Laparoscopic Management of Inguinal Hernia: A Systematic Review and Updated Network Meta-Analysis of Randomized Controlled Trials.

Various surgical approaches for inguinal hernia repair have been outlined in medical literature. In most cases, these lesions are repaired by general surgeons. A variety of surgical techniques for the treatment of inguinal hernias have been documented in the medical literature. In 2018, the European Hernia Society (EHS) recommended laparo-endoscopic repair as a preferred approach for adults. This method involves a combination of laparoscopic and endoscopic techniques for hernia repair. The goal of this systematic review is to conduct a thorough examination of the total extraperitoneal vs. transabdominal preperitoneal comparison in inguinal hernia repair, with an emphasis on randomized controlled trials (RCTs). It also intends to conduct a trial sequential analysis (TSA) in order to determine whether more trials and investigations are required or whether there is sufficient evidence to draw a firm conclusion. The study's systematic review and meta-analysis were carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We used the PubMed and Google Scholar databases to conduct a thorough web search for articles published between January 2019 and December 2023. The meta-analysis was carried out using Resource Manager Revman version 5.4.1 (Revman International, Inc., New York City, New York). After a review of the studies was done, ten studies were selected to be used in conducting the systematic review and meta-analysis. The recurrence rate of TEP treatment was found to be slightly lower than transabdominal preperitoneal (TAPP). The two techniques did not differ in terms of postoperative complications; however, TEP had a marginally lower rate of postoperative pain. Further, the study revealed that there was a decreased risk of wound infections, seromas, and hematomas with total extraperitoneal (TEP) as opposed to transabdominal preperitoneal (TAPP). TEP also reduced the amount of recovery time needed. After conducting successful hernia treatments, total extraperitoneal and transabdominal preperitoneal both had low rates of complications and recurrence. Based on the information obtained from the study analysis, this meta-analysis provides evidence for the efficacy of TAPP and TEP techniques in the management of inguinal hernias. Though there was a statistically significant difference while applying both methods in the treatment of hernia (p=0.001), TEPs have been shown to have a lower recurrence rate than TAPPs. Similarly, the TEP method has been revealed to have a slight reduction in postoperative pain compared to transabdominal preperitoneal. However, the two techniques have been shown to have no significant difference in postoperative complications. Further, laparoscopic procedures have proved to be a little bit safer and more effective than open procedures. This has been shown by reduced risk of wound infection, hematoma, seroma, and decreased sensibility while using this method. It accelerated the healing process as well. Thus, depending on the needs of the patients and the experience level of the surgeons responsible for the treatments, inguinal hernias can be repaired using either transabdominal preperitoneal or total extraperitoneal techniques since both treatment techniques have generally minimal chance of complications or recurrence as both have proved to safer method.

Safety and efficacy of elbasvir/grazoprevir in patients infected with hepatitis C virus genotype 4 in Qassim region of Saudi Arabia.

Objective: Untreated hepatitis C virus (HCV) infection can lead to cirrhosis, hepatocellular cancer, and even death and also increases liver diseases. The elbasvir/grazoprevir (EBR-GZR) treatment regimen when given in HCV genotype (GT) 1 and GT4 infection for 8 or 12 weeks showed a high sustained virolgical response (SVR) rates in different populations. This study was assessed the effectiveness as well as safety of EBR-GZR in 12 week treatment regimen in HCV GT4-infected treatment-naïve Saudi patients. Methods: This study conducted from June 2017 and December 2020 on Saudi HCV patients infected with GT4. Treatment protocol was given for 12 weeks in treatment-naive HCV GT4 infected cirrhotic and non-cirrhotic participants which were later followed for a total of 24 weeks for safety and efficacy of EBR-GZR. Results: We analyzed data of 54 participants with HCV GT 4 infection. Mean age was (53.46 ± 14.94) Treatment regimen was given to 14 cirrhotic (F4) and 40 non-cirrhotic (F0-F3). SVR was seen in 98.1% of participants with tolerable side effects and improved model for end stage liver disease (MELD) scores as fall in percentage seen from 18.5% to 14.8% in participants with MELD > 10. Conclusion: This retrospective study confirms that EBR-GZR for 12 weeks is a safe and effective treatment regimen in HCV GT4 patients in studied Saudi population. Treatment completion was followed by high SVR12 rates with improvement in prognostic markers of liver disease in participants with compensated cirrhosis. In short, the EBR-GZR combination showed efficacy in achieving the SVR12 in Child-Pugh B cirrhotic and non-cirrhotic population with a favorable safety profile.

