Search results for: cardio vascular pathologies

Authors: Nandhakumar Elumalai, Purushothaman Ayyakannu, Sachidanandam T. Panchanatham

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Background: Understanding the basic mechanisms and factors underlying the tumor growth and invasion has gained attention in recent times. The processes of angiogenesis and apoptosis are known to play a vital role in various stages of cancer. The vascular endothelial growth factor (VEGF) is well established as one of the key regulators of tumor angiogenesis while MMPs are known for their exclusive ability to degrade ECM. Objective: The present study was designed to evaluate the pro apoptotic and anti angiogenic activity of the herbal formulation Shemamruthaa. The anticancer activity of Shemamruthaa was tested in breast cancer cell line (MCF-7). Results of MTT, trypan blue and flow cytometric analysis of apoptotis suggested that Shemamruthaa can induce cytotoxicity in cancer cells, in a concentration- and time dependent manner and induce apoptosis. With these results, we further evaluated the antiangiogenic and pro-apoptotic activities of Shemamruthaa in DMBA induced mammary carcinoma in Sprague Dawley rats. Flavono tumour was induced in 8-week-old Sprague-Dawley rats by gastric intubation of 25 mg DMBA in 1ml olive oil. After 90 days of induction period, the rats were orally administered with Shemamruthaa (400 mg/kg body wt) for 45 days. Treatment with the drug SM significantly modulated the expression of p53, MMP-2, MMP-3, MMP-9 and VEGF by means of its anti angiogenic and protease inhibiting activity. Conclusion: Based on these results, it might be concluded that the formulation, Shemamruthaa, constituted of dried flowers of Hibiscus rosa-sinensis, fruits of Emblica officinalis, and honey has been found to exhibit pronounced antiproliferative and apoptotic effects. This enhanced anticancer effect of Shemamruthaa might be attributed to the synergistic action of polyphenols such as flavonoids, tannins, alkaloids, glycosides, saponins, steroids, terpenoids, vitamin C, niacin, pyrogallol, hydroxymethylfurfural, trilinolein, and other compounds present in the formulation. Collectively, these results demonstrate that Shemamruthaa holds potential to be developed as a potent chemotherapeutic agent against mammary carcinoma.

Keywords: Shemamruthaa, flavonoids, MCF-7 cell line, mammary cancer

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Authors: Doran C. Kalmin

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The descending genicular artery (DGA) perforator free flap provides an alternative to free flap reconstruction based on a review of the literature detailing both anatomical and clinical studies. The descending genicular artery (DGA) supplies skin, muscle, tendon, and bone located around the medial aspect of the knee that has been used in several pioneering reports in reconstructing defects located in various areas throughout the body. After the success of the medial femoral condyle flap in early studies, a small number of studies have been published detailing the use of the DGA in free flap reconstruction. Despite early success in the use of the DGA flap, acceptance within the Plastic and Reconstructive Surgical community has been limited due primarily to anatomical variations of the pedicle. This literature review is aimed at detailing the progression of the DGA perforator free flap and its variations as an alternative and reliable free flap for reconstruction of composite defects with an exploration into both anatomical and clinical studies. A literature review was undertaken, and the progression of the DGA flap is explored from the early review by Acland et al. pioneering the saphenous free flap to exploring modern changes and studies of the anatomy of the DGA. An extensive review of the literature was undertaken that details the anatomy and its variations, approaches to harvesting the flap, the advantages, and disadvantages of the DGA perforator free flap as well as flap outcomes. There are 15 published clinical series of DGA perforator free flaps that incorporate cutaneous, osteoperiosteal, cartilage, osteocutaneous, osteoperiosteal and muscle, osteoperiosteal and subcutaneous and tendocutatenous. The commonest indication for using a DGA free flap was for non-union of bone, particularly that of the scaphoid whereby the medial femoral condyle could be used. In the case series, a success rate of over 90% was established, showing that these early studies have had good success with a wide range of tissue transfers. The greatest limitation is the anatomical variation of the DGA and therefore, the challenges associated with raising the flap. Despite the variation in anatomy and around 10-15% absence of the DGA, the saphenous artery can be used as well as the superior medial genicular artery if the vascular bone is required as part of the flap. Despite only a handful of anatomical and clinical studies describing the DGA perforator free flap, it ultimately provides a reliable flap that can include a variety of composite structure used for reconstruction in almost any area throughout the body. Although it has limitations, it provides a reliable option for free flap reconstruction that can routinely be performed as a single-stage procedure.

Keywords: anatomical study, clinical study, descending genicular artery, literature review, perforator free flap reconstruction

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Authors: Mende Mensa Sorato, Majid Davari, Abbas Kebriaeezadeh, Nizal Sarrafzadegan, Tamiru Shibru, Behzad Fatemi

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Markov model, like cardiovascular disease (CVD) policy model based simulation, is being used for evaluating the cost-effectiveness of hypertension treatment. Stroke, angina, myocardial infarction (MI), cardiac arrest, and all-cause mortality were included in this model. Hypertension is a risk factor for a number of vascular and cardiac complications and CVD outcomes. Objective: This systematic review was conducted to evaluate the comprehensiveness of this model across different regions globally. Methods: We searched articles written in the English language from PubMed/Medline, Ovid/Medline, Embase, Scopus, Web of Science, and Google scholar with a systematic search query. Results: Thirteen cohort studies involving a total of 2,165,770 (1,666,554 hypertensive adult population and 499,226 adults with treatment-resistant hypertension) were included in this scoping review. Hypertension is clearly associated with coronary heart disease (CHD) and stroke mortality, unstable angina, stable angina, MI, heart failure (HF), sudden cardiac death, transient ischemic attack, ischemic stroke, subarachnoid hemorrhage, intracranial hemorrhage, peripheral arterial disease (PAD), and abdominal aortic aneurism (AAA). Association between HF and hypertension is variable across regions. Treatment resistant hypertension is associated with a higher relative risk of developing major cardiovascular events and all-cause mortality when compared with non-resistant hypertension. However, it is not included in the previous CVD policy model. Conclusion: The CVD policy model used can be used in most regions for the evaluation of the cost-effectiveness of hypertension treatment. However, hypertension is highly associated with HF in Latin America, the Caribbean, Eastern Europe, and Sub-Saharan Africa. Therefore, it is important to consider HF in the CVD policy model for evaluating the cost-effectiveness of hypertension treatment in these regions. We do not suggest the inclusion of PAD and AAA in the CVD policy model for evaluating the cost-effectiveness of hypertension treatment due to a lack of sufficient evidence. Researchers should consider the effect of treatment-resistant hypertension either by including it in the basic model or during setting the model assumptions.

Keywords: cardiovascular disease policy model, cost-effectiveness analysis, hypertension, systematic review, twelve major cardiovascular events

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Authors: Lamia Bouzgarrou, Amira Omrane, Malika Azzouzi, Asma Kheder, Amira Saadallah, Ilhem Boussarsar, Kamel Rejeb

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Introduction: Increasing the women’s labor force participation is a political issue in countries with developed economies and those with low growth prospects. However, in the labor market, women continue to face several obstacles, either for the integration or for the maintenance at work. This study aims to assess the prevalence of premature withdrawal from working life -due to invalidity or medical justified early retirement- among active women in the Tunisian center and to identify its determinants. Material and methods: We conducted a cross-sectional study, over one year, focusing on the agreement for invalidity or early retirement for premature usury of the body- delivered by the medical commission of the National Health Insurance Fund (CNAM) in the central Tunisian district. We exhaustively selected women's files. Data related to Socio-demographic characteristics, professional and medical ones, were collected from the CNAM's administrative and medical files. Results: During the period of one year, 222 women have had an agreement for premature departure of their professional activity. Indeed, 149 women (67.11%) benefit of from invalidity agreement and 20,27% of them from favorable decision for early retirement. The average age was 50 ± 6 years with extremes of 23 and 62 years, and 18.9% of women were under 45 years. Married women accounted for 69.4% and 59.9% of them had at least one dependent child in charge. The average professional seniority in the sector was 23 ± 8 years. The textile-clothing sector was the most affected, with 70.7% of premature departure. Medical reasons for withdrawal from working life were mainly related to neuro-degenerative diseases in 46.8% of cases, rheumatic ones in 35.6% of cases and cardiovascular diseases in 22.1% of them. Psychiatric and endocrine disorders motivated respectively 17.1% and 13.5% of these departures. The evaluation of the sequels induced by these pathologies concluded to an average permanent partial disability equal to 61.4 ± 17.3%. The analytical study concluded that the agreement of disability or early retirement was correlated with the insured ‘age (p = 10-3), the professional seniority (p = 0.003) and the permanent partial incapacity (PPI) rate assessed by the expert physician (p = 0.04). No other social or professional factors were correlated with this decision. Conclusion: Despite many advances in labour law and Tunisian legal text on employability, women still exposed to several social and professional inequalities (payment inequality, precarious work ...). Indeed, women are often pushed to accept working in adverse conditions, thus they are more vulnerable to develop premature wear on the body and being forced to premature departures from the world of work. These premature withdrawals from active life are not only harmful to the concerned women themselves, but also associated with considerable costs for the insurance organism and the society. In order to ensure maintenance at work for women, a political commitment is imperative in the implementation of global prevention strategies and the improvement of working conditions, particularly in our socio-cultural context.

