Search results for: renal ischemia-reperfusion injury

Authors: Janki Shankar, Shu-Ping Chen

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This Canadian study explored the perspectives of recent immigrant workers regarding occupational health and safety (OHS) and workplace conditions that increase workers’ vulnerability to sustaining injury or illness. Using an interpretive research approach and semi structured qualitative interviews, 42 recent immigrant workers from a range of industries operating in two cities in a province in Canada were interviewed. A constant comparative approach was used to identify key themes across the workers’ experiences. The findings revealed that these workers have an incomplete understanding of OHS. In many workplaces, poor job training, little worker support, lack of power in the workplace, and a poor workplace safety culture make it difficult for recent immigrant workers to acquire OHS information and implement safe work practices. This study proposes workplace policies and practices that will improve worker OHS awareness and make workplaces safer for immigrant workers.

Keywords: new immigrant workers, occupational health and safety, workplace challenges, policy, practice

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Authors: Nitesh Kumar, Eoin Twohig, jasparl cheema, Sadiq mawji, Yousif al najjar

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Basal cell carcinoma (BCC) is the commonest cutaneous malignancy affecting humans. Despite this, distant spread is exceptionally rare. Metastatic BCC (mBCC) is estimated to occur in 0.0028 - 0.5%. it aim to illustrate with the aid of histological slides, a case of mBCC occurring in a fit and well 67-year-old. Initial diagnosis of desmoplastic BCC was made in 2006 from a scalp biopsy with the lesion then being excised. Re-excision of local recurrence was undertaken the following year. In 2014 the patient presented with an ipsilateral level 2a mass. Fine Needle Aspiration raised the suspicion of metastatic carcinoma. The patient had excision of two nodes from the left neck alongside pharyngeal tonsillectomy and tongue base biopsies. Histologically, the nodes closely resembled the immunophenotype of the initial scalp lesion. The patient subsequently had a modified radical neck dissection, and residual mBCC was excised from the left Sternocleidomastoid muscle. In 2023 the patient developed haematuria. On further investigation bilateral lung lesions on CT were noted with subsequent biopsy confirming mBCC. Spinal and renal lesions have also been found. Histopathology showed clear resemblance of the lung metastases to both those in the neck and the primary (scalp BCC) – with no squamous differentiation seen. The time span from primary to occurrence of lung metastasis (18 years) affirms the indolent and slow growing nature of BCC.  This case fulfils Lattes and Kessler diagnostic criteria. High risk cases are described as those with advanced local presentation, primary tumour on the Head and Neck and locally recurrent lesions.

Keywords: BCC, metastasis, rare, skin cancer

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Authors: Bouaziz H., Soudania N., Essafia M., Ben Amara I., Hakim A., Jamoussi K., Zeghal Km, Zeghal N.

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In this investigation, we have evaluated the effects of arsenic trioxide on hepatic function in pregnant and lactating Swiss albino mice and their suckling pups. Experiments were carried out on female mice given 175 ppm As2O3 in their drinking water from the 14th day of pregnancy until day 14 after delivery. Our results showed a significant decrease in plasma levels of total protein and albumin, cholesterol and triglyceride in As2O3 treated mice and their pups. The hyperbilirubinemia and the increased plasma total alkaline phosphatase activity suggested the presence of cholestasis. Transaminase activities as well as lactate deshydrogenase activity in plasma, known as biomarkers of hepatocellular injury, were elevated indicating hepatic cells’damage after treatment with As2O3. Exposure to arsenic led to an increase of liver thiobarbituric acid reactive substances level along with a concomitant decrease in the activities of superoxide dismutase, catalase and glutathione peroxidase and in glutathione.

Keywords: antioxidant status, arsenic trioxide, hepatotoxicity, mice, oxidative stress

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Authors: Bajraktarevic Adnan, Djukic Branka, Sporisevic Lutvo, Krdzalic Zecevic Belma, Uzicanin Sajra, Hadzimuratovic Admir, Hadzimuratovic Hadzipasic Emina, Abduzaimovic Alisa, Kustric Amer, Suljevic Ismet, Serafi Ismail, Tahmiscija Indira, Khatib Hakam, Semic Jusufagic Aida, Haas Helmut, Vladicic Aleksandra, Aplenc Richard, Kadic Deovic Aida

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Introduction: Joubert syndrome has an autosomal recessive pattern of inheritance. It is referred as the brain malfunctioning and caused due to the underdevelopment of the cerebellar vermis. Associated conditions involving the eye, the kidney, and ocular disease are well described. Aims: Research helps us better understand this diseases, Joubert syndrome and can lead to advances in diagnosis and treatment. Methods: Different several conditions have been described in which the molar tooth sign and characteristics of Joubert syndrome in ten different places in the world. Carrier testing and diagnosis are available if one of these gene mutations has been identified in an affected family member. Results: Authors have described eleven cases during twenty years of Joubert syndrome. It is a clinically and genetically heterogeneous group of disorders characterized by hypoplasia of the cerebellar vermis with the characteristic neuroradiologic molar tooth sign, and accompanying neurologic symptoms, including dysregulation of breathing pattern and developmental delay. We made confirmation of diagnosis in twin sisters with Joubert syndrome with renal anomalies. Ocular symptoms have existed in seven cases (63.64%) from total eleven. Eleven cases were different sex, five boys (45.45%) and six girls (54.44%). Conclusions: Joubert syndrome is inherited as an autosomal recessive genetic disorder with several features of the disease.

Keywords: Joubert syndrome, cerebellooculorenal syndrome, autosomal recessive genetic disorder (ARGD), children

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Authors: S. B. R. Slagmulder

