Awareness of Current Surgical Practice for Congenital Scoliosis and Optimal Timing of Treatment Among Physicians and Patients' Families in Saudi Arabia.

BACKGROUND: Congenital scoliosis (CS) is a developmental spinal deformity characterized by an abnormal curvature of the spine, affecting one in 1,000 births. The mainstay of treatment involves either observation or surgery in significant curve progression. The optimal timing of surgical intervention is debated, with early intervention preferred. Therefore, understanding physicians' and patients' families' perspectives is crucial for optimizing surgical outcomes in CS. OBJECTIVE: To assess the awareness and knowledge of physicians and patients' families regarding current, as well as new surgical practices and the optimal timing of treatment for CS. METHODS: A cross-sectional study was conducted in Saudi Arabia using an online self-administered questionnaire distributed through social media platforms and neurosurgery clinics. Levels of awareness were assessed by a knowledge-scoring system. RESULTS: The study involved 403 participants, primarily patients' families (85.1%, N = 343) and physicians (14.9%, N = 60). The results show that physicians had a significantly higher correct response than patients' families regarding the ideal age for surgical correction of CS, the timing of surgical intervention whether before or after maturity, and the role of conservative management, as evident from statistically significant p-values of <0.001, 0.031, and <0.001, respectively. On the contrary, patients' families excelled in understanding interventions irrespective of symptomatic status if Cobb's angle is 40 degrees or above, with a statistically significant p-value of 0.031. Both groups exhibited a good level of overall knowledge, as evidenced by mean awareness scores of 12.18 and 11.64, respectively. Additionally, physicians had a statistically significant higher level of awareness compared to patients' families, with a p-value of (0.014). However, both groups demonstrated poor knowledge of the latest techniques, including distraction-based magnetically controlled growing rods (MCGRs), growth-guided modern Luque trolleys, and posterior dynamic deformity correction (ApiFix). CONCLUSION: The mean awareness score of both physicians and patients' families indicates a good level of knowledge. However, both groups exhibited poor knowledge in relation to the optimal timing of treatment and new surgical techniques.

A Comparative Analysis of Botulinum Toxin Use Versus Other Therapies for Temporomandibular Disorders: A Systematic Review.

Existing literature regarding the efficacy of Botulinum toxin A (BoNT-A) therapy in improving the clinical outcomes of temporomandibular disorders (TMDs) is ambiguous and lacks consistency. Thus, this study aimed to evaluate the efficacy of BoNT-A in reducing pain, occlusal force, electromyographic (EMG) changes, and maximum mouth opening compared with placebo and other interventions. An electronic database search was conducted using MEDLINE, PubMed, Google Scholar, the Cochrane Library, and ClinicalTrials.gov from January 2000 to June 2024 to identify randomized controlled trials (RCTs). A manual search complemented the electronic search. The Risk of Bias 2 (RoB 2) assessment was used to evaluate the internal validity of the included studies. A total of 1719 studies were identified, of which 23 fulfilled the inclusion criteria. Nineteen of these studies evaluated pain levels (primary outcome) after BoTN-A therapy, with six of them observing a decrease. In terms of secondary outcomes, seven of 10 studies noted an increase in maximum mouth opening, while all six reported a drop in EMG activity, and all four found a decrease in occlusal force following BoNT-A therapy. Muscle activity and biting force were significantly reduced in the therapeutic groups. Clinicians must consider these adverse events before treating patients with BoNT-A therapy. Additional regulatory guidelines and standardization of injection protocols are essential in improving therapeutic outcomes and patient safety. These findings suggest that BoNT-A may be a feasible option for TMD management but should be used with caution in clinical settings.

Relative Uptake of Tomato Carotenoids by In Vitro Intestinal and Prostate Cancer Cells.