Keywords: Active Women , Early Retirement , Invalidity , Maintenance at Work

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Authors: Ghasem Yazdanpanah, Mona Kakavand, Hassan Niknejad

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Objectives: An important issue in tissue engineering (TE) is hemocompatibility. The current engineered vessels are seriously at risk of thrombus formation and stenosis. Amnion (AM) is the innermost layer of fetal membranes that consists of epithelial and mesenchymal sides. It has the advantages of low immunogenicity, anti-inflammatory and anti-bacterial properties as well as good mechanical properties. We recently introduced the amnion as a natural biomaterial for tissue engineering. In this study, we have evaluated hemocompatibility of amnion as potential biomaterial for tissue engineering. Materials and Methods: Amnions were derived from placentas of elective caesarean deliveries which were in the gestational ages 36 to 38 weeks. Extracted amnions were washed by cold PBS to remove blood remnants. Blood samples were obtained from healthy adult volunteers who had not previously taken anti-coagulants. The blood samples were maintained in sterile tubes containing sodium citrate. Plasma or platelet rich plasma (PRP) were collected by blood sample centrifuging at 600 g for 10 min. Hemocompatibility of the AM samples (n=7) were evaluated by measuring of activated partial thromboplastin time (aPTT), prothrombin time (PT), hemolysis, and platelet aggregation tests. P-selectin was also assessed by ELISA. Both epithelial and mesenchymal sides of amnion were evaluated. Glass slide and expanded polytetrafluoroethylene (ePTFE) samples were defined as control. Results: In comparison with glass as control (13.3 ± 0.7 s), prothrombin time was increased significantly while each side of amnion was in contact with plasma (p<0.05). There was no significant difference in PT between epithelial and mesenchymal surfaces (17.4 ± 0.7 s vs. 15.8 ± 0.7 s, respectively). However, aPPT was not significantly changed after incubation of plasma with amnion epithelial and mesenchymal surfaces or glass (28.61 ± 1.39 s, 31.4 ± 2.66 s, glass, 30.76 ± 2.53 s, respectively, p>0.05). Amnion surfaces, ePTFE and glass samples have less hemolysis induction than water considerably (p<0.001), in which no differences were detected. Platelet aggregation measurements showed that platelets were less stimulated by the amnion epithelial and mesenchymal sides, in comparison with ePTFE and glass. In addition, reduction in amount of p-selectin, as platelet activation factor, after incubation of samples with PRP indicated that amnion has less stimulatory effects on platelets than ePTFE and glass. Conclusion: Amnion as a natural biomaterial has the potential to be used in tissue engineering. Our results suggest that amnion has appropriate hemocompatibility to be employed as a vascular substitute.

Keywords: amnion, hemocompatibility, tissue engineering, biomaterial

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Authors: Daphne Meza, Louie Abejar, David A. Rubenstein, Wei Yin

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Endothelial cell (ECs) morphology and function is highly impacted by the mechanical stresses these cells experience in vivo. Any change in the mechanical environment can trigger pathological EC responses. A detailed understanding of EC morphological response and function upon subjection to individual and simultaneous mechanical stimuli is needed for advancement in mechanobiology and preventive medicine. To investigate this, a programmable device capable of simultaneously applying physiological fluid shear stress (FSS) and cyclic strain (CS) has been developed, characterized and validated. Its validation was performed both experimentally, through tracer tracking, and theoretically, through the use of a computational fluid dynamics model. The effectiveness of the device was evaluated through EC morphology changes under mechanical loading conditions. Changes in cell morphology were evaluated through: cell and nucleus elongation, cell alignment and junctional actin production. The results demonstrated that the combined FSS-CS stimulation induced visible changes in EC morphology. Upon simultaneous fluid shear stress and biaxial tensile strain stimulation, cells were elongated and generally aligned with the flow direction, with stress fibers highlighted along the cell junctions. The concurrent stimulation from shear stress and biaxial cyclic stretch led to a significant increase in cell elongation compared to untreated cells. This, however, was significantly lower than that induced by shear stress alone, indicating that the biaxial tensile strain may counteract the elongating effect of shear stress to maintain the shape of ECs. A similar trend was seen in alignment, where the alignment induced by the concurrent application of shear stress and cyclic stretch fell in between that induced by shear stress and tensile stretch alone, indicating the opposite role shear stress and tensile strain may play in cell alignment. Junctional actin accumulation was increased upon shear stress alone or simultaneously with tensile stretch. Tensile stretch alone did not change junctional actin accumulation, indicating the dominant role of shear stress in damaging EC junctions. These results demonstrate that the shearing-stretching device is capable of applying well characterized dynamic shear stress and tensile strain to cultured ECs. Using this device, EC response to altered mechanical environment in vivo can be characterized in vitro.

Keywords: cyclic stretch, endothelial cells, fluid shear stress, vascular biology

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Authors: Amelia J. McFarland, Andrew K. Davey, Shailendra Anoopkumar-Dukie

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Microglia are the resident macrophage population of the central nervous system (CNS), contributing to both innate and adaptive immune response, and brain homeostasis. Activation of microglia occurs in response to a multitude of pathogenic stimuli in their microenvironment; this induces morphological and functional changes, resulting in a state of acute neuroinflammation which facilitates injury resolution. Adequate microglial function is essential for the health of the neuroparenchyma, with microglial dysfunction implicated in numerous CNS pathologies. Given the critical role that these macrophage-derived cells play in CNS homeostasis, there is a high demand for microglial models suitable for use in neuroscience research. The isolation of primary human microglia, however, is both difficult and costly, with microglial activation an unwanted but inevitable result of the extraction process. Consequently, there is a need for the development of alternative experimental models which exhibit morphological, biochemical and functional characteristics of human microglia without the difficulties associated with primary cell lines. In this study, our aim was to evaluate whether THP-1 human peripheral blood monocytes would display microglial-like qualities following an induced differentiation, and, therefore, be suitable for use as surrogate microglia. To achieve this aim, THP-1 human peripheral blood monocytes from acute monocytic leukaemia were differentiated with a range of phorbol 12-myristate 13-acetate (PMA) concentrations (50-200 nM) using two different protocols: a 5-day continuous PMA exposure or a 3-day continuous PMA exposure followed by a 5-day rest in normal media. In each protocol and at each PMA concentration, microglial-like cell morphology was assessed through crystal violet staining and the presence of CD-14 microglial / macrophage cell surface marker. Lipopolysaccharide (LPS) from Escherichia coli (055: B5) was then added at a range of concentrations from 0-10 mcg/mL to activate the PMA-differentiated THP-1 cells. Functional microglial-like behavior was evaluated by quantifying the release of prostaglandin (PG)-E2 and pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α using mediator-specific ELISAs. Furthermore, production of global reactive oxygen species (ROS) and nitric oxide (NO) were determined fluorometrically using dichlorodihydrofluorescein diacetate (DCFH-DA) and diaminofluorescein diacetate (DAF-2-DA) respectively. Following PMA-treatment, it was observed both differentiation protocols resulted in cells displaying distinct microglial morphology from 10 nM PMA. Activation of differentiated cells using LPS significantly augmented IL-1β, TNF-α and PGE2 release at all LPS concentrations under both differentiation protocols. Similarly, a significant increase in DCFH-DA and DAF-2-DA fluorescence was observed, indicative of increases in ROS and NO production. For all endpoints, the 5-day continuous PMA treatment protocol yielded significantly higher mediator levels than the 3-day treatment and 5-day rest protocol. Our data, therefore, suggests that the differentiation of THP-1 human monocyte cells with PMA yields a homogenous microglial-like population which, following stimulation with LPS, undergo activation to release a range of pro-inflammatory mediators associated with microglial activation. Thus, the use of PMA-differentiated THP-1 cells represents a suitable microglial model for in vitro research.

