Common Cause Research Articles

1H, 13C and 15N backbone resonance assignments of hepatocyte nuclear factor-1-beta (HNF1β) POUS and POUHD.

Hepatocyte nuclear factor 1β (HNF1β) is a transcription factor that plays a key role in the development and function of the liver, pancreas, and kidney. HNF1β plays a key role in early vertebrate development and the morphogenesis of these organs. In humans, heterozygous mutations in the HNF1B gene can result in organ dysplasia, making it the most common cause of developmental renal diseases, including renal cysts, renal malformations, and familial hypoplastic glomerular cystic kidney disease. Pathogenic variants in the HNF1B gene are known to cause various diseases, including maturity-onset diabetes of the young and developmental renal diseases. This study presents the backbone resonance assignments of HNF1β POUS and POUHD domains, which are highly conserved domains required for the recognition of double-stranded DNA. Our data will be useful for NMR studies to verify the altered structures and functions of mutant HNF1B proteins that can induce developmental renal diseases, including renal cysts, renal malformations, and familial hypoplastic glomerular cystic kidney disease. This study will provide the structural basis for future studies to elucidate the molecular mechanisms underlying how mutations in HNF1β cause diseases.

The protective effects of statins in traumatic brain injury.

Traumatic brain injury (TBI), often referred to as the "silent epidemic", is the most common cause of mortality and morbidity worldwide among all trauma-related injuries. It is associated with considerable personal, medical, and economic consequences. Although remarkable advances in therapeutic approaches have been made, current treatments and clinical management for TBI recovery still remain to be improved. One of the factors that may contribute to this gap is that existing therapies target only a single event or pathology. However, brain injury after TBI involves various pathological mechanisms, including inflammation, oxidative stress, blood-brain barrier (BBB) disruption, ionic disturbance, excitotoxicity, mitochondrial dysfunction, neuronal necrosis, and apoptosis. Statins have several beneficial pleiotropic effects (anti-excitotoxicity, anti-inflammatory, anti-oxidant, anti-thrombotic, immunomodulatory activity, endothelial and vasoactive properties) in addition to promoting angiogenesis, neurogenesis, and synaptogenesis in TBI. Supposedly, using agents such as statins that target numerous and diverse pathological mechanisms, may be more effective than a single-target approach in TBI management. The current review was undertaken to investigate and summarize the protective mechanisms of statins against TBI. The limitations of conducted studies and directions for future research on this potential therapeutic application of statins are also discussed.

Mortality in adults with sickle cell disease: Results from the sickle cell disease implementation consortium (SCDIC) registry.

The cause of death in people affected by sickle cell disease (SCD) is often challenging to define as prior studies have used retrospective or administrative data for analysis. We used a prospective longitudinal registry to assess mortality and clinical co-morbidities among subjects enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. At enrollment, we collected the following data: patient-reported demographics, SCD phenotype, baseline laboratory values, comorbidities, and current medications. Subjects were followed for a median of 4.7 years before the present analysis. The relationship of clinical co-morbidities (at time of enrollment) to mortality was determined using survival analysis, adjusting for SCD phenotype and gender. There was a total of 2439 people with SCD enrolled in the SCDIC registry. One hundred and twenty-eight participants (5%) died during the observation period (2017-2022). Six people died from trauma and were excluded from further analysis. Proximate cause of death was unwitnessed in 17% of the deaths, but commonest causes of death include cardiac (18%), acute chest or respiratory failure (11%), sudden unexplained death (8%). Enrollment characteristics of the individuals who died (n = 122) were compared to those of survivors (n = 2317). Several co-morbidities at enrollment increased the odds of death on univariate analysis. All co-morbidities were included in a multivariable model. After backward elimination, iron overload, pulmonary hypertension, and depression, remained statistically significant predictors of the risk of death. SCD reduces life expectancy. Improved comprehensive and supportive care to prevent end-organ damage and address comorbidities is needed for this population.

