Search results for: bone tissue

Authors: Nayeon, Lee, Won-Young, Cho, Hyun Joo, Jang, Chi-Ho, Lee

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This study investigated the effects of the dietary supplementation of the Allium hookeri root, and processed sulfur, on the growth performance of guinea pigs. The guinea pigs were fed a control diet (CON), as well as the control diet including 1% freeze-dried Allium hookeri root (AH), or 0.1% processed sulfur (S), or including both the freeze-dried Allium hookeri root and the processed sulfur (AHS). The weight of perirenal adipose tissue (PAT) and the epididymal adipose tissue (EAT) in the AH were significantly lower than CON (p < 0.05). The serum cholesterols levels of the AH and the AHS were significantly lower than the S (p < 0.05). While the total saturated fatty acid content in the serum of the AH and AHS groups showed a tendency to decrease, the total monounsaturated fatty acid increased. The results of this study suggested that dietary consumption of Allium hookeri root may help to decrease fat accumulation, lower serum cholesterol levels, and control serum free fatty acid contents in the guinea pigs.

Keywords: Allium hookeri, dietary supplementation, growth performance, processed sulfur, Guinea pig

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Authors: Muhammad Younus, Muhammad Sajid, Muti-ur-Rehman Khan, Aftab Ahmad Anjum, Muhammad Asif Idrees, Iahtasham Khan, Aman Ullah Khan, Sajid Umar, Raheela Akhtar

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The present study was conducted to investigate the hazardous effects of lead on health and edible organs of Lohi sheep. The adult Lohi sheep (n=48) were randomly divided into two equal groups. The first group was administered lead acetate at dose of 70 mg/kg live body weight daily as 10% solution by oral route for a period of 90 days and the second group served as a negative control. Blood and tissue samples were collected at day 0, 30, 60 and 90 and analyzed for lead concentration by atomic absorption spectrophotometry. The kidney showed the highest lead concentration (p < 0.05) followed by liver and then muscle. Lead acetate treated sheep showed structural and behavioral changes during the last month of trial. Liver showed necrosis, hemorrhages and hyperactivation of macrophages. Kidney showed degenerative and necrotic changes in glomeruli and tubules and the characteristic intranuclear inclusion bodies in tubular epithelial cells on H and E staining. It was concluded that Lohi sheep is affected by lead intoxication at low dose for longer period and hence exhibits lead accumulation in edible tissues.

Keywords: Lohi sheep, lead acetate, edible tissue, histopathology

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Authors: Kazeem Adesina Dauda, Waheed Babatunde Yahya

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To design a tree that maximizes within-node homogeneity, there is a need for a homogeneity measure that is appropriate for event history data with multiple risks. We consider the use of Deviance and Modified Cox-Snell residuals as a measure of impurity in Classification Regression Tree (CART) and compare our results with the results of Fiona (2008) in which homogeneity measures were based on Martingale Residual. Data structure approach was used to validate the performance of our proposed techniques via simulation and real life data. The results of univariate competing risk revealed that: using Deviance and Cox-Snell residuals as a response in within node homogeneity classification tree perform better than using other residuals irrespective of performance techniques. Bone marrow transplant data and double-blinded randomized clinical trial, conducted in other to compare two treatments for patients with prostate cancer were used to demonstrate the efficiency of our proposed method vis-à-vis the existing ones. Results from empirical studies of the bone marrow transplant data showed that the proposed model with Cox-Snell residual (Deviance=16.6498) performs better than both the Martingale residual (deviance=160.3592) and Deviance residual (Deviance=556.8822) in both event of interest and competing risks. Additionally, results from prostate cancer also reveal the performance of proposed model over the existing one in both causes, interestingly, Cox-Snell residual (MSE=0.01783563) outfit both the Martingale residual (MSE=0.1853148) and Deviance residual (MSE=0.8043366). Moreover, these results validate those obtained from the Monte-Carlo studies.

Keywords: within-node homogeneity, Martingale residual, modified Cox-Snell residual, classification and regression tree

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Authors: Robnier Reyes, Andrew J. P. Marques, Joel Ramjist, Chris R. Pasarikovski, Victor X. D. Yang

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Over the past three decades, surgical robotic systems have demonstrated their ability to improve surgical outcomes. The LBR Med is a collaborative robotic arm that is meant to work with a surgeon to streamline surgical workflow. It has 7 degrees of freedom and thus can be easily oriented. Position and torque sensors at each joint allow it to maintain a position accuracy of 150 µm with real-time force and torque feedback, making it ideal for complex surgical procedures. Spinal fusion procedures involve the placement of as many as 20 pedicle screws, requiring a great deal of accuracy due to proximity to the spinal canal and surrounding vessels. Any deviation from intended path can lead to major surgical complications. Assistive surgical robotic systems are meant to serve as collaborative devices easing the workload of the surgeon, thereby improving pedicle screw placement by mitigating fatigue related inaccuracies. Moreover, robotic spinal systems have shown marked improvements over conventional freehanded techniques in both screw placement accuracy and fusion quality and have greatly reduced the need for screw revision, intraoperatively and post-operatively. However, current assistive spinal fusion robots, such as the ROSA Spine, are limited in functionality to positioning surgical instruments. While they offer a small degree of improvement in pedicle screw placement accuracy, they do not alleviate surgeon fatigue, nor do they provide real-time force and torque feedback during screw insertion. We propose a semi-autonomous surgical robot workflow for spinal fusion where the surgeon guides the robot to its initial position and orientation, and the robot drives the pedicle screw accurately into the vertebra. Here, we demonstrate feasibility by inserting pedicle screws into ex-vivo bovine rib bone. The robot monitors position, force and torque with respect to predefined values selected by the surgeon to ensure the highest possible spinal fusion quality. The workflow alleviates the strain on the surgeon by having the robot perform the screw placement while the ability to monitor the process in real-time keeps the surgeon in the system loop. The approach we have taken in terms of level autonomy for the robot reflects its ability to safely collaborate with the surgeon in the operating room without external navigation systems.

