An update on the development on tubulin inhibitors for the treatment of solid tumors.

INTRODUCTION: Microtubules play a vital role in cancer therapeutics. They are implicated in tumorigenesis, thus inhibiting tubulin polymerization in cancer cells, and have now become a significant target for anticancer drug development. A plethora of drug molecules has been crafted to influence microtubule dynamics and presently, numerous tubulin inhibitors are being investigated. This review discusses the recently developed inhibitors including natural products, and also examines the preclinical and clinical data of some potential molecules. AREA COVERED: The current review article summarizes the development of tubulin inhibitors while detailing their specific binding sites. It also discusses the newly designed inhibitors that may be useful in the treatment of solid tumors. EXPERT OPINION: Microtubules play a crucial role in cellular processes, especially in cancer therapy where inhibiting tubulin polymerization holds promise. Ongoing trials signify a commitment to revolutionizing cancer treatment and exploring targeted therapies. Challenges in microtubule modulation, like resistance and off-target effects, demand focused efforts, emphasizing combination therapies and personalized treatments. Beyond microtubules, promising avenues in cancer research include immunotherapy, genomic medicine, CRISPR gene editing, liquid biopsies, AI diagnostics, and stem cell therapy, showcasing a holistic approach for future advancements.

Do orthopaedics surgeons have any idea what predatory journals are?:(cross-sectional study).

Objective: The legitimacy of published research confronts a real challenge posed by predatory journals. These journals not only distribute inadequately written articles but also undermine the prospects of acknowledgment and citation for high-quality content. It is essential, nevertheless, to differentiate between predatory journals and reputable open-access ones. A worldwide anti-predatory movement seeks to enhance awareness about such journals. Hence, our objective was to assess the awareness, attitudes, and practices of Sudanese orthopedic surgeons concerning both predatory and open-access publishing. Methods: Conducted between January and April 2023, this cross-sectional electronic survey involved Sudanese orthopedic surgeons. The survey, comprising five domains to gauge knowledge, attitudes, and practices related to predatory and open-access publishing, was shared via the Sudanese Orthopedic Surgeons Association email distribution list among the 561 registered surgeons. The targeted sample size was 286. Categorical variables were reported using frequencies, while continuous variables were presented as medians and interquartile ranges. Nonparametric tests and ordinal regression were employed for inferential statistics. Results: Of the 561 surgeons, 104 participants completed the questionnaire, resulting in a response rate of 18.5 %. Approximately 49% exhibited poor knowledge, with 56% unfamiliar with the term "predatory journals," and 74% unaware of Beall's list. Overall attitudes toward publication in open-access and predatory journals were neutral for 60% of participants, and only 26% demonstrated good overall publication practices. Higher knowledge scores positively correlated with attitude and practice scores. Ordinal regression analysis identified variables such as employment in university hospitals, higher academic rank, publication experience, and working in well-resourced countries as factors increasing the likelihood of higher knowledge, attitude, and practice scores. Conclusion: The majority of the study participants reported very low knowledge of predatory journals and their possible detrimental consequences on the integrity and quality of scientific publications. Therefore, educational efforts on the negative impact of predatory publication practices in orthopedics are needed.

Hepatitis C Virus-Related One-Year Hepatocellular Carcinoma Recurrence After Directly Acting Antivirals: A Randomized Controlled Trial.