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Monitoring inspiratory effort and dynamic lung stress in patients on pressure support ventilation in the ICU is important for protecting against self inflicted lung injury (P-SILI) and diaphragm dysfunction. Strategies to address the detrimental effects of respiratory drive and effort can lead to improved patient outcomes. Two non-invasive estimation methods, occlusion pressure (Pocc) and P0.1, have been proposed for achieving lung and diaphragm protective ventilation. However, their relationship and interpretation in neuro ICU patients is not well understood. P0.1 is the airway pressure measured during a 100-millisecond occlusion of the inspiratory port. It reflects the neural drive from the respiratory centers to the diaphragm and respiratory muscles, indicating the patient's respiratory drive during the initiation of each breath. Occlusion pressure, measured during a brief inspiratory pause against a closed airway, provides information about the inspiratory muscles' strength and the system's total resistance and compliance. Research Objective: Understanding the relationship between Pocc and P0.1 in brain-injured patients can provide insights into the interpretation of these values in pressure support ventilation. This knowledge can contribute to determining extubation readiness and optimizing ventilation strategies to improve patient outcomes. The central goal is to asses a study protocol for determining the relationship between Pocc and P0.1 in brain-injured patients on pressure support ventilation and their ability to predict successful extubation. Additionally, comparing these values between brain-damaged and non-brain-damaged patients may provide valuable insights. Key Areas of Inquiry: 1. How do Pocc and P0.1 values correlate within brain injury patients undergoing pressure support ventilation? 2. To what extent can Pocc and P0.1 values serve as predictive indicators for successful extubation in patients with brain injuries? 3. What differentiates the Pocc and P0.1 values between patients with brain injuries and those without? Methodology: P0.1 and occlusion pressures are standard measurements for pressure support ventilation patients, taken by attending doctors as per protocol. We utilize electronic patient records for existing data. Unpaired T-test will be conducted to compare P0.1 and Pocc values between both study groups. Associations between P0.1 and Pocc and other study variables, such as extubation, will be explored with simple regression and correlation analysis. Depending on how the data evolve, subgroup analysis will be performed for patients with and without extubation failure. Results: While it is anticipated that neuro patients may exhibit high respiratory drive, the linkage between such elevation, quantified by P0.1, and successful extubation remains unknown The analysis will focus on determining the ability of these values to predict successful extubation and their potential impact on ventilation strategies. Conclusion: Further research is pending to fully understand the potential of these indices and their impact on mechanical ventilation in different patient populations and clinical scenarios. Understanding these relationships can aid in determining extubation readiness and tailoring ventilation strategies to improve patient outcomes in this specific patient population. Additionally, it is vital to account for the influence of sedatives, neurological scores, and BMI on respiratory drive and occlusion pressures to ensure a comprehensive analysis.

Keywords: brain damage, diaphragm dysfunction, occlusion pressure, p0.1, respiratory drive

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Authors: Diane Ghanem, Arjun Gupta, Rohan Vijayan, Ali Uneri, Babar Shafiq

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Introduction: Ankle sprains and fractures often result in syndesmosis injuries. Unstable syndesmotic injuries result from relative motion between the distal ends of the tibia and fibula, anatomic juncture which should otherwise be rigid, and warrant operative management. Clinical and radiological evaluations of intraoperative syndesmosis stability remain a challenging task as traditional 2D fluoroscopy is limited to a uniplanar translational displacement. The purpose of this pilot cadaveric study is to compare the 2D fluoroscopy and 3D cone beam computed tomography (CBCT) stress-induced syndesmosis displacements. Methods: Three fresh-frozen lower legs underwent 2D fluoroscopy and 3D CIOS CBCT to measure syndesmosis position before dissection. Syndesmotic injury was simulated by resecting the (1) anterior inferior tibiofibular ligament (AITFL), the (2) posterior inferior tibiofibular ligament (PITFL) and the inferior transverse ligament (ITL) simultaneously, followed by the (3) interosseous membrane (IOM). Manual external rotation and Cotton stress test were performed after each of the three resections and 2D and 3D images were acquired. Relevant 2D and 3D parameters included the tibiofibular overlap (TFO), tibiofibular clear space (TCS), relative rotation of the fibula, and anterior-posterior (AP) and medial-lateral (ML) translations of the fibula relative to the tibia. Parameters were measured by two independent observers. Inter-rater reliability was assessed by intraclass correlation coefficient (ICC) to determine measurement precision. Results: Significant mismatches were found in the trends between the 2D and 3D measurements when assessing for TFO, TCS and AP translation across the different resection states. Using 3D CBCT, TFO was inversely proportional to the number of resected ligaments while TCS was directly proportional to the latter across all cadavers and ‘resection + stress’ states. Using 2D fluoroscopy, this trend was not respected under the Cotton stress test. 3D AP translation did not show a reliable trend whereas 2D AP translation of the fibula was positive under the Cotton stress test and negative under the external rotation. 3D relative rotation of the fibula, assessed using the Tang et al. ratio method and Beisemann et al. angular method, suggested slight overall internal rotation with complete resection of the ligaments, with a change < 2mm - threshold which corresponds to the commonly used buffer to account for physiologic laxity as per clinical judgment of the surgeon. Excellent agreement (>0.90) was found between the two independent observers for each of the parameters in both 2D and 3D (overall ICC 0.9968, 95% CI 0.995 - 0.999). Conclusions: The 3D CIOS CBCT appears to reliably depict the trend in TFO and TCS. This might be due to the additional detection of relevant rotational malpositions of the fibula in comparison to the standard 2D fluoroscopy which is limited to a single plane translation. A better understanding of 3D imaging may help surgeons identify the precise measurements planes needed to achieve better syndesmosis repair.

Keywords: 2D fluoroscopy, 3D computed tomography, image processing, syndesmosis injury

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Authors: Susanna Menis

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‘Unconscious’ bias is widespread, affecting society on all levels of decision-making and beyond. Placed in the law context, this study will explore the direct effect of the psycho-social and cultural evolution of unconscious bias on how a judicial decision was made. The aim of this study is to contribute to socio-legal scholarship by examining the formation of unconscious bias and its influence on the creation of legal rules that judges believe reflect social solidarity and protect against violence. The study seeks to understand how concepts like criminalization and unlawfulness are constructed by the common law. The study methodology follows two theoretical approaches: historical genealogy and emotions as sociocultural phenomena. Both methods have the ‘tracing back’ of the original formation of a social way of seeing and doing things in common. The significance of this study lies in the importance of reflecting on the ways unconscious bias may be formed; placing judges’ decisions under this spotlight forces us to challenge the status quo, interrogate justice, and seek refinement of the law.

Keywords: legal geneology, emotions, disgust, criminal law

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Authors: Fathia Ehmouda Zaid, Reim Abudelnbi