Keywords: ex vivo bovine bone, pedicle screw, surgical robot, surgical workflow

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Authors: Rayhana Begum, Manju Sharma

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Careya arborea Roxb. belongs to the Lecythidaceae family, is traditionally used in tumors, anthelmintic, bronchitis, epileptic fits, astringents, inflammation, an antidote to snake-venom, skin disease, diarrhea, dysentery with bloody stools, dyspepsia, ulcer, toothache, and ear pain. The present study was focused on investigating the anti-arthritic effect of coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem bark in the chronic inflammatory model and further assessing its possible mechanism on the modulation of inflammatory biomarkers. Arthritis was induced by injecting 0.1 ml of Complete Freund’s Adjuvant (5 mg/ml of heat killed Mycobacterium tuberculosis) into the subplantar region of the left hind paw. Treatment with coumaroyl lupendioic acid (10 and 20 mg/kg, p.o.) and reference drugs (indomethacin and dexamethasone at the dose of 5 mg/kg, p.o.) were started on the day of induction and continued up to 28 days. The progression of arthritis was evaluated by measuring paw volume, tibio tarsal joint diameters, and arthritic index. The effect of coumaroyl lupendioic acid (CLA) on the production PGE₂, NO, MPO, NF-κB, TNF-α, IL-1β, and IL-6 on serum level as well as inflamed paw tissue were also assessed. In addition, ankle joints and spleen were collected and prepared for histological examination. CLA in inflamed rats resulted in significant amelioration of paw edema, tibio-tarsal joint swelling and arthritic score as compared to CFA control group. The results indicated that CLA treated groups markedly decreased the levels of inflammatory mediators (PGE₂, NO, MPO and NF-κB levels) and down-regulated the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in paw tissue homogenates as well as in serum. However, the more pronounced effect was observed in the inflamed paw tissue homogenates. CLA also revealed a protective effect to the tibio-tarsal joint cartilage and spleen. These results suggest that coumaroyl lupendioic acid inhibits inflammation may be through the suppression of the cascade of proinflammatory mediators via the down-regulation of NF-ҡB.

Keywords: complete Freund’s adjuvant , Coumaroyl lupendioic acid, pro-inflammatory cytokines, prostaglandin E2

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Authors: Macie Matta, Ahmad Jabri, Stephanie Jackson

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Introduction: In the absence of hypotension, pulmonary embolism (PE) causing right ventricular dysfunction or strain, whether confirmed by imaging or cardiac biomarkers, is deemed to be an intermediate-risk category. Urgent treatment of intermediate-risk PE can prevent progression to hemodynamic instability and death. Management options include thrombolysis, thrombectomy, or systemic anticoagulation. We aim to evaluate the short-term outcomes of a half-dose tissue plasminogen activator (tPA) for the management of intermediate-risk PE. Methods: We retrospectively identified adult patients diagnosed with intermediate-risk PE between the years 2000 and 2021. Demographic data, lab values, imaging, treatment choice, and outcomes were all obtained through chart review. Primary outcomes measured include major bleeding events and in-hospital mortality. Patients on standard systemic anticoagulation without receiving thrombolysis or thrombectomy served as controls. Patient data were analyzed using SAS®️ Software (version 9.4; Cary, NC) to compare individuals that received half-dose tPA with controls, and statistical significance was set at a p-value of 0.05. Results: We included 57 patients in our final analysis, with 19 receiving tPA. Patient characteristics and comorbidities were comparable between both groups. There was a significant difference between PE location, presence of acute deep vein thrombosis, and peak troponin level between both groups. The thrombolytic cohort was more likely to demonstrate a 60/60 sign and thrombus in transit finding on echocardiography than controls. The thrombolytic group was more likely to have major bleeding (17% vs 7.9%, p= 0.4) and in-hospital mortality (5.3% vs 0%, p=0.3); however, this was not statistically significant. Patients who received half-dose tPA had non-significantly higher rates of major bleeding and in-hospital mortality. Larger scale, randomized control trials are needed to establish the benefit and safety of thrombolytics in patients with intermediate-risk PE.

Keywords: pulmonary embolism, half dose thrombolysis, tissue plasminogen activator, cardiac biomarkers, echocardiographic findings, major bleeding event

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Authors: Hannah Nagel, Hayley Lang, Albert Sole Guitart, Natasha Lean, Rachel Allavena, Cleide Sprohnie-Barrera, Alex Young

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Aggressive neoplasia of the hoof is a rare occurrence in horses and has been only sporadically described in the literature. In the few cases reported intra-hoof wall, aggressive neoplasia has been documented radiographically and has been described with variable imaging characteristics. These include a well-defined osteolytic area, a smoothly outlined semi-circular defect, an extensive draining tract beneath the hoof wall, as well as an additional large area of osteolysis or an extensive central lytic region. A 20-year-old Quarterhorse gelding and a 10-year-old Thoroughbred gelding were both presented for chronic reoccurring lameness in the left forelimb and left hindlimb, respectively. Both of the cases displayed radiographic lesions that have been previously described but also displayed osteoproliferative expansile regions of additional bone formation. Changes associated with hoof neoplasia are often non-specific due to the nature and capacity of bone to react to pathological insult, which is either to proliferate or be absorbed. Both cases depict and describe imaging findings seen on radiography, contrast radiography, computed tomography, and magnetic resonance imaging before reaching a histological diagnosis of malignant melanoma and squamous cell carcinoma. Although aggressive hoof wall neoplasia is rare, there are some imaging features which may raise our index of suspicion for an aggressive hoof wall lesion. This case report documents two horses with similar imaging findings who underwent multiple assessments, surgical interventions, and imaging modalities with a final diagnosis of malignant neoplasia.

Keywords: horse, hoof, imaging, radiography, neoplasia

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Authors: Bui Phuong Linh, Yuki Sakakibara, Ryuto Tanaka, Elizabeth H. Pigney, Taishi Hashiguchi

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NASH is an increasingly prevalent chronic liver disease that can progress to hepatocellular carcinoma and now is attracting interest worldwide. The STAM™ model is a clinically-correlated murine NASH model which shows the same pathological progression as NASH patients and has been widely used for pharmacological and basic research. The multiple parallel hits hypothesis suggests abnormalities in adipocytokines, intestinal microflora, and endotoxins are intertwined and could contribute to the development of NASH. In fact, NASH patients often exhibit gut dysbiosis and dysfunction in adipose tissue and metabolism. However, the analysis of the STAM™ model has only focused on the liver. To clarify whether the STAM™ model can also mimic multiple pathways of NASH progression, we analyzed the organ crosstalk interactions between the liver and the gut and the phenotype of adipose tissue in the STAM™ model. NASH was induced in male mice by a single subcutaneous injection of 200 µg streptozotocin 2 days after birth and feeding with high-fat diet after 4 weeks of age. The mice were sacrificed at NASH stage. Colon samples were snap-frozen in liquid nitrogen and stored at -80˚C for tight junction-related protein analysis. Adipose tissue was prepared into paraffin blocks for HE staining. Blood adiponectin was analyzed to confirm changes in the adipocytokine profile. Tight junction-related proteins in the intestine showed that expression of ZO-1 decreased with the progression of the disease. Increased expression of endotoxin in the blood and decreased expression of Adiponectin were also observed. HE staining revealed hypertrophy of adipocytes. Decreased expression of ZO-1 in the intestine of STAM™ mice suggests the occurrence of leaky gut, and abnormalities in adipocytokine secretion were also observed. Together with the liver, phenotypes in these organs are highly similar to human NASH patients and might be involved in the pathogenesis of NASH.

