Inappropriate Emergency Department Visits: Insights on Incidence, Associated, and Predictive Factors From 5,429 Visits.

INTRODUCTION: Inappropriate visits (IVs) and overcrowded emergency departments (EDs) can result in many complications for patients and medical staff. This study aimed to assess the incidence, associated factors, and predictive factors of IVs to ED. METHODS: This retrospective cohort single-center study was conducted in the ED of King Abdulaziz Medical City, Jeddah, Saudi Arabia. All ED visits in February 2023 were included. They were considered appropriate if the patient required investigation tests, underwent a procedure, was admitted to an inpatient ward, was admitted to the short-stay unit, was referred for follow-up at a specialist outpatient clinic after discharge from the ED, or was referred to the ED of another hospital. Failure to have at least one of these factors led to the visit being considered inappropriate. RESULTS: A total of 5,429 visits were included. The incidence rate of IVs was 1128 (20.7%). Of the visits, 1,028 (18.9%) were attended by patients aged <10 years, and 2,825 (52.0%) by female patients. The most reported complaints were pulmonological in 1,029 visits (18.9%). Patients with appropriate visits (AVs) had significantly higher median BMI scores than those with IVs (25.9 (20 - 3) vs. 23.7 (16.36 - 29), P = <0.0001). Visits with pulmonological (447 (39.6%) vs. 582 (13.5%)) and otorhinolaryngologic (54 (4.7%) vs. 94 (2.1%)) complaints were significantly more likely to be inappropriate (P = <0.0001). In multiple logistic regression, being a male (OR: 1.3, CI: 1.1 - 1.5, P = <0.0001), being non-Saudi (OR: 2.7, CI: 2.0 - 3.6, P = <0.0001), and visiting on the weekend (OR: 1.1, CI: 1.0 - 1.3, P = 0.0366) were significantly predictive of the visits being inappropriate. CONCLUSIONS: Our findings revealed a high incidence of IVs in the ED, with several factors predictive of IVs. Highlighting these factors can help minimize the incidence of IVs and, therefore, improve the quality of healthcare delivered to patients in need and their clinical outcomes.

The known and unknown about attention deficit hyperactivity disorder (ADHD) genetics: a special emphasis on Arab population.

Attention deficit hyperactivity disorder (ADHD) is a clinically and genetically heterogeneous neurodevelopmental syndrome characterized by behavioral appearances such as impulsivity, inattention, and hyperactivity. The prevalence of ADHD is high in childhood when compared to adults. ADHD has been significantly advanced by genetic research over the past 25 years. However, it is logically conceivable that both genetic and/or non-genetic factors, such as postnatal environmental and social influences, are associated with ADHD phenotype in Arab populations. While genetic influences are strongly linked with the etiology of ADHD, it remains obscure how consanguinity which is an underlying factor for many genetic diseases, contributes to ADHD subtypes. Arabian Gulf Nations have one the highest rates of consanguineous marriages, and consanguinity plays an important contributing factor in many genetic diseases that exist in higher percentages in Arabian Gulf Nations. Therefore, the current review aims to shed light on the genetic variants associated with ADHD subtypes in Arabian Gulf nations and Saudi Arabia in particular. It also focuses on the symptoms and the diagnosis of ADHD before turning to the neuropsychological pathways and subgroups of ADHD. The impact of a consanguinity-based understanding of the ADHD subtype will help to understand the genetic variability of the Arabian Gulf population in comparison with the other parts of the world and will provide novel information to develop new avenues for future research in ADHD.

Molecular Dynamical and Quantum Mechanical Exploration of the Site-Specific Dynamics of Cy3 Dimers Internally Linked to dsDNA.

