Carotid artery stenosis is related to cerebral small vessel disease magnetic resonance imaging burden.

Background: Cerebral small vessel disease (CSVD) encompasses conditions that affect small blood vessels of the brain, the most common being atherosclerosis. Magnetic resonance imaging (MRI) CSVD markers include lacunar strokes (LS), white matter hyperintensities (WMH), microbleeds, enlarged perivascular spaces (EPVS), and brain atrophy. Large and small cerebral arteries share an anatomical and functional connection, but the role of large vessel atherosclerosis in atherosclerotic CSVD hasn't been established. The aim of this study was to evaluate the involvement of large vessel pathology in atherosclerotic CSVD. Methods: This cross-sectional study included 98 patients treated at the Neurology Clinic of the University Clinical Center of Serbia in Belgrade, from February 2018 to December 2023, who had atherosclerotic CSVD confirmed by neuroimaging and underwent extracranial color duplex sonography. Data on patients' gender, age, cerebrovascular risk factors (dyslipidemia, hypertension, diabetes mellitus, smoking status), ultrasonography findings (intima-media thickness - IMT, carotid and vertebral artery stenosis, and hemodynamics), and CSVD imaging markers were collected, and the CSVD MRI burden score was calculated. Results: Age correlated with LS and WMH (p < 0.05 for both). Hypertension correlated with WMH (p = 0.016), and smoking with LS (p = 0.043). Brain atrophy was more common in women (p = 0.016). The majority of patients had low-grade (<50 %) carotid stenosis. There was a strong correlation between all morphological parameters of internal carotid artery stenosis and the CSVD burden score (p < 0.05 for all). The hemodynamic parameters of internal carotid artery stenosis and morphological and hemodynamic parameters of vertebral artery stenosis didn't correlate with the CSVD burden score. Conclusions: This study shows a strong correlation between cerebral large and small vessel pathology. We recommend the use of extracranial color duplex sonography in the evaluation of patients with CSVD as a supplementary method for follow-up, as this would allow the identification of patients whose condition might progress.

Biosensors for Cancer Biomarkers Based on Mesoporous Silica Nanoparticles.

Mesoporous silica nanoparticles (MSNs) exhibit highly beneficial characteristics for devising efficient biosensors for different analytes. Their unique properties, such as capabilities for stable covalent binding to recognition groups (e.g., antibodies or aptamers) and sensing surfaces, open a plethora of opportunities for biosensor construction. In addition, their structured porosity offers capabilities for entrapping signaling molecules (dyes or electroactive species), which could be released efficiently in response to a desired analyte for effective optical or electrochemical detection. This work offers an overview of recent research studies (in the last five years) that contain MSNs in their optical and electrochemical sensing platforms for the detection of cancer biomarkers, classified by cancer type. In addition, this study provides an overview of cancer biomarkers, as well as electrochemical and optical detection methods in general.

Serum Biomarker Analysis in Pediatric ADHD: Implications of Homocysteine, Vitamin B12, Vitamin D, Ferritin, and Iron Levels.

The current diagnosis of attention deficit hyperactivity disorder (ADHD) is based on history, clinical observation, and behavioral tests. There is a high demand to find biomarkers for the diagnosis of ADHD. The aim of this study is to analyze the serum profiles of several biomarkers, including homocysteine (Hcy), vitamin B12, vitamin D, ferritin, and iron, in a cohort of 133 male subjects (6.5-12.5 years), including 67 individuals with an ADHD diagnosis based on DSM-V criteria and 66 age-matched healthy boys (healthy controls, HC). Assessments for ADHD included the Iowa Conners' Teacher Rating Scale (CPRS) and the ADHDT test, as well as cognitive assessments using the Wechsler Intelligence Scale for Children-Revised (WISC-R) and the TROG-2 language comprehension test. Hcy and iron were quantified using spectrophotometry, while vitamin B12 and total 25-hydroxy vitamin D levels were determined using an electrochemiluminescence immunoassay (ECLIA) and ferritin was measured using a particle-enhanced immunoturbidimetric assay. The results showed significantly increased Hcy levels and decreased vitamin B12 levels in ADHD patients compared to HCs. Multiple logistic regression analysis indicated that Hcy is a potential prognostic indicator for ADHD. These results suggest that elevated homocysteine and decreased vitamin B12 may serve as markers for the diagnosis and prognosis of ADHD.

