Search results for: chromosome abnormalities

Authors: Mitakshara Sharma, S. K. Nema, Sanjeev Narang

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Diabetes mellitus (DM) is a group of metabolic disorders characterized by metabolic abnormalities, chronic hyperglycaemia and long term macrovascular & microvascular complications. Vascular complications are due to platelet hyperactivity and dysfunction, increased inflammation, altered coagulation and endothelial dysfunction. Large proportion of patients with Type II DM suffers from preventable vascular angiopathies, and there is need to develop risk factor modifications and interventions to reduce impact of complications. These complications are attributed to platelet activation, recognised by increase in Platelet Volume Indices (PVI) including Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW). The current study is prospective analytical study conducted over 2 years. Out of 1100 individuals, 930 individuals fulfilled inclusion criteria and were segregated into three groups on basis of glycosylated haemoglobin (HbA1C): - (a) Diabetic, (b) Non-Diabetic and (c) Subjects with Impaired fasting glucose (IFG) with 300 individuals in IFG and non-diabetic groups & 330 individuals in diabetic group. Further, diabetic group was divided into two groups on the basis of presence or absence of known diabetes related vascular complications. Samples for HbA1c and PVI were collected using Ethylene diamine tetraacetic acid (EDTA) as anticoagulant and processed on SYSMEX-X-800i autoanalyser. The study revealed gradual increase in PVI from non-diabetics to IFG to diabetics. PVI were markedly increased in diabetic patients. MPV and PDW of diabetics, IFG and non diabetics were (17.60 ± 2.04)fl, (11.76 ± 0.73)fl, (9.93 ± 0.64)fl and (19.17 ± 1.48)fl, (15.49 ± 0.67)fl, (10.59 ± 0.67)fl respectively with a significant p value 0.00 and a significant positive correlation (MPV-HbA1c r = 0.951; PDW-HbA1c r = 0.875). MPV & PDW of subjects with diabetes related complications were higher as compared to those without them and were (17.51±0.39)fl & (15.14 ± 1.04)fl and (20.09 ± 0.98) fl & (18.96 ± 0.83)fl respectively with a significant p value 0.00. There was a significant positive correlation between PVI and duration of diabetes across the groups (MPV-HbA1c r = 0.951; PDW-HbA1c r = 0.875). However, a significant negative correlation was found between glycaemic levels and total platelet count (PC- HbA1c r =-0.164). This is multi-parameter and comprehensive study with an adequately powered study design. It can be concluded from our study that PVI are extremely useful and important indicators of impending vascular complications in all patients with deranged glycaemic control. Introduction of automated cell counters has facilitated the availability of PVI as routine parameters. PVI is a useful means for identifying larger & active platelets which play important role in development of micro and macro angiopathic complications of diabetes leading to mortality and morbidity. PVI can be used as cost effective markers to predict and prevent impending vascular events in patients with Diabetes mellitus especially in developing countries like India. PVI, if incorporated into protocols for management of diabetes, could revolutionize care and curtail the ever increasing cost of patient management.

Keywords: diabetes, IFG, HbA1C, MPV, PDW, PVI

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Authors: M. S. Raza, A. Kapil, Sonu Tyagi, H. Gautam, S. Mohapatra, R. Chaudhry, S. Sood, V. Goyal, R. Lodha, V. Sreenivas, B. K. Das

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Background: Acute bacterial meningitis remains the major cause of mortality and morbidity. More than half of the survivors develop the significant lifelong neurological abnormalities. Diagnosis of the hospital acquired acute bacterial meningitis (HAABM) is challenging as it appears either in the post operative patients or patients acquire the organisms from the hospital environment. In both the situations, pathogens are exposed to high dose of antibiotics. Chances of getting multidrug resistance organism are very high. We have performed this experiment to find out the etiological agents of HAABM and its antibiotics susceptibility pattern. Methodology: A perspective study was conducted at the Department of Microbiology, All India Institute of Medical Sciences, New Delhi. From March 2015 to April 2018 total 400 Cerebro spinal fluid samples were collected aseptically. Samples were processed for cell count, Gram staining, and culture. Culture plates were incubated at 37°C for 18-24 hours. Organism grown on blood and MacConkey agar were identified by MALDI-TOF Vitek MS (BioMerieux, France) and antibiotic susceptibility tests were performed by Kirby Bauer disc diffusion method as per CLSI 2015 guideline. Results: Of the 400 CSF samples processed, 43 (10.75%) were culture positive for different bacteria. Out of 43 isolates, the most prevalent Gram-positive organisms were S. aureus 4 (9.30%) followed by E. faecium 3 (6.97%) & CONS 2 (4.65%). Similarly, E. coli 13 (30.23%) was the commonest Gram-negative isolates followed by A. baumannii 12 (27.90%), K. pneumonia 5 (11.62%) and P. aeruginosa 4(9.30%). Most of the antibiotics tested against the Gram-negative isolates were resistance to them. Colistin was most effective followed by Meropenem and Imepenim for all Gram-negative HAABM isolates. Similarly, most of antibiotics tested were susceptible to S. aureus and CONS. However, E. faecium (100%) were only susceptible to vancomycin and teicoplanin. Conclusion: Hospital acquired acute bacterial meningitis (HAABM) is becoming the emerging challenge as most of isolates are showing resistance to commonly used antibiotics. Gram-negative organisms are emerging as the major player of HAABM. Great care needs to be taken especially in tertiary care hospitals. Similarly, antibiotic stewardship should be followed and antibiotic susceptibility test (AST) should be performed regularly to update the antibiotic patter and to prevent from the emergence of resistance. Updated information of the AST will be helpful for the better management of the meningitis patient.

Keywords: CSF, MALDI-TOF, hospital acquired acute bacterial meningitis, AST

Procedia PDF Downloads 127

Authors: Yun-Shan Tsai, Si-Ping Lin, En-Chieh Lin, Xin-Hong Chen, Shin-Yun Ho, Shin-Hong Huang, Ching-ju Hsieh

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Background and significance: Uncorrected refractive errors and cataracts are the main visually debilitating ophthalmological abnormalities in adult participants with intellectual disability (ID). However, not all adult participants with ID may receive a regular and timely ophthalmological assessment. Consequently, some of the ocular diseases may not be diagnosed until late, thereby causing unnecessary ocular morbidity. In addition, recent clinical practice and researches have also suggested that eye-care services for this group are neglected. Purpose: To investigate the unmet need for eye care services, clinical characteristics of cataract, visual function, surgical outcome and prognostic predictors in adult participants with ID at Taipei City Hospital in Taiwan. Methods: This is a one-year prospective clinical study. We recruited about 120 eyes of 60 adult participants with ID who were received cataract surgery. Caregivers of all participants received a questionnaire on current eye care services. Clinical demographic data, such as age, gender, and associated systemic diseases or syndromes, were collected. All complete ophthalmologic examinations were performed 1 month preoperatively and 3 months postoperatively, including ocular biometry, visual function, refractive status, morphology of cataract, associated ocular features, anesthesia methods, surgical types, and complications. Morphology of cataract, visual and surgical outcome was analyzed. Results: A total of 60 participants with mean age 43.66 ± 13.94 years, including 59.02% male and 40.98% female, took part in comprehensive eye-care services. The prevalence of unmet need for eye care services was high (about 70%). About 50% of adult participants with ID have bilateral cataracts at the time of diagnosis. White cataracts were noted in about 30% of all adult participants with ID at the time of presentation. Associated ocular disorders were included myopic maculopathy (4.54%), corneal disorders (11.36%), nystagmus (20.45%), strabismus (38.64%) and glaucoma (2.27%). About 26.7% of adult participants with ID underwent extracapsular cataract extraction whereas a phacoemulsification was performed in 100% of eyes. Intraocular lens implantation was performed in all eyes. The most common postoperative complication was posterior capsular opacification (30%). The mean best-corrected visual acuity was significantly improved from preoperatively (mean log MAR 0.48 ± 0.22) to at 3 months postoperatively (mean log MAR 0.045 ± 0.22) (p < .05). Conclusions: Regular follow up will help address the need for eye-care services in participants with ID. A high incidence of bilateral cataracts, as well as white cataracts, was observed in adult participants with ID. Because of early diagnosis and early intervention of cataract, the visual and surgical outcomes of cataract are good, but the visual outcomes are suboptimal due to associated ocular comorbidities.

Keywords: adult participants with intellectual disability, cataract, cataract surgery

Procedia PDF Downloads 278

Authors: Emanuela Chiarella, Annamaria Aloisio, Nisticò Clelia, Maria Mesuraca

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ZNF521 is a stem cell-associated transcription co-factor, that plays a crucial role in the homeostatic regulation of the stem cell compartment in the hematopoietic, osteo-adipogenic, and neural system. In normal hematopoiesis, primary human CD34+ hematopoietic stem cells display typically a high expression of ZNF521, while its mRNA levels rapidly decrease when these progenitors progress towards erythroid, granulocytic, or B-lymphoid differentiation. However, most acute myeloid leukemias (AMLs) and leukemia-initiating cells keep high ZNF521 expression. In particular, AMLs are often characterized by chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene, which MLL gene includes a variety of fusion oncogenes arisen from genes normally required during hematopoietic development; once they are fused, they promote epigenetic and transcription factor dysregulation. The chromosomal translocation t(9;11)(p21-22;q23), fusing the MLL gene with AF9 gene, results in a monocytic immune phenotype with an aggressive course, frequent relapses, and a short survival time. To better understand the dysfunctional transcriptional networks related to genetic aberrations, AML gene expression profile datasets were queried for ZNF521 expression and its correlations with specific gene rearrangements and mutations. The results showed that ZNF521 mRNA levels are associated with specific genetic aberrations: the highest expression levels were observed in AMLs involving t(11q23) MLL rearrangements in two distinct datasets (MILE and den Boer); elevated ZNF521 mRNA expression levels were also revealed in AMLs with t(7;12) or with internal rearrangements of chromosome 16. On the contrary, relatively low ZNF521 expression levels seemed to be associated with the t(8;21) translocation, that in turn is correlated with the AML1-ETO fusion gene or the t(15;17) translocation and in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. Invitro, we found that the enforced co-expression of ZNF521 in cord blood-derived CD34+ cells induced a significant proliferative advantage, improving MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome profiling of CD34+ cells transduced with either MLL-AF9, ZNF521, or a combination of the two transgenes highlighted specific sets of up- or down-regulated genes that are involved in the leukemic phenotype, including those encoding transcription factors, epigenetic modulators, and cell cycle regulators as well as those engaged in the transport or uptake of nutrients. These data enhance the functional cooperation between ZNF521 and MA9, resulting in the development, maintenance, and clonal expansion of leukemic cells. Finally, silencing of ZNF521 in MLL-AF9-transformed primary CD34+ cells inhibited their proliferation and led to their extinction, as well as ZNF521 silencing in the MLL-AF9+ THP-1 cell line resulted in an impairment of their growth and clonogenicity. Taken together, our data highlight ZNF521 role in the control of self-renewal and in the immature compartment of malignant hematopoiesis, which, by altering the gene expression landscape, contributes to the development and/or maintenance of AML acting in concert with the MLL-AF9 fusion oncogene.