Performing spectroscopic measurements on biomolecules labeled with fluorescent probes is a powerful approach to locating the molecular behavior and dynamics of large systems at specific sites within their local environments. The indocarbocyanine dye Cy3 has emerged as one of the most commonly used chromophores. The incorporation of Cy3 dimers into DNA enhances experimental resolution owing to the spectral characteristics influenced by the geometric orientation of excitonically coupled monomeric units. Various theoretical models and simulations have been utilized to aid in the interpretation of the experimental spectra. In this study, we employ all-atom molecular dynamics simulations to study the structural dynamics of Cy3 dimers internally linked to the dsDNA backbone. We used quantum mechanical calculations to derive insights from both the linear absorption spectra and the circular dichroism data. Furthermore, we explore potential limitations within a commonly used force field for cyanine dyes. The molecular dynamics simulations suggest the presence of four possible Cy3 dimeric populations. The spectral simulations on the four populations show one of them to agree better with the experimental signatures, suggesting it to be the dominant population. The relative orientation of Cy3 in this population compares very well with previous predictions from the Holstein-Frenkel Hamiltonian model.

Primary pulmonary mucosa-associated lymphoid tissue lymphoma with extensive lung involvement and negative autoimmune and inflammatory background: A case report and literature review.

Primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is a very rare presentation of MALT lymphoma. The presence of a completely negative autoimmune and inflammatory background makes it a real challenge and very rare presentation (probably the second reported case in the literature). We report a case of primary pulmonary MALT lymphoma with negative autoimmune background, demonstrating as multifocal bulky variceal masses causing significant clinical symptoms.

Cerebral microbleeds in acute ischemic stroke after intravenous thrombolysis and their impact on short term outcome of stroke.

OBJECTIVES: Strong evidence suggests the occurrence of cerebral microbleeds (CMBs) in 5-13% of stroke patients within the first week after stroke onset. The aim of this work was to study risk factors associated with occurrence of CMBs in patients with stroke who received intravenous thrombolysis, and to clarify their impact on the clinical outcome. METHODS: This prospective observational study was conducted on 61 acute ischemic stroke patients eligible for treatment with recombinant tissue plasminogen activator (rt-PA). Assessment of stroke-related neurologic deficit was done using National Institute of Health Stroke Scale (NIHSS). Assessment of stroke related disability after 3 months from stroke onset was done using Modified Rankin Scale (mRS). CMBs were detected by T2*-weighed gradient-recalled echo (T2*-GRE) and susceptibility-weighted imaging (SWI) magnetic resonance imaging (MRI) sequences. RESULTS: There was a statistically significant impact of age, mean arterial pressure (MAP) at stroke onset, history of hypertension (HTN), and white matter changes assessed by Fazekas scale on the occurrence of CMBs in the included stroke patients (P-value= 0.002, <0.001, <0.001, 0.008 respectively). There was no statistically significant difference between patients with favorable and those with unfavorable outcome regarding the total number of CMBs (P-value =0.542). There was also no statistically significant difference between patients who developed complications from rt-PA and those who didn't develop regarding the total number of CMBs (P-value =0.186). CONCLUSION: Cerebral microbleeds are more likely to occur in older stroke patients and in those who had high MAP at stroke onset, history of HTN, and white matter changes.

Supersolubilization and Amorphization of a Weakly Acidic Drug, Flurbiprofen, by applying Acid-Base supersolubilization (ABS) principle.

Improvement in drug solubility is a major challenge for developing pharmaceutical products. It was demonstrated earlier that aqueous solubilities of weakly basic drugs could be increased greatly by interaction with weak acids that would not form salts with the drugs, and the highly concentrated solutions thus produced converted to amorphous solids upon drying. The technique was called acid-base supersolubilization (ABS). The current investigation explored whether the ABS principle could also be applied to weakly acidic drugs. By taking flurbiprofen (pKa 4.09; free acid solubility 0.011 mg/mL) as the model weakly acidic drug and tromethamine, lysine, meglumine, and NaOH as bases, it was studied which of the bases would result in ABS. While in the presence of NaOH and tromethamine, flurbiprofen converted to salts having aqueous solubility of 11-19 mg/mL, the solubility increased to > 399 mg/mL with lysine and > 358 mg/mL with meglumine, producing supersolubilization. However, crystallization of lysine salt was observed with time, followed by some decrease in solubility after reaching maximum solubility with lysine. In contrast, the supersolubilization was maintained with meglumine, and no crystallization of meglumine salt was observed. Upon drying, flurbiprofen-meglumine solutions produced amorphous materials that dissolved rapidly and produced high drug concentrations in aqueous media. Thus, the ABS principle also applies to acidic drugs depending on the weak base used.

