Search results for: Asymptomatic dengue

Authors: Tin Yee Ling, Kavita Maravar, Ruzica Ardalic

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Background: Uterine torsion (UT) in pregnancy of more than 45-degree along the longitudinal axis is a rare occurrence, and the aetiology remains unclear. Case: A 34-year-old G2P1 woman with a history of one previous caesarean section presented at 36+2 weeks with sudden onset lower abdominal pain, syncopal episode, and tender abdomen on examination. She was otherwise haemodynamically stable. Cardiotocography showed a pathological trace with initial prolonged bradycardia followed by a subsequent tachycardia with reduced variability. An initial diagnosis of uterine dehiscence was made, given the history and clinical presentation. She underwent an emergency caesarean section which revealed a 180-degree UT along the longitudinal axis, with oedematous left round ligament lying transverse anterior to the uterus and a segment of large bowel inferior to the round ligament. Detorsion of uterus was performed prior to delivery of the foetus, and anterior uterine wall was intact with no signs of rupture. There were no anatomical uterine abnormalities found other than stretched left ovarian and round ligaments, which were repaired. Delivery was otherwise uneventful, and she was discharged on day 2 postpartum. Discussion: UT is rare as the number of reported cases is within the few hundreds worldwide. Generally, the uterus is supported in place by uterine ligaments, which limit the mobility of the structure. The causes of UT are unknown, but risk factors such as uterine abnormalities, increased uterine ligaments’ flexibility in pregnancy, and foetal malposition has been identified. UT causes occlusion of uterine vessels, which can lead to ischaemic injury of the placenta causing premature separation of the placenta, preterm labour, and foetal morbidity and mortality if delivery is delayed. Diagnosing UT clinically is difficult as most women present with symptoms similar to placenta abruption or uterine rupture (abdominal pain, vaginal bleeding, shock), and one-third are asymptomatic. The management of UT involves surgical detorsion of the uterus and delivery of foetus via caesarean section. Extra vigilance should be taken to identify the anatomy of the uterus experiencing torsion prior to hysterotomy. There have been a few cases reported with hysterotomy on posterior uterine wall for delivery of foetus as it may be difficult to identify and reverse a gravid UT when foetal well-being is at stake. Conclusion: UT should be considered a differential diagnosis of acute abdominal pain in pregnancy. It is crucial that the torsion is addressed immediately as it is associated with maternal and foetal morbidity and mortality.

Keywords: uterine torsion, pregnancy complication, abdominal pain, torted uterus

Procedia PDF Downloads 126

Authors: Taurino S. R. Neto, Epitácio D. S. Neto, Flávio Signorelli, Gustavo G. M. Balbi, Alex H. Higashi, Mário Luiz R. Monteiro, Eloisa Bonfá, Danieli C. O. Andrade, Leandro C. Zacharias

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Purpose: To perform a multimodal evaluation, including the use of Optical Coherence Angiotomography (OCTA), in patients with primary antiphospholipid syndrome (PAPS) without ocular complaints and to compare them with healthy individuals. Methods: A complete structural and functional ophthalmological evaluation using OCTA and microperimetry (MP) exam in patients with PAPS, followed at a tertiary rheumatology outpatient clinic, was performed. All ophthalmologic manifestations were recorded and then statistical analysis was performed for comparative purposes; p <0.05 was considered statistically significant. Results: 104 eyes of 52 subjects (26 patients with PAPS without ocular complaints and 26 healthy individuals) were included. Among PAPS patients, 21 were female (80.8%) and 21 (80.8%) were Caucasians. Thrombotic PAPS was the main clinical criteria manifestation (100%); 65.4% had venous and 34.6% had arterial thrombosis. Obstetrical criteria were present in 34.6% of all thrombotic PAPS patients. Lupus anticoagulant was present in all patients. 19.2% of PAPS patients presented ophthalmologic findings against none of the healthy individuals. The most common retinal change was paracentral acute middle maculopathy (PAMM) (3 patients, 5 eyes), followed by drusen-like deposits (1 patient, 2 eyes) and pachychoroid pigment epitheliopathy (1 patient, 1 eye). Systemic hypertension and hyperlipidaemia were present in 100% of the PAPS patients with PAMM, while only six patients (26.1%) with PAPS without PAMM presented these two risk factors together. In the quantitative OCTA evaluation, we found significant differences between PAPS patients and controls in both the superficial vascular complex (SVC) and deep vascular complex (DVC) in the high-speed protocol, as well as in the SVC in the high-resolution protocol. In the analysis of the foveal avascular zone (FAZ) parameters, the PAPS group had a larger area of FAZ in the DVC using the high-speed method compared to the control group (p=0.047). In the quantitative analysis of the MP, the PAPS group had lower central (p=0.041) and global (p<0.001) retinal sensitivity compared to the control group, as well as in the sector analysis, with the exception of the inferior sector. In the quantitative evaluation of fixation stability, there was a trend towards worse stability in the PAPS subgroup with PAMM in both studied methods. Conclusions: PAMM was observed in 11.5% of PAPS patients with no previous ocular complaints. Systemic hypertension concomitant with hyperlipidemia was the most commonly associated risk factor for PAMM in patients with PAPS. PAPS patients present lower vascular density and retinal sensitivity compared to the control group, even in patients without PAMM.

Keywords: antiphospholipid syndrome, optical coherence angio tomography, optical coherence tomography, retina

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Authors: Wafa Al Jabri

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Background: In Middle Eastern Countries (MECs), there is a high prevalence of genetic blood disorders (GBDs), particularly sickle cell disease and thalassemia. The GBDs are considered a major public health concern that place a huge burden to individuals, families, communities, and health care systems. The high rates of consanguineous marriages, along with the unacceptable termination of at-risk pregnancy in MECs, reduce the possible solutions to control the high prevalence of GBDs. Since the early 1970s, most of MECs have started introducing premarital screening services (PSS) as a preventive measure to identify the asymptomatic carriers of GBDs and to provide genetic counseling to help couples plan for healthy families; yet, the success rate of PSS is very low. Purpose: This paper aims to highlight the factors that affect the success of PSS in MECs. Methods: An integrative review of articles located in CINAHL, PubMed, SCOPUS, and MedLine was carried out using the following terms: “premarital screening,” “success,” “effectiveness,” and “ genetic blood disorders”. Second, a hand search of the reference lists and Google searches were conducted to find studies that did not exist in the primary database searches. Only studies which are conducted in MECs and published after 2010 were included. Studies that were not published in English were excluded. Results: Eighteen articles were included in the review. The results showed that PSS in most of the MECs was successful in achieving its objective of identifying high-risk marriages; however, the service failed to meet its ultimate goal of reducing the prevalence of GBDs. Various factors seem to hinder the success of PSS, including poor public awareness, late timing of the screening, culture and social stigma, lack of prenatal diagnosis services and therapeutic abortion, emotional factors, religious beliefs, and lack of genetic counseling services. However, poor public awareness, late timing of the screening, religious misbeliefs, and the lack of adequate counseling services were the most common barriers identified. Conclusion and Implications: The review help in providing a framework for an effective preventive measure to reduce the prevalence of GBDs in MECS. This framework focuses primarily in overcoming the identified barriers by providing effective health education programs in collaboration with religious leaders, offering the screening test to young adults at an earlier stage, and tailoring the genetic counseling to consider people’s values, beliefs, and preferences.

