ovary syndrome involves an overproduction of androgens primarily originating from ovarian thecal cells. Two major external triggers promote androgen overproduction in the ovaries: the increased secretion of luteinizing hormone, a consequence of aberrant hypothalamic gonadotropin-releasing hormone secretion dynamics, and compensatory hyperinsulinemia resulting from insulin resistance. Obesity interacts with polycystic ovary syndrome in multiple ways, but a major role of obesity in its pathophysiology is the exacerbation of insulin resistance. Additionally, obesity contributes to polycystic ovary syndrome by facilitating the conversion of precursor hormones to testosterone within adipose cells. Moreover, obesity can lead to relative hyperandrogenemia, which is marked by lower levels of sex hormone binding globulin and increased availability of free testosterone to target tissues. Also, obesity affects the secretion of gonadotropins, resulting in heightened luteinizing hormone secretion or increased sensitivity of thecal cells to luteinizing hormone. Obesity-related insulin resistance might be amplified by alterations in adipokine and inflammatory cytokine production. Ultimately, obesity and polycystic ovary syndrome might share a common genetic predisposition. The cornerstone of managing polycystic ovary syndrome is to address individual symptoms such as hyperandrogenism (hirsutism, acne, and female type boldness), menstrual irregularities, and infertility stemming from anovulation. However, obesity is integral to the pathophysiology of polycystic ovary syndrome and exacerbates all of its features. Therefore, lifestyle modifications aimed at weight reduction should be the primary strategy in overweight or obese women with polycystic ovary syndrome.

Approach to the patient with Cyclical Cushing Syndrome.

Cyclic Cushing's syndrome is a sub-entity of Cushing's syndrome, characterized by repeated episodes of excess cortisol (peaks) followed by spontaneous periods of normal or low cortisol secretion (troughs). Although considered rare, its prevalence reaches 70/514 to 91/514 (14 to 18%) in patients with Cushing's syndrome according to its definition in some reported series and can concern all etiologies of Cushing's syndrome. Physicians should be alert to the presence of cyclical Cushing's syndrome in patients with fluctuating symptoms or where the results of biochemical investigations indicate eu- or hypocortisolism in patients with clinical Cushing's syndrome. Cyclicity leads to difficulties in establishing the diagnosis of CS and discovering its etiology, since patients may have paradoxical/aberrant results in biochemical investigations, including inferior petrosal sinus sampling. Similarly, cyclicity complicates the interpretation of therapeutic outcomes and interferes with medical treatments of Cushing's syndrome. Apart from cyclicity, variability of hypercortisolism is a more common phenomenon seen in Cushing's syndrome but can cause similar problems. Since the pathophysiology and molecular basis of cyclic Cushing's syndrome are largely unknown, a marked variability in cortisol secretion can be considered as representing a milder aspect of cyclicity within the same continuum. In this issue of "Approach to the patient", the characteristics, main diagnostic and therapeutic pitfalls, as well as strategies for diagnosing and managing cyclicity and marked variability in Cushing's syndrome, are discussed from the clinician's perspective using three clinical cases.

(Un)Tying the Knot: Oxidative Stress, Inflammatory Markers, and Lipid Status in Dogs with Hypercortisolism.

The aim of this study was to revisit the complex relationship between inflammation, oxidative stress and lipid metabolism in dogs with hypercortisolism (HC). Fourteen dogs newly diagnosed with HC and an equal number of healthy counterparts of similar age and markers of oxidative stress (AOPP, TBARS, TAC, GSH, PON-1, and UA) and inflammation (NLR, PLR, SII, HPT, CHE, CP, and Hcy) were included in the study. To determine the lipid profiles, cholesterol, and triglyceride levels were measured, and the electrophoretic separation of lipoproteins was performed. The results revealed that dogs with HC had higher levels of AOPP and TBARS, but only greater levels of GSH among antioxidants. Uric acid levels were higher in HC dogs, suggesting a pro-oxidative role. Elevated NLR, PLR, SII, and HPT levels were detected, but they did not seem to be associated with inflammation. Notable changes were detected in the HDL fraction, alongside hypercholesterolaemia and hypertriglyceridaemia. Correlation analysis revealed links between lipid markers and both oxidative stress and inflammatory indices. In conclusion, the data acquired may prove useful in further understanding of the intricate pathophysiology of Cushing's syndrome.