Dermatological conditions in the intensive care unit at a tertiary care hospital in Riyadh, Saudi Arabia.

OBJECTIVES: To evaluate the various skin conditions diagnosed in intensive care unit (ICU) patients. METHODS: This is a descriptive retrospective study of all adults, pediatric, and neonatal patients who were admitted to the ICU and had a dermatological manifestation during hospital stay or patients who had dermatological condition that requires ICU admission. All skin conditions were categorized and analyzed. RESULTS: A total of 344 ICU patients with 365 different dermatological conditions were included in the study. The age of patients ranged from less than 1-96 years, with a mean age of 43.6±30.1 years. Of the patients, 189 (54.9%) were males. The top 3 general disease categories observed were skin infections, inflammatory and autoimmune diseases, and drug reactions. The most commonly reported dermatological disorders included morbilliform drug eruption (6.8%), contact dermatitis (6.3%), vasculitis (5.5%), herpes zoster (4.6%), purpura due to thrombocytopenia (3.8%), dermatitis/eczema (3.8%), candidiasis (3.8%), infantile hemangioma (2.7%), unclassified drug reaction (2.5%), intertrigo (2.5%), and herpes simplex virus (2.5%). CONCLUSION: Dermatological disorders can occur at various levels of severity in the ICU. Skin infections, inflammatory and autoimmune diseases, and drug reactions were found to be the most prevalent conditions.

Anesthetic Management of a Patient With Wolff-Parkinson-White Syndrome Undergoing Gynecological Robotic Surgery.

Robotic surgery provides precision and safety for minimally invasive gynecological operations but introduces unique anesthetic challenges, especially for individuals with pre-existing conditions like Wolff-Parkinson-White (WPW) syndrome. This case report addresses the anesthetic management of a 32-year-old female with WPW syndrome undergoing a myomectomy. A thorough pre-operative evaluation, including an ECG, echocardiogram, and Holter monitoring, was performed to assess the anesthetic and cardiac risks. The patient was administered a combination of loco-regional and general anesthesia, with an emphasis on neuromuscular monitoring, antiarrhythmic preparedness, and pain management to effectively manage the complexities introduced by WPW syndrome and robotic surgery. The anesthetic protocol comprised premedication with midazolam, induction using sufentanil, propofol, and rocuronium, and maintenance with desflurane, along with techniques to mitigate the effects of pneumoperitoneum and Trendelenburg positioning. Employing these strategies, the surgery concluded successfully without any anesthetic or surgical complications. The patient experienced a rapid and complete awakening, achieved optimal pain control, and was able to mobilize early, leading to her discharge 24 hours post-surgery. This case demonstrates the essential nature of customized anesthetic management for patients with WPW syndrome undergoing robotic surgery. It underscores the necessity of an exhaustive pre-operative assessment, diligent intraoperative monitoring, and active postoperative care to ensure patient safety and promote swift recovery.

Long-Term Survival and Reintervention Following Thoracic Endovascular Aortic Repair in Blunt Traumatic Thoracic Aortic Injury: A Systematic Review and Meta-Analysis.