Keywords: premarital screening, middle east, genetic blood disorders, factors

Procedia PDF Downloads 56

Authors: Mariana Branco, Nahida Sobrino, Cristina Neves, Márcia Santos, Afonso Granja, João Rosa Oliveira, Joana Costa, Luísa Castro Leite

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This case reports a COVID-19 infection in an unvaccinated adult man with no history of COVID-19 and no relevant clinical history besides anabolic steroid use, undergoing weaning with tamoxifen after a bodybuilding competition. The patient presented a 4cm cervical mass 3 weeks after COVID-19 infection in his cohabitants. He was otherwise asymptomatic and tested negative to multiple RT-PCR tests. Nevertheless, the IgG COVID-19 antibody was positive, suggesting the previous infection. This report raises a potential link between anabolic steroid use and atypical COVID-19 onset. Objectives: The goals of this paper are to raise a potential link between anabolic steroid use and atypical COVID-19 onset but also to report an uncommon case of COVID-19 infection with consecutive negative gold standard tests. Methodology: The authors used CARE guidelines for case report writing. Introduction: This case reports a COVID-19 infection case in an unvaccinated adult man, with multiple serial negative reverse transcription polymerase chain reaction (RT-PCR) test results, presenting with single cervical lymphadenopathy. Although the association between COVID-19 and lymphadenopathy is well established, there are no cases with this presentation, and consistently negative RT-PCR tests have been reported. Methodologies: The authors used CARE guidelines for case report writing. Case presentation: This case reports a 28-year-old Caucasian man with no previous history of COVID-19 infection or vaccination and no relevant clinical history besides anabolic steroid use undergoing weaning with tamoxifendue to participation in a bodybuilding competition. He visits his primary care physician because of a large (4 cm) cervical lump, present for 3 days prior to the consultation. There was a positive family history for COVID-19 infection 3 weeks prior to the visit, during which the patient cohabited with the infected family members. The patient never had any previous clinical manifestation of COVID-19 infection and, despite multiple consecutive RT-PCR testing, never tested positive. The patient was treated with an NSAID and a broad-spectrum antibiotic, with little to no effect. Imagiological testing was performed via a cervical ultrasound, followed by a needle biopsy for histologic analysis. Serologic testing for COVID-19 immunity was conducted, revealing a positive Anti-SARS-CoV-2 IgG (Spike S1) antibody, suggesting the previous infection, given the unvaccinated status of our patient Conclusion: In patients with a positive epidemiologic context and cervical lymphadenopathy, physicians should still consider COVID-19 infection as a differential diagnosis, despite negative PCR testing. This case also raises a potential link between anabolic steroid use and atypical COVID-19 onset, never before reported in scientific literature.

Keywords: COVID-19, cervical lymphadenopathy, anabolic steroids, primary care

Procedia PDF Downloads 85

Authors: Gunta Resevica, Nikita Zrelovs, Ivars Silamikelis, Ieva Kalnciema, Helvijs Niedra, Gunārs Lācis, Toms Bartulsons, Inga Moročko-Bičevska, Arturs Stalažs, Kristīne Drevinska, Andris Zeltins, Ina Balke

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Newly discovered viruses provide novel knowledge for basic phytovirus research, serve as tools for biotechnology and can be helpful in identification of epidemic outbreaks. Blackcurrant-associated rhabdovirus (BCaRV) have been discovered in USA germplasm collection samples from Russia and France. As it was reported in one accession originating from France it is unclear whether the material was already infected when it entered in the USA or it became infected while in collection in the USA. Due to that BCaRV was definite as non-EU viruses. According to ICTV classification BCaRV is representative of Blackcurrant betanucleorhabdovirus specie in genus Betanucleorhabdovirus (family Rhabdoviridae). Nevertheless, BCaRV impact on the host, transmission mechanisms and vectors are still unknown. In RNA-seq data pool from Ribes plants resistance gene study by high throughput sequencing (HTS) we observed differences between sample group gene transcript heat maps. Additional analysis of the whole data pool (total 393660492 of 150 bp long read pairs) by rnaSPAdes v 3.13.1 resulted into 14424 bases long contig with an average coverage of 684x with shared 99.5% identity to the previously reported first complete genome of BCaRV (MF543022.1) using EMBOSS Needle. This finding proved BCaRV presence in EU and indicated that it might be relevant pathogen. In this study leaf tissue from twelve asymptomatic blackcurrant cv. Mara Eglite plants (negatively tested for blackcurrant reversion virus (BRV)) from Dobele, Latvia (56°36'31.9"N, 23°18'13.6"E) was collected and used for total RNA isolation with RNeasy Plant Mini Kit with minor modifications, followed by plant rRNA removal by a RiboMinus Plant Kit for RNA-Seq. HTS libraries were prepared using MGI Easy RNA Directional Library Prep Set for 16 reactions to obtain 150 bp pair-end reads. Libraries were pooled, circularized and cleaned and sequenced on DNBSEQ-G400 using PE150 flow cell. Additionally, all samples were tested by RT-PCR, and amplicons were directly sequenced by Sanger-based method. The contig representing the genome of BCaRV isolate Mara Eglite was deposited at European Nucleotide Archive under accession number OU015520. Those findings indicate a second evidence on the presence of this particular virus in the EU and further research on BCaRV prevalence in Ribes from other geographical areas should be performed. As there are no information on BCaRV impact on the host this should be investigated, regarding the fact that mixed infections with BRV and nucleorhabdoviruses are reported.