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Cardiovascular disease is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Patients and method: Cross-section study (68) patients diagnosed as systemic lupus erythematosus (SLE), who visited the outpatient clinic of rheumatology, these patients were interviewed with a structured questionnaire about their past and current clinically for presence of Cardiovascular disease in systemic lupus and use SLEDAI, specific tests [ECG –ECHO –CXRAY] the data are analyzed statistically by Pearson's correlation coefficient was calculated and statistical significance was defined as P< 0.05,during period (2013-2014). Objective: Estimation Cardiovascular disease manifestation of systemic lupus erythematosus, correlation with disease activity, morbidity, and mortality. Result: (68) Patients diagnosed as systemic lupus erythematosus' age range from (18-48 years), M=(13±29Y), Sex were female 66/68 (97.1%), male 2/68 (2.9%),duration of disease range[1-15year], M =[7±8y], we found Cardiovascular disease manifestation of systemic lupus erythematosus 32/68 (47.1%), correlation with disease activity use SLEDAI,(r= 476** p=0.000),Morbidity,(r= .554**; p=0.000) and mortality (r=.181; p=.139), Cardiovascular disease manifestations of systemic lupus erythematosus are pericarditis 8/68 (11.8%), pericardial effusion 6/68 (8.8%), myocarditis 4/68 (5.9 %), valvular lesions (endocarditis) 1/68 (1.5%), pulmonary hypertension (PAH) 12/68 (17.6%), coronary artery disease 1/68 (1.5%), none of patients have conduction abnormalities involvement. Correlation with disease activity use SLEDAI, pericarditis (r= .210, p=.086), pericardial effusion (r= 0.079, p=.520), myocarditis (r= 272*, p=.027), valvular lesions (endocarditis) (r= .112, p= .362), pulmonary hypertension (PAH) (r= .257*, p=.035) and coronary artery disease (r=.075, p=.544) correlation between cardiovascular disease manifestations of systemic lupus erythematosus and specific organ involvement we found Mucocutaneous (r=.091 p= .459), musculoskeletal (MSK) (r=.110 p=.373), Renal disease (r=.278*, p=.022), neurologic disease (r=.085, p=.489) and Hematologic disease (r=-.264*, p=.030). Conclusion: Cardiovascular manifestation is more frequent symptoms with systemic lupus erythematosus (SLE) is 47 % correlation with disease activity and morbidity but not with mortality. Recommendations: Focus research to evaluation and an adequate assessment of cardiovascular complications on the morbidity and mortality of the patients with SLE are still required.

Keywords: cardiovascular disease, systemic lupus erythematosus, disease activity, mortality

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Authors: Nirav P. Vaghela

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Work-related musculoskeletal symptoms (WMS) are a major health issue in many occupations all over the world. Past research on hospital workers have mainly been focused on nurses [8] and very few studies have examined musculoskeletal symptoms among doctors in various specialties. The work of surgeons can involve high levels of mental concentration and very precise movements that can be categorized as mild-to-moderate physical demands. Design: Forty-three surgeons were enrolled in this study. To investigate musculoskeletal disorder among the surgeons we had used Standardised Nordic Questionnaire, Quick Exposure Check (QEC) and Workstyle Short Form. Result: In the current study, total 43 surgeons participants out of 30 males and 13 females. Their mean age was 42.07 ± 12.35, and the mean working years of the group were 15.14years ±9.017. On the average, they worked a total of about 8.58 h (±1.967) per day. The prevalence of work related musculoskeletal symptoms among the surgeons indicating 83.70% surgeons had atleast one joint affected while 16.30% had no symptoms at all. Conclusion: The present survey study has shown high prevalence rates of neck, back and shoulder musculoskeletal symptoms in surgeons.

Keywords: repetitive stress injury, pain, occupational hazards, disability, abneetism, physical health, quality of life

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Authors: Bulus Kpame, Mukhtar Mohammed Alhaji, Garba Jibril

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In any team sport, the most important variables that should be used to measure performance are physical condition, and technical and tactical performance. In a complex game like football, it is extremely difficult to measure the relative importance of each of these variables. However, physical fitness itself has been shown to consist of several components, like endurance, strength, flexibility, agility, coordination and speed. Each of these components has been shown to consist of several subcomponents. This paper attempts to describe a test battery to assess and evaluate physical performance in football players. This battery comprises a functional, structured training session of about 2.5hrs. it consists of quality rating of the warm-up procedure, tests of flexibility, football skills, power, speed, and endurance. Acceptable values for performance in each of the tests are also presented under each test. It is hoped that this battery of tests will be helpful to the coach in determining the effect of a specific training program. It would also be helpful to train physician and trainer, to monitor progress during rehabilitation after sustaining any injury.

Keywords: assessment, evaluation, performance, programs

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Authors: Priya Kulkarni, Soumya Koppikar, Datta Shinde, Shantanu Deshpande, Narendrakumar Wagh, Abhay Harsulkar

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Osteoarthritis (OA) is associated with multiple and overlapping aetiologies. IL-1β is produced by stressed tissue and known to aggravate disease pathologies. We selected 10 patients with elevated IL-1β in their synovial fluids (SF). We hypothesized IL-1β as nodal-point connecting different pathologies. IL-1β was higher in all meniscal tear (MT) patients perhaps as the earliest response to injury. Since MT above age of 30 leads to OA in less than 5 years, it is attributed that IL-1β modulates OA pathology. Among all bilateral OA patients, an interesting case operated for Total-Knee-Replacement revealed differential cartilage degeneration demonstrating strong association with higher IL-1β. Symptoms like acute-pain, effusion and redness were correlated with higher IL-1β and NO (Nitric-oxide). However, higher IL-1β was also found without typical-inflammation characterized by infiltration of neutrophils and macrophages. Cultured synoviocytes responded to IL-1β by releasing NO. In conclusion, IL-1β in SF acquires central position influencing different OA pathologies and aetiologies.

Keywords: IL-1β, meniscal tear, osteoarthritis, synovial fluid

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Authors: Mohammed Saleem Tariq

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The enthusiasm for gluten avoidance in a growing market is met by improvements in sensitive detection methods for analysing gluten content. Paradoxically, manufacturers employ no such systems in the production process but continue to market their product as gluten free, a significant risk posed to an undetermined coeliac population. The paper resonates with an immunological response that causes gastrointestinal scarring and villous atrophy with the conventional description of personal injury. The current developing regime in the UK however, it is discussed, has avoided creating specific rules to provide an adequate level of protection for this type of vulnerable ‘characteristic’. Due to the struggle involved with identifying an appropriate cause of action, this paper analyses whether a claim brought in misrepresentation, negligence and/or under the Consumer Protect Act 1987 could be sustained. A necessary comparison is then made with the approach adopted by the Americans with Disability Act 1990 which recognises this chronic disease as a disability. The ongoing failure to introduce a level of protection which matches that afforded to those who fall into any one of the ‘protected characteristics’ under the Equality Act 2010, is inconceivable given the outstanding level of legal vulnerability.