BACKGROUND: Blunt thoracic aortic injury (BTAI) represents one of the most devastating scenarios of vascular trauma. Different management strategies are available with varying clinical outcomes. However, thoracic endovascular aortic repair (TEVAR) has become the first-line option for most BTAI patients, mainly owing to its minimally invasive nature, yielding improved immediate results. This meta-analysis aims to investigate mortality, long-term survival, and reintervention following TEVAR in BTAI. MATERIAL AND METHODS: A systematic review conducted a comprehensive literature search on multiple electronic databases using strict search terms. Twenty-seven studies met the set inclusion/exclusion criteria. A proportional meta-analysis of extracted data was conducted using the Comprehensive Meta-Analysis Software, v.4. RESULTS: 1498 BTAI patients who underwent TEVAR were included. Using the SVS grading system, 2.6% of the population had Grade 1 injuries, 13.6% Grade 2, 62.2% Grade 3, 19.6% Grade 4, and 1.9% unspecific. All-cause mortality did not exceed 20% in all studies except one outlier with a 37% mortality rate. Using the random effects model, the pooled estimate of overall mortality was 12% (95% confidence interval [CI], 5.35-8.55%; I2 = 70.6%). This was 91% (95% CI, 88.6-93.2; I2 = 30.2%) at 6 months, 90.1% (95% CI, 86.7-92.3; I2 = 53.6%) at 1 year, 89.2% (95% CI, 85.2-91.8; I2 = 62.3%) at 2 years, and 88.1% (95% CI, 83.3-90.9; I2 = 69.6%) at 5 years. Moreover, the pooled estimate of reintervention was 6.4% (95% CI, 0.1-0.49%; I2 = 81.7%). CONCLUSIONS: Despite the high morbidity and mortality associated with BTAI, TEVAR has proven to be a safe and effective management strategy with favorable long-term survival and minimal need for reintervention. Nevertheless, diagnosis of BTAI requires a high index of suspicion with appropriate grading and prompt transfer to trauma centers with appropriate TEVAR facilities.

Carvedilol alleviates the detrimental effects of azathioprine on hepatic tissues in experimental rats: Focusing on redox system, inflammatory and apoptosis pathways.

PURPOSE: Drug-induced liver injury is becoming an increasingly important topic in drug research and clinical practice. Due to a lack of experimental animal models, predicting drug-induced liver injury in humans is challenging. Azathioprine (AZA) is a classical immunosuppressant with hepatotoxic adverse effects. The present study aimed to address the hepatoprotective effect of carvedilol (CAR) against AZA-induced hepatocellular injury via assessing redox-sensitive signals. METHOD: To achieve this purpose, rats were allocated into four groups: control, CAR only, AZA only, and CAR plus AZA groups. The induction of hepatic injury was induced by a single intraperitoneal injection of AZA at a dose of 50 mg/kg on the 6th day of the experiment. Each experimental protocol was approved and supervised by the Ethics Committee for Animal Experiments. RESULTS: The results of the present study revealed that CAR administration significantly diminished AZA-induced hepatic dysfunction, as evidenced by relief of hepatic function biomarkers and histopathological aberration induced by AZA injection. Besides, CAR restored oxidant/antioxidant balance as well as NRF2 expression. In addition, CAR suppressed inflammatory response induced by AZA challenge as evidenced by downregulation of TLR4, TNF-α, MPO, and eNOS/iNOS levels in hepatic tissue. Moreover, CAR recovered apoptotic/anti-apoptotic status by modulation of caspase-3/Bcl2 expression. CONCLUSION: Taken together, CAR protects against AZA-induced hepatic injury via antioxidant, anti-inflammatory, and anti-apoptotic activities. These findings revealed that CAR could be a good candidate for hepatic injury protection and can be added to AZA therapeutic regimen to reduce their adverse effect.

The Arabic Version of Compulsive Exercise Test among Saudi Population; Translation and Validation.