European stroke organisation (ESO) guideline on cerebral small vessel disease, part 2, lacunar ischaemic stroke.

A quarter of ischaemic strokes are lacunar subtype, typically neurologically mild, usually resulting from intrinsic cerebral small vessel pathology, with risk factor profiles and outcome rates differing from other stroke subtypes. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations to assist with clinical decisions about management of lacunar ischaemic stroke to prevent adverse clinical outcomes. The guideline was developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We addressed acute treatment (including progressive lacunar stroke) and secondary prevention in lacunar ischaemic stroke, and prioritised the interventions of thrombolysis, antiplatelet drugs, blood pressure lowering, lipid lowering, lifestyle, and other interventions and their potential effects on the clinical outcomes recurrent stroke, dependency, major adverse cardiovascular events, death, cognitive decline, mobility, gait, or mood disorders. We systematically reviewed the literature, assessed the evidence and where feasible formulated evidence-based recommendations, and expert concensus statements. We found little direct evidence, mostly of low quality. We recommend that patients with suspected acute lacunar ischaemic stroke receive intravenous alteplase, antiplatelet drugs and avoid blood pressure lowering according to current acute ischaemic stroke guidelines. For secondary prevention, we recommend single antiplatelet treatment long-term, blood pressure control, and lipid lowering according to current guidelines. We recommend smoking cessation, regular exercise, other healthy lifestyle modifications, and avoid obesity for general health benefits. We cannot make any recommendation concerning progressive stroke or other drugs. Large randomised controlled trials with clinically important endpoints, including cognitive endpoints, are a priority for lacunar ischaemic stroke.

Trace element content in commercial complementary food formulated for infants and toddlers: Health risk assessment.

The study aimed to analyze trace elements content in baby purees and fruit juices and to evaluate the health risk of young children. The average daily dose, hazard quotient, hazard index and total diet hazard quotient were calculated to assess the potential health risk on per capita and consumers only groups of infants and toddlers. There was no significant health risk for studied groups regarding the intake of trace elements via purees and juices consumption. Health risk for lead was not estimated since the oral reference dose for this metal was not yet established and PTWI value was withdrawn. The average daily dose of lead for infants (0.32 - 0.46 µg/kg bw/day) and toddlers (2.01 - 2.29 µg/kg bw/day) were in accordance with the daily lead exposure intervals estimated by EFSA. Applying statistical analysis, the products were classified into three groups according to the content of trace elements.

PHACTR1 genetic variability is not critical in small vessel ischemic disease patients and PcomA recruitment in C57BL/6J mice.

Recently, several genome-wide association studies identified PHACTR1 as key locus for five diverse vascular disorders: coronary artery disease, migraine, fibromuscular dysplasia, cervical artery dissection and hypertension. Although these represent significant risk factors or comorbidities for ischemic stroke, PHACTR1 role in brain small vessel ischemic disease and ischemic stroke most important survival mechanism, such as the recruitment of brain collateral arteries like posterior communicating arteries (PcomAs), remains unknown. Therefore, we applied exome and genome sequencing in a multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic brain small vessel ischemic disease and CADASIL-like Caucasian patients from US, Portugal, Finland, Serbia and Turkey and in 2 C57BL/6J stroke mouse models (bilateral common carotid artery stenosis [BCCAS] and middle cerebral artery occlusion [MCAO]), characterized by different degrees of PcomAs patency. We report 3 very rare coding variants in the small vessel ischemic disease-CADASIL-like cohort (p.Glu198Gln, p.Arg204Gly, p.Val251Leu) and a stop-gain mutation (p.Gln273*) in one MCAO mouse. These coding variants do not cluster in PHACTR1 known pathogenic domains and are not likely to play a critical role in small vessel ischemic disease or brain collateral circulation. We also exclude the possibility that copy number variants (CNVs) or a variant enrichment in Phactr1 may be associated with PcomA recruitment in BCCAS mice or linked to diverse vascular traits (cerebral blood flow pre-surgery, PcomA size, leptomeningeal microcollateral length and junction density during brain hypoperfusion) in C57BL/6J mice, respectively. Genetic variability in PHACTR1 is not likely to be a common susceptibility factor influencing small vessel ischemic disease in patients and PcomA recruitment in C57BL/6J mice. Nonetheless, rare variants in PHACTR1 RPEL domains may influence the stroke outcome and are worth investigating in a larger cohort of small vessel ischemic disease patients, different ischemic stroke subtypes and with functional studies.

