An overview of deep learning techniques for COVID-19 detection: methods, challenges, and future works.

The World Health Organization (WHO) declared a pandemic in response to the coronavirus COVID-19 in 2020, which resulted in numerous deaths worldwide. Although the disease appears to have lost its impact, millions of people have been affected by this virus, and new infections still occur. Identifying COVID-19 requires a reverse transcription-polymerase chain reaction test (RT-PCR) or analysis of medical data. Due to the high cost and time required to scan and analyze medical data, researchers are focusing on using automated computer-aided methods. This review examines the applications of deep learning (DL) and machine learning (ML) in detecting COVID-19 using medical data such as CT scans, X-rays, cough sounds, MRIs, ultrasound, and clinical markers. First, the data preprocessing, the features used, and the current COVID-19 detection methods are divided into two subsections, and the studies are discussed. Second, the reported publicly available datasets, their characteristics, and the potential comparison materials mentioned in the literature are presented. Third, a comprehensive comparison is made by contrasting the similar and different aspects of the studies. Finally, the results, gaps, and limitations are summarized to stimulate the improvement of COVID-19 detection methods, and the study concludes by listing some future research directions for COVID-19 classification.

A MobileNet-based CNN model with a novel fine-tuning mechanism for COVID-19 infection detection.

COVID-19 is a virus that causes upper respiratory tract and lung infections. The number of cases and deaths increased daily during the pandemic. Once it is vital to diagnose such a disease in a timely manner, the researchers have focused on computer-aided diagnosis systems. Chest X-rays have helped monitor various lung diseases consisting COVID-19. In this study, we proposed a deep transfer learning approach with novel fine-tuning mechanisms to classify COVID-19 from chest X-ray images. We presented one classical and two new fine-tuning mechanisms to increase the model's performance. Two publicly available databases were combined and used for the study, which included 3616 COVID-19 and 1576 normal (healthy) and 4265 pneumonia X-ray images. The models achieved average accuracy rates of 95.62%, 96.10%, and 97.61%, respectively, for 3-class cases with fivefold cross-validation. Numerical results show that the third model reduced 81.92% of the total fine-tuning operations and achieved better results. The proposed approach is quite efficient compared with other state-of-the-art methods of detecting COVID-19.

Investigating the magnetic resonance imaging cross-section area that best correlates with intraoperative hamstring autograft size.

OBJECTIVE: This study aimed to find out the level of the gracilis and semitendinosus tendons that would provide the closest information about the size of the quadruple-stranded hamstring autograft using magnetic resonance images before anterior cruciate ligament reconstruction. METHODS: Ninety-six patients (44 males, 52 females) who underwent anterior cruciate ligament reconstruction with quadruple hamstring tendon autografts between January 2015 and March 2020 were retrospectively analyzed. The cross-sectional areas of the gracilis and the semitendinosus tendons at 6 different levels (pes anserinus insertion site, tibial tuberosity, fibular head, tibial plateau, and the proximal insertion sites of the anterior cruciate ligament and the medial collateral ligament were measured on the magnetic resonance images. In addition, the harvested hamstring tendons were measured together (quadrupled) using a standardized graft-sizing block. RESULTS: There was no significant difference between genders in terms of the tendon sizes measured in all levels using magnetic resonance images. There was a strong correlation between the graft size and the measurements made at the tibial plateau level (P < .0001, r=0.590). CONCLUSION: Intraoperative quadruple hamstring tendon sizes were most correlated with the magnetic resonance image measurements at the tibial plateau level. To use a hamstring autograft with a diameter of at least 8 mm for anterior cruciate ligament reconstruction, the total area of the 2 tendons should be at least 18.11 mm2 in the magnetic resonance image measurements made at the tibial plateau level. LEVEL OF EVIDENCE: Level IV, Diagnostic Study.

Genome-wide characterization of two Aubrieta taxa: Aubrieta canescens subsp. canescens and Au. macrostyla (Brassicaceae).