Keywords: Non-alcoholic steatohepatitis, hepatocellular carcinoma, fibrosis, organ crosstalk, leaky gut

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Authors: O. O. Onafowokan, K. Anderson, M. R. Norton, R. G. Middleton

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Revision total hip arthroplasty (THA) is known to be a challenging procedure with potential for poor outcomes. Due to its lack of metaphyseal encroachment, hip resurfacing arthroplasty (HRA) is classified as a bone conserving procedure. Although the literature postulates that this is an advantage at time of revision surgery, there is no evidence to either support or refute this claim. We identified 129 hips that had undergone HRA and 129 controls undergoing first revision THA. We recorded the clinical assessment and survivorship of implants in a multi-surgeon, single centre, retrospective case control series for both arms. These were matched for age and sex. Data collected included demographics, indications for surgery, Oxford Hip Score (OHS), length of surgery, length of hospital stay, blood transfusion, implant complexity and further surgical procedures. Significance was taken as p < 0.05. Mean follow up was 7.5 years (1 to 15). There was a significant 6 point difference in postoperative OHS in favour of the revision resurfacing group (p=0.0001). The revision HRA group recorded 48 minutes less length of surgery (p<0.0001), 2 days less in length of hospital stay (p=0.018), a reduced need for blood transfusion (p=0.0001), a need for less complexity in revision implants (p=0.001) and a reduced probability of further surgery being required (P=0.003). Whilst we acknowledge the limitations of this study our results suggest that, in contrast to THA, the bone conservation element of HRA may make for a less traumatic revision procedure with better functional outcomes. Use of HRA has seen a dramatic decline as a result of concerns regarding metallosis. However, this information remains of relevance when counselling young active patients about their arthroplasty options and may become pertinent in the future if the promise of ceramic hip resurfacing is ever realized.

Keywords: hip resurfacing, metallosis, revision surgery, total hip arthroplasty

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Authors: Lucille McWilliams

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As water temperatures drop in November, Kemp’s Ridley, Loggerhead, and Green sea turtles cold-stun in Cape Cod Bay. The foraging ecology of these sea turtles remains an understudied area of research. In this study, we aim to assess the diet of these turtles using a multi-tissue stable isotope analysis of cold-stunned kemp’s ridley, loggerhead, and green sea turtles stranded from 2015 to 2020. Stable isotope ratios of carbon and nitrogen were measured in blood, front and rear flipper, liver, muscle, skin, and scute tissue samples. We predict an elevated level of Nitrogen isotope ratios in kemp’s ridley and loggerhead turtles compared to green turtles due to the carnivorous loggerheads and kemp ridleys’ carnivorous diet and the greens herbivorous diet. We anticipate empty stomachs due to starvation while stranded, and a variety of foraging strategies, migration patterns, and trophic positions between these species. Data collected from this study will add to the knowledge of these turtles’ prey species and aid managers in the preservation of these species as a mitigation strategy for these turtles' extinction.

Keywords: sea turtles, kemp's ridleys, greens, loggerheads, cold-stunning, diet analysis, stable isotope analysis, environmental science, marine biology

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Authors: Preet Shah, Om Shrivastav

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Introduction : In India, Leishmania donovani is the only parasite causing Leishmaniasis. The parasite infects the reticuloendothelial system and is found in the bone marrow, spleen and liver. Treatment of choice is amphotericin-B with sodium stibogluconate being an alternative. Miltefosine is useful in refractory cases. In our case, Leishmaniasis occurred in a person residing in western India (which is quite rare) and it failed to respond to two different drugs (again an uncommon feature) before it finally responded to a third one. Description: A 50 year old lady, a resident of western India, with no history of recent travel, presented with an ulcer on the left side of the nose since 8 months. She was apparently alright 8 months back, when she noticed a small ulcerated lesion on the left ala of the nose which was immediately biopsied. The biopsy revealed amastigotes of Leishmania for which she was administered intra-lesional sodium stibogluconate for 1 month (4 doses every 8 days).Despite this, there was no regression of the ulcer and hence she presented to us for further management. On examination, her vital parameters were normal. Barring an ulcer on the left side of the nose, rest of the examination findings were unremarkable. Complete blood count was normal. Ultrasound abdomen showed hepatomegaly. PET-CT scan showed increased metabolic activity in left ala of nose, hepatosplenomegaly and increased metabolic activity in spleen and bone marrow. Bone marrow biopsy was done which showed hypercellular marrow with erythroid preponderance. Considering a diagnosis of leishmaniasis which had so far been unresponsive to sodium stibogluconate, she was started on liposomal amphotericin-B. At the time of admission, her creatinine level was normal, but it started rising with the administration of liposomal amphotericin-B, hence the dose was reduced. Despite this, creatinine levels did not improve, and she started developing hypokalemia and hypomagnesemia as side effects of the drug, hence further reductions in the dosage were made. Despite a total of 3 weeks of liposomal amphotericin-B, there was no improvement in the ulcer. As had so far failed to respond to sodium stibogluconate and liposomal amphotericin-B, it was decided to start her on miltefosine. She received the miltefosine for a total of 12 weeks. At the end of this duration, there was a marked regression of the cutaneous lesion. Conclusion: Refractoriness to amphotericin-B in leishmaniasis may be seen in up to 5 % cases. Here, an alternative drug such as miltefosine is useful and hence we decided to use it, to which she responded adequately. Furthermore, although leishmaniasis is common in the eastern part of India, it is a relatively unknown entity in the western part of the country with the occurrence being very rare. Because of these 2 reasons, we consider our case to be a unique one.

Keywords: amphotericin-b, leishmaniasis, miltefosine, tropical diseases

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Authors: Polina Prokopovich

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Despite the well-established dependence of cartilage mechanical properties on the frequency of the applied load, most research in the field is carried out in either load-free or constant load conditions because of the complexity of the equipment required for the determination of time-dependent properties. These simpler analyses provide a limited representation of cartilage properties thus greatly reducing the impact of the information gathered hindering the understanding of the mechanisms involved in this tissue replacement, development and pathology. More complex techniques could represent better investigative methods, but their uptake in cartilage research is limited by the highly specialised training required and cost of the equipment. There is, therefore, a clear need for alternative experimental approaches to cartilage testing to be deployed in research and clinical settings using more user-friendly and financial accessible devices. Frequency dependent material properties can be determined through rheometry that is an easy to use requiring a relatively inexpensive device; we present how a commercial rheometer can be adapted to determine the viscoelastic properties of articular cartilage. Frequency-sweep tests were run at various applied normal loads on immature, mature and trypsinased (as model of osteoarthritis) cartilage samples to determine the dynamic shear moduli (G*, G′ G″) of the tissues. Moduli increased with increasing frequency and applied load; mature cartilage had generally the highest moduli and GAG depleted samples the lowest. Hydraulic permeability (KH) was estimated from the rheological data and decreased with applied load; GAG depleted cartilage exhibited higher hydraulic permeability than either immature or mature tissues. The rheometer-based methodology developed was validated by the close comparison of the rheometer-obtained cartilage characteristics (G*, G′, G″, KH) with results obtained with more complex testing techniques available in literature. Rheometry is relatively simpler and does not require highly capital intensive machinery and staff training is more accessible; thus the use of a rheometer would represent a cost-effective approach for the determination of frequency-dependent properties of cartilage for more comprehensive and impactful results for both healthcare professional and R&D.