Compulsive exercise is a condition characterized by uncontrollable exercise behaviour that may lead to severe and harmful physical and psychological consequences. Indeed, compulsive exercise is among the early symptoms of eating disorders that may affect different age groups. Globally and among Arab countries, compulsive exercise is common, while the screening methods used to assess compulsive exercise are limited. Thus, the Compulsive Exercise Test (CET) has emerged as a tool to assess cognitive, behavioural, and emotional factors related to compulsive exercise. The CET is a self-report, Likert-type scale comprising five distinct subscales. The increase in the CET scores is more likely associated with worsened pathology. Since the Arab countries lack such an assessment tool, we aimed to translate the CET into Arabic, validate the translated version, confirm the factor structures, and assess the internal consistency of the different subscales. Herein, we used the forward-backward translation method as recommended by the World Health Organization (WHO). The overall validity index of the translated version showed a score higher than 0.78, while the scale-level content validity index based on the average calculating method (S-CVI/Ave) and the agreement method (S-CVI/UA) were 0.91 and 0.58, respectively. Moreover, we recruited 399 Arabs living in Saudi to measure the internal consistency, and the value of the substantive internal consistency with Cronbach's α was 0.81. Subsequently, four of the Arabic-CET subscales had substantive internal consistency with Cronbach's α values higher than or equal to 0.70. Furthermore, the exploratory factor analysis results supported the substantial use of the five-subscale model. Taken together, our study supports using the Arabic-CET version to measure exercise compulsiveness among Arabs.

Insights of early feeding regime supplemented with glutamine and various levels of omega-3 in broiler chickens: growth performance, muscle building, antioxidant capacity, intestinal barriers health and defense against mixed Eimeria spp infection.

Early nutritional management approach greatly impacts broilers' performance and resistance against coccidiosis. The current study explored the impact of post-hatch feeding with a combination of glutamine (Glut) and different levels of omega-3 on broiler chickens' growth performance, muscle building, intestinal barrier, antioxidant ability and protection against avian coccidiosis. A total of six hundred Cobb 500 was divided into six groups: first group (fed basal diet and unchallenged (control) and challenged (negative control, NC) groups were fed a basal diet without additives, and the other groups were infected with Eimeria spp and supplemented with 1.5% Glut alone or with three different levels of omega-3 (0.25, 0.5 and 1%) during the starter period. Notable improvement in body weight gain was observed in the group which fed basal diet supplemented with glut and 1% omega 3 even after coccidia infection (increased by 25% compared challenged group) while feed conversion ratio was restored to control. Myogeneis was enhanced in the group supplemented with Glut and omega-3 (upregulation of myogenin, MyoD, mechanistic target of rapamycin kinase and insulin like growth factor-1 and downregulating of myostatin genes). Groups supplemented with Glut and higher levels of omega-3 highly expressed occluding, mucin-2, junctional Adhesion Molecule 2, b-defensin-1 and cathelicidins-2 genes. Group fed 1% Glut + omega-3 showed an increased total antioxidant capacity and glutathione peroxidase and super oxide dismutase enzymes activities with reduced levels of malondialdehyde, reactive oxygen species and H2O2. Post-infection, dietary Glut and 1% omega-3 increased intestinal interleukin-10 (IL) and secretory immunoglobulin-A and serum lysozyme, while decreased the elevated inflammatory mediators comprising interleukin IL-6, tumor necrosis factor-alpha, nitric oxide (NO) and inducible NO synthase. Fecal oocyst excretion and lesions score severity were lowered in the group fed 1% Glut and omega 3. Based on these findings, dietary Glut and omega-3 supplementation augmented restored overall broilers' performance after coccidial challenge.

An overview of RAF kinases and their inhibitors (2019-2023).