Keywords: AML, human zinc finger protein 521 (hZNF521), mixed lineage leukemia gene (MLL) AF9 (MLLT3 or LTG9), cord blood-derived hematopoietic stem cells (CB-CD34+)

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Authors: Sahar Heidary

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Radiography and radiotherapy have emerged as crucial pillars of modern medical practice, revolutionizing diagnostics and treatment for a myriad of health conditions. This abstract highlights the pivotal role of radiography and radiotherapy in favor of healthcare and society. Radiography, a non-invasive imaging technique, has significantly advanced medical diagnostics by enabling the visualization of internal structures and abnormalities within the human body. With the advent of digital radiography, clinicians can obtain high-resolution images promptly, leading to faster diagnoses and informed treatment decisions. Radiography plays a pivotal role in detecting fractures, tumors, infections, and various other conditions, allowing for timely interventions and improved patient outcomes. Moreover, its widespread accessibility and cost-effectiveness make it an indispensable tool in healthcare settings worldwide. On the other hand, radiotherapy, a branch of medical science that utilizes high-energy radiation, has become an integral component of cancer treatment and management. By precisely targeting and damaging cancerous cells, radiotherapy offers a potent strategy to control tumor growth and, in many cases, leads to cancer eradication. Additionally, radiotherapy is often used in combination with surgery and chemotherapy, providing a multifaceted approach to combat cancer comprehensively. The continuous advancements in radiotherapy techniques, such as intensity-modulated radiotherapy and stereotactic radiosurgery, have further improved treatment precision while minimizing damage to surrounding healthy tissues. Furthermore, radiography and radiotherapy have demonstrated their worth beyond oncology. Radiography is instrumental in guiding various medical procedures, including catheter placement, joint injections, and dental evaluations, reducing complications and enhancing procedural accuracy. On the other hand, radiotherapy finds applications in non-cancerous conditions like benign tumors, vascular malformations, and certain neurological disorders, offering therapeutic options for patients who may not benefit from traditional surgical interventions. In conclusion, radiography and radiotherapy stand as indispensable tools in modern medicine, driving transformative improvements in patient care and treatment outcomes. Their ability to diagnose, treat, and manage a wide array of medical conditions underscores their favor in medical practice. As technology continues to advance, radiography and radiotherapy will undoubtedly play an ever more significant role in shaping the future of healthcare, ultimately saving lives and enhancing the quality of life for countless individuals worldwide.

Keywords: radiology, radiotherapy, medical imaging, cancer treatment

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Authors: Vanessa Bennemann, Gabriela Laste, Márcia Inês Goettert

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The gestational period is a phase in which the pregnant woman undergoes constant physiological and hormonal changes, which are part of the woman’s biological cycle, the development of the fetus, childbirth, and lactation. These are factors of response to the immunological adaptation of the human reproductive process that is directly related to the pregnancy’s well-being and development. Although most pregnancies occur without complications, about 15% of pregnant women will develop potentially fatal complications, implying maternal and fetal risk. Therefore, requiring specialized care for high-risk pregnant women (HRPW) with obstetric interventions for the survival of the mother and/or fetus. Among the risk factors that characterize HRPW are the women's age, gestational diabetes mellitus (GDM), autoimmune diseases, infectious diseases such as syphilis and HIV, hypertension (SAH), preeclampsia, eclampsia, HELLP syndrome, uterine contraction abnormalities, and premature placental detachment (PPD), thyroid disorders, among others. Thus, pregnancy has an impact on the thyroid gland causing changes in the functioning of the mother's thyroid gland, altering the thyroid hormone (TH) profiles and production as pregnancy progresses. Considering, throughout the gestational period, the interpretation of the results of the tests to evaluate the thyroid functioning depends on the stage in which the pregnancy is. Thyroid disorders are directly related to adverse obstetric outcomes and in child development. Therefore, the adequate release of TH is important for a pregnancy without complications and optimal fetal growth and development. Objective: Investigate the physiological effects caused by thyroid disorders in the gestational period. Methods: A search for articles indexed in PubMed, Scielo, and MDPI databases, was performed using the term “AND”, with the descriptors: Pregnancy, Thyroid. With several combinations that included: Melatonin, Thyroidopathy, Inflammatory processes, Cytokines, Anti-inflammatory, Antioxidant, High-risk pregnancy. Subsequently, the screening was performed through the analysis of titles and/or abstracts. The criteria were: including clinical studies in general, randomized or not, in the period of 10 years prior to the research, in the English literature; excluded: experimental studies, case reports, research in the development phase. Results: In the preliminary results, a total of studies (n=183) were found, (n=57) excluded, such as studies of cancer, diabetes, obesity, and skin diseases. Conclusion: To date, it has been identified that thyroid diseases can impair the fetus’s brain development. Further research is suggested on this matter to identify new substances that may have a potential therapeutic effect to aid the gestational period with thyroid diseases.

Keywords: pregnancy, thyroid, melatonin, high-risk pregnancy

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Authors: Shagufta Jabeen, Faez J. Firdaus Abdullah, Zunita Zakaria, Nurulfiza M. Isa, Yung C. Tan, Wai Y. Yee, Abdul R. Omar

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Pasteurella multocida (PM) is an important veterinary opportunistic pathogen particularly associated with septicemic pasteurellosis, pneumonic pasteurellosis and hemorrhagic septicemia in cattle and buffaloes. P. multocida serotype A has been reported to cause fatal pneumonia and septicemia. Pasteurella multocida subspecies multocida of serotype A Malaysian isolate PMTB2.1 was first isolated from buffaloes died of septicemia. In this study, the genome of P. multocida strain PMTB2.1 was sequenced using third-generation sequencing technology, PacBio RS2 system and analyzed bioinformatically via de novo analysis followed by in-depth analysis based on comparative genomics. Bioinformatics analysis based on de novo assembly of PacBio raw reads generated 3 contigs followed by gap filling of aligned contigs with PCR sequencing, generated a single contiguous circular chromosome with a genomic size of 2,315,138 bp and a GC content of approximately 40.32% (Accession number CP007205). The PMTB2.1 genome comprised of 2,176 protein-coding sequences, 6 rRNA operons and 56 tRNA and 4 ncRNAs sequences. The comparative genome sequence analysis of PMTB2.1 with nine complete genomes which include Actinobacillus pleuropneumoniae, Haemophilus parasuis, Escherichia coli and five P. multocida complete genome sequences including, PM70, PM36950, PMHN06, PM3480, PMHB01 and PMTB2.1 was carried out based on OrthoMCL analysis and Venn diagram. The analysis showed that 282 CDs (13%) are unique to PMTB2.1and 1,125 CDs with orthologs in all. This reflects overall close relationship of these bacteria and supports the classification in the Gamma subdivision of the Proteobacteria. In addition, genomic distance analysis among all nine genomes indicated that PMTB2.1 is closely related with other five Pasteurella species with genomic distance less than 0.13. Synteny analysis shows subtle differences in genetic structures among different P.multocida indicating the dynamics of frequent gene transfer events among different P. multocida strains. However, PM3480 and PM70 exhibited exceptionally large structural variation since they were swine and chicken isolates. Furthermore, genomic structure of PMTB2.1 is more resembling that of PM36950 with a genomic size difference of approximately 34,380 kb (smaller than PM36950) and strain-specific Integrative and Conjugative Elements (ICE) which was found only in PM36950 is absent in PMTB2.1. Meanwhile, two intact prophages sequences of approximately 62 kb were found to be present only in PMTB2.1. One of phage is similar to transposable phage SfMu. The phylogenomic tree was constructed and rooted with E. coli, A. pleuropneumoniae and H. parasuis based on OrthoMCL analysis. The genomes of P. multocida strain PMTB2.1 were clustered with bovine isolates of P. multocida strain PM36950 and PMHB01 and were separated from avian isolate PM70 and swine isolates PM3480 and PMHN06 and are distant from Actinobacillus and Haemophilus. Previous studies based on Single Nucleotide Polymorphism (SNPs) and Multilocus Sequence Typing (MLST) unable to show a clear phylogenetic relatedness between Pasteurella multocida and the different host. In conclusion, this study has provided insight on the genomic structure of PMTB2.1 in terms of potential genes that can function as virulence factors for future study in elucidating the mechanisms behind the ability of the bacteria in causing diseases in susceptible animals.

