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Item 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.Item Open Access CELIAC DISEASE IN JUVENILE IDIOPATHIC ARTHRITIS AND OTHER PEDIATRIC RHEUMATIC DISORDERS(Journal of Clinical Medicine, 2022) Poddighe, Dimitri; Romano, Micol; Dossybayeva, Kuanysh; Abdukhakimova, Diyora; Galiyeva, Dinara; Demirkaya, ErkanCeliac Disease (CD) is an immune-mediated and gluten-related disorder whose prevalence is higher in children affected with other autoimmune disorders, including diabetes mellitus type 1, autoimmune thyroiditis, and others. As regards Juvenile Idiopathic Arthritis (JIA) and other pediatric rheumatic disorders, there is no clear recommendation for CD serological screening. In this review, we analyze all the available clinical studies investigating CD among children with JIA (and other rheumatic diseases), in order to provide objective data to better understand the necessity of CD serological screening during the follow-up. Based on the present literature review and analysis, >2.5% patients with JIA were diagnosed with CD; however, the CD prevalence in JIA patients may be even higher (>3–3.5%) due to several study limitations that could have underestimated CD diagnosis to a variable extent. Therefore, serological screening for CD in children affected with JIA could be recommended due to the increased CD prevalence in these patients (compared to the general pediatric population), and because these JIA patients diagnosed with CD were mostly asymptomatic. However, further research is needed to establish a cost-effective approach in terms of CD screening frequency and modalities during the follow-up for JIA patients. Conversely, at the moment, there is no evidence supporting a periodical CD screening in children affected with other rheumatic diseases (including pediatric systemic lupus erythematosus, juvenile dermatomyositis, and systemic sclerosis).Item Open Access WOMEN’S HEALTH AND GYNECOLOGY: OLD CHALLENGES AND NEW INSIGHTS(International Journal of Environmental Research and Public Health, 2022) Sarría-Santamera, Antonio; Laganà, Antonio Simone; Terzic, MilanThe complexity of women’s health goes far beyond medical and surgical knowledge and the achievements of the clinical specialty of Obstetrics and Gynecology, spanning not just the research dimensions of molecular biology, genetics, epidemiology, or health services but also being influenced by gender, social, and psychological relevant factors. Those involved in and who are responsible for the clinical or health policy management of women’s health services should reflect on the findings to improve women’s quality of life and healthcare.Item Open Access THE PREVALENCE, INDICATIONS, OUTCOMES OF THE MOST COMMON MAJOR GYNECOLOGICAL SURGERIES IN KAZAKHSTAN AND RECOMMENDATIONS FOR POTENTIAL IMPROVEMENTS INTO PUBLIC HEALTH AND CLINICAL PRACTICE: ANALYSIS OF THE NATIONAL ELECTRONIC HEALTHCARE SYSTEM (2014–2019)(International Journal of Environmental Research and Public Health, 2022) Sakko, Yesbolat; Aimagambetova, Gulzhanat; Terzic, Milan; Ukybassova, Talshyn; Bapayeva, Gauri; Gusmanov, Arnur; Zhakhina, Gulnur; Zhantuyakova, Almira; Gaipov, AbduzhapparObjectives: Major gynecological surgeries are indicated for the treatment of female genital pathologies. It is key to examine trends in gynecologic surgical procedures and updated recommendations by international gynecological societies to find opportunities for improvement of local guidelines. To date, a very limited number of reports have been published on the epidemiology of gynecological surgeries in Kazakhstan. Moreover, some local guidelines for gynecological conditions do not comply with the international recommendations. Thus, this study aims to investigate the prevalence, indications, and outcomes of the most common major gynecological surgeries by analyzing large-scale Kazakhstani healthcare data, and identifying possible opportunities for improvement of the local public health and clinical practice. Methods: A descriptive, population-based study among women who underwent a gynecological surgery in healthcare settings across the Republic of Kazakhstan during the period of 2014–2019 was performed. Data were collected from the Unified Nationwide Electronic Health System (UNEHS). Results: In total, 80,401 surgery cases were identified and analyzed in the UNEHS database for a period of 6 years (2014–2019). The median age of the participants was 40 years old, with 61.1% in reproductive age. The most prevalent intervention was a unilateral salpingectomy—29.4%, with 72.6% patients aged between 18–34 years. The proportion of different types of hysterectomies was 49.4%. In 20% of cases, subtotal abdominal hysterectomy was performed due to uterine leiomyoma. The proportion of laparoscopic procedures in Kazakhstani gynecological