Keywords: coeliac, litigation, misrepresentation, negligence

Procedia PDF Downloads 353

Authors: Aniekan Peter, ECS Naidu, Edidiong Akang, U. Offor, R. Kalhapure, A. A. Chuturgoon, T. Govender, O. O. Azu

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Introduction: Nano-drugs are novel innovations in the management of human immunodeficiency virus (HIV) pandemic, especially resistant strains of the virus in their sanctuary sites: testis and the brain. There are safety concerns to be addressed to achieve the full potential of this new drug delivery system. Aim of study: Our study was designed to investigate toxicity profile of Tenofovir Nanoparticle (TDF-N) synthesized by University of Kwazulu-Natal (UKZN) Nano-team for prevention and treatment of HIV infection. Methodology: Ten adult male Sprague-Dawley rats maintained at the Animal House of the Biomedical Resources Unit UKZN were used for the study. The animals were weighed and divided into two groups of 5 animal each. Control animals (A) were administered with normal saline. Therapeutic dose (4.3 mg/kg) of TDF-N was administered to group B. At the end of four weeks, animals were weighed and sacrificed. Liver and kidney were removed fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT), liver function test (LFT) and full blood count (FBC) using appropriate analysers. Cellular measurements were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, values < 0.05 were significant. Results: We reported no histological alterations in the liver, kidney, FBC, LFT and RFT between the TDF-N animals and saline control. There were no significant differences in weight, organo-somatic index and histological measurements in the treatment group when compared with saline control. Conclusion/recommendations: TDF-N is not toxic to the liver, kidney and blood cells in our study. More studies using human subjects is recommended.

Keywords: tenofovir nanoparticles, liver, kidney, blood cells

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Authors: Gopal Lamichhane, Biswash Sapkota, Grinsun Sharma, Mahendra Adhikari

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Urolithiasis is a condition in which insoluble or less soluble salts like oxalate, phosphate etc. precipitate in urinary tract and causes obstruction in ureter resulting renal colic or sometimes haematuria. It is the third most common disorder of urinary tract affecting nearly 2% of world’s population. Poor urinary drainage, microbial infection, oxalate and calcium containing diet, calciferol, hyperparathyroidism, cysteine in urine, gout, dysfunction of intestine, drought environment, lifestyle, exercise, stress etc. are risk factors for urolithiasis. Wide ranges of treatments are available in allopathic system of medicine but reoccurrence is unpreventable even with the surgical removal of stone or lithotripsy. So, people prefer alternative medicinal systems such as Unani, homeopathic, ayurvedic etc. systems of medicine due to their fewer side effects over allopathic counterpart. Different plants based ethnomedicines are being well established by their continuous effective use in human since long time in treatment of urinary problem. Many studies have scientifically proved those ethnomedicines for antiurolithiatic effect in animal and in vitro model. Plant-based remedies were found to be therapeutically effective for both prevention as well as cure of calcium oxalate urolithiasis. Plants were known to show these effects through a combination of many effects such as antioxidant, diuretic, hypocalciuric, urine alkalinizing effect in them. Berberine, triterpenoids, lupeol are the phytochemicals established for antiurolithiatic effect. Hence, plant-based medicine can be the effective herbal alternative as well as means of discovery of novel drug molecule for curing urolithiatic disorder and should be focused on further research to discover their value in coming future.

Keywords: urolithiasis, herbal medicine, ethnomedicine, kidney stone, calcium oxalate

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Authors: Kai Pei Huang, Ting Chung Hung, Li Ching Wu

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Amyloidosis refers to a variety of conditions wherein amyloid proteins are abnormally deposited in organ or tissues and cause harm. Among the several forms of amyloidosis, the principal types of that in inpatient medical services are the AL amyloidosis (primary) and AA amyloidois (secondary). AL Amyloidois is due to deposition of protein derived from overproduction of immunoglobulin light chain in plasma cell myeloma. Furthermore, it is a systemic disorder that can present with a variety of symptoms, including heavy proteinemia and edema, heptosplenomegaly, otherwise unexplained heart failure. We reported a 78-year-old female presenting dysuria, oliguria and leg edema for several months. Laboratory data showed proteinuria (UPCR:1679.8), leukocytosis (WBC:16.2 x 10^3/uL), results of serum urea nitrogen (39mg/dL), creatinine (0.76 mg/dL), IgG (748 mg/dL.), IgA (635 mg/dL), IgM (63 mg/dL), kappa light chain(18.8 mg/dL), lambda light chain (110.0 mg/dL) and kappa/lambda ratio (0.17). Renal biopsy found amyloid fibrils in glomerular mesangial area, and Congo red stain highlights amyloid deposition in glomeruli. Additional lab studies included serum protein electrophoresis, which shows a major monoclonal peak in β region and minor small peak in gamma region, and the immunotyping studies for serum showed two IgA/λ type. We treated sample with beta-mercaptoethanol which reducing the polymerized immunoglobulin to clarify two IgA/λ are secreted from the same plasma cell clone in bone marrow. Later examination confirmed it existed plasma cell infiltration in bone marrow, and the immunohistochemical staining showed monotypic for λ light chain and are positive for IgA. All findings mentioned above reveal it is a case of plasma cell myeloma with λ Light Chain Amyloidosis.

Keywords: amyloidosis, immunoglobulin light chain, plasma cell myeloma, serum protein electrophoresis

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Authors: Hanen Bouaziz, Moez Rafrafi, Ghada Ben Salah, Kamel Jamoussi, Tahia Boudawara, Najiba Zeghal

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The present study investigated the protective role of Hyparrhenia hirta against sodium nitrate (NaNO3)-induced nephrotoxicity. A high-performance liquid chromatography coupled with a mass spectrometer (HPLC-MS) method was developed to separate and identify flavonoids in Hyparrhenia hirta. Seven flavonoids were identified as 3-O-methylquercetin, luteolin-7-O-glucoside, luteolin, apigenin-7-O-glucoside, apigenin-8-C-glucoside, luteolin-8-C-glucoside and luteolin-6-C-glucoside. Wistar rats were randomly divided into three groups: a control group and two treated groups during 50 days with NaNO3 administered either alone in drinking water or co-administered with Hyparrhenia hirta. NaNO3 treatment induced a significant increase in plasma levels of creatinine, urea and uric while urinary level decreased significantly. Nephrotoxicity induced by NaNO3 was characterized by significant increase in creatinine clearance. In parallel, a significant increase in malondialdehyde level along with a concomitant decrease in total glutathione content and superoxide dismutase, catalase and glutathione peroxidase activities were observed in the kidney after NaNO3 treatment. The histopathological changes in kidney after NaNO3 administration were shrunken. There were renal tubule cell degeneration and infiltration of mononuclear cells. Most glomeruli revealed shrinkage, a wide capsular space and a peri-glomerular mononuclear cells infiltration. Hyparrhenia hirta supplementation showed a remarkable amelioration of the abnormalities cited above. The results concluded that the treatment with Hyparrhenia hirta had a significant role in protecting the animals from nitrate-induced kidney dysfunction.