Keywords: comparative genomics, DNA sequencing, phage, phylogenomics

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Authors: Goutam Kumar Ghorai, Sandip Sadhukhan, Arpita Sarkar, Debprasad Sinha, G. Sarkar, Ashis K. Dhara

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Diabetes mellitus is one of the most common chronic diseases in all countries and continues to increase in numbers significantly. Diabetic retinopathy (DR) is damage to the retina that occurs with long-term diabetes. DR is a major cause of blindness in the Indian population. Therefore, its early diagnosis is of utmost importance towards preventing progression towards imminent irreversible loss of vision, particularly in the huge population across rural India. The barriers to eye examination of all diabetic patients are socioeconomic factors, lack of referrals, poor access to the healthcare system, lack of knowledge, insufficient number of ophthalmologists, and lack of networking between physicians, diabetologists and ophthalmologists. A few diabetic patients often visit a healthcare facility for their general checkup, but their eye condition remains largely undetected until the patient is symptomatic. This work aims to focus on the design and development of a fully automated intelligent decision system for screening retinal fundus images towards detection of the pathophysiology caused by microaneurysm in the early stage of the diseases. Automated detection of microaneurysm is a challenging problem due to the variation in color and the variation introduced by the field of view, inhomogeneous illumination, and pathological abnormalities. We have developed aconvolutional neural network for efficient detection of microaneurysm. A loss function is also developed to handle severe class imbalance due to very small size of microaneurysms compared to background. The network is able to locate the salient region containing microaneurysms in case of noisy images captured by non-mydriatic cameras. The ground truth of microaneurysms is created by expert ophthalmologists for MESSIDOR database as well as private database, collected from Indian patients. The network is trained from scratch using the fundus images of MESSIDOR database. The proposed method is evaluated on DIARETDB1 and the private database. The method is successful in detection of microaneurysms for dilated and non-dilated types of fundus images acquired from different medical centres. The proposed algorithm could be used for development of AI based affordable and accessible system, to provide service at grass root-level primary healthcare units spread across the country to cater to the need of the rural people unaware of the severe impact of DR.

Keywords: retinal fundus image, deep convolutional neural network, early detection of microaneurysms, screening of diabetic retinopathy

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Authors: Nouha Bouayed Abdelmoula, Rim Louati, Nawel Abdellaoui, Balkiss Abdelmoula, Oldez Kaabi, Walid Smaoui, Samir Aloulou

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Background and Aims: Cardiofaciocutaneous syndrome (CFC) is an autosomal dominant disorder with the vast majority of cases arising by a new mutation of BRAF, MEK1, MEK2, or rarely, KRAS genes. Here, we report a rare Tunisian case of CFC syndrome for whom we identify SOS1 mutation. Methods: Genomic DNA was obtained from peripheral blood collected in an EDTA tube and extracted from leukocytes using the phenol/chloroform method according to standard protocols. High resolution melting (HRM) analysis for screening of mutations in the entire coding sequence of PTPN11 was conducted first. Then, HRM assays to look for hot spot mutations coding regions of the other genes of the RAS-MAPK pathway (RAt Sarcoma viral oncogene homolog Mitogen-Activated Protein Kinases Pathway): SOS1, SHOC2, KRAS, RAF1, KRAS, NRAS, CBL, BRAF, MEK1, MEK2, HRAS, and RIT1, were applied. Results: Heterozygous SOS1 point mutation clustered in exon 10, which encodes for the PH domain of SOS1, was identified: c.1655 G > A. The patient was a 9-year-old female born from a consanguineous couple. She exhibited pulmonic valvular stenosis as congenital heart disease. She had facial features and other malformations of Noonan syndrome, including macrocephaly, hypertelorism, ptosis, downslanting palpebral fissures, sparse eyebrows, a short and broad nose with upturned tip, low-set ears, high forehead commonly associated with bitemporal narrowing and prominent supraorbital ridges, short and/or webbed neck and short stature. However, the phenotype is also suggestive of CFC syndrome with the presence of more severe ectodermal abnormalities, including curly hair, keloid scars, hyperkeratotic skin, deep plantar creases, and delayed permanent dentition with agenesis of the right maxillary first molar. Moreover, the familial history of the patient revealed recurrent brain malignancies in the paternal family and epileptic disease in the maternal family. Conclusions: This case report of an overlapping RASopathy associated with SOS1 mutation and familial history of brain tumorigenesis is exceptional. The evidence suggests that RASopathies are truly cancer-prone syndromes, but the magnitude of the cancer risk and the types of cancer partially overlap.

Keywords: cardiofaciocutaneous syndrome, CFC, SOS1, brain cancer, germline mutation

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Authors: Mia Bahar, Özlem Bozkurt

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Obsessive-compulsive disorder (OCD) is a typical, persistent, and long-lasting mental health condition in which a person experiences uncontrollable, recurrent thoughts (or "obsessions") and/or activities (or "compulsions") that they feel compelled to engage in repeatedly. Obsessive-compulsive disorder is both underdiagnosed and undertreated. It frequently manifests in a variety of medical settings and is persistent, expensive, and burdensome. Obsessive-compulsive neurosis was long believed to be a condition that offered valuable insight into the inner workings of the unconscious mind. Obsessive-compulsive disorder is now recognized as a prime example of a neuropsychiatric condition susceptible to particular pharmacotherapeutic and psychotherapy therapies and mediated by pathology in particular neural circuits. An obsessive-compulsive disorder which is called OCD, usually has two components, one cognitive and the other behavioral, although either can occur alone. Obsessions are often repetitive and intrusive thoughts that invade consciousness. These obsessions are incredibly hard to control or dismiss. People who have OCD often engage in rituals to reduce anxiety associated with intrusive thoughts. Once the ritual is formed, the person may feel extreme relief and be free from anxiety until the thoughts of contamination intrude once again. These thoughts are strengthened through a manifestation of negative reinforcement because they allow the person to avoid anxiety and obscurity. These thoughts are described as autogenous, meaning they most likely come from nowhere. These unwelcome thoughts are related to actions which we can describe as Thought Action Fusion. The thought becomes equated with an action, such as if they refuse to perform the ritual, something bad might happen, and so people perform the ritual to escape the intrusive thought. In almost all cases of OCD, the person's life gets extremely disturbed by compulsions and obsessions. Studies show OCD is an estimated 1.1% prevalence, making it a challenging issue with high co-morbidities with other issues like depressive episodes, panic disorders, and specific phobias. The first to reveal brain anomalies in OCD were numerous CT investigations, although the results were inconsistent. A few studies have focused on the orbitofrontal cortex (OFC), anterior cingulate gyrus (AC), and thalamus, structures also implicated in the pathophysiology of OCD by functional neuroimaging studies, but few have found consistent results. However, some studies have found abnormalities in the basal ganglion. There have also been some discussions that OCD might be genetic. OCD has been linked to families in studies of family aggregation, and findings from twin studies show that this relationship is somewhat influenced by genetic variables. Some Research has shown that OCD is a heritable, polygenic condition that can result from de novo harmful mutations as well as common and unusual variants. Numerous studies have also presented solid evidence in favor of a significant additive genetic component to OCD risk, with distinct OCD symptom dimensions showing both common and individual genetic risks.

Keywords: compulsions, obsessions, neuropsychiatric, genetic

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Authors: Franck kem Acho

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This is a chronic metabolic disorder which is a fast-growing global problem with a huge social, health, and economic consequences. It is estimated that in 2010 there were globally 285 million people (approximately 6.4% of the adult population) suffering from this disease. This number is estimated to increase to 430 million in the absence of better control or cure. An ageing population and obesity are two main reasons for the increase. Diabetes mellitus is a chronic heterogeneous metabolic disorder with a complex pathogenesis. It is characterized by elevated blood glucose levels or hyperglycemia, which results from abnormalities in either insulin secretion or insulin action or both. Hyperglycemia manifests in various forms with a varied presentation and results in carbohydrate, fat, and protein metabolic dysfunctions. Long-term hyperglycemia often leads to various microvascular and macrovascular diabetic complications, which are mainly responsible for diabetes-associated morbidity and mortality. Hyperglycemia serves as the primary biomarker for the diagnosis of diabetes as well. Furthermore, it has been shown that almost 50% of the putative diabetics are not diagnosed until 10 years after onset of the disease, hence the real prevalence of global diabetes must be astronomically high. This study was conducted in a locality to access the level of knowledge, awareness and risk factors associated with people leaving with diabetes mellitus. A month before the screening was to be conducted, a health screening in some selected churches and on the local community radio as well as on relevant WhatsApp groups were advertised. A general health talk was delivered by the head of the screening unit to all attendees who were all educated on the procedure to be carried out with benefits and any possible discomforts after which the attendee’s consent was obtained. Evaluation of the participants for any leads to the diabetes selected for the screening was done by taking adequate history and physical examinations such as excessive thirst, increased urination, tiredness, hunger, unexplained weight loss, feeling irritable or having other mood changes, having blurry vision, having slow-healing sores, getting a lot of infections, such as gum, skin and vaginal infections. Out of the 94 participants the finding show that 78 were females and 16 were males, 70.21% of participants with diabetes were between the ages of 60-69yrs.The study found that only 10.63% of respondents declared a good level of knowledge of diabetes. Out of 3 symptoms of diabetes analyzed in this study, high blood sugar (58.5%) and chronic fatigue (36.17%) were the most recognized. Out of 4 diabetes risk factors analyzed in this study, obesity (21.27%) and unhealthy diet (60.63%) were the most recognized diabetes risk factors, while only 10.6% of respondents indicated tobacco use. The diabetic foot was the most recognized diabetes complication (50.57%), but some the participants indicated vision problems (30.8%),or cardiovascular diseases (20.21%) as diabetes complications.

Keywords: diabetes mellitus, non comunicable disease, general health talk, hyperglycemia

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Authors: Giovana Vesentini, Fernanda Piculo, Gabriela Marini, Debora Damasceno, Angelica Barbosa, Selma Martheus, Marilza Rudge

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Problem statement: Skeletal muscle is highly adaptable, muscle fiber composition and size can respond to a variety of stimuli, such physiologic, as pregnancy, and metabolic abnormalities, as Diabetes mellitus. This study aimed to analyze the effects of pregnancy-associated diabetes on the rectus abdominis muscle (RA), and to compare this changes in rats and women. Methods: Female Wistar rats were maintained under controlled conditions and distributed in Pregnant (P) and Long-term mild pregnant diabetic (LTMd) (n=3 r/group). Diabetes in rats was induced by streptozotocin (100mg/Kg, sc) on the first day of life, for a hyperglycemic state between 120-300 mg/dL in adult life. Female rats were mated overnight, at day 21 of pregnancy were anesthetized, and killed for the harvesting of maternal RA. Pregnant women who attended the Diabetes Prenatal Care Clinic of Botucatu Medical School were distributed in Pregnant non-diabetic (Pnd) and Gestational Diabetic (GDM) (n=3 w/group). The diagnosis of GDM was established according to ADA’s criteria (2016). The harvesting of RA was during the cesarean section. Transversal cross-sections of the RA of both women and rats were analyzed by transmission electron microscopy. All procedures were approved by the Ethics Committee on Animal Experiments of the Botucatu Medical School (Protocol Number 1003/2013) and by the Botucatu Medical School Ethical Committee for Human Research in Medical Sciences (CAAE: 41570815.0.0000.5411). Results: The photomicrographs of the RA of rats revealed disorganized Z lines, thinning sarcomeres, and a usual quantity of intermyofibrillar mitochondria in the P group. The LTMd group showed swollen sarcoplasmic reticulum, dilated T tubes and areas with sarcomere disruption. The ultrastructural analysis of Pnd non-diabetic women in the RA showed well-organized myofibrils forming intact sarcomeres, organized Z lines and a normal distribution of intermyofibrillar mitochondria. The GDM group revealed increase in intermyofibrillar mitochondria, areas with sarcomere disruption and increased lipid droplets. Conclusion: Pregnancy and diabetes induce adaptations in the ultrastructure of the rectus abdominis muscle for both women and rats, changing the architectural design of these tissues. However, in rats these changes are more severe maybe because, besides the high blood glucose levels, the quadrupedal animal may suffer an excessive mechanical tension during pregnancy by gravity. Probably, these findings may suggest that these alterations are a risk factor that contributes to the development of muscle dysfunction in women with GDM and may motivate treatment strategies in these patients.