Epidemiology, clinical features, and classification of 3,404 patients with uveitis: Colombian Uveitis Multicenter Study (COL-UVEA).

To describe the epidemiology, clinical features, and classification of uveitis in a large cohort of Colombian patients. Data were collected from seven ophthalmological referral centers in the four main cities in Colombia. The study included patients with a confirmed diagnosis of uveitisfrom January 2010 to December 2022. Information on demographics, ophthalmic examination findings, uveitis classification, and etiology was recorded. The study reviewed 3,404 clinical records of patients with uveitis. The mean age at diagnosis was 41.1 (SD 19.0) years, and 54.2% of the patients were female. Overall, 1,341(39.4%) were infectious, 626 (18.4%) non-infectious, and four masquerade syndromes (0.1%). The most common types of uveitis were unilateral (66.7%), acute (48.3%), and non-granulomatous (83%). Anterior uveitis was the most common anatomical localization (49.5%), followed by posterior uveitis (22.9%), panuveitis (22.3%), and intermediate uveitis (5.2%). A diagnosis was established in 3,252 (95.5%) cases; idiopathic was the most common cause (27.7%), followed by toxoplasmosis (25.3%) and virus-associated uveitis (6.4%). The age group between 30 and 50 exhibited the highest frequency of uveitis. This multicenter study comprehensively describes uveitis characteristics in Colombian patients, providing valuable insights into its demographic and clinical features. The study findings emphasize the need to continue updating the changing patternsof uveitis to improve diagnosis and treatment strategies for diseases associated with intraocular inflammation.

Multiple sclerosis: modern diagnostic markers and prognostic factors of disease progression

Multiple sclerosis (MS) is one of the most common causes of disability in young people of working age. The prevalence of this disease has increased significantly in recent years and today amounts to more than 2 900 000 people worldwide. The transition from relapsing-remitting MS to secondary progressive MS is observed in 25 % of cases within 10 years the disease duration, and with further time the proportion of patients with secondary progressive MS increases. Despite the importance of preventing patient disability, today the diagnosis of secondary progressive MS is established retrospectively, which makes the issue of identifying early markers of disease progression extremely relevant. The most promising diagnostic markers allow the differentiation of progressive MS with a sensitivity of up to 87 % and a specificity of up to 90 %. This review will consider the most promising clinical, instrumental and biological signs of early progression of MS.

Positive effect of microvascular proliferation on functional recovery in experimental cervical spondylotic myelopathy.

Cervical Spondylotic Myelopathy (CSM), the most common cause of spinal cord dysfunction globally, is a degenerative disease that results in non-violent, gradual, and long-lasting compression of the cervical spinal cord. The objective of this study was to investigate whether microvascular proliferation could positively affect neural function recovery in experimental cervical spondylotic myelopathy (CSM). A total of 60 male adult Sprague-Dawley (SD) were randomly divided into four groups: Control (CON), Compression (COM), Angiostasis (AS), and Angiogenesis (A G),with 15 rats in each group. Rats in the AS group received SU5416 to inhibit angiogenesis, while rats in the AG group received Deferoxamine (DFO) to promote angiogenesis. Motor and sensory functions were assessed using the Basso Beattie Bresnahan (BBB) scale and somatosensory evoked potential (SEP) examination. Neuropathological degeneration was evaluated by the number of neurons, Nissl bodies (NB), and the de-myelination of white matter detected by Hematoxylin & Eosin(HE), Toluidine Blue (TB), and Luxol Fast Blue (LFB) staining. Immunohistochemical (IHC) staining was used to observe the Neurovascular Unit (NVU). Rats in the CON group exhibited normal locomotor function with full BBB score, normal SEP latency and amplitude. Among the other three groups, the AG group had the highest BBB score and the shortest SEP latency, while the AS group had the lowest BBB score and the most prolonged SEP latency. The SEP amplitude showed an opposite performance to the latency. Compared to the COM and AS groups, the AG group demonstrated significant neuronal restoration in gray matter and axonal remyelination in white matter. DFO promoted microvascular proliferation, especially in gray matter, and improved the survival of neuroglial cells. In contrast, SU-5416 inhibited the viability of neuroglial cells by reducing micro vessels. The microvascular status was closely related to NVU remodeling an-d functional recovery. Therefore, proliferation of micro vessels contributed to function -al recovery in experimental CSM, which may be associated with NVU remodeling.

