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Item Open Access Investigating the Suitability of Mare’s Milk-Derived Exosomes as Potential Drug Carriers.(MDPI, 2024) Sergazy, S.; Zhetkenev, S; Shulgau, Z.; Chulenbayeva, L.; Kamyshanskiy, Y.; Nurgaziyev, M.; Nurgozhina, A.; Mukhanbetzhanova, Z.; Berikkhanova, K.; Gulyayev, A.; Aljofan M.Exosomes are cell-derived, membrane-surrounded particles that deliver bioactive molecules to various cells. Due to their small size, low immunogenicity, extended blood circulation, and involvement in cellular communication, they hold potential as effective drug carriers. Exosomes are present in various biological fluids, including mare’s milk, a traditional drink in Central Asia. This study aims to compare exosome isolation methodologies and determine the stability of mare’s milk-derived exosomes as potential therapeutic carriers. Three extraction methods—immunoprecipitation, size exclusion chromatography, and total exosome isolation—were compared in terms of exosome characteristics, purity, and content. The isolated exosomes were then loaded with quercetin, and their ability to increase its bioavailability was tested in vitro and in vivo. Total exosome isolation was identified as the most efficient method for producing high-quality exosomes. These exosomes were loaded with quercetin and compared to free quercetin and exosomes alone. Exosomes loaded with 80 µM quercetin significantly restored β-galactosidase activity and cellular viability in doxorubicin-treated cells, exhibiting similar potency to 160 µM free quercetin. In aged model animals, treatment with quercetin-loaded exosomes resulted in significantly less acute and subacute damage to the myocardium, kidneys, and liver compared to untreated control animals. This study provides a proof-of-concept that mare’s milk-derived exosomes can be effectively absorbed by cells and animal tissues, supporting their potential use as drug carriers.Item Open Access Antiproliferative and Cytotoxic Activity of Geraniaceae Plant Extracts Against Five Tumor Cell Lines(Taylor & Francis, 2021) Sergazy Shynggys; Vetrova Anastassiya; Orhan Ilkay Erdogan; Senol Deniz Fatma Sezer; Kahraman Ahmet; Zhang Jian_Ye; Aljofan MohamadAim: To determine the antiproliferative and cytotoxic activities of Geranium and Erodium species against human cancer and noncancer cell lines, respectively. Methods: Twenty-one species of Geranium and Erodium were extracted and screened against cancerous and noncancerous human cell lines. Results: In a dose-response manner, G. glaberrimum, G. asphodeloides, E. brandianum and E. leucanthum were able, with variable potency, to inhibit cellular proliferation. Except for E. brandianum, all extracts induced cellular autophagy in tumor cells with similar levels to that of rapamycin; but, only E. brandianum induced cellular apoptosis, likely through Bcl2 and BAX protein expressions. Discussion: This is the first study to report the potential antiproliferative effects of ethanol extracts of several Geraniaceae species. Lay abstract Several plant species of the genera Geranium and Erodium were extracted and screened against five tumor cell lines for their potential antitumor activities. Out of the tested species, four showed potential antitumor action against all the tumor cells used. Interestingly, they appeared to achieve their antitumor activities by inducing important cellular defense mechanisms called autophagy and apoptosis. The current work is the first to test the antiproliferative potential of these species against different tumor cells.Item Open Access Blueberry and cranberry extracts mitigate CCL4-induced liver damage, suppressing liver fibrosis, inflammation and oxidative stress.