Keywords: gestational diabetes, muscle dysfunction, pregnancy, rectus abdominis

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Authors: Antonio Ruiz Gonzalez, Kwang-Leong Choy

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The measurement of electrolytes has a high value in the clinical routine. Ions are present in all body fluids with variable concentrations and are involved in multiple pathologies such as heart failures and chronic kidney disease. In the case of dissolved potassium, although a high concentration in the blood (hyperkalemia) is relatively uncommon in the general population, it is one of the most frequent acute electrolyte abnormalities. In recent years, the integration of thin films technologies in this field has allowed the development of highly sensitive biosensors with ultra-low limits of detection for the assessment of metals in liquid samples. However, despite the current efforts in the miniaturization of sensitive devices and their integration into portable systems, only a limited number of successful examples used commercially can be found. This fact can be attributed to a high cost involved in their production and the sustained degradation of the electrodes over time, which causes a signal drift in the measurements. Thus, there is an unmet necessity for the development of low-cost and robust sensors for the real-time monitoring of analyte concentrations in patients to allow the early detection and diagnosis of diseases. This paper reports a thin film ion-selective sensor for the evaluation of potassium ions in aqueous samples. As an alternative for this fabrication method, aerosol assisted chemical vapor deposition (AACVD), was applied due to cost-effectivity and fine control over the film deposition. Such a technique does not require vacuum and is suitable for the coating of large surface areas and structures with complex geometries. This approach allowed the fabrication of highly homogeneous surfaces with well-defined microstructures onto 50 nm thin gold layers. The degradative processes of the ubiquitously employed poly (vinyl chloride) membranes in contact with an electrolyte solution were studied, including the polymer leaching process, mechanical desorption of nanoparticles and chemical degradation over time. Rational design of a protective coating based on an organosilicon material in combination with cellulose to improve the long-term stability of the sensors was then carried out, showing an improvement in the performance after 5 weeks. The antifouling properties of such coating were assessed using a cutting-edge quartz microbalance sensor, allowing the quantification of the adsorbed proteins in the nanogram range. A correlation between the microstructural properties of the films with the surface energy and biomolecules adhesion was then found and used to optimize the protective film.

Keywords: hyperkalemia, drift, AACVD, organosilicon

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Authors: C. Bel, J. Nevado, F. Ciceri, M. Ropacki, T. Hoffmann, P. Lapunzina, C. Buesa

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Background: The Phelan-McDermid syndrome (PMS) is a genetic disorder caused by the deletion of the terminal region of chromosome 22 or mutation of the SHANK3 gene. Shank3 disruption in mice leads to dysfunction of synaptic transmission, which can be restored by epigenetic regulation with both Lysine Specific Demethylase 1 (LSD1) inhibitors. PMS subjects result in a variable degree of intellectual disability, delay or absence of speech, autistic spectrum disorders symptoms, low muscle tone, motor delays and epilepsy. Vafidemstat is an LSD1 inhibitor in Phase II clinical development with a well-established and favorable safety profile, and data supporting the restoration of memory and cognition defects as well as reduction of agitation and aggression in several animal models and clinical studies. Therefore, vafidemstat has the potential to become a first-in-class precision medicine approach to treat PMS patients. Aims: The goal of this research is to perform an observational trial to psychometrically characterize individuals carrying deletions in SHANK3 and build a foundation for subsequent precision psychiatry clinical trials with vafidemstat. Methodology: This study is characterizing the clinical profile of 20 to 40 subjects, > 16-year-old, with genotypically confirmed PMS diagnosis. Subjects will complete a battery of neuropsychological scales, including the Repetitive Behavior Questionnaire (RBQ), Vineland Adaptive Behavior Scales, Escala de Observación para el Diagnostico del Autismo (Autism Diagnostic Observational Scale) (ADOS)-2, the Battelle Developmental Inventory and the Behavior Problems Inventory (BPI). Results: By March 2021, 19 patients have been enrolled. Unsupervised hierarchical clustering of the results obtained so far identifies 3 groups of patients, characterized by different profiles of cognitive and behavioral scores. The first cluster is characterized by low Battelle age, high ADOS and low Vineland, RBQ and BPI scores. Low Vineland, RBQ and BPI scores are also detected in the second cluster, which in contrast has high Battelle age and low ADOS scores. The third cluster is somewhat in the middle for the Battelle, Vineland and ADOS scores while displaying the highest levels of aggression (high BPI) and repeated behaviors (high RBQ). In line with the observation that female patients are generally affected by milder forms of autistic symptoms, no male patients are present in the second cluster. Dividing the results by gender highlights that male patients in the third cluster are characterized by a higher frequency of aggression, whereas female patients from the same cluster display a tendency toward higher repetitive behavior. Finally, statistically significant differences in deletion sizes are detected comparing the three clusters (also after correcting for gender), and deletion size appears to be positively correlated with ADOS and negatively correlated with Vineland A and C scores. No correlation is detected between deletion size and the BPI and RBQ scores. Conclusions: Precision medicine may open a new way to understand and treat Central Nervous System disorders. Epigenetic dysregulation has been proposed to be an important mechanism in the pathogenesis of schizophrenia and autism. Vafidemstat holds exciting therapeutic potential in PMS, and this study will provide data regarding the optimal endpoints for a future clinical study to explore vafidemstat ability to treat shank3-associated psychiatric disorders.

Keywords: autism, epigenetics, LSD1, personalized medicine

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Authors: Asma'u Mahe, Abdullahi A. Imam, Adamu J. Alhassan, Nasiru Abdullahi, Sadiya A. Bichi, Nura Lawal, Kamaluddeen Babagana

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Malaria is a disease with global health significance. It is caused by parasites and transmitted by Anopheles mosquitoes. Increase in insecticide resistance threatens the disease vector control. The strength of selection pressure acting on a mosquito population in relation to insecticide resistance can be assess by determining the genetic diversity of a fragment spanning exon- 20 of IIS6 of the voltage gated sodium channel (VGSC). Larval samples reared to adulthood were identified and kdr (knock down resistance) profile was determined. The DNA sequences were used to assess the patterns of genetic differentiation by determining the levels of genetic variability between the Anopheles mosquitoes. Genetic differentiation of the Anopheles mosquitoes based on a portion of the voltage gated sodium channel gene was obtained. Polymorphisms were detected; sequence variation and analysis were presented as a phylogenetic tree. Phylogenetic tree of VGSC haplotypes was constructed for samples of the Anopheles mosquitoes using the maximum likelihood method in MEGA 6.0 software. DNA sequences were edited using BioEdit sequence editor. The edited sequences were aligned with reference sequence (Kisumu strain). Analyses were performed as contained in dnaSP 5.10. Results of genetic parameters of polymorphism and haplotype reconstruction were presented in count. Twenty sequences were used for the analysis. Regions selected were 1- 576, invariable (monomorphic) sites were 460 while variable (polymorphic) sites were 5 giving the number of total mutations observed in this study. Mutations obtained from the study were at codon 105: TTC- Phenylalanine replaces TCC- Serine, codon 513: TAG- Termination replaces TTG- Leucine, codon 153, 300 and 553 mutations were non-synonymous. From the constructed phylogenetic tree, some groups were shown to be closer with Exon20Gambiae Kisumu (Reference strain) having some genetic distance, while 5-Exon20Gambiae-F I13.ab1, 18-Exon20Gambiae-F C17.ab1, and 2-Exon20Gambiae-F C13.ab1 clustered together genetically differentiated away from others. Mutations observed in this study can be attributed to the high insecticide resistance profile recorded in the study areas. Haplotype networks of pattern of genetic variability and polymorphism for the fragment of the VGSC sequences of sampled Anopheles mosquitoes revealed low haplotypes for the present study. Haplotypes are set of closely linked DNA variation on X-chromosome. Haplotypes were scaled accordingly to reflect their respective frequencies. Low haplotype number, four VGSC-1014F haplotypes were observed in this study. A positive association was previously established between low haplotype number of VGSC diversity and pyrethroid resistance through kdr mechanism. Significant values at (P < 0.05) of Tajima D and Fu and Li D’ were observed for some of the results indicating possible signature of positive selection on the fragment of VGSC in the study. This is the first report of VGSC-1014F in the study site. Based on the results, the mutation was present in low frequencies. However, the roles played by the observed mutations need further investigation. Mutations, environmental factors among others can affect genetic diversity. The study area has recorded increase in insecticide resistance that can affect vector control in the area. This finding might affect the efforts made against malaria. Sequences were deposited in GenBank for Accession Number.

