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1.
Int Nurs Rev ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38650476

ABSTRACT

AIMS: This study aimed to determine the peak hours of sleepiness and the factors affecting the sleepiness levels of nurses. BACKGROUND: Sleepiness is commonly seen in individuals working night shifts. However, in case of nurses, this sleepiness can be a major threat to patient and staff safety. METHOD: This was a prospective cross-sectional study. Data were collected between July and September 2023, and a stratified sampling method was used according to the departments in which the nurses worked. Data were collected using the Personal Information Form and Visual Analog Scale. Nurses reported their sleepiness levels at the beginning of each hour between midnight and 8:00 am. EQUATOR CHECKLIST: The study adhered to the STROBE checklist for reporting. RESULTS: The mean sleepiness levels of emergency department nurses, intensive care nurses, internal or surgical clinic nurses, and all nurses were 59.75 ± 15.50, 43.53 ± 20.49, 44.67 ± 18.88, and 49.15 ± 19.67, respectively. The highest sleepiness level of the nurses was at 05:00 am. A significant correlation was found between the variables of age, gender, marital status, sleep quality, number of patients cared, working style and satisfaction with working in the department, and sleepiness level (P < 0.05). CONCLUSION: Nurses working night shifts experience sleepiness (highest at 5:00 am). In addition, the sleepiness levels of nurses are affected by some personal and clinical factors. IMPLICATIONS FOR NURSING AND NURSING POLICY: Based on the results, there is a need for necessary policies regarding nurses' working hours and working conditions. To protect patient and employee safety, necessary strategies should be devised regarding the hours when nurses experience the highest sleepiness and the factors affecting sleepiness levels.

2.
Pharmaceuticals (Basel) ; 16(7)2023 Jul 06.
Article in English | MEDLINE | ID: mdl-37513880

ABSTRACT

Histone deacetylases (HDAC) represent promising epigenetic targets for several diseases including different cancer types. The HDAC inhibitors approved to date are pan-HDAC inhibitors and most show a poor selectivity profile, side effects, and in particular hydroxamic-acid-based inhibitors lack good pharmacokinetic profiles. Therefore, the development of isoform-selective non-hydroxamic acid HDAC inhibitors is a highly regarded field in medicinal chemistry. In this study, we analyzed different ligand-based and structure-based drug design techniques to predict the binding mode and inhibitory activity of recently developed alkylhydrazide HDAC inhibitors. Alkylhydrazides have recently attracted more attention as they have shown promising effects in various cancer cell lines. In this work, pharmacophore models and atom-based quantitative structure-activity relationship (QSAR) models were generated and evaluated. The binding mode of the studied compounds was determined using molecular docking as well as molecular dynamics simulations and compared with known crystal structures. Calculated free energies of binding were also considered to generate QSAR models. The created models show a good explanation of in vitro data and were used to develop novel HDAC3 inhibitors.

3.
Vasc Health Risk Manag ; 19: 127-132, 2023.
Article in English | MEDLINE | ID: mdl-36923496

ABSTRACT

Many factors are considered to affect vascular physiology. It is known that one of the reasons for many diseases is a pathology at the microvascular level. Therefore, the relationship between endothelial dysfunction and many diseases is currently being investigated. The clinical evaluations of arterial stiffness have made it possible to perform necessary risk assessment regarding cardiovascular diseases. In this way, protective measures can be taken against microvascular pathologies in many organs. In this paper, we present a review of studies investigating the relationship between urological conditions and the cardio-ankle vascular index (CAVI), a marker of arterial stiffness. As with erectile dysfunction, some studies have shown that conditions such as lower urinary tract symptoms, overactive bladder, and chronic kidney disease are also associated with an elevated CAVI. The association of erectile dysfunction and chronic kidney disease with vascular pathologies has been clearly demonstrated. In addition, lower urinary tract symptoms may be the first sign of silent vascular dysfunction. Assessing arterial stiffness with CAVI can help prevent future cardiovascular events in these patients.