PURPOSE: Available data on hepatocellular carcinoma (HCC) recurrence after direct-acting antivirals (DAAs) treatment for hepatitis C virus (HCV) are conflicting. No randomized trials were done. This study aims to compare the 1-year HCC recurrence rates in patients who received DAAs after tumor ablation versus those who postponed HCV treatment for 1 year. METHODS: Included patients were randomized after complete HCC ablation into two groups: a postponed DAAs group for whom DAAs initiation was postponed for 12 months and a DAAs group who were given sofosbuvir/velpatasvir. Patients were followed for 1 year. RESULTS: Eighty-four HCV patients with a mean age of 56.35 ± 8.12 years were included; 78.57% of them were males. The number of lesions per patient ranged from 1 to 3 lesions, and the size of the largest lesion ranged from 1.5 to 5 cm. There were no statistically significant differences between both groups regarding baseline characteristics. In the DAAs group (43 patients), 11 patients had HCC recurrence, while 25 patients in the postponed DAAs group (41 patients) had HCC recurrence. Using Kaplan-Meier analysis, the 1-year recurrence-free survival (RFS) was significantly higher in the DAAs group (72.2% vs. 38%, P = 0.001). On multivariate analysis, both higher albumin levels (HR 0.147, 95% CI 0.066-0.329) and receiving DAAs (HR 0.358, 95% CI 0.176-0.730) 1 year after ablation were associated with significantly lower recurrence. CONCLUSION: Direct-acting antiviral usage after complete hepatocellular carcinoma ablation significantly decreases the 1-year HCC recurrence rates, but the risk of recurrence is still not eliminated. The study registration number on clinicaltrials.gov : NCT04653818 (initial release on 28/11/2020).

PI3K and tankyrase inhibitors as therapeutic targets in colorectal cancer.

INTRODUCTION: The pathways like Wingless-related integration (Wnt/ß-catenin) and PI3K play an important role in colorectal cancer (CRC) development; however, their roles are distinct in the process of oncogenesis. Despite their differences, these pathways interact through feedback mechanisms and regulate the common effectors both in the upstream and the downstream processes in normal and pathological conditions. Their ability to reciprocally control each other is a primary resistance mechanism for the selective inhibitors in CRC. AREA COVERED: This review highlights the Wnt/ß-catenin and PI3K pathways that are interrelated in CRC, recent advances and some key perspectives in developing inhibitors that could target the tankyrase enzyme and PI3K, apart from a brief description of the potential of dual inhibitors of PI3K and Tankyrases (TNKS). EXPERT OPINION: Recent research has focused on overcoming the challenges particularly relating to the resistance and efficacy of dual inhibitors targeting PI3K and tankyrase proteins. Despite these challenges, PI3K as well as tankyrases remain promising therapeutic targets for the treatment of solid tumors. The design of potent inhibitors is crucial to effectively block these protein signaling pathways. Moreover, it is essential to explore the potential of dual-target inhibition of other signaling pathways in conjunction with PI3K and tankyrase.

Titania/graphene nanocomposites from scalable gas-phase synthesis for high-capacity and high-stability sodium-ion battery anodes.

In sodium-ion batteries (SIBs), TiO2or sodium titanates are discussed as cost-effective anode material. The use of ultrafine TiO2particles overcomes the effect of intrinsically low electronic and ionic conductivity that otherwise limits the electrochemical performance and thus its Na-ion storage capacity. Especially, TiO2nanoparticles integrated in a highly conductive, large surface-area, and stable graphene matrix can achieve an exceptional electrochemical rate performance, durability, and increase in capacity. We report the direct and scalable gas-phase synthesis of TiO2and graphene and their subsequent self-assembly to produce TiO2/graphene nanocomposites (TiO2/Gr). Transmission electron microscopy shows that the TiO2nanoparticles are uniformly distributed on the surface of the graphene nanosheets. TiO2/Gr nanocomposites with graphene loadings of 20 and 30 wt% were tested as anode in SIBs. With the outstanding electronic conductivity enhancement and a synergistic Na-ion storage effect at the interface of TiO2nanoparticles and graphene, nanocomposites with 30 wt% graphene exhibited particularly good electrochemical performance with a reversible capacity of 281 mAh g-1at 0.1 C, compared to pristine TiO2nanoparticles (155 mAh g-1). Moreover, the composite showed excellent high-rate performance of 158 mAh g-1at 20 C and a reversible capacity of 154 mAh g-1after 500 cycles at 10 C. Cyclic voltammetry showed that the Na-ion storage is dominated by surface and TiO2/Gr interface processes rather than slow, diffusion-controlled intercalation, explaining its outstanding rate performance. The synthesis route of these high-performing nanocomposites provides a highly promising strategy for the scalable production of advanced nanomaterials for SIBs.

