Pathophysiological States Research Articles

Role of perivascular cells in kidney homeostasis, inflammation, repair and fibrosis.

Perivascular niches in the kidney comprise heterogeneous cell populations, including pericytes and fibroblasts, with distinct functions. These perivascular cells have crucial roles in preserving kidney homeostasis as they maintain microvascular networks by stabilizing the vasculature and regulating capillary constriction. A subset of kidney perivascular cells can also produce and secrete erythropoietin; this ability can be enhanced with hypoxia-inducible factor-prolyl hydroxylase inhibitors, which are used to treat anaemia in chronic kidney disease. In the pathophysiological state, kidney perivascular cells contribute to the progression of kidney fibrosis, partly via transdifferentiation into myofibroblasts. Moreover, perivascular cells are now recognized as major innate immune sentinels in the kidney that produce pro-inflammatory cytokines and chemokines following injury. These mediators promote immune cell infiltration, leading to persistent inflammation and progression of kidney fibrosis. The crosstalk between perivascular cells and tubular epithelial, immune and endothelial cells is therefore a key process in physiological and pathophysiological states. Here, we examine the multiple roles of kidney perivascular cells in health and disease, focusing on the latest advances in this field of research.

Moderate-carbohydrate diet without caloric or lipid restriction for Japanese adult patients with nonalcoholic fatty liver disease: A prospective cohort study.

Although a low-calorie diet with lipid restriction is recommended in clinical practice guidelines for nonalcoholic fatty liver disease (NAFLD), both compliance and adherence are poor. The present study aimed to evaluate the compliance, adherence, and effectiveness of a moderate-carbohydrate diet without caloric or lipid restrictions. Participants comprised 300 patients with NAFLD with elevated ALT levels who received counseling in carbohydrate restriction (150-200g/day). Complete response (CR) was defined as ALT normalization and partial response as a ≥30% reduction in ALT from baseline without CR. Dropout rates were 3% (10 of 300) after 6months and 8% (23 of 300) after 12months. Achievement rates of carbohydrate intake ≤200g/day after 1, 3, 6, and 12months were 80%, 81%, 80%, and 73%, respectively. CR and partial response rates were 60% and 31% after 6months, and 65% and 25% after 12months, respectively. Rates of achieving a ≥7% weight reduction after 6 and 12months were 51% and 49%, respectively. Significant reductions in percentage body fat and visceral fat area were obtained, along with a significant increase in liver/spleen attenuation ratio. Serum lipids, uric acid, homeostatic model assessment for insulin resistance, hemoglobin A1c, C-reactive protein, ferritin, immunoglobulin, blood cell, shear wave velocity in the liver, and Mac-2-binding protein glycosylated isomers all decreased significantly. Compliance and adherence to a moderate-carbohydrate diet without caloric or lipid restriction is high. The sustained high effectiveness of this therapy would improve the pathophysiological state of NAFLD.

Some aspects of anti-inflammatory therapy of osteoarthritis

In the article, the authors discuss the therapy of OA as one of the common diseases of the musculoskeletal system, which leads to disability of people of working age. Focusing on modern concepts of pathogenesis, the article draws attention to pain and the mechanisms of its formation in OA. The recommendations of the world’s leading communities (EULAR, ARC OARSI) and the conclusions of the consensus resolution of experts of the Russian Federation on the diagnosis and treatment of osteoarthritis 2022 are also given. The article draws attention to some aspects of pain therapy. The data of studies and meta-analyses demonstrating the effectiveness of NSAIDs in pain associated with OA are presented. Among the variety of NSAIDs, the article provides data on the efficacy and safety of nimesulide, as well as its additional properties such as inhibition of cancer cell proliferation, neuroprotective and gastroprotective effects. The conclusions of the consensus meetings of 2005, the purpose of which was to provide a continuous and up-to-date assessment of the clinical profile and safety profile of nimesulide, and 2014, the purpose of which was to familiarize with the current state of pathophysiology and treatment of acute pain with a special focus on nimesulide, are presented. The article also provides data on the safety and efficacy of nimesulide in the treatment of OA in comparison with drugs such as diclofenac, naproxen and ibuprofen. One of the little-studied aspects of pain therapy is the patient’s preference. The article presents data from studies of the effectiveness of various forms of NSAIDs and patient preferences in therapy. The authors of the article conclude that the most acceptable from the point of view of efficacy, safety, the rate of onset of the effect, as well as the preferences of patients is nimesulide in the form of granules for the preparation of a solution.