practice is as low—11.59%. Conclusions: The Kazakhstani public health and gynecological care sector should reinforce implementation of contemporary treatment methods and up-to-date policies and guidelines. The overall trends in surgical procedures performed for gynecological pathologies, including uterine leiomyoma and ectopic pregnancy treatment, should be changed in favor of the minimally invasive methods in order to adopt a fertility-sparing approach.Item Open Access QUALITY-OF-LIFE ASSESSMENT OFWOMEN UNDERGOING IN VITRO FERTILIZATION IN KAZAKHSTAN(International Journal of Environmental Research and Public Health, 2022) Suleimenova, Meruyert; Lokshin, Vyacheslav; Glushkova, Natalya; Karibayeva, Sholpan; Terzic, MilanInfertility is a problem that affects millions of couples worldwide and has a significant impact on their quality of life. The recently introduced “Fertility Quality of Life Questionnaire (FertiQoL)” quickly became a gold standard for evaluation of the quality of life of patients suffering from infertility. The aim of this study was to determine the quality of life of Kazakhstani women coping with infertility problems by FertiQoL and assess the validity of the questionnaire. This cross-sectional study involved women of reproductive age undergoing an in vitro fertilization (IVF) cycle at a large IVF center in Kazakhstan in the period from 1 September 2020 to 31 September 2021. A total of 453 women out of 500 agreed to participate in the study, and the response rate was 90.6%. The overall Core FertiQoL was 56.95 14.05, and the Treatment FertiQoL was 66.18 11.13 points. Respondents with secondary infertility had statistically significantly higher Emotional (p < 0.001), Mind–body (p = 0.03), Social (p < 0.001), Environment (p = 0.02), and Treatment (p < 0.001) domains of FertiQoL than women with primary infertility. Respondents with a low income had the lowest levels of Total FertiQoL (56.72 11.65). The longer duration of infertility of women undergoing IVF treatment presented the worse scale of Treatment and Total FertiQoL. Cronbach’s alpha revealed good internal reliability for all FertiQoL subscales on the Kazakhstan women’s questionnaire and averaged 0.8, which is an indicator of a high degree of reliability. The Total FertiQoL of Kazakhstan women undergoing IVF treatment was 59.6 11.5, which is considerably lower than European countries. We identified statistically significant differences across medical and demographic groups. As this questionnaire had validity in Kazakhstan survey it possibly be used for both medical counseling and future investigation in our country.Item Open Access URINARY PROTEIN PROFILING FOR POTENTIAL BIOMARKERS OF CHRONIC KIDNEY DISEASE: A PILOT STUDY(Diagnostics, 2022) Gaipov, Abduzhappar; Makhammajanov, Zhalaliddin; Dauyey, Zhanna; Markhametova, Zhannur; Mussina, Kamilla; Nogaibayeva, Assem; Kozina, Larissa; Auganova, Dana; Tarlykov, Pavel; Bukasov, Rostislav; Utegulov, Zhandos; Turebekov, Duman; Soler, Maria Jose; Ortiz, Alberto; Kanbay, MehmetProteinuria is a risk factor for chronic kidney disease (CKD) progression and associated complications. However, there is insufficient information on individual protein components in urine and the severity of CKD. We aimed to investigate urinary proteomics and its association with proteinuria and kidney function in early-stage CKD and in healthy individuals. A 24 h urine sample of 42 individuals (21-CKD and 21-healthy individuals) was used for mass spectrometry-based proteomics analysis. An exponentially modified protein abundance index (emPAI) was calculated for each protein. Data were analyzed by Mascot software using the SwissProt database and bioinformatics tools. Overall, 298 unique proteins were identified in the cohort; of them, 250 proteins belong to the control group with median (IQR) emPAI 39.1 (19–53) and 142 proteins belong to the CKD group with median (IQR) emPAI 67.8 (49–117). The level of 24 h proteinuria positively correlated with emPAI (r = 0.390, p = 0.011). The emPAI of some urinary proteomics had close positive (ALBU, ZA2G, IGKC) and negative (OSTP, CD59, UROM, KNG1, RNAS1, CD44, AMBP) correlations (r < 0.419, p < 0.001) with 24 h proteinuria levels. Additionally, a few proteins (VTDB, AACT, A1AG2, VTNC, and CD44) significantly correlated with kidney function. In this proteomics study, several urinary proteins correlated with proteinuria and kidney function. Pathway analysis identified subpathways potentially related to early proteinuric CKD, allowing the design of prospective studies that explore their response to therapy and their relationship to long-term outcomes.Item Open Access ANALYSIS OF PERIPHERAL BLOOD BASOPHILS IN PEDIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS(Diagnostics, 