Keywords: BCaRV, Betanucleorhabdovirus, Ribes, RNA-seq

Procedia PDF Downloads 159

Authors: Marina Shargorodsky

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Aim: Gestational weight gain (GWG) has been related to altering future weight-gain curves and increased risks of obesity later in life. Obesity may contribute to vascular atherosclerotic changes as well as excess cardiovascular morbidity and mortality observed in these patients. Noninvasive arterial testing, such as ultrasonographic measurement of carotid IMT, is considered a surrogate for systemic atherosclerotic disease burden and is predictive of cardiovascular events in asymptomatic individuals as well as recurrent events in patients with known cardiovascular disease. Currently, there is no consistent evidence regarding the vascular impact of excessive GWG. The present study was designed to investigate the impact of GWG on early atherosclerotic changes during late pregnancy, using intima-media thickness, as well as placental vascular circulation and inflammatory lesions and pregnancy outcomes. Methods: The study group consisted of 59 pregnant women who gave birth and underwent a placental histopathological examination at the Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Israel, in 2019. According to the IOM guidelines the study group has been divided into two groups: Group 1 included 32 women with pregnancy weight gain within recommended range; Group 2 included 27 women with excessive weight gain during pregnancy. The IMT was measured from non-diseased intimal and medial wall layers of the carotid artery on both sides, visualized by high-resolution 7.5 MHz ultrasound (Apogee CX Color, ATL). Placental histology subdivided placental findings to lesions consistent with maternal vascular and fetal vascular malperfusion according to the criteria of the Society for Pediatric Pathology, subdividing placental findings to lesions consistent with maternal vascular and fetal vascular malperfusion, as well as the inflammatory response of maternal and fetal origin. Results: IMT levels differed between groups and were significantly higher in Group 1 compared to Group 2 (0.7+/-0.1 vs 0.6+/-0/1, p=0.028). Multiple linear regression analysis of IMT included variables based on their associations in univariate analyses with a backward approach. Included in the model were pre-gestational BMI, HDL cholesterol and fasting glucose. The model was significant (p=0.001) and correctly classified 64.7% of study patients. In this model, pre-pregnancy BMI remained a significant independent predictor of subclinical atherosclerosis assessed by IMT (OR 4.314, 95% CI 0.0599-0.674, p=0.044). Among placental lesions related to fetal vascular malperfusion, villous changes consistent with fetal thrombo-occlusive disease (FTOD) were significantly higher in Group 1 than in Group 2, p=0.034). In Conclusion, the present study demonstrated that excessive weight gain during pregnancy is associated with an adverse effect on early stages of subclinical atherosclerosis, placental vascular circulation and neonatal complications. The precise mechanism for these vascular changes, as well as the overall clinical impact of weight control during pregnancy on IMT, placental vascular circulation as well as pregnancy outcomes, deserves further investigation.

Keywords: obesity, pregnancy, complications, weight gain

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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 178

Authors: H. I. Obadiah, S. N. Wieser, E. A. Omudu, B. O. Atu, O. Byanet, L. Schnittger, M. Florin-Christensen

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Sarcocystis sp. are Apicomplexan protozoan parasites with a life cycle that involves a predator and a prey as final and intermediate hosts, respectively. In tissues of the intermediate hosts, the parasites produce sarcocysts that vary in size and morphology according to the species. When a suitable predator ingests sarcocyst-containing meat, the parasites are released in the intestine and undergo sexual reproduction producing infective sporocysts, which are excreted with the feces into the environment. The cycle is closed when a prey ingests sporocyst-contaminated water or pasture; the parasites gain access to the circulation, and eventually invade tissues and reproduce asexually yielding sarcocysts. Pig farming is a common practice in Nigeria as well as in many countries around the world. In addition to its importance as protein source, pork is also a source of several pathogens relevant to humans. In the case of Sarcocystis, three species have been described both in domestic and wild pigs, namely, S. miescheriana, S. porcifelis and S. suihominis. Humans can act both as final and aberrant intermediate hosts of S. suihominis, after ingesting undercooked sarcocyst-infested pork. Infections are usually asymptomatic but can be associated with inappetence, nausea, vomiting and diarrhea, or with muscle pain, fever, eosinophilia and bronchospasm, in humans acting as final or intermediate hosts, respectively. Moreover, excretion of infective forms with human feces leads to further dissemination of the infection. In this study, macroscopic sarcocysts of white color, oval shape and a size range of approximately 3-5 mm were observed in the skeletal muscle of a slaughtered pig in an abattoir in Makurdi, Benue State, Nigeria, destined to human consumption. Sarcocysts were excised and washed in distilled water, and genomic DNA was extracted using a commercial kit. The near-complete length of the 18S rRNA gene was analyzed after PCR amplification of two overlapping fragments, each of which were submitted to direct sequencing. In addition, the mitochondrial cytochrome oxidase (cox-1) gene was PCR-amplified and directly sequenced. Two phylogenetic trees containing the obtained sequences along with available relevant 18S rRNA and cox-1 sequences were constructed by neighbor joining after alignment, using the corresponding sequences of Toxoplasma gondii as outgroup. The results showed in both cases that the analyzed sequences grouped with S. suihominis with high bootstrap value, confirming the identity of this macroscopic sarcocyst-forming parasite as S. suihominis. To the best of our knowledge, these results represent the first demonstration of this parasite in pigs of Nigeria and the largest sarcocysts described so far for S. suihominis. The close proximity between pigs and humans in pig farms, and the frequent poor sanitary conditions in human dwellings strongly suggest that the parasite undergoes the sexual stages of its life cycle in humans as final hosts. These findings provide an important reference for the examination and control of Sarcocystis species in pigs of Nigeria.

Keywords: nigeria, pork, sarcocystis suihominis, zoonotic parasite

Procedia PDF Downloads 55

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

Procedia PDF Downloads 133

Authors: Ana L. M. Pavan, Guilherme Giacomini, Allan F. F. Alves, Marcela De Oliveira, Fernando A. B. Neto, Maria E. D. Rosa, Andre P. Trindade, Diana R. De Pina

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Mammography is a worldwide image modality used to diagnose breast cancer, even in asymptomatic women. Due to its large availability, mammograms can be used to measure breast density and to predict cancer development. Women with increased mammographic density have a four- to sixfold increase in their risk of developing breast cancer. Therefore, studies have been made to accurately quantify mammographic breast density. In clinical routine, radiologists perform image evaluations through BIRADS (Breast Imaging Reporting and Data System) assessment. However, this method has inter and intraindividual variability. An automatic objective method to measure breast density could relieve radiologist’s workload by providing a first aid opinion. However, pectoral muscle is a high density tissue, with similar characteristics of fibroglandular tissues. It is consequently hard to automatically quantify mammographic breast density. Therefore, a pre-processing is needed to segment the pectoral muscle which may erroneously be quantified as fibroglandular tissue. The aim of this work was to develop an automatic algorithm to segment and extract pectoral muscle in digital mammograms. The database consisted of thirty medio-lateral oblique incidence digital mammography from São Paulo Medical School. This study was developed with ethical approval from the authors’ institutions and national review panels under protocol number 3720-2010. An algorithm was developed, in Matlab® platform, for the pre-processing of images. The algorithm uses image processing tools to automatically segment and extract the pectoral muscle of mammograms. Firstly, it was applied thresholding technique to remove non-biological information from image. Then, the Hough transform is applied, to find the limit of the pectoral muscle, followed by active contour method. Seed of active contour is applied in the limit of pectoral muscle found by Hough transform. An experienced radiologist also manually performed the pectoral muscle segmentation. Both methods, manual and automatic, were compared using the Jaccard index and Bland-Altman statistics. The comparison between manual and the developed automatic method presented a Jaccard similarity coefficient greater than 90% for all analyzed images, showing the efficiency and accuracy of segmentation of the proposed method. The Bland-Altman statistics compared both methods in relation to area (mm²) of segmented pectoral muscle. The statistic showed data within the 95% confidence interval, enhancing the accuracy of segmentation compared to the manual method. Thus, the method proved to be accurate and robust, segmenting rapidly and freely from intra and inter-observer variability. It is concluded that the proposed method may be used reliably to segment pectoral muscle in digital mammography in clinical routine. The segmentation of the pectoral muscle is very important for further quantifications of fibroglandular tissue volume present in the breast.