Keywords: flavonoids, hyparrhenia hirta, kidney, nitrate toxicity, oxidative stress, rat

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Authors: Mark McGuire, Eric Shannon, John Parmigiani

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Timber harvesting increasingly involves mechanized equipment. This has increased the efficiency of harvesting, but has also introduced worker-safety concerns. One such concern arises from the use of harvesters. During operation, harvesters subject saw chain to large dynamic mechanical stresses. These stresses can, under certain conditions, cause the saw chain to fracture. The high speed of harvester saw chain can cause the resulting open chain loop to fracture a second time due to the dynamic loads placed upon it as it travels through space. If a second fracture occurs, it can result in a projectile consisting of one-to-several chain links. This projectile is referred to as a chain shot. It has speeds similar to a bullet but typically has greater mass and is a significant safety concern. Numerous examples exist of chain shots penetrating bullet-proof barriers and causing severe injury and death. Improved harvester-cab barriers can help prevent injury however a comprehensive scientific understanding of chain shot is required to consistently reduce or prevent it. Obtaining this understanding requires a test machine with the capability to cause chain shot to occur under carefully controlled conditions and accurately measure the response. Worldwide few such test machine exist. Those that do focus on validating the ability of barriers to withstand a chain shot impact rather than obtaining a scientific understanding of the chain shot event itself. The purpose of this paper is to describe the design, fabrication, and use of a test machine capable of a comprehensive scientific investigation of chain shot. The capabilities of this machine are to test all commercially-available saw chains and bars at chain tensions and speeds meeting and exceeding those typically encountered in harvester use and accurately measure the corresponding key technical parameters. The test machine was constructed inside of a standard shipping container. This provides space for both an operator station and a test chamber. In order to contain the chain shot under any possible test conditions, the test chamber was lined with a base layer of AR500 steel followed by an overlay of HDPE. To accommodate varying bar orientations and fracture-initiation sites, the entire saw chain drive unit and bar mounting system is modular and capable of being located anywhere in the test chamber. The drive unit consists of a high-speed electric motor with a flywheel. Standard Ponsse harvester head components are used to bar mounting and chain tensioning. Chain lubrication is provided by a separate peristaltic pump. Chain fracture is initiated through ISO standard 11837. Measure parameters include shaft speed, motor vibration, bearing temperatures, motor temperature, motor current draw, hydraulic fluid pressure, chain force at fracture, and high-speed camera images. Results show that the machine is capable of consistently causing chain shot. Measurement output shows fracture location and the force associated with fracture as a function of saw chain speed and tension. Use of this machine will result in a scientific understanding of chain shot and consequently improved products and greater harvester operator safety.

Keywords: chain shot, safety, testing, timber harvesters

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Authors: M. Naveed Akhter, Jawad Aslam, Omer Gillani

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To aid and rehabilitate increasing number of patients suffering from spinal cord injury (SCI) and stroke, a lightweight, wearable, and 3D printable exoskeletal glove has been developed. Unlike previously developed metal or fabric-based exoskeletons, this research presents the development of soft exoskeletal glove made of thermoplastic polyurethane (TPU). The drive mechanism consists of a single motor-driven antagonistic tendon to perform extension or flexion of middle and index finger. The tendon-based differential drive has been incorporated to allow for grasping of irregularly shaped objects. The design features easy 3D-printability with TPU without a need for supports. The overall weight of the glove and the actuation unit is approximately 500g. Performance of the glove was tested on a custom test-bench with integrated load cells, and the grip strength was tested to be around 30N per finger while grasping objects of irregular shape.

Keywords: 3D printable, differential drive, exoskeletal glove, rehabilitation, single motor driven

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Authors: Lajeesh Jabbar, Shibu T. Varghese

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Being under pain is a very distressing factor that it prolongs the healing of any kind of trauma and add to the post traumatic stressful state. Alleviating the pain from acute traumatic conditions like fracture, degloving injury etc will help in faster recovery and also decrease the incidence of post traumatic stress disorder. Most of the emergency departments in INDIA are using IV opioid analgesics to relieve the patient from pain in cases of acute traumatic injuries. None of the Emergency Departments practice regional blocks in the country. In this study, we are comparing the efficacy of Regional Blocks in relieving the pain in lower limb fractures versus the use of IV analgesics for the same in the emergency department. The site of study is Malabar Institute Of Medical Sciences in Calicut in Kerala in India and is a place which receives approximately 10-20 traumatic fracture cases per day. The fracture sites used for the study purpose are femur fracture and phalangeal fractures.

Keywords: regional blocks, IV analgesia, acute traumatic pain, femur fractures, phalanx fractures

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Authors: P. P. Chandrasekera, P. B. Hewavithana, S. Rosairo, M. H. M. N. Herath, D. M. R. D. Mirihella

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Periventricular Leukomalacia (PVL) is a White Matter Injury (WMI) of preterm neonatal brain. Objectives of the study were to assess the neuro-developmental outcome at one year of age and to determine a good protocol of cranial ultrasonography to detect PVL. Two hundred and sixty four preterm neonates were included in the study. Series of cranial ultrasound scans were done by using a dedicated neonatal head probe 4-10 MHz of Logic e portable ultrasound scanner. Clinical history of seizures, abnormal head growth (hydrocephalus or microcephaly) and developmental milestones were assessed and neurological examinations were done until one year of age. Among live neonates, 57% who had cystic PVL (Grades2 and 3) manifested as cerebral palsy. In conclusion cystic PVL has permanent neurological disabilities like cerebral palsy. Good protocol of real time cranial ultrasonography to detect PVL is to perform scans at least once a week until one month and at term (40 weeks of gestation).

Keywords: cerebral palsy, cranial ultrasonography, Periventricular Leukomalacia, preterm neonates

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Authors: Fernanda Piculo, Giovana Vesentini, Gabriela Marini, Debora Cristina Damasceno, Angelica Mercia Pascon Barbosa, Marilza Vieira Cunha Rudge