Polyethylene glycol-based isolation of urinary extracellular vesicles, an easily adoptable protocol

Urine is a highly advantageous biological specimen for biomarker research and is a non-invasive source. Most of the urinary biomarkers are non-specific, volatile and need extensive validation before clinical adoption. Extracellular vesicles are secreted by almost all cells and are involved in homoeostasis, intercellular communication, and cellular processes in healthy and pathophysiological states. Urinary extracellular vesicles (UEVs) are released from the urogenital system and mirror the molecular processes of physiological and pathological states of their source cells. Therefore, UEVs serve as a valuable source of biomarkers for the non-invasive diagnosis of various pathologies. They hold a promising source of multiplex biomarkers suitable for prognosis, diagnosis, and therapy monitoring. UEVs are easily accessible, non-invasive, and suited for longitudinal sampling. Although various techniques are available for isolating UEVs, there is yet to be a consensus on a standard and ideal protocol. We have optimized an efficient, reliable, and easily adoptable polyethylene glycol (PEG) based UEV isolation technique following MISEV guidelines. The method is suitable for various downstream applications of UEVs. This could be a cost-effective, consistent, and accessible procedure for many clinical labs and is most suited for longitudinal analysis. Adopting the protocol will pave the way for establishing UEVs as the ideal biomarker source. •Urine can be collected non-invasively and repeatedly, hence a very useful specimen for biomarker discovery. Urinary EVs (UEVs), derived from urine, offer a stable diagnostic tool, but standardised isolation and analysis approaches are warranted.•To have enough UEVs for any study, large volumes of urine sample are necessary, which limits different isolation methods by cost, yield, and time.•The protocol developed could help researchers by offering a cost-effective and dependable UEV isolation method and may lay the foundation for UEVs adoption in clinical space.

LEFT VENTRICULAR REMODELING IN HEART FAILURE (PART ІI): PHENOTYPIC HETEROGENEITY AS A RATIONALE FOR PERSONALIZED PATIENTS` MANAGEMENT

Aim: to provide a literature review of the current conсepts on phenotypic heterogeneity of left ventricular (LV) remodeling in heart failure (HF), and highlight the significance of such a diversity for an implementation of personalized patients` management. This paper is a second part of the review, devoted to the current state of pathophysiology of LV remodeling in HF.
 Material and methods. The thematic scientific papers, published predominantly during the last decade, constituted the study material. The research methodology involved bibliosemantic method and structural and logical analysis.
 Results and discussion. HF is a heterogeneous, multifactorial and rising epidemic syndrome. To date, the LV ejection fraction (EF) is used as a substantial criterion for HF classification and management. However, the existing research data has revealed the significant overlapping between different LV EF-based HF patterns in terms of the risk factors, comorbidities and disease modifiers; bidirectional transitions of LV EF due to disease treatment and progression; myocardial fibrosis and dysfunction; effectiveness of neurohumoral inhibitors etc.
 Moreover, the «spectrum» paradigm has been recently proposed, positioning HF as a spectrum across different phenotypes. Particularly, each HF phenotype is the result of a patient-specific trajectory, being an exceptional and unique «track» for the heart transition towards different remodeling patterns.
 The HF phenotyping may be an innovative approach to the study of myocardial remodeling and HF, which is potentially an important prerequisite for the development of individualized patients` treatment. Personalized medicine can offer the particular options for managing HF patients, that, in turn, will better identify responders, non-responders, and those at high risk of adverse events, and ultimately improve of the treatment efficacy and safety.
 Conclusions. The baseline heterogeneity of the structural and functional patients` characteristics, including those describing the LV remodeling, and their dynamic change over time, creates a spectrum across overlapping HF phenotypes, challenging a categorical HF classification based solely on LV EF. Such an approach to treat the HF phenotypic heterogeneity may provide further insights into the pathomechanisms, related to LV remodeling in HF, and has the potential to improve the personalized patients` management.