Aubrieta canescens complex is divided into two subspecies, Au. canescens subsp. canescens, Au. canescens subsp. cilicica and a distinct species, Au. macrostyla, based on molecular phylogeny. We generated a draft assembly of Au. canescens subsp. canescens and Au. macrostyla using paired-end shotgun sequencing. This is the first attempt at genome characterization for the genus. In the presented study, ~165 and ~157 Mbp of the genomes of Au. canescens subsp. canescens and Au. macrostyla were assembled, respectively, and a total of 32 425 and 31 372 gene models were predicted in the genomes of the target taxa, respectively. We corroborated the phylogenomic affinity of taxa with some core Brassicaceae species (Clades A and B) including Arabis alpina. The orthology-based tree suggested that Aubrieta species differentiated from A. alpina 1.3-2.0 mya (million years ago). The genome-wide syntenic comparison of two Aubrieta taxa revealed that Au. canescens subsp. canescens (46 %) and Au. macrostyla (45 %) have an almost identical syntenic gene pair ratio. These novel genome assemblies are the first steps towards the chromosome-level assembly of Au. canescens and understanding the genome diversity within the genus.

Anatomical Factors Which Influence the Formation of Peroneal Tendon Tears: A Retrospective Comparative Study.

This study aims to investigate the anatomical factors that are effective in the formation of peroneal tendon tears comparing with the control group. The patients with ankle magnetic resonance imaging (MRI) due to pain on the lateral side of the ankle were retrospectively analyzed using the clinical archive between July 2015 and January 2020. Peroneal tendon tears, peroneal tubercle type and size, presence of peroneal quartus, presence and type of retromalleolar groove, retromalleolar groove area, lateral malleolus type, presence of os peroneum, peroneus brevis-lateral malleolus distance (PBLMD), and accompanying pathologies in coronal, axial, and sagittal planes MRI were evaluated. PBLMD was measured as 27.1 ± 12.3 mm in Group 1. With PBLMD, it was measured as 39.6 ± 11.68 mm in Group 2. There was a significant relationship between low-lying peroneus brevis muscle and peroneal tear (p < .001). Peroneal tendon tear was more common in patients with peroneal quartus muscle (p < .001). There was a relationship between the retromalleolar groove type and the presence of peroneal tear (p = .004). More peroneal tears were observed in the concave retromalleolar groove type. The presence of concave type retromalleolar groove, peroneus quartus, and low-lying peroneus brevis muscle was found to be associated with peroneal tendon tears.

Lessons from a ten-year-long journey: building a student-driven computational biology society across Turkey.

The Regional Student Group Turkey (RSG-Turkey) is officially associated with the International Society for Computational Biology (ISCB) Student Council (SC). At the RSG-Turkey, we aim to contribute to the early-career researchers in computational biology and bioinformatics fields by providing opportunities for improving their academic and technical skills in the field. Over the last ten years, we have built a well-known student-driven academic society in Turkey that organizes numerous events every year and continues to grow with over 650 current members. Celebrating the 10th anniversary of RSG-Turkey, in this communication, we share our experiences, five main lessons we learned, and the steps to establish a long-standing academic community: having a clear mission, building a robust structure, effective communication, turning challenges into opportunities, and building collaborations. We believe that our experiences can help students and academics establish long-standing communities in fast-developing areas like bioinformatics.

A deep convolutional neural network model for hand gesture recognition in 2D near-infrared images.

The hand gesture recognition (HGR) process is one of the most vital components in human-computer interaction systems. Especially, these systems facilitate hearing-impaired people to communicate with society. This study aims to design a deep learning CNN model that can classify hand gestures effectively from the analysis of near-infrared and colored natural images. This paper proposes a new deep learning model based on CNN to recognize hand gestures improving recognition rate, training, and test time. The proposed approach includes data augmentation to boost training. Furthermore, five popular deep learning models are used for transfer learning, namely VGG16, VGG19, ResNet50, DenseNet121, and InceptionV3 and compared their results. These models are applied to recognize 10 different hand gestures for near-infrared images and 24 ASL hand gestures for colored natural images. The proposed CNN model, VGG16, VGG19, Resnet50, DenseNet121, and InceptionV3 models achieve recognition rates of 99.98%, 100%, 99.99%, 91.63%, 82.42% and 81.84%, respectively on near-infrared images. For colored natural ASL images, the models achieve recognition rates of 99.91%, 99.31%, 98.67%, 91.97%, 93.37%, and 93.21%, respectively. The proposed model achieves promising results spending the least amount of time.

A Study of the Effects of Metformin, a Biguanide Derivative, on Annulus Fibrosus and Nucleus Pulposus Cells.