Protein kinases (PKs) including RAF, perform a principal role in regulating countless cellular events such as cell growth, differentiation, and angiogenesis. Overexpression and mutation of RAF kinases are significant contributors to the development and spread of cancer. Therefore, RAF kinase inhibitors show promising outcomes as anti-cancer small molecules by suppressing the expression of RAF protein, blocking RAS/RAF interaction, or inhibiting RAF enzymes. Currently, there are insufficient reports about approving drugs with minimal degree of toxicity. Therefore, it is an urgent need to develop new RAF kinase inhibitors correlated with increased anticancer activity and lower cytotoxicity. This review outlines reported RAF kinase inhibitors for cancer treatment in patents and literature from 2019 to 2023. It highlights the available inhibitors by shedding light on their chemical structures, biochemical profiles, and current status. Additionally, we highlighted the hinge region-binding moiety of the reported compounds by showing the hydrogen bond patterns of representative inhibitors with the hinge region for each class. In recent years, RAF kinase inhibitors have gained considerable attention in cancer research and drug development due to their potential to be studied under clinical trials and their demonstration of various degrees of efficacy and safety profiles across different cancer types. However, addressing challenges related to drug resistance and safety represents a major avenue for the optimization and enhancement of RAF kinase inhibitors. Strategies to overcome such obstacles were discussed such as developing novel pan-RAF inhibitors, RAF dimer inhibitors, and combination treatments.

Intestinal Absorption Site-Guided Development and Evaluation of Oral Disintegrating Controlled Release Tablets of Mirabegron.

The aim was to employ site-dependent absorption of mirabegron (MB) as a guide for fabrication of oral disintegrating controlled release tablet (ODCRT) which undergoes instantaneous release of loading fraction followed by delayed release of the rest of MB. The goal was to release MB in a manner consistent with the chronobiology of overactive bladder (OAB) syndrome. In situ rabbit intestinal permeability of MB was adopted to assess absorption sites. MB was subjected to dry co-grinding with citric acid to develop the fast-dissolving fraction in the mouth. Delayed release fraction was formulated by ethanol-assisted co-processing with increasing proportions of Eudragit polymer (S100) as pH responsive polymer. The developed dry mixtures underwent thermal (DSC) and physical (X-ray diffraction) characterization, in addition to in vitro release behavior. Optimized fast dissolving and delayed release formulations were mixed with tablet excipient before compression in ODCRT which was assessed for release profile using continuous pH variation. MB underwent preferential permeation through ileum and colon. Co-grinding with citric acid provided co-amorphous powder with fast dissolution. Co-amorphization of MB with Eudragit S100 (1:5) showed pH-dependent release to release most of the dose at pH 7.4. The developed ODCRT released 43.5% of MB in the buccal environment and retained MB at acidic pH to start release at pH 7.4. The study successfully fabricated ODCRT guided by site-dependent absorption. The ODCRT instantaneously released loading fraction to support the patient after administration with delayed fraction to sustain the effect.

Lightweight attention mechanisms for EEG emotion recognition for brain computer interface.

BACKGROUND: In the realm of brain-computer interfaces (BCI), identifying emotions from electroencephalogram (EEG) data is a difficult endeavor because of the volume of data, the intricacy of the signals, and the several channels that make up the signals. NEW METHODS: Using dual-stream structure scaling and multiple attention mechanisms (LDMGEEG), a lightweight network is provided to maximize the accuracy and performance of EEG-based emotion identification. Reducing the number of computational parameters while maintaining the current level of classification accuracy is the aim. This network employs a symmetric dual-stream architecture to assess separately time-domain and frequency-domain spatio-temporal maps constructed using differential entropy features of EEG signals as inputs. RESULT: The experimental results show that after significantly lowering the number of parameters, the model achieved the best possible performance in the field, with a 95.18 % accuracy on the SEED dataset. COMPARISON WITH EXISTING METHODS: Moreover, it reduced the number of parameters by 98 % when compared to existing models. CONCLUSION: The proposed method distinct channel-time/frequency-space multiple attention and post-attention methods enhance the model's ability to aggregate features and result in lightweight performance.

Histopathological risk assessment in multisite epithelial dysplasia: A meta-analysis.