(Elsevier, 2023) Sergazy Shynggys; Shulgau Zarina; Kamyshanskiy Yevgeniy; Zhumadilov Zhaxybay; Krivyh Elena; Gulyayev Alexander; Aljofan MohamadThe current study aims to evaluate potential hepatoprotective effect of lingonberry, cranberry and blueberry polyphenols on carbon tetrachloride (CCL-4)-induced acute and subacute liver injury in rats. A total of 55 male Wistar rats, divided into six experimental and control groups. With the exception of the negative control group, all groups received an intraperitoneal injection of CCl-4, twice a week for 14 days. An extract of lingonberry, cranberry, blueberry polyphenols and the positive control, silymarin were administered daily via intragastric route, for 14 consecutive days. The untreated control group showed characteristic of classical oxidative stress-mediated liver damage with vacuolization of the hepatocyte cytoplasm, infiltration by immune cells and proliferation of collagen fibers, decrease in body weight and increase in liver weight; increased levels of AST and ALT in serum, an increased lipid peroxidation in the liver. However, the use of cranberry and blueberry polyphenols significantly suppressed liver damage, exerting an effect comparable to the hepatoprotective effect of the positive control. The extracts prevented and reduced inflammatory liver damage by reducing IL-6, TNF-α and IFN-γ levels. In conclusion, blueberry and cranberry extracts have a protective effect against acute and subacute CCl4-induced hepatotoxicity in rats.Item Open Access Establishment and validation of mare’s milkderived exosomes extraction method(Springer, 2022) Aljofan M.; Issayev A.; Sergazy S.; Zhetkenev S.Exosomes are nanosized (30-150nm) extracellular vesicles with double layer lipid membrane, that present in milk of farm animals. These vesicles maintain endocrine, paracrine and autocrine signaling. They produced by parental cell as major substance of cell-cell communications. Their main physiological function is to transmit cellular signals and are capable of carrying big and charged molecules, which otherwise would not be able to penetrate the plasma membraneItem Open Access Antioxidant and cytoprotective properties of quercetin-loaded mare’s milk exosomes(Wiley, 2023) Sergazy Shynggys; Zhetkenev Sanzhar; Chulenbayeva Laura; Aljofan Mohamad; Gulyayev AlexandrMare's milk is the national drink of the indigenous population of Kazakhstan. Similar to other milk types, mare's milk is a rich source of EVs, which can be loaded with flavonoids such as quercetin that may have some valuable therapeutic properties. In this study, we examine cytoprotective properties of quercetin-loaded exosomes (ExoQuer) on doxorubicin induced cellular toxicity as well as antioxidant and radical scavenging activityItem Open Access Establishment and validation of mare’s milk-derived exosomes extraction method(Wiley, 2023) Nurgozhina Ayaulym; Sergazy Shynggys; Chulenbayeva Laura; Zhetkenev Sanzhar; Aljofan Mohamadextracellular vesicles, drug delivery, drug discovery, biopharmaceuticalsItem Open Access Antiradical and Cytoprotective Properties of Allium nutans L. Honey Against CCL4-Induced Liver Damage in Rats(Frontiers, 2021) Sergazy, S.; Gulyayev, A.; Amangeldiyeva, A.; Nurgozhina, A.; Nurgaziyev, M.; Shulgau, Z.; Chulenbayeva, L.; Khassenbekova, Z.; Kushugulova, A.; Aljofan, M.The aim of this study is determine the in vitro and in vivo antiradical properties and the cytoprotective activity of Allium nutans L. honey extract. The antiradical properties of the extracts were investigated in rabbit alveolar macrophages and human foreskin fibroblast (hFFs) cells in the presence of doxorubicin, a cytotoxic substance using DPPH and ABTS assays. The cytoprotective activities were determined using 18 Wistar rats divided into three different groups, a negative control, and two other groups with experimentally induced hepatotoxicity by a single intraperitoneal injection of 50% carbon tetrachloride (CCl4) oil solution. A positive control group, received