AIM: To investigate the effects of metformin, a drug used widely for the treatment of type 2 diabetes mellitus, on human primary cell cultures prepared from uninjured segment of disc material intervertebral disk tissues. MATERIAL AND METHODS: Primary cell cultures were prepared using the tissues of six patients (three males and three females) who had undergone lumbar microdiscectomy and sequestrectomy. Untreated samples served as the control group, and metformintreated samples served as the experimental group. All the samples were evaluated using an inverted light microscope, acridine orange/propidium iodide staining (AO/PI), and a fluorescence microscope. The cytostatic and cytotoxic effects of metformin, which was administered to the samples using a commercial MTT assay kit, were also evaluated. The data obtained were statistically assessed, and the alpha significance value was accepted as less than 0.05. In addition, for the groups’ changes in the expressions of chondroadherin (CHAD), cartilage oligomeric matrix protein (COMP), interleukin-1β (IL-1β) matrix metalloproteinase 7 (MMP-7), and matrix metalloproteinase 19 (MMP-19), genes related to the extracellular matrix synthesis and degradation were determined using gene-specific TaqMan Gene Expression Assays. RESULTS: The administration of the drug adversely affected nucleus pulposus (NP)/annulus fibrosus (AF) cells and extracellular matrixâ€"like structures. This was statistically significant (p < 0.05). CONCLUSION: Clinicians should not disregard the adverse effects of metformin, which is used widely in clinical practice, on the components of intervertebral disk tissues.

Effect of sedation anesthesia on kinesiophobia and early outcomes after total knee arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) operation is an effective treatment method in severe osteoarthritis worldwide. However, the number of patients with chronic pain and functional limitations in the postoperative period will continue to increase. Kinesiphobia is an important factor that affects the functional outcomes postoperatively. The aim of this study is to investigate the effects of intraoperative consciousness of the patients during surgery on kinesiophobia development and early functional outcomes of TKA. METHODS: Sixty patients with the diagnosis of primary knee osteoarthritis were enrolled in the study. Tampa Scale of Kinesiophabia (TSK) was obtained for each patient at multiple time periods. Regional anaesthesia and deep sedation were performed on group 1 (n = 30), while regional anaesthesia and light sedation were performed on group 2 (n = 30). The same surgical procedures were applied to all participants. Functional tests were performed on the patients at the postoperative 2nd and 5th days. Visual Analogue Scale (VAS) scores and knee flexion angles were also measured postoperatively. RESULTS: The mean age of the participants (19 men (31.7%) and 41women (68.3%)) was 67.7 ± 6.7 (54-82) years. TSK ≥ 40 was detected in 18 (30%) patients preoperatively and 33 patients (55%) postoperatively. The number of kinesiophobic patients showed statistically significant increase after operation (20/30 (66.7%)) according to preoperative period (9/30 (30%)) in group 2 (p = 0.003). Postoperative functional scores, knee flexion angles and VAS scores were better in non-kinesiophobic patients. Conclusion: Patient's consciousness during TKA operations is an important factor that interferes with the postoperative kinesiophobia development, which may play a pivotal role affecting the early mobility and functional outcomes.

Global network of computational biology communities: ISCB's Regional Student Groups breaking barriers.

Regional Student Groups (RSGs) of the International Society for Computational Biology Student Council (ISCB-SC) have been instrumental to connect computational biologists globally and to create more awareness about bioinformatics education. This article highlights the initiatives carried out by the RSGs both nationally and internationally to strengthen the present and future of the bioinformatics community. Moreover, we discuss the future directions the organization will take and the challenges to advance further in the ISCB-SC main mission: "Nurture the new generation of computational biologists".

Investigation of the Effects of Methylphenidate, an Amphetamine Derivative, on Intervertebral Disc Tissue Cell Cultures and Matrix Structures.

AIM: To investigate the effects of methylphenidate (MPH), on intervertebral disc tissue (IVD) cell cultures and extracellular matrix structures. Changes in the expression of some important marker genes involved in anabolic and catabolic mechanisms of IVD extracellular matrix formation were also evaluated. MATERIAL AND METHODS: Primary cultures of nucleus pulposus cells (NPCs) and annulus fibrosus cells (AFCs) were isolated from tissues obtained from the operated patients. Cell viability and proliferation were tested, and the cell surface morphologies were evaluated by microscopy. The expressions of the chondroadherin (CHAD), cartilage oligomeric matrix protein (COMP), interleukin-1 beta (IL-1ß) and matrix metalloproteinase (MMP) -7 and MMP-19 genes were evaluated using the quantitative real-time polymerase chain reaction (qRT-PCR). A value of p < 0.05 was considered statistically significant. RESULTS: The viability and proliferation of intervertebral disc tissue cells decreased in response to MPH treatment and the expression of the investigated genes also changed. CONCLUSION: The data obtained from in-vitro studies may not directly adaptable to clinical applications. However, the fact that the central nervous system stimulant MPH can suppress proliferation of cells derived from IVD tissue should be considered carefully by clinicians.