OBJECTIVE: Histopathological grading of oral epithelial dysplasia (OED) is the current standard for stratifying cancer progression risk but is associated with subjectivity and variability. This problem is not commonly seen regarding the grading of epithelial dysplasia in other sites. This systematic review aims to compare grading systems for oral, anal, penile, and cervical epithelial dysplasia to determine their predictive accuracy for recurrence and malignant transformation (MT) outcomes. METHODS: The review protocol was registered in PROSPERO (CRD42023403035) and was reported according to the PRISMA checklist. A comprehensive search was performed in the main databases and gray literature. The risk of bias in individual studies was analyzed using the Joanna Briggs Institute checklist for each study design. RESULTS: Forty-six studies were deemed eligible and included in this systematic review, of which 45 were included in the quantitative analysis. Meta-analysis revealed that the binary system demonstrated a higher predictive ability for MT/recurrence of OED compared to multilevel systems. Higher predictive accuracy of MT was also observed for binary grading systems in anal intraepithelial neoplasia. CONCLUSIONS: No significant difference was found between the current grading systems of epithelial dysplasia in different body parts. However, binary grading systems have shown better clinical outcomes.

CBCT Evaluation of Root Canal Morphology of Maxillary First Premolar in Saudi Subpopulation.

Background and Objective: Clinicians must possess a comprehensive understanding of variations in canal morphology and configuration during endodontic procedures to enhance treatment success. This study aims to assess and analyze the canal configurations of maxillary first premolars using Cone-Beam Computed Tomography within the sub-population of Western Saudi Arabia. Materials and Methods: In this cross-sectional study, following the acquisition of ethical clearance from Batterjee Medical College in Jeddah, Saudi Arabia, a retrospective examination of Cone-Beam Computed Tomography (CBCT) scans of maxillary first premolars in adult patients was conducted. The study focused on quantifying the number of canals and characterizing their configurations, with classification based on Vertucci's categorization. Results: The study examined 399 CBCT images of maxillary first premolars, revealing that type IV canal configurations were the predominant morphology (56.9%), followed by type V (24.6%). Significant gender-related disparities were observed, with females displaying a higher incidence of types I and V canals. At the same time, males exhibited a greater prevalence of types IV and VI canals. Notably, no substantial associations were discerned between canal types and age groups. Conclusion: Within the context of maxillary first premolars, type IV canal configuration emerged as the most prevalent. Gender-based distinctions were evident, with females predominantly presenting types I and V canal configurations, whereas males displayed a higher occurrence of types IV and VI canal configurations.

Design, synthesis, biological evaluation, and in silico studies of novel pyridopyridine derivatives as anticancer candidates targeting FMS kinase.

Design and synthesis of novel 4-carboxamidopyrido[3,2-b]pyridine derivatives as novel rigid analogues of sorafenib are reported herein. The target compounds showed potent antiproliferative activities against a panel of NCI-60 cancer cell lines as well as hepatocellular carcinoma cell line. Compounds 8g and 9f were among the most promising derivatives in terms of effectiveness and safety. Therefore, they were further examined to demonstrate their ability to induce apoptosis and alter cell cycle progression in hepatocellular carcinoma cells. The most potent compounds were tested against a panel of kinases that indicated their selectivity against FMS kinase. Compounds 8g and 8h showed the most potent activities against FMS kinase with IC50 values of 21.5 and 73.9 nM, respectively. The two compounds were also tested in NanoBRET assay to investigate their ability to inhibit FMS kinase in cells (IC50 = 563 nM (8g) and 1347 nM (8h) vs. IC50 = 1654 nM for sorafenib). Furthermore, compounds 8g and 8h possess potent inhibitory activities against macrophages when investigated in bone marrow-derived macrophages (BMDM) assay (IC50 = 56 nM and 167 nM, respectively, 164 nM for sorafenib). The safety and selectivity of these compounds were confirmed when tested against normal cell lines. Their safety profile was further confirmed using hERG assay. In silico studies were carried out to investigate their binding modes in the active site of FMS kinase, and to develop a QSAR model for these new motifs.

