Search results for: sciatic neuropathy
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 85

Search results for: sciatic neuropathy

55 Effect of Various Durations of Type 2 Diabetes on Muscle Performance

Authors: Santosh Kumar Yadav, Shobha Keswani, Nishat Quddus, Sohrab Ahmad Khan, Zuheb Ahmad Shiddiqui, Varsha Chorsiya

Abstract:

Introduction: Early onset diabetes is more aggressive than the late onset diabetes. Diabetic individual has a greater spectrum of life period to suffer from its damage, complications, and long-term disability. This study aimed at assessing knee joint muscle performance under various durations of diabetes. Method and Materials: A total of 30 diabetic subjects (18 male and 12 females) without diabetic neuropathy were included for the study. They were divided into three groups with 5 years, 10 years and 15 years of duration of disease each. Muscle performance was evaluated through strength and flexibility. Peak torque for quadriceps muscle was measured using isokinetic dynamometer. Flexibility for quadriceps and hamstring muscles were measured through Ducan’s Elys test and 90/90 test. Results: The result showed significant difference in muscle strength (p<0.05), flexibility (p≤0.05) between groups. Discussion: Optimal muscle strength and flexibility are vital for musculoskeletal health and functional independence. Conclusion: The reduced muscle performance and functional impairment in nonneuropathic diabetic patients suggest that other mechanism besides neuropathy that contribute to altered biomechanics. These findings of this study project early management of these altered parameters through disease-specific physical therapy and assessment-based intervention. Clinical Relevance: Managing disability is more costly than managing disease. Prompt and timely identification and management strategy can dramatically reduce the cost of care for diabetic patients.

Keywords: muscle flexibility, muscle performance, muscle torque, type 2 diabetes

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54 Risk Factors for Diabetic Foot: Upper Egypt Experience

Authors: Ali Kassem, Mohamed Alsenbasy, Ahmed Nagaah

Abstract:

Background: Diabetic foot is one of the often neglected complications of diabetes mellitus It was reported that patients of diabetic foot ulcer (DFU) have considerable morbidity and mortality. Due to arterial abnormalities, diabetic neuropathy, as well as the tendency to delayed wound healing, foot infection and or gangrene is relatively common in diabetic patients. Foot related problems are responsible for up to 50% of diabetic related hospital admissions. Aim of work: The aim of the present study is to assess the risk factors for DFU in diabetic patients attending Sohag University Hospitals (Upper Egypt) Material and methods: The present study includes 100 diabetic foot patients attending the diabetic outpatient clinic of Sohag University Hospitals. For all of the studied patients the following were done: Full medical history and clinical examination; thorough foot examination; Laboratory tests including: Blood glucose level, HBA1c, serum lipids and renal function tests, ECG and Echocardiography, Doppler study on the lower limbs. Results: Sixty eight percent of the affected patients were males versus 32 % female patients. All male patients and none of the female were smoker. Seventy nine percent of patients were living in rural areas versus 14 % in urban areas. Duration of diabetes was more than 12 years in 74%, less than 12 years in 26% of patients. Fifty percent of patients have associated hypertension, 46% have dyslipidemia, 18% have ischemic heart disease or old myocardial infarction and 8% have impaired renal function. History of previous foot ulcers was reported in 11 % and foot amputation in 2% of patients. Conclusion: Male gender, low socioeconomic status, smoking, long duration of diabetes, other cardiovascular risk factors particularly hypertension and previous history of foot ulceration are the major risk factors for diabetic foot in our locality.

Keywords: diabetic foot, diabetic neuropathy, foot gangrene, risk factors for diabetic complications

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53 Role of Onion Extract for Neuro-Protection in Experimental Stroke Model

Authors: Richa Shri, Varinder Singh, Kundan Singh Bora, Abhishek Bhanot, Rahul Kumar, Amit Kumar, Ravinder Kaur

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The term ‘neuroprotection’ means preserving/salvaging function and structure of neurons. Neuroprotection is an adjunctive treatment option for neurodegenerative disorders. Oxidative stress is considered a major culprit in neurodegenerative disorders; hence, management strategies include use of antioxidants. Our search for a neuroprotective agent began with Allium cepa L. or onions, (family Amaryllidaceae) - a potent antioxidant. We have investigated the neuroprotective potential of onions in experimental models of ischemic stroke, diabetic neuropathy, neuropathic pain, and dementia. In pre and post-ischemic stroke model, the methanol extract of outer scales of onion bulbs (MEOS) prevented memory loss and motor in-coordination; reduced oxidative stress and cerebral infarct size. This also prevented and ameliorated diabetic neuropathy in mice. The MEOS was fractionated to yield a flavonoid rich fraction (FRF) that successfully reversed ischemia-reperfusion induced neuronal damage, thereby demonstrating that the flavonoids are responsible for the activity. The FRF effectively ameliorated chronic constriction induced neuropathic pain in rats. The FRF was subjected to bioactivity-guided fractionated. It was seen that FRF is more effective as compared to the isolated components probably due to synergism among the constituents (i.e., quercetin and quercetin glucosides) in the FRF. The outer scales of onion bulbs have great potential for prevention as well as for treatment of neuronal disorders. Red onions, with higher amounts of flavonoids as compared to the white onions, produced more significant neuroprotection. Thus, the standardized FRF from the waste material of a commonly used vegetable, especially the red variety, may be developed as a valuable neuroprotective agent.

Keywords: Allium cepa, antioxidant activity, flavonoid rich fraction, neuroprotection

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52 Community Engagement Strategies to Assist with the Development of an RCT Among People Living with HIV

Authors: Joyce K. Anastasi, Bernadette Capili

Abstract:

Community Engagement Strategies to Assist with the Development of an RCT Among People Living with HIV Our research team focuses on developing and testing protocols to manage chronic symptoms. For many years, our team designed and implemented symptom management studies for people living with HIV (PLWH). We identify symptoms that are not curative and are not adequately controlled by conventional therapies. As an exemplar, we describe how we successfully engaged PLWH in developing and refining our research feasibility protocol for distal sensory peripheral neuropathy (DSP) associated with HIV. With input from PLWH with DSP, our research received National Institutes of Health (NIH) research funding support. Significance: DSP is one of the most common neurologic complications in HIV. It is estimated that DSP affects 21% to 50% of PLWH. The pathogenesis of DSP in HIV is complex and unclear. Proposed mechanisms include cytokine dysregulation, viral protein-produced neurotoxicity, and mitochondrial dysfunction associated with antiretroviral medications. There are no FDA-approved treatments for DSP in HIV. Purpose: Aims: 1) to explore the impact of DSP on the lives of PLWH, 2) to identify patients’ perspectives on successful treatments for DSP, 3) to identify interventions considered feasible and sensitive to the needs of PLWH with DSP, and 4) to obtain participant input for protocol/study design. Description of Process: We conducted a needs assessment with PLWH with DSP. From our needs assessment, we learned from the patients’ perspective detailed descriptions of their symptoms; physical functioning with DSP; self-care remedies tried, and desired interventions. We also asked about protocol scheduling, instrument clarity, study compensation, study-related burdens, and willingness to participate in a randomized controlled trial (RCT) with a placebo and a waitlist group. Implications: We incorporated many of the suggestions learned from the need assessment. We developed and completed a feasibility study that provided us with invaluable information that informed subsequent NIH-funded studies. In addition to our extensive clinical and research experience working with PLWH, learning from the patient perspective helped in developing our protocol and promoting a successful plan for recruitment and retention of study participants.