A Near Miss of a Retropharyngeal Abscess with MRSA in a 5-Week-Old Boy Due to an Unusual Presentation

A retropharyngeal abscess (RPA) in early childhood is not uncommon due to at-risk lymph nodes in this deep neck space and is typified by fever, odynophagia, and a constellation of respiratory manifestations. However, RPA is exceedingly rare in the neonatal subpopulation and not part of the usual differential diagnosis algorithm in this age range. Herein, we present a unique case of a previously healthy 5-week-old male infant with protracted “congestion” and difficulty in oral feeding, whose clinical course is confounded by intermittent, positional bradycardia and subsequent apnea. He was eventually diagnosed with a methicillin-resistant Staphylococcus aureus (MRSA) RPA, leading to concurrent vascular and airways compromise in the form of baroreceptor-mediated bradycardia from mass-effect carotid body compression. This clinical case is an important reminder that any infant with positional vital sign changes should prompt urgent and thorough investigation for extraordinary and otherwise uncommon pathophysiologic states. The case also highlights the power of multidisciplinary collaboration across multiple specialties and parental advocacy in unifying a diagnosis for rare pediatric illnesses. Keywords: deep neck infections, retropharyngeal abscess, MRSA, positional bradycardia, neonatal infection

CREB-H is a stress-regulator of hepcidin gene expression during early postnatal development.

Hepcidin, the hepatic iron hormone, is the central regulator of iron homeostasis. Cyclic AMP-Responsive Element-Binding protein 3-like 3 (CREB3L3/CREB-H) is a liver homeostatic regulator of essential nutrients (i.e. glucose and lipids) and has been previously involved in hepcidin response to pathologic stress signals. Here, we asked whether CREB-H has also a physiologic role in iron homeostasis through hepcidin. To this end, we analyzed hepcidin gene expression and regulation in the liver of wild type and Creb3l3 knockout mice during early postnatal development, as a model of "physiologic" stressful condition. The effect of iron challenge in vivo and BMP6 stimulation in vitro have been also addressed. In addition, we investigated the BMP signaling pathway and hepcidin promoter activity following CREB3L3 silencing and hepcidin promoter mutation in HepG2 cells. Creb3l3 knockout suckling and young-adult mice showed a prominent serum and hepatic iron accumulation, respectively, due to impaired hepcidin mRNA expression which progressively returned to normal level in adult mice. Interestingly, upon iron challenge, while the upstream BMP/SMAD signaling pathway controlling hepcidin was equally responsive in both strains, hepcidin gene expression was impaired in knockout mice and more iron accumulated in the liver. Accordingly, hepcidin gene response to BMP6 was blunted in primary CREB-H knockout hepatocytes and in HepG2 cells transfected with CREB-H siRNA or carrying a hepcidin promoter mutated in the CREB-H binding site. In conclusion, CREB-H has a role in maintaining the homeostatic balance of iron traffic through hepcidin during the critical postnatal period and in response to iron challenge. KEY MESSAGES: CREB-H KO mice develop liver iron overload shortly after weaning that normalizes in adulthood. CHEB-H is involved in hepcidin gene response to oral iron in vivo. CREB-H loss hampers hepcidin promoter response to BMP6. CREB-H is a key stress-sensor controlling hepcidin gene transcription in physiologic and pathophysiologic states.