Keywords: active contour, fibroglandular tissue, hough transform, pectoral muscle

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Authors: Jatinder Pal Singh, Harpreet Singh, Gagandeep Singh Digra, Mandeep Kaur Sidhu, Pawan Kumar

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Introduction: Ganglion cyst is a benign condition in which there is a cystic lesion in relation to a joint or a tendon sheath arising from myxoid degeneration of fibrous connective tissue. These can be unilocular or multilocular. In rare cases, there may be multiple ganglion cysts, known as cystic ganglionosis. They can occur at any age but are commonly seen in adults. Clinically they may be asymptomatic or present as swelling or mass effect in adjacent structures. These are common in extremities such as hands and feet. Case Presentation: 11-year-old female child presented with slowly progressive painless swelling of her right hand since the age of 4. Antenatal and perinatal history was unremarkable. Her family history was negative. She denies fever, malaise, morning stiffness, weight loss, fatigue, restriction of joint movements, or any sensory and motor deficit. Lab parameters were negative for inflammatory or infectious etiology. No other joint or extremity involvement was present. On physical examination, the swelling was present on the dorsum and palmer aspect of the right hand and wrist. They were non-tender on palpation without any motor or sensory deficit. MRI hand revealed multiple well-defined fluid signal intensity cystic appearing lesions in periarticular/intraarticular locations in relation to distal radio-ulnar, radio-carpal, intercarpal, carpometacarpal, metacarpophalangeal and interphalangeal joints as well as peritendinous location around flexor tendons more so in the region of wrist, palm, 1st and 5th digit and along extensor tendons in the region of wrist, largest one noted along flexor pollicis longus tendon in thenar region and along 1st digit measuring approx. 4.6 x 1.2 x 1.2 centimeter. Pressure erosions and bone remodelling were noted in the bases of the 2nd to 5th metacarpals, capitate, trapezoid, the distal shaft of 1st metacarpal, and proximal phalanx of 1st digit. Marrow edema was noted in the base and proximal shaft of the 4th metacarpal and proximal shaft of the 3rd metacarpal – likely stress or pressure related. The patient was advised of aspiration, but the family refused the procedure. Therefore the patient was kept on conservative treatment. Conclusion: Cystic ganglionosis is a rare condition with very few cases reported in the medical literature. Its prevalence and association are not known because of the rarity of this condition. It should be considered as an important differential in patients presenting with soft tissue swelling in extremities. Treatment option includes conservative management, aspiration, and surgery. Aspiration has a high recurrence rate. Although surgery has a low recurrence rate, it carries a high rate of complications. Imaging with MRI is essential for confirmation of the cystic nature of lesions and their relation with the joint capsules or tendons. This helps in differentiating from other soft tissue lesions and presurgical planning.

Keywords: radiology, rare, cystic ganglionosis, child

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Authors: Asim Abbasi, Muhammad Sufyan, Iqra, Hafiza Javaria Ashraf

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The share of vector-borne diseases (VBDs) in the global burden of infectious diseases is almost 17%. The advent of new drugs and latest research in medical science helped mankind to compete with these lethal diseases but still diseases transmitted by different mosquito species, including filariasis, malaria, viral encephalitis and dengue are serious threats for people living in disease endemic areas. Injudicious and repeated use of pesticides posed selection pressure on mosquitoes leading to development of resistance. Hence biological control agents are under serious consideration of scientific community to be used in vector control programmes. Fish have a history of predating immature stages of different aquatic insects including mosquitoes. The noteworthy examples in Africa and Asia includes, Aphanius discolour and a fish in the Panchax group. Moreover, common mosquito fish, Gambusia affinis predates mostly on temporary water mosquitoes like anopheline as compared to permanent water breeders like culicines. Mosquitoes belonging to genus Toxorhynchites have a worldwide distribution and are mostly associated with the predation of other mosquito larvae habituating with them in natural and artificial water containers. These species are harmless to humans as their adults do not suck human blood but feeds on floral nectar. However, their activity is mostly temperature dependent as Toxorhynchites brevipalpis consume 359 Aedes aegypti larvae at 30-32 ºC in contrast to 154 larvae at 20-26 ºC. Although many bacterial species were isolated from mosquito cadavers but those belonging to genus Bacillus are found highly pathogenic against them. The successful species of this genus include Bacillus thuringiensis and Bacillus sphaericus. The prime targets of B. thuringiensis are mostly the immatures of genus Aedes, Culex, Anopheles and Psorophora while B. sphaericus is specifically toxic against species of Culex, Psorophora and Culiseta. The entomopathogenic nematodes belonging to family, mermithidae are also pathogenic to different mosquito species. Eighty different species of mosquitoes including Anopheles, Aedes and Culex proved to be highly vulnerable to the attack of two mermithid species, Romanomermis culicivorax and R. iyengari. Cytoplasmic polyhedrosis virus was the first described pathogenic virus, isolated from the cadavers of mosquito specie, Culex tarsalis. Other viruses which are pathogenic to culicine includes, iridoviruses, cytopolyhedrosis viruses, entomopoxviruses and parvoviruses. Protozoa species belonging to division microsporidia are the common pathogenic protozoans in mosquito populations which kill their host by the chronic effects of parasitism. Moreover, due to their wide prevalence in anopheline mosquitoes and transversal and horizontal transmission from infected to healthy host, microsporidia of the genera Nosema and Amblyospora have received much attention in various mosquito control programmes. Fungal based mycopesticides are used in biological control of insect pests with 47 species reported virulent against different stages of mosquitoes. These include both aquatic fungi i.e. species of Coelomomyces, Lagenidium giganteum and Culicinomyces clavosporus, and the terrestrial fungi Metarhizium anisopliae and Beauveria bassiana. Hence, it was concluded that the integrated use of all these biological control agents can be a healthy contribution in mosquito control programmes and become a dire need of the time to avoid repeated use of pesticides.