Subject(s)
Cardiovascular Diseases , Erectile Dysfunction , Urologic Diseases , Vascular Stiffness , Male , Humans , Ankle/blood supply , Cardio Ankle Vascular Index , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/prevention & control , Ankle Brachial Index
4.
Bioorg Chem ; 131: 106331, 2023 02.
Article in English | MEDLINE | ID: mdl-36587505

ABSTRACT

In order to develop novel inhibitors of the bacterial deacetylase LpxC bearing a substituent to target the UDP binding site of the enzyme, a series of aldotetronic acid-based hydroxamic acids was accessed in chiral pool syntheses starting from 4,6-O-benzylidene-d-glucose and l-arabinitol. The synthesized hydroxamic acids were tested for LpxC inhibitory activity in vitro, revealing benzyl ether 17a ((2S,3S)-4-(benzyloxy)-N,3-dihydroxy-2-[(4-{[4-(morpholinomethyl)phenyl]ethynyl}benzyl)oxy]butanamide) as the most potent LpxC inhibitor. This compound was additionally tested for antibacterial activity against a panel of clinically relevant Gram-negative bacteria, bacterial uptake, and susceptibility to efflux pumps. Molecular docking studies were performed to rationalize the observed structure-activity relationships.


Subject(s)
Amidohydrolases , Anti-Bacterial Agents , Enzyme Inhibitors , Escherichia coli , Amidohydrolases/antagonists & inhibitors , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacteria/metabolism , Binding Sites , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Hydroxamic Acids/pharmacology , Hydroxamic Acids/chemistry , Molecular Docking Simulation , Structure-Activity Relationship
5.
Aktuelle Urol ; 54(1): 30-36, 2023 02.
Article in English | MEDLINE | ID: mdl-36702134

ABSTRACT

OBJECTIVES: To compare the efficacy of in-vivo and in-vitro stone attenuation in the prediction of stone composition using non-contrast-enhanced abdominal computed tomography (NCCT). METHODS: This study included a total of 104 patients with renal stones who received percutaneous nephrolithotomy treatment for renal stones between December 2016 and December 2019 and underwent NCCT before the procedure. Preoperative (in-vivo) and postoperative (in-vitro) kidney stone attenuations were compared using the NCCT images of the patients. Renal stone fragments were analysed with the infrared spectrophotometer method. RESULTS: The mean age of the 104 patients was 49.5 (interquartile range: 37-61) years. According to the receiver operating characteristics analysis, the cut-off values for the prediction of uric acid stones were determined to be 556 HU for the in-vivo and 774 HU for the in-vitro attenuation measurement. Sensitivity and specificity were 100% and 96.6%, respectively, for the in-vivo and 90.9 and 91%, respectively, for the in-vitro images. The cut-off values for the prediction of calcium stones were determined to be 824 HU and 1065 HU for the in-vivo and in-vitro attenuation measurements, respectively. Sensitivity and specificity were 97.3 and 96% for the in-vivo and 96 and 96% for the in-vitro images. CONCLUSIONS: In-vivo stone attenuation measurement in NCCT was slightly superior to in-vitro measurement due to the reduction in the composition and size of the stone. Our findings show that NCCT in-vivo stone attenuation might differentiate uric acid and calcium stones from the other stone types.


Subject(s)
Calcium , Kidney Calculi , Humans , Adult , Middle Aged , Uric Acid , Tomography, X-Ray Computed/methods , Kidney Calculi/diagnostic imaging , Kidney Calculi/surgery , Sensitivity and Specificity
6.
Aktuelle Urol ; 54(1): 37-43, 2023 02.
Article in English | MEDLINE | ID: mdl-36473485

ABSTRACT

PURPOSE: To examine the parameters affecting the need for additional procedures in the primary ureteroscopy treatment in patients with ureteral stones above the iliac crest level. METHODS: Seventy-one patients were included in the study who were ≥ 18 years old and had undergone ureteroscopy (URS) for ureteral stones above the iliac crest level between 2018-2020 and had a non-contrast-enhanced abdominal computed tomography before the procedures were included in the study. Patients and stone characteristics were prospectively collected. The results were evaluated six weeks after URS. The absence of any residual fragment was thought to indicate stone-free status. The patients with failure were referred for the additional procedures. RESULTS: The median patient age was 51 years [interquartile range (IQR): 18-66]. The median transverse stone diameter was 9.5 mm (IQR: 7.1-11.4), and the median ureteral wall thickness (UWT) was 5.8 mm (IQR: 4.3-6.5). In the univariate analysis, UWT (p < 0.001), presence of multiple stones (p = 0.008), and stone length (p = 0.022) affected stone-free status. The multivariate analysis revealed UWT as the only independent factor affecting the need for additional procedures after URS (p = 0.028). In the receiver operating characteristic curve analysis, the best threshold value for UWT according to the outcomes was identified as 5.8 mm. CONCLUSION: Ureteral wall thickness was the only independent parameter determining the need for additional procedures and affecting the treatment outcomes after the URS procedure.