Keywords: clinical trial development, peripheral neuropathy, traditional medicine, HIV, AIDS

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51 Bio-Functionalized Silk Nanofibers for Peripheral Nerve Regeneration

Authors: Kayla Belanger, Pascale Vigneron, Guy Schlatter, Bernard Devauchelle, Christophe Egles

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A severe injury to a peripheral nerve leads to its degeneration and the loss of sensory and motor function. To this day, there still lacks a more effective alternative to the autograft which has long been considered the gold standard for nerve repair. In order to overcome the numerous drawbacks of the autograft, tissue engineered biomaterials may be effective alternatives. Silk fibroin is a favorable biomaterial due to its many advantageous properties such as its biocompatibility, its biodegradability, and its robust mechanical properties. In this study, bio-mimicking multi-channeled nerve guidance conduits made of aligned nanofibers achieved by electrospinning were functionalized with signaling biomolecules and were tested in vitro and in vivo for nerve regeneration support. Silk fibroin (SF) extracted directly from silkworm cocoons was put in solution at a concentration of 10wt%. Poly(ethylene oxide) (PEO) was added to the resulting SF solution to increase solution viscosity and the following three electrospinning solutions were made: (1) SF/PEO solution, (2) SF/PEO solution with nerve growth factor and ciliary neurotrophic factor, and (3) SF/PEO solution with nerve growth factor and neurotrophin-3. Each of these solutions was electrospun into a multi-layer architecture to obtain mechanically optimized aligned nanofibrous mats. For in vitro studies, aligned fibers were treated to induce β-sheet formation and thoroughly rinsed to eliminate presence of PEO. Each material was tested using rat embryo neuron cultures to evaluate neurite extension and the interaction with bio-functionalized or non-functionalized aligned fibers. For in vivo studies, the mats were rolled into 5mm long multi-, micro-channeled conduits then treated and thoroughly rinsed. The conduits were each subsequently implanted between a severed rat sciatic nerve. The effectiveness of nerve repair over a period of 8 months was extensively evaluated by cross-referencing electrophysiological, histological, and movement analysis results to comprehensively evaluate the progression of nerve repair. In vitro results show a more favorable interaction between growing neurons and bio-functionalized silk fibers compared to pure silk fibers. Neurites can also be seen having extended unidirectionally along the alignment of the nanofibers which confirms a guidance factor for the electrospun material. The in vivo study has produced positive results for the regeneration of the sciatic nerve over the length of the study, showing contrasts between the bio-functionalized material and the non-functionalized material along with comparisons to the experimental control. Nerve regeneration has been evaluated not only by histological analysis, but also by electrophysiological assessment and motion analysis of two separate natural movements. By studying these three components in parallel, the most comprehensive evaluation of nerve repair for the conduit designs can be made which can, therefore, more accurately depict their overall effectiveness. This work was supported by La Région Picardie and FEDER.

Keywords: electrospinning, nerve guidance conduit, peripheral nerve regeneration, silk fibroin

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50 Theoretical Study of Carbonic Anhydrase-Ii Inhibitors for Treatment of Glaucoma

Authors: F. Boukli Hacene, W. Soufi, S. Ghalem

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Glaucoma disease is a progressive degenerative optic neuropathy, with irreversible visual field deficits and high eye pressure being one of the risk factors. Sulfonamides are carbonic anhydrase-II inhibitors that aim to decrease the secretion of aqueous humor by direct inhibition of this enzyme at the level of the ciliary processes. These drugs present undesirable effects that are difficult to accept by the patient. In our study, we are interested in the inhibition of carbonic anhydrase-II by different natural ligands (curcumin analogues) using molecular modeling methods using molecular operating environment (MOE) software to predict their interaction with this enzyme.

Keywords: carbonic anhydrase-II, curcumin analogues, drug research, molecular modeling

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49 Evaluating the Effectiveness of Plantar Sensory Insoles and Remote Patient Monitoring for Early Intervention in Diabetic Foot Ulcer Prevention in Patients with Peripheral Neuropathy

Authors: Brock Liden, Eric Janowitz

Abstract:

Introduction: Diabetic peripheral neuropathy (DPN) affects 70% of individuals with diabetes1. DPN causes a loss of protective sensation, which can lead to tissue damage and diabetic foot ulcer (DFU) formation2. These ulcers can result in infections and lower-extremity amputations of toes, the entire foot, and the lower leg. Even after a DFU is healed, recurrence is common, with 49% of DFU patients developing another ulcer within a year and 68% within 5 years3. This case series examines the use of sensory insoles and newly available plantar data (pressure, temperature, step count, adherence) and remote patient monitoring in patients at risk of DFU. Methods: Participants were provided with custom-made sensory insoles to monitor plantar pressure, temperature, step count, and daily use and were provided with real-time cues for pressure offloading as they went about their daily activities. The sensory insoles were used to track subject compliance, ulceration, and response to feedback from real-time alerts. Patients were remotely monitored by a qualified healthcare professional and were contacted when areas of concern were seen and provided coaching on reducing risk factors and overall support to improve foot health. Results: Of the 40 participants provided with the sensory insole system, 4 presented with a DFU. Based on flags generated from the available plantar data, patients were contacted by the remote monitor to address potential concerns. A standard clinical escalation protocol detailed when and how concerns should be escalated to the provider by the remote monitor. Upon escalation to the provider, patients were brought into the clinic as needed, allowing for any issues to be addressed before more serious complications might arise. Conclusion: This case series explores the use of innovative sensory technology to collect plantar data (pressure, temperature, step count, and adherence) for DFU detection and early intervention. The results from this case series suggest the importance of sensory technology and remote patient monitoring in providing proactive, preventative care for patients at risk of DFU. This robust plantar data, with the addition of remote patient monitoring, allow for patients to be seen in the clinic when concerns arise, giving providers the opportunity to intervene early and prevent more serious complications, such as wounds, from occurring.