drinking water only and an experimental group that was treated with Allium nutans L. honey extracts for 7 days. In vitro treatment with Allium nutans L. honey extracts resulted in 78% reduction in radical activity in DPPH and 91.6% inhibition using the ABTS. Also, honey extracts were able to preserve 100% of cell viability in the presence of the cytotoxic, doxorubicin. Furthermore, the treatment with honey extracts resulted in a significant reduction in damage to the structure of liver tissue, as well significant reduction in the levels of ALT and AST in the experimental group compared to the control groupItem Open Access Proteomic and transcriptomic characterization of mare’s milk derived exosomes(Wiley, 2023) Nurgaziyev Madiyar; Nurgozhina Ayaulym; Sergazy Shynggys; Gulyayev Alexandr; Chulenbayeva Laura; Zhetkenev Sanzhar; Aljofan MohamadExtracellular vesicles, drug delivery, drug discovery, biopharmaceuticalsItem Open Access COMBINED SUPPLEMENTATION OF COENZYME Q10 AND OTHER NUTRIENTS IN SPECIFIC MEDICAL CONDITIONS(Nutrients, 2022) Tippairote, Torsak; Bjørklund, Geir; Gasmi, Amin; Semenova, Yuliya; Peana, Massimiliano; Chirumbolo, Salvatore; Hangan, TonyCoenzyme Q10 (CoQ10) is a compound with a crucial role in mitochondrial bioenergetics and membrane antioxidant protection. Despite the ubiquitous endogenous biosynthesis, specific medical conditions are associated with low circulating CoQ10 levels. However, previous studies of oral CoQ10 supplementation yielded inconsistent outcomes. In this article, we reviewed previous CoQ10 trials, either single or in combination with other nutrients, and stratified the study participants according to their metabolic statuses and medical conditions. The CoQ10 supplementation trials in elders reported many favorable outcomes. However, the single intervention was less promising when the host metabolic statuses were worsening with the likelihood of multiple nutrient insufficiencies, as in patients with an established diagnosis of metabolic or immune-related disorders. On the contrary, the mixed CoQ10 supplementation with other interacting nutrients created more promising impacts in hosts with compromised nutrient reserves. Furthermore, the results of either single or combined intervention will be less promising in far-advanced conditions with established damage, such as neurodegenerative disorders or cancers. With the limited high-level evidence studies on each host metabolic category, we could only conclude that the considerations of whether to take supplementation varied by the individuals’ metabolic status and their nutrient reserves. Further studies are warranted.Item Open Access CELIAC DISEASE AND GALLBLADDER: PATHOPHYSIOLOGICAL ASPECTS AND CLINICAL ISSUES(Nutrients, 2022) Poddighe, Dimitri; Dossybayeva, Kuanysh; Abdukhakimova, Diyora; Akhmaltdinova, Lyudmila; Ibrayeva, AigulCeliac Disease (CD) is an immune-mediated disorder which primarily affects the small intestine; however, extra-intestinal organs are often affected by the pathological process, too. As regards the digestive system, liver alterations in CD patients have been widely described, which can also extend to the biliary tract. Notably, gallbladder function can be altered in CD patients. In this review, we specifically analyze and summarize the main pathophysiological aspects and clinical evidence of gallbladder dysfunction in CD patients, in order to discuss the potential medical complications and clinical research gaps. In addition to some perturbations of bile composition, CD patients can develop gallbladder dysmotility, which mainly expresses with an impaired emptying during the digestive phase. The main pathophysiological determinant is a perturbation of cholecystokinin secretion by the specific duodenal enteroendocrine cells in response to the appropriate nutrient stimulation in CD patients. This