Imaging Biomarkers of VCI: A Focused Update.

Vascular cognitive impairment is common after stroke, in memory clinics, medicine for the elderly services, and undiagnosed in the community. Vascular disease is said to be the second most common cause of dementia after Alzheimer disease, yet vascular dysfunction is now known to predate cognitive decline in Alzheimer disease, and most dementias at older ages are mixed. Neuroimaging has a major role in identifying the proportion of vascular versus other likely pathologies in patients with cognitive impairment. Here, we aim to provide a pragmatic but evidence-based summary of the current state of potential imaging biomarkers, focusing on magnetic resonance imaging and computed tomography, which are relevant to diagnosing, estimating prognosis, monitoring vascular cognitive impairment, and incorporating our own experiences. We focus on markers that are well-established, with a known profile of association with cognitive measures, but also consider more recently described, including quantitative tissue markers of vascular injury. We highlight the gaps in accessibility and translation to more routine clinical practice.

Therapeutic plasma exchange decreases serum triglyceride level rapidly and reduces early recurrence rate but no advantages in improving outcomes for patients with hyperlipidemic acute pancreatitis: a retrospective propensity score matching analysis based on twenty year’s experience

BackgroundHyperlipidaemic acute pancreatitis (HLAP) has become the most common cause of acute pancreatitis (AP) not due to gallstones or alcohol (Mosztbacher et al, Pancreatology 20:608-616, 2020; Yin et al, Pancreas 46:504-509, 2017). Therapeutic plasma exchange (TPE) has been reported to be effective in reducing serum TG levels which is important in management of HLAP (World J Clin Cases 9:5794-803, 2021). However, studies on TPE are mostly focusing on cases reports, TPE remains poorly evaluated till date and need to be compared with conservative therapy with a well-designed study.MethodsA retrospectively cohort study on HLAP patients between January 2003 and July 2023 was conducted. Factors correlated with efficacy of TPE were included in a propensity model to balance the confounding factors and minimize selection bias. Patients with and without TPE were matched 1:2 based on the propensity score to generate the compared groups. Lipid profiles were detected on admission and consecutive 7 days. The triglyceride (TG) level decline rates, percentage of patients to reach the target TG levels, early recurrence rate, local complications and mortality were compared between groups.ResultsA total of 504 HLAP patients were identified. Since TPE was scarcely performed on patients with TG < 11.3 mmol/L, 152 patients with TG level 5.65 to 11.3 mmol/L were excluded while 352 with TG ≧11.3 mmol/L were enrolled. After excluding 25 cases with incomplete data or pregnancy, 327 patients, of whom 109 treated without TPE while 218 treated with TPE, were included in data analysis. One-to-two propensity-score matching generated 78 pairs, 194 patients with well-balanced baseline characteristics. Of 194 patients enrolled after matching done, 78 were treated without while 116 with TPE. In the matched cohort (n = 194), patients treated with TPE had a higher TG decline rate in 48 h than those without TPE (70.00% vs 54.00%, P = 0.001); the early recurrence rates were 8.96% vs 1.83%, p = 0.055. If only SAP patients were analyzed, the early recurrence rates were 14.81% vs 0.00% (p = 0.026) respectively. For patients with CT severity index (CTSI) rechecked within 14 days, early CTSI improment rate were 40.90% vs 31.91%. Local complications checked 6 months after discharge were 44.12% vs 38.30%. Mortality was 1.28% vs 1.72%. No differences were found in early stage CTSI improment rate (P = .589), local complications (P = .451) or motality between two groups.ConclusionsTPE reduces TG levels more quickly in 48 h compared with those with conservative treatment, but no difference in the consecutive days. TPE tends to reduce the early recurrence rate comparing with conventional therapy, but TPE has no advantages in improving CTSI in early stage, and no improvement for outcomes including local complications and mortalty.