Keywords: diabetic foot ulcer, DFU prevention, digital therapeutics, remote patient monitoring

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48 Metachromatic Leukodystrophy: A Case Report

Authors: Mary Rose Eunice S. Gundayao, Manolo M. Fernandez

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Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disorder with an autosomal recessive inheritance pattern. Lysosomal storage disorders are often severe, follow a progressively neurodegenerative path, and may result in multi-organ failure, potentially leading to death within 5 to 6 years in cases of early-onset forms. There are limited data regarding cases of MLD in Filipino children. This is the case of a 2-year-old Filipino girl who presented with progressive neurological deterioration and was diagnosed with metachromatic leukodystrophy by molecular genetic testing. This case report aims to present this patient’s clinical history, neurological findings, diagnosis and novel genetic mutations causing MLD. A concise review of updated literature on MLD will be discussed.

Keywords: metachromatic leukodystrophy, ARSA gene, peripheral neuropathy, case report, demyelinating disease

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47 A Paradigm Shift in the Cost of Illness of Type 2 Diabetes Mellitus over a Decade in South India: A Prevalence Based Study

Authors: Usha S. Adiga, Sachidanada Adiga

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Introduction: Diabetes Mellitus (DM) is one of the most common non-communicable diseases which imposes a large economic burden on the global health-care system. Cost of illness studies in India have assessed the health care cost of DM, but have certain limitations due to lack of standardization of the methods used, improper documentation of data, lack of follow up, etc. The objective of the study was to estimate the cost of illness of uncomplicated versus complicated type 2 diabetes mellitus in Coastal Karnataka, India. The study also aimed to find out the trend of cost of illness of the disease over a decade. Methodology: A prevalence based bottom-up approach study was carried out in two tertiary care hospitals located in Coastal Karnataka after ethical approval. Direct Medical costs like annual laboratory costs, pharmacy cost, consultation charges, hospital bed charges, surgical /intervention costs of 238 diabetics and 340 diabetic patients respectively from two hospitals were obtained from the medical record sections. Patients were divided into six groups, uncomplicated diabetes, diabetic retinopathy(DR), nephropathy(DN), neuropathy(DNeu), diabetic foot(DF), and ischemic heart disease (IHD). Different costs incurred in 2008 and 2017 in these groups were compared, to study the trend of cost of illness. Kruskal Wallis test followed by Dunn’s test were used to compare median costs between the groups and Spearman's correlation test was used for correlation studies. Results: Uncomplicated patients had significantly lower costs (p <0.0001) compared to other groups. Patients with IHD had highest Medical expenses (p < 0.0001), followed by DN and DF (p < 0.0001 ). Annual medical costs incurred were 1.8, 2.76, 2.77, 1.76, and 4.34 times higher in retinopathy, nephropathy, diabetic foot, neuropathy and IHD patients as compared to the cost incurred in managing uncomplicated diabetics. Other costs also showed a similar pattern of rising. A positive correlation was observed between the costs incurred and duration of diabetes, a negative correlation between the glycemic status and cost incurred. The cost incurred in the management of DM in 2017 was found to be elevated 1.4 - 2.7 times when compared to that in 2008. Conclusion: It is evident from the study that the economic burden due to diabetes mellitus is substantial. It poses a significant financial burden on the healthcare system, individual and society as a whole. There is a need for the strategies to achieve optimal glycemic control and operationalize regular and early screening methods for complications so as to reduce the burden of the disease.

Keywords: COI, diabetes mellitus, a bottom up approach, economics

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46 A Clinico-Bacteriological Study and Their Risk Factors for Diabetic Foot Ulcer with Multidrug-Resistant Microorganisms in Eastern India

Authors: Pampita Chakraborty, Sukumar Mukherjee

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This study was done to determine the bacteriological profile and antibiotic resistance of the isolates and to find out the potential risk factors for infection with multidrug-resistant organisms. Diabetic foot ulcer is a major medical, social, economic problem and a leading cause of morbidity and mortality, especially in the developing countries like India. 25 percent of all diabetic patients develop a foot ulcer at some point in their lives which is highly susceptible to infections and that spreads rapidly, leading to overwhelming tissue destruction and subsequent amputation. Infection with multidrug resistant organisms (MDRO) may increase the cost of management and may cause additional morbidity and mortality. Proper management of these infections requires appropriate antibiotic selection based on culture and antimicrobial susceptibility testing. Early diagnosis of microbial infections is aimed to institute the appropriate antibacterial therapy initiative to avoid further complications. A total of 200 Type 2 Diabetic Mellitus patients with infection were admitted at GD Hospital and Diabetes Institute, Kolkata. 60 of them who developed ulcer during the year 2013 were included in this study. A detailed clinical history and physical examination were carried out for every subject. Specimens for microbiological studies were obtained from ulcer region. Gram-negative bacilli were tested for extended spectrum Beta-lactamase (ESBL) production by double disc diffusion method. Staphylococcal isolates were tested for susceptibility to oxacillin by screen agar method and disc diffusion. Potential risk factors for MDRO-positive samples were explored. Gram-negative aerobes were most frequently isolated, followed by gram-positive aerobes. Males were predominant in the study and majority of the patients were in the age group of 41-60 years. The presence of neuropathy was observed in 80% cases followed by peripheral vascular disease (73%). Proteus spp. (22) was the most common pathogen isolated, followed by E.coli (17). Staphylococcus aureus was predominant amongst the gram-positive isolates. S.aureus showed a high rate of resistance to antibiotic tested (63.6%). Other gram-positive isolates were found to be highly resistant to erythromycin, tetracycline and ciprofloxacin, 40% each. All isolates were found to be sensitive to Vancomycin and Linezolid. ESBL production was noted in Proteus spp and E.coli. Approximately 70 % of the patients were positive for MDRO. MDRO-infected patients had poor glycemic control (HbA1c 11± 2). Infection with MDROs is common in diabetic foot ulcers and is associated with risk factors like inadequate glycemic control, the presence of neuropathy, osteomyelitis, ulcer size and increased the requirement for surgical treatment. There is a need for continuous surveillance of resistant bacteria to provide the basis for empirical therapy and reduce the risk of complications.