Subject(s)
Lithotripsy , Ureter , Ureteral Calculi , Humans , Middle Aged , Adolescent , Ureteroscopy/methods , Ilium , Lithotripsy/methods , Ureter/surgery , Ureteral Calculi/diagnostic imaging , Ureteral Calculi/surgery , Treatment Outcome , Retrospective Studies
7.
Int Urol Nephrol ; 55(3): 605-611, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36536101

ABSTRACT

PURPOSE: In this study, we aimed to compare the results of split-cuff nipple and modified Lich-Gregoir ureteroneocystostomy, which are the most commonly used techniques in stage ≥ 3 iatrogenic distal ureteral injuries. METHODS: The files of patients who were treated for iatrogenic distal ureteral injuries in our clinic between January 2013 and January 2019 were retrospectively reviewed. A total of 60 patients who underwent either intra-vesical split-cuff nipple ureteroneocystostomy (Group A) or extra-vesical modified Lich-Gregoir ureteroneocystostomy (Group B) operations were included in the study. The success of ureteroneocystostomy was defined as no additional surgery requirement, no progression of hydronephrosis on imaging, and normal contrast transition on imaging. RESULTS: Thirty-four patients underwent split-cuff nipple and 26 patients underwent modified Lich-Gregoir ureteroneocystostomy. The treatment was successful in 53 (88.3%) patients and failed in seven (11.7%). Complications occurred in 19 (31.7%) patients, of whom 14 (23.3%) had minor and five (8.3%) had major complications. The rate of postoperative complications was significantly higher in Group A than in Group B (p = 0.019). There was no significant difference between Group A and Group B in terms of the success ratio (p = 1), rate of major complications (p = 0.372), and postoperative hospitalization times (p = 0.254). CONCLUSION: In this study, a higher complication rate was found in patients with iatrogenic ureteral injuries who underwent ureteroneocystostomy with the split-cuff ureteral nipple technique compared to those who underwent this operation with the modified Lich-Gregoir technique. However, no significant difference was observed between these two techniques in terms of treatment success and major complications.


Subject(s)
Kidney Transplantation , Ureter , Humans , Retrospective Studies , Nipples , Tertiary Care Centers , Kidney Transplantation/methods , Ureter/surgery , Iatrogenic Disease
8.
Rev Assoc Med Bras (1992) ; 68(10): 1464-1469, 2022.
Article in English | MEDLINE | ID: mdl-36417654

ABSTRACT

OBJECTIVE: Acute appendicitis represents one of the most common causes of acute intra-abdominal emergencies worldwide. In this case-control study, we aimed to investigate associations of Rho-kinase gene expression and polymorphisms with acute appendicitis in a Turkish population. We also aimed to study the effects of gender on these parameters. METHODS: A total of 93 unrelated patients with acute appendicitis and 93 healthy controls in the Department of Emergency Medicine, Erciyes University, between June 2019 and June 2021 were included in this study. Genomic DNA was isolated from peripheral leukocytes, and the LightCycler 480 II real-time polymerase chain reaction was utilized to detect Rho-kinase1 gene rs35996865 and Rho-kinase2 gene rs2230774 (Thr431Asn) polymorphisms. Quantitative real-time polymerase chain reaction was applied to determine Rho-kinase1 and Rho-kinase2 gene expressions. RESULTS: There was a marked increase in Rho-kinase1, but not in Rho-kinase2, mRNA expression, and this increase was evident only in male patients (p=0.0008). No significant differences were found in allele and genotype frequencies for Rho-kinase1 gene rs35996865 and Rho-kinase2 gene rs2230774 polymorphisms between the patients with acute appendicitis and the control group. CONCLUSIONS: Our data imply that Rho-kinase1 (rs35996865) and Rho-kinase2 (rs2230774) gene variants are not risk factors for the development of acute appendicitis in the Turkish population. However, increased mRNA expression of the Rho-kinase1 gene in males indicated that Rho-kinase1 is involved in the pathogenesis of acute appendicitis in a gender-specific way.