Keywords: tissue, rheometer, biomaterial, cartilage

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Authors: Mahmoud M. Zakaria, Omnia F. Elmoursi, Mahmoud M. Gabr, Camelia A. AbdelMalak, Mohamed A. Ghoneim

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Many protocols were publicized for differentiation of human mesenchymal stem cells (MSCS) into insulin-producing cells (IPCs) in order to excrete insulin hormone ingoing to treat diabetes disease. Our aim is to evaluate relative gene expression for each independent protocol. Human bone marrow cells were derived from three volunteers that suffer diabetes disease. After expansion of mesenchymal stem cells, differentiation of these cells was done by three different protocols (the one-step protocol was used conophylline protein, the two steps protocol was depending on trichostatin-A, and the three-step protocol was started by beta-mercaptoethanol). Evaluation of gene expression was carried out by real-time PCR: Pancreatic endocrine genes, transcription factors, glucose transporter, precursor markers, pancreatic enzymes, proteolytic cleavage, extracellular matrix and cell surface protein. Quantitation of insulin secretion was detected by immunofluorescence technique in 24-well plate. Most of the genes studied were up-regulated in the in vitro differentiated cells, and also insulin production was observed in the three independent protocols. There were some slight increases in expression of endocrine mRNA of two-step protocol and its insulin production. So, the two-step protocol was showed a more efficient in expressing of pancreatic endocrine genes and its insulin production than the other two protocols.

Keywords: mesenchymal stem cells, insulin producing cells, conophylline protein, trichostatin-A, beta-mercaptoethanol, gene expression, immunofluorescence technique

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Authors: Ananya Hazare, Ranjit Kamble

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Introduction: Patients with Cleft lip and palate (CL/P) can present with a maxillary retrution after cleft repair. Anterior Maxillary distraction osteogenesis (AMD) is a technique that provides simultaneous skeletal advancement and expansion of the soft tissues related to an anterior segment of the maxilla. This case presented is a case of AMD. The advantage of this technique is that the occlusion in the posterior segment can be maintained, and only the segment in cross bite is advanced for correction of the midfacial deficiency. The other alternative treatment is anterior movement by a Lefort 1 osteotomy. When a Lefort 1 osteotomy is compared with the Distraction osteogenesis or AMD, the disadvantages of the Le Fort 1 include a higher risk of morbidity, requirement of fixation, relapse tendency and unexpected changes in the nasal form. These complications were eliminated by AMD technique. This was followed by placement of the implant in the bone formed after AMD. Hence complete surgical, orthodontic and prosthodontics rehabilitation of the patient was done by an interdisciplinary approach. Methods: Patient presented with repaired UCL/P of the right side with midfacial retrusion. Intro-oral examination revealed a good occlusion in the posterior arch and anterior Crossbite from canine to canine. Patient's both maxillary lateral incisors were missing. The lower arch was well aligned with all teeth present. The study models when scored according to GOSLON yardstick received a score of 4. After pre-surgical orthodontic phase was completed an intraoral distractor was fabricated by modification of HYRAX expansion screw. After surgery, low subapical osteotomy cuts were placed and the distractor was fixed. The latency period of 5 days was observed after which the distraction was started. Distraction was done at a rate of 1 mm/day with a rhythm of 0.5mm in morning and 0.5mm in the evening. The total distraction of 12 mm was done. After a consolidation period, the distractor was removed, and retention by a removable partial denture was given. Radiographic examination confirmed mature bone formation in the distracted segment. Implants were placed and allowed to osseointegrate for approximately 4 months and were then loaded with abutments. Results: Total distraction done was 12mm and after relapse it was 8mm. After consolidation phase the radiographic examination revealed a B2 quality of bone according to the Misch's classification and sufficient height from the maxillary sinus. These findings were indicative for placement of implants in the distracted bone formed in premolar region. Implants were placed and after radiographic evidence of osseointegration was seen they were loaded with abutments. Thus resulting in a complete rehabilitation of a cleft patient by an interdisciplinary approach. Conclusion: Anterior maxillary distraction can be used as an alternative method instead of complete distraction osteogenesis or Lefort 1 advancement of maxilla in cases where the advancement needed is minimum. Use of HYRAX expansion screw modified as intra-oral distractor can be used in such cases, which significantly reduces the cost of treatment, as expensive distractors are not used. This technique is very useful and efficient in countries like India where the patient cannot afford expensive treatment options.

Keywords: cleft lip and palate, distraction osteogenesis, anterior maxillary distraction, orthodontics and dentofacial orthopaedics, hyrax expansion screw modification

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Authors: Lukasz Kaniuk, Mateusz M. Marzec, Andrzej Bernasik, Urszula Stachewicz

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Electrospinning is one of the commonly used methods to produce micro- or nano-fibers. The properties of electrospun fibers allow them to be used to produce tissue scaffolds, biodegradable bandages, or purification membranes. The morphology of the obtained fibers depends on the composition of the polymer solution as well as the processing parameters. Interesting properties such as high fiber porosity can be achieved by changing humidity during electrospinning. Moreover, by changing voltage polarity in electrospinning, we are able to alternate functional groups at the surface of fibers. In this study, electrospun fibers were made of natural, thermoplastic polyester – PHBV (poly(3-hydroxybutyric acid-co-3-hydrovaleric acid). The fibrous mats were obtained using both positive and negative voltage polarities, and their surface was characterized using X-ray photoelectron spectroscopy (XPS, Ulvac-Phi, Chigasaki, Japan). Furthermore, the effect of the humidity on surface morphology was investigated using scanning electron microscopy (SEM, Merlin Gemini II, Zeiss, Germany). Electrospun PHBV fibers produced with positive and negative voltage polarity had similar morphology and the average fiber diameter, 2.47 ± 0.21 µm and 2.44 ± 0.15 µm, respectively. The change of the voltage polarity had a significant impact on the reorientation of the carbonyl groups what consequently changed the surface potential of the electrospun PHBV fibers. The increase of humidity during electrospinning causes porosity in the surface structure of the fibers. In conclusion, we showed within our studies that the process parameters such as humidity and voltage polarity have a great influence on fiber morphology and chemistry, changing their functionality. Surface properties of polymer fiber have a significant impact on cell integration and attachment, which is very important in tissue engineering. The possibility of changing surface porosity allows the use of fibers in various tissue engineering and drug delivery systems. Acknowledgment: This study was conducted within 'Nanofiber-based sponges for atopic skin treatment' project., carried out within the First TEAM programme of the Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund, project no POIR.04.04.00-00- 4571/18-00.