Unveiling the Potential of Cannabinoids in Multiple Sclerosis and the Dawn of Nano-Cannabinoid Medicine.

Multiple sclerosis is the predominant autoimmune disorder affecting the central nervous system in adolescents and adults. Specific treatments are categorized as disease-modifying, whereas others are symptomatic treatments to alleviate painful symptoms. Currently, no singular conventional therapy is universally effective for all patients across all stages of the illness. Nevertheless, cannabinoids exhibit significant promise in their capacity for neuroprotection, anti-inflammation, and immunosuppression. This review will examine the traditional treatment for multiple sclerosis, the increasing interest in using cannabis as a treatment method, its role in protecting the nervous system and regulating the immune system, commercially available therapeutic cannabinoids, and the emerging use of cannabis in nanomedicine. In conclusion, cannabinoids exhibit potential as a disease-modifying treatment rather than merely symptomatic relief. However, further research is necessary to unveil their role and establish the safety and advancements in nano-cannabinoid medicine, offering the potential for reduced toxicity and fewer adverse effects, thereby maximizing the benefits of cannabinoids.

Habitat suitability modelling of Koklass pheasant (Pucrasia macrolopha) in moist temperate forest.

The decreasing status of on IUCN of Koklass pheasant (Pucrasia macrolopha) belongs to the family Phasianidae and the order Galliform needs the attention of researchers. The species with habitats as low as 6,000 feet and as high as 11,000 feet certainly cover a broad variety of habitats, such a wide altitude range embraces a diverse range of habitats. Insufficient research has been conducted on the suitability of moist temperate forests as a potential habitat for the Koklass pheasant. Therefore, this study was carried out to explore habitat suitability in 15 different sites which were located in the 4 districts of Hazara Division using GIS data science and environmental variables. A random sampling technique was used for laying out the transect. Overall, 45 line transects (Length 2-4 km, Width 10-30 m) were laid out in study sites. The size of sample plots for trees was 10x10m, for shrubs (4 x4m), and herbs and grasses 1x1m. The other habitat parameters like elevation, slope, cover, and frequency of plant at each point were also considered. We found the uneven distribution of Koklass pheasant in the Hazara Division. There were 59 occurrence points identified and highlighted the distribution of Koklass pheasant in the study area. Although all environmental variables were preferred by Koklass pheasant in its habitat statistical analysis proved that slope, level of disturbance, tree and shrub frequency of habitat contributed mostly to the presence of Koklass in each study site except the contribution of soil and herbs. The potential suitable habitat of Koklass pheasant was estimated to be 439.6 km2 areas starting from Abbottabad to Mansehra in the Hazara division. Awareness and enforcing legal protection are recommended for the conservation of Koklass Pheasant in Moist temperate forest.

ß2-Adrenergic receptor agonists as a treatment for diabetic kidney disease.

We have previously shown that the long-acting ß2-adrenergic receptor (ß2-AR) agonist formoterol induced recovery from acute kidney injury in mice. To determine whether formoterol protected against diabetic nephropathy, the most common cause of end-stage kidney disease (ESKD), we used a high-fat diet (HFD), a murine type 2 diabetes model, and streptozotocin, a murine type 1 diabetes model. Following formoterol treatment, there was a marked recovery from and reversal of diabetic nephropathy in HFD mice compared with those treated with vehicle alone at the ultrastructural, histological, and functional levels. Similar results were seen after formoterol treatment in mice receiving streptozotocin. To investigate effects in humans, we performed a competing risk regression analysis with death as a competing risk to examine the association between Veterans with chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD), who use ß2-AR agonists, and Veterans with CKD but no COPD, and progression to ESKD in a large national cohort of Veterans with stage 4 CKD between 2011 and 2013. Veterans were followed until 2016 or death. ESKD was defined as the initiation of dialysis and/or receipt of kidney transplant. We found that COPD was associated with a 25.6% reduction in progression from stage 4 CKD to ESKD compared with no COPD after adjusting for age, diabetes, sex, race-ethnicity, comorbidities, and medication use. Sensitivity analysis showed a 33.2% reduction in ESKD in Veterans with COPD taking long-acting formoterol and a 20.8% reduction in ESKD in Veterans taking other ß2-AR agonists compared with those with no COPD. These data indicate that ß2-AR agonists, especially formoterol, could be a treatment for diabetic nephropathy and perhaps other forms of CKD.NEW & NOTEWORTHY Diabetic nephropathy is the most common cause of ESKD. Formoterol, a long-acting ß2-adrenergic receptor (ß2-AR) agonist, reversed diabetic nephropathy in murine models of type 1 and 2 diabetes. In humans, there was an association with protection from progression of CKD in patients with COPD, by means of ß2-AR agonist intake, compared with those without COPD. These data indicate that ß2-AR agonists, especially formoterol, could be a new treatment for diabetic nephropathy and other forms of CKD.