Keywords: entomopathogenic nematodes, protozoa, Toxorhynchites, vector-borne

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Authors: Ankita Baidya, Vanishri Ganakumar, Ranveer S. Jadon, Piyush Ranjan, Rita Sood

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Septic embolism can have varied presentations and clinical considerations. Infected central venous catheters are commonly associated with septic emboli but peripheral vascular catheters are rarely implicated. We describe a rare case of septic pulmonary emboli related to infected peripheral venous cannulation caused by an unusual etiological agent. A young male presented with complaints of fever, productive cough, sudden onset shortness of breath and cellulitis in both the upper limbs. He was recently hospitalised for dengue fever and administered intravenous fluids through peripheral venous line. The patient was febrile, tachypneic and in respiratory distress, there were multiple pus filled bullae in left hand alongwith swelling and erythema involving right forearm that started at the site of cannulation. Chest examination showed active accessory muscles of respiration, stony dull percussion at the base of right lung and decreased breath sounds at right infrascapular, infraaxillary and mammary area. Other system examination was within normal limits. Chest X-ray revealed bilateral multiple patchy heterogenous peripheral opacities and infiltrates with right-sided pleural effusion. Contrast-enhanced computed tomography (CECT) chest showed feeding vessel sign confirming the diagnosis as septic emboli. Venous Doppler and 2D-echocardiogarm were normal. Laboratory findings showed marked leucocytosis (22000/mm3). Pus aspirate, blood sample, and sputum sample were sent for microbiological testing. The patient was started empirically on ceftriaxone, vancomycin, and clindamycin. The Pus culture and sputum culture showed Klebsiella pneumoniae sensitive to cefoperazone-sulbactum, piperacillin-tazobactum, meropenem and amikacin. The antibiotics were modified accordingly to antimicrobial sensitivity profile to Cefoperazone-sulbactum. Bronchoalveolar lavage (BAL) was done and sent for microbiological investigations. BAL culture showed Klebsiella pneumoniae with same antimicrobial resistance profile. On day 6 of starting cefoperazone-sulbactum, he became afebrile. The skin lesions improved significantly. He was administered 2 weeks of cefoperazone–sulbactum and discharged on oral faropenem for 4 weeks. At the time of discharge, TLC was 11200/mm3 with marked radiological resolution of infection and healed skin lesions. He was kept in regular follow up. Chest X-ray and skin lesions showed complete resolution after 8 weeks. Till date, only couple of case reports of septic emboli through peripheral intravenous line have been reported in English literature. This case highlights that a simple procedure of peripheral intravenous cannulation can lead to catastrophic complication of septic pulmonary emboli and widespread cellulitis if not done with proper care and precautions. Also, the usual pathogens in such clinical settings are gram positive bacteria, but with the history of recent hospitalization, empirical therapy should also cover drug resistant gram negative microorganisms. It also emphasise the importance of appropriate healthcare practices to be taken care during all procedures.

Keywords: antibiotics, cannula, Klebsiella pneumoniae, septic emboli

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Authors: Lia Mania, Ketevan Nanobashvili

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Background: The coronavirus disease COVID-19 has become the cause of a global health crisis during the current pandemic. This study aims to fill the paucity of epidemiological studies on the impact of COVID-19 on the oral health of pediatric populations. Methods: It was conducted an observational, cross-sectional study in Georgia, in Tbilisi (capital of Georgia), among 7 to 12-year-old PCR or rapid test-confirmed post-Covid populations in all districts of Tbilisi (10 districts in total). 332 beneficiaries who were infected with Covid within one year were included in the study. The population was selected in schools of Tbilisi according to the principle of cluster selection. A simple random selection took place in the selected clusters. According to this principle, an equal number of beneficiaries were selected in all districts of Tbilisi. By July 1, 2022, according to National Center for Disease Control and Public Health data (NCDC.Ge), the number of test-confirmed cases in the population aged 0-18 in Tbilisi was 115137 children (17.7% of all confirmed cases). The number of patients to be examined was determined by the sample size. Oral screening, microbiological examination of saliva, and administration of oral health questionnaires to guardians were performed. Statistical processing of data was done with SPSS-23. Risk factors were estimated by odds ratio and logistic regression with 95% confidence interval. Results: Statistically reliable differences between the averages of oral health indicators in asymptomatic and symptomatic covid-infected groups are: for caries intensity (DMF+def) t=4.468 and p=0.000, for modified gingival index (MGI) t=3.048, p=0.002, for simplified oral hygiene index (S-OHI) t=4.853; p=0.000. Symptomatic covid-infection has a reliable effect on the oral microbiome (Staphylococcus aureus, Candida albicans, Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus epidermalis); (n=332; 77.3% vs n=332; 58.0%; OR=2.46, 95%CI: 1.318-4.617). According to the logistic regression, it was found that the severity of the covid infection has a significant effect on the frequency of pathogenic and conditionally pathogenic bacteria in the oral cavity B=0.903 AOR=2.467 (CL 1.318-4.617). Symptomatic covid-infection affects oral health indicators, regardless of the presence of other risk factors, such as parental employment status, tooth brushing behaviors, carbohydrate meal, fruit consumption. (p<0.05). Conclusion: Risk factors (parental employment status, tooth brushing behaviors, carbohydrate consumption) were associated with poorer oral health status in a post-Covid population of 7- to 12-year-old children. However, such a risk factor as symptomatic ongoing covid-infection affected the oral microbiome in terms of the abundant growth of pathogenic and conditionally pathogenic bacteria (Staphylococcus aureus, Candida albicans, Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus epidermalis) and further worsened oral health indicators. Thus, a close association was established between symptomatic covid-infection and microbiome changes in the post-covid period; also - between the variables of oral health indicators and the symptomatic course of covid-infection.

Keywords: oral microbiome, COVID-19, population based research, oral health indicators