Keywords: cells integration, electrospun fiber, PHBV, surface characterization

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Authors: Vita Strazdina, Aleksandrs Jemeljanovs, Vita Sterna

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Not all proteins have the same nutritional value, since protein quality strongly depends on its amino acid composition and digestibility. The meat of game animals could be a high protein source because of its well-balanced essential amino acids composition. Investigations about biochemical composition of game meat such as wild boar (Sus scrofa scrofa), roe deer (Capreolus capreolus) and beaver (Castor fiber) are not very much. Therefore, the aim of the investigation was evaluate protein composition of game meat hunted in Latvia. The biochemical analysis, evaluation of connective tissue and essential amino acids in meat samples were done, the amino acids score were calculate. Results of analysis showed that protein content 20.88-22.05% of all types of meat samples is not different statistically. The content of connective tissue from 1.3% in roe deer till 1.5% in beaver meat allowed classified game animal as high quality meat. The sum of essential amino acids in game meat samples were determined 7.05–8.26g100g-1. Roe deer meat has highest protein content and lowest content of connective tissues among game meat hunted in Latvia. Concluded that amino acid score for limiting amino acids phenylalanine and tyrosine is high and shows high biological value of game meat.

Keywords: dietic product, game meat, amino acids, scores

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Authors: Kave Moloudi, Heidi Abrahamse, Blassan P. George

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Radiotherapy (RT) and photodynamic therapy (PDT) are both forms of cancer treatment that aim to kill cancer cells while minimizing damage to healthy tissue. The similarity between RT and PDT lies in their mechanism of action. Both treatments use energy to damage cancer cells. RT uses high-energy radiation to damage the DNA of cancer cells, while PDT uses light energy to activate a photosensitizing agent, which produces reactive oxygen species (ROS) that damage the cancer cells. Both treatments require careful planning and monitoring to ensure the correct dose is delivered to the tumor while minimizing damage to surrounding healthy tissue. They are also often used in combination with other treatments, such as surgery or chemotherapy, to improve overall outcomes. However, there are also significant differences between RT and PDT. For example, RT is a non-invasive treatment that can be delivered externally or internally, while PDT requires the injection of a photosensitizing agent and the use of a specialized light source to activate it. Additionally, the side effects and risks associated with each treatment can vary. In this review, we focus on generalizing the 6Rs of radiobiology in PDT, which can open a window for the clinical application of Radio-photodynamic therapy with minimum side effects. Furthermore, this review can open new insight to work on and design new radio-photosensitizer agents in Radio-photodynamic therapy.

Keywords: radiobiology, photodynamic therapy, radiotherapy, 6Rs in radiobiology, ROS, DNA damages, cellular and molecular mechanism, clinical application.

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Authors: Naghmeh Zamani, Ashkan Pourkand, David Grow

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This paper presents the design and mechanical model of a hybrid impedance/admittance haptic device optimized for applications, like bone drilling, spinal awl probe use, and other surgical techniques were high force is required in the tool-axial direction, and low impedance is needed in all other directions. The performance levels required cannot be satisfied by existing, off-the-shelf haptic devices. This design may allow critical improvements in simulator fidelity for surgery training. The device consists primarily of two low-mass (carbon fiber) plates with a rod passing through them. Collectively, the device provides 6 DOF. The rod slides through a bushing in the top plate and it is connected to the bottom plate with a universal joint, constrained to move in only 2 DOF, allowing axial torque display the user’s hand. The two parallel plates are actuated and located by means of four cables pulled by motors. The forward kinematic equations are derived to ensure that the plates orientation remains constant. The corresponding equations are solved using the Newton-Raphson method. The static force/torque equations are also presented. Finally, we present the predicted distribution of location error, cables velocity, cable tension, force and torque for the device. These results and preliminary hardware fabrication indicate that this design may provide a revolutionary approach for haptic display of many surgical procedures by means of an architecture that allows arbitrary workspace scaling. Scaling of the height and width can be scaled arbitrarily.

Keywords: cable direct driven robot, haptics, parallel plates, bone drilling

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Authors: Da-Ming Huang, Ya-Ting Tsai, Shyh-Hau Wang

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Ultrasound signals backscattered from the soft tissues are mainly depending on the size, density, distribution, and other elastic properties of scatterers in the interrogated sample volume. The quantitative analysis of ultrasonic backscattering is frequently implemented using the statistical approach due to that of backscattering signals tends to be with the nature of the random variable. Thus, the statistical analysis, such as Nakagami statistics, has been applied to characterize the density and distribution of scatterers of a sample. Yet, the accuracy of statistical analysis could be readily affected by the receiving signals associated with the nature of incident ultrasound wave and acoustical properties of samples. Thus, in the present study, efforts were made to explore such effects as the ultrasound operational modes and attenuation of biological tissue on the estimation of corresponding Nakagami statistical parameter (m parameter). In vitro measurements were performed from healthy and pathological fibrosis porcine livers using different single-element ultrasound transducers and duty cycles of incident tone burst ranging respectively from 3.5 to 7.5 MHz and 10 to 50%. Results demonstrated that the estimated m parameter tends to be sensitively affected by the use of ultrasound operational modes as well as the tissue attenuation. The healthy and pathological tissues may be characterized quantitatively by m parameter under fixed measurement conditions and proper calibration.

Keywords: ultrasound backscattering, statistical analysis, operational mode, attenuation

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Authors: Mahmut Sozmen, Alparslan Kadir Devrim, Yonca Betil Kabak, Tuba Devrim

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Acute myocardial infarction is the leading cause of deaths in the worldwide. Mature cardiomyocytes do not have the ability to regenerate instead fibrous tissue proliferate and granulation tissue to fill out. Periostin is an extracellular matrix protein from fasciclin family and it plays an important role in the cell adhesion, migration, and growth of the organism. Periostin prevents apoptosis while stimulating cardiomyocytes. The main objective of this project is to investigate the effects of the recombinant murine periostin peptide administration for the cardiomyocyte regeneration in a rat model of acute myocardial infarction. The experiment was performed on 84 male rats (6 months old) in 4 group each contains 21 rats. Saline applied subcutaneously (1 ml/kg) two times with 24 hours intervals to the rats in control group (Group 1). Recombinant periostin peptide (1 μg/kg) dissolved in saline applied intraperitoneally in group 2 on 1, 3, 7, 14 and 21. days on same dates in group 4. Isoproterenol dissolved in saline applied intraperitoneally (85mg/kg/day) two times with 24 hours intervals to the groups 3 and 4. Rats in group 4 further received recombinant periostin peptide (1 μg/kg) dissolved in saline intraperitoneally starting one day after the final isoproterenol administration on days 1, 3, 7, 14 and 21. Following the final application of periostin rats continued to feed routinely with pelleted chow and water ad libitum for further seven days. At the end of 7th day rats sacrificed, blood and heart tissue samples collected for the immunohistochemical and biochemical analysis. Angiogenesis in response to tissue damage, is a highly dynamic process regulated by signals from the surrounding extracellular matrix and blood serum. In this project, VEGF, ANGPT, bFGF, TGFβ are the key factors that contribute to cardiomyocyte regeneration were investigated. Additionally, the relationship between mitosis and apoptosis (Bcl-2, Bax, PCNA, Ki-67, Phopho-Histone H3), cell cycle activators and inhibitors (Cyclin D1, D2, A2, Cdc2), the origin of regenerating cells (cKit and CD45) were examined. Present results revealed that periostin stimulated cardiomyocye cell-cycle re-entry in both normal and MCA damaged cardiomyocytes and increased angiogenesis. Thus, periostin contributes to cardiomyocyte regeneration during the healing period following myocardial infarction which provides a better understanding of its role of this mechanism, improving recovery rates and it is expected to contribute the lack of literature on this subject. Acknowledgement: This project was financially supported by Turkish Scientific Research Council- Agriculture, Forestry and Veterinary Research Support Group (TUBİTAK-TOVAG; Project No: 114O734), Ankara, TURKEY.

