Depression and type 2 diabetes: A causal relationship and mechanistic pathway.

Depression is a mood disorder that may increase risk for the development of insulin resistance (IR) and type 2 diabetes (T2D), and vice versa. However, the mechanistic pathway linking depression and T2D is not fully elucidated. The aim of this narrative review, therefore, was to discuss the possible link between depression and T2D. The coexistence of T2D and depression is twice as great compared to the occurrence of either condition independently. Hyperglycaemia and dyslipidaemia promote the incidence of depression by enhancing inflammation and reducing brain serotonin (5-hydroxytryptamine [5HT]). Dysregulation of insulin signalling in T2D impairs brain 5HT signalling, leading to the development of depression. Furthermore, depression is associated with the development of hyperglycaemia and poor glycaemic control. Psychological stress and depression promote the development of T2D. In conclusion, T2D could be a potential risk factor for the development of depression through the induction of inflammatory reactions and oxidative stress that affect brain neurotransmission. In addition, chronic stress in depression may induce the development of T2D through dysregulation of the hypothalamic-pituitary-adrenal axis and increase circulating cortisol levels, which triggers IR and T2D.

Evaluation of the Milled and Three-Dimensional Digital Manufacturing, 10-Degree and 20-Degree Preparation Taper, Groove and Box Auxiliary Retentive Features, and Conventional and Resin-Based Provisional Cement Type on the Adhesive Failure Stress of 3 mm Short Provisional Crowns.

BACKGROUND This study evaluated the effects of milling (CADCAM), 3D printing, preparation taper angles (10-degree and 20-degree), auxiliary retentive features (groove and box), and provisional cement types (conventional and resin-based) on the adhesive failure stress of 3-mm short provisional crowns (PC). The research was motivated by the need to understand how digital dentistry technologies impact the retention and durability of provisional crowns. MATERIAL AND METHODS A total of 160 working models (3D-printed) and PCs [80 milled (CopraTemp)/80 printed (Asiga)] were fabricated from two 10- and 20-degree typodont master models and two 20-degree 3D-printed master models (groove and box), simulating a 3 mm high all-ceramic short PC. After provisional cementation with conventional (Kerr TempBond) and resin-based (ProviTemp) cements, 16 subgroups (n=10 each) underwent thermocycling (10 000 cycles; 5-55°C) and pull-off tests on a universal testing machine. Statistical analysis was performed using one-way ANOVA and post hoc Tukey test. RESULTS Conventional cement failed at lower stress for milled (47.68 to 73.54) and printed (48.40 to 77.91) as compared to resin cement for milled (104.2 to 137.27) and printed (184.85 to 328.84), respectively, with significant differences. Increased taper and groove decreased failure load except for the printed PC/resin cement combination. Use of proximal box preparation increased retention significantly. Except for 20-degree taper cemented with conventional cement, the differences in auxiliary retentive features for milled and printed provisional crowns were statistically significant at P≤0.05. CONCLUSIONS 3D-printed PC, resin-based cement, 10-degree taper, and proximal box preparation were associated with higher retention than milled, conventional cements, 20-degree taper, and vertical groove.

Influence of Chairside Simulated Adjustment (Finishing and Polishing) Protocol and Chlorhexidine Mouthwash Immersion on Color Stability and Translucency of 2 and 3 Preshaded Multilayered Monolithic Zirconia.

BACKGROUND Preshaded monolithic zirconia (MLZ) is reported to have high translucency. This study aimed to assess the effect of chlorhexidine gluconate (ChG) mouthwash on color and translucency parameter (TP) of 2 different preshaded MLZ dental ceramics after clinical adjustment. MATERIAL AND METHODS Two MLZ disk-shaped specimens [NPM (Nacera Pearl Multi-Shade) (n=72) and CZM (Ceramill Zolid FX Multilayer)] (n=72) were simulated for clinical adjustment, finished, and polished using 2 adjustment kits [recommended kit, third-party kit: Diasynt Plus and SUN (n=12 each)] and later immersed in ChG mouthwash (Avohex) for 2 weeks. Difference in color (ΔE) and TP (Y) were calculated using the CIELab formula after measuring the coordinates (Lab) with a colorimeter. Individual changes in color and TP were assessed on the Clinical acceptance (perceptible) threshold (CAT/CPT) and Translucency perception threshold (TPT), respectively. Differences between the 2 ceramics were assessed using one-way ANOVA and post hoc tests, with all differences considered significant at P<0.05. RESULTS NPM and CZM differed in color at baseline despite having the same Vita shade combination. Between the 2 preshaded MLZ ceramics, NPM showed significant changes in color when adjusted with a third-party kit. Chlorhexidine produced changes in color and TP that were designated as clinically perceptible (ΔE=1.0 to 3.3) on the CAT/CPT and TPT scales, irrespective of the adjustment kit used. ChG produced the least or no changes in glazed MLZ specimens. CONCLUSIONS ChG mouthwash, whenever prescribed for preshaded MLZ restoration, should be adjusted prior to final glazing to avoid clinical adjustments that adversely affects color and translucency of the restoration.