Keywords: differentiation, lipopolysaccharide, microglia, monocyte, neuroscience, THP-1

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Authors: Alla Ovsyannikova, Oksana Rymar, Elena Shakhtshneider, Mikhail Voevoda

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In Siberia endocrinologists increasingly noted young patients with the course of diabetes mellitus differing from 1 and 2 types. Therefore we did a molecular genetic study for this group of patients to verify the monogenic forms of diabetes mellitus in them and researched the characteristics of this pathology. When confirming the monogenic form of diabetes, we performed a correction therapy for many patients (transfer from insulin to tablets), prevented specific complications, examined relatives and diagnosed their diabetes at the preclinical stage, revealed phenotypic characteristics of the pathology which led to the high significance of this work. Materials and Methods: We observed 5 patients (4 families). We diagnosed MODY (Maturity Onset Diabetes of the Young) during the molecular genetic testing (direct automatic sequencing). All patients had a full clinical examination, blood samples for biochemical research, determination of C-peptide and TSH, antibodies to b-cells, microalbuminuria, abdominal ultrasound, heart and thyroid ultrasound, examination of ophthalmologist. Results: We diagnosed 3 rare types of MODY: two women had MODY8, one man – MODY6 and man and his mother - MODY12. Patients with types 8 and 12 had clinical features. Age of onset hyperglycemia ranged from 26 to 34 years. In a patient with MODY6 fasting hyperglycemia was detected during a routine examination. Clinical symptoms, complications were not diagnosed. The patient observes a diet. In the first patient MODY8 was detected during first pregnancy, she had itchy skin and mostly postprandial hyperglycemia. Upon examination we determined glycated hemoglobin 7.5%, retinopathy, non-proliferative stage, peripheral neuropathy. She uses a basic bolus insulin therapy. The second patient with MODY8 also had clinical manifestations of hyperglycemia (pruritus, thirst), postprandial hyperglycemia and diabetic nephropathy, a stage of microalbuminuria. The patient was diagnosed autoimmune thyroiditis. She used inhibitors of DPP-4. The patient with MODY12 had an aggressive course. In the detection of hyperglycemia he had complaints of visual impairment, intense headaches, leg cramps. The patient had a history of childhood convulsive seizures of non-epileptic genesis, without organic pathology, which themselves were stopped at the age of 12 years. When we diagnosed diabetes a patient was 28 years, he had hypertriglyceridemia, atherosclerotic plaque in the carotid artery, proliferative retinopathy (lacerocoagulation). Diabetes and early myocardial infarction were observed in three cases in family. We prescribe therapy with sulfonylureas and SGLT-2 inhibitors with a positive effect. At the patient's mother diabetes began at a later age (30 years) and a less aggressive course was observed. She also has hypertriglyceridemia and uses oral hypoglycemic drugs. Conclusions: 1) When young patients with hyperglycemia have extrapancreatic pathologies and diabetic complications with a short duration of diabetes we can assume they have one of type of MODY diabetes. 2) In patients with monogenic forms of diabetes mellitus, the clinical manifestations of hyperglycemia in each succeeding generation are revealed at an earlier age. Research had increased our knowledge of the monogenic forms of diabetes. The reported study was supported by RSCF, research project No. 14-15-00496-P.

Keywords: diabetes mellitus, MODY diabetes, monogenic forms, young patients

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Authors: Clara Luwe, Oliver Harness, Helena Meally, Kim Martin, Alexandra Harrington

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Background: The role of ‘Renal Specialist Podiatrist’ originated in 2022 due to prevailing evidence of patients with diabetes and end-stage renal disease (ESRD) on haemodialysis (HD) and active ulcerations that were at higher risk of rapid deterioration, foot-related hospital admissions, and lower limb amputations. This role started in April 2022 with the aim of screening all patients on haemodialysis and instigating preventative measures to reduce serious foot related complications. Methods: A comprehensive neurovascular foot assessment was completed to establish baseline vascular status and identify those with peripheral arterial disease (PAD) for all patients on HD. Individual’s foot risk was stratified, advice and education tailored and issued. Identifying all diabetes patients on HD as high-risk for diabetic foot complications. Major Findings: All patients screened revealed over half of the caseload had diabetes, and more than half had a clinical presentation of PAD. All those presenting with ulcerations had a diagnosis of diabetes. Of the presenting ulcerations, the majority of these ulcers predated the renal specialist post and were classified as severe >3 SINBAD Score. Since April’22, complications have been identified quicker, reducing the severity (SINBAD<3 or below), and have improved healing times, in line with the national average. During the eight months of the role being in place, we have seen a reduction in minor amputations and no major amputations. Conclusion: By screening all patients on haemodialysis and focusing on education, early recognition of complications, appropriate treatment, and timely onward referral, we can reduce the risk of foot Diabetic foot ulcerations and lower limb amputations. Having regular podiatry input to stratify and facilitate high-risk, active wound patients across different services has helped to keep these patients stable, prevent amputations, and reduce foot-related hospital admissions and mortality from foot-related disease. By improving the accessibility to a specialist podiatrist, patients felt able to raise concerns sooner. This has helped to implement treatment at the earliest possible opportunity, enabling the identification and healing of ulcers at an earlier and less complex stage (SINBAD <3), thus, preventing potential limb-threatening complications.

Keywords: renal, podiatry, haemodialysis, prevention, early detection

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Authors: Manali Jain, Neeta Singh, Raunaq Fatima, Soniya Nityanand, Mandakini Pradhan, Chandra Prakash Chaturvedi

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Isolated Congenital Heart Defect (ICHD) is the major cause of neonatal death worldwide among all forms of CHDs. A significant proportion of fetuses with ICHD die in the neonatal period if no treatment is provided. Recently, stem cell therapies have emerged as a potential approach to ameliorate ICHD in children. ICHD is characterized by cardiac structural abnormalities during embryogenesis due to alterations in the cardiomyogenic properties of a pool of cardiac progenitors/ stem cells associated with fetal heart development. The stem cells present in the amniotic fluid (AF) are of fetal origin and may reflect the physiological and pathological changes in the fetus during embryogenesis. Therefore, in the present study, the cardiomyogenic potential of AF-MSCs derived from fetuses with ICHD (ICHD AF-MSCs) has been evaluated and compared with that of AF-MSCs of structurally normal fetuses (normal AF-MSCs). Normal and ICHD AF-MSC were analyzed for the expression of cardiac progenitor markers viz., stage-specific embryonic antigen-1 (SSEA-1), vascular endothelial growth factor 2 (VEGFR-2) and platelet-derived growth factor receptor-alpha (PDGFR-α) by flow cytometry. The immunophenotypic characterization revealed that ICHD AF-MSCs have significantly lower expression of cardiac progenitor markers VEGFR-2 (0.14% ± 0.6 vs.48.80% ± 0.9; p <0.01), SSEA-1 (70.86% ± 2.4 vs. 88.36% ±2.7; p <0.01), and PDGFR-α (3.92% ± 1.8 vs. 47.59% ± 3.09; p <0.01) in comparison to normal AF-MSCs. Upon induction with 5’-azacytidine for 21 days, ICHD AF-MSCs showed a significantly down-regulated expression of cardiac transcription factors such as GATA-4 (0.4 ± 0.1 vs. 6.8 ± 1.2; p<0.01), ISL-1 (2.3± 0.6 vs. 14.3 ± 1.12; p<0.01), NK-x 2-5 (1.1 ± 0.3 vs. 14.1 ±2.8; p<0.01), TBX-5 (0.4 ± 0.07 vs. 4.4 ± 0.3; p<0.001), and TBX-18 (1.3 ± 0.2 vs. 4.19 ± 0.3; p<0.01) when compared with the normal AF-MSCs. Furthermore, immunocytochemical staining revealed that both types of AF-MSCs could differentiate into cardiovascular lineages and express cardiomyogenic, endothelial, and smooth muscle actin markers, viz., cardiac troponin (cTNT), CD31, and alpha-smooth muscle actin (α-SMA). However, normal AF-MSCs showed an enhanced expression of cTNT (p<0.001), CD31 (p<0.01), and α-SMA (p<0.05), compared to ICHD AF-MSCs. Overall, these results suggest that the ICHD-AF-MSCs have a defective cardiomyogenic differentiation potential and that the defects in these stem cells may have a role in the pathogenesis of ICHD.

Keywords: amniotic fluid, cardiomyogenic potential, isolated congenital heart defect, mesenchymal stem cells

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Authors: Norimichi Nagano, Yoshio Hirano, Tsutomu Yasukawa

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Mesenchymal stem cells are thought to confer neuroprotection, facilitate tissue regeneration and exert their effects on retinal degenerative diseases, however, adverse events such as proliferative vitreoretinopathy and preretinal membrane disease associated with cell suspension transplantation have also been reported. We have recently developed human (allogeneic) adipose tissue-derived mesenchymal stem cell (adMSC) sheets through our proprietary sheet transformation technique, which could potentially mitigate these adverse events. To clarify the properties of our adMSC sheets named PAL-222, we performed in vitro studies such as viability testing, cytokine secretions by ELISA, immunohistochemical study, and migration assay. The viability of the cells exceeded 70%. Vascular Endothelial Growth Factor (VEGF) and Pigment Epithelium-Derived Factor (PEDF), which are quite important cytokines for the retinal area, were observed. PAL-222 expressed type I collagen, a strength marker, type IV collagen, a marker of the basement membrane, and elastin, an elasticity marker. Finally, the migration assay was performed and showed negative, which means that PAL-222 is stably kept in the topical area and does not come to pieces. Next, to evaluate the efficacy in vivo, we transplanted PAL-222 into the subretinal space of the eye of Royal College of Surgeons rats with congenital retinal degeneration and assessed it for three weeks after transplantation. We confirmed that PAL-222 suppressed the decrease in the thickness of the outer nuclear layer, which means that the photoreceptor protective effect treated with PAL-222 was significantly higher than that in the sham group. (p < 0.01). This finding demonstrates that PAL-222 showed their retinoprotective effect in a model of congenital retinal degeneration. As the study suggested the efficacy of PAL-222 in both in vitro and in vivo studies, we are presently engaged in clinical trials of PAL-222 for myopic chorioretinal atrophy, which is one of the retinal degenerative diseases, for the purpose of regenerative medicine.