Keywords: cardiotoxicity, immunohistochemistry, isoproterenol, periostin

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Authors: Maha J. Balgoon, Gehan A. Raouf, Safaa Y. Qusti, Soad S. Ali

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The main cause of Alzheimer disease (AD) was believed to be mainly due to the accumulation of free radicals owing to oxidative stress (OS) in brain tissue. The mechanism of the neurotoxicity of Aluminum chloride (AlCl3) induced AD in hippocampus Albino wister rat brain tissue, the curative & the protective effects of Lipidium sativum group (LS) water extract were assessed after 8 weeks by attenuated total reflection spectroscopy ATR-IR and histologically by light microscope. ATR-IR results revealed that the membrane phospholipid undergo free radical attacks, mediated by AlCl3, primary affects the polyunsaturated fatty acids indicated by the increased of the olefinic -C=CH sub-band area around 3012 cm-1 from the curve fitting analysis. The narrowing in the half band width(HBW) of the sνCH2 sub-band around 2852 cm-1 due to Al intoxication indicates the presence of trans form fatty acids rather than gauch rotomer. The degradation of hydrocarbon chain to shorter chain length, increasing in membrane fluidity, disorder and decreasing in lipid polarity in AlCl3 group were indicated by the detected changes in certain calculated area ratios compared to the control. Administration of LS was greatly improved these parameters compared to the AlCl3 group. Al influences the Aβ aggregation and plaque formation, which in turn interferes to and disrupts the membrane structure. The results also showed a marked increase in the β-parallel and antiparallel structure, that characterize the Aβ formation in Al-induced AD hippocampal brain tissue, indicated by the detected increase in both amide I sub-bands around 1674, 1692 cm-1. This drastic increase in Aβ formation was greatly reduced in the curative and protective groups compared to the AlCl3 group and approaches nearly the control values. These results were supported too by the light microscope. AlCl3 group showed significant marked degenerative changes in hippocampal neurons. Most cells appeared small, shrieked and deformed. Interestingly, the administration of LS in curative and protective groups markedly decreases the amount of degenerated cells compared to the non-treated group. Also the intensity of congo red stained cells was decreased. Hippocampal neurons looked more/or less similar to those of control. This study showed a promising therapeutic effect of Lipidium sativum group (LS) on AD rat model that seriously overcome the signs of oxidative stress on membrane lipid and restore the protein misfolding.

Keywords: aluminum chloride, alzheimer disease, ATR-IR, Lipidium sativum

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Authors: Omar Khan, Shana Krstevska, Edwin George, Veronica Gorden, Fen Bao, Christina Caon, NP-C, Carla Santiago, Imad Zak, Navid Seraji-Bozorgzad

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Objective: To quantify cellular injury in the substantia nigra (SN) in patients with Parkinson's disease (PD) and to examine the effect of rasagiline of tissue injury in the SN in patients with PD. Background: N-acetylaspartate (NAA) quantified with MRS is a reliable marker of neuronal metabolic function. Fractional anisotropy (FA) and mean diffusivity (MD) obtained with DTI, characterize tissue alignment and integrity. Rasagline, has been shown to exert anti-apototic effect. We applied these advanced MRI techniques to examine: (i) the effect of rasagiline on cellular injury and metabolism in patients with early PD, and (ii) longitudinal changes seen over time in PD. Methods: We conducted a prospective longitudinal study in patients with mild PD, naive to dopaminergic treatment. The imaging protocol included multi-voxel proton-MRS and DTI of the SN, acquired on a 3T scanner. Scans were performed at baseline and month 3, during which the patient was on no treatment. At that point, rasagiline 1 mg orally daily was initiated and MRI scans are were obtained at 6 and 12 months after starting rasagiline. The primary objective was to compare changes during the 3-month period of “no treatment” to the changes observed “on treatment” with rasagiline at month 12. Age-matched healthy controls were also imaged. Image analysis was performed blinded to treatment allocation and period. Results: 25 patients were enrolled in this study. Compared to the period of “no treatment”, there was significant increase in the NAA “on treatment” period (-3.04 % vs +10.95 %, p= 0.0006). Compared to the period of “no treatment”, there was significant increase in following 12 month in the FA “on treatment” (-4.8% vs +15.3%, p<0.0001). The MD increased during “no treatment” and decreased in “on treatment” (+2.8% vs -7.5%, p=0.0056). Further analysis and clinical correlation are ongoing. Conclusions: Advanced MRI techniques quantifying cellular injury in the SN in PD is a feasible approach to investigate dopaminergic neuronal injury and could be developed as an outcome in exploratory studies. Rasagiline appears to have a stabilizing effect on dopaminergic cell loss and metabolism in the SN in PD, that warrants further investigation in long-term studies.

Keywords: substantia nigra, Parkinson's disease, MRI, neuronal loss, biomarker

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Authors: Sheikha Turki Alketbi