TOXOPLASMA GONDII EXPOSURE IN FELINES: AN ALARMING FACTOR TO PUBLIC HEALTH FROM MINEIROS, GOIÁS

Toxoplasmosis is a cosmopolitan disease caused by Toxoplasma gondii, an obligate protozoan that affects endothermic animals, including man. Being a zoonosis that can cause abortions, fetal malformations and blindness. Cats are the definitive hosts, acting as a source of dissemination. In order to collect epidemiological data on the distribution of T. gondii in Mineiros, Goiás, samples of domestic cats were analyzed to verify the circulation of the protozoan and reinforce preventive measures. Ninety-four samples of domestic cats, regardless of gender, age and breed, were randomly processed in the neighborhoods of Mineiros, Goiás. They were submitted to the indirect fluorescent antibody test for antibodies against T. gondii, using tachyzoites as antigens and anti-cat IgG conjugate (1:16 were positive). Of the 94 samples analyzed, 35 (37.2%) were reagents, of which four had a titration of 1:16, ten of 1:32, eleven of 1:64, eight of 1:128 and two of 1:256. All cats were semi-domiciled, but lifestyle and diet were not assessed. T. gondii infection is rarely symptomatic and the severity depends on the pathophysiological state. Brazil has high prevalence rates and requires effective care in the management of cats. In Mineiros, 29 reports of infected pregnant women were identified. Although infection in humans occurs primarily through consumption of undercooked meat, ingestion of oocysts in feces of cats is a possibility. Therefore, state public health institutions and veterinarians should promote health education, highlighting food hygiene. Since, when symptomatic, the disease presents severe clinical conditions and, in some cases, irreversible.

Expression of nutrient transporters in placentas affected by gestational diabetes: role of leptin.

Gestational diabetes mellitus (GDM) is the most frequent pathophysiological state of pregnancy, which in many cases produces fetuses with macrosomia, requiring increased nutrient transport in the placenta. Recent studies by our group have demonstrated that leptin is a key hormone in placental physiology, and its expression is increased in placentas affected by GDM. However, the effect of leptin on placental nutrient transport, such as transport of glucose, amino acids, and lipids, is not fully understood. Thus, we aimed to review literature on the leptin effect involved in placental nutrient transport as well as activated leptin signaling pathways involved in the expression of placental transporters, which may contribute to an increase in placental nutrient transport in human pregnancies complicated by GDM. Leptin appears to be a relevant key hormone that regulates placental transport, and this regulation is altered in pathophysiological conditions such as gestational diabetes. Adaptations in the placental capacity to transport glucose, amino acids, and lipids may underlie both under- or overgrowth of the fetus when maternal nutrient and hormone levels are altered due to changes in maternal nutrition or metabolic disease. Implementing new strategies to modulate placental transport may improve maternal health and prove effective in normalizing fetal growth in cases of intrauterine growth restriction and fetal overgrowth. However, further studies are needed to confirm this hypothesis.

PreCancer Atlas: Present and Future

Abstract Precancer atlases have the potential to revolutionize how we think about the topographic and morphologic structures of precancerous lesions in relation to cellular, molecular, genetic, and pathophysiologic states. This mini review uses the Human Tumor Atlas Network (HTAN), established by the National Cancer Institute (NCI), to illustrate the construction of cellular and molecular three-dimensional atlases of human cancers as they evolve from precancerous lesions to advanced disease. We describe the collaborative nature of the network and the research to determine how and when premalignant lesions progress to invasive cancer, regress or obtain a state of equilibrium. We have attempted to highlight progress made by HTAN in building precancer atlases and discuss possible future directions. It is hoped that the lessons from our experience with HTAN will help other investigators engaged in the construction of precancer atlases to crystallize their thoughts on logistics, rationale, and implementation.

Shaping mitochondria through fed-fast and circadian cycles.

Energy and metabolic homeostasis at the level of the whole body are dictated by the balance between nutrient intake/utilization, bioenergetic potential, and energy expenditure, which are tightly coupled with fed/fast cycles and circadian oscillation. Emerging literature has highlighted the importance of each of these mechanisms that are essential to maintain physiological homeostasis. Lifestyle changes predominantly associated with altered fed-fast and circadian cycles are well established to affect systemic metabolism and energetics, and hence contribute to pathophysiological states. Therefore, it is not surprising that mitochondria have emerged as being pivotal in maintaining physiological homeostasis through daily oscillations/fluctuations in nutrient inputs and light-dark/sleep-wake cycles. Moreover, given the inherent association between mitochondrial dynamics/morphology and functions, it is important to understand the phenomenological and mechanistic underpinnings of fed-fast and circadian cycles dependent remodeling of mitochondria. In this regard, we have summarized the current status of the field in addition to providing a perspective vis-a-vis the complexity of cell-autonomous and non-cell-autonomous signals that dictate mitochondrial dynamics. We also highlight the lacunae besides speculating on prospective efforts that will possibly redefine our insights into the diurnal orchestration of fission/fusion events, which are ultimately coupled to the mitochondrial output.