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Authors: Luciano Tarantino

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Gas gangrene is a rare, severe infection with a very high mortality rate caused by Clostridium species. The infection causes a non-suppurative localized producing gas lesion from which harmful toxins that impair the inflammatory response cause vessel damage and multiple organ failure. Gas gangrene of the liver is very rare and develops suddenly, often as a complication of abdominal surgery and liver transplantation. The present paper deals with a case of gas gangrene of the liver that occurred after percutaneous MW ablation of hepatocellular carcinoma, resulting in progressive liver necrosis and multi-organ failure in spite of specific antibiotics administration. The patient was successfully treated with percutaneous Radiofrequency ablation. Case report: Female, 76 years old, Child A class cirrhosis, treated with synchronous insertion of 3 MW antennae for large HCC (5.5 cm) in the VIII segment. 24 hours after treatment, the patient was asymptomatic and left the hospital . 2 days later, she complained of fever, weakness, abdominal swelling, and pain. Abdominal US detected a 2.3 cm in size gas-containing area, eccentric within the large (7 cm) ablated area. The patient was promptly hospitalized with the diagnosis of anaerobic liver abscess and started antibiotic therapy with Imipenem/cilastatine+metronidazole+teicoplanine. On the fourth day, the patient was moved to the ICU because of dyspnea, congestive heart failure, atrial fibrillation, right pleural effusion, ascites, and renal failure. Blood tests demonstrated severe leukopenia and neutropenia, anemia, increased creatinine and blood nitrogen, high-level FDP, and high INR. Blood cultures were negative. At US, unenhanced CT, and CEUS, a progressive enlargement of the infected liver lesion was observed. Percutaneous drainage was attempted, but only drops of non-suppurative brownish material could be obtained. Pleural and peritoneal drainages gave serosanguineous muddy fluid. The Surgeon and the Anesthesiologist excluded any indication of surgical resection because of the high perioperative mortality risk. Therefore, we asked for the informed consent of the patient and her relatives to treat the gangrenous liver lesion by percutaneous Ablation. Under conscious sedation, percutaneous RFA of GG was performed by double insertion of 3 cool-tip needles (Covidien LDT, USA ) into the infected area. The procedure was well tolerated by the patient. A dramatic improvement in the patient's condition was observed in the subsequent 24 hours and thereafter. Fever and dyspnea disappeared. Normalization of blood tests, including creatinine, was observed within 4 days. Heart performance improved, 10 days after the RFA the patient left the hospital and was followed-up with weekly as an outpatient for 2 months and every two months thereafter. At 18 months follow-up, the patient is well compensated (Child-Pugh class B7), without any peritoneal or pleural effusion and without any HCC recurrence at imaging (US every 3 months, CT every 6 months). Percutaneous RFA could be a valuable therapy of focal GG of the liver in patients non-responder to antibiotics and when surgery and liver transplantation are not feasible. A fast and early indication is needed in case of rapid worsening of patient's conditions.

Keywords: liver tumor ablation, interventional ultrasound, liver infection, gas gangrene, radiofrequency ablation

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Authors: Swati Gautam, Salman Akhtar, S. P. Jaiswar, Amita Jain

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Background: FGTB is now a major global health problem mostly in developing countries including India. In humans, Mycobacterium Tuberculosis (M.tb) is a causating agent of infection. High index of suspicion is required for early diagnosis due to asymptomatic presentation of FGTB disease. In macrophages Toll Like Receptor-2 (TLR-2) is one which mediated host’s immune response to M.tb. The expression of TLR-2 on macrophages is important to determine the fate of innate immune responses to M.tb. TLR-2 have two work. First its high expression on macrophages worsen the outer of infection and another side, it maintains M.tb to its dormant stage avoids activation of M.tb from latent phase. Single Nucleotide Polymorphism (SNP) of TLR-2 gene plays an important role in susceptibility to TB among different populations and subsequently, in the development of infertility. Methodology: This Case-Control study was done in the Department of Obs and Gynae and Department of Microbiology at King George’s Medical University, U.P, Lucknow, India. Total 300 subjects (150 Cases and 150 Controls) were enrolled in the study. All subjects were enrolled only after fulfilling the given inclusion and exclusion criteria. Inclusion criteria: Age 20-35 years, menstrual-irregularities, positive on Acid-Fast Bacilli (AFB), TB-PCR, (LJ/MGIT) culture in Endometrial Aspiration (EA). Exclusion criteria: Koch’s active, on ATT, PCOS, and Endometriosis fibroid women, positive on Gonococal and Chlamydia. Blood samples were collected in EDTA tubes from cases and healthy control women (HCW) and genomic DNA extraction was carried out by salting-out method. Genotyping of TLR2 genetic variants (Arg753Gln and Arg677Trp) were performed by using single amplification refractory mutation system (ARMS) PCR technique. PCR products were analyzed by electrophoresis on 1.2% agarose gel and visualized by gel-doc. Statistical analysis of the data was performed using the SPSS 16.3 software and computing odds ratio (OR) with 95% CI. Linkage Disequiliribium (LD) analysis was done by SNP stats online software. Results: In TLR-2 (Arg753Gln) polymorphism significant risk of FGTB observed with GG homozygous mutant genotype (OR=13, CI=0.71-237.7, p=0.05), AG heterozygous mutant genotype (OR=13.7, CI=0.76-248.06, p=0.03) however, G allele (OR=1.09, CI=0.78-1.52, p=0.67) individually was not associated with FGTB. In TLR-2 (Arg677Trp) polymorphism a significant risk of FGTB observed with TT homozygous mutant genotype (OR= 0.020, CI=0.001-0.341, p < 0.001), CT heterozygous mutant genotype (OR=0.53, CI=0.33-0.86, p=0.014) and T allele (OR=0.463, CI=0.32-0.66, p < 0.001). TT mutant genotype was only found in FGTB cases and frequency of CT heterozygous more in control group as compared to FGTB group. So, CT genotype worked as protective mutation for FGTB susceptibility group. In haplotype analysis of TLR-2 genetic variants, four possible combinations, i.e. (G-T, A-C, G-C, and A-T) were obtained. The frequency of haplotype A-C was significantly higher in FGTB cases (0.32). Control group did not show A-C haplotype and only found in FGTB cases. Conclusion: In conclusion, study showed a significant association with both genetic variants of TLR-2 of FGTB disease. Moreover, the presence of specific associated genotype/alleles suggest the possibility of disease severity and clinical approach aimed to prevent extensive damage by disease and also helpful for early detection of disease.

Keywords: ARMS, EDTA, FGTB, TLR

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Authors: Raham El-Kahlout, Hadi Yassin, Asmaa Athani, Marwan Abou Madi, Gheyath Nasrallah