Computed Tomographic Evaluation of the Sagittal Ridge of the Third Metacarpal Bone in Young Thoroughbred Racehorses: A Longitudinal Study.

Metacarpophalangeal joint region pain is a common cause of lameness in racehorses. Radiological abnormalities in the sagittal ridge (SR) of the third metacarpal bone have been associated with joint effusion, lameness and reduced sales prices. The aims were to describe computed tomographic (CT) appearance of the SR in racehorses, and to document the progression of these findings over three assessments. Forty yearlings were enrolled at the first examination (time 0). Re-examinations were performed twice, approximately six months apart on 31 (time 1) and 23 (time 2) horses, respectively. Computed tomographic examinations of both metacarpophalangeal regions were performed with the horses in a standing position. Computed tomographic reconstructions were analysed subjectively and objectively. The mean Hounsfield Unit values (Hus) of eight radial segments and location, size and shape of hypoattenuating lesions were recorded. Mean Hus at time 1 were higher than at time 0. There was no difference between mean HU at times 1 and 2. The mean HU values of the dorsal half were higher in the right forelimbs and in fillies. Hypoattenuation was identified in 33/80 (41.3%) limbs at time 0, in 22/62 (35.5%) limbs at time 1 and in 14/46 (30.4%) limbs at time 2. All hypoattenuations were located in the dorsodistal aspect of the SR. The most common shapes were hypoattenuating lesions elongated proximodistally and those extending towards trabecular bone. An increase in attenuation of the SR occurred in the first six months of training. Hypoattenuating lesions could decrease in size and could resolve during early training. In this population, these lesions were not associated with lameness.

The Most Important Metabolic Diseases in Dairy Cattle during the Transition Period.