Doppler identified venous congestion in septic shock: protocol for an international, multi-centre prospective cohort study (Andromeda-VEXUS)

IntroductionVenous congestion is a pathophysiological state where high venous pressures cause organ oedema and dysfunction. Venous congestion is associated with worse outcomes, particularly acute kidney injury (AKI), for critically ill...

Analysis of Factors That Cause the Target of Laboratory Critical Value Report Has Not Been Reached: Study at the Clinical Pathology Department at Haji General Hospital Surabaya

Background: A laboratory critical value is a laboratory test result represents a pathophysiologic state at such variance with normal which threaten patient’s life if a medical action is not taken immediately and for which an effective action is possible. The reporting of laboratory critical value at the Clinical Pathology Department at Haji General Hospital Surabaya for the January-July 2020 period had not reached 100%. Objectives: This study analyzed the factors cause the target of laboratory critical value report has not been reached at the Clinical Pathology Department at Haji General Hospital Surabaya based on psychological and organizational factors. Methods: This study was a descriptive observational study with cross-sectional approach. The samples were 23 people in total sampling. The data were collected by questionnaire that had been tested for validity and reliability. Results: The results showed that 73.9% of respondents had high motivation, 91.3% of respondents had good perceptions, 82.6% of respondents had type B personality, 69.6% of respondents had good learning, 78.3% respondents had low work stress, 52.2% of respondents stated that leadership was quite good, 95.7% of respondents said moderate rewards, 60.9% of respondents stated that the work design was according to the profession, 87.0% of the organizational structure was effective. Conclusion: Factors that caused target of laboratory critical value report has not been reached at the Clinical Pathology Department at Haji General Hospital Surabaya for the January-July 2020 period, based on the 80/20 Pareto Principle are motivation, learning, leadership, and job design. Health analysts should increase self-motivation, make experiences as learning, leaders as co-workers, work well willingly and the Clinical Pathology Department to reward the best employees, conduct evaluations, provide understanding and explanation in decision making, regulate the rotation of the division of tasks.

Deconvoluting human Brodmann area 8 based on its unique structural and functional connectivity.

Brodmann area 8 (BA8) is traditionally defined as the prefrontal region of the human cerebrum just anterior to the premotor cortices and enveloping most of the superior frontal gyrus. Early studies have suggested the frontal eye fields are situated at its most caudal aspect, causing many to consider BA8 as primarily an ocular center which controls contralateral gaze and attention. However, years of refinement in cytoarchitectural studies have challenged this traditional anatomical definition, providing a refined definition of its boundaries with neighboring cortical areas and the presence of meaningful subdivisions. Furthermore, functional imaging studies have suggested its involvement in a diverse number of higher-order functions, such as motor, cognition, and language. Thus, our traditional working definition of BA8 has likely been insufficient to truly understand the complex structural and functional significance of this area. Recently, large-scale multi-modal neuroimaging approaches have allowed for improved mapping of the neural connectivity of the human brain. Insight into the structural and functional connectivity of the brain connectome, comprised of large-scale brain networks, has allowed for greater understanding of complex neurological functioning and pathophysiological diseases states. Simultaneously, the structural and functional connectivity of BA8 has recently been highlighted in various neuroimaging studies and detailed anatomic dissections. However, while Brodmann's nomenclature is still widely used today, such as for clinical discussions and the communication of research findings, the importance of the underlying connectivity of BA8 requires further review.

Renin-Angiotensin System: Updated Understanding and Role in Physiological and Pathophysiological States.

The classical view of the renin-angiotensin system (RAS) is that of the circulating hormone pathway involved in salt and water homeostasis and blood pressure regulation. It is also involved in the pathogenesis of cardiac and renal disorders. This led to the creation of drugs blocking the actions of this classical pathway, which improved cardiac and renal outcomes. Our understanding of the RAS has significantly expanded with the discovery of new peptides involved in this complex pathway. Over the last two decades, a counter-regulatory or protective pathway has been discovered that opposes the effects of the classical pathway. Components of RAS are also implicated in the pathogenesis of obesity and its metabolic diseases. The continued discovery of newer molecules also provides novel therapeutic targets to improve disease outcomes. This article aims to provide an overview of an updated understanding of the RAS, its role in physiological and pathological processes, and potential novel therapeutic options from RAS for managing cardiorenal disorders, obesity, and related metabolic disorders.