New Opportunities for Endometrial Health by Modifying Uterine Microbial Composition: Present or Future?

Current knowledge suggests that the uterus harbours its own microbiota, where the microbes could influence the uterine functions in health and disease; however, the core uterine microbial composition and the host-microbial relationships remain to be fully elucidated. Different studies are indicating, based on next-generation sequencing techniques, that microbial dysbiosis could be associated with several gynaecological disorders, such as endometriosis, chronic endometritis, dysfunctional menstrual bleeding, endometrial cancer, and infertility. Treatments using antibiotics and probiotics and/or prebiotics for endometrial microbial dysbiosis are being applied. Nevertheless there is no unified protocol for assessing the endometrial dysbiosis and no optimal treatment protocol for the established dysbiosis. With this review we outline the microbes (mostly bacteria) identified in the endometrial microbiome studies, the current treatments offered for bacterial dysbiosis in the clinical setting, and the future possibilities such as pro- and prebiotics and microbial transplants for modifying uterine microbial composition.

Altered organization of collagen fibers in the uninvolved human colon mucosa 10 cm and 20 cm away from the malignant tumor.

Remodelling of collagen fibers has been described during every phase of cancer genesis and progression. Changes in morphology and organization of collagen fibers contribute to the formation of microenvironment that favors cancer progression and development of metastasis. However, there are only few data about remodelling of collagen fibers in healthy looking mucosa distant from the cancer. Using SHG imaging, electron microscopy and specialized softwares (CT-FIRE, CurveAlign and FiberFit), we objectively visualized and quantified changes in morphology and organization of collagen fibers and investigated possible causes of collagen remodelling (change in syntheses, degradation and collagen cross-linking) in the colon mucosa 10 cm and 20 cm away from the cancer in comparison with healthy mucosa. We showed that in the lamina propria this far from the colon cancer, there were changes in collagen architecture (width, straightness, alignment of collagen fibers and collagen molecules inside fibers), increased representation of myofibroblasts and increase expression of collagen-remodelling enzymes (LOX and MMP2). Thus, the changes in organization of collagen fibers, which were already described in the cancer microenvironment, also exist in the mucosa far from the cancer, but smaller in magnitude.

Faecal occult blood screening for colorectal cancer in Serbia: a pilot study.

Colorectal cancer (CRC) is becoming a major public health problem in the Republic of Serbia. Organized mass screening has been shown to decrease CRC mortality and even its incidence. The aim of this study was to assess the acceptability of a faecal immunochemical test for haemoglobin proposed by primary care physicians. From August to November 2013, a pilot study for CRC screening was organized in individuals aged 50 to 74 years. The study included 50 primary healthcare centres from all 25 administrative regions of Serbia. A qualitative immunochromatographic faecal immunochemical test for human haemoglobin detection was used. Overall, 50 894 individuals were invited. The participation rate was 67.8 and 3.4% of the tests were positive. Among individuals with a positive test, 69.7% agreed to undergo colonoscopy. The positive predictive value was 27.1% for adenoma and 14.6% for carcinoma. This was the first CRC screening project encompassing approximately one-third of primary healthcare facilities in all regions across the country. It showed a good response of the target population and satisfactory cooperation of the healthcare professionals involved.