Imaging Modalities for Identifying Causes of Vocal Fold Paralysis: A Systematic Review and Meta-Analysis.

BACKGROUND: Vocal fold paralysis (VFP), involving one or both vocal folds, often indicates underlying pathologies. Identifying VFP causes is vital for excluding malignancies and focusing on treating the cause. While various imaging methods are used to investigate VFP causes, their detection abilities remain unclear. This study aims to assess the detection prevalence of different imaging techniques in determining the causes of VFP. METHODS: In September 2023 a comprehensive search was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines across multiple databases, including Web of Science, PubMed, Scopus, Cochrane CENTRAL, and EMBASE. Following the search, the retrieved studies were screened based on the predefined eligibility criteria. Data extraction from the included studies was carried out independently by two authors. Outcomes were analyzed using pooled proportions and 95% confidence intervals. RESULTS: Our meta-analysis encompassed 14 studies with 1492 VFP patients included. Malignant causes for VFP identification were most prevalent in F-fluorodeoxyglucose Positron Emission Tomography (PET)/Computed Tomography (CT) (41.5%) followed by Magnetic resonance imaging (MRI) (40%), with CT being the lowest (17.1%). Conversely, benign causes had the highest prevalence in F-fluorodeoxyglucose PET/CT (10.8%), followed by MRI (6.7%) and CT (4%). In the VFP cause identification, MRI had the highest detection prevalence (58.1%), followed by CT (30.1%), and Ultra Sound (US) had the lowest (26.8%). In chest lesion detection, CT had the highest prevalence (17.6%), followed by Chest X-ray (CXR) (6.5%). Head lesions were detected with CT at a prevalence of 15%, while neck lesion detection showed CT prevalence at 38.9% and US at 20.6%. CONCLUSION: Our study revealed varying prevalence rates for the identification of malignant and benign causes across different imaging modalities. MRI demonstrated the highest overall detection prevalence for VFP causes, while CT was most commonly used and had the highest prevalence for specific lesions detection in various regions. These findings provide valuable insights into the diagnostic utility of different imaging techniques in the evaluation of VFP.

Structural gonadal lesions observed in Japanese quail (Coturnix coturnix japonica) following exposure during puberty to the neonicotinoid pesticide, imidacloprid.

Exposure to the neonicotinoid insecticide, imidacloprid (IMI), causes reproductive toxicity in mammals and reptiles. However, reports on the effects of IMI on the gonads in birds are grossly lacking. Therefore, this study investigated the effects of pubertal exposure to IMI on the histology, ultrastructure, as well as the cytoskeletal proteins, desmin, smooth muscle actin and vimentin, of the gonads of Japanese quail (Coturnix coturnix japonica). Quails were randomly divided into four groups at 5 weeks of age. The control group was given only distilled water, whereas, the other three experimental groups, IMI was administered by oral gavage at 1.55, 3.1, and 6.2 mg/kg, twice per week for 4 weeks. Exposure to IMI doses of 3.1 and 6.2 mg/kg caused dose-dependent histopathological changes in the ovary and testis. In the ovary, accumulation of lymphocytes, degenerative changes, and necrosis with granulocyte infiltrations were observed, while in the testis, distorted seminiferous tubules, germ cell sloughing, vacuolisations, apoptotic bodies, autophagosomes, and mitochondrial damage were detected. These changes were accompanied by a decreased number of primary follicles (P ≤ 0.05) in the ovary and a decrease (P ≤ 0.05) in the epithelial height, luminal, and tubular diameters of seminiferous tubules at the two higher dosages. In addition, IMI had a negative effect on the immunostaining intensity of desmin, smooth muscle actin, and vimentin in the ovarian and testicular tissue. In conclusion, exposure to IMI during puberty can lead to a range of histopathological alterations in the gonads of Japanese quails, which may ultimately result in infertility.