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Background: Since its first isolation in September 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has diffused across 27 countries infecting more than two thousand individuals with a high case fatality rate. MERS-CoV–specific antibodies are widely found in Dromedary camel along with viral shedding of similar viruses detected in human at same region, suggesting that MERS epidemiology may be central role by camel. Interestingly, MERS-CoV has also been also reported to be asymptomatic or to cause influenza-like mild illnesses. Therefore, in a country like Qatar (bordered Saudi Arabia), where camels are widely spread, serological surveys are important to explore the role of camels in MERS-CoV transmission. However, widespread strategic serological surveillances of MERS-CoV among populations, particularly in endemic country, are infrequent. In the absence of clear epidemiological view, cross-sectional MERS antibody surveillances in human populations are of global concern. Method: We performed a comparative serological screening of 4719 healthy blood donors, 135 baseline case contacts (high risk individual), and four MERS confirmed patients (by PCR) for the presence of anti-MERS IgG. Initially, samples were screened using Euroimmune anti- MERS-CoV IgG ELISA kit, the only commercial kit available in the market and recommended by the CDC as a screening kit. To confirm ELISA test results, farther serological testing was performed for all borderline and positive samples using two assays; the anti MERS-CoV IgG and IgM Euroimmune indirect immunofluorescent test (IIFT) and pseudoviral particle neutralizing assay (PPNA). Additionally, to test cross reactivity of anti-MERS-CoV antibody with other family members of coronavirus, borderline and positive samples were tested for the presence of the of IgG antibody of the following viruses; SARS, HCoV-229E, HKU1 using the Euroimmune IIFT for SARS and HCoV-229E and ELISA for HKU1. Results: In all of 4858 screened 15 samples [10 donors (0.21%, 10/4719), 1 case contact (0.77 %, 1/130), 3 patients (75%, 3/4)] anti-MERS IgG reactive/borderline samples were seen in ELISA. However, only 7 (0.14%) of them gave positive with in IIFT and only 3 (0.06%) was confirmed by the specific anti-MERS PPNA. One of the interesting findings was, a donor, who was selected in the control group as a negative anti-MERS IgG ELISA, yield reactive for anti-MERS IgM IIFT and was confirmed with the PPNA. Further, our preliminary results showed that there was a strong cross reactivity between anti- MERS-COV IgG with both HCoV-229E or anti-HKU1 IgG, yet, no cross reactivity of SARS were found. Conclusions: Our findings suggest that MERS-CoV is not heavily circulated among the population of Qatar and this is also indicated by low number of confirmed cases (only 18) since 2012. Additionally, the presence of antibody of other pathogenic human coronavirus may cause false positive results of both ELISA and IIFT, which stress the need for more evaluation studies for the available serological assays. Conclusion: this study provides an insight about the epidemiological view for MERS-CoV in Qatar population. It also provides a performance evaluation for the available serologic tests for MERS-CoV in a view of serologic status to other human coronaviruses.

Keywords: seroprevalence, MERS-CoV, healthy individuals, Qatar

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Authors: Artem Kim, Clara Savary, Christele Dubourg, Wilfrid Carre, Houda Hamdi-Roze, Valerie Dupé, Sylvie Odent, Marie De Tayrac, Veronique David

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Holoprosencephaly (HPE) is a rare congenital brain malformation resulting from the incomplete separation of the two cerebral hemispheres. It is characterized by a wide phenotypic spectrum and a high degree of locus heterogeneity. Genetic defects in 16 genes have already been implicated in HPE, but account for only 30% of cases, suggesting that a large part of genetic factors remains to be discovered. HPE has been recently redefined as a complex multigenic disorder, requiring the joint effect of multiple mutational events in genes belonging to one or several developmental pathways. The onset of HPE may result from accumulation of the effects of multiple rare variants in functionally-related genes, each conferring a moderate increase in the risk of HPE onset. In order to decipher the genetic basis of HPE, unconventional patterns of inheritance involving multiple genetic factors need to be considered. The primary objective of this study was to uncover possible disease causing combinations of multiple rare variants underlying HPE by performing trio-based Whole Exome Sequencing (WES) of familial cases where no molecular diagnosis could be established. 39 families were selected with no fully-penetrant causal mutation in known HPE gene, no chromosomic aberrations/copy number variants and without any implication of environmental factors. As the main challenge was to identify disease-related variants among a large number of nonpathogenic polymorphisms detected by WES classical scheme, a novel variant prioritization approach was established. It combined WES filtering with complementary gene-level approaches: transcriptome-driven (RNA-Seq data) and clinically-driven (public clinical data) strategies. Briefly, a filtering approach was performed to select variants compatible with disease segregation, population frequency and pathogenicity prediction to identify an exhaustive list of rare deleterious variants. The exome search space was then reduced by restricting the analysis to candidate genes identified by either transcriptome-driven strategy (genes sharing highly similar expression patterns with known HPE genes during cerebral development) or clinically-driven strategy (genes associated to phenotypes of interest overlapping with HPE). Deeper analyses of candidate variants were then performed on a family-by-family basis. These included the exploration of clinical information, expression studies, variant characteristics, recurrence of mutated genes and available biological knowledge. A novel bioinformatics pipeline was designed. Applied to the 39 families, this final integrated workflow identified an average of 11 candidate variants per family. Most of candidate variants were inherited from asymptomatic parents suggesting a multigenic inheritance pattern requiring the association of multiple mutational events. The manual analysis highlighted 5 new strong HPE candidate genes showing recurrences in distinct families. Functional validations of these genes are foreseen.

Keywords: complex genetic disorder, holoprosencephaly, multiple rare variants, whole exome sequencing

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Authors: Judy M. Obliosca, Olivia Vest, Sandra Poulos, Kelsi Smith, Tammy Ferguson, Abigail Powers Lott, Alicia K. Smith, Yang Xu, Christopher K. Tison

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Post-Traumatic Stress Disorder (PTSD) is a mental health problem that people may develop after experiencing traumatic events such as combat, natural disasters, and major emotional challenges. Tragically, the number of military personnel with PTSD correlates directly with the number of veterans who attempt suicide, with the highest rate in the Army. Research has shown epigenetic risks in those who are prone to several psychiatric dysfunctions, particularly PTSD. Once initiated in response to trauma, epigenetic alterations in particular, the DNA methylation in the form of 5-methylcytosine (5mC) alters chromatin structure and represses gene expression. Current methods to detect DNA methylation, such as bisulfite-based genomic sequencing techniques, are laborious and have massive analysis workflow while still having high error rates. A faster and simpler detection method of high sensitivity and precision would be useful in a clinical setting to confirm potential PTSD etiologies, prevent other psychiatric disorders, and improve military health. A nano-enhanced Surface Plasmon Resonance imaging (SPRi)-based assay that simultaneously detects site-specific 5mC base (termed as PTSD base) in methylated genes related to PTSD is being developed. The arrays on a sensing chip were first constructed for parallel detection of PTSD bases using synthetic and genomic DNA (gDNA) samples. For the gDNA sample extracted from the whole blood of a PTSD patient, the sample was first digested using specific restriction enzymes, and fragments were denatured to obtain single-stranded methylated target genes (ssDNA). The resulting mixture of ssDNA was then injected into the assay platform, where targets were captured by specific DNA aptamer probes previously immobilized on the surface of a sensing chip. The PTSD bases in targets were detected by anti-5-methylcytosine antibody (anti-5mC), and the resulting signals were then enhanced by the universal nanoenhancer. Preliminary results showed successful detection of a PTSD base in a gDNA sample. Brighter spot images and higher delta values (control-subtracted reflectivity signal) relative to those of the control were observed. We also implemented the in-house surface activation system for detection and developed SPRi disposable chips. Multiplexed PTSD base detection of target methylated genes in blood DNA from PTSD patients of severity conditions (asymptomatic and severe) was conducted. This diagnostic capability being developed is a platform technology, and upon successful implementation for PTSD, it could be reconfigured for the study of a wide variety of neurological disorders such as traumatic brain injury, Alzheimer’s disease, schizophrenia, and Huntington's disease and can be extended to the analyses of other sample matrices such as urine and saliva.