Leptomeningeal carcinomatosis can be presenting manifestation of breast carcinoma.

INTRODUCTION: Leptomeningeal carcinomatosis (LC) is a serious complication occuring in solid cancer patients with rather poor prognosis. CASE REPORT: We presented a 47-year-old woman with the 6-month history of diffuse headache, nausea and visual obscuration. Initially, clinical status and brain magnetic resonance imaging (MRI) indicated syndrome of idiopathic intracranial hypertension. Due to clinical progression and high papillary stasis, cerebrospinal fluid (CSF) examination was performed only after ventriculoperitoneal shunt was implanted. This led to a significant although transient clinical improvement. Futher investigations led to the diagnosis of invasive lobular breast carcinoma and repeated CSF analysis revealed malignant breast carcinoma cells. In this case LC was an initial presentation of a malignant-disease. CONCLUSION: In the presence of a high clinical suspicion of LC, in spite of initially negative findings, a clinician should persist in repeating relevant tests, such are MRI with larger amounts of gadolinium and high-volume cytological CSF analyses in order to make the diagnosis.

The structure of immunocompetent decidual cells in recurrent missed abortions.

Background/Aim: Recurrent or habitual missed abortions (RMA) are defined as three or more consecutive abortions. In the first trimester of pregnancy habitual missed abortions occur in about 1% of population. The aim of this immunohistochemical study of decidua in RMA of unknown etiology was to identify subpopulations of decidual lymphocytes in recurrent miscarriages and compare the distribution of immunocompetent cells in artificial abortions and RMA. Methods. The study included 30 women with at least 2 consecutive miscarriages in the first trimester of pregnancy. Curettements of the third missed abortion were immunohistochemically analyzed. The control group consisted of 20 women without loaded reproductive anamnesis, with the abortion for social reasons. Criteria for exclusion from the study were diagnosed uterine anomalies, positive screening for thrombophilia and women who suffered from diabetes mellitus and disorders in the function of the thyroid gland. Immunophenotyping was performed by immuno-alkaline phosphatase (APAAP) using monoclonal antibodies: CD 30, CD 45 RO, CD 56 and CD 57, CD 68. Methods: The number of missed abortions (1,223) was on the average 9.7% of all deliveriies during the test period. Among them RMA were registered in 52 (4.2%) patients and in 30 (57%) the exact etiology of abortions was not determined. RMA was most common in the 25-34 years of age group. The largest number of RMA showed the ultrasound characteristics of missed abortion in 60% of cases and was in nulliparous patients (76.7%). The number of NK CD56 positive cells did not differ significantly between the types of abortion. In the decidual tissue, a number of NK CD57 positive cells was significantly higher in missed abortions compared to artificial interruptions (p < 0.01). In artificial termination of pregnancy there was an absolute predominance of CD45RO lymphocyte subpopulations, whereas in the RMA group there was slightly greater predominance of CD30 positive cells. The completed analysis showed a significantly higher number of CD68 positive macrophages in a decidual tissue of RMA pregnancy (p < 0.01). Results: The number and phenotypic structure of NK cells are significantly different in normal pregnancy decidua and in RMA. The NK cell dominance is present in the RMA group, in favor of CD56+ and CD 57 of subpopulations with increased CD30 of T lymphocyte subpopulations. Macrophages are more numerous in the decidua of pregnancies ended in abortion, so the cause to RMA of unknown etiology in a number of cases could be disregulation of immunocompetent cells.

Drug treatment of vertigo in neurological disorders.