Keywords: diabetic foot ulcer, bacterial infection, multidrug-resistant organism, extended spectrum beta-lactamase

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45 Analgesic Efficacy of IPACK Block in Primary Total Knee Arthroplasty (90 CASES)

Authors: Fedili Benamar, Beloulou Mohamed Lamine, Ouahes Hassane, Ghattas Samir

Abstract:

 Background and aims: Peripheral regional anesthesia has been integrated into most analgesia protocols for total knee arthroplasty which considered among the most painful surgeries with a huge potential for chronicization. The adductor canal block (ACB) has gained popularity. Similarly, the IPACK block has been described to provide analgesia of the posterior knee capsule. This study aimed to evaluate the analgesic efficacy of this block in patients undergoing primary PTG. Methods: 90 patients were randomized to receive either an IPACK, an anterior sciatic block, or a sham block (30 patients in each group + multimodal analgesia and a catheter in the KCA adductor canal). GROUP 1 KCA GROUP 2 KCA+BSA GROUP 3 KCA+IPACK The analgesic blocks were done under echo-guidance preoperatively respecting the safety rules, the dose administered was 20 cc of ropivacaine 0.25% was used. We were to assess posterior knee pain 6 hours after surgery. Other endpoints included quality of recovery after surgery, pain scores, opioid requirements (PCA morphine)(EPI info 7.2 analysis). Results: -groups were matched -A predominance of women (4F/1H). -average age: 68 +/-7 years -the average BMI =31.75 kg/m2 +/- 4. -70% of patients ASA2 ,20% ASA3. -The average duration of the intervention: 89 +/- 19 minutes. -Morphine consumption (PCA) significantly higher in group 1 (16mg) & group 2 (8mg) group 3 (4mg) - The groups were matched . -There was a correlation between the use of the ipack block and postoperative pain Conclusions :In a multimodal analgesic protocol, the addition of IPACK block decreased pain scores and morphine consumption ,

Keywords: regional anesthesia, analgesia, total knee arthroplasty, the adductor canal block (acb), the ipack block, pain

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44 A Dynamic Model for Assessing the Advanced Glycation End Product Formation in Diabetes

Authors: Victor Arokia Doss, Kuberapandian Dharaniyambigai, K. Julia Rose Mary

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Advanced Glycation End (AGE) products are the end products due to the reaction between excess reducing sugar present in diabetes and free amino group in protein lipids and nucleic acids. Thus, non-enzymic glycation of molecules such as hemoglobin, collagen, and other structurally and functionally important proteins add to the pathogenic complications such as diabetic retinopathy, neuropathy, nephropathy, vascular changes, atherosclerosis, Alzheimer's disease, rheumatoid arthritis, and chronic heart failure. The most common non-cross linking AGE, carboxymethyl lysine (CML) is formed by the oxidative breakdown of fructosyllysine, which is a product of glucose and lysine. CML is formed in a wide variety of tissues and is an index to assess the extent of glycoxidative damage. Thus we have constructed a mathematical and computational model that predicts the effect of temperature differences in vivo, on the formation of CML, which is now being considered as an important intracellular milieu. This hybrid model that had been tested for its parameter fitting and its sensitivity with available experimental data paves the way for designing novel laboratory experiments that would throw more light on the pathological formation of AGE adducts and in the pathophysiology of diabetic complications.

Keywords: advanced glycation end-products, CML, mathematical model, computational model

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43 CMT4G: Rare Form of Charcot-Marie-Tooth Disease in Slovak Roma Patient

Authors: Dana Gabriková, Martin Mistrík, Jarmila Bernasovská, Iveta Tóthová, Jana Kisková

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The Roma (Gypsies) is a transnational minority with a high degree of consanguineous marriages. Similar to other genetically isolated founder populations, the Roma harbor a number of unique or rare genetic disorders. This paper discusses about a rare form of Charcot-Marie-Tooth disease – type 4G (CMT4G), also called Hereditary Motor and Sensory Neuropathy type Russe, an autosomal recessive disease caused by mutation private to Roma characterized by abnormally increased density of non-myelinated axons. CMT4G was originally found in Bulgarian Roma and in 2009 two putative causative mutations in the HK1 gene were identified. Since then, several cases were reported in Roma families mainly from Bulgaria and Spain. Here we present a Slovak Roma family in which CMT4G was diagnosed on the basis of clinical examination and genetic testing. This case is a further proof of the role of the HK1 gene in pathogenesis of the disease. It confirms that mutation in the HK1 gene is a common cause of autosomal recessive CMT disease in Roma and should be considered as a common part of a diagnostic procedure.

Keywords: gypsies, HK1, HSMN-Russe, rare disease

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42 Injection of Bradykinin in Femoral Artery Elicits Cardiorespiratory Reflexes Involving Perivascular Afferents in Rat Models

Authors: Sanjeev K. Singh, Maloy B. Mandal, Revand R.

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The physiology of baroreceptors and chemoreceptors present in large blood vessels of the heart is well known in regulation of cardiorespiratory functions. Since large blood vessels and peripheral blood vessels are of same mesodermal origin, therefore, involvement of the latter in regulation of cardiorespiratory system is expected. Role of perivascular nerves in mediating cardiorespiratory alterations produced after intra-arterial injection of a nociceptive agent (bradykinin) was examined in urethane anesthetized male rats. Respiratory frequency, blood pressure, and heart rate were recorded for 30 min after the retrograde injection of bradykinin/saline in the femoral artery. In addition, paw edema was determined and water content was expressed as percentage of wet weight. Injection of bradykinin produced immediate tachypnoeic, hypotensive and bradycardiac responses of shorter latency (5-8 s) favoring the neural mechanisms involved in it. Injection of equi-volume of saline did not produce any responses and served as time matched control. Paw edema was observed in the ipsilateral hind limb. Pretreatment with diclofenac sodium significantly attenuated the bradykinin-induced responses and also blocked the paw edema. Ipsilateral femoral and sciatic nerve sectioning attenuated bradykinin-induced responses significantly indicating the origin of responses from the local vascular bed. Administration of bradykinin in the segment of an artery produced reflex cardiorespiratory changes by stimulating the perivascular nociceptors involving prostaglandins. This is a novel study exhibiting the role of peripheral blood vessels in regulation of cardiorespiratory system.

Keywords: vasosensory reflex, cardiorespiratory changes, nociceptive agent, bradykinin, VR1 receptors

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41 Ophthalmic Hashing Based Supervision of Glaucoma and Corneal Disorders Imposed on Deep Graphical Model

Authors: P. S. Jagadeesh Kumar, Yang Yung, Mingmin Pan, Xianpei Li, Wenli Hu

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Glaucoma is impelled by optic nerve mutilation habitually represented as cupping and visual field injury frequently with an arcuate pattern of mid-peripheral loss, subordinate to retinal ganglion cell damage and death. Glaucoma is the second foremost cause of blindness and the chief cause of permanent blindness worldwide. Consequently, all-embracing study into the analysis and empathy of glaucoma is happening to escort deep learning based neural network intrusions to deliberate this substantial optic neuropathy. This paper advances an ophthalmic hashing based supervision of glaucoma and corneal disorders preeminent on deep graphical model. Ophthalmic hashing is a newly proposed method extending the efficacy of visual hash-coding to predict glaucoma corneal disorder matching, which is the faster than the existing methods. Deep graphical model is proficient of learning interior explications of corneal disorders in satisfactory time to solve hard combinatoric incongruities using deep Boltzmann machines.