21-OR: Insulin and Glucagon Regulate a Novel Bidirectional Long Noncoding RNA/Protein-Coding Gene Pair That Control Cell Sensitivity to Metabolic Stress

An imbalance of glucagon and insulin actions in type 2 diabetes (T2D) results in the dysregulation of glucose and lipid metabolism and metabolic stress throughout the body. Integrating gene expression data in multiple models of T2D and metabolic syndromes, we have identified a novel gene pair, that share the same bidirectional promoter, are coordinately upregulated by glucagon and downregulated by insulin in the liver in a variety of physiological and pathophysiological states. This gene pair consists of the long non-coding (lnc) RNA Gm15663 and the protein coding gene Tmtc2, an important regulator of endoplasmic reticulum (ER) Ca2+ flux. Gm15663/Tmtc2 are also upregulated when glucagon predominates insulin, such as during fasting, after high-fat or western diet and in ob/ob mice. Conversely, Gm15663/Tmtc2 are downregulated during feeding, when insulin predominates glucagon. This transcriptional regulation is mediated in part by the transcription factor Foxo1. Foxo1 binds with two promoter-distal enhancers, creating a spatial chromatin looping interaction with Gm15663/Tmtc2 promoter, which is involved in transcriptional regulation of this gene pair. Knockdown of Tmtc2 in hepatocytes results in a higher cytosolic Ca2+ level and lower ER Ca2+ level. This renders the cell more sensitive to both metabolic and ER stress, and impairs cell respiration, which is in part mediated by the increased cytosolic Ca2+ level and the activation of CaM kinase II (CamKII). In a unique mechanism, Gm15663 and Tmtc2 also cis-regulate the transcription of each other to maintain the homeostasis of their own expression levels. Thus, Gm15663/Tmtc2 gene pair are dynamically regulated by glucagon and insulin and serve as novel regulators of cell sensitivity to metabolic stress. This gene pair is also linked to a common subtype of T2D in GWAS studies, making them potential targets to treat or modify the development of T2D in these individuals. Disclosure X.Liu: None. C.Kahn: None.

Dynamic regulation of the extracellular matrix in reward memory processes: a question of time.

Substance use disorders are a global health problem with increasing prevalence resulting in significant socioeconomic burden and increased mortality. Converging lines of evidence point to a critical role of brain extracellular matrix (ECM) molecules in the pathophysiology of substance use disorders. An increasing number of preclinical studies highlight the ECM as a promising target for development of novel cessation pharmacotherapies. The brain ECM is dynamically regulated during learning and memory processes, thus the time course of ECM alterations in substance use disorders is a critical factor that may impact interpretation of the current studies and development of pharmacological therapies. This review highlights the evidence for the involvement of ECM molecules in reward learning, including drug reward and natural reward such as food, as well as evidence regarding the pathophysiological state of the brain's ECM in substance use disorders and metabolic disorders. We focus on the information regarding time-course and substance specific changes in ECM molecules and how this information can be leveraged for the development of therapeutic strategies.

Emerging diversity in extracellular vesicles and their roles in cancer.

Extracellular vesicles have undergone a paradigm shift from being considered as 'waste bags' to being central mediators of cell-to-cell signaling in homeostasis and several pathologies including cancer. Their ubiquitous nature, ability to cross biological barriers, and dynamic regulation during changes in pathophysiological state of an individual not only makes them excellent biomarkers but also critical mediators of cancer progression. This review highlights the heterogeneity in extracellular vesicles by discussing emerging subtypes, such as migrasomes, mitovesicles, and exophers, as well as evolving components of extracellular vesicles such as the surface protein corona. The review provides a comprehensive overview of our current understanding of the role of extracellular vesicles during different stages of cancer including cancer initiation, metabolic reprogramming, extracellular matrix remodeling, angiogenesis, immune modulation, therapy resistance, and metastasis, and highlights gaps in our current knowledge of extracellular vesicle biology in cancer. We further provide a perspective on extracellular vesicle-based cancer therapeutics and challenges associated with bringing them to the clinic.