The Effect of High Parity on the Occurrence of Anaemia in Pregnant Women.

OBJECTIVE: To compare high-para and low-para women with respect to haematological findings, determinants, and consequences secondary to anaemia. STUDY DESIGN: Descriptive cohort study. Place and Duration of the Study: Maternity and Child Hospital, Hail, Saudi Arabia and Specialist Care Hospital (private), Islamabad, Pakistan, from April 2022 to April 2023. METHODOLOGY: The study population comprised of pregnant women in the last trimester, with the exception of those women who had more than one fetus and history of haematological disease. Purposive non-probability sampling technique was adopted. Hospital data were retrieved retrospectively for the past obstetrical, contraception usage, and supplement history. Blood parameters, type of delivery, and maternofetal complications were noted down. For qualitative-variable and quantitative-variable comparisons, Chi-square test and t-test were applied, respectively. Significance level was kept at p ≤0.05. RESULTS: The frequency of severe anaemia in high-para was 52%. High parity and anaemia had a significant dose-response relationship (p <0.05). There was a significant difference (p <0.05) in blood parameters between high-para and low-para groups. Main determinants identified for anaemia were lack of intake of iron-rich food (36%) followed by inadequate intake of oral iron (25%). Preterm birth (68%) and post-partum haemorrhage (96%) were significantly associated (p <0.05) with high parity. There was a significantly high proportion (83%) of high-para women with more than 3 cesarean deliveries and admissions in ICU. CONCLUSION: High parity and anaemia had a significant dose-response relationship. High parity was the main determinant of maternal and fetal admissions in ICU. KEY WORDS: Parity, Comparison, Maternal anaemia, Haematological findings, Diet, Contraception, Cost-effective.

Effects of Dietary Microbial Muramidase on the Growth, Liver Histoarchitecture, Antioxidant Status, and Immunoexpression of Pro-Inflammatory Cytokines in Broiler Chickens.

The impact of microbial muramidase (MMUR) addition to broiler chicken rations was evaluated through growth parameters, liver histoarchitecture, antioxidant status, biochemical analysis, and expression of pro-inflammatory cytokines for 35 days. Four hundred three-day-old chicks (97.68 ± 0.59 g) were distributed to four distinct groups with ten duplicates each (100 chicks/group) consisting of: group 1 (G1): a basal diet without MMUR (control group); G2: a basal diet + 200 mg MMUR kg-1 G3: a basal diet + 400 mg MMUR kg-1; and G4: a basal diet + 600 mg MMUR kg-1. The results showed that the final body weight and total weight gain were increased (p = 0.015) in birds fed with diets supplemented with MMUR at 600 mg kg-1. The feed conversion ratio (FCR) was improved in all treatment groups compared with the control group. Birds fed with a diet supplemented with 600 mg MMUR kg-1 showed the highest body weight gain and improved FCR. The values of thyroxin hormones and growth hormones were increased in all MMUR-supplemented groups. Dietary MMUR increased the activities of antioxidant enzymes (total antioxidant activity, catalase, and superoxide dismutase) and decreased the activity of malondialdehyde (p < 0.05). In addition, it increased the values of interleukin 1 beta and interferon-gamma compared with the control group. Furthermore, dietary MMUR increased the expression of transforming growth factor-beta immunostaining in the liver and spleen tissues. Our results show that supplementing broilers' diets with 600 mg MMUR kg-1 could enhance the chicken growth rate and improve their antioxidant, inflammatory, and anti-inflammatory responses.