situation appears to be reversible with a gluten-free diet in most cases. Despite this gallbladder impairment, CD patients do not seem to be more predisposed to gallbladder complications, such as calculous and acalculous cholecystitis. However, very few clinical studies have actively investigated these clinical aspects, which may not be completely evidenced so far; alternatively, the substantial improvements in the last two decades regarding CD diagnosis, which have reduced the diagnostic delay (and related dietary treatment), may have lessened the potential clinical consequences of CD-related gallbladder dysfunction. Specific clinical studies focused on these aspects are needed for a better understanding of the clinical implications of gallbladder alterations in CD patients.Item Open Access IN SITU TRANSFORMATION OF ELECTROSPUN NANOFIBERS INTO NANOFIBER-REINFORCED HYDROGELS(Nanomaterials, 2022) Martin, Alma; Nyman, Jenny Natalie; Reinholdt, Rikke; Cai, Jun; Schaedel, Anna-Lena; J. A. van der Plas, Mariena; Malmsten, Martin; Rades, Thomas; Heinz, AndreaNanofiber-reinforced hydrogels have recently gained attention in biomedical engineering. Such three-dimensional scaffolds show the mechanical strength and toughness of fibers while benefiting from the cooling and absorbing properties of hydrogels as well as a large pore size, potentially aiding cell migration. While many of such systems are prepared by complicated processes where fibers are produced separately to later be embedded in a hydrogel, we here provide proof of concept for a one-step solution. In more detail, we produced core-shell nanofibers from the natural proteins zein and gelatin by coaxial electrospinning. Upon hydration, the nanofibers were capable of directly transforming into a nanofiber-reinforced hydrogel, where the nanofibrous structure was retained by the zein core, while the gelatin-based shell turned into a hydrogel matrix. Our nanofiber-hydrogel composite showed swelling to ~800% of its original volume and water uptake of up to ~2500% in weight. The physical integrity of the nanofiber-reinforced hydrogel was found to be significantly improved in comparison to a hydrogel system without nanofibers. Additionally, tetracycline hydrochloride was incorporated into the fibers as an antimicrobial agent, and antimicrobial activity against Staphylococcus aureus and Escherichia coli was confirmed.Item Open Access INTERACTIONS OF APIGENIN AND SAFRANAL WITH THE 5HT1A AND 5HT2A RECEPTORS AND BEHAVIORAL EFFECTS IN DEPRESSION AND ANXIETY: A MOLECULAR DOCKING, LIPID-MEDIATED MOLECULAR DYNAMICS, AND IN VIVO ANALYSIS(Molecules, 2022) Amin, Faiq; Ibrahim, Mahmoud A. A.; Rizwan-ul-Hasan, Syed; Khaliq, Saima; Gabr, Gamal A.; Khan, Asra; Sidhom, Peter A.; Tikmani, Prashant; Shawky, Ahmed M.; Ahmad, Saara; Abidi, Syed HaniThe current study utilizes in silico molecular docking/molecular dynamics to evaluate the binding affinity of apigenin and safranal with 5HT1AR/5HT2AR, followed by assessment of in vivo effects of these compounds on depressive and anxious behavior. Methods: The docking between apigenin and safranal and the 5HT1A and 5HT2A receptors was performed utilizing AutoDock Vina software, while MD and protein-lipid molecular dynamics simulations were executed by AMBER16 software. For in vivo analysis, healthy control (HC), disease control (DC), fluoxetine-, and apigenin-safranal-treated rats were tested for changes in depression and anxiety using the forced swim test (FST) and the elevated plus-maze test (EPMT), respectively. Results: The binding affinity estimations identified the superior interacting capacity of apigenin over safranal for 5HT1A/5HT2A receptors over 200 ns MD simulations. Both compounds exhibit oral bioavailability and absorbance. In the rodent model, there was a significant increase in the overall mobility time in the FST, while in the