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Introduction: Women with previous gestational diabetes mellitus (GDM) were significantly more likely to have urinary incontinence (UI) and pelvic floor muscle dysfunction compared to non-diabetic women two years after a cesarean section. Additional results demonstrated that induced diabetes causes detrimental effects on pregnant rat urethral muscle. These results indicate the need for exploration of the mechanistic role of a recovery factor in female UI. Chemokine ligand 7 (CCL7) was significantly over expressed in rat serum, urethral and vaginal tissues immediately following induction of stress UI in a rat model simulating birth trauma. CCL7 over expression has shown potency for stimulating targeted stem cell migration and provide a translational link (clinical measurement) which further provide opportunities for treatment. The aim of this study was to investigate the CCL7 levels profile in diabetic pregnant women with urinary incontinence during pregnancy over the first year postpartum. Methods: This study was conducted in the Perinatal Diabetes Research Center of the Botucatu Medical School/UNESP, and was approved by the Research Ethics Committee of the Institution (CAAE: 20639813.0.0000.5411). The diagnosis of GDM was established between 24th and 28th gestational weeks, by the 75 g-OGTT test according to ADA’s criteria. Urinary incontinence was defined according to the International Continence Society and the CCL7 levels was measured by ELISA (R&D Systems, Catalog Number DCC700). Two hundred twelve women were classified into four study groups: normoglycemic continent (NC), normoglycemic incontinent (NI), diabetic continent (DC) and diabetic incontinent (DI). They were evaluated at six-time-points: 12-18, 24-28 and 34-38 gestational weeks, 24-48 hours, 6 weeks and 6-12 months postpartum. Results: At 12-18 weeks, it was possible to consider only two groups, continent and incontinent, because at this early gestational period has not yet been the diagnosis of GDM. The group with GDM and UI (DI group) showed lower levels of CCL7 in all time points during pregnancy and postpartum, compared to normoglycemic groups (NC and NI), indicating that these women have not recovered from child birth induced UI during the 6-12 months postpartum compared to their controls, and that the progression of UI and/or lack of recovery throughout the first postpartum year can be related with lower levels of CCL7. Instead, serum CCL7 was significantly increased in the NC group. Taken together, these findings of overexpression of CCL7 in the NC group and decreased levels in the DI group, could confirm that diabetes delays the recovery from child birth induced UI, and that CCL7 could potentially be used as a serum marker of injury. Conclusion: This study demonstrates lower levels of CCL7 in the DI group during pregnancy and postpartum and suggests that the progression of UI in diabetic women and/or lack of recovery throughout the first postpartum year can be related with low levels of CCL7. This provides a translational potential where CCL7 measurement could be used as a surrogate for injury after delivery. Successful controlled CCL7 mediated stem cell homing to the lower urinary tract could one day introduce the potential for non-operative treatment or prevention of stress urinary incontinence.

Keywords: CCL7, gestational diabetes, pregnancy, urinary incontinence

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Authors: Bruno Kinyaga

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Motorcycles transport commonly known as (Boda boda) in Tanzania has been growing up in the recent years in both urban and rural areas. Since motorcycles have been authorized to carry passengers in Tanzania they have been associated with many accidents resulting in large number of deaths and injuries in the country. Most of the road traffic injury victims are passengers, motorcyclists and pedestrians. Males are over represented in all cases. Most of the deceased were 18-29 years old. The increase of motorcycles has been accompanied with the increase of motorcycle crashes causing deaths and injuries to passengers as well as riders. According to the data collected, the statistics shows that from January to December 2015, the total number of 4079 motorcycles was involved in accidents in the country, causing 1747 deaths and 4826 injuries. Compares to the report of January to December 2014 whereby the total number of motorcycles involved in accidents were 3710, causing 1423 deaths and 3622 injuries. This is according to the report provided by the Road safety Chief Commander in Tanzania.

Keywords: accidents, road, safety, Tanzania

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Authors: Ayeshmanthe Rathnayake, Siew Goh, Carmel Fenton, Ashutosh Hardikar

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Post-Operative Atrial Fibrillation (POAF) is the most frequent complication of cardiac surgery and is associated with reduced survival, increased rates of cognitive changes and cerebrovascular accident, heart failure, renal dysfunction, infection and length of stay, and hospital costs. Cardiac tamponade, although less common, carries high morbidity and mortality. Shed mediastinal blood in the pericardial space is a major source of intrapericardial oxidative stress and inflammation that triggers POAF. The utilisation of a left posterior pericardiotomy aims to shunt blood from the pericardium into the pleural space and have a role in the prevention of POAF as well as cardiac tamponade. 2118 patients had undergone isolated Coronary Artery Bypass Graft (CABG) at Royal Hobart Hospital from 2008-2021. They were divided into pericardiotomy vs control group. Patient baseline demographics, intraoperative data, and post-operative outcomes were reviewed retrospectively. Total incidence of new POAF and cardiac tamponade was 26.1% and 0.75%, respectively. Primary outcome of both the incidence of POAF(22.9% vs27.8%OR 0.77 p<0.05) and Cardiac Tamponade (0% vs 1.1% OR 0.85 p<0.05) were less in the pericardiotomy group.Increasing age, BMI, poor left ventricular function (EF <30%), and return to theatre were independent predictors of developing POAF. There were similar rates of return to theatre for bleeding however, no cases of tamponade in the pericardiotomy group. There were no complications attributable to left posterior pericardiotomy and the time added to the duration of surgery was minimal. Left posterior pericardiotomy is associated with a significant reduction in the incidence of POAFand cardiac tamponade and issafe and efficient.

Keywords: cardiac surgery, pericardiotomy, post-operative atrial fibrillation, cardiac tamponade

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Authors: Mariem Meddeb Sidhom, Souhayel Hedfi, Rjaibia Houda, Mehdi Dridi, Mohamed Ali Yousfi, Sâadia Gargouri

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Considering the important increase in costs of caspofungin treatments and ahead the evolution of its indication, pharmacy department was prompted to realize a review of the adequacy of prescriptions in the medical intensive care units (ICU). A retrospective observational study was conducted in Tunis military hospital concerning ICU prescriptions of caspofungin from 2008 until 2013. A pharmacist had returned to the patient’s medical records to collect data and to the microbiology department for parasitological results. The adequacy of prescriptions was evaluated by a pharmacist and an infectiologist parasitologist, referring to predefined scale of criteria resuming the indications of the marketing authorization (MA) and grade AI-AII of the guidelines of the Infectious Diseases Society of America (IDSA). Sixty two ICU patients have been treated with caspofungin during the period of study; however, 8 files were lost. Thus, 54 patients were included in the study having received 55 prescriptions of caspofungin. Males were a majority with 64.8% of the population. Mean age was 51 years. Caspofungin was indicated in accordance with the IDSA recommendations in 43.6% of the cases. The most case of non respect to the guidelines was the indication of caspofungin as empirical treatment in non neutropenic patients. Caspofungin was utilized as a first line treatment in 9 cases where it was possible to give fluconazole first, as germs were fluconazole- sensitive. Caspofungin was indicated in 2 patients with good renal function and in which nor amphotericin B, liposomal ampho B neither itraconazole had been previously used, as indicates the MA. The posology of caspofungin was respected in all prescriptions with a loading dose of 70 mg in the first day and a maintenance dose of 50 mg daily. Seven patients had received a daily dose of 70 mg, the recommended dose for people weighing more than 80 Kg. Caspofungin prescriptions are far to be adequately done. There is a clear need of optimization in indicating this molecule and that must be done in collaboration between the pharmacy department, the ICUs and parasitology department.