Prospects of Topoisomerase Inhibitors as Promising Anti-Cancer Agents.

Topoisomerases are very important enzymes that regulate DNA topology and are vital for biological actions like DNA replication, transcription, and repair. The emergence and spread of cancer has been intimately associated with topoisomerase dysregulation. Topoisomerase inhibitors have consequently become potential anti-cancer medications because of their ability to obstruct the normal function of these enzymes, which leads to DNA damage and subsequently causes cell death. This review emphasizes the importance of topoisomerase inhibitors as marketed, clinical and preclinical anti-cancer medications. In the present review, various types of topoisomerase inhibitors and their mechanisms of action have been discussed. Topoisomerase I inhibitors, which include irinotecan and topotecan, are agents that interact with the DNA-topoisomerase I complex and avert resealing of the DNA. The accretion of DNA breaks leads to the inhibition of DNA replication and cell death. On the other hand, topoisomerase II inhibitors like etoposide and teniposide, function by cleaving the DNA-topoisomerase II complex thereby effectively impeding the release of double-strand DNA breaks. Moreover, the recent advances in exploring the therapeutic efficacy, toxicity, and MDR (multidrug resistance) issues of new topoisomerase inhibitors have been reviewed in the present review.

Transhepatic ultrasound guided embolization as a successful novel technique in treatment of pediatric complex intrahepatic arterioportal fistula: a case report and review of the literature.

INTRODUCTION: Intrahepatic vascular shunts "IHVS" are abnormal communications between intra-hepatic vasculature involving the arterial, portal, or hepatic venous system. Arterio-portal fistula "APF" is an intrahepatic communication between the hepatic arterial system and the portal venous system without any communication with the systemic venous circulation. APF is considered a rare cause of portal hypertension and gastrointestinal bleeding in infancy. CASE PRESENTATION: A 3-month-old Mediterranean female with known cardiac congenital anomalies presented to us with abdominal distension and diarrhea. Ultrasonography revealed massive ascites and computerized tomography (CT) abdomen with intravenous (IV) contrast revealed a left hepatic lesion. On further evaluation, an intrahepatic arterio-portal vascular malformation was detected. Attempted trans arterial embolization failed and radiology team successfully carried out direct trans hepatic ultrasound guided coiling of the aneurysmal venous sac followed by successful resection of segment 4 of the liver with the vascular malformation avoiding life threatening intra operative bleeding. CONCLUSION: Any child with recurrent gastrointestinal bleeding, failure to thrive, vomiting, diarrhea, steatorrhea, splenomegaly, or ascites should be investigated for intrahepatic arterio-portal fistula "IAPF". Our novel technique of direct trans hepatic ultrasound guided coiling is an alternative method if trans arterial embolization "TAE" failed.

Comparison between bupivacaine injection and mini-tenotomy in the management of horizontal small angle strabismus in children.

PURPOSE: To compare the outcome of bupivacaine (BUP) injection vs mini-tenotomy of extra-ocular muscles in treating small angle horizontal strabismus in children. METHODS: A prospective comparative study that included a total of 40 patients. Twenty patients received 3 ml of 0.75% Bupivacaine (BUP) injection in both medial recti in case of exotropia and in both lateral recti in case of esotropia. MRI orbit was performed before and 30-60 days' post injection of bupivacaine to estimate changes in muscle size. Mini-tenotomy was done in the other 20 patients, performed on both lateral recti in case of exotropia and on both medial recti in case of esotropia. RESULTS: Mean change of alignment at the end of 6 months in exotropic patients in bupivacaine group was 5.50 ± 4.10 PD and in esotropia patients 4.00 ± 3.38 PD with an average increase in muscle thickness of 0.12 mm ± 0.08 and 0.13 mm ± 0.09 in exotropia and esotropia, respectively. There was an average increase in volume 23 mm3 ± 17.3 and 17.00 mm3 ± 9.50 in exotropia and esotropia, respectively, as measured with MRI. The mean change of alignment in mini-tenotomy was 5.33 ± 4.12 PD, 5.75 ± 4.95 PD in exotropia and esotropia, respectively. CONCLUSION: Bupivacaine and mini-tenotomy are safe and effective alternative treatment, that improved eye alignment in 65% of patients with small angle horizontal deviation.