BACKGROUND: Consumption of tomatoes and tomato carotenoids is associated with a reduced risk of prostate cancer. Prostate tissue accumulates tomato carotenoids, including lycopene, ß-carotene, and phytoene. Phytoene accumulation is relatively greater in the prostate than that of lycopene, but the metabolic determinants of tissue carotenoid profiles are poorly understood. OBJECTIVES: The purpose of this study was to determine if differences in stability, cellular uptake, and clearance of phytoene compared with lycopene or ß-carotene by prostate and intestinal cells may explain differences in observed tissue carotenoid profiles. METHODS: Gene and protein expression for carotenoid metabolism in prostate cell lines were analyzed by qRT-PCR and Western blot, respectively. Uptake, efflux, and clearance of phytoene, lycopene, or ß-carotene by prostate cell [LNCaP (Lymph Node Carcinoma of the Prostate cell line), RWPE-1 (a human prostate epithelial cell line), and PC-3 (aprostate cancer cell line)] and absorptive enterocyte (Caco-2) cultures were compared. The effect of scavenger receptor class B member 1 (SCARB1) inhibition on carotenoid uptake by LNCaP, RWPE-1, and Caco-2 cells was tested. RESULTS: SCARB1 was expressed across prostate cell lines. Lycopene, phytoene, and ß-carotene uptakes were similar in LNCaP and PC-3 cells, whereas RWPE-1 cells absorbed a smaller portion of the phytoene dose than lycopene or ß-carotene doses. The clearance rates of carotenoids from LNCaP cells did not differ. Intestinal cell uptake of phytoene was greatest, followed by ß-carotene and lycopene. SCARBI inhibitor treatment did not significantly reduce the uptake or efflux of carotenoids by LNCaP or Caco-2 cells at the dose concentration provided. CONCLUSIONS: Overall, this study suggests that greater bioavailability at the point of the intestine and greater stability of phytoene are determinants of the relative enrichment of phytoene in prostate tissue.

In situ structure and rotary states of mitochondrial ATP synthase in whole Polytomella cells.

Cells depend on a continuous supply of adenosine triphosphate (ATP), the universal energy currency. In mitochondria, ATP is produced by a series of redox reactions, whereby an electrochemical gradient is established across the inner mitochondrial membrane. The ATP synthase harnesses the energy of the gradient to generate ATP from adenosine diphosphate (ADP) and inorganic phosphate. We determined the structure of ATP synthase within mitochondria of the unicellular flagellate Polytomella by electron cryo-tomography and subtomogram averaging at up to 4.2-angstrom resolution, revealing six rotary positions of the central stalk, subclassified into 21 substates of the F1 head. The Polytomella ATP synthase forms helical arrays with multiple adjacent rows defining the cristae ridges. The structure of ATP synthase under native operating conditions in the presence of a membrane potential represents a pivotal step toward the analysis of membrane protein complexes in situ.

Genetic Implications and Management of Epidermolysis Bullosa in the Saudi Arabian Population.

Epidermolysis bullosa (EB) is a genetic skin disorder characterized by skin fragility and blister formation. This review explores the genetic basis and management of EB in the Saudi population, emphasizing the need for genetic insights to enable precise diagnosis, targeted treatments, and effective counseling. Diagnosis in Saudi Arabia relies on clinical assessments and genetic testing. Prenatal diagnosis may be suggested in families with children affected by EB, but it is not widely used in the Middle East. Current management focuses on symptom relief, while emerging experimental approaches such as gene and stem cell therapies are under extensive research. Challenges in EB research include developing effective targeted therapies and understanding the variability in how genotypes manifest phenotypically. Continuous research is crucial to enhance diagnostic methods, therapeutic approaches, and overall patient care.

Iron Homeostasis-Related Parameters and Hepcidin/Ferritin Ratio: Emerging Sex-Specific Predictive Markers for Metabolic Syndrome.