The Impact of Repeated Steam Sterilization Cycles on the Efficacy of Chairside Adjustment Kits for Polishing Monolithic Multi-Layered Zirconia Dental Restoration Material.

BACKGROUND Before insertion, chairside adjustment kits are heat sterilized for positioning and polishing dental restorations. This study aimed to evaluate the effects of 2 steam sterilization cycles on the efficacy of polishing highly translucent monolithic zirconia (HTMLZ) dental restoration material. MATERIAL AND METHODS 100 HTMLZ disc-shaped specimens were adjusted (grinding, finishing, polishing) with EVE Diacera kit. Two steam sterilization techniques [standard (Gp S), immediate/flash (Gp (F)] of CAK were further subgrouped based on number of sterilization cycles [cycle 1 (control), cycle 5, 10, 15, and 20 (experimental)] (n=10 each). Each subgroup accordingly was evaluated for average surface roughness (Ra) and root mean square roughness (Rq) using a profilometer. Mean and standard deviation of 5 subgroups were statistically analyzed using one-way ANOVA/post hoc Tukey's test. Scanning electron microscopy complemented Ra, Rq measurements. Statistical differences of P≤0.05 were considered significant. RESULTS HTMLZ specimens in both groups showed increased (Ra/Rq) values after repeated sterilization of EVE Diacera kit, with Gp F showing lesser increase than Gp S (20 cycles). Gp F at 10 cycles and Gp S at 15 cycles showed clinically unacceptable roughness threshold (0.25 µm). Differences between subgroups for Ra and Rq values were significant (P≤0.05) with less differences within groups observed in early cycles (1, 10). Results validate the manufacturer's recommendations of using flash sterilization/10 cycles for EVE Diacera kit. CONCLUSIONS Repeated sterilization reduces efficacy of chairside adjustment kit to produce smooth surfaces on HTMLZ. This study recommends flash sterilization to a maximum of 10 times to get the clinically acceptable results of Ra and Rq.

Development of progesterone electrospun nanofibers to coat Arabin pessaries as a dual preventive and therapeutic approach for preterm labor.

Preterm labor is a growing health problem that causes newborn death, and safe and effective therapy is significantly needed. Arabin pessaries and progesterone are preventive and therapeutic approaches that can be applied to managing the short cervix; hence, reducing the risk of preterm labor. The main goal of current work is to fabricate a novel nanofiber formulation based on polycaprolactone (PCL) and loaded with progesterone to coat for Arabin pessaries to be used as dual preventive and therapeutic approaches for local vaginal delivery. Several important criteria were considered in this study to assess the prepared nanofibers (i.e.; nanofiber diameter, progesterone loading efficiency, progesterone release profiles and in vitro cytotoxicity assessment). The results showed a dimeter of 397 ± 88 nm, drug loading of 142 ± 3 µg/mg and encapsulation efficiency of 99 ± 2 % for the progesterone-loaded nanofibers. Approximately, 17 % of progesterone was released from the nanofibers after 90 days. The in vitro assessment showed that the application of progesterone is safe upon 24 and 48-hours incubation on HFF-1 cell line at concentrations ≤ 32 µg/mL and within 72-hours at a dose of ≤ 8 µg/mL. To conclude, the data recommended that progesterone-loaded nanofibers can coat the Arabin pessaries with the potential of being a safe and effective dual preventive and therapeutic tool for preterm labor.

Fabrication and evaluation of ribavirin-loaded electrospun nanofibers as an antimicrobial wound dressing.