Effects of etanercept, a tumor necrosis factor receptor fusion protein, on primary cell cultures prepared from intact human intervertebral disc tissue.

The aim of the present study was to investigate the effects of etanercept (ETA), a tumor necrosis factor (TNF) inhibitor, on human cell cultures prepared from intact intervertebral disc tissue. ETA is used as a treatment for cases of rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis and ankylosing spondylitis accompanied by moderate or severe joint pain. ETA was applied to primary cell cultures [annulus fibrosus and nucleus pulposus (NP) from intact intervertebral disc tissue]. Cell cultures without ETA treatment served as the control group. Morphological and quantitative molecular analyses of the two groups were performed. The number of viable cells and cell proliferation decreased in the ETA-treated cultures as compared with those in the control group. Furthermore, in the treatment group, the chondroadherin gene, an NP-specific marker, was not expressed after 24 h. By contrast, the cartilage oligo matrix protein was expressed 24, 48 and 72 h post-ETA treatment, while its expression was significantly lower than that in the control group. In addition, the expression of interleukin-1ß, as well as matrix metallopeptidase-7 and -19, was markedly decreased. Overall, the cell proliferation and gene expression in the ETA-treated cells were significantly different from those in the control group (P<0.05). These results suggest that the treatment duration and dosage of TNF inhibitors, which are used to suppress active inflammation, should be considered in the clinical setting. These biological agents may delay the healing of intervertebral disc tissue damage by slowing cell proliferation and altering gene expression via anabolic and catabolic pathways.

Investigation of the effect of dipyrone on cells isolated from intervertebral disc tissue.

The present study aimed to evaluate the effects of dipyrone, an indispensable analgesic, anti-pyretic and anti-spasmodic used in emergency departments, on nucleus pulposus and annulus fibrosus cells in vitro. After surgical biopsy, primary cell cultures were prepared from intact intervertebral disc tissues. Dipyrone was administered to the cultures in the experimental groups except for the control group. The data obtained were statistically evaluated. The proliferation was identified to be suppressed via MTT analysis. The gene expression profile of the intervertebral disc cells in the dipyrone-treated groups was significantly changed. The expression of chondroadherin, cartilage oligo matrix protein, interleukin-1ß and metalloproteinase (MMP)-19 genes were decreased, but MMP-13 and MMP-7 genes expressions were increased, as determined via reverse transcription-quantitative PCR. AO/PI staining revealed that no apoptotic or other type of cell death was detectable after administration of dipyrone does not mean that the drug is innocuous. The occurrence of cellular senescence and/or the halt of cell proliferation may also be important mechanisms underlying the adverse inhibitory effects of dipyrone. Therefore, prior to administering dipyrone in clinical practice, all possible adverse effects of this drug should be considered.

Does Nimodipine, a Selective Calcium Channel Blocker, Impair Chondrocyte Proliferation or Damage Extracellular Matrix Structures?

BACKGROUND: The study aimed to investigate the effects of the active ingredient, nimodipine, on chondrocyte proliferation and extracellular matrix (ECM) structures in cartilage tissue cells. METHODS: Chondrocyte cultures were prepared from tissues resected via surgical operations. Nimodipine was then applied to these cultures and molecular analysis was performed. The data obtained were statistically calculated. RESULTS: Both, the results of the (3-(4,5 dimethylthiazol2-yl)-2,5-diphenyltetrazolium (MTT) assay and the fluorescence microscope analysis [a membrane permeability test carried out with acridine orange/ propidium iodide staining (AO/PI)] confirmed that the active ingredient, nimodipine, negatively affects the cell cultures. CONCLUSION: Nimodipine was reported to suppress cellular proliferation; chondroadherin (CHAD) and hypoxia-inducible factor-1 alpha (HIF-1α) expression thus decreased by 2.4 and 1.7 times, respectively, at 24 hrs when compared to the control group (p < 0.05). Furthermore, type II collagen (COL2A1) expression was not detected (p < 0.05). The risk that a drug prescribed by a clinician in an innocuous manner to treat a patient by relieving the symptoms of a disease may affect the proliferation, differentiation, and viability of other cells and/or tissues at the molecular level, beyond its known side effects or adverse events, should not be forgotten.