Subject(s)
Appendicitis , rho-Associated Kinases , Adult , Humans , Male , rho-Associated Kinases/genetics , Appendicitis/genetics , Case-Control Studies , Genetic Predisposition to Disease , Acute Disease , Gene Expression , RNA, Messenger
9.
J Med Chem ; 65(24): 16313-16337, 2022 12 22.
Article in English | MEDLINE | ID: mdl-36449385

ABSTRACT

Histone deacetylases (HDACs) are epigenetic regulators and additionally control the activity of non-histone substrates. We recently demonstrated that inhibition of HDAC8 overexpressed in various of cancers reduces hepatocellular carcinoma tumorigenicity in a T cell-dependent manner. Here, we present alkylated hydrazide-based class I HDAC inhibitors in which the n-hexyl side chain attached to the hydrazide moiety shows HDAC8 selectivity in vitro. Analysis of the mode of inhibition of the most promising compound 7d against HDAC8 revealed a substrate-competitive binding mode. 7d marked induced acetylation of the HDAC8 substrates H3K27 and SMC3 but not tubulin in CD4+ T lymphocytes, and significantly upregulated gene expressions for memory and effector functions. Furthermore, intraperitoneal injection of 7d (10 mg/kg) in C57BL/6 mice increased interleukin-2 expression in CD4+ T cells and CD8+ T cell proportion with no apparent toxicity. This study expands a novel chemotype of HDAC8 inhibitors with T cell modulatory properties for future therapeutic applications.


Subject(s)
Histone Deacetylase Inhibitors , Repressor Proteins , Mice , Animals , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/chemistry , Mice, Inbred C57BL , Histone Deacetylases/metabolism , Hydrazines
10.
Rev. Assoc. Med. Bras. (1992, Impr.) ; 68(10): 1464-1469, Oct. 2022. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1406570

ABSTRACT

SUMMARY OBJECTIVE: Acute appendicitis represents one of the most common causes of acute intra-abdominal emergencies worldwide. In this case-control study, we aimed to investigate associations of Rho-kinase gene expression and polymorphisms with acute appendicitis in a Turkish population. We also aimed to study the effects of gender on these parameters. METHODS: A total of 93 unrelated patients with acute appendicitis and 93 healthy controls in the Department of Emergency Medicine, Erciyes University, between June 2019 and June 2021 were included in this study. Genomic DNA was isolated from peripheral leukocytes, and the LightCycler 480 II real-time polymerase chain reaction was utilized to detect Rho-kinase1 gene rs35996865 and Rho-kinase2 gene rs2230774 (Thr431Asn) polymorphisms. Quantitative real-time polymerase chain reaction was applied to determine Rho-kinase1 and Rho-kinase2 gene expressions. RESULTS: There was a marked increase in Rho-kinase1, but not in Rho-kinase2, mRNA expression, and this increase was evident only in male patients (p=0.0008). No significant differences were found in allele and genotype frequencies for Rho-kinase1 gene rs35996865 and Rho-kinase2 gene rs2230774 polymorphisms between the patients with acute appendicitis and the control group. CONCLUSIONS: Our data imply that Rho-kinase1 (rs35996865) and Rho-kinase2 (rs2230774) gene variants are not risk factors for the development of acute appendicitis in the Turkish population. However, increased mRNA expression of the Rho-kinase1 gene in males indicated that Rho-kinase1 is involved in the pathogenesis of acute appendicitis in a gender-specific way.

11.
Biochemistry ; 61(17): 1705-1722, 2022 09 06.
Article in English | MEDLINE | ID: mdl-35972884

ABSTRACT

Sirtuins are protein deacylases regulating metabolism and stress responses and implicated in aging-related diseases. Modulators of the human sirtuins 1-7 are sought as chemical tools and potential therapeutics, for example, for treatment of cancer. We were able to show that 3-aryl-mercapto-succinylated- and 3-benzyl-mercapto-succinylated peptide derivatives yield selective Sirt5 inhibitors with low nM Ki values. Here, we synthesized and characterized 3-aryl-mercapto-butyrylated peptide derivatives as effective and selective sirtuin 2 inhibitors with KD values in the low nanomolar range. According to kinetic measurements and microscale thermophoresis/surface plasmon resonance experiments, the respective inhibitors bind with the 3-aryl-mercapto moiety in the selectivity pocket of Sirtuin 2, inducing a rearrangement of the active site. In contrast, 3-aryl-mercapto-nonalyl or palmitoyl derivatives are characterized by a switch in the binding mode blocking both the hydrophobic channel by the fatty acyl chain and the nicotinamide pocket by the 3-aryl-mercapto moiety.