Application of a life table approach to assess duration of BNT162b2 vaccine-derived immunity by age using COVID-19 case surveillance data during the Omicron variant period.

BACKGROUND: SARS-CoV-2 Omicron variants have the potential to impact vaccine effectiveness and duration of vaccine-derived immunity. We analyzed U.S. multi-jurisdictional COVID-19 vaccine breakthrough surveillance data to examine potential waning of protection against SARS-CoV-2 infection for the Pfizer-BioNTech (BNT162b) primary vaccination series by age. METHODS: Weekly numbers of SARS-CoV-2 infections during January 16, 2022-May 28, 2022 were analyzed by age group from 22 U.S. jurisdictions that routinely linked COVID-19 case surveillance and immunization data. A life table approach incorporating line-listed and aggregated COVID-19 case datasets with vaccine administration and U.S. Census data was used to estimate hazard rates of SARS-CoV-2 infections, hazard rate ratios (HRR) and percent reductions in hazard rate comparing unvaccinated people to people vaccinated with a Pfizer-BioNTech primary series only, by age group and time since vaccination. RESULTS: The percent reduction in hazard rates for persons 2 weeks after vaccination with a Pfizer-BioNTech primary series compared with unvaccinated persons was lowest among children aged 5-11 years at 35.5% (95% CI: 33.3%, 37.6%) compared to the older age groups, which ranged from 68.7%-89.6%. By 19 weeks after vaccination, all age groups showed decreases in the percent reduction in the hazard rates compared with unvaccinated people; with the largest declines observed among those aged 5-11 and 12-17 years and more modest declines observed among those 18 years and older. CONCLUSIONS: The decline in vaccine protection against SARS-CoV-2 infection observed in this study is consistent with other studies and demonstrates that national case surveillance data were useful for assessing early signals in age-specific waning of vaccine protection during the initial period of SARS-CoV-2 Omicron variant predominance. The potential for waning immunity during the Omicron period emphasizes the importance of continued monitoring and consideration of optimal timing and provision of booster doses in the future.

Multicomponent Domino Reaction for Concise Access to 2-Amino-Substituted 1,3,4 Oxadiazoles via Smiles Rearrangement.

A multicomponent domino reaction has been developed for the preparation of N-substituted 2-amino-1,3,4-oxadiazoles directly from various hydrazides (32 examples). The formation of 2-amino-1,3,4-oxadiazole involves the Smiles rearrangement of thiazolidinone, which results in the formation of carbodiimide intermediate that concomitantly undergoes amide-imidic acid tautomerism followed by cyclization. The protocol developed has wide applicability and provides the desired 2-amino-1,3,4-oxadiazole in excellent yields. The GSD studies of NMR spectra of aliphatic substrates (4di, 4dh) revealed the formation of three products, whereas, in the case of allylic and benzylic substrates, thiazolidinones were obtained as the sole products. Furthermore, to elucidate the plausible mechanism, DFT studies were performed affirming carbodiimide as the crucial intermediate for the interconversion of thiazolidinone to oxadiazole.

A Multicenter Experience of Inducible Clindamycin Resistance in Staphylococcus aureus Infection among 800 Egyptian Patients with or without Diabetes Mellitus.