Keywords: anopheles mosquitoes, insecticide resistance, kdr, malaria, voltage gated sodium channel

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Authors: Shiamaa Eltantawy, Gihan Sobhy, Alif Alaam

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Wilson disease, or hepatolenticular degeneration, is an autosomal recessive disease that results in excess copper buildup in the body. It primarily affects the liver and basal ganglia of the brain, but it can affect other organ systems. Musculoskeletal abnormalities, including premature osteoarthritis, skeletal deformity, and pathological bone fractures, can occasionally be found in WD patients with a hepatic or neurologic type. The aim was to assess the prevalence of osteoporosis and osteopenia in Wilson’s disease patients. This case-control study was conducted on ninety children recruited from the inpatient ward and outpatient clinic of the Paediatric Hepatology, Gastroenterology, and Nutrition department of the National Liver Institute at Menofia University, aged from 1 to 18 years. Males were 49, and females were 41. Children were divided into three groups: (Group I) consisted of thirty patients with WD; (Group II) consisted of thirty patients with chronic liver disease other than WD; (Group III) consisted of thirty age- and sex-matched healthy The exclusion criteria were patients with hyperparathyroidism, hyperthyroidism, renal failure, Cushing's syndrome, and patients on certain drugs such as chemotherapy, anticonvulsants, or steroids. All patients were subjected to the following: 1- Full history-taking and clinical examination. 2-Laboratory investigations: (FBC,ALT,AST,serum albumin, total protein, total serum bilirubin,direct bilirubin,alkaline phosphatase, prothrombin time, serum critine,parathyroid hormone, serum calcium, serum phosphrus). 3-Bone mineral density (BMD, gm/cm2) values were measured by dual-energy X-ray absorptiometry (DEXA). The results revealed that there was a highly statistically significant difference between the three groups regarding the DEXA scan, and there was no statistically significant difference between groups I and II, but the WD group had the lowest bone mineral density. The WD group had a large number of cases of osteopenia and osteoporosis, but there was no statistically significant difference with the group II mean, while a high statistically significant difference was found when compared to group III. In the WD group, there were 20 patients with osteopenia, 4 patients with osteoporosis, and 6 patients who were normal. The percentages were 66.7%, 13.3%, and 20%, respectively. Therefore, the largest number of cases in the WD group had osteopenia. There was no statistically significant difference found between WD patients on different treatment regimens regarding DEXA scan results (Z-Score). There was no statistically significant difference found between patients in the WD group (normal, osteopenic, or osteoporotic) regarding phosphorus (mg/dL), but there was a highly statistically significant difference found between them regarding ionised Ca (mmol/L). Therefore, there was a decrease in bone mineral density when the Ca level was decreased. In summary, Wilson disease is associated with bone demineralization. The largest number of cases in the WD group in our study had osteopenia (66.7%). Different treatment regimens (zinc monotherapy, Artamin, and zinc) as well as different laboratory parameters have no effect on bone mineralization in WD cases. Decreased ionised Ca is associated with low BMD in WD patients. Children with WD should be investigated for BMD.

Keywords: wilson disease, Bone mineral density, liver disease, osteoporosis

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Authors: Einat Waizbard, Emilio Ferrer, Meghan Miller, Brianna Heath, Derek S. Andrews, Sally J. Rogers, Christine Wu Nordahl, Marjorie Solomon, David G. Amaral

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Background: Autism symptoms are comprised of social-communication deficits and restricted/repetitive behaviors (RRB). The severity of these symptoms can change during childhood, with differences between boys and girls. From the literature, it was found that young autistic girls show a stronger tendency to decrease and a weaker tendency to increase their overall autism symptom severity levels compared to young autistic boys. It is not clear, however, which symptoms are driving these sex differences across childhood. In the current study, we evaluated the trajectories of independent autism symptoms across childhood and compared the patterns of change in such symptoms between boys and girls. Method: The study included 183 children diagnosed with autism (55 girls) evaluated three times across childhood, at ages 3, 6 and 11. We analyzed 22 independent items from the Autism Diagnostic Observation Scheudule-2 (ADOS-2), the gold-standard assessment tool for autism symptoms, each item representing a specific autism symptom. First, we used latent growth curve models to estimate the trajectories for the 22 ADOS-2 items for each child in the study. Second, we extracted the factor scores representing the individual slopes for each ADOS-2 item (i.e., slope representing that child’s change in that specific item). Third, we used factor analysis to identify common patterns of change among the ADOS-2 items, separately for boys and girls, i.e., which autism symptoms tend to change together and which change independently across childhood. Results: The best-emerging patterns for both boys and girls identified four common factors: three factors representative of changes in social-communication symptoms and one factor describing changes in RRB. Boys and girls showed the same pattern of change in RRB, with four items (e.g., speech abnormalities) changing together across childhood and three items (e.g., mannerisms) changing independently of other items. For social-communication deficits in boys, three factors were identified: the first factor included six items representing initiating and engaging in social-communication (e.g., quality of social overtures, conversation), the second factor included five items describing responsive social-communication (e.g., response to name) and the third factor included three items related to different aspects of social-communication (e.g., level of language). Girls’ social-communications deficits also loaded onto three factors: the first factor included five items (e.g., unusual eye contact), the second factor included six items (e.g., quality of social response), and the third factor included four items (e.g., showing). Some items showed similar patterns of change for both sexes (e.g., responsive joint attention), while other items showed differences (e.g., shared enjoyment). Conclusions: Girls and boys had different patterns of change in autism symptom severity across childhood. For RRB, both sexes showed similar patterns. For social-communication symptoms, however, there were both similarities and differences between boys and girls in the way symptoms changed over time. The strongest patterns of change were identified for initiating and engaging in social communication for boys and responsive social communication for girls.

Keywords: autism spectrum disorder, autism symptom severity, symptom trajectories, sex differences

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Authors: Shanza Akram, Sameen Toor, Heba Harb Abu Alkass, Zainab Abdulsalam Altaha, Sara Taha Abdulla, Saleem Imran

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Acute pulmonary embolism (PE) is a common disease and can be fatal. The clinical presentation is variable and nonspecific, making accurate diagnosis difficult. Testing patients with suspected acute PE has increased dramatically. However, the overuse of some tests, particularly CT and D-dimer measurement, may not improve care while potentially leading to patient harm and unnecessary expense. CTPA is the investigation of choice for PE. Its easy availability, accuracy and ability to provide alternative diagnosis has lowered the threshold for performing it, resulting in its overuse. Guidelines have recommended the use of clinical pretest probability tools such as ‘Wells score’ to assess risk of suspected PE. Unfortunately, implementation of guidelines in clinical practice is inconsistent. This has led to low risk patients being subjected to unnecessary imaging, exposure to radiation and possible contrast related complications. Aim: To study the diagnostic yield of CT PA, clinical pretest probability of patients according to wells score and to determine whether or not there was an overuse of CTPA in our service. Methods: CT scans done on patients with suspected P.E in our hospital from 1st January 2014 to 31st December 2014 were retrospectively reviewed. Medical records were reviewed to study demographics, clinical presentation, final diagnosis, and to establish if Wells score and D-Dimer were used correctly in predicting the probability of PE and the need for subsequent CTPA. Results: 100 patients (51male) underwent CT PA in the time period. Mean age was 57 years (24-91 years). Majority of patients presented with shortness of breath (52%). Other presenting symptoms included chest pain 34%, palpitations 6%, collapse 5% and haemoptysis 5%. D Dimer test was done in 69%. Overall Wells score was low (<2) in 28 %, moderate (>2 - < 6) in 47% and high (> 6) in 15% of patients. Wells score was documented in medical notes of only 20% patients. PE was confirmed in 12% (8 male) patients. 4 had bilateral PE’s. In high-risk group (Wells > 6) (n=15), there were 5 diagnosed PEs. In moderate risk group (Wells >2 - < 6) (n=47), there were 6 and in low risk group (Wells <2) (n=28), one case of PE was confirmed. CT scans negative for PE showed pleural effusion in 30, Consolidation in 20, atelactasis in 15 and pulmonary nodule in 4 patients. 31 scans were completely normal. Conclusion: Yield of CT for pulmonary embolism was low in our cohort at 12%. A significant number of our patients who underwent CT PA had low Wells score. This suggests that CT PA is over utilized in our institution. Wells score was poorly documented in medical notes. CT-PA was able to detect alternative pulmonary abnormalities explaining the patient's clinical presentation. CT-PA requires concomitant pretest clinical probability assessment to be an effective diagnostic tool for confirming or excluding PE. . Clinicians should use validated clinical prediction rules to estimate pretest probability in patients in whom acute PE is being considered. Combining Wells scores with clinical and laboratory assessment may reduce the need for CTPA.

Keywords: CT PA, D dimer, pulmonary embolism, wells score

Procedia PDF Downloads 192

Authors: Mohammad Karimi Moridani, Mohammad Abdi Zadeh, Zahra Shahiazar Mazraeh

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In recent years, the use of intelligent systems in biomedical engineering has increased dramatically, especially in the diagnosis of various diseases. Also, due to the relatively simple recording of the electrocardiogram signal (ECG), this signal is a good tool to show the function of the heart and diseases associated with it. The aim of this paper is to design an intelligent system for automatically detecting a normal electrocardiogram signal from abnormal one. Using this diagnostic system, it is possible to identify a person's heart condition in a very short time and with high accuracy. The data used in this article are from the Physionet database, available in 2016 for use by researchers to provide the best method for detecting normal signals from abnormalities. Data is of both genders and the data recording time varies between several seconds to several minutes. All data is also labeled normal or abnormal. Due to the low positional accuracy and ECG signal time limit and the similarity of the signal in some diseases with the normal signal, the heart rate variability (HRV) signal was used. Measuring and analyzing the heart rate variability with time to evaluate the activity of the heart and differentiating different types of heart failure from one another is of interest to the experts. In the preprocessing stage, after noise cancelation by the adaptive Kalman filter and extracting the R wave by the Pan and Tampkinz algorithm, R-R intervals were extracted and the HRV signal was generated. In the process of processing this paper, a new idea was presented that, in addition to using the statistical characteristics of the signal to create a return map and extraction of nonlinear characteristics of the HRV signal due to the nonlinear nature of the signal. Finally, the artificial neural networks widely used in the field of ECG signal processing as well as distinctive features were used to classify the normal signals from abnormal ones. To evaluate the efficiency of proposed classifiers in this paper, the area under curve ROC was used. The results of the simulation in the MATLAB environment showed that the AUC of the MLP and SVM neural network was 0.893 and 0.947, respectively. As well as, the results of the proposed algorithm in this paper indicated that the more use of nonlinear characteristics in normal signal classification of the patient showed better performance. Today, research is aimed at quantitatively analyzing the linear and non-linear or descriptive and random nature of the heart rate variability signal, because it has been shown that the amount of these properties can be used to indicate the health status of the individual's heart. The study of nonlinear behavior and dynamics of the heart's neural control system in the short and long-term provides new information on how the cardiovascular system functions, and has led to the development of research in this field. Given that the ECG signal contains important information and is one of the common tools used by physicians to diagnose heart disease, but due to the limited accuracy of time and the fact that some information about this signal is hidden from the viewpoint of physicians, the design of the intelligent system proposed in this paper can help physicians with greater speed and accuracy in the diagnosis of normal and patient individuals and can be used as a complementary system in the treatment centers.