Subject(s)
Sirtuin 2 , Sirtuins , Catalytic Domain , Humans , Lysine/metabolism , Niacinamide , Peptides , Sirtuin 2/metabolism , Sirtuins/metabolism
12.
J Endourol ; 36(11): 1425-1430, 2022 11.
Article in English | MEDLINE | ID: mdl-35521656

ABSTRACT

Objectives: To compare the surgical outcomes of open and laparoscopic ureterolysis procedures in patients requiring surgical treatment for ureteral obstruction caused by retroperitoneal fibrosis (RPF). Materials: This study was designed retrospectively. The clinical records of patients who underwent ureterolysis between January 2005 and April 2019 because of ureteral obstruction caused by RPF were examined. According to the type of surgery, the patients were divided into two groups as Group 1 (open ureterolysis) and Group 2 (laparoscopic ureterolysis). Demographic features, preoperative-postoperative renal functions, duration of follow-up with ureteral stents, and perioperative-postoperative complications were examined. The requirement of ureteral stent placement during the follow-up period was accepted as unsuccessful ureterolysis. Results: Ureterolysis was performed in 13 patients and 23 renal units. Eleven of these patients were men and two were women. The median age of the patients was 54 (44-68) years. There were six patients and 12 renal units in Group 1 and seven patients and 11 renal units in Group 2. Postoperatively, a total of four patients (30%) had minor complications (Clavien-Dindo 1-2) and one patient had a major complication (Clavien-Dindo 3a). Ureterolysis was determined to be effective in 21 of the renal units (91%) [11/12 (92%) in Group 1 vs 10/11 (91%) in Group 2]. No statistically significant difference was found between the groups in terms of the success and complication rates (p = 1 and p = 0.529, respectively). Postoperative hospitalization length and recovery time to return to normal preoperative activities were significantly shorter in Group 2 than in Group 1 (p = 0.011 and p = 0.041, respectively). Conclusions: The success and complication rates were similar between the open and laparoscopic methods for ureterolysis. Laparoscopic approach was advantageous over open approach in terms of postoperative hospitalization length and recovery time to return to normal preoperative activities.


Subject(s)
Laparoscopy , Retroperitoneal Fibrosis , Ureteral Obstruction , Male , Humans , Female , Middle Aged , Aged , Retroperitoneal Fibrosis/complications , Retroperitoneal Fibrosis/surgery , Ureteral Obstruction/surgery , Ureteral Obstruction/complications , Retrospective Studies , Tertiary Care Centers , Laparoscopy/methods
13.
Molecules ; 27(8)2022 Apr 14.
Article in English | MEDLINE | ID: mdl-35458724

ABSTRACT

Class I histone deacetylases, HDAC1, HDAC2, and HDAC3, represent potential targets for cancer treatment. However, the development of isoform-selective drugs for these enzymes remains challenging due to their high sequence and structural similarity. In the current study, we applied a computational approach to predict the selectivity profile of developed inhibitors. Molecular docking followed by MD simulation and calculation of binding free energy was performed for a dataset of 2-aminobenzamides comprising 30 previously developed inhibitors. For each HDAC isoform, a significant correlation was found between the binding free energy values and in vitro inhibitory activities. The predictive accuracy and reliability of the best preforming models were assessed on an external test set of newly designed and synthesized inhibitors. The developed binding free-energy models are cost-effective methods and help to reduce the time required to prioritize compounds for further studies.


Subject(s)
Histone Deacetylase Inhibitors , Pyrazines , Histone Deacetylase 1 , Histone Deacetylase 2 , Histone Deacetylase Inhibitors/chemistry , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylases/metabolism , Molecular Docking Simulation , Protein Isoforms , Pyrazines/chemistry , Reproducibility of Results
14.
Andrology ; 10(5): 926-930, 2022 07.
Article in English | MEDLINE | ID: mdl-35466575