EPMT, there was a decrease in latency and an increase in the number of entries for the treated and HC rats compared with the DC rats, suggesting a reduction in depressive/anxiety symptoms after treatment. Conclusions: Our analyses suggest apigenin and safranal as prospective medication options to treat depression and anxiety.Item Open Access ANALYSIS OF THE ANTIMICROBIAL AND ANTI-BIOFILM ACTIVITY OF NATURAL COMPOUNDS AND THEIR ANALOGUES AGAINST STAPHYLOCOCCUS AUREUS ISOLATES(Molecules, 2022) Mastoor, Sobia; Nazim, Fizza; Rizwan-ul-Hasan, Syed; Ahmed, Khalid; Khan, Shabnam; Nawazish Ali, Syed; Abidi, Syed HaniStaphylococcus aureus (S. aureus) is one of the most frequent causes of biofilm-associated infections. With the emergence of antibiotic-resistant, especially methicillinresistant S. aureus (MRSA), there is an urgent need to discover novel inhibitory compounds against this clinically important pathogen. In this study, we evaluated the antimicrobial and anti-biofilm activity of 11 compounds, including phenyl propenes and phenolic aldehydes, eugenol, ferulic acid, sinapic acid, salicylaldehyde, vanillin, cinnamoyl acid, and aldehydes, against drug-resistant S. aureus isolates. (2) Methods: Thirty-two clinical S. aureus isolates were obtained from Alkhidmat Diagnostic Center and Blood Bank, Karachi, Pakistan, and screened for biofilm-forming potential, and susceptibility/resistance against ciprofloxacin, chloramphenicol, ampicillin, amikacin, cephalothin, clindamycin, streptomycin, and gentamicin using the Kirby-Bauer disk diffusion method. Subsequently, 5 representative clinical isolates were selected and used to test the antimicrobial and anti-biofilm potential of 11 compounds using both qualitative and quantitative assays, followed by qPCR analysis to examine the differences in the expression levels of biofilm-forming genes (ica-A, fnb-B, clf-A and cna) in treated (with natural compounds and their derivatives) and untreated isolates. (3) Results: All isolates were found to be multi-drug resistant and dominant biofilm formers. The individual Minimum Inhibitory Concentration (MIC) of natural compounds and their analogues ranged from 0.75–160 mg/mL. Furthermore, the compounds, Salicylaldehyde (SALI), Vanillin (VAN), -methyl-trans-cinnamaldehyde (A-MT), and trans-4-nitrocinnamic acid (T4N) exhibited significant (15–92%) biofilm inhibition/reduction percentage capacity at the concentration of 1–10 mg/mL. Gene expression analysis showed that salicylaldehyde, -methyl-trans-cinnamaldehyde, and -bromotrans- cinnamaldehyde resulted in a significant (p < 0.05) downregulation of the expression of ica-A, clf -A, and fnb-A genes compared to the untreated resistant isolate. (4) Conclusions: The natural compounds and their analogues used in this study exhibited significant antimicrobial and anti-biofilm activity against S. aureus. Biofilms persist as the main concern in clinical settings. These compounds may serve as potential candidate drug molecules against biofilm forming S. aureus.Item Open Access NURSES’ PERCEPTION OF SAFETY CULTURE IN MEDICAL SURGICAL UNITS IN HOSPITALS IN SAUDI ARABIA(Medicina, 2022) Alrasheadi, Bader A.; Alamri, Majed S.; Aljohani, Khalid A.; AL-Dossary, Reem; Albaqawi, Hamdan; Alharbi, Jalal; Al Hosis, Khaled; Aljohani, Mohammed S.; Almadani, Noura; Falatah, Rawaih; Alotaibi, Jazi S.; Almazan, Joseph U.Introduction: Patient safety captures the essence of the primary principle of medical ethics, primum non nocere, first do no harm; this is an important concern in the health care system. Nurses are indispensable members of this system and are the largest group of health care providers involved in the direct delivery of patient care. As an integral part of the health care system, it is important to know nurses’ opinions on patient safety culture. Objectives: First, to evaluate and measure the existing