Effects of tranexamic acid on the recovery of osteochondral defects treated by microfracture and acellular matrix scaffold: an experimental study.

BACKGROUND: Microfracture and scaffold application in the treatment of osteochondral defects is still one of the most frequently used methods in the clinic. The most important step in this treatment method is the stabilization of fibrin clot. Tranexamic acid (TA) is an antifibrinolytic agent commonly used in orthopedic surgery in recent years. This study evaluated the effect of local TA application on healing of experimentally induced osteochondral defects on rabbits. METHODS: This paper contains an animal in vivo data and histological outcomes on the effect of TA. Eighteen New Zealand white rabbits were treated unilaterally and cylindrical defects having a width of 4 mm and depth of 5 mm were created in the weight-bearing surfaces of the medial and lateral condyles of the right femur. They were divided into two groups, as group 1 study and group 2 control groups, respectively. One milliliter (ml) of TA was injected into the knee joints of the subjects in group 1. All animals were sacrificed for the extraction of the femur condyles for histologic study at the fourth and eighth weeks after surgery. Histological evaluations were performed by Brittberg and O'Driscoll scores to all samples. Data were organized in a Standard Statistical Package System v.22 software package (SPSS/PC Inc., Chicago, IL.) and reported as mean and median (min-max). Repeated measures ANOVA test was used to compare groups and condyle effects together for each week. p values below 0.05 were considered as statistically significant. RESULTS: Samples were taken in the fourth and eighth weeks. The regularity of the surface in group 1 was smoother, and the tissue stability was more robust. Mean Brittberg scores in both weeks were statistically higher in group 1 when compared with group 2. In the microscopic evaluation, it was observed that the regeneration of subchondral and cartilage tissues were more rapid and organized in group 1, and the mean O' Driscoll scores in both weeks were statistically higher in group 1. CONCLUSIONS: Application of TA improves the healing time and tissue stability in osteochondral defects which are implanted a-cellular scaffold after microfracture and should be applicable to humans for the treatment of osteochondral defects.

Simple, stable, compact implementation of frequency-division-multiplexed microscopy by inline interferometry.

Frequency-division-multiplexed (FDM) imaging is a powerful method for high-speed imaging that surpasses the speed limit of conventional imaging constrained by the frame rate of image sensors. However, its complexity, instability, and bulkiness deriving from the implementation with a Mach-Zehnder interferometer hamper its practical applications. Here we demonstrate a simple, stable, and compact implementation of FDM imaging by inline interferometry that makes the method readily available to practical situations. As a proof-of-concept demonstration, we demonstrate 2D bright-field and fluorescence image acquisition of fluorescent beads, microalgal cells, and breast cancer cells within 65.5 µs, corresponding to 15,300 frames per second.

Asymmetric bilateral hip dislocations and unilateral femoral head fracture: A CASE report.

Hip is a stabilized joint due to the surrounding ligaments, and muscles, which can dislocate as a result of high energy trauma, high-level falls, and motor vehicle accidents. Traumatic hip dislocations can either be isolated or simultaneously with acetabular and proximal femur fractures. At the same time injury of sciatic, femoral or obturator nerves can be seen. However, avascular necrosis of femoral head, posttraumatic osteoarthritis, and heterotopic ossifications can be seen as prolonged complications. The period prior to the reduction, severity of the trauma, and performing open or close reductions are the major contributors of the prognosis. As an extremely rare entity, bilateral asymmetrical hip dislocations are reported as the 0.01-0.02% of all joint dislocations. Accompanying proximal femoral fractures are pointed out 17%, one of them is femoral head fractures which are orthopedic emergencies that need to be fixed with surgery. However, high incidence of AVN is reported at the end of 2 years even if following early reductions. In our article, traumatic bilateral asymmetric hip dislocations and femoral head fracture is described in the context of a diagnosis, treatment and follow-up.

Pregabalin treatment for neuropathic pain may damage intervertebral disc tissue.