Alterations of fractional anisotropy and white matter integrity in irritable bowel syndrome: a systematic review and meta-analysis of diffusion tensor imaging studies.

The neurological processes responsible for irritable bowel syndrome (IBS) pathophysiology and its clinical potentials are not fully understood. The current study aimed to examine white matter microstructural abnormalities and the reasons behind white matter impairment in individuals with irritable bowel syndrome by performing a meta-analysis of diffusion tensor imaging studies. PubMed, Scopus and Web of Science were searched until April 2024. Chosen articles based on our defined eligibility criteria were extracted for the data relating to fractional anisotropy and brain connectivity. Webplot digitizer was used to extract digital data. We used the latest version of STATA(ver18) to meta-analyze the data. Quality assessment of studies was done using a critical appraisal tool. Egger's test for minor study effects assessed the publication bias. 543 IBS cases and 472 healthy controls were included in this study. The mean age of the case and control group was 35.2 ± 17.4 and 33.6 ± 15.8 (mean ± SD), respectively. There was no statistically significant difference in age between groups (p > 0.05). Analyzed Standard mean difference using a fixed model for Fractional anisotropy of regions of interest (ROI) associated with sensory processing, such as the thalamus, insula, primary somatosensory cortex, dorsal cingulum and the fornix in selected studies showcased decreased white matter interactivity in case group however this decrease was not statistically different [SMD -88, 95%CI (-1.32, -0.44), p > 0.05]. Further investigation is necessary to ascertain whether the modified structural connectivity mentioned in this study is a contributing factor to IBS, an outcome of the condition, a risk factor for it, or, more probably, a consequence of a mutually influential relationship between the changes observed in the white matter tract and IBS symptoms.

Microbial involvement in myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and disabling disease related to persistent fatigue, exercise intolerance, post-exertional malaise, cognitive dysfunction, and musculoskeletal/joint pain. Gastrointestinal comorbidities, including irritable bowel syndrome, have been reported in affected individuals, indicating a potential role of gut microbiota in disease progression. In this paper, bacterial and metabolomic dysbiosis in subjects with ME/CFS are reviewed, and phenotypic, microbial, and metabolic biomarkers specific to individual cohorts are also identified. Furthermore, microbiome fluctuations or metabolic endotoxemia are proposed as possible disorder biomarkers. Based on the fact that gut microbiota dysbiosis reverts to a state of eubiosis in long-term patients with this condition, it may be hypothesized that disease progression begins with the loss of beneficial gut microorganisms, particularly short-chain fatty acid producers, leading to more widespread gastrointestinal phenotypes that are subsequently reflected in plasma metabolite levels. These alterations, specific of each individual, thereby result in metabolic and phenotypic shifts and in ME/CFS.

New insight on the potential detrimental effect of metabolic syndrome on the Alzheimer disease neuropathology: Mechanistic role.

The metabolic syndrome or syndrome X is a clustering of different components counting insulin resistance (IR), glucose intolerance, visceral obesity, hypertension and dyslipidemia. It has been shown that IR and dysregulation of insulin signalling play a critical role in the development of metabolic syndrome by initiating the pathophysiology of metabolic syndrome through induction of glucolipotoxicity, impairment of glucose disposal and triggering of pro-inflammatory response. Furthermore, metabolic syndrome unfavourably affects the cognitive function and the development of different neurodegenerative diseases such as Alzheimer disease (AD) by inducing oxidative stress, neuroinflammation and brain IR. These changes together with brain IR impair cerebrovascular reactivity leading to cognitive impairment. In addition, metabolic syndrome increases the risk for the development of AD. However, the central mechanisms by which metabolic syndrome amplify AD risk are not completely elucidated. Consequently, this narrative review aims to revise from published articles the association between metabolic syndrome and AD regarding cellular and subcellular pathways. In conclusion, metabolic syndrome is regarded as a potential risk factor for the induction of AD neuropathology by different signalling pathways such as initiation of brain IR, activation of inflammatory signalling pathways and neuroinflammation.

A nomogram to predict the risk of insulin resistance in Chinese women with polycystic ovary syndrome.