Keywords: corneal disorders, deep Boltzmann machines, deep graphical model, glaucoma, neural networks, ophthalmic hashing

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40 Support Vector Machine Based Retinal Therapeutic for Glaucoma Using Machine Learning Algorithm

Authors: P. S. Jagadeesh Kumar, Mingmin Pan, Yang Yung, Tracy Lin Huan

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Glaucoma is a group of visual maladies represented by the scheduled optic nerve neuropathy; means to the increasing dwindling in vision ground, resulting in loss of sight. In this paper, a novel support vector machine based retinal therapeutic for glaucoma using machine learning algorithm is conservative. The algorithm has fitting pragmatism; subsequently sustained on correlation clustering mode, it visualizes perfect computations in the multi-dimensional space. Support vector clustering turns out to be comparable to the scale-space advance that investigates the cluster organization by means of a kernel density estimation of the likelihood distribution, where cluster midpoints are idiosyncratic by the neighborhood maxima of the concreteness. The predicted planning has 91% attainment rate on data set deterrent on a consolidation of 500 realistic images of resolute and glaucoma retina; therefore, the computational benefit of depending on the cluster overlapping system pedestal on machine learning algorithm has complete performance in glaucoma therapeutic.

Keywords: machine learning algorithm, correlation clustering mode, cluster overlapping system, glaucoma, kernel density estimation, retinal therapeutic

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39 Heart Rate Variability Responses Pre-, during, and Post-Exercise among Special Olympics Athletes

Authors: Kearney Dover, Viviene Temple, Lynneth Stuart-Hill

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Heart Rate Variability (HRV) is the beat-to-beat variation in adjacent heartbeats. HRV is a non-invasive measure of the autonomic nervous system (ANS) and provides information about the sympathetic (SNS) and parasympathetic (PNS) nervous systems. The HRV of a well-conditioned heart is generally high at rest, whereas low HRV has been associated with adverse outcomes/conditions, including congestive heart failure, diabetic neuropathy, depression, and hospital admissions. HRV has received very little research attention among individuals with intellectual disabilities in general or Special Olympic athletes. Purpose: 1) Having a longer post-exercise rest and recovery time to establish how long it takes for the athletes’ HRV components to return to pre-exercise levels, 2) To determine if greater familiarization with the testing processes influences HRV. Participants: Two separate samples of 10 adult Special Olympics athletes will be recruited for 2 separate studies. Athletes will be between 18 and 50 years of age and will be members of Special Olympics BC. Anticipated Findings: To answer why the Special Olympics athletes display poor cardiac responsiveness to changes in autonomic modulation during exercise. By testing the cortisol levels in the athletes, we can determine their stress levels which will then explain their measured HRV.

Keywords: 6MWT, autonomic modulation, cortisol levels, intellectual disability

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38 A Study of Ocular Morbidity in Road Traffic Accidents

Authors: Nikhat Iqbal Tamboli

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INTRODUCTION: road traffic accidents (RTAs) are one of the leading and common causes of ocular injuries especially in developing countries like India which are preventable with certain measures and so it is of public health importance. AIM: To study incidence and clinical presentation of ocular morbidity in road traffic accidents. METHOD: Prospective cross-sectional study was conducted on 360 patients reported in department of ophthalmology. Detailed ocular examination and relevant investigations done. RESULTS: Incidence of ocular injuries is 23%. male:female ratio is 4.5:1.Cases having Sub conjunctival haemorrhage [74].eccymosis[217]. lid lcerations [164]orbital fracture[12] corneal tear [7]corneal abrasion[2] sclera tear[6] hyphaema[4] traumatic mydriasis [7]traumatic cataract [2]vitreous haemorrhage [1]traumatic optic neuropathy[1].Maximum cases in age group 20-40 years, with two wheeler vehicles 94.7% .Under influence of alcohol 13.3%. CONCLUSION: Younger age group with male preponderance is involved in ocular trauma due to road traffic accidents .maximum cases reported are with anterior segment injuries. Alcohol and two wheeler vehicles are common risk factors. Injuries involving cornea had bad prognosis and involving retina had worst prognosis.

Keywords: ocular morbidity, eye trauma, RTA, eye injury

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37 The Biomechanical Analysis of Pelvic Osteotomies Applied for Developmental Dysplasia of the Hip Treatment in Pediatric Patients

Authors: Suvorov Vasyl, Filipchuk Viktor

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Developmental Dysplasia of the Hip (DDH) is a frequent pathology in pediatric orthopedist’s practice. Neglected or residual cases of DDH in walking patients are usually treated using pelvic osteotomies. Plastic changes take place in hinge points due to acetabulum reorientation during surgery. Classically described hinge points and a traditional division of pelvic osteotomies on reshaping and reorientation are currently debated. The purpose of this article was to evaluate biomechanical changes during the most commonly used pelvic osteotomies (Salter, Dega, Pemberton) for DDH treatment in pediatric patients. Methods: virtual pelvic models of 2- and 6-years old patients were created, material properties were assigned, pelvic osteotomies were simulated and biomechanical changes were evaluated using finite element analysis (FEA). Results: it was revealed that the patient's age has an impact on pelvic bones and cartilages density (in younger patients the pelvic elements are more pliable - p<0.05). Stress distribution after each of the abovementioned pelvic osteotomy was assessed in 2- and 6-years old patients’ pelvic models; hinge points were evaluated. The new term "restriction point" was introduced, which means a place where restriction of acetabular deformity correction occurs. Pelvic ligaments attachment points were mainly these restriction points. Conclusions: it was found out that there are no purely reshaping and reorientation pelvic osteotomies as previously believed; the pelvic ring acts as a unit in carrying out the applied load. Biomechanical overload of triradiate cartilage during Salter osteotomy in 2-years old patient and in 2- and 6-years old patients during Pemberton osteotomy was revealed; overload of the posterior cortical layer in the greater sciatic notch in 2-years old patient during Dega osteotomy was revealed. Level of Evidence – Level IV, prognostic.