Vertigo is a common symptom in everyday clinical practice. The treatment depends on the specific etiology. Vertigo may be secondary to inner ear pathology, or any existing brainstem or cerebellar lesion but may also be psychogenic. Central vertigo is a consequence of a central nervous system lesion. It is often associated with a focal neurological deficit. Peripheral vertigo is secondary to dysfunction of the peripheral vestibular system and is usually characterized by an acute vertigo with loss of balance, sensation of spinning in the space or around self, and is exaggerated with changes of the head and body position; no other neurological deficit is present. Some medications may also cause vertigo. Depending on the cause of the vertigo, drugs with different mechanisms of action, physical therapy, psychotherapy, as well as surgery may be used to combat this disabling malady. Symptomatic treatment has a particularly important role, regardless of the etiology of vertigo. We reviewed the current medications recommended for patients with vertigo, their mechanisms of action and their most frequent side effects.

Long-term outcomes of septal reduction for obstructive hypertrophic cardiomyopathy.

BACKGROUND: Surgical myectomy and alcohol septal ablation (ASA) aim to decrease left ventricular outflow tract (LVOT) gradient in hypertrophic cardiomyopathy (HCM). Outcome of myectomy beyond 10 years has rarely been described. We describe 20 years of follow-up of surgical myectomy and 5 years of follow-up for ASA performed for obstructive HCM. METHODS: We studied 171 patients who underwent myectomy for symptomatic LVOT obstruction between 1972 and 2006. In addition, we studied 52 patients who underwent ASA for the same indication and who declined surgery. Follow-up of New York Heart Association (NYHA) functional class, echocardiographic data, and vital status were obtained from patient records. Mortality rates were compared with expected mortality rates of age- and sex-matched populations. RESULTS: Surgical myectomy improved NYHA class (2.74±0.65 to 1.54±0.74, p<0.001), reduced resting gradient (67.4±43.4mmHg to 11.2±16.4mmHg, p<0.001), and inducible LVOT gradient (98.1±34.7mmHg to 33.6±34.9mmHg, p<0.001). Similarly, ASA improved functional class (2.99±0.35 to 1.5±0.74, p<0.001), resting gradient (67.1±26.9mmHg to 23.9±29.4mmHg, p<0.001) and provoked gradient (104.4±34.9mmHg to 35.5±38.6mmHg, p<0.001). Survival after myectomy at 5, 10, 15, and 20 years of follow-up was 92.9%, 81.1%, 68.9%, and 47.5%, respectively. Of note, long-term survival after myectomy was lower than for the general population [standardized mortality ratio (SMR)=1.40, p<0.005], but still compared favorably with historical data from non-operated HCM patients. Survival after ASA at 2 and 5 years was 97.8% and 94.7%, respectively. Short-term (5 year) survival after ASA (SMR=0.61, p=0.48) was comparable to that of the general population. CONCLUSION: Long-term follow-up of septal reduction strategies in obstructive HCM reveals that surgical myectomy and ASA are effective for symptom relief and LVOT gradient reduction and are associated with favorable survival. While overall prognosis for the community HCM population is similar to the general population, the need for surgical myectomy may identify a sub-group with poorer long-term prognosis. We await long-term outcomes of more extensive myectomy approaches adopted in the past 10 years at major institutions.

Are there any association between polycistic ovary syndrome and congenital abnormalities of Müllerian ducts.

BACKGROUND/AIM: There are many specificities of merital infertility and sometimes surprising connections between some thinks with no connections at first sight. Examinations of these patients imply diagnostic actions such as the blood basal hormone sample, doing hysterosalpingography, ultrahysterosonography, ultrasound examinations, and sometimes laparoscopy and hysteroscopy if there are necessary. The aim of the study was to determine the characteristics of the connection between policystic ovary (PCO) syndrome (Sy) and congenital Müllerian ducts abnormalities. METHODS: This study included 356 patients treated in the period from January 1, to December 31, 2009, in the Department of Infertility of the Clinic for Obstetrics and Gynecology in Nis, Serbia. Exclusion criteria were no myoma, ovary cysts, tubal and male factors of infertility. RESULTS: A total of 180 patients were divided into 3 groups: the group I with PCO sy, the group II with uterine congenital malformation and the group III with a combination of these disorders. The middle age of patients was 29.6 +/- 4.8, body mass index (BMI) was 26.1 +/- 4,8 kg/m2 the middle thicknes of endometrium was 5.2 + 2.7 mm, and there were no significant differences between the examined groups. There were no significant among in a number of miscarriages in the examined groups. We found that PCO Sy and congenital abnormalities of Müllerian ducts were conjoint in 30% of examined patients. CONCLUSION: Conjoined PCO Sy and congenital abnormalities of Müllerian ducts do not result in a higher number of miscarriages than only either PCO Sy or abnormalities of Müllerian ducts. It is important to check BMI, basal level of follicle stimulating hormone and number of antral follicles because the induction protocol and concentracion of inductors depends on these characteristics, thus, the succsessful cycles and pregnancy.