Insulin resistance (IR) is considered a major driver of the pathophysiology of polycystic ovary syndrome (PCOS), mediating the progression of hyperandrogenism and metabolic and reproductive dysfunction in patients with PCOS. Early detection of the risk of concurrent IR is essential for women with PCOS. To address this need, this study developed a predictive nomogram for assessing the risk of IR in women with PCOS, aiming to provide a tool for risk stratification and assist in clinical decision-making. Patients with untreated PCOS-IR diagnosed in a single-center retrospective cohort study from January 2023 to December 2023 were included for nomogram construction and validation. The area under the ROC curve (AUC), calibration curve, Hosmer-Lemeshow (H-L) goodness-of-fit test, and decision curve analysis (DCA) were used to evaluate the nomogram's discrimination, calibration, and clinical decision performance. A risk stratification model based on the nomogram was then developed. A total of 571 patients were included in the study; 400 patients enrolled before September 2023 were divided into the training and validation sets, and 171 patients enrolled later were used as the external validation set. The variables identified by logistic regression and the random forest algorithm-body mass index (BMI, OR 1.43), triglycerides (TG, OR 1.22), alanine aminotransferase (ALT, OR 1.03), and fasting plasma glucose (FPG, OR 5.19)-were used to build the nomogram. In the training, internal validation, and external validation sets, the AUCs were 0.911 (95% CI 0.878-0.911), 0.842 (95% CI 0.771-0.842), and 0.901 (95% CI 0.856-0.901), respectively. The nomogram showed good agreement between predicted and observed outcomes, and patients were categorized into low-, medium-, and high-risk groups based on their scores. Independent predictors of untreated PCOS-IR risk were incorporated into a nomogram that effectively classifies patients into risk groups, providing a practical tool for guiding clinical management and early intervention.

Exploring the pathophysiology of restless leg syndrome: focus on white matter structure and function.

Restless legs syndrome (RLS) is a sleep disorder characterized by an irresistible urge to move the legs, with pathogenesis involving genetic, environmental, and neurobiological factors. Recent advancements in imaging techniques have provided valuable insights into the pathophysiological mechanisms of RLS. To synthesize recent research on white matter fiber alterations in RLS and their role in disease pathology. This review synthesized recent research on RLS, focusing on neuroimaging findings, particularly white matter fiber alterations, and their implications for disease mechanisms. Studies involving structural and functional MRI were analyzed. Imaging studies suggested that RLS was associated with white matter integrity changes, affecting areas linked to sensory and motor control. These alterations may reflect disruptions in central nervous system pathways regulating movement. White matter changes provide valuable insights into the pathophysiology of RLS, enhancing our understanding of the disorder and potentially guiding future therapeutic strategies.

Itacitinib for Prevention of Graft-Versus-Host Disease and Cytokine Release Syndrome in Haploidentical Transplantation

Haploidentical hematopoietic cell transplantation (haplo-HCT) is an increasingly used treatment for hematologic malignancies. Although post-transplant cyclophosphamide (PtCy) has improved graft vs. host disease (GvHD) prophylaxis in haplo-HCT, patients continue to experience life-threatening complications. IFN-γ and IL-6 are central in the pathophysiology of GvHD and cytokine release syndrome (CRS), and both cytokines signal through Janus kinase (JAK)-1. We tested the effect of adding the JAK-1 selective inhibitor, itacitinib, to PtCy-haplo-HCT to mitigate these complications and improve overall survival. This open-label, single-arm study evaluated the safety and efficacy of itacitinib combined with standard GvHD prophylaxis after haplo-HCT. A total of 42 patients were treated with itacitinib 200 mg daily from day -3 through +100 or +180, followed by a taper. Itacitinib resulted in low CRS grades, all patients had grade 0 (22%) or grade 1 (78%) CRS and there were no cases of grade 2-5 CRS. There were no cases of primary graft failure. No patients developed grade 3-4 aGvHD through day +180. The cumulative incidence of grade 2 aGvHD at day +100 was 21.9%. The 1-year cumulative incidence of moderate or severe chronic GvHD was 5%. The cumulative incidence of relapse at 2 years was 14%. Overall survival (OS) at 1 year was 80%. The cumulative incidence of nonrelapse mortality at day 180 was 8%. Itacitinib, when added to standard GvHD prophylaxis, was well tolerated and resulted in low rates of CRS, acute and chronic GvHD, NRM and encouraging rates of GvHD-free relapse-free survival (GRFS) and OS after haplo-HCT. NCT03755414