Metabolic syndrome (MetS) is a worldwide public health challenge. Accumulating evidence implicates elevated serum ferritin and disruptions in iron metabolism as potential elements linked to an increased risk of MetS. This study investigates the relationship between iron homeostasis-including hepcidin levels, serum iron concentration, unsaturated iron-binding capacity (UIBC), and the hepcidin/ferritin (H/F) ratio-and MetS. In this descriptive cross-sectional study, 209 participants aged 24-70 were categorized into two groups: 103 with MetS and 106 without MetS. All participants underwent medical assessment, including anthropometric measures, indices of glycemic control, lipid profiles, and iron-related parameters. Participants were further stratified by the Homeostasis Model Assessment-Insulin Resistance index into three subgroups: insulin-sensitive (IS) (<1.9), early insulin resistance (EIR) (>1.9 to <2.9), and significant insulin resistance (SIR) (>2.9). Notable increments in serum ferritin and hepcidin were observed in the SIR group relative to the IS and EIR groups, with a significant association between metabolic parameters. The UIBC and serum ferritin emerged as significant predictors of MetS, particularly in men, with an area under the curve (AUC) of 0.753 and 0.792, respectively (p ≤ 0.001). In contrast, hepcidin was notably correlated with MetS in women, with an AUC of 0.655 (p = 0.007). The H/F ratio showed superior predictive capability for MetS across both sexes (at cutoff level = 0.67). Among women, this ratio had an AUC of 0.639 (p = 0.015), and for men, it had an AUC of 0.792 (p < 0.001). Hypertension proved an independent risk factor for MetS, affirming its role in metabolic dysregulation. The findings highlight a significant interconnection between iron homeostasis parameters and MetS, with sex-specific variations underscoring the importance of personalized diagnostic criteria. The crucial role of the H/F ratio and the UIBC as emerging predictive markers for MetS indicates their potential utility in identifying at-risk individuals. Further longitudinal research is essential to establish causality and explore the interplay between these biomarkers and MetS.

Safflower Improves Memory, Learning, and Behavior in Rats Subjected to Sleep Deprivation.

BACKGROUND: Sleep is a physiological process that provides the body with a window for recovery and restoration. Intriguingly, even short-term sleep deprivation can impair brain memory, emotional capacity, information processing, and attention. Safflower (Carthamus tinctorius L.) has been shown to attenuate memory loss and improve anxiety and depression. OBJECTIVE: This study aims to study the possible therapeutic effect of safflower on sleep deprivation-dependent effects on memory and behavior. MATERIALS AND METHODS: Thirty young male Wistar albino rats were acclimatized, trained, and then assigned to three random groups: control (C), sleep-deprived (SD), and sleep-deprived Safflower-treated (SD+Sf) groups. Morris Water Maze (MWM) and Elevated Plus Maze (EPM) tests were used to study spatial memory and learning and anxiety-related behavior, respectively, in the study groups. RESULTS: There was a significant deterioration in learning and memory, as tested by the MWM in the SD group, compared to the C group. This included prolonged test duration, reduced average speed, and longer travel distance. Treatment with safflower significantly improved MWM test performance in the SD+Sf group when compared to the SD group. When compared to the C group, rats in the SD group demonstrated altered EPM test parameters suggestive of anxiety-like behavior. These included spending more time in the closed arms, spending less time in the open arms, and having fewer entries in the open arms. Rats in the SD+Sf group showed improved EPM test parameters when compared to the SD group. CONCLUSION: Safflower significantly ameliorated sleep deprivation induced by memory loss and altered behavior. Safflower supplementation may provide potential memory-enhancing and preserving, anxiolytic, and antidepressant therapeutic roles.

Neoadjuvant nivolumab or nivolumab plus ipilimumab in early-stage triple-negative breast cancer: a phase 2 adaptive trial.

Immune checkpoint inhibition (ICI) with chemotherapy is now the standard of care for stage II-III triple-negative breast cancer; however, it is largely unknown for which patients ICI without chemotherapy could be an option and what the benefit of combination ICI could be. The adaptive BELLINI trial explored whether short combination ICI induces immune activation (primary end point, twofold increase in CD8+ T cells or IFNG), providing a rationale for neoadjuvant ICI without chemotherapy. Here, in window-of-opportunity cohorts A (4 weeks of anti-PD-1) and B (4 weeks of anti-PD-1 + anti-CTLA4), we observed immune activation in 53% (8 of 15) and 60% (9 of 15) of patients, respectively. High levels of tumor-infiltrating lymphocytes correlated with response. Single-cell RNA sequencing revealed that higher pretreatment tumor-reactive CD8+ T cells, follicular helper T cells and shorter distances between tumor and CD8+ T cells correlated with response. Higher levels of regulatory T cells after treatment were associated with nonresponse. Based on these data, we opened cohort C for patients with high levels of tumor-infiltrating lymphocytes (≥50%) who received 6 weeks of neoadjuvant anti-PD-1 + anti-CTLA4 followed by surgery (primary end point, pathological complete response). Overall, 53% (8 of 15) of patients had a major pathological response (<10% viable tumor) at resection, with 33% (5 of 15) having a pathological complete response. All cohorts met Simon's two-stage threshold for expansion to stage II. We observed grade ≥3 adverse events for 17% of patients and a high rate (57%) of immune-mediated endocrinopathies. In conclusion, neoadjuvant immunotherapy without chemotherapy demonstrates potential efficacy and warrants further investigation in patients with early triple-negative breast cancer. ClinicalTrials.gov registration: NCT03815890 .