Background: Skin is regarded as an essential first line of defense against harmful pathogens and it hosts an ecosystem of microorganisms that create a widely diverse skin microbiome. In chronic wounds, alterations in the host-microbe interactions occur forming polymicrobial biofilms that hinder the process of wound healing. Ribavirin, an antiviral drug, possesses antimicrobial activity, especially against Pseudomonas aeruginosa and Candida albicans, which are known as the main opportunistic pathogens in chronic wounds. Rationale: In this study, electrospun nanofiber systems loaded with ribavirin were developed as a potential wound dressing for topical application in chronic wounds. Ribavirin was chosen in this study owing to the emerging cases of antimicrobial (antibiotics and antifungal) resistance and the low attempts to discover new antimicrobial agents, which encouraged the repurposing use of current medication as an alternative solution in case of resistance to the available agents. Additionally, the unique mechanism of action of ribavirin, i.e., perturbing the bacterial virulence system without killing or stopping their growth and rendering the pathogens disarmed, might be a promising choice to prevent drug resistance. Cyclodextrin (CD) was utilized to formulate ribavirin as an electrospun nanofibers delivery system to enhance the absorption and accelerate the release of ribavirin for topical use. Results: The results demonstrated a successful ribavirin nanofibers fabrication that lacked beads and pores on the nanofibrous surfaces. Ribavirin underwent a physical transformation from crystalline to amorphous form, as confirmed by X-ray diffraction analysis. This change occurred due to the molecular dispersion after the electrospinning process. Additionally, the CD enhanced the encapsulation efficiency of ribavirin in the nanofibers as observed from the drug-loading results. Polyvinylpyrrolidone (PVP) and CD increased ribavirin released into the solution and the disintegration of fibrous mats which shrank and eventually dissolved into a gel-like substance as the ribavirin-loaded fibers began to break down from their border toward the midpoint. Cytotoxicity of ribavirin and CD was evaluated against human dermal fibroblasts (HFF-1) and the results showed a relatively safe profile of ribavirin upon 24-hour cell exposure, while CD was safe within 24- and 48-hour. Conclusion: This study provides valuable insights into the potential application of our nanofibrous system for treating chronic wounds; however, further antimicrobial and in-vivo studies are required to confirm its safety and effectiveness.

Development and evaluation of sildenafil/glycyrrhizin-loaded nanofibers as a potential novel buccal delivery system for erectile dysfunction.

Erectile dysfunction (ED) is a growing health condition that needs safe and effective therapy. One of the main common treatments is sildenafil which is used in clinics for managing erectile dysfunction by enhancing the blood supply to the penis. In the current study, sildenafil was formulated as nanofibers and mixed with the root extract of Glycyrrhiza glabra (glycyrrhizin) as a natural sweetener to be administrated in the buccal cavity for enhanced drug bioavailability, rapid drug absorption and improved patient compliance. The formulated dual-loaded nanofibers were evaluated by measuring diameter, disintegration, drug loading efficiency, drug release profile, and in vitro cell viability assessment. The results showed that the sildenafil/glycyrrhizin-loaded fibers had a diameter of 0.719 ± 0.177 µm and lacked any beads and pores formation on their surfaces. The drug loading and encapsulation efficiency for sildenafil were measured as 52 ± 7 µg/mg and 67 ± 9 %, respectively, while they were 290 ± 32 µg/mg and 94 ± 10 %, respectively, for glycyrrhizin. The release rate of sildenafil and glycyrrhizin demonstrated a burst release in the first minute, followed by a gradual increment until a complete release after 120 min. The in vitro cell viability evaluation exhibited that the application of sildenafil and glycyrrhizin is safe upon 24-hour treatment on human skin fibroblast cells at all used concentrations (i.e., ≤ 1,000 and 4,000 µg/mL, respectively). However, the application of sildenafil-glycyrrhizin combination (in a ratio of 1:4) demonstrated more than 80 % cell viability at concentrations of ≤ 250 and 1000 µg/mL, respectively, following 24-hour cell exposure. Therefore, sildenafil/glycyrrhizin dual-loaded PVP nanofibers showed a potential buccal therapeutic approach for erectile dysfunction management.

Who have a better-kidney-related quality of life: peritoneal dialysis or hemodialysis patients? A cross sectional study from Saudi Arabia.