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Objectives: 1. Documenting the spontaneous resolution of AML following the initiation of anti-TB therapy. 2. Presenting an uncommon type of relapse in Acute Myeloid Leukemia. 3. Highlighting the role of immune markers in the diagnosis of Leukemia cutis. 4. Exploring and highlighting the possibility of skin relapse as the exclusive manifestation, even when skin involvement is known secondary manifestation in AML. Background: Spontaneous remission of Acute Myeloid Leukemia (AML) is a rare phenomenon that has only been reported in some case reports, usually following severe infections. Some studies have described the occurrence of tuberculosis (TB) infection with AML, usually after starting chemotherapy. Spontaneous resolution of AML after starting anti TB therapy (ATT), without starting chemotherapy has never been described in the literature. Moreover, Leukemia cutis is another rare skin manifestation of Acute Myeloid Leukemia as a result of infiltration of the skin or subcutaneous tissue by leukemic cells, in which can present during, precedes, after or independently of systemic leukemia. Methods: Here, we present a case of a 13-year-old male who presented with fever, weight loss, lethargy, epistaxis, bruising and dry cough and was later diagnosed with AML. Before initiating leukemia treatment, the patient was tested for TB and was found to have active TB infection. His leukemia treatment was postponed to clear the TB infection and he was commenced on ATT. Two months later, repeat blood film and bone marrow biopsy showed resolution of his AML. The patient remained in remission for 1 month, after which he presented with symmetrical blue purple well-defined round indurated plaques on the chest and thighs. Our differentials were leukemia cutis and Kaposi sarcoma. Results: Skin Biopsy with immune markers done, showed a picture of Acute Myeloid Leukemia. Immunohistochemistry (IHC) showed neoplastic cells diffusely and strongly positive for LCA, CD2, CD31, MPO, CD117, Lysozymes and TDT, and moderately positive for CD34, CD99, CD43 and CD6 And patchy for CD68. Ki67 showed 60% proliferation index. They were negative for the remaining markers. This suggested acute myeloid leukemia (AML). Conclusion: In summary, we present a rare case of TB with AML that resolved after treatment of TB with ATT but relapsed later as leukemia cutis. While skin involvement might occur as a secondary manifestation of AML, Skin relapse could be the only one.

Keywords: Leukemia cutis, Leukemia relapse, Acute Myeloid Leukemia, spontaneous resolution of AML

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Authors: Fatma Sahir- Halouane, Sonia Hamid, Farida Tihar-Benzina, Fatiha Bouhlali, Souad Lourchane

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The Culicidae are biting insects, the most harmful to people, they are almost all bloodsuckers, and they are responsible of the spread of many important diseases such as malaria, yellow fever, and elephantiasis. Entomopathogenic microorganisms occupy an important place among the alternative methods of fighting against pests insect. The fungus Beauveria bassiana is an entomopathogenic agent naturally present in the ecosystems. It offers a very interesting potential for controlling populations of mosquitoes. This study aimed to show the histological changes that occured in Culex pipiens larvae infected with Beauveria bassiana. The 4th instar larvae were infected with B. bassiana in 10-7 spore/ml dilution, the histological section was studied showing that the fungi infected all the body parts specially Cuticle, Epiderms, fat bodies and midgut. After then the insect have a white appearance and covered with a thick coat of hyphea. The obtained results show that the application of Beauveria bassiana on cuticle of the fourth stage larvae of Culex pipiens was dependent of an apparent disturbance on the structure of the cuticle or there has been the degeneration of its different parts, infection of the fungus does not stop at the body walls. Therefore, it affects even the Adipose tissue, epidermal cells and intestine.

Keywords: Culex pipiens, Beauveria bassiana, histological changes, cuticle, intestine and adipose tissue

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Authors: Z. Arabshahi, I. Afara, A. Oloyede, H. Moody, J. Kashani, T. Klein

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Articular cartilage is a fluid-swollen tissue of synovial joints that functions by providing a lubricated surface for articulation and to facilitate the load transmission. The biomechanical function of this tissue is highly dependent on the integrity of its ultrastructural matrix. Any alteration of articular cartilage matrix, either by injury or degenerative conditions such as osteoarthritis (OA), compromises its functional behaviour. Therefore, the assessment of articular cartilage is important in early stages of degenerative process to prevent or reduce further joint damage with associated socio-economic impact. Therefore, there has been increasing research interest into the functional assessment of articular cartilage. This study developed a characterization parameter for articular cartilage assessment based on the response of cartilage surface to loading/unloading. This is because the response of articular cartilage to compressive loading is significantly depth-dependent, where the superficial zone and underlying matrix respond differently to deformation. In addition, the alteration of cartilage matrix in the early stages of degeneration is often characterized by PG loss in the superficial layer. In this study, it is hypothesized that the response of superficial layer is different in normal and proteoglycan depleted tissue. To establish the viability of this hypothesis, samples of visually intact and artificially proteoglycan-depleted bovine cartilage were subjected to compression at a constant rate to 30 percent strain using a ring-shaped indenter with an integrated ultrasound probe and then unloaded. The response of articular surface which was indirectly loaded was monitored using ultrasound during the time of loading/unloading (deformation/recovery). It was observed that the rate of cartilage surface response to loading/unloading was different for normal and PG-depleted cartilage samples. Principal Component Analysis was performed to identify the capability of the cartilage surface response to loading/unloading, to distinguish between normal and artificially degenerated cartilage samples. The classification analysis of this parameter showed an overlap between normal and degenerated samples during loading. While there was a clear distinction between normal and degenerated samples during unloading. This study showed that the cartilage surface response to loading/unloading has the potential to be used as a parameter for cartilage assessment.

Keywords: cartilage integrity parameter, cartilage deformation/recovery, cartilage functional assessment, ultrasound

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Authors: Ananya Ananya, Karthik Rao

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Accurate segmentation of knee cartilage in 3-D magnetic resonance (MR) images for quantitative assessment of volume is crucial for studying and diagnosing osteoarthritis (OA) of the knee, one of the major causes of disability in elderly people. Radiologists generally perform this task in slice-by-slice manner taking 15-20 minutes per 3D image, and lead to high inter and intra observer variability. Hence automatic methods for knee cartilage segmentation are desirable and are an active field of research. This paper presents design and experimental evaluation of 2D convolutional neural networks based fully automated methods for knee cartilage segmentation in 3D MRI. The architectures are validated based on 40 test images and 60 training images from SKI10 dataset. The proposed methods segment 2D slices one by one, which are then combined to give segmentation for whole 3D images. Proposed methods are modified versions of U-net and dilated convolutions, consisting of a single step that segments the given image to 5 labels: background, femoral cartilage, tibia cartilage, femoral bone and tibia bone; cartilages being the primary components of interest. U-net consists of a contracting path and an expanding path, to capture context and localization respectively. Dilated convolutions lead to an exponential expansion of receptive field with only a linear increase in a number of parameters. A combination of modified U-net and dilated convolutions has also been explored. These architectures segment one 3D image in 8 – 10 seconds giving average volumetric Dice Score Coefficients (DSC) of 0.950 - 0.962 for femoral cartilage and 0.951 - 0.966 for tibia cartilage, reference being the manual segmentation.