Keywords: developmental dysplasia of the hip, pelvic osteotomy, finite element analysis, hinge point, biomechanics

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36 Influence of HbA1c on Nitric Oxide Level in Patients with Type 2 Diabetes Mellitus

Authors: Dara Kutsyk, Olga Bondarenko, Mariya Sorochka

Abstract:

In 21-century type 2 diabetes (T2D) has become a global health and social problem in the whole world. The goal of treatment for patients with T2D is to prevent complications of diabetes - macrovascular diseases (heart disease, stroke, and peripheral vascular disease) and microvascular diseases (retinopathy, neuropathy and nephropathy). Nitric oxide (NO) plays an important role in maintaining vascular homeostasis. Loss of NO function is one of the earliest indicators of disease and its progression especially in patients with T2D. Aim: To compare NO level between patients with well and bad controlled glycemia in T2D. Methods: The study included 32 patients with T2D. The diagnosis of T2D was confirmed due to International Diabetes Federation (IDF) criteria 2015. Patients were divided into two groups: with well controlled glycaemia (HbA1c < 7%) and bad controlled glycaemia (HbA1c > 7%). The control group consists of 15 healthy subjects. Results: NO level in patients with T2D is significantly higher (27,2 ±3,1 µmol), compared to controls (18,86±0,9 µmol; p < 0,001). A significant difference in NO level was found between patients with bad controlled glycaemia (25,9±2,2 µmol) and well controlled glycaemia (28,7 ± 3,0 µmol; p<0,01). The study showed a moderate negative correlation between NO level and HbA1c (-0,399; р< 0,05). Conclusions: Production of NO is impaired in patients with T2D, especially with badly controlled glycaemia. With the increase in HbAc serum NO decreases. This can be the main target for prevention vascular complication in T2D.

Keywords: type 2 diabetes, glycated hemoglobin, nitric oxide, Diabetes mellitus

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35 Evaluation of the Effectiveness of the Argon Plasma Jet on Healing Process of the Wagner Grade 2 Diabetic Foot Ulcer

Authors: M. Khaledi Pour, P. Akbartehrani, M. Amini, M. Khani, M. Mohajeri Tehrani, R. Radi, B. Shokri

Abstract:

Diabetic Foot Ulcer (DFU) is one of the costly severe complications of diabetes. Neuropathy and Peripheral Arterial Disease (PAD) due to diabetes are significant causes of this complication. In 10 years the patients with DFUs are twice as likely to die as patients without DFUs. Cold Atmospheric Plasma (CAP) is a promising tool for medical purposes. CAP generate reactive species at room temperature and are effective in killing bacteria and fibroblast proliferation. These CAP-based tools produce NO, which has bactericidal and angiogenesis properties. It also showed promising effects in the DFUs surface reduction and the time to wound closure. In this paper, we evaluated the effect of the Argon Plasma Jet (APJ) on the healing process of the Wagner Grade 2 DFUs in a randomized clinical trial. The 20 kHz sinusoidal voltage frequency derives the APJ. Patients (n=20) were randomly double-blinded assigned into two groups. These groups receive the standard care (SC, n=10) and the standard care with APJ treatment (SC+APJ, n=10) for five sessions in four weeks. The results showed that the APJ treatment along standard care could reduce the wound surface by 20 percent more than the standard care. Also, It showed a more influential role in controlling wound infection.

Keywords: argon plasma jet, cold atmospheric plasma, diabetes, diabetic foot ulcer

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34 Association of AGT (M268T) Gene Polymorphism in Diabetes and Nephropathy in Pakistan

Authors: Syed M. Shahid, Rozeena Shaikh, Syeda N. Nawab, Abid Azhar

Abstract:

Diabetes mellitus (DM) is a prevalent non-communicable disease worldwide. DM may lead to many vascular complications like hypertension, nephropathy, retinopathy, neuropathy and foot infections. Pathogenesis of diabetic nephropathy (DN) is implicated by the polymorphisms in genes encoding the specific components of renin angiotensin aldosterone system (RAAS) which include angiotensinogen (AGT), angiotensin-II receptor and angiotensin converting enzyme (ACE) genes. This study was designed to explore the possible association of AG (M268T) polymorphism in the patients of diabetes and nephropathy in Pakistan. Study subjects included 100 controls, 260 diabetic patients without renal insufficiency and 190 diabetic nephropathy patients with persistent albuminuria. Fasting blood samples were collected from all the subjects after getting institutional ethical approval and informed consent. The biochemical estimations, PCR amplification and direct sequencing for the specific region of AGT gene was carried out. A significantly high frequency of TT genotype and T allele of AGT (M268T) was observed in the patients of diabetes with nephropathy as compared to controls and diabetic patients without any known renal impairment. The TT genotype and T allele of AGT (M268T) polymorphism may be considered as a genetic risk factor for the development and progression of nephropathy in diabetes. Further cross sectional population studies would be of help to establish and confirm the observed possible association of AGT gene variations with development of nephropathy in diabetes.

Keywords: RAAS, AGT (M268T), diabetes, nephropathy

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33 Morphological and Molecular Abnormalities of the Skeletal Muscle Tissue from Pediatric Patient Affected by a Rare Genetic Chaperonopathy Associated with Motor Neuropathy

Authors: Leila Noori, Rosario Barone, Francesca Rappa, Antonella Marino Gammazza, Alessandra Maria Vitale, Giuseppe Donato Mangano, Giusy Sentiero, Filippo Macaluso, Kathryn H. Myburgh, Francesco Cappello, Federica Scalia

Abstract:

The neuromuscular system controls, directs, and allows movement of the body through the action of neural circuits, which include motor neurons, sensory neurons, and skeletal muscle fibers. Protein homeostasis of the involved cytotypes appears crucial to maintain the correct and prolonged functions of the neuromuscular system, and both neuronal cells and skeletal muscle fibers express significant quantities of protein chaperones, the molecular machinery responsible to maintain the protein turnover. Genetic mutations or defective post-translational modifications of molecular chaperones (i.e., genetic or acquired chaperonopathies) may lead to neuromuscular disorders called as neurochaperonopathies. The limited knowledge of the effects of the defective chaperones on skeletal muscle fibers and neurons impedes the progression of therapeutic approaches. A distinct genetic variation of CCT5 gene encoding for the subunit 5 of the chaperonin CCT (Chaperonin Containing TCP1; also known as TRiC, TCP1 Ring Complex) was recently described associated with severe distal motor neuropathy by our team. In this study, we investigated the histopathological abnormalities of the skeletal muscle biopsy of the pediatric patient affected by the mutation Leu224Val in the CCT5 subunit. We provide molecular and structural features of the diseased skeletal muscle tissue that we believe may be useful to identify undiagnosed cases of this rare genetic disorder. We investigated the histological abnormalities of the affected tissue via hematoxylin and eosin staining. Then we used immunofluorescence and qPCR techniques to explore the expression and distribution of CCT5 in diseased and healthy skeletal muscle tissue. Immunofluorescence and immunohistochemistry assays were performed to study the sarcomeric and structural proteins of skeletal muscle, including actin, myosin, tubulin, troponin-T, telethonin, and titin. We performed Western blot to examine the protein expression of CCT5 and some heat shock proteins, Hsp90, Hsp60, Hsp27, and α-B crystallin, along with the main client proteins of the CCT5, actin, and tubulin. Our findings revealed muscular atrophy, abnormal morphology, and different sizes of muscle fibers in affected tissue. The swollen nuclei and wide interfiber spaces were seen. Expression of CCT5 had been decreased and showed a different distribution pattern in the affected tissue. Altered expression, distribution, and bandage pattern were detected by confocal microscopy for the interested muscular proteins in tissue from the patient compared to the healthy control. Protein levels of the studied Hsps normally located at the Z-disk were reduced. Western blot results showed increased levels of the actin and tubulin proteins in the diseased skeletal muscle biopsy compared to healthy tissue. Chaperones must be expressed at high levels in skeletal muscle to counteract various stressors such as mechanical, oxidative, and thermal crises; therefore, it seems relevant that defects of molecular chaperones may result in damaged skeletal muscle fibers. So far, several chaperones or cochaperones involved in neuromuscular disorders have been defined. Our study shows that alteration of the CCT5 subunit is associated with the damaged structure of skeletal muscle fibers and alterations of chaperone system components and paves the way to explore possible alternative substrates of chaperonin CCT. However, further studies are underway to investigate the CCT mechanisms of action to design applicable therapeutic strategies.