Bioaccumulation of arsenic and cadmium in birch and lime from the Bor region.

Copper production in the Bor region (east Serbia) during the last 100 years has influenced the quality of soil, water, and air. This pollution has endangered not only the biotope but all living organisms, including humans. Contents of arsenic (As) and cadmium (Cd) were analyzed in Betula sp. (birch) and Tillia sp. (lime) within the Bor region with the aim to investigate the bioaccumulation of these highly toxic, nonessential trace elements in selected plants, which may be important for biomonitoring and bioremediation purposes. The results of statistical data analysis showed that several factors influenced the bioaccumulation of trace elements in the examined plants, of which soil pH, soil content, and mechanism of accumulation were the main factors. The greatest As and Cd concentrations were found in plant material from the Bor center sampling site in the urban/industrial zone, which is in close proximity to the pollution source, due to the greatest metal concentrations in soil and the lowest soil pH. The low values of biological accumulation coefficients (bioconcentration factor <1, mobility ratio <1) pointed to a low rate of uptake and accumulation of As and Cd in lime and birch. Trace elements showed different patterns of behavior and accumulation in the trees. Lime showed a high ability of assimilation through leaves, whereas birch showed a better potential to express a linear correlation between concentrations in plant parts and soil.

Chemical composition of two different extracts of berries harvested in Serbia.

Total phenolic content (TPC), total anthocyanin content (TAC), free and total ellagic acid content, sugars, minerals, and radical-scavenging activity were determined in nine berries harvested in Serbia. More than 30 phenolic compounds were identified; among them, 11 polyphenols and cis,trans-abscisic acid were quantified using UHPLC coupled with an LTQ-Orbitrap XL mass analyzer. For the first time chrysin, naringenin, pinocembrin, and galangin were quantified in some of the investigated berry species. The extraction efficiency of the two extraction systems, methanol and acetone, was investigated. It was found that acetone is a better extracting solvent for TPC, whereas more TAC was extracted by methanol. TPC in acetone extracts ranged from 177.51 to 459.71 mg gallic acid equiv/100 g frozen weight. TAC ranged from 5.39 to 96.94 mg cyanidin-3-glucoside/100 g frozen weight in methanol extracts. The amounts of both free and total ellagic acid were found to be higher in the acetone extract in comparison to the methanol extract.

A novel Notch3 Gly89Cys mutation in a Serbian CADASIL family.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common heritable cause of stroke and vascular dementia in adults. We present a family from Serbia presenting with stroke and depression in the lack of vascular risk factors, with brain MRI indicating CADASIL. A novel NOTCH3 Gly89Cys mutation was located in exon 3. This report illustrates that in the setting of a positive family history with typical clinical and MRI features, even with an atypical form of pedigree, a high suspicion of CADASIL should lead to genetic testing.