Keywords: cell sheet, clinical trial, mesenchymal stem cell, myopic chorioretinal atrophy

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Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche

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It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.

Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells

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Authors: D. Signore, M. Ferraiuolo, P. Caramuta, O. Petrella, C. Toscano

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The Digital Image Correlation (DIC) is a newly developed optical technique that is spreading in all engineering sectors because it allows the non-destructive estimation of the entire surface deformation without any contact with the component under analysis. These characteristics make the DIC very appealing in all the cases the global deformation state is to be known without using strain gages, which are the most used measuring device. The DIC is applicable to any material subjected to distortion caused by either thermal or mechanical load, allowing to obtain high-definition mapping of displacements and deformations. That is why in the civil and the transportation industry, DIC is very useful for studying the behavior of metallic materials as well as of composite materials. DIC is also used in the medical field for the characterization of the local strain field of the vascular tissues surface subjected to uniaxial tensile loading. DIC can be carried out in the two dimension mode (2D DIC) if a single camera is used or in a three dimension mode (3D DIC) if two cameras are involved. Each point of the test surface framed by the cameras can be associated with a specific pixel of the image, and the coordinates of each point are calculated knowing the relative distance between the two cameras together with their orientation. In both arrangements, when a component is subjected to a load, several images related to different deformation states can be are acquired through the cameras. A specific software analyzes the images via the mutual correlation between the reference image (obtained without any applied load) and those acquired during the deformation giving the relative displacements. In this paper, a metrological characterization of the digital image correlation is performed on aluminum and composite targets both in static and dynamic loading conditions by comparison between DIC and strain gauges measures. In the static test, interesting results have been obtained thanks to an excellent agreement between the two measuring techniques. In addition, the deformation detected by the DIC is compliant with the result of a FEM simulation. In the dynamic test, the DIC was able to follow with a good accuracy the periodic deformation of the specimen giving results coherent with the ones given by FEM simulation. In both situations, it was seen that the DIC measurement accuracy depends on several parameters such as the optical focusing, the parameters chosen to perform the mutual correlation between the images and, finally, the reference points on image to be analyzed. In the future, the influence of these parameters will be studied, and a method to increase the accuracy of the measurements will be developed in accordance with the requirements of the industries especially of the aerospace one.

Keywords: accuracy, deformation, image correlation, mechanical analysis

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Authors: C. Sancho Salvatierra, J. M. Martinez Nieto, R. García Gonzalez-Gordon, M. I. Martinez Bellido

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Introduction: Nature could act as an asset for human health protecting against possible diseases and promoting the state of both physical and mental health. Goals: This paper aims to determine which natural elements present evidence that show positive influence on human health, on which particular aspects and how. It also aims to determine the best biomarkers to measure such influence. Method: A systematic literature review was carried out. First, a general free text search was performed in databases, such as Scopus, PubMed or PsychInfo. Secondly, a specific search was performed combining keywords in order of increasing complexity. Also the Snowballing technique was used and it was consulted in the CSIC’s (The Spanish National Research Council). Databases: Of the 130 articles obtained and reviewed, 80 referred to natural elements that influenced health. These 80 articles were classified and tabulated according to the nature elements found, the health aspects studied, the health measurement parameters used and the measurement techniques used. In this classification the results of the studies were codified according to whether they were positive, negative or neutral both for the elements of nature and for the aspects of health studied. Finally, the results of the 80 selected studies were summarized and categorized according to the elements of nature that showed the greatest positive influence on health and the biomarkers that had shown greater reliability to measure said influence. Results: Of the 80 articles studied, 24 (30.0%) were reviews and 56 (70.0%) were original research articles. Among the 24 reviews, 18 (75%) found positive results of natural elements on health, and 6 (25%) both positive and negative effects. Of the 56 original articles, 47 (83.9%) showed positive results, 3 (5.4%) both positive and negative, 4 (7.1%) negative effects, and 2 (3.6%) found no effects. The results reflect positive effects of different elements of nature on the following pathologies: diabetes, high blood pressure, stress, attention deficit hyperactivity disorder, psychotic, anxiety and affective disorders. They also show positive effects on the following areas: immune system, social interaction, recovery after illness, mood, decreased aggressiveness, concentrated attention, cognitive performance, restful sleep, vitality and sense of well-being. Among the elements of nature studied, those that show the greatest positive influence on health are forest immersion, natural views, daylight, outdoor physical activity, active transport, vegetation biodiversity, natural sounds and the green residences. As for the biomarkers used that show greater reliability to measure the effects of natural elements are the levels of cortisol (both in blood and saliva), vitamin D levels, serotonin and melatonin, blood pressure, heart rate, muscle tension and skin conductance. Conclusions: Nature is an asset for health, well-being and quality of life. Awareness programs, education and health promotion are needed based on the elements that nature brings us, which in turn generate proactive attitudes in the population towards the protection and conservation of nature. The studies related to this subject in Spain are very scarce. Aknowledgements. This study has been promoted and partially financed by the Environmental Foundation Jaime González-Gordon.

Keywords: health, green areas, nature, well-being

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Authors: Demet Devrimsel Dogan, Ecem Deniz Kirkpantur, Muharrem Dogan, Ahmet Aykut, Ebru Unal Akoglu, Ozge Ecmel Onur

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Introduction: Median Arcuate Ligament Syndrome (MALS) is a rare cause of chronic abdominal pain due to external compression of the celiac trunk by a fibrous arch that unites diaphragmatic crura on each side of the aortic hiatus. While 10-24% of the population may suffer from compression of celiac trunk, it rarely causes patients to develop symptoms. The typical clinical triad of symptoms includes postprandial epigastric pain, weight loss and vomiting. The diagnosis can be made using thin section multi-detector computed tomography (CT) scans which delineate the ligament and the compressed vessel. The treatment of MALS is aimed at relieving the compression of the celiac artery to restore adequate blood flow through the vessel and neurolysis to address chronic pain. Case: A 68-year-old male presented to our clinic with acute postprandial epigastric pain. This was patients’ first attack, and the pain was the worst pain of his life. The patient did not have any other symptoms like nausea, vomiting, chest pain or dyspnea. In his medical history, the patient has had an ischemic cerebrovascular stroke 5 years ago which he recovered with no sequel, and he was using 75 mg clopidogrel and 100 mg acetylsalicylic acid. He was not using any other medication and did not have a story of cardiovascular disease. His vital signs were stable (BP:113/72 mmHg, Spo2:97, temperature:36.3°C, HR:90/bpm). In his electrocardiogram, there was ST depression in leads II, III and AVF. In his physical examination, there was only epigastric tenderness, other system examinations were normal. Physical examination through his upper gastrointestinal system showed no bleeding. His laboratory results were as follows: creatinine:1.26 mg/dL, AST:42 U/L, ALT:17 U/L, amylase:78 U/L, lipase:26 U/L, troponin:10.3 pg/ml, WBC:28.9 K/uL, Hgb:12.7 gr/dL, Plt:335 K/uL. His serial high-sensitive troponin levels were also within normal limits, his echocardiography showed no segmental wall motion abnormalities, an acute myocardial infarction was excluded. In his abdominal ultrasound, no pathology was founded. Contrast-enhanced abdominal CT and CT angiography reported ‘thickened diaphragmatic cruras are compressing and stenosing truncus celiacus superior, this is likely compatible with MALS’. The patient was consulted to general surgery, and they admitted the patient for laparoscopic ligament release. Results: MALS is a syndrome that causes postprandial pain, nausea and vomiting as its most common symptoms. Affected patients are normally young, slim women between the ages of 30 and 50 who have undergone extensive examinations to find the source of their symptoms. To diagnose MALS, other underlying pathologies should initially be excluded. The gold standard is aortic angiography. Although diagnosis and treatment of MALS are unclear, symptom resolution has been achieved with multiple surgical modalities, including open, laparoscopic or robotic ligament release as well as celiac ganglionectomy, which often requires celiac artery revascularisation.