This review paper provides an in-depth analysis of three critical metabolic diseases affecting dairy cattle such as subacute ruminal acidosis (SARA), ketosis, and hypocalcemia. SARA represents a disorder of ruminal fermentation that is characterized by extended periods of depressed ruminal pH below 5.5-5.6. In the long term, dairy herds experiencing SARA usually exhibit secondary signs of the disease, such as episodes of laminitis, weight loss and poor body condition despite adequate energy intake, and unexplained abscesses usually 3-6 months after an episode of SARA. Depressed milk-fat content is commonly used as a diagnostic tool for SARA. A normal milk-fat test in Holstein dairy cows is >4%, so a milk-fat test of <3% can indicate SARA. However, bulk tank testing of milk fat is inappropriate to diagnose SARA at the herd level, so when >4 cows out of 12 and <60 days in milk are suspected to have SARA it can be considered that the herd has a problem. The rapid or abrupt introduction of fresh cows to high-concentrate diets is the most common cause of SARA. Changes in ruminal bacterial populations when exposed to higher concentrate rations require at least about 3 weeks, and it is recommended that concentrate levels increase by no more than 400 g/day during this period to avoid SARA. Ketosis, a prevalent metabolic disorder in dairy cattle, is scrutinized with a focus on its etiological factors and the physiological changes leading to elevated ketone bodies. In total mix ration-fed herds, an increased risk of mastitis and reduced fertility are usually the first clinical signs of ketosis. All dairy cows in early lactation are at risk of ketosis, with most cases occurring in the first 2-4 weeks of lactation. Cows with a body condition score ≥3.75 on a 5-point scale at calving are at a greater risk of ketosis than those with lower body condition scores. The determination of serum or whole blood acetone, acetoacetate, beta-hydroxybutyrate (BHB) concentration, non-esterified fatty acids (NEFA), and liver biopsies is considered the best way to detect and monitor subclinical ketosis, while urine or milk cowside tests can also be used in on-farm monitoring programs. Concentrations >1.0 mmol/L or 1.4 mmol/L blood or serum BHB are considered diagnostic of subclinical ketosis. The standard threshold used for blood is 1.2 mmol/L, which corresponds to thresholds of 100 mcmol/L for milk and 15 mg/dL for urine. Oral administration of propylene glycol (250-400 g, every 24 h for 3-5 days) is the standard and most efficacious treatment, as well as additional therapy with bolus glucose treatment. Hypocalcemia is a disease of adult dairy cows in which acute hypocalcemia causes acute to peracute, afebrile, flaccid paralysis that occurs most commonly at or soon after parturition. Dairy cows are at considerable risk for hypocalcemia at the onset of lactation, when daily calcium excretion suddenly increases from about 10 g to 30 g per day. Cows with hypocalcemia have a more profound decrease in blood calcium concentration-typically below 5.5 mg/dL. The prevention of parturient paresis has been historically approached by feeding cows low-calcium diets during the dry period. Negative calcium balance triggers calcium mobilization before calving and better equips the cow to respond to the massive calcium needs at the onset of lactation. Calcium intake must be limited to <20 g per day for calcium restriction to be effective. The most practical and proven method for monitoring hypocalcemia is by feeding cows an acidogenic diet for ~3 weeks before calving. Throughout the review, emphasis is placed on the importance of early diagnosis and proactive management strategies to mitigate the impact of these metabolic diseases on dairy cattle health and productivity. The comprehensive nature of this paper aims to serve as a valuable resource for veterinarians, researchers, and dairy farmers seeking a deeper understanding of these prevalent metabolic disorders in dairy cattle.

MicroRNA-1225-5p Promotes the Development of Fibrotic Cataracts via Keap1/Nrf2 Signaling

Purpose Fibrotic cataracts, including anterior subcapsular cataract (ASC) as well as posterior capsule opacification (PCO), are a common vision-threatening cause worldwide. Still, little is known about the underlying mechanisms. Here, we demonstrate a miRNA-based pathway regulating the pathological fibrosis process of lens epithelium. Methods Gain- and loss-of-function approaches, as well as multiple fibrosis models of the lens, were applied to validate the crucial role of two miR-1225 family members in the TGF-β2 induced PCO model of human LECs and injury-induced ASC model in mice. Results Both miR-1225-3p and miR-1225-5p prominently stimulate the migration and EMT process of lens epithelial cells (LECs) in vitro as well as lens fibrosis in vivo. Moreover, we demonstrated that the underlying mechanism for these effects of miR-1225-5p is via directly targeting Keap1 to regulate Keap1/Nrf2 signaling. In addition, evidence showed that Keap1/Nrf2 signaling is activated in the TGF-β2 induced PCO model of human LECs and injury-induced ASC model in mice, and inhibition of the Nrf2 pathway can significantly reverse the process of LECs EMT as well as lens fibrosis. Conclusions These results suggest that blockade of miR-1225-5p prevents lens fibrosis via targeting Keap1 thereby inhibiting Nrf2 activation. The ‘miR-1225-Keap1-Nrf2’ signaling axis presumably holds therapeutic promise in the treatment of fibrotic cataracts.

A 30 YEAR (1991-2020) RETROSPECTIVE MORTALITY REVIEW OF GIRAFFIDS (GIRAFFA SPP. AND OKAPIA JOHNSTONI) IN MANAGED CARE.