BACKGROUND: End-stage kidney disease (ESKD) substantially impacts different aspects of patients' lives, including mental and physical health, and overall quality of life. The aim of our study is to assess the quality of life (QoL) and the associated predictors in ESKD Saudi Arabian patients receiving either hemodialysis (HD) or peritoneal dialysis (PD). Saudi Ministry of health (MOH) is advancing dialysis care in the country with more focus on patients' satisfaction and QoL. However, the data regarding QoL in Saudi Arabian dialysis patients is limited. METHODS: A cross sectional study was carried out using Kidney Disease Quality of Life scale (KDQOL-36) to assess the QoL. We disturbed a validated formal arabic version of the questionnaire. Patients older than 18-year-old and attending dialysis clinics in Aseer region, Saudi Arabia, were invited to participate in the study. RESULTS: A total of 152 responses were analyzed, which were separated into two primary groups: the HD group (98 patients) and the PD group (54 patients). Our results showed no significant differences between the two groups except for the KDQOL-SF-36 physical composite score at which the PD group had a higher mean than the HD group 44.75 vs 37.84, respectively (p < 0.001). However, more PD patients reported feeling depressed compared to HD patients. CONCLUSIONS: Kidney Disease Quality of Life scale scores were comparable between HD and PD groups except for the physical composite score. On the other hand, PD patients tend to suffer from depression more than HD patients. Interventions to attenuate the physical deconditioning and depressive symptoms in HD and PD patients, respectively, are crucial. Future prospective studies with larger sample sizes are warranted.

Bronchodilator reversibility testing in morbidly obese non-smokers: fluticasone/salmeterol efficacy versus salbutamol bronchodilator.

A positive response in reversibility testing is widely used to diagnose patients with airway limitations. However, despite its simple procedure, it doesn't accurately reflect the exact airway irreversibility. This study aimed to investigate the efficacy of a bronchodilation reversibility test using salbutamol and fluticasone/salmeterol combination in obese non-smoker subjects.The study included patients without a history of obstructive lung disease or bronchodilators. A sub-classification of patients based on body mass index (BMI) was carried out into normal (< 24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (BMI ≥ 30). Spirometry measurements were performed before and after salbutamol or fluticasone/salmeterol administration.The study included 415 (49.9% male) patients with a mean age of 40.92 ± 10.86 years. Obese subjects showed a high prevalence of restrictive patterns (23.4%), with non-significantly lower spirometric values compared to normal and overweight subjects (p > 0.05). The magnitude of bronchodilation, as identified by spirometry, following fluticasone/salmeterol was higher in all participants, with a significant increase in obese subjects with a p-value of 0.013, 0.002, and 0.035 for FEV1, FEV1% predicted, and FEV1/FVC, respectively.Fluticasone/salmeterol combination increases FEV1, FEV1% of predicted, and FEV1/FVC ratio than the conventional test using salbutamol inhaler, and it can be a potential candidate for assessment of airway obstruction using reversibility test, especially among the obese population.

The prevalence of depressive and anxiety symptoms among first-year and fifth-year medical students during the COVID-19 pandemic: a cross-sectional study.

BACKGROUND: Medical students have higher risk of psychological disorders due to the relatively stressful environment. Educators are becoming increasingly aware of the impact of stresses on the students general well-being. The objective of the current study was to examine the prevalence of and risk factors for depressive and anxiety symptoms among first-year and fifth-year medical students. Additionally, we aimed to determine whether the COVID-19 pandemic has affected students' mental well-being. METHODS: A cross-sectional study was performed at the College of Medicine at King Saud University between September 2020 and January 2021. The target population was first-year and fifth-year medical students. Depressive symptoms were screened using the 9-item Patient Health Questionnaire (PHQ-9), while anxiety symptoms were screened using the 7-item Generalized Anxiety Disorder assessment (GAD-7). Students were also directly asked about the effect of the COVID-19 pandemic on their mental well-being. Outcomes were compared between groups using the chi-squared test and Student's t test. Multivariate logistic regression analysis was performed to identify factors associated with depressive and anxiety symptoms. RESULTS: A total of 182 medical students were included. Depressive symptoms (52.9% versus 35.8%, p = 0.020) and anxiety symptoms (35.6% versus 26.3%, p = 0.176) were higher in the first-year students than in the fifth-year students. Approximately 19.2% of the students were worried about acquiring COVID-19, 49.4% were worried about academic performance, and 30.8% were feeling sad, depressed or anxious during the COVID-19 pandemic. Independent risk factors for depressive symptoms included having concomitant anxiety, being worried about acquiring COVID-19, being worried about academic performance, and feeling sad, depressed or anxious. Independent risk factors for anxiety included having a lower grade point average and having concomitant depressive symptoms. CONCLUSION: Medical students have an alarmingly high prevalence of depressive and anxiety symptoms, which might have been negatively impacted by the COVID-19 pandemic. There is a need for a special mental health program targeting new and current medical students.