Keywords: differential diagnosis, epigastric pain, median arcuate ligament syndrome, celiac trunk

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Authors: Kasra Afsahi, Maryam Soheilifar, S. Hossein Hosseini

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Background: There is growing evidence that Cerebral Vascular Accident (CVA) can be a consequence of Covid-19 infection. Understanding novel treatment approaches are important in optimizing patient outcomes. Case: This case explores the use of Virtual Reality (VR) in the treatment of a 23-year-old COVID-positive female presenting with left hemiparesis in August 2020. Imaging showed right globus pallidus, thalamus, and internal capsule ischemic stroke. Conventional rehabilitation was started two weeks later, with virtual reality (VR) included. This game-based virtual reality (VR) technology developed for stroke patients was based on upper extremity exercises and functions for stroke. Physical examination showed left hemiparesis with muscle strength 3/5 in the upper extremity and 4/5 in the lower extremity. The range of motion of the shoulder was 90-100 degrees. The speech exam showed a mild decrease in fluency. Mild lower lip dynamic asymmetry was seen. Babinski was positive on the left. Gait speed was decreased (75 steps per minute). Intervention: Our game-based VR system was developed based on upper extremity physiotherapy exercises for post-stroke patients to increase the active, voluntary movement of the upper extremity joints and improve the function. The conventional program was initiated with active exercises, shoulder sanding for joint ROMs, walking shoulder, shoulder wheel, and combination movements of the shoulder, elbow, and wrist joints, alternative flexion-extension, pronation-supination movements, Pegboard and Purdo pegboard exercises. Also, fine movements included smart gloves, biofeedback, finger ladder, and writing. The difficulty of the game increased at each stage of the practice with progress in patient performances. Outcome: After 6 weeks of treatment, gait and speech were normal and upper extremity strength was improved to near normal status. No adverse effects were noted. Conclusion: This case suggests that VR is a useful tool in the treatment of a patient with covid-19 related CVA. The safety of newly developed instruments for such cases provides new approaches to improve the therapeutic outcomes and prognosis as well as increased satisfaction rate among patients.

Keywords: covid-19, stroke, virtual reality, rehabilitation

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Authors: Dalal Alghawas, Jetty Lee, Kaisa Poutanen, Hani El-Nezami

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Oat β-glucan a water soluble non starch linear polysaccharide has been approved as a cholesterol lowering agent by various food safety administrations and is commonly used to reduce the risk of heart disease. The molecular weight of oat β-glucan can vary depending on the extraction and fractionation methods. It is not clear whether the molecular weight has a significant impact at reducing the acceleration of atherosclerosis. The aim of this study was to investigate three different oat β-glucan fractionations on the development of atherosclerosis in vivo. With special focus on plaque stability and the intestinal barrier function. To test this, ApoE-/- female mice were fed a high fat diet supplemented with oat bran, high molecular weight (HMW) oat β-glucan fractionate and low molecular weight (LMW) oat β-glucan fractionate for 16 weeks. Atherosclerosis risk markers were measured in the plasma, heart and aortic tree. Plaque size was measured in the aortic root and aortic tree. ICAM-1, VCAM-1, E-Selectin, P-Selectin, protein levels were assessed from the aortic tree to determine plaque stability at 16 weeks. The expression of p22phox at the aortic root was evaluated to study the NADPH oxidase complex involved in nitric oxide bioavailability and vascular elasticity. The tight junction proteins E-cadherin and beta-catenin from western blot analyses were analysed as an intestinal barrier function test. Plasma LPS, intestinal D-lactate levels and hepatic FMO gene expression were carried out to confirm whether the compromised intestinal barrier lead to endotoxemia. The oat bran and HMW oat β-glucan diet groups were more effective than the LMW β-glucan diet group at reducing the plaque size and showed marked improvements in plaque stability. The intestinal barrier was compromised for all the experimental groups however the endotoxemia levels were higher in the LMW β-glucan diet group. The oat bran and HMW oat β-glucan diet groups were more effective at attenuating the development of atherosclerosis. Reasons for this could be due to the LMW oat β-glucan diet group’s low viscosity in the gut and the inability to block the reabsorption of cholesterol. Furthermore the low viscosity may allow more bacterial endotoxin translocation through the impaired intestinal barrier. In future food technologists should carefully consider how to incorporate LMW oat β-glucan as a health promoting food.

Keywords: Atherosclerosis, beta glucan, endotoxemia, intestinal barrier function

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Authors: Ageliki I. Katsarou, Andriana C. Kaliora, Antonia Chiou, Apostolos Papalois, Nick Kalogeropoulos, Nikolaos K. Andrikopoulos

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Chronic inflammation plays a pivotal role in CVD development, while phytochemicals have been shown to reduce CVD risk. Several studies have correlated olive oil consumption with CVD prevention and CVD risk reduction. However, the effect of individual olive oil macro- or micro-constituents and possible synergisms among them needs to be further elucidated. Herein, extra virgin olive oil (EVOO) lipidic and polar phenolics fractions were evaluated for their effect on inflammatory markers in cholesterol-fed rats. Oils combining different characteristics as to their polar phenolic content and lipid profile were used. Male Wistar rats were fed for 9 weeks on either a high-cholesterol diet (HCD) or a HCD supplemented with oils, either commercially available, i.e. EVOO, sunflower oil (SO), or modified as to their polar phenol content, i.e. phenolics deprived-EVOO (EVOOd), SO enriched with the EVOO phenolics (SOe). Post-intervention, aorta and blood samples were collected. HCD induced dyslipidemia, manifested by serum total cholesterol and low-density lipoprotein cholesterol elevation. Additionally, HCD resulted in higher adhesion molecules’ levels in rat aorta. In the case of E-selectin, this increase was attenuated by HCD supplementation with EVOO and EVOOd, while no alterations were observed in SO and SOe groups. No differences were observed between pairs of commercial and modified oils, indicating that oleates may be the components responsible for aorta E-selectin levels lowering. The same was true for vascular adhesion molecule-1 (VCAM-1); augmentation in cholesterol-fed animals was attenuated by EVOO and EVOOd diets, highlighting oleates effect. In addition, VCAM-1 levels were higher in SO group compared to the respective SOe, indicating that in the presence of phenolic compounds linoleic acid have become less prone to oxidation. Intercellular adhesion molecule-1 (ICAM-1) levels were higher in cholesterol-fed rats, however not affected by any of the oils supplemented during the intervention. Overall, EVOO was found superior in regulating adhesion molecule levels in rat aorta compared to SO. EVOO and EVOOd exhibited analogous effects on all adhesion molecules assessed, indicating that EVOO major constituents (oleates) improve E-selectin and VCAM-1 levels in rat aorta, independently from phenolics presence. Further research is needed to elucidate the effect of phenolics and oleates in other tissues.

Keywords: extra virgin olive oil, cholesterol-fed rats, polar phenolics, adhesion molecules

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Authors: Anjali Roy, Mirza S. Baig

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Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid rich plaque enriched with necrotic core, modified lipid accumulation, smooth muscle cells, endothelial cells, leucocytes and macrophages. Macrophage foam cells play a critical role in the occurrence and development of inflammatory atherosclerotic plaque. Foam cells are the fat-laden macrophages in the initial stage atherosclerotic lesion formation. Foam cells are an indication of plaque build-up, or atherosclerosis, which is commonly associated with increased risk of heart attack and stroke as a result of arterial narrowing and hardening. The mechanisms that drive atherosclerotic plaque progression remain largely unknown. Dissecting the molecular mechanism involved in process of macrophage foam cell formation will help to develop therapeutic interventions for atherosclerosis. To investigate the mechanism, we studied the role of nitric oxide synthase 1(NOS1)-mediated nitric oxide (NO) on low-density lipoprotein (LDL) uptake by bone marrow derived macrophages (BMDM). Using confocal microscopy, we found that incubation of macrophages with NOS1 inhibitor, TRIM (1-(2-Trifluoromethylphenyl) imidazole) or L-NAME (N omega-nitro-L-arginine methyl ester) prior to LDL treatment significantly reduces the LDL uptake by BMDM. Further, addition of NO donor (DEA NONOate) in NOS1 inhibitor treated macrophages recovers the LDL uptake. Our data strongly suggest that NOS1 derived NO regulates LDL uptake by macrophages and foam cell formation. Moreover, we also checked proinflammatory cytokine mRNA expression through real time PCR in BMDM treated with LDL and copper oxidized LDL (OxLDL) in presences and absences of inhibitor. Normal LDL does not evoke cytokine expression whereas OxLDL induced proinflammatory cytokine expression which significantly reduced in presences of NOS1 inhibitor. Rapid NOS-1-derived NO and its stable derivative formation act as signaling agents for inducible NOS-2 expression in endothelial cells, leading to endothelial vascular wall lining disruption and dysfunctioning. This study highlights the role of NOS1 as critical players of foam cell formation and would reveal much about the key molecular proteins involved in atherosclerosis. Thus, targeting NOS1 would be a useful strategy in reducing LDL uptake by macrophages at early stage of disease and hence dampening the atherosclerosis progression.