Keywords: neart rate variability, signal processing, linear and non-linear features, classification methods, ROC Curve

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Authors: Ayse Gul Bilen

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Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants that are used clinically for the treatment of anxiety disorders, obsessive-compulsive disorder (OCD), panic disorders and eating disorders. The first SSRI, fluoxetine (sold under the brand names Prozac and Sarafem among others), had an adverse effect profile better than any other available antidepressant when it was introduced because of its selectivity for serotonin receptors. They have been considered almost free of side effects and have become widely prescribed, however questions about the safety and tolerability of SSRIs have emerged with their continued use. Most SSRI side effects are dose-related and can be attributed to serotonergic effects such as nausea. Continuous use might trigger adverse effects such as hyponatremia, tremor, nausea, weight gain, sleep disturbance and sexual dysfunction. Moderate toxicity can be safely observed in the hospital for 24 hours, and mild cases can be safely discharged (if asymptomatic) from the emergency department once cleared by Psychiatry in cases of intentional overdose and after 6 to 8 hours of observation. Although fluoxetine is relatively safe in terms of overdose, it might still be cardiotoxic and inhibit platelet secretion, aggregation, and plug formation. There have been reported clinical cases of seizures, cardiac conduction abnormalities, and even fatalities associated with fluoxetine ingestions. While the medical literature strongly suggests that most fluoxetine overdoses are benign, emergency physicians need to remain cognizant that intentional, high-dose fluoxetine ingestions may induce seizures and can even be fatal due to cardiac arrhythmia. Our case is a 35-year old female patient who was sent to ER with symptoms of confusion, amnesia and loss of orientation for time and location after being found wandering in the streets unconsciously by police forces that informed 112. Upon laboratory examination, no pathological symptom was found except sinus tachycardia in the EKG and high levels of aspartate transaminase (AST) and alanine transaminase (ALT). Diffusion MRI and computed tomography (CT) of the brain all looked normal. Upon physical and sexual examination, no signs of abuse or trauma were found. Test results for narcotics, stimulants and alcohol were negative as well. There was a presence of dysrhythmia which required admission to the intensive care unit (ICU). The patient gained back her conscience after 24 hours. It was discovered from her story afterward that she had been using fluoxetine due to post-traumatic stress disorder (PTSD) for 6 months and that she had attempted suicide after taking 3 boxes of fluoxetine due to the loss of a parent. She was then transferred to the psychiatric clinic. Our study aims to highlight the need to consider toxicologic drug use, in particular, the abuse of selective serotonin reuptake inhibitors (SSRIs), which have been widely prescribed due to presumed safety and tolerability, for diagnosis of patients applying to the emergency room (ER).

Keywords: abuse, amnesia, fluoxetine, intoxication, SSRI

Procedia PDF Downloads 177

Authors: Fangfang Wang, Tianjing Wang, Leyi Fu, Feng Yun, Ningning Xie, Jue Zhou, Fan Qu

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Background: Ferroptosis, a recently discovered form of programmed cell death characterized by iron-dependent lipid peroxidation, may be linked to polycystic ovary syndrome (PCOS). Diseases marked by iron overload have been correlated with ferroptosis. Coincidently, investigations have revealed anomalies in iron metabolism among women with PCOS; however, there were inconsistencies in the evidence. Objective and Rationale: This review aimed to comprehensively explore the potential relationship between ferroptosis and PCOS by investigating the differences in iron metabolism among women with PCOS in comparison to a control group. Additionally, a narrative synthesis was provided on the past research status regarding the association between PCOS and ferroptosis. Methods: A systematic search of the literature was performed using PubMed, Embase, Web of Science from inception up to December 2022. Search terms relating to assisted PCOS, ferroptosis, and iron metabolism were used. PRISMA guidance was followed. RevMan 5.4 was utilized for conducting the meta-analysis, wherein the investigated outcomes included iron status (ferritin, iron, transferrin saturation) and a systemic iron-regulatory hormone (hepcidin). A narrative synthesis was performed to explore the correlation between PCOS and ferroptosis. Results: In the meta-analysis comprising a total of 16 studies, significant differences in serum ferritin levels between the PCOS group and the control group were observed (15 studies, standardized mean difference (SMD): 0.41, 95% CI: 0.22 to 0.59, P<0.01). This indicates elevated serum ferritin levels in PCOS patients compared to women without PCOS. The transferrin saturation in PCOS patients was significantly higher than that in the control group (3 studies, mean difference (MD): 4.39, 95% CI: 1.67 to 7.11, P<0.01). Regarding serum iron (6 studies, SMD: 0.05, 95% CI: -0.24 to 0.33, P=0.75) and serum hepcidin (4 studies, SMD: -0.44, 95% CI: -1.41 to 0.52, P=0.37), no statistically significant differences were observed between the PCOS group and the control group. Other studies have found that ferroptosis is involved in the occurrence and development of PCOS, offering valuable insights for guiding potential treatment measures and prognosis evaluation of PCOS. In addition, ferroptosis is involved in the miscarriage of PCOS-like rats; thus, controlling ferroptosis might improve pregnancy outcomes in PCOS. Conclusions: The observation of a significant elevation in serum ferritin and transferrin saturation levels in women with PCOS may suggest an underlying disturbance in iron metabolism, potentially inducing the activation of ferroptosis. Further research is imperative to elucidate the underlying pathophysiology, providing insights for potential preventive measures and therapeutic strategies. Limitation: There are some limitations as follows: First, due to limited extractable information, we excluded purely abstract publications and non-English publications. Second, the majority of original articles were case-control studies, making it difficult to determine the causal relationship between iron metabolism abnormalities and the onset of PCOS. Third, there is substantial heterogeneity in the definition of PCOS.

Keywords: polycystic ovary syndrome, ferroptosis, iron metabolism, systematic review and meta-analysis

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Authors: Orkide Donma, Mustafa M. Donma

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Childhood obesity, which may lead to increased risk for heart diseases in children as well as adults, is one of the most important health problems throughout the world. Prevalences of morbid obesity and metabolic syndrome (MetS) are being increased during childhood age group. MetS is a cluster of metabolic and vascular abnormalities including hypercoagulability and an increased risk of cardiovascular diseases (CVDs). There are also some relations between some components of MetS and leukocytes. The aim of this study is to investigate complete blood cell count parameters that differ between morbidly obese boys and girls with MetS diagnosis. A total of 117 morbid obese children with MetS consulted to Department of Pediatrics in Faculty of Medicine Hospital at Namik Kemal University were included into the scope of the study. The study population was classified based upon their genders (60 girls and 57 boys). Their heights and weights were measured and body mass index (BMI) values were calculated. WHO BMI-for age and sex percentiles were used. The values above 99 percentile were defined as morbid obesity. Anthropometric measurements were performed. Waist-to-hip and head-to-neck ratios as well as homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. Components of MetS (central obesity, glucose intolerance, high blood pressure, high triacylglycerol levels, low levels of high density lipoprotein cholesterol) were determined. Hematological variables were measured. Statistical analyses were performed using SPSS. The degree for statistical significance was p ≤ 0.05. There was no statistically significant difference between the ages (11.2±2.6 years vs 11.2±3.0 years) and BMIs (28.6±5.2 kg/m² vs 29.3±5.2 kg/m²) of boys and girls (p ≥ 0.05), respectively. Significantly increased waist-to-hip ratios were obtained for boys (0.94±0.08 vs 0.91±0.06; p=0.023). Significantly elevated values of hemoglobin (13.55±0.98 vs 13.06±0.82; p=0.004), mean corpuscular hemoglobin concentration (33.79±0.91 vs 33.21±1.14; p=0.003), eosinophils (0.300±0.253 vs 0.196±0.197; p=0.014), and platelet (347.1±81.7 vs 319.0±65.9; p=0.042) were detected for boys. There was no statistically significant difference between the groups in terms of neutrophil/lymphocyte ratios as well as HOMA-IR values (p ≥ 0.05). Statistically significant gender-based differences were found for hemoglobin as well as mean corpuscular hemoglobin concentration and hence, separate reference intervals for two genders should be considered for these parameters. Eosinophils may contribute to the development of thrombus in acute coronary syndrome. Eosinophils are also known to make an important contribution to mechanisms related to thrombosis pathogenesis in acute myocardial infarction. Increased platelet activity is observed in patients with MetS and these individuals are more susceptible to CVDs. In our study, elevated platelets described as dominant contributors to hypercoagulability and elevated eosinophil counts suggested to be related to the development of CVDs observed in boys may be the early indicators of the future cardiometabolic complications in this gender.