Identifying common causes of mortality in zoo giraffe (Giraffa spp.) and okapi (Okapia johnstoni) provides an opportunity to help improve welfare and population management for these endangered species. Mortality reports from 1,024 giraffe and 95 okapi in zoos were compiled from the Species 360 Zoological Information Management Software (ZIMS) utilizing the Morbidity & Mortality Analysis tool. Thirty years of mortality reports (1991-2020) were evaluated to help identify trends and evaluate the impacts, if any, of changes over time in husbandry and management practices. The most common causes of death for giraffe from 1991 to 2015 were neonatal issues (234/845, 27.7%), trauma (213/845, 25.2%), noninfectious disease (190/845, 22.5%), and infectious disease (188/845, 22.2%). In comparison, the most common causes of mortality for giraffe from 2016 to 2020, were noninfectious disease (78/179, 43.6%), trauma (39/179, 21.8%), neonatal issues (39/179, 21.8%), and infectious disease (17/179, 9.5%). The most common cause of death for okapi from 1991 to 2015 were neonatal issues (29/64, 45.3%), infectious disease (13/64, 20.3%), noninfectious disease (11/64, 17.2%), and trauma (10/64, 15.6%). In comparison, the most common cause of death for okapi from 2016 to 2020 was noninfectious disease (15/31, 48.4%), neonatal issues (8/31, 25.8%), and infectious disease (5/31, 16.1%). The results suggest that zoo giraffids have had a relative decrease in mortality from infectious diseases in recent years, whereas death from noninfectious causes has increased significantly. Trauma-related giraffe mortalities and neonatal mortality in both giraffe and okapi, although decreasing in prevalence between time periods, continue to be important causes of death in zoos. This is the first descriptive mortality review for the Giraffidae family and provides data on potential giraffe and okapi health issues that zoos could proactively address.

Aetio-pathological profile of anaemic children belonging to upper socioeconomic society in a tertiary care hospital of North India

Introduction: Anaemia is a major public health problem especially in the preschool age group. It is rampant even in children of upper and middle classes of the society.Objectives: To study the aetio-pathology of anaemia in children belonging to upper and upper middle socio-economic scale and to correlate it with their nutritional status. Method: It was a cross-sectional descriptive study on 165 preschool children aged 6-59 months who presented with pallor on clinical examination. They were advised to undergo a complete haemogram and further specific tests as required. Results: The most common cause of anaemia was nutritional, including iron deficiency (92%), combined iron and B12 deficiency (2%) and isolated B12 deficiency (0.6%). Thalassaemia was the next common cause (3%) followed by B-acute lymphoblastic leukaemia (1%) and microangiopathic haemolytic anaemia (0.6%). Maternal education and nutritional awareness had positive correlation with anaemia. Majority of children were normally nourished despite being anaemic, However, undernourished children were more severely anaemic. Conclusions: Nutritional anaemia is the commonest cause of anaemia even in children belonging to higher socio-economic classes.

Long Non-coding RNA ANRIL and Its Role in the Development of Age-Related Diseases.

ANRIL is known as a lncRNA that has many linear and circular isoforms and its polymorphisms are observed to be associated with the pathogenesis of many diseases including age-related diseases. Age-related diseases including atherosclerosis, ischemic heart disease, and Alzheimer's and Parkinson's disease are the most common cause of mortality in both developed and undeveloped countries and that is why a better understanding of their pathogenesis and underlying mechanisms is necessary for controlling their healthcare burden.In this review, we aim to gather the data of researches which have investigated the role of ANRIL in aging and its related diseases. The conclusions of this paper might give a new insight for decreasing the mortality rate of these diseases.