Elucidating the pathophysiology of polycystic ovary syndrome: Construction and analysis of a ceRNA network in cumulus cells

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder with elusive molecular mechanisms. This study explores the competitive endogenous RNA (ceRNA) regulatory network in the cumulus cells of PCOS patients. ceRNAs are transcripts like mRNAs, miRNAs, and lncRNAs that competitively bind shared miRNAs, regulating gene expression post-transcriptionally. We analyzed mRNA, microRNA (miRNA), and long non-coding RNA (lncRNA) from two cohorts: 12 PCOS patients and 11 healthy controls (dataset GSE10946), and 5 PCOS patients and 5 healthy controls (dataset GSE72274). These microarray datasets, obtained from the Gene Expression Omnibus (GEO), helped us identify differentially expressed mRNAs, miRNAs, and lncRNAs. Our analysis revealed a significant ceRNA network, which may play a crucial role in the pathophysiology of PCOS. In this network, 5 lncRNAs, 3 miRNAs, and 36 mRNAs were identified as differentially expressed. These elements form a complex regulatory schema influencing key cellular processes related to the disease, such as cell cycle regulation and response to estrogen. The HOXA11-AS-hsa-miR-454–3p-CCND2 network emerged as a potentially valuable biomarker for PCOS diagnosis, supported by Receiver Operating Characteristic (ROC) curve analysis indicating strong predictive power. Our findings suggest that the ceRNA interactions in PCOS cumulus cells provide a deeper understanding of the disease's molecular basis and offer new avenues for therapeutic intervention. This in silico study lays the groundwork for further experimental validation of these ceRNA networks as targets for PCOS treatment.

Transient Perivascular Inflammation of the Carotid Artery Syndrome: A Case Report with Diagnostic Insights from Vessel Wall Imaging and Contrast-enhanced Ultrasonography

Transient perivascular inflammation of the carotid artery (TIPIC) syndrome is a rare disease accompanied by acute neck pain and specific pathologic changes in the carotid artery and surrounding tissue. Here, we present a case diagnosed with typical imaging features, including extensive enhancement with luminal narrowing on vessel wall imaging and the presence of microbubbles on contrast-enhanced ultrasonography. These findings provide valuable insights into the pathophysiology of TIPIC syndrome and importance of imaging modalities for early detection and management.

Sequelae of Acute Pulmonary Embolism: From Post-Pulmonary Embolism Functional Impairment to Chronic Thromboembolic Disease.

Among survivors of acute pulmonary embolism (PE), roughly half report persistent dyspnea, impaired functional status, and decreased quality of life. Post-pulmonary embolism syndrome (PPES) is a broad condition which has been increasingly recognized in recent years and may be due to post-pulmonary embolism functional impairment, chronic thromboembolic disease, or the most severe long-term complication of PE, chronic thromboembolic pulmonary hypertension. Despite guideline recommendations for appropriate follow-up for post-pulmonary embolism patients, PPES remains underrecognized and diagnostic testing underutilized. Patients with symptoms suggestive of PPES at follow-up should undergo a transthoracic echocardiogram to screen for the presence of pulmonary hypertension; additional testing, such as a ventilation/perfusion scan, right heart catheterization, and cardiopulmonary exercise testing may be indicated. The pathophysiology of post-pulmonary embolism syndrome is complex and heterogeneous. In chronic thromboembolic pulmonary hypertension, the pathophysiology reflects persistent pulmonary arterial thrombi and a progressive small vessel vasculopathy. In patients with chronic thromboembolic disease or chronic thromboembolic pulmonary hypertension, medical therapy, balloon pulmonary angioplasty, or pulmonary thromboendarterectomy should be considered, and in cases of chronic thromboembolic pulmonary hypertension, pulmonary thromboendarterectomy significantly improves mortality. In all causes of post-pulmonary embolism syndrome, rehabilitation is a safe treatment option that may improve quality of life.