Keywords: caspofungin, prescription, intensive care units, marketing authorization, Tunisian hospital cohort

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Authors: Said Ghalem

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Honey is primarily composed of sugars: glucose and fructose. Depending honey, it's either fructose or glucose predominates. More the fructose concentration and the less the glycemic index (GI) is high. Thus, changes in the insulin response shows a decrease of the amount of insulin secreted at an increased fructose honey. Honey is also a compound that can reduce the lipid in the blood. Several studies on animals, but which remain to be checked in humans, have shown that the honey can have interesting effects when combined with other molecules: associated with Metformin (a medicine taken by diabetics), it shows the benefits and effects of diabetes preserves the tissue; associated ginger, it increases the antioxidant activity and thus avoids neurologic complications, neuropathic. Molecular modeling techniques are widely used in chemistry, biology, and the pharmaceutical industry. Most of the currently existing drugs target enzymes. Inhibition of DPP-4 is an important approach in the treatment of type 2 diabetes. We have chosen for the inhibition of DPP-4 the following molecules: Linagliptin (BI1356), Sitagliptin (Januvia), Vildagliptin, Saxagliptin, Alogliptin, and Metformin (Glucophage), that are involved in the disease management of type 2 diabetes and added to honey. For this, we used software Molecular Operating Environment. A Wistar rat study was initiated in our laboratory with a well-studied protocol; after sacrifice, according to international standards and respect for the animal This theoretical approach predicts the mode of interaction of a ligand with its target. The honey can have interesting effects when combined with other molecules, it shows the benefits and effects of honey preserves the tissue, it increases the antioxidant activity, and thus avoids neurologic complications, neuropathic or macrovascular. The organs, especially the kidneys of Wistar, shows that the parameters to renal function let us conclude that damages caused by diabetes are slightly perceptible than those observed without the addition of a high concentration of fructose honey.

Keywords: honey, molecular modeling, DPP4 enzyme, metformin

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Authors: Rukia Yosuf

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Diabetes is a national healthcare crisis related to both macrovascular and microvascular complications. We hypothesized that higher levels of physical activity are associated with lower total and visceral fat mass, lower systolic blood pressure, and increased insulin sensitivity. Participant inclusion criteria: 21-50 years old, BMI ≥ 30 kg/m2, hemoglobin A1C 5.7-6.4, fasting glucose 100-125 mg/dL, and HOMA IR ≥ 2.5. Exclusion criteria: history of diabetes, hypertension, HIV, renal disease, hearing loss, alcoholic intake over four drinks daily, use of organic nitrates or PDE5 inhibitors, and decreased cardiac function. Total physical activity was measured using accelerometers, body composition using DXA, and insulin resistance via fsIVGTT. Clinical and biochemical cardiometabolic risk factors, blood pressure and heart rate were obtained using a calibrated sphygmomanometer. Anthropometric measures, fasting glucose, insulin, lipid profile, C-reactive protein, and BMP were analyzed using standard procedures. Within our study, we found correlations between levels of physical activity in a heterogeneous group of prediabetic adults. Patients with more physical activity had a higher degree of insulin sensitivity, lower blood pressure, total visceral adipose tissue, and overall lower total mass. Total physical activity levels showed small, but significant correlations with systolic blood pressure, visceral fat, lean mass and insulin sensitivity. After normalizing for the race, age, and gender using multiple regression, these associations were no longer significant considering our small sample size. More research into prediabetes will decrease the population of diabetics overall. In the future, we could increase sample size and conduct cross sectional and longitudinal studies in various populations with prediabetes.

Keywords: diabetes, kidney disease, nephrology, prediabetes

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Authors: Chung Yan Natalia Yeung, Man Kit Indy Ho, Kin Yu Stan Chan, Ho Pui Kipper Lam, Man Wah Genie Tong, Tze Chung Jim Luk

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Excessive foot pronation is a well-known risk factor of knee and foot injuries such as patellofemoral pain, patellar and Achilles tendinopathy, and plantar fasciitis. Low-Dye taping (LDT) application is not uncommon for basketball players to control excessive foot pronation for pain control and injury prevention. The primary potential benefits of using LDT include providing additional supports to medial longitudinal arch and restricting the excessive midfoot and subtalar motion in weight-bearing activities such as running and landing. Meanwhile, restrictions provided by the rigid tape may also potentially limit functional joint movements and sports performance. Coaches and athletes need to weigh the potential benefits and harmful effects before making a decision if applying LDT technique is worthwhile or not. However, the influence of using LDT on basketball-related performance such as explosive and reactive strength is not well understood. Therefore, the purpose of this study was to investigate the change of drop jump (DJ) and countermovement jump (CMJ) performance before and after LDT application for collegiate male basketball players. In this within-subject crossover study, 12 healthy male basketball players (age: 21.7 ± 2.5 years) with at least 3-year regular basketball training experience were recruited. Navicular drop (ND) test was adopted as the screening and only those with excessive pronation (ND ≥ 10mm) were included. Participants with recent lower limb injury history were excluded. Recruited subjects were required to perform both ND, DJ (on a platform of 40cm height) and CMJ (without arms swing) tests in series during taped and non-taped conditions in the counterbalanced order. Reactive strength index (RSI) was calculated by using the flight time divided by the ground contact time measured. For DJ and CMJ tests, the best of three trials was used for analysis. The difference between taped and non-taped conditions for each test was further calculated through standardized effect ± 90% confidence intervals (CI) with clinical magnitude-based inference (MBI). Paired samples T-test showed significant decrease in ND (-4.68 ± 1.44mm; 95% CI: -3.77, -5.60; p < 0.05) while MBI demonstrated most likely beneficial and large effect (standardize effect: -1.59 ± 0.27) in LDT condition. For DJ test, significant increase in both flight time (25.25 ± 29.96ms; 95% CI: 6.22, 44.28; p < 0.05) and RSI (0.22 ± 0.22; 95% CI: 0.08, 0.36; p < 0.05) were observed. In taped condition, MBI showed very likely beneficial and moderate effect (standardized effect: 0.77 ± 0.49) in flight time, possibly beneficial and small effect (standardized effect: -0.26 ± 0.29) in ground contact time and very likely beneficial and moderate effect (standardized effect: 0.77 ± 0.42) in RSI. No significant difference in CMJ was observed (95% CI: -2.73, 2.08; p > 0.05). For basketball players with pes planus, applying LDT could substantially support the foot by elevating the navicular height and potentially provide acute beneficial effects in reactive strength performance. Meanwhile, no significant harmful effect on CMJ was observed. Basketball players may consider applying LDT before the game or training to enhance the reactive strength performance. However since the observed effects in this study could not generalize to other players without excessive foot pronation, further studies on players with normal foot arch or navicular height are recommended.