Keywords: epigenetic assay, DNA methylation, PTSD, whole blood, multiplexing

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Authors: Kartik Gupta, Virendra Kumar, Sanjeev Sinha, N. Jagannathan

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Introduction: A significant number of patients having human immunodeficiency virus (HIV) infection show a neurocognitive decline (NCD) ranging from minor cognitive impairment to severe dementia. The possible causes of NCD in HIV-infected patients include brain injury by HIV before cART, neurotoxic viral proteins and metabolic abnormalities. In the present study, we compared the level of NCD in asymptomatic HIV-infected patients with changes in brain metabolites measured by using magnetic resonance spectroscopy (MRS). Methods: 43 HIV-positive patients (30 males and 13 females) coming to ART center of the hospital and HIV-seronegative healthy subjects were recruited for the study. All the participants completed MRI and MRS examination, detailed clinical assessments and a battery of neuropsychological tests. All the MR investigations were carried out at 3.0T MRI scanner (Ingenia/Achieva, Philips, Netherlands). MRI examination protocol included the acquisition of T2-weighted imaging in axial, coronal and sagittal planes, T1-weighted, FLAIR, and DWI images in the axial plane. Patients who showed any apparent lesion on MRI were excluded from the study. T2-weighted images in three orthogonal planes were used to localize the voxel in left frontal lobe white matter (FWM) and left basal ganglia (BG) for single voxel MRS. Single voxel MRS spectra were acquired with a point resolved spectroscopy (PRESS) localization pulse sequence at an echo time (TE) of 35 ms and a repetition time (TR) of 2000 ms with 64 or 128 scans. Automated preprocessing and determination of absolute concentrations of metabolites were estimated using LCModel by water scaling method and the Cramer-Rao lower bounds for all metabolites analyzed in the study were below 15\%. Levels of total N-acetyl aspartate (tNAA), total choline (tCho), glutamate + glutamine (Glx), total creatine (tCr), were measured. Cognition was tested using a battery of tests validated for Indian population. The cognitive domains tested were the memory, attention-information processing, abstraction-executive, simple and complex perceptual motor skills. Z-scores normalized according to age, sex and education standard were used to calculate dysfunction in these individual domains. The NCD was defined as dysfunction with Z-score ≤ 2 in at least two domains. One-way ANOVA was used to compare the difference in brain metabolites between the patients and healthy subjects. Results: NCD was found in 23 (53%) patients. There was no significant difference in age, CD4 count and viral load between the two groups. Maximum impairment was found in the domains of memory and simple motor skills i.e., 19/43 (44%). The prevalence of deficit in attention-information processing, complex perceptual motor skills and abstraction-executive function was 37%, 35%, 33% respectively. Subjects with NCD had a higher level of Glutamate in the Frontal region (8.03 ± 2.30 v/s. 10.26 ± 5.24, p-value 0.001). Conclusion: Among newly diagnosed, ART-naïve retroviral disease patients from India, cognitive decline was found in 53\% patients using tests validated for this population. Those with neurocognitive decline had a significantly higher level of Glutamate in the left frontal region. There was no significant difference in age, CD4 count and viral load at initiation of ART between the two groups.

Keywords: HIV, neurocognitive decline, neurometabolites, magnetic resonance spectroscopy

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Authors: Anisa Suraya Ab Razak, Izza Hayat

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Introduction: The diagnosis and management of severe hyponatremia in neuropsychiatric patients present a significant challenge to physicians. Several factors contribute, including diagnostic shadowing and attributing abnormal behavior to intellectual disability or psychiatric conditions. Hyponatraemia is the commonest electrolyte abnormality in the inpatient population, ranging from mild/asymptomatic, moderate to severe levels with life-threatening symptoms such as seizures, coma and death. There are several documented fatal case reports in the literature of severe hyponatremia secondary to psychogenic polydipsia, often diagnosed only in autopsy. This paper presents a case study of acute severe hyponatremia in a neuropsychiatric patient with early diagnosis and admission to intensive care. Case study: A 21-year old Caucasian male with known epilepsy and learning disability was admitted from residential living with generalized tonic-clonic self-terminating seizures after refusing medications for several weeks. Evidence of superficial head injury was detected on physical examination. His laboratory data demonstrated mild hyponatremia (125 mmol/L). Computed tomography imaging of his brain demonstrated no acute bleed or space-occupying lesion. He exhibited abnormal behavior - restlessness, drinking water from bathroom taps, inability to engage, paranoia, and hypersexuality. No collateral history was available to establish his baseline behavior. He was loaded with intravenous sodium valproate and leveritircaetam. Three hours later, he developed vomiting and a generalized tonic-clonic seizure lasting forty seconds. He remained drowsy for several hours and regained minimal recovery of consciousness. A repeat set of blood tests demonstrated profound hyponatremia (117 mmol/L). Outcomes: He was referred to intensive care for peripheral intravenous infusion of 2.7% sodium chloride solution with two-hourly laboratory monitoring of sodium concentration. Laboratory monitoring identified dangerously rapid correction of serum sodium concentration, and hypertonic saline was switched to a 5% dextrose solution to reduce the risk of acute large-volume fluid shifts from the cerebral intracellular compartment to the extracellular compartment. He underwent urethral catheterization and produced 8 liters of urine over 24 hours. Serum sodium concentration remained stable after 24 hours of correction fluids. His GCS recovered to baseline after 48 hours with improvement in behavior -he engaged with healthcare professionals, understood the importance of taking medications, admitted to illicit drug use and drinking massive amounts of water. He was transferred from high-dependency care to ward level and was initiated on multiple trials of anti-epileptics before achieving seizure-free days two weeks after resolution of acute hyponatremia. Conclusion: Psychogenic polydipsia is often found in young patients with intellectual disability or psychiatric disorders. Patients drink large volumes of water daily ranging from ten to forty liters, resulting in acute severe hyponatremia with mortality rates as high as 20%. Poor outcomes are due to challenges faced by physicians in making an early diagnosis and treating acute hyponatremia safely. A low index of suspicion of water intoxication is required in this population, including patients with known epilepsy. Monitoring urine output proved to be clinically effective in aiding diagnosis. Early referral and admission to intensive care should be considered for safe correction of sodium concentration while minimizing risk of fatal complications e.g. central pontine myelinolysis.

Keywords: epilepsy, psychogenic polydipsia, seizure, severe hyponatremia

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