Cytotoxicity by endocrine disruptors through effects on ER Ca2+ transporters, aberrations in Ca2+ signalling pathways and ER stress.

Concerns regarding man-made organic chemicals pervading our ecosystem and having adverse and detrimental effects upon organisms, including man, have now been studied for several decades. Since the 1970s, some environmental pollutants were identified as having endocrine disrupting affects. These endocrine disrupting chemicals (EDC) were initially shown to have estrogenic or anti-estrogenic properties and some were also shown to bind to a variety of hormone receptors. However, since the 1990s it has also been identified that many of these EDC additionally, have the ability of causing abnormal alterations in Ca2+ signalling pathways (also commonly involved in hormone signalling), leading to exaggerated elevations in cytosolic [Ca2+] levels, that is known to cause activation of a number of cell death pathways. The major emphasis of this review is to present a personal perspective of the evidence for some types of EDC, specifically alkylphenols and brominated flame retardants (BFRs), causing direct effects on Ca2+ transporters (mainly the SERCA Ca2+ ATPases), culminating in acute cytotoxicity and cell death. Evidence is also presented to indicate that this Ca2+ATPase inhibition, which leads to abnormally elevated cytosolic [Ca2+], as well as a decreased luminal ER [Ca2+], which triggers the ER stress response, are both involved in acute cytotoxicity.

The Role of Screening, Risk Factors, and Early Intervention in Preventing Diabetes in the Obese Population: A Systematic Review.

With its rising global prevalence, diabetes has become one of the most significant and challenging health problems afflicting the world's population today. The increasing burden of diabetes and its associated complications calls for immediate action for prevention which primarily includes addressing the risk factors. The most significant risk factor for the onset of diabetes is obesity. Obesity and diabetes rates have been rising simultaneously, posing a threat to patient mortality and driving up community healthcare costs. A weight loss of five percent or more of total body weight has been shown to improve the quality of life, reduce the need for pharmacological therapy for diabetes, and enhance glycemic control. This level of weight loss can have significant health benefits, particularly for individuals with diabetes or at risk for developing diabetes. We aim to conduct this systematic review to assess diverse risk factors contributing to the incidence of diabetes among the obese population and determine various preventive strategies and recommendations in practice for the prevention of diabetes in this cohort. As a result, we included original studies that recruited the obese and diabetic populations and defined preventive measures for early intervention. Additionally, we included studies published in the last 10 years (2014-2024) only for the latest evidence. Studies including obese populations with cardiovascular diseases and neurological disorders were excluded. The Newcastle-Ottoman Castle assessment tool was utilized to assess the quality of the studies. We included nine studies that recruited 60,645 patients and were published between 2015 and 2022. Findings suggest that obesity alone is a significant contributor to the occurrence or onset of diabetes. At the same time, the presence of other risk factors, including hypertension, dyslipidemia, elevated triglycerides, or HDL and LDL levels, may further increase the risk of diabetes and its associated complications among the obese population. Preventive strategies emphasize early intervention through increasing awareness and educating communities about risk factors and lifestyle interventions, including the limitations of fast food diets for the prevention of diabetes and weight control. Since obesity is considered to be an independent risk factor for the development of diabetes, addressing and managing it is of critical importance clinically. Targeted early interventions, including screening for risk factors, health promotion, and education activities, can aid in the adaptation of healthier lifestyles, which can reduce the burden of these diseases significantly.