Keywords: atherosclerosis, NOS1, inflammation, oxidized LDL

Procedia PDF Downloads 127

Authors: Sahar Heidary

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

Keywords: radiology, radiotherapy, medical imaging, cancer treatment

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Authors: Otuwose E. Agyeno, Adeniyi A. Jayeola, Bashir A. Ajala

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P. esculentus is indigenous to Nigeria yet no wild relation has been encountered or reported. This has made it difficult to establish proper lineages between the varieties and landraces under cultivation. The present work is the first to determine the apormophy of 135 morphoanatomical characters in organs of 46 accessions drawn from 23 populations of this species based on dicta. The character states were coded in accession x character-state matrices and only 83 were informative and utilised for neighbour joining clustering based on euclidean values, and heuristic search in parsimony analysis using PAST ver. 3.15 software. Compatibility and evolutionary trends between accessions were then explored from values and diagrams produced. The low consistency indices (CI) recorded support monophyly and low homoplasy in this taxon. Agglomerative schedules based on character type and source data sets divided the accessions into mainly 3 clades, each of complexes of accessions. Solenostemon rotundifolius (Poir) J.K Morton was the outgroup (OG) used, and it occurred within the largest clades except when the characters were combined in a data set. The OG showed better compatibility with accessions of populations of landrace Isci, and varieties Riyum and Long’at. Otherwise, its aerial parts are more consistent with those of accessions of variety Bebot. The highly polytomous clades produced due to anatomical data set may be an indication of how stable such characters are in this species. Strict consensus trees with more than 60 nodes outputted showed that the basal nodes were strongly supported by 3 to 17 characters across the data sets, suggesting that populations of this species are more alike. The OG was clearly the first diverging lineage and closely related to accessions of landrace Gwe and variety Bebot morphologically, but different from them anatomically. It was also distantly related to landrace Fina and variety Long’at in terms of root, stem and leaf structural attributes. There were at least 5 other clades with each comprising of complexes of accessions from different localities and terrains within the study area. Spherical stem in cross section, size of vascular bundles at the stem corners as well as the alternate and whorl phyllotaxy are attributes which may have facilitated each other’s evolution in all accessions of the landrace Gwe, and they may be innovative since such states are not characteristic of the larger Lamiaceae, and Plectranthus L’Her in particular. In conclusion, this study has provided valuable information about infraspecific diversity in this taxon. It supports recognition of the varietal statuses accorded to populations of P. esculentus, as well as the hypothesis that the wild gene might have been distributed on the Jos Plateau. However, molecular characterisation of accessions of populations of this species would resolve this problem better.

Keywords: clustering, lineage, morphoanatomical characters, Nigeria, phylogenetics, Plectranthus esculentus, population

Procedia PDF Downloads 135

Authors: Elif Erdem, Nalan Kaya, Gonca Ozan, Durrin Ozlem Dabak, Enver Ozan

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This study was carried out to determine the histological and biochemical changes in the lungs of the rat pups exposed to tobacco smoke during pregnancy period and to investigate the protective effects of alpha lipoic acid, which is administered during pregnancy, on these changes. In our study, 24 six-week old Spraque-Dawley female rats weighing 160 ± 10 g were used (n:7). Rats were randomly divided into four equal groups: group I (control), group II (tobacco smoke), group III (tobacco smoke + alpha lipoic acid) and group IV (alpha lipoic acid). Rats in the group II, group III were exposed to tobacco smoke twice a day for one hour starting from eight weeks before mating and during pregnancy. In addition to tobacco smoke, 20 mg/kg of alpha lipoic acid was administered via oral gavage to the rats in the group III. Only alpha lipoic acid was administered to the rats in the group IV. Once after the delivery, all administrations were stopped. On the 7 and 21th days, the seven pups of all groups were decapitated. A portion of the lung was taken and stained with HE, PAS and Masson. In addition to immunohistochemical staining of surfactant protein A, vascular endothelial growth factor, caspase-3, TUNEL method was also used to determine apoptosis. Biochemical analyzes were performed with some part of the lung tissue specimens. In the histological evaluations performed under light microscopy, inflammatory cell increase, hemorrhagic areas, edema, interalveolar septal thickening, alveolar numbers decrease, degeneration of some bronchi and bronchial epithelium, epithelial cells that were fallen into the lumen and hyaline membrane formation were observed in tobacco smoke group. These findings were ameliorated in tobacco smoke + ALA group. Hyaline membrane formation was not detected in this group. The TUNEL positive cell numbers a significant increase was detected in the tobacco smoke group, whereas a significant decrease was detected in the tobacco smoke + ALA group. In terms of the immunoreactivity of both SP-A and VEGF, a significant decrease was observed in the tobacco smoke group, and a significant increase was observed in the tobacco smoke + ALA group. Regarding the immunoreactivity of caspase-3, there was a significant increase in the group of tobacco smoke and a significant decrease in the group of tobacco smoke + ALA. The malondialdehyde levels were determined to be significantly increased in the tobacco smoke group, and a significant decreased in the tobacco smoke + ALA. Glutathione and superoxide dismutase enzyme activities showed a significant decrease in the group of tobacco smoke and a significant increase in the tobacco smoke + ALA group. In conclusion, we suggest that the exposure to tobacco smoke during pregnancy leads to morphological, histopathological and functional changes on lung development by causing oxidative damage in lung tissues of neonatal rats and the maternal use of alpha lipoic acid can provide a protective effect on the neonatal lung development against this oxidative stress originating from tobacco smoke.

Keywords: alpha lipoic acid, lung, neonate, tobacco smoke, pregnancy

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Authors: Sergey N. Ermoliev, Margarita A. Belousova, Aida D. Goncharenko

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Application of the diagnostic complex of highly informative functional methods (electromyography, reodentography, laser Doppler flowmetry, reoperiodontography, vital computer capillaroscopy, optical tissue oximetry, laser fluorescence diagnosis) allows to perform a multifactorial analysis of the dental status and to prescribe complex etiopathogenetic treatment. Introduction. It is necessary to create a complex of innovative highly informative and safe functional diagnostic methods for improvement of the quality of patient treatment by the early detection of stomatologic diseases. The purpose of the present study was to investigate the etiology and pathogenesis of functional disorders identified in the pathology of hard tissue, dental pulp, periodontal, oral mucosa and chewing function, and the creation of new approaches to the diagnosis of dental diseases. Material and methods. 172 patients were examined. Density of hard tissues of the teeth and jaw bone was studied by intraoral ultrasonic densitometry (USD). Electromyographic activity of masticatory muscles was assessed by electromyography (EMG). Functional state of dental pulp vessels assessed by reodentography (RDG) and laser Doppler flowmetry (LDF). Reoperiodontography method (RPG) studied regional blood flow in the periodontal tissues. Microcirculatory vascular periodontal studied by vital computer capillaroscopy (VCC) and laser Doppler flowmetry (LDF). The metabolic level of the mucous membrane was determined by optical tissue oximetry (OTO) and laser fluorescence diagnosis (LFD). Results and discussion. The results obtained revealed changes in mineral density of hard tissues of the teeth and jaw bone, the bioelectric activity of masticatory muscles, regional blood flow and microcirculation in the dental pulp and periodontal tissues. LDF and OTO methods estimated fluctuations of saturation level and oxygen transport in microvasculature of periodontal tissues. With LFD identified changes in the concentration of enzymes (nicotinamide, flavins, lipofuscin, porphyrins) involved in metabolic processes Conclusion. Our preliminary results confirmed feasibility and safety the of intraoral ultrasound densitometry technique in the density of bone tissue of periodontium. Conclusion. Application of the diagnostic complex of above mentioned highly informative functional methods allows to perform a multifactorial analysis of the dental status and to prescribe complex etiopathogenetic treatment.