ABSTRACT

BACKGROUND: It has been reported that there is a relationship between erectile dysfunction and endothelial dysfunction. However, a practical and non-invasive method to clinically evaluate this relationship has not yet been determined. The cardio-ankle vascular index is a marker of arteriosclerosis that develops as a result of endothelial dysfunction. OBJECTIVE: To investigate the correlation between the cardio-ankle vascular index and the presence and severity of erectile dysfunction. MATERIALS/METHODS: This was a case-control study including 74 patients that presented to the urology department of our institution with erectile dysfunction (without cardiovascular risk factors) and 86 healthy individuals of similar age. The patients with erectile dysfunction and the control group were evaluated using the five-item version of the International Index of Erectile Function (IIEF-5). Cardio-ankle vascular index and ankle-brachial pressure index measurements were performed using the VaSera VS-1000 (Fukuda-Denshi Company, Ltd, Tokyo, Japan) device. RESULTS: The mean age was 59.8 ± 1.3 years for the erectile dysfunction group and 57.9 ± 1.1 years for the control group. The mean right (R)-cardio-ankle vascular index values of the erectile dysfunction and control groups were 9.20 ± 2.6 and 8.11 ± 1.8, respectively (p = 0.014), and their mean left (L)-cardio-ankle vascular index values were 9.08 ± 2.7 and 7.96 ± 1.2, respectively (p = 0.008). The mean International Index of Erectile Function score of the patients with erectile dysfunction was 10.1 ± 3.6. An inverse correlation was found between the R-cardio-ankle vascular index and L-cardio-ankle vascular index and the International Index of Erectile Function score (r = -0.411, p = 0.011, and r = -0.454, p < 0.001, respectively). DISCUSSION AND CONCLUSION: According to our findings, the cardio-ankle vascular index was higher in patients with erectile dysfunction than in healthy individuals.


Subject(s)
Erectile Dysfunction , Vascular Diseases , Ankle/blood supply , Ankle Brachial Index , Case-Control Studies , Erectile Dysfunction/diagnosis , Humans , Male , Middle Aged
15.
Am J Emerg Med ; 54: 102-106, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35152117

ABSTRACT

BACKGROUND: It is thought vaccines allowed for emergency use significantly reduce hospitalizations and emergency room visits. It is a matter of curiosity how many of the patients who come to the emergency department (ED) are vaccinated. We aimed to examine the characteristics of ED patients needing hospitalizations related to moderate and severe COVID-19 by vaccination status. METHODS: A retrospective study of 559 rRT-PCR-confirmed SARS-CoV-2 infection cases with moderate or severe COVID-19 needing hospitalization was performed in August 2021. Univariate and multivariate logistic regression analyses were performed for factors associated with mortality. RESULTS: The mean age of the patients was 60.8 ± 18.1 years old, and 54.2% (n = 303) of the patients were women. The most common comorbidities were hypertension (37.2%), diabetes mellitus (31.1%) and chronic obstructive pulmonary disease (13.8%), respectively. The number of patients with alpha variant was 399 (71.4%), and delta variant was 83 (14.8%). Fifty point 6% (n = 283) of the patients were fully vaccinated. The total number of patients who died in the study was 114 (20.4%), and the number of patients hospitalized in the intensive care unit was 168 (30.1%). The day between the last dose of vaccine and hospitalization was 117 ± 45.9 days. In multivariate logistic regression analysis: age (odds ratio (OR), 1.05; 95% confidence intervals (95% CI) 1.03-1.08- year increase), male gender (OR, 1.8; 95% CI, 1.1-2.9), presence of at least one comorbid disease (OR, 2; 95% CI, 1.1-3.7) and partial (OR, 0.24;95% CI, 0.09-0.6) and fully vaccinated status (OR, 0.1; 95% CI, 0.05-0.18) were associated with mortality among COVID-19 patients. CONCLUSIONS: In this study, age older than 65, unvaccinated, and comorbidities had significantly higher mortality. In multivariate regression analyses, age, vaccination status, comorbidities and the male gender were associated with mortality. Our study did not evaluate the vaccine efficacy but, a lower mortality rate was observed in those fully vaccinated with CoronaVac and Pfizer-BioNTech. Additionally, Alpha, Delta and other variants had the same mortality rates.


Subject(s)
COVID-19 Vaccines , COVID-19 , Hospitalization , Vaccination , Adult , Aged , COVID-19/epidemiology , COVID-19/mortality , COVID-19/prevention & control , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Vaccination/statistics & numerical data
16.
Drug Dev Res ; 83(2): 470-484, 2022 04.
Article in English | MEDLINE | ID: mdl-34532880

ABSTRACT

Novel 2-[2-(chroman-4-ylidene)hydrazinyl]-4/5-substituted thiazole derivatives (2a-i) were synthesized and investigated for their anticancer activity. Cytotoxic activity on A549 and NIH/3T3 cell lines was determined, most of the compounds exhibited high cytotoxic profile with selectivity. Selected compounds 2b, 2c, 2e, 2g, 2h, and 2i were tested to determine induction of apoptosis, mitochondrial membrane depolarization, and cell cycle arrest. The results showed that the compounds induced apoptosis intrinsically that they triggered loss of mitochondrial potential through increasing the accumulation of cells in G2/M. Besides, intrinsic apoptotic pathway was supported by down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of proapoptotic protein Bax. Molecular docking study for compounds 2b, 2c, and 2g was promoted experimental outcomes.