Staphylococcus aureus causes a wide range of illnesses, from skin infections and persistent bone infections to life-threatening septicemia and endocarditis. Methicillin-resistant S. aureus (MRSA) is one of the most common bacteria that cause nosocomial and community-acquired infections. Clindamycin is one of the most effective treatments for several bacterial infections. Despite this, these infections may develop inducible clindamycin resistance during treatment, leading to treatment failure. This study determined the incidence of inducible clindamycin resistance among S. aureus clinical isolates. A total of 800 S. aureus strains were identified from clinical samples collected from several university hospitals in Egypt. All isolates were examined for the presence of MRSA using cefoxitin (30 µg) and the Kirby Bauer disk diffusion technique. The induction phenotypes of all 800 S. aureus strains were evaluated using the disk approximation test (D test), as recommended by the Clinical and Laboratory Standard Institute. Of the 800 strains of S. aureus, 540 (67.5%) were identified as MRSA and 260 (32.5%) were classified as methicillin-sensitive S. aureus (MSSA). In MRSA infections, clindamycin constitutive and inducible resistance was more frequent than in MSSA infections (27.8% versus 11.5% and 38.9% versus 15.4%, respectively). Clindamycin-sensitive strains were more prevalent in MSSA (53.8%) than in MRSA (20.4%) infections. In conclusion, the frequency of constitutive and inducible clindamycin resistance in MRSA isolates emphasizes the need to use the D test in routine antimicrobial susceptibility testing to evaluate clindamycin susceptibility, as the inducible resistance phenotype can inhibit the action of clindamycin and thus affect treatment efficacy.

The Role of Methylene Blue Spray to Keep Parathyroid Gland and Recurrent Laryngeal Nerve Safe During Thyroidectomy.

Background: The main postoperative complications of thyroidectomy are hypoparathyroidism and recurrent laryngeal nerve (RLN) palsy. Methylene blue, which is a drug and dye, is safe and easy to get, and we can use it to avoid complications during thyroidectomy. Objectives: We aim to assess that we can spray Methylene blue to allow the identification of important structures intraoperative which are the parathyroid gland and recurrent laryngeal nerve. Also, to evaluate that this technique is safe, effective, technically feasible, and less dangerous than other techniques. Methods: Our study is a prospective cohort study of patients, patients who presented with simple nodular goiter, solitary thyroid nodule, controlled toxic goiter, and failed medical treatment with the indication for thyroidectomy, suspected malignancy, and retrosternal goiters at El-Demerdash Hospital from the period of August 2021 to August 2022. In the specified study period of 1 year from 1/8/2021 to 31/7/2022. Results: Sixty patients underwent thyroidectomy 54 underwent total while 6 only underwent hemithyroidectomy. The time taken to wash out the dye over the thyroid gland was 15 to 25 minutes, the parathyroid gland was 4 to 7 minutes and the recurrent laryngeal nerve (RLN) was almost 0 to 1 minute and this indicated that the RLN almost did not take the dye. In the controlled group, two patients had symptoms and signs of hypocalcemia only one of them had signs of tetany, 8 patients had laboratory hypocalcemia, two patients suffered from a change of voice and another two patients suffered difficulty breathing one of which needed temporary tracheostomy while in the interventional group, only one patient had symptoms and signs of hypocalcemia no one had signs of tetany, two patients had laboratory hypocalcemia, one patient suffered from the change of voice and another two patients suffered the difficulty of breathing but no one needed a tracheostomy tube. Conclusions: It is safe, useful, and suitable to use Methylene blue spraying to keep the parathyroid gland and RLN during thyroidectomy, which led us to reduce the percentage of incidence of postoperative complications. Also, it helped us to find the parathyroid gland and RLN during the surgery, despite some surgeons seeing that searching for the parathyroid and RLN can lead to harmful effects and increase the incidence of injury.

Susceptibility patterns and virulence genotypes of Helicobacter pylori affecting eradication therapy outcomes among Egyptian patients with gastroduodenal diseases.