Pre-selection blade size choice for the microsurgical clipping of cerebral artery aneurysms: A numerical study

BackgroundBrain strokes comprise the third leading cause of death worldwide. Microsurgical clipping is recognized as being one of the most effective approaches to the treatment of brain aneurysms. The incomplete closure of the distal-side aneurysm neck is the most common cause of the persistent filling of the dome. Since the diameter of the neck increases when the neck of the aneurysm is squeezed closed by the blades of the clip, the blades should be correspondingly longer. This study provided an assessment of whether the presurgical selection of clips using a 3D planning system is feasible in terms of selecting the most suitable clip for aneurysm occlusion. MethodsThe computational model was created based on computer tomography data obtained from nine brain aneurysms. The closing of the aneurysm was provided in two steps. The first the length of the blades used for closing corresponded to the length of the aneurysm neck as confirmed by the radiological measurements. The second the length of the blades was adjusted according to stage one, so as to determine the minimum required for the closure of all the gaps in the interior space of the aneurysm neck. ResultsNo differences were detected between the radiological measurement of the aneurysm neck size and the measurements obtained from the reconstructed stereolithographic 3D models. It was observed that the size of the aneurysm neck increased following clipping by 40% to 60% of its original size. The larger the aneurysm neck, the greater the deformation of the aneurysm. ConclusionFirstly, the 3D reconstruction of CT/MRI data did not result in any loss of accuracy and the measurement of the neck of the aneurysm was the same for both of the methods employed. The second, and more important, outcome was that the deformation of the neck of the cerebral aneurysm is at least 1.4x greater than its original size. This information is essential in terms of the pre-selection of the size of the clip.

Investigating the impacts of autonomous vehicles on crash severity and traffic safety

Traffic accidents are a nationwide public health concern, but autonomous vehicles (AVs) have the potential to significantly reduce accident severity and frequency by eliminating their most common cause, human error. By analyzing the data published by California’s Department of Motor Vehicles, researchers have identified the factors that influence AV crash severity, however, none do so through a literature review. This paper’s aims are multi-faceted: to understand AVs’ operation on public roadways by identifying and classifying the factors contributing to accident severity, to develop a list of strategies that address the public’s safety concerns, and to acknowledge the ethics of unavoidable collisions. To fulfill these objectives, a comprehensive literature review was conducted based on a keyword search. Following a multi-step screening and exclusion process, detailed review was performed of 107 relevant publications, and the factors contributing to increased crash severity were classified into 14 categories. The literature revealed that AVs are not at fault in most accidents, although they have a higher propensity than conventional cars to be involved in rear-end collisions, and they are specifically designed to minimize the number of accidents, but may face unavoidable ones. For the benefit of policymakers and manufacturers, 11 strategies that address the moral dilemma of these accidents and 7 strategies that address concerns about AV safety to improve public perception were identified.

Spontaneous intracerebral hemorrhage to reversible cerebral vasoconstriction syndrome: Case report

Spontaneous intracerebral hemorrhage (sICH) is a common cause of morbidity and mortality in many countries. Hemorrhagic stroke occurs due to the internal hemorrhage inside the brain as a result of blood vessel rupture. Reversible cerebral vasoconstriction syndrome (RCVS) is multifocal arterial constriction and dilation in the cerebral vasculature and can cause subarachnoid hemorrhage and intracerebral hemorrhage (ICH). We present a case of diagnostic studies of sICH to RCVS in a patient with alcohol chronic consumption history.

Genetics of inborn errors of immunity: Diagnostic strategies and new approaches to CNV detection.

Genetic diagnosis of inborn errors of immunity (IEI) is complex due to the large number of genes involved and their molecular features. Missense variants have been reported as the most common cause of IEI. However, the frequency of copy number variants (CNVs) may be underestimated since their detection requires specific quantitative techniques. At this point, the use of Next Generation Sequencing (NGS) is acquiring relevance. In this article, we present our experience in the genetic diagnosis of IEI based on three diagnostic algorithms that allowed the detection of single nucleotide variants (SNVs) and CNVs. Following this approximation, 703 index cases were evaluated between 2014 and 2021. Sanger sequencing, MLPA, CGH array, breakpoint spanning PCR or a customized NGS-based multigene-targeted panel were performed. A genetic diagnosis was reached in 142 of the 703 index cases (20%), 19 of them presented deletions as causal variants. Deletions were also detected in 5 affected relatives and 16 healthy carriers during the family studies. Additionally, we compile, characterize and present all the CNVs detected by our diagnostic algorithms, representing the largest cohort of deletions related to IEI to date. Furthermore, three bioinformatic tools (LACONv, XHMM, VarSeq™) based on NGS data were evaluated. VarSeq™ was the most sensitive and specific bioinformatic tool; detecting 21/23 (91%) deletions located in captured regions. Based on our results, we propose a strategy to guide the molecular diagnosis that can be followed by expert and non-expert centres in the field of IEI.