Prevalence of bruxism in obstructive sleep apnea syndrome (OSAS) patients: A systematic review conducted according to PRISMA guidelines and the cochrane handbook for systematic reviews of interventions.

BACKGROUND: Sleep bruxism (SB) and obstructive sleep apnea syndrome (OSAS) are two sleep-related conditions that have been associated with significantly conflicting results in literature. Understanding the prevalence of bruxism among OSA patients is crucial for identifying possible comorbidities and optimising treatment strategies. OBJECTIVE: This systematic review aimed at analysing the prevalence of SB in OSAS sufferers and understanding the association between the two. METHODS: Five online databases were searched for relevant articles in accordance with the PRISMA guidelines for conduction of systematic reviews. Studies reporting the prevalence of bruxism in OSAS patients and diagnosed through clinical assessments or polysomnography were included. Data extraction and quality assessment were performed independently by two reviewers. Methodological quality of the included studies was assessed using Risk of Bias In Non-randomised Studies of Interventions (ROBINS-I). RESULTS: A thorough search of literature yielded only two studies were eligible for this review. SB was found to be significantly present in the OSAS group. Despite methodological variations, the majority of studies reported higher rates of bruxism in OSAS patients compared to the general population or control groups. CONCLUSION: The results of this systematic review point to a significant association between bruxism and obstructive sleep apnea. Further research is required to determine a more precise prevalence rate and investigate the potential therapeutic implications of the bruxism-OSAS association that uses a standardised assessment techniques and larger sample sizes.

Green Synthesis of Silver Nanoparticles Using Jacobaea maritima and the Evaluation of Their Antibacterial and Anticancer Activities.

Much attention has been gained on green silver nanoparticles (green-AgNPs) in the medical field due to their remarkable effects against multi-drug resistant (MDR) microorganisms and targeted cancer treatment. In the current study, we demonstrated a simple and environment-friendly (i.e., green) AgNP synthesis utilizing Jacobaea maritima aqueous leaf extract. This leaf is well-known for its medicinal properties and acts as a reducing and stabilizing agent. Nanoparticle preparation with the desired size and shape was controlled by distinct parameters; for instance, temperature, extract concentration of salt, and pH. The characterization of biosynthesized AgNPs was performed by the UV-spectroscopy technique, dynamic light scattering, scanning electron microscopy, X-ray diffraction, and Fourier-transform infrared. The successful formation of AgNPs was confirmed by a surface plasmon resonance at 422 nm using UV-visible spectroscopy and color change observation with a particle size of 37± 10 nm and a zeta potential of -10.9 ± 2.3 mV. SEM further confirmed the spherical size and shape of AgNPs with a size varying from 28 to 52 nm. Antibacterial activity of the AgNPs was confirmed against all Gram-negative and Gram-positive bacterial reference and MDR strains that were used in different inhibitory rates, and the highest effect was on the E-coli reference strain (MIC = 25 µg/mL). The anticancer study of AgNPs exhibited an IC50 of 1.37 µg/mL and 1.98 µg/mL against MCF-7 (breast cancer cells) and A549 (lung cancer cells), respectively. Therefore, this green synthesis of AgNPs could have a potential clinical application, and further in vivo study is required to assess their safety and efficacy.

Radiographic Evaluation of the Gap between Cemented Post and Remaining Gutta-Percha in Endodontically Treated Teeth Performed by Undergraduate Students: A Retrospective Cross-Sectional Study.