Keywords: children, complete blood count, gender, metabolic syndrome

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Authors: Anthony S. Machi, Joseph Minardi

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We present a case report of left atrial myxoma diagnosed by bedside transesophageal (TEE) ultrasound. Left atrial myxoma is the most common benign cardiac tumor and can obstruct blood flow and cause valvular insufficiency. Common symptoms consist of dyspnea, pulmonary edema and other features of left heart failure in addition to thrombus release in the form of tumor fragments. The availability of bedside ultrasound equipment is essential for the quick diagnosis and treatment of various emergency conditions including cardiac neoplasms. A 48-year-old Caucasian female with a four-year history of an untreated renal mass and anemia presented to the ED with two months of sharp, intermittent, bilateral flank pain radiating into the abdomen. She also reported intermittent vomiting and constipation along with generalized body aches, night sweats, and 100-pound weight loss over last year. She had a CT in 2013 showing a 3 cm left renal mass and a second CT in April 2016 showing a 3.8 cm left renal mass along with a past medical history of diverticulosis, chronic bronchitis, dyspnea on exertion, uncontrolled hypertension, and hyperlipidemia. Her maternal family history is positive for breast cancer, hypertension, and Type II Diabetes. Her paternal family history is positive for stroke. She was a current everyday smoker with an 11 pack/year history. Alcohol and drug use were denied. Physical exam was notable for a Grade II/IV systolic murmur at the right upper sternal border, dyspnea on exertion without angina, and a tender left lower quadrant. Her vitals and labs were notable for a blood pressure of 144/96, heart rate of 96 beats per minute, pulse oximetry of 96%, hemoglobin of 7.6 g/dL, hypokalemia, hypochloremia, and multiple other abnormalities. Physicians ordered a CT to evaluate her flank pain which revealed a 7.2 x 8.9 x 10.5 cm mixed cystic/solid mass in the lower pole of the left kidney and a filling defect in the left atrium. Bedside TEE was ordered to follow up on the filling defect. TEE reported an ejection fraction of 60-65% and visualized a mobile 6 x 3 cm mass in the left atrium attached to the interatrial septum extending into the mitral valve. Cardiothoracic Surgery and Urology were consulted and confirmed a diagnosis of left atrial myxoma and clear cell renal cell carcinoma. The patient returned a week later due to worsening nausea and vomiting and underwent emergent nephrectomy, lymph node dissection, and colostomy due to a necrotic colon. Her condition declined over the next four months due to lung and brain metastases, infections, and other complications until she passed away.

Keywords: bedside ultrasound, echocardiography, emergency medicine, left atrial myxoma

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Authors: Signe Svensson, Remy Rey, Anna-Lisa Osvalder, Henrik Artman, Lars Nordström

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The electric power system is undergoing significant changes. Thereby, the operation and control are becoming partly modified, more multifaceted and automated, and thereby supplementary operator skills might be required. This paper discusses developing operational challenges in future power system control rooms, posed by the evolving landscape of sustainable power systems, driven in turn by the shift towards electrification and renewable energy sources. A literature review followed by interviews and a comparison to other related domains with similar characteristics, a descriptive analysis was performed from a human factors perspective. Analysis is meant to identify trends, relationships, and challenges. A power control domain taxonomy includes a temporal domain (planning and real-time operation) and three operational domains within the power system (generation, switching and balancing). Within each operational domain, there are different control actions, either in the planning stage or in the real-time operation, that affect the overall operation of the power system. In addition to the temporal dimension, the control domains are divided in space between a multitude of different actors distributed across many different locations. A control room is a central location where different types of information are monitored and controlled, alarms are responded to, and deviations are handled by the control room operators. The operators’ competencies, teamwork skills, team shift patterns as well as control system designs are all important factors in ensuring efficient and safe electricity grid management. As the power system evolves with sustainable energy technologies, challenges are found. Questions are raised regarding whether the operators’ tacit knowledge, experience and operation skills of today are sufficient to make constructive decisions to solve modified and new control tasks, especially during disturbed operations or abnormalities. Which new skills need to be developed in planning and real-time operation to provide efficient generation and delivery of energy through the system? How should the user interfaces be developed to assist operators in processing the increasing amount of information? Are some skills at risk of being lost when the systems change? How should the physical environment and collaborations between different stakeholders within and outside the control room develop to support operator control? To conclude, the system change will provide many benefits related to electrification and renewable energy sources, but it is important to address the operators’ challenges with increasing complexity. The control tasks will be modified, and additional operator skills are needed to perform efficient and safe operations. Also, the whole human-technology-organization system needs to be considered, including the physical environment, the technical aids and the information systems, the operators’ physical and mental well-being, as well as the social and organizational systems.

Keywords: operator, process control, energy system, sustainability, future control room, skill

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Authors: Katarzyna Drela, Miroslaw Wielgos, Mikolaj Wrobel, Barbara Lukomska

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Mesenchymal stem cells (MSCs) have a great potential in regenerative medicine. Since the initial number of isolated MSCs is limited, in vitro propagation is often required to reach sufficient numbers of cells for therapeutic applications. During long-term culture MSCs may undergo genetic or epigenetic alterations that subsequently increase the probability of spontaneous malignant transformation. Thus, factors that influence genomic stability of MSCs following long-term expansions need to be clarified before cultured MSCs are employed for clinical application. The aim of our study was to investigate the potential for spontaneous transformation of human neonatal cord blood (HUCB-MSCs) and adult bone marrow (BM-MSCs) derived MSCs. Materials and Methods: HUCB-MSCs and BM-MSCs were isolated by standard Ficoll gradient centrifugations method. Isolated cells were initially plated in high density 106 cells per cm2. After 48 h medium were changed and non-adherent cells were removed. The malignant transformation of MSCs in vitro was evaluated by morphological changes, proliferation rate, ability to enter cell senescence, the telomerase expression and chromosomal abnormality. Proliferation of MSCs was analyzed with WST-1 reduction method and population doubling time (PDT) was calculated at different culture stages. Then the expression pattern of genes characteristic for mesenchymal or epithelial cells, as well as transcriptions factors were examined by RT-PCR. Concomitantly, immunocytochemical analysis of gene-related proteins was employed. Results: Our studies showed that MSCs from all bone marrow isolations ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUCB-MSCs from one of the 15 donors displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. In this sample we observed two different cell phenotypes: one mesenchymal-like exhibited spindle shaped morphology and express specific mesenchymal surface markers (CD73, CD90, CD105, CD166) with low proliferation rate, and the second one with round, densely package epithelial-like cells with significantly increased proliferation rate. The PDT of epithelial-like populations was around 1day and 100% of cells were positive for proliferation marker Ki-67. Moreover, HUCB-MSCs showed a positive expression of human telomerase reverse transcriptase (hTERT), cMYC and exhibit increased number of CFU during the long-term culture in vitro. Furthermore, karyotype analysis revealed chromosomal abnormalities including duplications. Conclusions: Our studies demonstrate that HUCB-MSCs are susceptible to spontaneous malignant transformation during long-term culture. Spontaneous malignant transformation process following in vitro culture has enormous effect on the biosafety issues of future cell-based therapies and regenerative medicine regimens.

Keywords: mesenchymal stem cells, spontaneous, transformation, long-term culture

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Authors: Mrunal Phatak, Suvarna Raut

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Introduction: Thyroid hormone is important for the normal function of the auditory system. Hearing impairment can occur insidiously in subclinical hypothyroidism. The present study was undertaken with the aims of evaluating audiological tests like tuning fork tests, pure tone audiometry, brainstem evoked auditory potentials (BAEPs), and auditory reaction time (ART) in hypothyroid women and in age and sex matched controls so as to evaluate the effect of thyroid hormone on hearing. The objective of the study was to investigate hearing status by the audiological profile in hypothyroidism (group 1) and healthy controls ( group 2) to compare the audiological profile between these groups and find the correlation of levels of TSH, T3, and T4 with the above parameters. Material and methods: A total sample size of 124 women in the age group of 30 to 50 years was recruited and divided into the Cases group comprising of 62 newly diagnosed hypothyroid women and the Control group having 62 women with normal thyroid profile. Otoscopic examination, tuning fork tests, Pure tone audiometry tests (PTA). Brain Stem Auditory Evoked Potential (BAEP) and Auditory Reaction Time (ART) were done in both ears, i.e. total 248 ears of all subjects. Results: By BAEPs, hearing impairment was detected in total 64 ears (51.61%). A significant increase was seen in Wave V latency, IPL I-V, and IPL III-V, and the decrease was seen in the amplitude of Wave I and V in both the ears in cases. Positive correlation of Wave V latency of Right and Left ears is seen with TSH levels (p < 0.001) and a negative correlation with T3 (>0.05) and with T4 (p < 0.01). Negative correlation of wave V amplitude of Right and Left ears is seen with TSH levels (p < 0.001), and a significant positive correlation is seen with T3 and T4. Pure tone audiometry parameters showed hearing impairment of conductive (31.29%), sensorineural (36.29%), as well as the mixed type (15.32%). Hearing loss was mild in 65.32% of ears and moderate in 17.74% of ears. Pure tone averages (PTA) were significantly increased in cases than in controls in both the ears. Significant positive correlation of PTA of Right and Left ears is seen with TSH levels (p<0.05). Negative correlation with T3 and T4 is seen. A significant increase in HF ART and LF ART is seen in cases as compared to controls. Positive correlation of ART of high frequency and low frequency is seen with TSH levels and a negative correlation with T3 and T4 (p > 0.05). Conclusion: The abnormal BAEPs in hypothyroid women suggest an impaired central auditory pathway. BAEP abnormalities are indicative of a nonspecific injury in the bulbo-ponto-mesencephalic centres. The results of auditory investigations suggest a causal relationship between hypothyroidism and hearing loss. The site of lesion in the auditory pathway is probably at several levels, namely, in the middle ear and at cochlear and retrocochlear sites. Prolonged ART also suggests the impairment in central processing mechanisms. The results of the present study conclude that the probable reason for hearing impairment in hypothyroidism may be delayed impulse conduction in acoustic nerve up to the level of the midbrain (IPL I-V, III-V), particularly inferior colliculus (wave V). There is also impairment in central processing mechanisms, as shown by prolonged ART.