Keywords: electromyography (EMG), reodentography (RDG), laser Doppler flowmetry (LDF), reoperiodontography method (RPG), vital computer capillaroscopy (VCC), optical tissue oximetry (OTO), laser fluorescence diagnosis (LFD)

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Authors: Sundaresan Soundararajan, Chor Ngee Tan

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Introduction: Pyogenic spondylitis, otherwise treated conservatively with long term antibiotics, would require surgical debridement and reconstruction in about 10% to 20% of cases. The classical approach adopted many surgeons have always been anterior approach in ensuring thorough and complete debridement. This, however, comes with high rates of morbidity due to the nature of its access. Direct lateral retroperitoneal approach, which has been growing in usage in degenerative lumbar diseases, has the potential in treating pyogenic spondylitis with its ease of approach and relatively low risk of complications. Aims/Objectives: The objective of this study was to evaluate the effectiveness and clinical outcome of using lateral approach surgery in the surgical management of pyogenic spondylitis of the lumbar spine. Methods: Retrospective chart analysis was done on all patients who presented with pyogenic spondylitis (lumbar discitis/vertebral osteomyelitis) and had undergone direct lateral retroperitoneal lumbar vertebral debridement and posterior instrumentation between 2014 and 2016. Data on blood loss, surgical operating time, surgical complications, clinical outcomes and fusion rates were recorded. Results: A total of 6 patients (3 male and 3 female) underwent this procedure at a single institution by a single surgeon during the defined period. One patient presented with infected implant (PLIF) and vertebral osteomyelitis while the other five presented with single level spondylodiscitis. All patients underwent lumbar debridement, iliac strut grafting and posterior instrumentation (revision of screws for infected PLIF case). The mean operating time was 308.3 mins for all 6 cases. Mean blood loss was reported at 341cc (range from 200cc to 600cc). Presenting symptom of back pain resolved in all 6 cases while 2 cases that presented with lower limb weakness had improvement of neurological deficits. One patient had dislodged strut graft while performing posterior instrumentation and needed graft revision intraoperatively. Infective markers normalized for all patients subsequently. All subjects also showed radiological evidence of fusion on 6 months follow up. Conclusions: Lateral approach in treating pyogenic spondylitis is a viable option as it allows debridement and reconstruction without the risk that comes with other anterior approaches. It allows efficient debridement, short surgical time, moderate blood loss and low risk of vascular injuries. Clinical outcomes and fusion rates by this approach also support its use as practical MIS option surgery for such infection cases.

Keywords: lateral approach, minimally invasive, pyogenic spondylitis, XLIF

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Authors: L. C. Sánchez, L. C. Corrales, A. G. Lancheros, E. Castañeda, Y. Ariza, L. S. Fuentes, L. Sierra, J. L. Cuervo

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The importance of environment friendly alternatives in agricultural processes is the reason why the research group Ceparium, the Colegio Mayor de Cundinamarca University, Colombia, investigated the genus Bacillus and its applicability for improving crops of economic importance in Colombia. In this investigation, we presented a study in which the genus Bacillus plays a leading role as beneficial microorganism. The objective was to identify the biochemical potential of three indigenous species of Bacillus, which were able to carry out actions for biological control against pathogens and pests or promoted growth to improve productivity of crops in Colombia. The procedures were performed in three phases: first, the production of biomass of an indigenous strain and a reference strain starting from culture media for production of spores and toxins were made. Spore count was done in a Neubauer chamber, concentrations of spores of Bacillus sphaericus were prepared and a bioassay was done at the Laboratory of Entomology at the University Jorge Tadeo Lozano of Plutella xylostella larvae, insect pest of crucifers in several Colombian regions. The second phase included the extraction in the liquid state fermentation, a secondary metabolite that has antibiosis action against fungi, call iturin B, and was obtained from strains of Bacillus subtilis. The molecule was identified using High Resolution Chromatography (HPLC) and its biocontrol effect on Fusarium sp fungus causes vascular wilt in economically important plant varieties, was confirmed using testing of antagonism in Petri dish. In the third phase, an initial procedure in that let recover and identify microorganisms of the genus Bacillus from the rhizosphere in two aromatic herbs, Rosmarinus officinalis and Thymus vulgaris L. was used. Subsequently, testing of antagonism against Fusarium sp were made and an assay was done under greenhouse conditions to observe biocontrol and growth promoting action by comparing growth in length and dry weight. In the first experiment, native Bacillus sphaericus was lethal to 92% Plutella xylostella larvae in 10 DDA. In the second experiment, iturin B was identified and biological control of Fusarium sp was demonstrated. In the third study, all strains demonstrated biological control and the B14 strain identified as Bacillus megaterium increased root length and productivity of the two plants in terms of weight. It was concluded that the native microorganisms of the genus Bacillus has a great biochemical potential that provides a beneficial interactions with plants, improve their growth and development and therefore a greater impact on production.

Keywords: genus bacillus, biological control, PGPRs, biochemical potential

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Authors: Aziza Barnawi

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Background: Regular exercise reduces risk factors associated with cardiovascular diseases. Over the past decade, exercise interventions have been introduced to reduce the risk of and prevent coronary artery disease (CAD). Elevated low-density lipoproteins (LDL) contribute to the formation of atherosclerosis, its manifestations on the endothelial narrow the coronary artery and affect the endothelial function. Therefore, flow-mediated dilation (FMD) technique is used to assess the function. The results of previous studies have been inconsistent and difficult to interpret across different types of exercise programs. The relationship between exercise therapy and lipid levels has been extensively studied, and it is known to improve the lipid profile and endothelial function. However, the effectiveness of exercise in altering LDL levels and improving blood flow is controversial. Objective: This review aims to explore the evidence and quantify the impact of exercise training on LDL levels and vascular function by FMD. Methods: Electronic databases were searched PubMed, Google Scholar, Web of Science, the Cochrane Library, and EBSCO using the keywords: “low and/or moderate aerobic training”, “blood flow”, “atherosclerosis”, “LDL mediated blood flow”, “Cardiac Rehabilitation”, “low-density lipoproteins”, “flow-mediated dilation”, “endothelial function”, “brachial artery flow-mediated dilation”, “oxidized low-density lipoproteins” and “coronary artery disease”. The studies were conducted for 6 weeks or more and influenced LDL levels and/or FMD. Studies with different intensity training and endurance training in healthy or CAD individuals were included. Results: Twenty-one randomized controlled trials (RCTs) (14 FMD and 7 LDL studies) with 776 participants (605 exercise participants and 171 control participants) met eligibility criteria and were included in the systematic review. Endurance training resulted in a greater reduction in LDL levels and their subfractions and a better FMD response. Overall, the training groups showed improved physical fitness status compared with the control groups. Participants whose exercise duration was ≥150 minutes /week had significant improvement in FMD and LDL levels compared with those with <150 minutes/week.Conclusion: In conclusion, although the relationship between physical training, LDL levels, and blood flow in CAD is complex and multifaceted, there are promising results for controlling primary and secondary prevention of CAD by exercise. Exercise training, including resistance, aerobic, and interval training, is positively correlated with improved FMD. However, the small body of evidence for LDL studies (resistance and interval training) did not prove to be significantly associated with improved blood flow. Increasing evidence suggests that exercise training is a promising adjunctive therapy to improve cardiovascular health, potentially improving blood flow and contributing to the overall management of CAD.

Keywords: exercise training, low density lipoprotein, flow mediated dilation, coronary artery disease

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Authors: Kristina Karapetyan, Flora Tkhruni, Tsovinar Balabekyan, Arevik Israyelyan, Tatyana Khachatryan

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The ability of the lactic acid bacteria (LAB) to prevent and cure a variety of diseases, their protective role against infections and colonization of pathogenic microorganisms in the digestive tract, has lead to the coining of the term probiotics or pro-life. LAB inhibiting the growth of pathogenic and food spoilage microorganisms, maintaining the nutritive quality and improving the shelf life of foods. They have also been used as flavor and texture producers. Enterococcus strains have been used for treatment of diseases such as diarrhea or antibiotic associated diarrhea, inflammatory pathologies that affect colon such as irritable bowel syndrome, or immune regulation, diarrhea caused by antibiotic treatments. The obtaining and investigation of biological properties of proteinoceous antibiotics, on the basis of probiotic LAB shown, that bacteriocins, metabiotics, and peptides of LAB represent bactericides have a broad range of activity and are excellent candidates for development of new prophylactic and therapeutic substances to complement or replace conventional antibiotics. The genotyping by 16S rRNA sequencing for LAB were used. Cell free culture broth (CFC) broth was purified by the Gel filtration method on the Sephadex Superfine G 25 resin. Antimicrobial activity was determined by spot-on-lawn method and expressed in arbitrary units (AU/ml). The diversity of multidrug-resistance (MDR) of pathogenic strains to antibiotics, most widely used for treatment of human diseases in the Republics of Armenia and Nagorno Karabakh were examined. It was shown, that difference of resistance of pathogens to antibiotics depends on their isolation sources. The influences of partially purified antimicrobial preparations (AMP), obtained from the different strains of Enterococcus genus on the growth of MDR pathogenic bacteria were investigated. It was shown, that bacteriocin containing partially purified preparations, obtained from different strains of Enterococcus faecium and durans species, possess bactericidal or bacteriostatic activity against antibiotic resistant intestinal, spoilage and food-borne pathogens such as Listeria monocytogenes, Staphylococcus aureus, E. coli, and Salmonella. Endemic strains of LAB, isolated from Matsoni made from donkey, buffalo and goat milk, shown broad spectrum of activity against food spoiling microorganisms, moulds and fungi, such as Salmonella sp., Esherichia coli, Aspergillus and Penicillium species. Highest activity against MDR pathogens shown bacteria, isolated from goat milk products. High stability of the investigated strains of the genus Enerococcus, isolated from samples of matsun from different regions of Nagorno-Karabakh (NKR) to the antibiotics was shown. The obtained data show high stability of the investigated different strains of the genus Enerococcus. The high genetic diversity in Enterococcus group suggests adaptations for specific mutations in different environments. Thus, endemic strains of LAB are able to produce bacteriocins with high and different inhibitory activity against broad spectrum of microorganisms isolated from different sources and belong to different taxonomic group. Prospect of the use of certain antimicrobial preparations against pathogenic strains is obvious. These AMP can be applied for long term use against different etiology antibiotic resistant pathogens for prevention or treatment of infectional diseases as an alternative to antibiotics.