The coronal seal in root canal-treated teeth may be compromised depending on the accuracy of post space preparation and post cementation along with remaining gutta-percha. Root canal treatment can be compromised by endotoxins released by the coronal bacteria as a result of microleakage. The study was conducted by undergraduate students to measure the gap between the cemented post and residual gutta-percha. In total, 217 endodontically treated teeth were evaluated with intraoral peri-apical radiographs. Based on the intraoral periapical radiographic examination in the CS-R4 program, Group I had no gap, Group II had a gap of >0 to 2 mm, and Group III had a gap of more than 2 mm between the end of the cemented post and the remaining gutta-percha. In total, 40% (n = 87) of the teeth had no gap, 59% (127) had a gap of >0 to 2 mm, and 1% (n = 3) had a gap of more than 2 mm between the cemented post end and remaining gutta. Chi square test revealed a significant difference in the gap between the post and remaining gutta-percha between males and females students (p < 0.001). In terms of the gap between the cemented post end and the residual gutta-percha, the root canal treated teeth with post and core by undergraduates were clinically acceptable.

Accuracy Comparison between Robot-Assisted Dental Implant Placement and Static/Dynamic Computer-Assisted Implant Surgery: A Systematic Review and Meta-Analysis of In Vitro Studies.

Background and Objectives: The present systematic review and meta-analysis undertake a comparison of studies that examine the accuracy of robot-assisted dental implant placement in relation to static computer-assisted implant surgery (SCAIS), dynamic computer-assisted implant surgery (DCAIS), and freehand procedures. This study aims to provide a comprehensive understanding of the precision of robot-assisted dental implant placement and its comparative efficacy in relation to other placement techniques. Methods: The guidelines recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were used to organize and compose this review. Four electronic databases (PubMed, Web of Science, Scopus, and Cochrane) were systematically searched for pertinent articles. Articles were selected following the inclusion and exclusion criteria. Qualitative and quantitative analyses of the selected articles were performed. Results: The initial electronic search resulted in 1087 hits. Based on the inclusion and exclusion criteria, five articles were selected for qualitative analysis, out of which three were considered for quantitative analysis. Three parameters were considered for accuracy evaluation (angular, coronal, and apical deviation). The mean angular deviation was -1.22 degrees (95% CI, -1.06--1.39), the mean coronal deviation was -0.15 mm (95% CI, -0.24--0.07), and the mean apical deviation was -0.19 mm (95% CI, -0.27--0.10). Conclusions: The robotic implant system was found to have significantly lower angular deviations and insignificantly lower coronal and apical deviations compared to DCAIS. Within the limitations of this review, it can be concluded that robot-assisted implant placement in resin models permits higher accuracy compared to DCAIS and SCAIS systems. However, due to the limited number of comparative studies with high heterogeneity, the findings of this review should be interpreted with caution. Further research is necessary to confirm the clinical application of robotics in implant surgery.

Awareness of isotretinoin use and safety in Saudi Arabia: A nationwide cross-sectional study.

Introduction: Acne is a prevalent skin condition that affects numerous adolescents and adults worldwide. The most effective treatment for acne is isotretinoin, but its usage is associated with a wide range of adverse effects, and regular monitoring is necessary. Hence, appropriate usage with awareness of potential side effects is crucial. This study aimed to assess the knowledge and awareness of isotretinoin use and safety among individuals with acne in Saudi Arabia. Methods: A national cross-sectional survey was conducted through an online self-administered questionnaire distributed via social media platforms. The questionnaire consisted of 27 questions in multiple-choice and Likert scale formats, covering demographics, patient awareness of isotretinoin use and side effects, satisfaction with clinical consultation and information provided. Descriptive statistics were used to summarize data. Results: 1315 participants completed the survey, of which most were female (74.1%), single (67.5%), and aged 18-25 years (48.9%). Dryness and teratogenicity were the most commonly known side effects of isotretinoin use (85.5% and 64.9% respectively). However, most participants were unaware of other side effects, such as psychiatric disorders (62.9%), altered liver enzyme concentrations (65.2%), hyperlipidemia (68.1%), anemia (92.4%), and decreased platelet count (96%). Moreover, 36% of sexually active females initiated isotretinoin without contraception. Regarding satisfaction with the information provided during clinical consultation, 63.2% of participants were very satisfied or satisfied. Doctors were the primary source of information (86.8%), followed by the internet (17.8%). Only 45% were informed to avoid blood donation during and after treatment for at least two months. Conclusion: The study highlights the significance of providing patients with comprehensive information about the potential side effects of isotretinoin, including the need to use contraception and avoid blood donation during and after treatment. Effective communication between physicians and patients is critical in ensuring the safe and effective use of isotretinoin.