Explainable Classification of Patients with Primary Hyperparathyroidism Using Highly Imbalanced Clinical Data Derived from Imaging and Biochemical Procedures

Primary hyperthyroidism (PHPT) is a common endocrine disorder characterized by hypercalcemia and elevated parathyroid hormone (PTH) levels. The most common cause is a single parathyroid adenoma, though the rest of the cases are due to multiglandular disease [double adenoma/hyperplasia]. The main focus driving this work is to develop a computer-aided classification model relying on clinical data to classify PHPT instances and, at the same time, offer explainability for the classification process. A highly imbalanced dataset was created using biometric and clinical data from 134 patients (six total features, 20.2% multiglandular instances). The features used by the current study are age, sex, max diameter index, number of deficiencies, Wisconsin index, and the reference variable indicating the type of PHPT. State-of-the-art machine learning (ML) classification algorithms were used in order to create trained prediction models and give predicted classifications based on all features/indexes. Of the ML models considered (Support Vector Machines, CatBoost, LightGBM, and AdaBoost), LightGBM was able to procure the best performing prediction model. Given the highly imbalanced nature of the particular dataset, oversampling was opted for, so as to increase prediction robustness for both classes. The ML model’s performance was then evaluated using common metrics and stratified ten-fold validation. The significance of this work is rooted in two axes: firstly, in the incorporation of oversampling to smooth out the highly imbalanced dataset and offer good prediction accuracy for both classes, and secondly, in offering an explainability aspect to an otherwise black-box ML prediction model. The maximum achievable accuracy for adenoma is 86.9% and for multigland disease 81.5%. Summarizing the above, this study demonstrates the potential for an ML approach to improve the diagnosis of PHPT and also highlights the importance of explainable artificial intelligence (AI).

Evaluation of the structural integrity of different spinal cord tracts with magnetization transfer ratio in degenerative cervical myelopathy.

Degenerative cervical myelopathy (DCM) is a common cause of spinal cord dysfunction. In this study, we explored the potential of magnetization transfer ratio (MTR) for evaluating the structural integrity of spinal cord tracts in patients with clinically significant DCM. Fifty-three patients with DCM and 41 patients with cervical radiculopathy were evaluated using high-resolution cervical spinal cord magnetic resonance imaging (MRI), which included the magnetization transfer technique. MRI data were analyzed with the Spinal Cord Toolbox (v5.5); MTR values in each spinal tract were calculated and compared between groups after correction for patient age and sex. Correlations between MTR values and patients' clinical disability rate were also evaluated. A statistically significant reduction in the average MTR of the spinal cord white matter, as well as the MTR of the ventral columns and lateral funiculi, was revealed in the DCM group (adjusted p < 0.01 for all comparisons). Furthermore, reductions in MTR values in the fasciculus cuneatus, spinocerebellar, rubrospinal, and reticulospinal tracts were found in patients with DCM (adjusted p < 0.01 for all comparisons). Positive correlations between the JOA score and the MTR within the ventral columns of the spinal cord (R = 0.38, adjusted p < 0.05) and the ventral spinocerebellar tract (R = 0.41, adjusted p < 0.05) were revealed. The findings of our study indicate that demyelination in patients with DCM primarily affects the spinal tracts of the extrapyramidal system, and the extent of these changes is related to the severity of the condition.