BACKGROUND: Helicobacter pylori (H. pylori) is a significant human pathogen that is responsible for a variety of illnesses, including mucosa-associated lymphoid tissue lymphoma, gastric cancer, peptic ulcers, and gastritis. AIM: To investigate the frequency of H. pylori infection and its resistance patterns among Egyptian patients and to determine the influence of H. pylori virulence genetic determinants on the eradication success of 14-d triple therapy regimen. METHODS: H. pylori infections were investigated in 72 patients with gastroduodenal complications suggestive of H. pylori infection. The cagA and vacA genotypes of cultured strains were studied using polymerase chain reaction. The patients underwent 14 d of triple-therapy treatment. The treatment response was examined using histology and a rapid urease test 6 wk after therapy discontinuation. RESULTS: The intention-to-treat eradication rate was 59.2% (95%CI: 48.2%-70.3%). Rates of H. pylori resistance to clarithromycin, amoxicillin, and metronidazole were 52.8%, 81.9%, and 100%, respectively. Successful eradication of H. pylori was more significantly associated with vacA s1-positive strains [adjusted odds ratio (aOR) = 0.507, 95%CI: 0.175-0.822]. A significant association was found between failed eradication rate and H. pylori strains resistant to clarithromycin (aOR = 0.204, 95%CI: -0.005 to 0.412) and amoxicillin (aOR = 0.223, 95%CI: 0.026-0.537). CONCLUSION: This study's low H. pylori eradication rate following 14-d triple therapy is concerning and worrying. H. pylori pan-resistance to metronidazole followed by the high resistance to ciprofloxacin, amoxicillin, and clarithromycin in this research is challenging and of great concern.

Artificial intelligence in orthopedics: A qualitative exploration of the surgeon perspective.

Artificial intelligence (AI) is currently integrated into many medical services. AI is utilized in many aspects of orthopedic surgery. The scope ranges from diagnosis to complex surgery. To evaluate the perceptions, attitudes, and interests of Sudanese orthopedic surgeons regarding the different applications of AI in orthopedic surgery. This qualitative questionnaire-based study was conducted through an anonymous electronic survey using Google Forms distributed among Sudanese orthopedic surgeons. The questionnaire entailed 4 sections. The first section included the participants' demographic data. The remaining 3 sections included questions for the assessment of the perception, attitude, and interest of surgeons toward (AI). The validity and reliability of the questionnaire were tested and piloted before the final dissemination. One hundred twenty-nine surgeons responded to the questionnaires. Most respondents needed to be more aware of the basic concepts of AI. However, most respondents were aware of its use in spinal and joint replacement surgeries. Most respondents had doubts regarding the safety of (AI). However, they were highly interested in utilizing (AI) in many orthopedic surgical aspects. Orthopedic surgery is a rapidly evolving branch of surgery that involves adoption of new technologies. Therefore, orthopedic surgeons should be encouraged to enroll in research activities to generate more studies and reviews to assess the usefulness and safety of emerging technologies.

Long non-coding RNAs BACE1-AS and BC200 in multiple sclerosis and their relation to cognitive function: A gene expression analysis.

Cognitive impairment is a common and debilitating feature of multiple sclerosis (MS), and the dysregulation of synaptic plasticity is one of its direct causes. Long non-coding RNAs (lncRNAs) have been shown to play a role in synaptic plasticity, but their role in cognitive impairment in MS has not been fully explored. In this study, using quantitative real-time PCR, we examined the relative expression of two specific lncRNAs, BACE1-AS and BC200, in the serum of two cohorts of MS patients with and without cognitive impairment. Both lncRNAs were overexpressed in both cognitively impaired and non-cognitively impaired MS patients, with consistently higher levels in the cohort with cognitive impairment. We also found a strong positive correlation between the expression levels of these two lncRNAs. Notably, BACE1-AS was consistently higher in the remitting cases of both relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) groups than in the respective relapse cases of the same subtype, with the SPMS-Remitting group of cognitively impaired MS patients showing the highest expression of BACE1-AS among all MS groups. Additionally, we observed that the primary progressive MS (PPMS) group had the highest expression of BC200 in both cohorts of MS. Furthermore, we developed a model called Neuro_Lnc-2, which showed better diagnostic performance than either BACE1-AS or BC200 alone in predicting MS. Our findings suggest that these two lncRNAs may have a significant impact on the pathogenesis of the progressive types of MS and on the cognitive function of the patients. Future research is required to confirm these findings.