Keywords: molecular chaperones, neurochaperonopathy, neuromuscular system, protein homeostasis

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32 Caring for a Spinal Cord Injury Patient with Diabetic Nephropathy Receiving Hospice Palliative Care

Authors: Li-Ting Kung, Hui-Zhu Chen, Hsin-Tzu Lee, Wan-Yin Hsu

Abstract:

Patients with spinal cord injury combined with diabetic nephropathy may under a lot of painful conditions due to complications related to the illness itself or treatments, such as recurrent pressure ulcers, autonomic and peripheral neuropathy, as well as dialysis, for long term. This case report illustrated the nursing experience of transferring a spine cord injure patient who received hemodialysis due to adverse lifestyle-induced diabetic nephropathy to the hospice ward. Nursing care was provided in this patient from July 25th to August 30th, 2015. The tool of 'Gordon’s 11-item functional health assessment' and clinical observation, interviews as well as physical examination were used as data collections. Based on results of health assessment as above, the patient’s health problems were identified as the following: impaired skin integrity, chronic pain, and hopeless. Besides to relieve the symptom of pain due to disease or the treatment of hemodialysis and provide wound care, the first author also played a role to assist the patient to achieve his goal of receiving the hospice palliative care. Finally, with much effort of nurses to communicate with medical teams between the surgical and hospice wards, the patient was transferred to the hospice ward to have fulfilled his last wish of having a good death. We hope this nursing experience can be applied to other similar cases in the future.

Keywords: diabetic nephropathy, hospice care, palliative care, spinal cord injury

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31 Peripheral Nerves Cross-Sectional Area for the Diagnosis of Diabetic Polyneuropathy: A Meta-Analysis of Ultrasonographic Measurements

Authors: Saeed Pourhassan, Nastaran Maghbouli

Abstract:

1) Background It has been hypothesized that, in individuals with diabetes mellitus, the peripheral nerve is swollen due to sorbitol over-accumulation. Additionally growing evidence supported electro diagnostic study of diabetes induced neuropathy as a method having some challenges. 2) Objective To examine the performance of sonographic cross-sectional area (CSA) measurements in the diagnosis of diabetic polyneuropathy (DPN). 3) Data Sources Electronic databases, comprising PubMed and EMBASE and Google scholar, were searched for the appropriate studies before Jan 1, 2020. 4) Study Selection Eleven trials comparing different peripheral nerve CSA measurements between participants with and without DPN were included. 5) Data Extraction Study design, participants' demographic characteristics, diagnostic reference of DPN, and evaluated peripheral nerves and methods of CSA measurement. 6) Data Synthesis Among different peripheral nerves, Tibial nerve diagnostic odds ratios pooled from five studies (713 participants) were 4.46 (95% CI, 0.35–8.57) and the largest one with P<0.0001, I²:64%. Median nerve CSA at wrist and mid-arm took second and third place with ORs= 2.82 (1.50-4.15), 2.02(0.26-3.77) respectively. The sensitivities and specificities pooled from two studies for Sural nerve were 0.78 (95% CI, 0.68–0.89), and 0.68 (95% CI, 0.53–0.74). Included studies for other nerves were limited to one study. The largest sensitivity was for Sural nerve and the largest specificity was for Tibial nerve. 7) Conclusions The peripheral nerves CSA measured by ultrasound imaging is useful for the diagnosis of DPN and is most significantly different between patients and participants without DPN at the Tibial nerve. Because the Tibial nerve CSA in healthy participants, at various locations, rarely exceeds 24 mm2, this value can be considered as a cutoff point for diagnosing DPN.

Keywords: diabetes, diagnosis, polyneuropathy, ultrasound

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30 Neo-Adjuvant B-CAT Chemotherapy in Triple Negative Breast Cancer

Authors: Muneeb Nasir, Misbah Masood, Farrukh Rashid, Abubabakar Shahid

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Introduction: Neo-adjuvant chemotherapy is a potent option for triple negative breast cancer (TNBC) as these tumours lack a clearly defined therapeutic target. Several recent studies lend support that pathological complete remission (pCR) is associated with improved disease free survival (DFS) and overall survival (OS) and could be used as surrogate marker for DFS and OS in breast cancer patients. Methods: We have used a four-drug protocol in T3 and T4 TNBC patients either N+ or N- in the neo-adjuvant setting. The 15 patients enrolled in this study had a median age of 45 years. 12 patients went on to complete four planned cycles of B-CAT protocol. The chemotherapy regimen included inj. Bevacizumab 5mg/kg D1, inj. Adriamycin 50mg/m2 D1 and Docetaxel 65mg/m2 on D1. Inj. Cisplatin 60mg/m2 on D2. All patients received GCF support from D4 to D9 of each cycle. Results: Radiological assessment using ultrasound and PET-CT revealed a high percentage of responses. Radiological CR was documented in half of the patients (6/12) after four cycles. Remaining patients went on to receive 2 more cycles before undergoing radical surgery. pCR was documented in 7/12 patients and 3 more had a good partial response. The regimen was toxic and grade ¾ neutropenia was seen in 58% of patients. Four episodes of febrile neutropenia were reported and managed. Non-hematatological toxicities were common with mucositis, diarrhea, asthenia and neuropathy topping the list. Conclusion: B-CAT is a very active combination with very high pCR rates in TNBC. Toxicities though frequent, were manageable on outpatient basis. This protocol warrants further investigation.