safety culture and safety of patients in medicalsurgical wards (MSW) in hospitals located in the Qassim region, in the Kingdom of Saudi Arabia. Second, to survey the opinion of registered nurses and supervisors/managers about safety culture and issues concerned with safety in hospitals in the region. Materials and Methods: A validated cross-sectional survey, namely the Hospital Survey on Patient Safety Culture (HSOPSC), was used. This survey queried 300 nurses in different MSWs in four hospitals in the Qassim Region. Results: Overall, a positive culture of safety exists in MSWs, with 69% of RNs rating their wards as having great/excellent safety culture. Notably, some participants felt it was problematic that blame was assigned to nurses for reported errors. While 55.9% of participants noted that all errors or narrowly avoided errors had been reported, less than half actually reported errors in the last year. Conclusion: The perceived safety culture was largely positive; however, the results also indicated that a culture of safety comes with some risk and blame.Item Open Access ANTI-INFLAMMATORY, ANTIOXIDANT, AND ANTI-ATHEROSCLEROTIC EFFECTS OF NATURAL SUPPLEMENTS ON PATIENTS WITH FMF-RELATED AA AMYLOIDOSIS: A NON-RANDOMIZED 24-WEEK OPEN-LABEL INTERVENTIONAL STUDY(life, 2022) Romano, Micol; Garcia-Bournissen, Facundo; Piskin, David; Rodoplu, Ulkumen; Piskin, Lizzy; Elzagallaai, Abdelbaset A.; Tuncer, Tunc; Sezer, Siren; Ucuncuoglu, Didar; Honca, Tevfik; Poddighe, Dimitri; Yavuz, Izzet; Stenvinkel, Peter; Yilmaz, Mahmut Ilker; Demirkaya, ErkanWe aimed to evaluate the effect of a combination of natural products on parameters related to inflammation, endothelial dysfunction, and oxidative stress in a cohort of familial Mediterranean fever (FMF) patients with Serum Amyloid A amyloidosis, in a non-randomized, 24-week open-label interventional study. Morinda citrifolia (anti-atherosclerotic-AAL), omega-3 (anti-inflammatory-AIC), and extract with Alaskan blueberry (antioxidant-AOL) were given to patients with FMF-related biopsy-proven AA amyloidosis. Patients were >18 years and had proteinuria (>3500 mg/day) but a normal estimated glomerular filtration rate (eGFR). Arterial flow-mediated dilatation (FMD), carotid intima media thickness (CIMT), and serum biomarkers asymmetric dimethylarginine (ADMA), high sensitivity C-reactive protein (hs-CRP), pentraxin (PTX3), malondialdehyde (MDA), Cu/Znsuperoxide dismutase (Cu/Zn-SOD), and glutathione peroxidase (GSH-Px) were studied at baseline and after 24 weeks of treatment. A total of 67 FMF-related amyloidosis patients (52 male (77.6%); median age 36 years (range 21–66)) were enrolled. At the end of a 24-week treatment period with AAL, AIC, and AOL combination therapy, ADMA, MDA, PTX3, hsCRP, cholesterol, and proteinuria were significantly decreased compared to baseline, while CuZn-SOD, GSH-Px, and FMD levels were significantly increased. Changes in inflammatory markers PTX3, and hsCRP were negatively correlated with FMD change, and positively correlated with decreases in proteinuria, ADMA, MDA, cholesterol, and CIMT. Treatment with AAL, AIC and AOL combination for 24 weeks were significantly associated with reduction in inflammatory markers, improved endothelial functions, and oxidative state. Efficient control of these three mechanisms can have long term cardiovascular and renal benefits for patients with AA amyloidosis.Item Open Access ASSESSMENT OF SURROGATE MARKERS FOR CARDIOVASCULAR DISEASE IN FAMILIAL MEDITERRANEAN FEVER-RELATED AMYLOIDOSIS PATIENTS HOMOZYGOUS FOR M694V MUTATION IN MEFV GENE(Life, 2022) Sahin, Sezgin; Romano, Micol; Guzel, Ferhat; Piskin, David; Poddighe, Dimitri; Sezer, Siren; Kasapcopur, Ozgur; Appleton, C. Thomas; Yilmaz, Ilker; Demirkaya, ErkanCardiovascular disease (CVD) remains underestimated in familial Mediterranean feverassociated AA amyloidosis (FMF-AA).We aimed to compare early markers of endothelial dysfunction and atherosclerosis in FMF-AA with a homozygous M694V mutation (Group 1 = 76 patients) in the Mediterranean fever (MEFV) gene and in patients with other genotypes (Group 2 = 93 patients). Measures of increased risk for future CVD events and endothelial dysfunction, including flowmediated dilatation (FMD), pentraxin-3 (PTX3), and carotid intima-media thickness (cIMT), and fibroblast growth factor 23 (FGF23) as a marker of atherosclerotic vascular disease were compared between groups. The frequency of clinical FMF manifestations did not differ between the two groups apart from arthritis (76.3% in Group 1 and 59.1% in Group 2, p < 0.05). FMD was significantly lower in Group 1 when compared with Group 2 (MD [95% CI]: 0.6 [(0.89)–(0.31)]). cIMT, FGF23, and PTX3 levels were higher in Group 1 (cIMT MD [95% CI]: 0.12 [0.08–0.16]; FGF23 MD [95% CI]: 12.8 [5.9–19.6]; PTX3 MD [95% CI]: 13.3 [8.9–17.5]). In patients with FMF-AA, M694V homozygosity is associated with lower FMD values and higher cIMT, FGF23, and PTX3 levels, suggesting increased CVD risk profiles. These data suggest that a genotype–phenotype association exists in terms of endothelial dysfunction and atherosclerosis in patients with FMF-AA.Item Open Access PREDICTIVE VALUE OF BASAL SERUM PROGESTERONE FOR SUCCESSFUL IVF IN ENDOMETRIOSIS PATIENTS: THE NEED FOR A PERSONALIZED APPROACH(Journal of Personalized Medicine, 2022) Bila, Jovan; Dotlic, Jelena; Spremovic Radjenovic, Svetlana; Vidakovic, Snezana; Tulic, Lidija; Micic, Jelena; Stojnic, Jelena; Babovic, Ivana; Dmitrovic, Aleksandar; Chiantera, Vito; Laganà, Antonio Simone; Terzic, MilanThe data regarding the role of progesterone (P4) in reproductive events of endometriosis patients are limited. This prospective study aimed to examine the predictive value of basal P4 serum levels for successful in vitro fertilization (IVF) in patients with primary infertility and endometriosis. The study included 73 patients divided according to endometriosis treatment (surgery vs. control—no treatment). The general data, basal hormonal status, and pregnancy rates were determined for every patient. Clinical pregnancy was achieved in 40.3% of patients, and more often in patients treated for endometriosis before IVF. The regression analysis showed that higher basal P4 serum levels were associated with achieving pregnancy through IVF. When regression was adjusted for the patient and IVF characteristics, higher basal P4 serum levels were associated with pregnancy achievement in both groups of women, along with the basal serum levels of FSH, LH, and AMH; EFI score; and stimulation protocol. The ROC analysis showed that the basal P4 serum level for successful IVF should be 0.7ng/mL. The basal P4 serum level cut-off for IVF success in endometriosis patients was determined for the first time. Constructed models for IVF success prediction emphasize the importance of determining the basal P4 serum levels for the personalized treatment of endometriosisrelated infertility.Item Open Access HISTORY OF ENDOMETRIOSIS IS INDEPENDENTLY ASSOCIATED WITH AN INCREASED RISK OF OVARIAN CANCER(Journal of Personalized Medicine, 2022) Sarría-Santamera, Antonio; Khamitova, Zaukiya; Gusmanov, Arnur; Terzic, Milan; Polo-Santos, Mar; Ortega, Miguel A.; Asúnsolo, AngelEndometriosis is a complex gynecologic disorder that has been associated with a higher risk of ovarian cancer. The purpose of this work is to determine to what extent a history of endometriosis is a risk factor for ovarian cancer in a Spanish population. Methods: A retrospective case–control study was conducted using de-identified data from the Spanish National Health System’s “Primary Care Clinical Database” and “Hospital Minimum Basic Data Set” for the period 2013–2017. Multiple logistics regression analysis was conducted