A novel class of phenylpyrazolone-sulphonamides rigid synthetic anticancer molecules selectively inhibit the isoform IX of carbonic anhydrases guided by molecular docking and orbital analyses.

All the previously reported phenylpyrazoles as carbonic anhydrase inhibitors (CAIs) were found to have small sizes and high levels of flexibility, and hence showed low selectivity profiles toward a particular isoform of CA. Herein, we report the development of a more rigid ring system bearing a sulfonamide hydrophilic head and a lipophilic tail to develop novel molecules that are suggested to have a better selectivity toward a special CA isoform. Accordingly, three novel sets of pyrano[2,3-c]pyrazoles attached with sulfonamide head and aryl hydrophobic tail were synthesized to enhance the selectivity toward a specific isoform of human carbonic anhydrases (hCAs). The impact of both attachments on the potency and selectivity has been extensively discussed in terms of in vitro cytotoxicity evaluation under hypoxic conditions, structure-activity relationship and carbonic anhydrase enzyme assay. All of the new candidates displayed good cytotoxic activities against breast and colorectal carcinomas. Results of the carbonic anhydrase enzyme assay demonstrated the preferential of compounds 22, 24 and 27 to inhibit the isoform IX of hCAs selectively. Wound-healing assay has also been performed and revealed the potential of 27 to decrease the wound closure percentage in MCF-7 cells. Molecular docking and molecular orbital analysis have finally been conducted. Results indicate the potential binding interactions of 24 and 27 with several crucial amino acids of the hCA IX.Communicated by Ramaswamy H. Sarma.

Incidence and Risk Factors for Retinal Detachment Following Cataract Surgery at a Tertiary Center in Jeddah, Saudi Arabia.

Introduction The incidence of retinal detachment in the general population is 0.08%, it has been reported to reach 0.7% or higher following cataract surgery. One of the most important risk factors for retinal detachment is posterior capsular rupture during cataract surgery. Additional risk factors include high myopia, history of ocular trauma, young age, male sex, and diabetes. In this study, we aimed to investigate the incidence and risk factors of retinal detachment following cataract surgery in patients treated at our hospital. Materials and methods This retrospective cohort study was conducted at King Abdulaziz University Hospital (KAUH), a tertiary center in Jeddah, Saudi Arabia. The medical records of 365 patients (365 eyes) who underwent cataract surgery from 2017 to 2021 were reviewed. Results The average age of the 365 patients was 63 years, and 47.7% (n=174) of patients were male. The incidence of retinal detachment was 3.3% (n=12). The risk of RD was 2.8 times higher for the right eye than for the left eye. The incidence of RD was significantly more in eyes with intraoperative posterior capsular rupture, zonular dehiscence, corneal trauma, and surgery combined with anterior vitrectomy than in other eyes. The most common complication of cataract surgery is corneal edema, which was observed in 22.7% of the eyes; our analysis revealed a significant relationship between corneal edema and the duration of surgery. Conclusion In our study, we highlighted the higher incidence of retinal detachment compared to those in other studies; most cases occurred one month postoperatively.

Ferula sinkiangensis (Chou-AWei, Chinese Ferula): Traditional Uses, Phytoconstituents, Biosynthesis, and Pharmacological Activities.

Ferula is the third largest genus of the Apiaceae family, its species are utilized as a remedy for diverse ailments all over the world. F. sinkiangensis K. M. Shen (Chou-AWei, Chinese Ferula) is mainly found in Xin-jiang Uygur Autonomous Region, China. Traditionally, it is utilized for treating various illnesses such as digestive disorders, rheumatoid arthritis, wound infection, baldness, bronchitis, ovarian cysts, intestinal worms, diarrhea, malaria, abdominal mass, cold, measles, and bronchitis. It can produce different classes of metabolites such as sesquiterpene coumarins, steroidal esters, lignans, phenylpropanoids, sesquiterpenes, monoterpenes, coumarins, organic acid glycosides, and sulfur-containing compounds with prominent bioactivities. The objective of this work is to point out the reported data on F. sinkiangensis, including traditional uses, phytoconstituents, biosynthesis, and bioactivities. In the current work, 194 metabolites were reported from F. sinkiangensis in the period from 1987 to the end of 2022. Nevertheless, future work should be directed to conduct in vivo, mechanistic, and clinical assessments of this plant`s metabolites to confirm its safe usage.

Tailoring and optimization of a honey-based nanoemulgel loaded with an itraconazole-thyme oil nanoemulsion for oral candidiasis.