Subject(s)
Antineoplastic Agents , Lung Neoplasms , A549 Cells , Antineoplastic Agents/pharmacology , Apoptosis , Cell Proliferation , Drug Screening Assays, Antitumor , Humans , Lung Neoplasms/drug therapy , Molecular Docking Simulation , Molecular Structure , Structure-Activity Relationship , Thiazoles/pharmacology
17.
Andrology ; 10(3): 560-566, 2022 03.
Article in English | MEDLINE | ID: mdl-34939748

ABSTRACT

BACKGROUND: In the literature, there is not sufficient data on factors affecting the development of complications in patients with penile fracture after early surgical intervention. OBJECTIVES: To investigate the predictors of long-term complications in patients who underwent immediate surgical repair for penile fracture. MATERIALS/METHODS: This clinical study included a total of 31 cases of penile fracture in which surgical treatment was performed within the first 24 h and penile fracture was confirmed during the operation. The patients with and without late complications were compared in terms of parameters such as age, tear size of the tunica albuginea of the penis, bilateral involvement of the corpora cavernosa involvement, urethral injuries, and duration from penile fracture to surgery. RESULTS: The median age of the patients was 42 years (interquartile range: 34-51 years). The median time from penile fracture to surgery was 13 h (8-18 h). The median tear size was 16 mm (11-21 mm). Late complications were seen in 13 (41.9%) patients in the post-operative period. Erectile dysfunction developed in five (16.1%) patients in the post-operative period. There was no statistically significant relationship between age, tear size, time from penile fracture to surgery, and bilateral corporeal involvement in terms of erectile dysfunction development. Painful erections, penile deviations, urethral strictures, tunical scars, and re-fracture were the other late complications. There was a significant relationship between the development of any complication and time from penile fracture to surgery (p = 0.028) and tear size (p = 0.031). In the receiver operating characteristic analysis of complication development, the cut-off value for the time from penile fracture to surgery was 13.5 h. DISCUSSION AND CONCLUSION: We found that the longer time interval between penile fracture and surgery worsened the patient outcomes. In addition, tear size was determined to be a predictor for long-term complications. In our opinion, early treatment of penile fracture can prevent severe complications in these cases.


Subject(s)
Erectile Dysfunction , Penile Diseases , Adult , Erectile Dysfunction/etiology , Humans , Male , Middle Aged , Penile Diseases/etiology , Penile Diseases/surgery , Penis/injuries , Penis/surgery , Rupture/complications , Rupture/surgery , Tertiary Care Centers
18.
J Pediatr Urol ; 17(6): 796.e1-796.e8, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34750075

ABSTRACT

INTRODUCTION: We retrospectively assessed the role of ureteral wall thickness (UWT) at the ureteral stone site in predicting the stone-free status and the complication rates in children undergoing semi-rigid ureterorenoscopy (URS). PATIENTS AND METHODS: The children who underwent URS and had undergone non-contrast abdominal computerized tomography before the URS were included in the study. The following protocol was used to determine the outcome. Immediately before removing the stent, all children were evaluated by ultrasound (US) and plain film (KUB) for residual stones in the upper urinary tract and after removing the double J stent, the presence of stone fragments in the ureter was checked with URS. The children were considered stone-free if no residual fragments were identified in radiologic imaging and the evaluation of the ureter by URS. The case was accepted as a failure if any fragments were seen on immediate US, KUB, and/or during URS just after the stent removal. The patients who could not complete the standard primary URS procedure due to stone-related reasons (patients for whom we could not pass the safety guidewire behind the stone and/or the procedure was terminated due to pyuria during the procedure) were also accepted as a failure. The possible factors related to the patient, stone, ureter, and the operation that could affect the outcome and the complications following the URS were evaluated. RESULTS: The children's median age was six years (1-17 years). Among the 89 children included in the study, 69 (78%) were stone-free, and 20 (22%) presented residual stone after the first URS session. The ROC analysis revealed that a UWT value of 4.5 mm (sensitivity 60%, specificity 92%) was the optimal cut-off value predictive of the URS outcome. The regression analysis revealed UWT >4.5 mm (p = 0.006) and multiple stone presentation (p = 0.005) as independent risk factors for residual stone. Complications were detected in 15 (17%) children. Thick ureteral wall (p = 0.012) and longer operative time (p = 0.016) were defined as the independent risk factors for complications. DISCUSSION: Increased UWT is associated with the adverse outcomes of URS due to tissue hypertrophy, edema, and mucosal bleeding may cause difficulty in removing the stone. The thick ureteral wall might increase the risk of complications due to the necessity of manipulating the instruments or the involuntary forceful use of instruments while removing the stone. CONCLUSION: UWT was the only independent variable affecting both increased failure and complication rates in children undergoing URS.