Approach in inputs & outputs selection of Data Envelopment Analysis (DEA) efficiency measurement in hospitals: A systematic review.

The efficiency and productivity evaluation process commonly employs Data Envelopment Analysis (DEA) as a performance tool in numerous fields, such as the healthcare industry (hospitals). Therefore, this review examined various hospital-based DEA articles involving input and output variable selection approaches and the recent DEA developments. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was utilised to extract 89 English articles containing empirical data between 2014 and 2022 from various databases (Web of Science, Scopus, PubMed, ScienceDirect, Springer Link, and Google Scholar). Furthermore, the DEA model parameters were determined using information from previous studies, while the approaches were identified narratively. This review grouped the approaches into four sections: literature review, data availability, systematic method, and expert judgement. An independent single strategy or a combination with other methods was then applied to these approaches. Consequently, the focus of this review on various methodologies employed in hospitals could limit its findings. Alternative approaches or techniques could be utilised to determine the input and output variables for a DEA analysis in a distinct area or based on different perspectives. The DEA application trend was also significantly similar to that of previous studies. Meanwhile, insufficient data was observed to support the usability of any DEA model in terms of fitting all model parameters. Therefore, several recommendations and methodological principles for DEA were proposed after analysing the existing literature.

The immunomicrotope of Leishmania control and persistence.

Leishmania is an intracellular protozoan transmitted by sand fly vectors; it causes cutaneous, mucocutaneous, or visceral disease. Its growth and survival are impeded by type 1 T helper cell responses, which entail interferon (IFN)-γ-mediated macrophage activation. Leishmania partially escapes this host defense by triggering immune cell and cytokine responses that favor parasite replication rather than killing. Novel methods for in situ analyses have revealed that the pathways of immune control and microbial evasion are strongly influenced by the tissue context, the micro milieu factors, and the metabolism at the site of infection, which we collectively term the 'immunomicrotope'. Understanding the components and the impact of the immunomicrotope will enable the development of novel strategies for the treatment of chronic leishmaniasis.

Gene expression profile of immune-check point in response to Trastuzumab therapy in patients with HER-2 positive breast cancer.

OBJECTIVE: Aim: To clarify the association between response to Trastuzumab and molecular expression of TIM-3 and FOXP-3 immune checkpoints. PATIENTS AND METHODS: Materials and Methods: FOXP-3 and TIM-3 expression in peripheral blood was analyzed using qPCR, and the serum level of Trastuzumab was estimated using an immune sorbent enzyme assay. RESULTS: Results: During treatment with Trastuzumab, the FOXP-3 gene expression showed a significant decline throughout one year of treatment, going from 0.85 at cycle 9 to 0.75 at cycle 17. While the TIM-3 gene expression showed a significant up regulation at cycle 9 to 2.8 fold, followed by a reduction in the fold change from 2.8 to 1.7 in the font of reference gene expression. CONCLUSION: Conclusions:FOXP-3 and TIM-3 have the potential to be suggestive markers that can anticipate the response to Trastuzumab, but they are not capable of predicting the likelihood of recurrence.

MLIP and Its Potential Influence on Key Oncogenic Pathways.

Muscle-enriched A-type lamin-interacting protein (MLIP) is an emerging protein involved in cellular homeostasis and stress adaptation. Eukaryotic cells regulate various cellular processes, including metabolism, DNA repair, and cell cycle progression, to maintain cellular homeostasis. Disruptions in this homeostasis can lead to diseases such as cancer, characterized by uncontrolled cell growth and division. This review aims to explore for the first time the unique role MLIP may play in cancer development and progression, given its interactions with the PI3K/Akt/mTOR pathway, p53, MAPK9, and FOXO transcription factors, all critical regulators of cellular homeostasis and tumor suppression. We discuss the current understanding of MLIP's involvement in pro-survival pathways and its potential implications in cancer cells' metabolic remodeling and dysregulated homeostasis. Additionally, we examine the potential of MLIP as a novel therapeutic target for cancer treatment. This review aims to shed light on MLIP's potential impact on cancer biology and contribute to developing innovative therapeutic strategies.

Unveiling G-protein coupled receptors as potential targets for ovarian cancer nanomedicines: from RNA sequencing data analysis to in vitro validation.