The use of essential oil-based nanoemulsions (NEs) has been the subject of extensive research on a variety of conditions affecting the oral cavity. NEs are delivery methods that improve the solubility and distribution of lipid medicines to the intended areas. Because of their antibacterial and antifungal properties, itraconazole and thyme oil-based self-nanoemulsifying drug delivery systems (ItZ-ThO-SNEDDS) were created to protect oral health against oral microorganisms. The ItZ-ThO-SNEDDS were created utilizing an extreme verices mixture design, and varying concentrations of ThO (10% and 25%), labrasol (40% and 70%), and transcutol (20% and 40%) were used. The ItZ-ThO-SNEDDS had droplet sizes of less than 250 nm, a drug-loading efficiency of up to 64%, and a fungal growth inhibition zone of up to 20 mm. The accepted design was used to obtain the ideal formulation, which contained ThO in the amount of 0.18 g/ml, labrasol 0.62 g/ml, and transcutol 0.2 g/ml. The best ItZ-ThO-SNEDDS formulation was incorporated into a honey-based gel, which demonstrated improved release of ItZ in vitro and improved transbuccal permeation ex vivo. In addition, when compared with various formulations tested in rats, the optimized loaded emulgel decreased the ulcer index. This study therefore demonstrated that the ItZ-ThO-SNEDDS could offer an effective defense against oral diseases caused by microbial infections.

Secondary Psychosis Following Neoadjuvant AC-T Chemotherapy for Triple-Negative Breast Cancer: Case Report and Literature Review of Psychosis Postchemotherapy.

Triple-negative breast cancer is a unique subtype among breast cancers. Management includes a neoadjuvant chemotherapy regimen. Psychiatric complications of the regimen have not been reported before. We present a case of acute psychosis after the second cycle of chemotherapy in a 42-year-old woman with triple-negative breast cancer. The patient presented with sudden irritability, agitation, disorganization in speech and behavior, and paranoia involving her coworkers conspiring against her and causing her trouble with the law for 4 days. She was in her usual state of health until after her second cycle of chemotherapy. This was the first presentation of psychotic symptoms in her life. She was conscious and oriented. There were no neurologic deficits. She denied any change in her mood and any features of hallucinations. She was uncooperative, restless, had flight of ideas, and persecutory delusions. The remainder of the examination was normal. An autoimmune process, nervous system infection, or psychosis secondary to the chemotherapy were suspected. Serum electrolytes and other biochemical parameters were normal. Imaging of the brain showed no signs of acute brain insults or intracranial metastasis. Cerebrospinal fluid analysis and culture showed no abnormality or growth. The work-up revealed that neurologic, infectious, or autoimmune causes of her psychotic symptoms were less likely. Thus, a diagnosis of psychosis secondary to chemotherapy was considered. Treatment was with paliperidone, risperidone, clonazepam, and sertraline. Over the course of treatment, she showed substantial improvement and completed all of the chemotherapy sessions without adverse effects. In summary, we report a case of a patient whose initial chemotherapy course was complicated by psychosis. Since the neurotoxic and psychiatric effects of chemotherapeutics are not yet sufficiently elucidated, our case emphasizes that early signs of behavioral changes in patients receiving chemotherapy should trigger comprehensive psychiatric evaluation and monitoring of the patient's mental state.

Rapid oral transmucosal delivery of zaleplon-lavender oil utilizing self-nanoemulsifying lyophilized tablets technology: development, optimization and pharmacokinetic evaluation.

Based on the administration convenience, transmucosal buccal drug delivery allows special strength points over peroral routes for systemic delivery. It could achieve local or systemic effect and boost drugs' bioavailability for agents with first pass metabolism. The current study aimed to manufacture and optimize a lavender oil-based nanoemulsion loaded with zaleplon and incorporate it into fast-disintegrating tablets to promote its dissolution and oral bioavailability via oral mucosa. Zaleplon-loaded nanoemulsions were devised with various levels of lavender oil (10% to 25%), the surfactant Sorbeth-20 (35% to 65%), and the co-surfactant HCO-60 (20% to 40%); the extreme vertices mixture statistical design was adopted. The droplet size and drug-loading efficiency were the evaluated. The optimal formulation was transformed into self-nanoemulsified lyophilized tablets (ZP-LV-SNELTs), which were tested for their uniformity of content, friability, and disintegration time with in-vitro release. Finally, the pharmacokinetic parameters of the ZP-LV-SNELTs were determined and compared with those of marketed formulations. The optimal nanoemulsion had a droplet size of 87 nm and drug-loading capacity of 185 mg/mL. ZP-LV-SNELTs exhibited acceptable friability and weight uniformity and a short disintegration time. The in-vitro release of ZP-LV-SNELTs was 17 times faster than that of the marketed tablet. Moreover, the optimal ZP-LV-SNELTs increased the bioavailability of zaleplon in rabbits by 1.6-fold compared with the commercial tablets. Hence, this investigation revealed that ZP-LV-SNELTs delivered zaleplon with enhanced solubility, a fast release, and boosted bioavailability thru oral mucosa which provided a favorable route for drug administration which is suggested to be clinically investigated in future studies.