Prevalence of microalbuminuria in patients with type 2 diabetes mellitus having diabetic retinopathy in a tertiary care hospital in eastern India: A cross-sectional study

Diabetic retinopathy is a common microvascular complication of diabetes mellitus and one of the leading causes of acquired blindness. Microalbuminuria reflects a pathophysiological state of vascular dysfunction and organ damage. It is noticed that a rise in urinary albumin excretion is seen in the early phase of diabetic retinopathy. The concordance of microalbuminuria and diabetic retinopathy has been well reported in type 1 diabetes; however, for type 2 diabetes, there is a paucity of data. To estimate the prevalence of microalbuminuria in diabetic retinopathy patients with type 2 diabetes attending the out-patient department (OPD) in a tertiary care center in eastern India and also to find out any association between microalbuminuria and severity of diabetic retinopathy. : The study included 200 patients with type 2 diabetic patients having diabetic retinopathy. The study populations were selected by thorough clinical examination and as per inclusion–exclusion criteria. Estimation of urinary albumin and albumin creatinine ratio was done by using Konelab 20 Autoanalyzer machine by the immunoturbidimetry method. Diabetic retinopathy was classified as per the International Clinical Diabetic Retinopathy Severity Scales into mild, moderate, severe, very severe non-proliferative as well as proliferative diabetic retinopathy. Data were analyzed with ratio, rate, percentage, and statistical significance was considered if p<0.5. : The prevalence of microalbuminuria was found in 36% (72 patients). The highest number of patients (88.24%) with microalbuminuria was found in severe NPDR. 93.06% of patients with microalbuminuria had clinically significant macular edema. A statistically significant correlation (p<0.001) was found between microalbuminuria and the degree of retinopathy in mild, moderate, and severe NPDR. A significant correlation was found between urinary microalbumin and the severity of diabetic retinopathy.

Classifying migraine using PET compressive big data analytics of brain's μ-opioid and D2/D3 dopamine neurotransmission.

Introduction: Migraine is a common and debilitating pain disorder associated with dysfunction of the central nervous system. Advanced magnetic resonance imaging (MRI) studies have reported relevant pathophysiologic states in migraine. However, its molecular mechanistic processes are still poorly understood in vivo. This study examined migraine patients with a novel machine learning (ML) method based on their central μ-opioid and dopamine D2/D3 profiles, the most critical neurotransmitters in the brain for pain perception and its cognitive-motivational interface. Methods: We employed compressive Big Data Analytics (CBDA) to identify migraineurs and healthy controls (HC) in a large positron emission tomography (PET) dataset. 198 PET volumes were obtained from 38 migraineurs and 23 HC during rest and thermal pain challenge. 61 subjects were scanned with the selective μ-opioid receptor (μOR) radiotracer [11C]Carfentanil, and 22 with the selective dopamine D2/D3 receptor (DOR) radiotracer [11C]Raclopride. PET scans were recast into a 1D array of 510,340 voxels with spatial and intensity filtering of non-displaceable binding potential (BPND), representing the receptor availability level. We then performed data reduction and CBDA to power rank the predictive brain voxels. Results: CBDA classified migraineurs from HC with accuracy, sensitivity, and specificity above 90% for whole-brain and region-of-interest (ROI) analyses. The most predictive ROIs for μOR were the insula (anterior), thalamus (pulvinar, medial-dorsal, and ventral lateral/posterior nuclei), and the putamen. The latter, putamen (anterior), was also the most predictive for migraine regarding DOR D2/D3 BPND levels. Discussion: CBDA of endogenous μ-opioid and D2/D3 dopamine dysfunctions in the brain can accurately identify a migraine patient based on their receptor availability across key sensory, motor, and motivational processing regions. Our ML-based findings in the migraineur's brain neurotransmission partly explain the severe impact of migraine suffering and associated neuropsychiatric comorbidities.