Genetic heterogeneity in ovarian cancer indicates the need for personalised treatment approaches. Currently, very few G-protein coupled receptors (GPCRs) have been investigated for active targeting with nanomedicines such as antibody-conjugated drugs and drug-loaded nanoparticles, highlighting a neglected potential to develop personalised treatment. To address the genetic heterogeneity of ovarian cancer, a future personalised approach could include the identification of unique GPCRs expressed in cancer biopsies, matched with personalised GPCR-targeted nanomedicines, for the delivery of lethal drugs to tumour tissue before, during and after surgery. Here we report on the systematic analysis of public ribonucleic acid-sequencing (RNA-seq) gene expression data, which led to prioritisation of 13 GPCRs as candidates with frequent overexpression in ovarian cancer tissues. Subsequently, primary ovarian cancer cells derived from ascites and ovarian cancer cell lines were used to confirm frequent gene expression for the selected GPCRs. However, the expression levels showed high variability within our selection of samples, therefore, supporting and emphasising the need for the future development of case-to-case personalised targeting approaches.

Assessing the correlation between the degree of tricuspid regurgitation and pulmonary hypertension: A comprehensive study.

OBJECTIVES: To evaluate the relationship between severity of tricuspid regurgitation (TR) and pulmonary hypertension. METHODS: Cross-sectional study of 118 patients with pulmonary hypertension was carried out at a single center in Jeddah, Saudi Arabia, between 2018-2021. Patients who had pulmonary or tricuspid valves organic diseases, previously undergone tricuspid or pulmonary valve surgeries, had permanent pacemakers or critically ill were excluded. RESULTS: A high proportion of patients were women (n=100, 85%) and obese (n=57, 48%). Patients with more than mild TR had higher systolic pulmonary artery pressure (sPAP) than those with trivial or mild regurgitation (p<0.001). There was a significant association between severity of TR (p<0.001) and right chambers size (p=0.001). Furthermore, pulmonary artery pressure (PAP) was significantly higher in patients with mild right ventricular impairment (p=0.001). CONCLUSION: Increase in degree of TR and right atrial size were predictors of elevated sPAP. Our findings highlight the interplay among TR, right heart size, ventricular function, and PAP. Understanding these associations can aid in risk stratification, monitoring disease progression, and potentially guiding treatment in those patients.

Tilting and Distortion in the Multiferroic Aurivillius Phase Bi6Ti3Fe1.5Mn0.5O18.

Aurivillius structured Bi6Ti3Fe1.5Mn0.5O18 (B6TFMO) has emerged as a rare room temperature multiferroic, exhibiting reversible magnetoelectric switching of ferroelectric domains under cycled magnetic fields. This layered oxide presents exceptional avenues for advancing data storage technologies owing to its distinctive ferroelectric and ferrimagnetic characteristics. Despite its immense potential, a comprehensive understanding of the underlying mechanisms driving multiferroic behavior remains elusive. Herein, we employ atomic resolution electron microscopy to elucidate the interplay of octahedral tilting and atomic-level structural distortions within B6TFMO, associating these phenomena with functional properties. Fundamental electronic features at varying bonding environments within this complex system are scrutinized using electron energy loss spectroscopy (EELS), revealing that the electronic nature of the Ti4+ cations within perovskite BO6 octahedra is influenced by position within the Aurivillius structure. Layer-by-layer EELS analysis shows an ascending crystal field splitting (Δ) trend from outer to center perovskite layers, with an average increase in Δ of 0.13 ± 0.06 eV. Density functional theory calculations, supported by atomic resolution polarization vector mapping of B-site cations, underscore the correlation between the evolving nature of Ti4+ cations, the extent of tetragonal distortion and ferroelectric behavior. Integrated differential phase contrast imaging unveils the position of light oxygen atoms in B6TFMO for the first time, exposing an escalating degree of octahedral tilting toward the center layers, which competes with the magnitude of BO6 tetragonal distortion. The observed octahedral tilting, influenced by B-site cation arrangement, is deemed crucial for juxtaposing magnetic cations and establishing long-range ferrimagnetic order in multiferroic B6TFMO.