Mania as a Rare Adverse Event Secondary to Steroid Eye Drops.

Since glucocorticoids (GCs) were introduced for the treatment of various diseases, they have been linked with the development of psychiatric adverse effects such as mania, depression, and psychosis. These behavioral or psychiatric adverse events usually appear within a few days after commencing GCs and are possibly to reverse with drug withdrawal. We present a rare case of a 75-year-old woman who developed mania during treatment with GC eye drops following cataract surgery. Management consisted of discontinuing prednisolone and administering olanzapine, which resulted in full recovery in a week. Olanzapine was then discontinued, and a diagnosis of steroid-induced mania was concluded for this case.

Preparation and optimization of aloe ferox gel loaded with Finasteride-Oregano oil nanocubosomes for treatment of alopecia.

Alopecia areata is a skin disorder characterized by scarless, localized hair loss that is usually managed by topical treatments that might further worsen the condition. Therefore, the current study aimed to develop nano-cubosomes loaded with finasteride (FI) and oregano oil (Or) to improve drug solubility and permeation through skin and then incorporate it into an aloe ferox gel base. An l-optimal coordinate exchange design was adopted to optimize nano-cubosomes. Phytantriol and Alkyl Acrylate were employed as the lipid material, and surfactant respectively for cubosomes manufacture. The produced formulations were assessed for their particle size, entrapment efficiency (EE%), FI steady-state flux (Jss) and minimum inhibitory concentration (MIC) against Pro-pionibacterium acnes. Optimal FI-Or-NCu had a particle size of 135 nm, EE% equals 70%, Jss of 1.85 µg/cm2.h, and MIC of 0.44 µg/ml. The optimum formulation loaded gel gained the highest drug release percent and ex vivo skin permeation compared to FI aqueous suspension, and pure FI loaded gel. Aloe ferox and oregano oil in the optimized gel formulation had a synergistic activity on the FI permeation across the skin and against the growth of p. acne bacteria which could favor their use in treating alopecia. Thus, this investigation affirms the ability of FI-Or-NCu loaded aloe ferox gel could be an effective strategy that would enhance FI release and permeation through skin and maximize its favorable effects in treating alopecia.

Incidence of Medication Errors in King Fahad Hospital Madina Saudi Arabia

Abstract This study aimed to evaluate the incidence of medication errors over a period of one year in King Fahad Hospital Madina Saudi Arabia. This retrospective, cross-sectional study was conducted over a period of one year from 2018 January to 2018 December using patient's records. King Fahad Hospital in Madina was selected for the study center. Data collected include the number and types of errors, severity, location of errors, errors by profession, and errors occurred in the medical wards. Statistical analysis was carried out using statistical package for social science version22. A total of twenty- six hundred and fifty-eight medication errors were reported during the study period. Among the reports 2567(96.5%) of the errors were due to near misses, followed by transcribing errors 1597(60%), ordering errors 928(34.9%), duplicative therapy 765(28.7%), wrong dose 454(%). The most common procedures involve medication errors were wrong documentation 442(16.6%), duration 168(6.3%) wrong quantity 162(6.4%). Majority of the medication errors were contributed by physicians (99.2%) and 0.7% of them were due to the pharmacist. In conclusion study findings reported that yet some kind of medication errors has been under reported and it was common in most hospital, further studies with intervention programs needed to control the incidence of medication errors in a Saudi hospital

Preparation and Optimization of Garlic Oil/Apple Cider Vinegar Nanoemulsion Loaded with Minoxidil to Treat Alopecia.