GL67 lipid-based liposomal formulation for efficient siRNA delivery into human lung cancer cells.

The efficient delivery of small interfering RNA (siRNA) to the targeted cells significantly affects the regulation of the overexpressed proteins involved in the progression of several genetic diseases. SiRNA molecules in naked form suffer from low internalization across the cell membrane, high susceptibility to degradation by nuclease enzyme and low stability, which hinder their efficacy. Therefore, there is an urge to develop a delivery system that can protect siRNA from degradation and facilitate their uptake across the cell membrane. In this study, the cationic lipid (GL67) was exploited, in addition to DC-Chol and DOPE lipids, to design an efficient liposomal nanocarrier for siRNA delivery. The physiochemical characterizations demonstrated that the molar ratio of 3:1 has proper particle size measurements from 144 nm to 332 nm and zeta potential of -9 mV to 47 mV that depends on the ratio of the GL67 in the liposomal formulation. Gel retardation assay exhibited that increasing the percentage of GL67 in the formulations has a good impact on the encapsulation efficiency compared to DC-Chol. The optimal formulations of the 3:1 M ratio also showed high metabolic activity against A549 cells following a 24 h cell exposure. Flow cytometry findings showed that the highest GL67 lipid ratio (100 % GL67 and 0 % DC-Chol) had the highest percentage of cellular uptake. The lipoplex nanocarriers based on GL67 lipid could potentially influence treating genetic diseases owing to the high internalization efficiency and safety profile.

The problem of pulmonary arterial hypertension in end-stage renal disease: can peritoneal dialysis be the solution.

BACKGROUND: Pulmonary arterial hypertension (PAH) in the setting of end-stage renal disease (ESRD) has important prognostic and therapeutic consequences. We estimated the prevalence of PAH among patients with ESRD treated with automated peritoneal dialysis (APD), investigated the effect of different variables and compared pulmonary artery pressure and cardiac function at the beginning and end of the study. METHODS: This is a 5-year study in which 31 ESRD patients on APD were recruited after fulfilling inclusion criteria. Blood samples were collected from all patients for the biochemical and hematological data at the beginning of the study and every month and at the study termination. Total body water (TBW) and extracellular water (ECW) were calculated using Watson's and Bird's calculation methods. All patients were followed-up at 3-month interval for cardiac evaluation. Logistic regression analysis was used to assess the relation between different variables and PAH. RESULTS: The mean age of the study population (n = 31) was 51.23 ± 15.24 years. PAH was found in 24.2% of the patients. Mean systolic pulmonary artery pressure (sPAP) and mean pulmonary artery pressure (mPAP) were significantly higher in the APD patients at study initiation than at the end of the study (40.75 + 10.61 vs 23.55 + 9.20 and 29.66 + 11.35 vs 18.24 + 6.75 mmHg respectively, p = 0.001). The median ejection fraction was significantly lower in patients with PAH at zero point than at study termination [31% (27-34) vs 50% (46-52), p = 0.002]. Hypervolemia decreased significantly at the end of study (p <  0.001) and correlated positively with the PAP (r = 0.371 and r = 0.369), p = 0.002). sPAP correlated with left ventricular mass index, hemoglobin level, and duration on APD. CONCLUSIONS: Long term APD (> 1 years) seemed to decrease pulmonary arterial pressure, right atrial pressure and improve left ventricular ejection fraction (LVEF). Risk factors for PAH in ESRD were hypervolemia, abnormal ECHO findings and low hemoglobin levels. Clinical and echocardiographic abnormalities and complications are not uncommon among ESRD patients with PAH. Identification of those patients on transthoracic echocardiography may warrant further attention to treatment with APD.

Predicting Attack Pattern via Machine Learning by Exploiting Stateful Firewall as Virtual Network Function in an SDN Network.