Skin and sural nerve biopsies: ultrastructural findings in the first genetically confirmed cases of CADASIL in Serbia.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited vascular disorder caused by Notch3 gene mutations. The main histopathological hallmark is granular osmiophilic material (GOM) deposited in the close vicinity of vascular smooth muscle cells (VSMCs). The authors report the first 7 ultrastructurally and genetically confirmed cases of CADASIL in Serbia. Samples of skin and sural nerve were investigated by transmission electron microscopy. GOM deposits were observed around degenerated VSMCs in all the skin biopsies examined. Sural nerve biopsies revealed severe alterations of nerve fibers, endoneurial blood vessels with GOM deposits, endoneurial fibroblasts, and perineurial myofibroblasts. Total genomic DNA was extracted from peripheral blood leukocytes, and exons 2-6 of the Notch3 gene were amplified by PCR and subsequently sequenced. Four different mutations in exons 2 (Cys65Tyr), 3 (Gly89Cys and Arg90Cys), and 6 (Ala319Cys), which determine the CADASIL disease, were detected among all described patients. A novel missense mutation Gly89Cys involving exon 3 was detected. Due to the difficulties in the determination of the Notch3 mutations, these data suggest that electron microscopic analysis for GOMs in dermal vessel wall provides a rapid and reliable screening method for this disease.

Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy.

Characterized by ventricular dilatation, systolic dysfunction, and progressive heart failure, dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy in patients. DCM is the most common diagnosis leading to heart transplantation and places a significant burden on healthcare worldwide. The advent of induced pluripotent stem cells (iPSCs) offers an exceptional opportunity for creating disease-specific cellular models, investigating underlying mechanisms, and optimizing therapy. Here, we generated cardiomyocytes from iPSCs derived from patients in a DCM family carrying a point mutation (R173W) in the gene encoding sarcomeric protein cardiac troponin T. Compared to control healthy individuals in the same family cohort, cardiomyocytes derived from iPSCs from DCM patients exhibited altered regulation of calcium ion (Ca(2+)), decreased contractility, and abnormal distribution of sarcomeric α-actinin. When stimulated with a ß-adrenergic agonist, DCM iPSC-derived cardiomyocytes showed characteristics of cellular stress such as reduced beating rates, compromised contraction, and a greater number of cells with abnormal sarcomeric α-actinin distribution. Treatment with ß-adrenergic blockers or overexpression of sarcoplasmic reticulum Ca(2+) adenosine triphosphatase (Serca2a) improved the function of iPSC-derived cardiomyocytes from DCM patients. Thus, iPSC-derived cardiomyocytes from DCM patients recapitulate to some extent the morphological and functional phenotypes of DCM and may serve as a useful platform for exploring disease mechanisms and for drug screening.

What are the differences between younger and older patients with symptomatic small vessel disease?

OBJECTIVE: Although typically linked to aging, small vessel disease (SVD) is also observed in younger adult patients, with common vascular risk factors (RF). We aimed to investigate features of SVD occurrence at an early adult age. PATIENTS AND METHODS: Vascular RF, functional and cognitive status and severity of lesions on MRI expressed as total score on Age-Related White Matter Changes (ARWMC) scale were analyzed in 200 consecutive patients with cerebral SVD admitted to a tertiary neurological hospital. Variables were compared between younger (35-55 years) and older (>56 years) patients. RESULTS: In this study, 63 (31.5%) of patients were 55 years or younger. Both age groups had comparable RF profiles, but smoking emerged as an independent predictor for SVD at a younger age (OR 2.9; 95% CI 1.5-5.5; p=0.002). Younger patients had better functional (OR 1.8; 95% CI 1.3-2.5; p=0.0001) and cognitive (χ(2) 13.94; p=0.0009) status compared to older patients. However, two thirds of younger patients had some degree of cognitive deficit. Total score on ARWMC scale was lower in younger patients (mean 12.3 in younger versus 15.2 in older, OR 1.11; 95% CI 1.0-1.18; p=0.001). There was a strong correlation in both groups between functional score, cognitive status and ARWMC score (p<0.0001). CONCLUSION: In our dataset, younger patients with SVD shared common vascular RF with older patients. In the group aged ≤55, better functional and cognitive status and less severe MRI changes were noted. However, a substantial number of younger SVD patients presenting with TIA or ischemic stroke had various deficits.