Keywords: flight time, pes planus, pronated foot, reactive strength index

Procedia PDF Downloads 146

Authors: Ahmed Shaboub, Yusuf Jasim Althawadi, Shadi Alaa Abdelaal, Mohamed Hussein Abdalla, Hatem Amr Elzahaby, Mohamed Mohamed, Hazem S. Ghaith, Ahmed Negida

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Objectives: We aimed to compare the safety and outcomes of the minimally invasive approaches versus conventional sternotomy procedures for aortic valve replacement. Methods: We conducted a PRISMA-compliant systematic review and meta-analysis. We ran an electronic search of PubMed, Cochrane CENTRAL, Scopus, and Web of Science to identify the relevant published studies. Data were extracted and pooled as standardized mean difference (SMD) or risk ratio (RR) using StataMP version 17 for macOS. Results: Forty-one studies with a total of 15,065 patients were included in this meta-analysis (minimally invasive approaches n=7231 vs. conventional sternotomy n=7834). The pooled effect size showed that minimally invasive approaches had lower mortality rate (RR 0.76, 95%CI [0.59 to 0.99]), intensive care unit and hospital stays (SMD -0.16 and -0.31, respectively), ventilation time (SMD -0.26, 95%CI [-0.38 to -0.15]), 24-h chest tube drainage (SMD -1.03, 95%CI [-1.53 to -0.53]), RBCs transfusion (RR 0.81, 95%CI [0.70 to 0.93]), wound infection (RR 0.66, 95%CI [0.47 to 0.92]) and acute renal failure (RR 0.65, 95%CI [0.46 to 0.93]). However, minimally invasive approaches had longer operative time, cross-clamp, and bypass times (SMD 0.47, 95%CI [0.22 to 0.72], SMD 0.27, 95%CI [0.07 to 0.48], and SMD 0.37, 95%CI [0.20 to 0.45], respectively). There were no differences between the two groups in blood loss, endocarditis, cardiac tamponade, stroke, arrhythmias, pneumonia, pneumothorax, bleeding reoperation, tracheostomy, hemodialysis, or myocardial infarction (all P>0.05). Conclusion: Current evidence showed higher safety and better operative outcomes with minimally invasive aortic valve replacement compared to the conventional approach. Future RCTs with long-term follow-ups are recommended.

Keywords: aortic replacement, minimally invasive, sternotomy, mini-sternotomy, aortic valve, meta analysis

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Authors: Hyun June Kim, Tailong Shi, Seden Akdagli, Sam Most, Yuling Yan

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Quantitative analysis of mouse whisker movement can be used to study functional recovery and regeneration of facial nerve after an injury. However, it is challenging to accurately track mouse whisker movements, and most whisker tracking methods require manual intervention, e.g. fixing the head of the mouse during a study. Here we describe a semi-automated image processing method that is applied to high-speed video recordings of free-moving mice to track whisker movements. We first track the head movement of a mouse by delineating the lower head contour frame-by-frame to locate and determine the orientation of its head. Then, a region of interest is identified for each frame, with subsequent application of the Hough transform to track individual whisker movements on each side of the head. Our approach is used to examine the functional recovery of damaged facial nerves in mice over a course of 21 days.

Keywords: mystacial macrovibrissae, whisker tracking, head tracking, facial nerve recovery

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Authors: Rijnbout-St.James Willem, Lindner Volkhard, Scholand Mary Beth, Ashton M. Tillett, Di Gennaro Michael Jude, Smith Silvia Enrica

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Introduction: Fibrosing lung diseases are characterized by changes in the lung interstitium and are classified based on etiology: 1) environmental/exposure-related, 2) autoimmune-related, 3) sarcoidosis, 4) interstitial pneumonia, and 4) idiopathic. Among interstitial lung diseases (ILD) idiopathic forms, idiopathic pulmonary fibrosis (IPF) is the most severe. Pathogenesis of IPF is characterized by an increased presence of proinflammatory mediators, resulting in alveolar injury, where injury to alveolar epithelium precipitates an increase in collagen deposition, subsequently thickening the alveolar septum and decreasing gas exchange. Identifying biomarkers implicated in the pathogenesis of lung fibrosis is key to developing new therapies and improving the efficacy of existing therapies. The transforming growth factor-beta (TGF-B1), a mediator of tissue repair associated with WNT5A signaling, is partially responsible for fibroblast proliferation in ILD and is the target of Pirfenidone, one of the antifibrotic therapies used for patients with IPF. Canonical TGF-B signaling is mediated by the proteins SMAD 2/3, which are, in turn, indirectly regulated by Collagen Triple Helix Repeat Containing 1 (CTHRC1). In this study, we tested the following hypotheses: 1) CTHRC1 is more elevated in the ILD cohort compared to unaffected controls, and 2) CTHRC1 is differently expressed among ILD types. Material and Methods: CTHRC1 levels were measured by ELISA in 171 plasma samples from the deidentified University of Utah ILD cohort. Data represent a cohort of 131 ILD-affected participants and 40 unaffected controls. CTHRC1 samples were categorized by a pulmonologist based on affectation status and disease subtypes: IPF (n = 45), sarcoidosis (4), nonspecific interstitial pneumonia (16), hypersensitivity pneumonitis (n = 7), interstitial pneumonia (n=13), autoimmune (n = 15), other ILD - a category that includes undifferentiated ILD diagnoses (n = 31), and unaffected controls (n = 40). We conducted a single-factor ANOVA of plasma CTHRC1 levels to test whether CTHRC1 variance among affected and non-affected participants is statistically significantly different. In-silico analysis was performed with Ingenuity Pathway Analysis® to characterize the role of CTHRC1 in the pathway of lung fibrosis. Results: Statistical analyses of CTHRC1 in plasma samples indicate that the average CTHRC1 level is significantly higher in ILD-affected participants than controls, with the autoimmune ILD being higher than other ILD types, thus supporting our hypotheses. In-silico analyses show that CTHRC1 indirectly activates and phosphorylates SMAD3, which in turn cross-regulates TGF-B1. CTHRC1 also may regulate the expression and transcription of TGFB-1 via WNT5A and its regulatory relationship with CTNNB1. Conclusion: In-silico pathway analyses demonstrate that CTHRC1 may be an important biomarker in ILD. Analysis of plasma samples indicates that CTHRC1 expression is positively associated with ILD affectation, with autoimmune ILD having the highest average CTHRC1 values. While characterizing CTHRC1 levels in plasma can help to differentiate among ILD types and predict response to Pirfenidone, the extent to which plasma CTHRC1 level is a function of ILD severity or chronicity is unknown.

Keywords: interstitial lung disease, CTHRC1, idiopathic pulmonary fibrosis, pathway analyses

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