The aim of the present study was to determine whether pharmaceutical preparations with pregabalin (PGB) as an active ingredient, which are widely prescribed by clinicians, exert toxic effects on human primary nucleus pulposus (NP) and annulus fibrosis (AF). Primary human cell cultures were obtained from intact (n=6) and degenerated (n=6) tissues resected from the two groups of patients. Different doses of PGB were applied to these cultures and cells were subjected to molecular analyses at 0, 24 and 48 h. Cell vitality, toxicity and proliferation were assessed using a spectrophotometer. The expression of chondroadherin (CHAD), a (member of the NP-specific protein family), hypoxia-inducible factor-1α (HIF-1α) and type II collagen (COL2A1) was measured using reverse transcription-quantitative polymerase chain reaction. The results revealed that cell intensity increased in a time-dependent manner and cell vitality continued in the cultures without pharmaceuticals. Cell proliferation was suppressed in the PGB-treated cultures independent from the dose and duration of application. PGB was demonstrated to suppress the expression of CHAD and HIF-1α. In contrast, COL2A1 gene expression was not revealed in any experimental group. The present study utilized an in vitro model and the PGB active ingredient used herein may not be representative of clinical applications; however, the results demonstrated that PGB has a toxic effect on NP/AF cell cultures containing primary human intervertebral disc tissue. In summary, the use of pharmacological agents containing PGB may suppress the proliferation and differentiation of NP/AF cells and/or tissues, which should be considered when deciding on an appropriate treatment regime.

The association between different molecular weights of hyaluronic acid and CHAD, HIF-1α, COL2A1 expression in chondrocyte cultures.

The aim of the present study was to investigate the effects of three different formulations of hyaluronic acid (HA): Low molecular weight (MW) Sinovial One®, medium MW Viscoplus® and high MW Durolane®, on chondrocyte proliferation and collagen type II (COL2A1), hypoxia-inducible factor 1α (HIF-1α) and chondroadherin (CHAD) expression in primary chondrocyte cultures. Standard primary chondrocyte cultures were established from osteochondral tissues surgically obtained from 6 patients with gonarthrosis. Cell morphology was evaluated using an inverted light microscope; cell proliferation was determined with a MTT assay and confirmed with acridine orange/propidium iodide staining. Levels of CHAD, COL2A1 and HIF-1α expression were assessed using specific TaqMan gene expression assays. The results demonstrated the positive effect of HA treatment on cell proliferation, which was independent from the MW. COL2A1 expression increased in the medium and high MW HA treated groups. It was observed that HIF-1α expression increased in the high MW treated group alone. CHAD expression increased only in the medium MW HA treated group. Evaluation of gene expression revealed that levels of expression increased as the duration of HA application increased, in the medium and high MW HA treated groups. In terms of increased viability and proliferation, a longer duration of HA application was more effective. Taken together, it may be concluded that the administration of medium and high MW HA may be a successful way of treating diseases affecting chondrocytes in a clinical setting.

Are We Using Slow-Acting Symptomatic Chondroprotective Drugs Conscious Enough?

BACKGROUND: Osteochondral injuries constitute an entity that is widespread and can be seen in patients of all ages. Actual treatment modalities aim to relieve pain, obtain full range of movement of the joint, and improve the quality of life. There are many slow-acting chondroprotective agents prevalently used in the United States that are classified as nutritional support but not as medicines . This study presents the importance of clinical adverse effect profiles as well as the pharmacological mechanism of action and application of combinations of drugs that are widely prescribed and not subjected to control. METHODS: Electronic databases were searched with keywords about the chondroprotective drugs without any language restriction. Evaluations of the descriptive statistics were represented via Microsoft Office Excel 2010 lists in the form of a mean±standard deviation or frequency (%). The first evaluation showed that 1502 studies were potentially relevant. Following exclusion of the 1277 studies which were not clinical, full versions of the remaining 225 studies were subjected to further evaluation. No controlled, blinded, randomized and/or comparative studies met the inclusion criteria of the study, and no studies evaluated the comparative clinical results of the hyaluronan of different molecular weights. RESULTS: The findings of this study concluded that especially when prescribing drugs with ingredients like GS and CS, many patients' pre-existing conditions must be considered, such as whether the patient has a glucose intolerance or not. Additionally, mineral toxication should be considered since the drugs contain minerals, and after the application of injected hyaluronan, complications should be considered. CONCLUSION: Clinical, controlled and comparative studies about the use of chondroprotective drugs must be performed to define the benefits of these drugs, if any, in order to determine the most suitable time for operative intervention.