Keywords: deafness, pure tone audiometry, brain stem auditory evoked potential, hyopothyroidism

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Authors: Mathula Thangarajh

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Duchenne muscular dystrophy (DMD) is a severe form of X-linked muscular dystrophy caused by mutations in the dystrophin gene resulting in progressive skeletal muscle weakness. Boys with DMD also have significant cognitive disabilities. The intelligence quotient of boys with DMD, compared to peers, is approximately one standard deviation below average. Detailed neuropsychological testing has demonstrated that boys with DMD have a global developmental impairment, with verbal memory and visuospatial skills most significantly affected. Furthermore, the total brain volume and gray matter volume are lower in children with DMD compared to age-matched controls. These results are suggestive of a significant structural and functional compromise to the developing brain as a result of absent dystrophin protein expression. There is also some genetic evidence to suggest that mutations in the 3’ end of the DMD gene are associated with more severe neurocognitive problems. Our working hypothesis is that (i) boys with DMD do not make gains in neurodevelopmental skills compared to typically developing children and (ii) women carriers of DMD mutations may have subclinical cognitive deficits. We also hypothesize that there may be an intergenerational vulnerability of cognition, with boys of DMD-carrier mothers being more affected cognitively than boys of non-DMD-carrier mothers. The objectives of this study are: 1. Assess the neurodevelopment in boys with DMD at 4-time points and perform baseline neuroradiological assessment, 2. Assess cognition in biological mothers of DMD participants at baseline, 3. Assess possible correlation between DMD mutation and cognitive measures. This study also explores functional brain abnormalities in people with DMD by exploring how regional and global connectivity of the brain underlies executive function deficits in DMD. Such research can contribute to a better holistic understanding of the cognition alterations due to DMD and could potentially allow clinicians to create better-tailored treatment plans for the DMD population. There are four study visits for each participant (baseline, 2-4 weeks, 1 year, 18 months). At each visit, the participant completes the NIH Toolbox Cognition Battery, a validated psychometric measure that is recommended by NIH Common Data Elements for use in DMD. Visits 1, 3, and 4 also involve the administration of the BRIEF-2, ABAS-3, PROMIS/NeuroQoL, PedsQL Neuromuscular module 3.0, Draw a Clock Test, and an optional fMRI scan with the N-back matching task. We expect to enroll 52 children with DMD, 52 mothers of children with DMD, and 30 healthy control boys. This study began in 2020 during the height of the COVID-19 pandemic. Due to this, there were subsequent delays in recruitment because of travel restrictions. However, we have persevered and continued to recruit new participants for the study. We partnered with the Muscular Dystrophy Association (MDA) and helped advertise the study to interested families. Since then, we have had families from across the country contact us about their interest in the study. We plan to continue to enroll a diverse population of DMD participants to contribute toward a better understanding of Duchenne Muscular Dystrophy.

Keywords: neurology, Duchenne muscular dystrophy, muscular dystrophy, cognition, neurodevelopment, x-linked disorder, DMD, DMD gene

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Authors: Margarita Ivanova, Julia Dao, Andrew Friedman, Neil Kasaci, Rekha Gopal, Ozlem Goker-Alpan

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In Fabry disease (FD), α-galactosidase A (α-Gal A) deficiency leads to the accumulation of globotriaosylceramide (Lyso-Gb3 and Gb3), triggering a pathologic cascade that causes the severity of organs damage. The heart is one of the several organs with high sensitivity to the α-Gal A deficiency. A subgroup of patients with significant residual of α-Gal A activity with primary cardiac involvement is occasionally referred to as “cardiac variant.” The cardiovascular complications are most frequently encountered, contributing substantially to morbidity, and are the leading cause of premature death in male and female patients with FD. The deposition of Lyso-Gb-3 and Gb-3 within the myocardium affects cardiac function with resultant progressive cardiovascular pathology. Gb-3 and Lyso-Gb-3 accumulation at the cellular level trigger a cascade of events leading to end-stage fibrosis. In the cardiac tissue, Lyso-Gb-3 deposition is associated with the increased release of inflammatory factors and transforming growth factors. Infiltration of lymphocytes and macrophages into endomyocardial tissue indicates that inflammation plays a significant role in cardiac damage. Moreover, accumulated data suggest that chronic inflammation leads to multisystemic FD pathology even under enzyme replacement therapy (ERT). NF-κB activation plays a subsequent role in the inflammatory response to cardiac dysfunction and advanced heart failure in the general population. TNFalpha/NF-κB signaling protects the myocardial evoking by ischemic preconditioning; however, this protective effect depends on the concentration of TNF-α. Thus, we hypothesize that TNF-α is a critical factor in determining the grade of cardio-pathology. Cardiac hypertrophy corresponds to the expansion of the coronary vasculature to maintain a sufficient supply of nutrients and oxygen. Coronary activation of angiogenesis and fibrosis plays a vital role in cardiac vascularization, hypertrophy, and tissue remodeling. We suggest that the interaction between the inflammatory pathways and cardiac vascularization is a bi-directional process controlled by secreted cytokines and growth factors. The co-coordination of these two processes has never been explored in FD. In a cohort of 40 patients with FD, biomarkers associated with inflammation and cardio hypertrophic remodeling were studied. FD patients were categorized into three groups based on LVmass/DSA, LVEF, and ECG abnormalities: FD with no cardio complication, FD with moderate cardio complication, and severe cardio complication. Serum levels of NF-kB, TNFalpha, Il-6, Il-2, MCP1, ING-gamma, VEGF, IGF-1, TGFβ, and FGF2 were quantified by enzyme-linked immunosorbent assays (ELISA). Among the biomarkers, MCP-1, INF-gamma, VEGF, TNF-alpha, and TGF-beta were elevated in FD patients. Some of these biomarkers also have the potential to correlate with cardio pathology in FD. Conclusion: The study provides information about the role of inflammatory pathways and biomarkers of cardio hypertrophic remodeling in FD patients. This study will also reveal the mechanisms that link intracellular accumulation of Lyso-GB-3 and Gb3 to the development of cardiomyopathy with myocardial thickening and resultant fibrosis.

Keywords: biomarkers, Fabry disease, inflammation, growth factors

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Authors: Tomaz Oliveira, Rui Medeiros, André Lacerda

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Introduction: Cleft lip and/or palate are the most frequent forms of congenital craniofacial anomalies, affecting mainly the middle third of the face and manifesting by functional and aesthetic changes. Bilateral cleft lip represents a reconstructive surgical challenge, not only for the labial component but also for the associated nasal deformation. Recently, the paradigm of the approach to this pathology has changed, placing the focus on muscle reconstruction and anatomical repositioning of the nasal cartilages in order to obtain the best aesthetic and functional results. The aim of this study is to carry out a systematic review of the surgical approach to bilateral cleft lip, retrospectively analyzing the case series of Plastic Surgery Service at Hospital Santa Maria (Lisbon, Portugal) regarding this pathology, the global assessment of the characteristics of the operated patients and the study of the different surgical approaches and their complications in the last 20 years. Methods: The present work demonstrates a retrospective and descriptive study of patients who underwent at least one reconstructive surgery for cleft lip and/or palate, in the CPRE service of the HSM, in the period between January 1 of 1997 and December 31 of 2017, in which the data relating to 361 individuals were analyzed who, after applying the exclusion criteria, constituted a sample of 212 participants. The variables analyzed were the year of the first surgery, gender, age, type of orofacial cleft, surgical approach, and its complications. Results: There was a higher overall prevalence in males, with cleft lip and cleft palate occurring in greater proportion in males, with the cleft palate being more common in females. The most frequently recorded malformation was cleft lip and palate, which is complete in most cases. Regarding laterality, alterations with a unilateral labial component were the most commonly observed, with the left lip being described as the most affected. It was found that the vast majority of patients underwent primary intervention up to 12 months of age. The surgical techniques used in the approach to this pathology showed an important chronological variation over the years. Discussion: Cleft lip and/or palate is a medical condition associated with high aesthetic and functional morbidity, which requires early treatment in order to optimize the long-term outcome. The existence of a nasolabial component and its respective surgical correction plays a central role in the treatment of this pathology. The high rates of post-surgical complications and unconvincing aesthetic results have motivated an evolution of the surgical technique, increasingly evident in recent years, allowing today to achieve satisfactory aesthetic results, even in bilateral cleft lip with high deformation complexity. The introduction of techniques that favor nasolabial reconstruction based on anatomical principles has been producing increasingly convincing results. The analyzed sample shows that most of the results obtained in this study are, in general, compatible with the results published in the literature. Conclusion: This work showed that the existence of small variations in the surgical technique can bring significant improvements in the functional and aesthetic results in the treatment of bilateral cleft lip.

Keywords: cleft lip, palate lip, congenital abnormalities, cranofacial malformations

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Authors: Abdou Elhendy

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Numerous study have shown the efficacy of the percutaneous intervention (PCI) and coronary stenting in improving left ventricular function and relieving exertional angina. Furthermore, PCI remains the main line of therapy in acute myocardial infarction. Improvement of procedural techniques and new devices have resulted in an increased number of PCI in those with difficult and extensive lesions, multivessel disease as well as total occlusion. Immediate and late outcome may be compromised by acute thrombosis or the development of fibro-intimal hyperplasia. In addition, progression of coronary artery disease proximal or distal to the stent as well as in non-stented arteries is not uncommon. As a result, complications can occur, such as acute myocardial infarction, worsened heart failure or recurrence of angina. In a stent, restenosis can occur without symptoms or with atypical complaints rendering the clinical diagnosis difficult. Routine invasive angiography is not appropriate as a follow up tool due to associated risk and cost and the limited functional assessment. Exercise and pharmacologic stress testing are increasingly used to evaluate the myocardial function, perfusion and adequacy of revascularization. Information obtained by these techniques provide important clues regarding presence and severity of compromise in myocardial blood flow. Stress echocardiography can be performed in conjunction with exercise or dobutamine infusion. The diagnostic accuracy has been moderate, but the results provide excellent prognostic stratification. Adding myocardial contrast agents can improve imaging quality and allows assessment of both function and perfusion. Stress radionuclide myocardial perfusion imaging is an alternative to evaluate these patients. The extent and severity of wall motion and perfusion abnormalities observed during exercise or pharmacologic stress are predictors of survival and risk of cardiac events. According to current guidelines, stress echocardiography and radionuclide imaging are considered to have appropriate indication among patients after PCI who have cardiac symptoms and those who underwent incomplete revascularization. Stress testing is not recommended in asymptomatic patients, particularly early after revascularization, Coronary CT angiography is increasingly used and provides high sensitive for the diagnosis of coronary artery stenosis. Average sensitivity and specificity for the diagnosis of in stent stenosis in pooled data are 79% and 81%, respectively. Limitations include blooming artifacts and low feasibility in patients with small stents or thick struts. Anatomical and functional cardiac imaging modalities are corner stone for the assessment of patients after PCI and provide salient diagnostic and prognostic information. Current imaging techniques cans serve as gate keeper for coronary angiography, thus limiting the risk of invasive procedures to those who are likely to benefit from subsequent revascularization. The determination of which modality to apply requires careful identification of merits and limitation of each technique as well as the unique characteristic of each individual patient.

Keywords: coronary artery disease, stress testing, cardiac imaging, restenosis

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