Decoupled data and control planes in Software Defined Networks (SDN) allow them to handle an increasing number of threats by limiting harmful network links at the switching stage. As storage, high-end servers, and network devices, Network Function Virtualization (NFV) is designed to replace purpose-built network elements with VNFs (Virtualized Network Functions). A Software Defined Network Function Virtualization (SDNFV) network is designed in this paper to boost network performance. Stateful firewall services are deployed as VNFs in the SDN network in this article to offer security and boost network scalability. The SDN controller's role is to develop a set of guidelines and rules to avoid hazardous network connectivity. Intruder assaults that employ numerous socket addresses cannot be adequately protected by these strategies. Machine learning algorithms are trained using traditional network threat intelligence data to identify potentially malicious linkages and probable attack targets. Based on conventional network data (DT), Bayesian Network (BayesNet), Naive-Bayes, C4.5, and Decision Table (DT) algorithms are used to predict the target host that will be attacked. The experimental results shows that the Bayesian Network algorithm achieved an average prediction accuracy of 92.87%, Native-Bayes Algorithm achieved an average prediction accuracy of 87.81%, C4.5 Algorithm achieved an average prediction accuracy of 84.92%, and the Decision Tree algorithm achieved an average prediction accuracy of 83.18%. There were 451 k login attempts from 178 different countries, with over 70 k source IP addresses and 40 k source port addresses recorded in a large dataset from nine honeypot servers.

Advances in Fungal Phenaloenones-Natural Metabolites with Great Promise: Biosynthesis, Bioactivities, and an In Silico Evaluation of Their Potential as Human Glucose Transporter 1 Inhibitors.

Phenaloenones are structurally unique aromatic polyketides that have been reported in both microbial and plant sources. They possess a hydroxy perinaphthenone three-fused-ring system and exhibit diverse bioactivities, such as cytotoxic, antimicrobial, antioxidant, and anti-HIV properties, and tyrosinase, α-glucosidase, lipase, AchE (acetylcholinesterase), indoleamine 2,3-dioxygenase 1, angiotensin-I-converting enzyme, and tyrosine phosphatase inhibition. Moreover, they have a rich nucleophilic nucleus that has inspired many chemists and biologists to synthesize more of these related derivatives. The current review provides an overview of the reported phenalenones with a fungal origin, including their structures, sources, biosynthesis, and bioactivities. Moreover, more than 135 metabolites have been listed, and 71 references have been cited. SuperPred, an artificial intelligence (AI) webserver, was used to predict the potential targets for selected phenalenones. Among these targets, we chose human glucose transporter 1 (hGLUT1) for an extensive in silico study, as it shows high probability and model accuracy. Among them, aspergillussanones C (60) and G (60) possessed the highest negative docking scores of -15.082 and -14.829 kcal/mol, respectively, compared to the native inhibitor of 5RE (score: -11.206 kcal/mol). The MD (molecular dynamics) simulation revealed their stability in complexes with GLUT1 at 100 ns. The virtual screening study results open up a new therapeutic approach by using some phenalenones as hGLUT1 inhibitors, which might be a potential target for cancer therapy.

Recent advances in mitochondrial diseases: From molecular insights to therapeutic perspectives.

Mitochondria are double-membraned cytoplasmic organelles that are responsible for the production of energy in eukaryotic cells. The process is completed through oxidative phosphorylation (OXPHOS) by the respiratory chain (RC) in mitochondria. Thousands of mitochondria may be present in each cell, depending on the function of that cell. Primary mitochondria disorder (PMD) is a clinically heterogeneous disease associated with germline mutations in mitochondrial DNA (mtDNA) and/or nuclear DNA (nDNA) genes, and impairs mitochondrial structure and function. Mitochondrial dysfunction can be detected in early childhood and may be severe, progressive and often multi-systemic, involving a wide range of organs. Understanding epigenetic factors and pathways mutations can help pave the way for developing an effective cure. However, the lack of information about the disease (including age of onset, symptoms, clinical phenotype, morbidity and mortality), the limits of current preclinical models and the wide range of phenotypic presentations hamper the development of effective medicines. Although new therapeutic approaches have been introduced with encouraging preclinical and clinical outcomes, there is no definitive cure for PMD. This review highlights recent advances, particularly in children, in terms of etiology, pathophysiology, clinical diagnosis, molecular pathways and epigenetic alterations. Current therapeutic approaches, future advances and proposed new therapeutic plans will also be discussed.