to determine associations between ovarian cancer and endometriosis controlled by sociodemographic characteristics and comorbidities. Results: Data from 608,980 women were analyzed, with 4505 presenting ovarian cancer. Endometriosis patients were shown to have a 2.66-fold increased risk of ovarian cancer when compared to those who did not have endometriosis by controlling age and other relevant comorbidities. Conclusions: This case–control study based on clinical administrative data has found that a history of endometriosis is independently associated with an increased risk of ovarian cancer. More research is needed to determine if a history of endometriosis affects survival results in ovarian cancer patients.Item Open Access RECAPPING THE FEATURES OF SARS-COV-2 AND ITS MAIN VARIANTS: STATUS AND FUTURE PATHS(Journal of Personalized Medicine, 2022) Ortega, Miguel A.; García-Montero, Cielo; Fraile-Martinez, Oscar; Colet, Paolo; Baizhaxynova, Ardak; Mukhtarova, Kymbat; Alvarez-Mon, Melchor; Kanatova, Kaznagul; Asúnsolo, Angel; Sarría-Santamera, AntonioOver the two years that we have been experiencing the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2 ) pandemic, our challenges have been the race to develop vaccines and the difficulties in fighting against new variants due to the rapid ability of the virus to evolve. In this sense, different organizations have identified and classified the different variants that have been emerging, distinguishing between variants of concern (VOC), variants of interest (VOI), or variants under monitoring (VUM). The following review aims to describe the latest updates focusing on VOC and already de-escalated variants, as well as to describe the impact these have had on the global situation. Understanding the intrinsic properties of SARS-CoV-2 and its interaction with the immune system and vaccination is essential to make out the underlying mechanisms that have led to the appearance of these variants, helping to determine the next steps for better public management of this pandemic.Item Open Access RISK FACTORS FOR POSTOPERATIVE OSTEOMYELITIS AMONG PATIENTS AFTER BONE FRACTURE: A MATCHED CASE–CONTROL STUDY(Journal of Clinical Medicine, 2022) Slyamova, Gulnur; Gusmanov, Arnur; Batpenov, Arman; Kaliev, Nurlan; Viderman, DmitriyThe healthcare burden of osteomyelitis is increasing. Postoperative and posttraumatic osteomyelitis account for 80% of all cases of osteomyelitis. The aim of this study was to find risk factors for postoperative osteomyelitis in Kazakhstan. We included 245 patients admitted to the National Scientific Center of Traumatology and Orthopedics from 2018 to 2020. Cases were matched with controls in a 1:4 ratio. Exact matching was performed by gender, ICD-10, and ICD-9 codes. The main variables included socio-demographics, diagnosis at admission, characteristics of fractures, comorbidities, complications, hospitalization milestones, and osteomyelitis characteristics. Descriptive analyses, along with bivariate analysis and multivariate conditional logistic regression, were performed. Open fracture (adjOR = 6.25; 95%CI 1.64–23.79), the presence of complications of initial fracture (adjOR = 3.46, 95%CI 1.13–10.56), comminuted fracture form (adjOR = 1.87; 95%CI 0.73–4.75), a positive history of diabetes or blood glucose >7 g/L (adjOR = 4.25; 95%CI 1.26–14.3), incision or wound length of more than 10 cm (adjOR = 6.53; 95%CI 1.1–38.6), additional implanted medical item (adjOR = 1.23; 95% CI 1.1–1.47), and unemployment or being retired (adjOR = 4.21; 95%CI 1.74–10.18) were found to be significant predictors of postoperative osteomyelitis. Almost all our findings are concordant with previous studies, except for the type of fracture. Different authors report conflicting results on the latter potential risk factor. Therefore, prospective studies on this issue are required.