Subject(s)
Ureter , Ureteral Calculi , Child , Humans , Retrospective Studies , Treatment Outcome , Ureter/diagnostic imaging , Ureter/surgery , Ureteral Calculi/diagnostic imaging , Ureteral Calculi/surgery , Ureteroscopy/adverse effects
19.
Bioorg Chem ; 117: 105403, 2021 12.
Article in English | MEDLINE | ID: mdl-34758434

ABSTRACT

The bacterial deacetylase LpxC is a promising target for the development of novel antibiotics being selectively active against Gram-negative bacteria. In chiral pool syntheses starting from d- and l-ribose, a series regio- and stereoisomeric monohydroxytetrahydrofuran derivatives was synthesized and tested for LpxC inhibitory and antibacterial activities. Molecular docking studies were performed to rationalize the obtained structure-activity relationships. The (2S,3R,5R)-configured 3-hydroxytetrahydrofuran derivative ent-8 ((2S,3R,5R)-N,3-Dihydroxy-5-(4-{[4-(morpholinomethyl)phenyl]ethynyl}phenyl)tetrahydrofuran-2-carboxamide) was found to be the most potent LpxC inhibitor (Ki = 3.5 µM) of the synthesized series of monohydroxytetrahydrofuran derivatives and to exhibit the highest antibacterial activity against E. coli BL21(DE3) and the D22 strain.


Subject(s)
Amidohydrolases/antagonists & inhibitors , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Glycosides/chemistry , Glycosides/pharmacology , Amidohydrolases/drug effects , Amidohydrolases/metabolism , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Enzyme Inhibitors/chemical synthesis , Escherichia coli/drug effects , Escherichia coli/enzymology , Escherichia coli Infections/drug therapy , Glycosides/chemical synthesis , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/enzymology , Gram-Negative Bacterial Infections/drug therapy , Humans , Molecular Docking Simulation
20.
Int J Clin Pract ; 75(7): e14264, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33891784

ABSTRACT

BACKGROUND: To investigate the relationship between ureteral wall thickness (UWT) and other variables of patients who underwent extracorporeal shock wave lithotripsy (SWL) in the primary treatment of the ureteral stone above the iliac crest level. MATERIAL AND METHODS: A total of 147 patients aged 18 years and older, who underwent SWL in our clinic between December 2016 and December 2019 for the treatment of ureteral stones above the iliac crest level and had non-contrast enhanced abdominal computed tomography scans before the procedure were included in the clinical study. The results were evaluated at 3 months after SWL. The absence of residual fragments was considered as stone-free status, and the existence of any size residual fragment was considered as treatment failure. RESULTS: In our study, the mean age of the patients was 42.4 ± 12.8 years, and the stone-free rate was 92.5%. The median transverse stone size was 7.5 mm (min 2.8-max 15), and the median UWT was 4.2 mm (1-8.7). In the multivariate analysis, UWT (P = .002) and multiple stone presence (P = .027) were found to be independent factors affecting stone-free status. In the receiver operating characteristic curve analysis, the optimal threshold value for UWT was determined as 5.25 mm. CONCLUSIONS: We found that UWT was the most important independent variable associated with increased failure in SWL treatment. The presence of multiple stones was another independent factor that increased the failure rates. Using SWL technology through experience accumulated with the mechanical hardware of the machine, we can select patients who are more suitable for this treatment and improve treatment outcomes.


Subject(s)
Lithotripsy , Ureteral Calculi , Adult , Humans , Ilium , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome , Ureteral Calculi/diagnostic imaging , Ureteral Calculi/therapy
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