Keywords: B-CAT:bevacizumab, cisplatin, adriamycin, taxotere, CR: complete response, pCR: pathological complete response, TNBC: triple negative breast cancer

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29 Mesenteric Vasculitis Causing Perforated Diverticulitis Mimicking Abdominal Sepsis

Authors: Christopher Leung, Assad Zahid

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Mesenteric vasculitis can often mimic abdominal sepsis in a postoperative setting leading to a predicament where steroids could improve mesenteric vasculitis whilst worsening abdominal sepsis. Here this study presents a unique and rare case of perforated sigmoid diverticulitis secondary to systemic vasculitis. A 68-year-old gentleman presented with perforated sigmoid diverticulitis requiring an emergency Hartmann’s procedure. Early in his postoperative course, he had painful and asymmetrical neuropathy that, after a careful history and examination, revealed a patient with mono neuritis multiplex on a background history of longstanding rheumatoid arthritis. On day seven of his postoperative course, he had rising inflammatory markers and a CT abdomen and pelvis showing fluid around the mesentery. Whilst contamination from sigmoid perforation was somewhat congruent with these signs, a diagnosis of polyarteritis nodosa, a common cause of mononeuritis multiplex, is also possible, although involvement of the large bowel in polyarteritis nodosa is extremely rare. The histopathology from the initial Hartmann’s procedure was re-examined, showing medium vessel disease vasculitis. Given his lack of fevers, absence of abdominal pain, and worsening neurology, he was given a provisional diagnosis of polyarteritis nodosa and was treated successfully, not on IV antibiotics but on steroids. Large bowel involvement of polyarteritis nodosa is extremely rare and this is the first case of polyarteritis nodosa causing perforated diverticulitis. The learning point here is to obtain a good clinical picture of a patient to identify mesenteric vasculitis as compared to abdominal sepsis as the treatment of one worsens the other.

Keywords: abdominal sepsis, diverticulitis, mesenteric vasculitis, polyarteritis nodosa

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28 Addressing Ophthalmic and Vascular Diabetic Complications in South Asians

Authors: Haaris Khan, Farhad Udwadia

Abstract:

South Asians are the fastest-growing immigrant population in Canada and are 3-4 times more likely to develop diabetes. In a primary care setting, language barriers continue to persist as a prominent obstacle when delivering crucial health information. Given the abundance of languages in the South Asian community and the varying levels of English fluency, there is compelling evidence that these language barriers can adversely impact health outcomes. The microvascular and macrovascular complications of poor diabetic management are well established and universally recognized. However, these are often difficult concepts to grasp for even individuals fluent in English. In order to lessen the burden of language barriers, we developed a comprehensive guide in various languages that discuss the complications and screening guidelines for diabetic and prediabetic patients. The guide is presented in the form of a pamphlet, with an electronic version being constructed as well, that provides basic information on diabetic retinopathy, neuropathy and nephropathy as well as the screening recommendations. We also conducted a review of the literature around the topic and incorporated our findings into our project. Our goal is for primary care physicians to have this resource and to be able to provide the link or pamphlet to patients in need. Our presentation also provides a comprehensive overview of some of the other barriers that individuals in the South Asian community face when seeking care. Given the staggering number of individuals in the South Asian community with diabetes and the morbidity and mortality associated with diabetes and its complications, effective community-specific strategies are needed to mitigate the potential consequences of poor diabetes management.

Keywords: diabetes, patient education, ophthalmology, vascular surgery

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27 Angiotensin Converting Enzyme (ACE) and Angiotensinogen (AGT) Gene Variants in Pakistani Patients of Diabetes Mellitus and Diabetic Nephropathy

Authors: Rozeena Shaikh, Syed M Shahid, Jamil Ahmad, Qaisar Mansoor, Muhammad Ismail, Abid Azhar

Abstract:

Introduction: Diabetes mellitus (DM) is a prevalent non-communicable disease worldwide. In most high-income countries as well as middle-income and low- income countries. DM is among the top causes of deaths. DM may lead to many vascular complications like hypertension, nephropathy, retinopathy, neuropathy, and foot. Diabetic nephropathy (DN) characterized by persistent albuminuria is a leading cause of end stage renal failure (ESRF). Pathogenesis of diabetic nephropathy is implicated by the polymorphisms in genes encoding the components of reninangiotensin- aldosteron system (RAAS) which include angiotensinogen (AGT), angiotensin-II receptor and particularly angiotensin converting enzyme (ACE) gene. Method: Study subjects include 110 control, 110 patients with DM without hypertension, 110 patients with DM with hypertension and 110 patients with DN. Blood samples were collected for Biochemical analysis and PCR and sequencing for the specific region of both genes. Results: The frequency of DD genotype and D allele of ACE (I/D) was significantly (p<0.05) high in DM normotensive, DM hypertensive and DN patients when compared to control. The ACE G2350A genotypes and allele frequencies were significantly different (p<0.05) in DM hypertensive patients as compared to control and DN, while no difference was observed between DM normotensive and DN when compared to control. The genotypes and alleles of AGT (M268T) polymorphism were significantly different (p<0.05) in DM normotensive, DM hypertensive and DN when compared to control. Conclusion: The DD genotype and D allele of ACE (I/D), GG genotype and G allele of ACE (G2350A) and the TT genotype and T allele of AGT (M268T) polymorphism have shown a significant difference in genotype and allele frequencies between controls and patients.

Keywords: genetic variations, ACE, AGT, diabetes mellitus, diabetic nephropathy, Pakistan

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26 Light and Electron Study of Acrylamide–Induced Hypothalamic Changes

Authors: Keivan Jamshidi

Abstract:

Distal swelling and eventual degeneration of axon in the CNS and PNS have been considered to be the characteristic neuropathological effects of acrylamide (ACR) neuropathy. This study was conducted to determine the neurotoxic effects of different doses of ACR (0.5, 5, 50, 100, and 500 mg/kg per day × 11days i. p.) on hypothalamus of rat using the de Olmos amino cupric-silver stain and electron microscopy. For this purpose 60 adult male rats (Wistar, approximately 250 g) were randomly assigned in 5 treatment groups as A, B, C, D, E) exposed to 0.5, 5, 50, 100, and 500 mg/kg per dayx11days i. p. and one control group as F received daily i. p. injections of 0.9% saline (3ml/kg). As indices of developing neurotoxicity, weight gain, gait scores and landing hindlimb foot splay were determined. After 11 days, two rats for silver stain, and two rats for EM were randomly selected; dissected and proper samples were collected from hypothalamus. Results did show no neurological behavior in groups A, B and F were observed in group C. Rats in groups D and E died within 1-2 hours due to sever toxemia. In histopathological studies based on de Olmos technique no argyrophilic neurons or processes were observed in stained sections obtained from hypothalamus of rats belong to groups A, B, and F while moderate to severe argyrophilic changes were observed in different nuclei and regions of stained sections obtained from hypothalamus of rats belong to group C. In ultra-structural studies some variations in the myelin sheet of injured axons including decompactation, interlaminar space formation, disruption of the laminar sheet, accumulation of neurofilaments, vacculation, and clumping inside the axolem, and finally complete disappearance of laminar sheet were observed.

Keywords: acrylamide, hypothalamus, rat, de Olmos amino cupric, silver stain, electron microscopy

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