Alopecia areata is a scarless, localized hair loss disorder that is typically treated with topical formulations that ultimately only further irritate the condition. Hence, the goal of this study was to develop a nanoemulsion with a base of garlic oil (GO) and apple cider vinegar (APCV) and loaded with minoxidil (MX) in order to enhance drug solubilization and permeation through skin. A distance coordinate exchange quadratic mixture design was used to optimize the proposed nanoemulsion. Span 20 and Tween 20 mixtures were used as the surfactant, and Transcutol was used as the co-surfactant. The developed formulations were characterized for their droplet size, minoxidil steady-state flux (MX Jss) and minimum inhibitory concentration (MIC) against Propionibacterium acnes. The optimized MX-GO-APCV nanoemulsion had a droplet size of 110 nm, MX Jss of 3 µg/cm2 h, and MIC of 0.275 µg/mL. The optimized formulation acquired the highest ex vivo skin permeation parameters compared to MX aqueous dispersion, and varying formulations lacked one or more components of the proposed nanoemulsion. GO and APCV in the optimized formulation had a synergistic, enhancing activity on the MX permeation across the skin membrane, and the percent permeated increased from 12.7% to 41.6%. Finally, the MX-GO-APCV nanoemulsion followed the Korsmeyer-Peppas model of diffusion, and the value of the release exponent (n) obtained for the formulations was found to be 1.0124, implying that the MX permeation followed Super case II transport. These results demonstrate that the MX-GO-APCV nanoemulsion formulation could be useful in promoting MX activity in treating alopecia areata.

Kinome Profiling Reveals Abnormal Activity of Kinases in Skeletal Muscle From Adults With Obesity and Insulin Resistance.

CONTEXT: Obesity-related insulin resistance (OIR) is one of the main contributors to type 2 diabetes and other metabolic diseases. Protein kinases are implicated in insulin signaling and glucose metabolism. Molecular mechanisms underlying OIR involving global kinase activities remain incompletely understood. OBJECTIVE: To investigate abnormal kinase activity associated with OIR in human skeletal muscle. DESIGN: Utilization of stable isotopic labeling-based quantitative proteomics combined with affinity-based active enzyme probes to profile in vivo kinase activity in skeletal muscle from lean control (Lean) and OIR participants. PARTICIPANTS: A total of 16 nondiabetic adults, 8 Lean and 8 with OIR, underwent hyperinsulinemic-euglycemic clamp with muscle biopsy. RESULTS: We identified the first active kinome, comprising 54 active protein kinases, in human skeletal muscle. The activities of 23 kinases were different in OIR muscle compared with Lean muscle (11 hyper- and 12 hypo-active), while their protein abundance was the same between the 2 groups. The activities of multiple kinases involved in adenosine monophosphate-activated protein kinase (AMPK) and p38 signaling were lower in OIR compared with Lean. On the contrary, multiple kinases in the c-Jun N-terminal kinase (JNK) signaling pathway exhibited higher activity in OIR vs Lean. The kinase-substrate-prediction based on experimental data further confirmed a potential downregulation of insulin signaling (eg, inhibited phosphorylation of insulin receptor substrate-1 and AKT1/2). CONCLUSIONS: These findings provide a global view of the kinome activity in OIR and Lean muscle, pinpoint novel specific impairment in kinase activities in signaling pathways important for skeletal muscle insulin resistance, and may provide potential drug targets (ie, abnormal kinase activities) to prevent and/or reverse skeletal muscle insulin resistance in humans.

Benchmarking a novel inorganic scintillation detector for applications in radiation therapy.

PURPOSE: The aim of this study was to investigate the contribution of Cerenkov radiation to the overall signal measured with a novel inorganic scintillating detector (ISD). METHODS: An ISD based on terbium doped gadolinium oxysulphide (Gd2O2S:Tb) was used. A hyperspectral technique separated the Cerenkov signal from the radioluminescence (RL) signal of the ISD. The relative contribution of Cerenkov radiation was evaluated under different conditions. The efficiency of using simple spectral correction to reduce the Cerenkov contribution was quantified. Other experiments investigated were the dose-per-pulse dependence observed in our previous study and the absorbed-dose energy dependence when acquiring percentage depth dose curves using Monte Carlo (MC) simulations. RESULTS: The maximum relative contribution of Cerenkov radiation was 2.10% for a 10 × 10 cm2 field at 10 cm depth. However, this percentage increased to 24% when the ISD was 7 cm out of field and exposed to a 10 × 10 cm2 field. Using 15 nm and 5 nm band-pass filters reduced the Cerenkov contribution across all experimental conditions by a maximum of 75% and 82%, respectively. The MC simulation results show discrepancies between the measured and simulated PDD profiles using the Gd2O2S:Tb scintillator at depth. CONCLUSION: This study showed that while Gd2O2S:Tb ISD provides high-signal intensity, the contribution of Cerenkov radiation under specific conditions can be significant. However, narrow band-pass filters can reduce the Cerenkov signal to a negligible level. The MC simulations suggest mechanisms other than the stem effect and the absorbed-dose energy dependence influence the response of the Gd2O2S:Tb scintillator measurements at depth.