Keywords: convolutional neural networks, dilated convolutions, 3 dimensional, fully automated, knee cartilage, MRI, segmentation, U-net

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Authors: Sachin K. Samuchiwal, Barbara Balestrieri, Amanda Paskavitz, Hannah Raff, Joshua A. Boyce

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IL-33, a recently discovered member of the IL-1 cytokine family, binds to the TLR/IL1R super family receptor ST2 and induces type 2 immune responses. IL-33 is constitutively expressed in structural cells at barrier sites such as skin, lung, and intestine, and also inducibly expressed by hematopoietic cells including macrophages. Stimulation of macrophages by Lipopolysaccharide (LPS) can induce de novo IL-33 expression, and also causes the production of prostaglandin-E2 (PGE2) via cyclooxygenase (COX)-2 and microsomal PGE2 synthase-1 (mPGES-1). Because PGE2 can regulate macrophage functions through both autocrine and paracrine mechanisms, the potential interplay of endogenous PGE2 on IL-33 production was explored. Bone-marrow derived murine macrophages (bmMF) that lack either mPGES-1 or EP2 receptor expression were stimulated with LPS in the absence or presence of exogenous PGE2 along with pharmacological agonists and antagonists. The study results demonstrate that endogenous PGE2 markedly enhances LPS-induced IL-33 production by bmMFs via EP2 receptors. Moreover, exogenous PGE2 can amplify LPS-induced IL-33 expression dominantly by EP2 and partly by EP4 receptors by a pathway involving cAMP and exchange protein activated by cAMP (EPAC), but not protein kinase A (PKA). Though both IL-33 production and PGE2 generation in response to LPS require activation of both p38 MAPK and NF-κB, PGE2 did not influence this activation. In conclusion, it is demonstrated that endogenous PGE2 signaling through EP2 and EP4 receptors is a prerequisite for LPS-induced IL-33 production in bmMFs and the underlying cAMP mediated pathway involves EPAC. Since IL-33 is a critical pro-inflammatory cytokine in various pathological disorders, this PGE2-EP2/EP4-cAMP mediated pathway can be exploited to intervene in IL-33 driven pathologies.

Keywords: bone marrow macrophages, EPAC, IL-33, PGE2

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Authors: Hager Elsheikh

Abstract:

Context: Pancreatitis is a condition characterized by inflammation in the pancreas, which can lead to serious complications if untreated. Both acute and chronic pancreatitis are associated with immune reactions and fibrosis, which further damage the pancreas. The type 2 immune response, primarily driven by alternative activated macrophages (AAMs), plays a significant role in the development of fibrosis. The IL-4/STAT6 pathway is a crucial signaling pathway for the activation of M2 macrophages. Pancreatic fibrosis is induced by dysregulated inflammatory responses and can result in the autodigestion and necrosis of pancreatic acinar cells. Research Aim: The aim of this study is to investigate the impact of STAT6, a crucial molecule in the IL-4/STAT6 pathway, on the severity and development of fibrosis during acute and chronic pancreatitis. The research also aims to understand the influence of the JAK/STAT6 signaling pathway on the balance between fibrosis and regeneration in the presence of different macrophage populations. Methodology: The research utilizes murine models of acute and chronic pancreatitis induced by cerulean injection. Animal models will be employed to study the effect of STAT6 knockout on disease severity and fibrosis. Isolation of acinar cells and cell culture techniques will be used to assess the impact of different macrophage populations on wound healing and regeneration. Various techniques such as PCR, histology, immunofluorescence, and transcriptomics will be employed to analyze the tissues and cells. Findings: The research aims to provide insights into the mechanisms underlying tissue fibrosis and wound healing during acute and chronic pancreatitis. By investigating the influence of the JAK/STAT6 signaling pathway and different macrophage populations, the study aims to understand their impact on tissue fibrosis, disease severity, and pancreatic regeneration. Theoretical Importance: This research contributes to our understanding of the role of specific signaling pathways, macrophage polarization, and the type 2 immune response in pancreatitis. It provides insights into the molecular mechanisms underlying tissue fibrosis and the potential for targeted therapies. Data Collection and Analysis Procedures: Data will be collected through the use of murine models, isolation and culture of acinar cells, and various experimental techniques such as PCR, histology, immunofluorescence, and transcriptomics. Data will be analyzed using appropriate statistical methods and techniques, and the findings will be interpreted in the context of the research objectives. Conclusion: By investigating the mechanisms of tissue fibrosis and wound healing during acute and chronic pancreatitis, this research aims to enhance our understanding of the disease progression and potential therapeutic targets. The findings have theoretical importance in expanding our knowledge of pancreatic fibrosis and the role of macrophage polarization in the context of the type 2 immune response.

Keywords: immunity in chronic diseases, pancreatitis, macrophages, immune response

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Authors: Raymond Limen Njinga, Adeneye Samuel Olaolu, Akinyode Ojumoola Ajimo

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Introduction: Measurement of entrance dose and dose at different depths is essential to avoid overdose and underdose of patients. The aim of this study is to verify the variation in the absorbed dose using a water-equivalent material. Materials and Methods: The plastic phantom was arranged on the couch of the halcyon linear accelerator by Varian, with the farmer ionization chamber inserted and connected to the electrometer. The image of the setup was taken using the High-Quality Single 1280x1280x16 higher on the service mode to check the alignment with the isocenter. The beam quality TPR₂₀,₁₀ (Tissue phantom ratio) was done to check the beam quality of the machine at a field size of 10 cm x 10 cm. The calibration was done using SAD type set-up at a depth of 5 cm. This process was repeated for ten consecutive weeks, and the values were recorded. Results: The results of the beam output for the teletherapy machine were satisfactory and accepted in comparison with the commissioned measurement of 0.62. The beam quality TPR₂₀,₁₀ (Tissue phantom ratio) was reasonable with respect to the beam quality of the machine at a field size of 10 cm x 10 cm. Conclusion: The results of the beam quality and the absorbed dose rate showed a good consistency over the period of ten weeks with the commissioned measurement value.

Keywords: linear accelerator, absorbed dose rate, isocenter, phantom, ionization chamber

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Authors: Francesco Angelucci, Katerina Veverova, Alžbeta Katonová, Lydia Piendel, Martin Vyhnalek, Jakub Hort

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Alzheimer's disease (AD) is a central nervous system (CNS) disease characterized by loss of memory, cognitive functions and neurodegeneration. Plasmin is an enzyme degrading many plasma proteins. In the CNS, plasmin may reduce the accumulation of A, and have other actions relevant to AD pathophysiology. Brain plasmin synthesis is regulated by two enzymes: one activating, the tissue plasminogen activator (tPA), and the other inhibiting, the plasminogen activator inhibitor-1 (PAI-1). We investigated whether tPA and PAI-1 serum levels in AD and amnestic mild cognitive impairment (aMCI) patients are altered compared to cognitively healthy controls. Moreover, we examined the PAI-1/tPA ratio in these patient groups. 40 AD, 40 aMCI and 10 healthy controls were recruited. Venous blood was collected and PAI-1 and tPA serum concentrations were quantified by sandwich ELISAs. The results showed that PAI-1 levels increased in AD and aMCI patients. This increase negatively correlated with cognitive deficit measured by MMSE. Similarly, the ratio between tPA and PAI-1 gradually increases in aMCI and AD patients. This study demonstrates that AD and aMCI patients have altered PAI-1 serum levels and PAI-1/tPA ratio. Since these enzymes are CNS regulators of plasmin, PAI-1 serum levels could be a marker reflecting a cognitive decline in AD.

Keywords: Alzheimer disease, amnestic mild cognitive impairment, plasmin, tissue-type plasminogen activator

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