2022) Dossybayeva, Kuanysh; Bexeitov, Yergali; Mukusheva, Zaure; Almukhamedova, Zhaina; Assylbekova, Maykesh; Abdukhakimova, Diyora; Rakhimzhanova, Marzhan; Poddighe, DimitriBasophils are the least abundant circulating leukocytes, and their immunological role has not yet been completely elucidated. There is evidence supporting their immunomodulatory role in several pathological settings; recently, studies in both experimental models and humans suggested that basophil homeostasis may be altered in systemic lupus erythematosus (SLE). Here, we first assessed circulating basophils in children affected with pediatric SLE (pSLE). In this cross-sectional study, circulating basophils were enumerated by fluorescence-based flow cytometry analysis in children affected with pSLE, in addition to children suffering from juvenile idiopathic arthritis (JIA) or non-inflammatory/non-rheumatic conditions. This study included 52 pediatric patients distributed in these three groups. We observed a statistically significant reduction of peripherally circulating basophils in children with pSLE compared to the other two groups of patients. This preliminary study is consistent with the available studies in adult patients with SLE showing a reduced number of circulating basophils. However, further research is needed to draw final conclusions on basophils’ homeostasis in pSLE, in addition to their correlation with the disease activity and concomitant therapies.Item Open Access PATIENTS RECEIVING HEMODIALYSIS DO NOT LOSE SARS-COV-2 ANTIBODIES MORE RAPIDLY THAN NON-RENAL CONTROLS: A PROSPECTIVE COHORT STUDY(Renal Failure, 2022) Parshina, Ekaterina; Zulkarnaev, Alexey; Tolkach, Alexey; Ivanov, Andrey; Kislyy, Pavel; Gaipov, AbduzhapparBackground Patients with end-stage kidney disease receiving maintenance hemodialysis (HD) are at increased risk for mortality after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared with the general population. However, it is currently unknown whether the long-term SARS-CoV-2 humoral and cellular immune responses in patients receiving HD are comparable to individuals with normal kidney function. Method The prospective cohort study included 24 patients treated with maintenance HD and 27 non-renal controls with confirmed history of coronavirus disease (COVID-19). In all participants the levels of specific IgG were quantified at three timepoints: 10, 18, and 26 weeks from disease onset. In a subgroup of patients, specific T-cell responses were evaluated. Results The seropositivity rate declined in controls over time and was 85% and 70.4% at weeks 18 and 26, respectively. All HD patients remained seropositive over the study period. Seropositivity rate at week 26 was greater among patients receiving HD: RR = 1.4 [95%CI: 1.17–1.94] (reciprocal of RR = 0.7 [95% CI: 0.52–0.86]), p = 0.0064. In both groups, IgG levels decreased from week 10 to week 26, but antibodies vanished more rapidly in controls than in HD group (ANOVA p = 0.0012). The magnitude of T-cell response was significantly lower in controls than in HD patients at weeks 10 (p = 0.019) and 26 (p = 0.0098) after COVID-19 diagnosis, but not at week 18. Conclusion Compared with non-renal adults, patients receiving HD maintain significant long-term humoral and cellular immune responses following natural COVID-19.Item Open Access ANTIRETROVIRAL THERAPY RESISTANCE MUTATIONS AMONG HIV INFECTED PEOPLE IN KAZAKHSTAN(Scientific Reports, 2022) Mukhatayeva, Ainur; Mustafa, Aidana; Dzissyuk, Natalya; Issanov, Alpamys; Mukhatayev, Zhussipbek; Bayserkin, Bauyrzhan; Vermund, Sten H.; Ali, SyedIn Kazakhstan, the number of people living with HIV (PLHIV) has increased steadily by 39% since 2010. Development of antiretroviral therapy (ART) resistance mutations (ARTRM) is a major hurdle in achieving effective treatment and prevention against HIV. Using HIV pol sequences from 602 PLHIV from Kazakhstan, we analyzed ARTRMs for their association with factors that may promote development of ARTRMs. 56% PLHIV were infected with HIV subtype A6 and 42% with CRF02_AG. The ARTRM Q174K was associated with increased viral load and decreased CD4+ cell count, while infection with CRF02_AG was associated with a lower likelihood of Q174K. Interestingly, CRF02_AG was positively associated with the ARTRM L10V that, in turn, was observed frequently with darunavir administration. Infection with CRF02_AG was positively associated with the ARTRM S162A that, in turn, was frequently observed with the administration of nevirapine, also associated with lower CD4 counts. Zidovudine or Nevirapine receipt was associated with the development of the ARTRM E138A, that, in turn, was associated with lower CD4 counts. Determination of a patient’s HIV variant can help guide ART choice in Kazakhstan. For example, PLHIV infected with CRF02_AG will benefit less from darunavir and nevirapine, and emtricitabine should replace zidovudine.