Keywords: antimicrobial biopreparation, endemic lactic acid bacteria, intra-species diversity, multidrug resistance of pathogens

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Authors: Stephanie PB Caligiuri, Harold M Aukema, Delfin Rodriguez-Leyva, Amir Ravandi, Randy Guzman, Grant N. Pierce

Abstract:

Background: Hypertension leads to cardiac and cerebral events and therefore is the leading risk factor attributed to death in the world. Oxylipins may be mediators in these events as they can regulate vascular tone and inflammation. Oxylipins are derived from fatty acids. Dietary flaxseed is rich in the n3 fatty acid, alpha-linolenic acid, and, therefore, may have the ability to change the substrate profile of oxylipins. As a result, this could alter blood pressure. Methods: A randomized, double-blinded, controlled clinical trial, the Flax-PAD trial, was used to assess the impact of dietary flaxseed on blood pressure (BP), and to also assess the relationship of plasma oxylipins to BP in 81 patients with peripheral arterial disease (PAD). Patients with PAD were chosen for the clinical trial as they are at an increased risk for hypertension and cardiac and cerebral events. Thirty grams of ground flaxseed were added to food products to consume on a daily basis for 6 months. The control food products contained wheat germ, wheat bran, and mixed dietary oils instead of flaxseed. Central BP, which is more significantly associated to organ damage, cardiac, and cerebral events versus brachial BP, was measured by pulse wave analysis at baseline and 6 months. A plasma profile of 43 oxylipins was generated using solid phase extraction, HPLC-MS/MS, and stable isotope dilution quantitation. Results: At baseline, the central BP (systolic/diastolic) in the placebo and flaxseed group were, 131/73 ± 2.5/1.4 mmHg and 128/71 ± 2.6/1.4 mmHg, respectively. After 6 months of intervention, the flaxseed group exhibited a decrease in blood pressure of 4.0/1.0 mmHg. The 6 month central BP in the placebo and flaxseed groups were, 132/74 ± 2.9/1.8 mmHg and 124/70 ± 2.6/1.6 mmHg (P<0.05). Correlation and logistic regression analyses between central blood pressure and oxylipins were performed. Significant associations were observed between central blood pressure and 17 oxylipins, primarily produced from arachidonic acid. Every 1 nM increase in 16-hydroxyeicosatetraenoic acid (HETE) increased the odds of having high central systolic BP by 15-fold, of having high central diastolic BP by 6-fold and of having high central mean arterial pressure by 15-fold. In addition, every 1 nM increase in 5,6-dihydroxyeicosatrienoic acid (DHET) and 11,12-DHET increased the odds of having high central mean arterial pressure by 45- and 18-fold, respectively. Flaxseed induced a significant decrease in these as well as 4 other vasoconstrictive oxylipins. Conclusion: Dietary flaxseed significantly lowered blood pressure in patients with PAD and hypertension. Plasma oxylipins were strongly associated with central blood pressure and may have mediated the flaxseed-induced decrease in blood pressure.

Keywords: hypertension, flaxseed, oxylipins, peripheral arterial disease

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Authors: Ho Sy Nam, Tang Ha Nam Anh

Abstract:

Background: Rotator cuff tears are a common problem in the aging population. The prevalence of massive rotator cuff tears varies in some studies from 10% to 40%. Of irreparable rotator cuff tears (IRCTs), which are mostly associated with massive tear size, 79% are estimated to have recurrent tears after surgical repair. Recent studies have shown that superior capsule reconstruction (SCR) in massive rotator cuff tears can be an efficient technique with optimistic clinical scores and preservation of stable glenohumeral stability. Superior capsule reconstruction techniques most commonly use either fascia lata autograft or dermal allograft, both of which have their own benefits and drawbacks (such as the potential for donor site issues, allergic reactions, and high cost). We propose a simple technique for superior capsule reconstruction that involves using the long head of the biceps tendon as a local autograft; therefore, the comorbidities related to graft harvesting are eliminated. The long head of the biceps tendon proximal portion is relocated to the footprint and secured as the SCR, serving to both stabilize the glenohumeral joint and maintain vascular supply to aid healing. Objective: The purpose of this study is to assess the clinical outcomes of patients with large to massive RCTs treated by SCR using LHBT. Materials and methods: A study was performed of consecutive patients with large to massive RCTs who were treated by SCR using LHBT between January 2022 and December 2022. We use one double-loaded suture anchor to secure the long head of the biceps to the middle of the footprint. Two more anchors are used to repair the rotator cuff using a single-row technique, which is placed anteriorly and posteriorly on the lateral side of the previously transposed LHBT. Results: The 3 men and 5 women had an average age of 61.25 years (range 48 to 76 years) at the time of surgery. The average follow-up was 8.2 months (6 to 10 months) after surgery. The average preoperative ASES was 45.8, and the average postoperative ASES was 85.83. The average postoperative UCLA score was 29.12. VAS score was improved from 5.9 to 1.12. The mean preoperative ROM of forward flexion and external rotation of the shoulder was 720 ± 160 and 280 ± 80, respectively. The mean postoperative ROM of forward flexion and external rotation were 1310 ± 220 and 630 ± 60, respectively. There were no cases of progression of osteoarthritis or rotator cuff muscle atrophy. Conclusion: SCR using LHBT is considered a treatment option for patients with large or massive RC tears. It can restore superior glenohumeral stability and function of the shoulder joint and can be an effective procedure for selected patients, helping to avoid progression to cuff tear arthropathy.

Keywords: superior capsule reconstruction, large or massive rotator cuff tears, the long head of the biceps, stabilize the glenohumeral joint

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Authors: Asghar Arif

Abstract:

Lung cancer has been recognized as one of the greatest common cancers, causing the annual mortality rate of about 1.2 million people in the world. Lung cancer is the most prevalent cancer in men and the third-most common cancer among women (after breast and digestive cancers).Recent evidences have shown the inflammatory process as one of the potential factors of cancer. Tuberculosis (TB), pneumonia, and chronic bronchitis are among the most important inflammation-inducing factors in the lungs, among which TB has a more profound role in the emergence of cancer.TB is one of the important mortality factors throughout the world, and 205,000 death cases are reported annually due to this disease. Chronic inflammation and fibrosis due to TB can induce genetic mutation and alternations. Parenchyma tissue of lung is involved in both diseases of TB and lung cancer, and continuous cough in lung cancer, morphological vascular variations, lymphocytosis processes, and generation of immune system mediators such as interleukins, are all among the factors leading to the hypothesis regarding the role of TB in lung cancer Some reports have shown that the induction of necrosis and apoptosis or TB reactivation, especially in patients with immune-deficiency, may result in increasing IL-17 and TNF_α, which will either decrease P53 activity or increase the expression of Bcl-2, decrease Bax-T, and cause the inhibition of caspase-3 expression due to decreasing the expression of mitochondria cytochrome oxidase. It has been also indicated that following the injection of BCG vaccine, the host immune system will be reinforced, and in particular, the rates of gamma interferon, nitric oxide, and interleukin-2 are increased. Therefore, CD4 + lymphocyte function will be improved, and the person will be immune against cancer.Numerous prospective studies have so far been conducted on the role of TB in lung cancer, and it seems that this disease is effective in that particular cancer.One of the main challenges of lung cancer is its correct and timely diagnosis. Unfortunately, clinical symptoms (such as continuous cough, hemoptysis, weight loss, fever, chest pain, dyspnea, and loss of appetite) and radiological images are similar in TB and lung cancer. Therefore, anti-TB drugs are routinely prescribed for the patients in the countries with high prevalence of TB, like Pakistan. Regarding the similarity in clinical symptoms and radiological findings of lung cancer, proper diagnosis is necessary for TB and respiratory infections due to nontuberculousmycobacteria (NTM). Some of the drug resistive TB cases are, in fact, lung cancer or NTM lung infections. Acid-fast staining and histological study of phlegm and bronchial washing, culturing and polymerase chain reaction TB are among the most important solutions for differential diagnosis of these diseases. Briefly, it is assumed that TB is one of the risk factors for cancer. Numerous studies have been conducted in this regard throughout the world, and it has been observed that there is a significant relationship between previous TB infection and lung cancer. However, to prove this hypothesis, further and more extensive studies are required. In addition, as the clinical symptoms and radiological findings of TB, lung cancer, and non-TB mycobacteria lung infections are similar, they can be misdiagnosed as TB.

Keywords: TB and lung cancer, TB people, TB servivers, TB and HIV aids

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