Vitamin D Alleviates Heavy Metal-Induced Cytotoxic Effects on Human Bone Osteoblasts Via the Induction of Bioenergetic Disruption, Oxidative Stress, and Apoptosis.

Cadmium (Cd) and lead (Pb) are heavy metals (HMs) that persistently contaminate the ecosystem, and bioaccumulation in bones is a health concern. We used biochemical and molecular assays to assess the cytoprotective effect of vitamin D (VD) on Cd- and Pd-induced chemical toxicity of human bone osteoblasts in vitro. Exposing Cd and Pb to human osteoblast cultures at concentrations of 0.1-1000 µM for 24-72 h significantly reduced osteoblast viability in an exposure time- and concentration-dependent manner. The cytotoxic effect of Cd on osteoblasts was more severe than Pb's, with 72-h exposure estimated half maximal effective concentration (EC50) of 8 and 12 µM, respectively, and VD (1 and 10 nM) alleviated cytotoxicity. Bioenergetics assays of ATP, mitochondrial membrane potential, and mitochondrial complex I and III activity showed that both Cd and Pb (1 and 10 µM) inhibited cellular bioenergetics after 72-h exposure. Cd and Pb increased lipid peroxidation and reactive oxygen species with reduced catalase/superoxide dismutase antioxidant activities and increased activity of caspases -3, -8, and -9. Co-treatment with VD (1 and 10 nM) counteracted bioenergetic disruption, oxidative damage, and apoptosis in a concentration-dependent manner. These findings suggest that VD is effective in managing the toxic effects of environmental pollutants and in treating bone diseases characterized by oxidative stress, apoptosis, and bioenergetic disruption.

The Impact of Age and Gender on Anterior Cruciate Ligament Injuries and Associated Knee Lesions: A Retrospective Study.

OBJECTIVES: This study aimed to evaluate the anterior cruciate ligament (ACL)-associated lesions in knee sports injuries in magnetic resonance imaging (MRI) and the effect of genders and ages on the patterns of the associated lesions in Arar, Northern Border region, Saudi Arabia. METHODS: This retrospective cohort study enrolled MRI of knee sports injuries with diagnosed ACL lesions during the period from January 2018 to December 2023 in Prince Abdulaziz Bin Musaed Hospital and Alkhibrah Health Center in Arar. RESULTS: A total of 505 knee MRI images were enrolled in the study. There were 104 (20.5%) females and 401 (79.5%) males with an average age of 34.5 years (range: 10-85 years) in this study. ACL lesions were reported in 191 (37.8%) cases. ACL was reported to be associated with other knee lesions in 185 (96.8%) cases. Joint effusion and posterior horn medial meniscus (PHMM) lesions were the most associated lesions found in 112 (58.9%) and 108 (56.5%) cases, respectively. Aging was found to significantly increase the incidence of PHMM and joint effusion associated with ACL tears, with estimated relative risks of 1.4 and 1.5 (odds ratio: 2.19 and 2.6), respectively. Also, the female gender was found to significantly increase the incidence of PHMM and associated ligament injuries with estimated relative risks of 1.5 and 4.1 (odds ratio: 3.6 and 5.1), respectively. CONCLUSION: Tears of ACL are prevalent patterns of knee sports injuries with different types of associated injuries, which can be affected by the ages and genders of the patients.

Trampoline Injuries in Children and Adolescents: A Jumping Threat.

OBJECTIVE: As trampoline use grows more popular in the United States, the frequency of injuries continues to climb. We hypothesized that toddlers would be at the highest risk for trampoline injuries requiring hospitalization. METHODS: The National Electronic Injury Surveillance System database was examined for trampoline injuries from 2009 to 2018. Patients were categorized into 3 main age groups: toddlers (<2 years), children (2-12 years), and adolescents (13-18 years). Regression models were used to identify patients at high risk for injury or hospitalization. RESULTS: There was a total of 800,969 meeting inclusion criteria, with 433,827 (54.2%) occurring at their own homes and 86,372 (18.1%) at the sporting venue. Of the total, 36,789 (4.6%) were admitted to a hospital. Fractures (N = 270,884, 34%), strain/sprain injuries (N = 264,990, 33%), followed by skin contusions/abrasions (N = 115,708, 14%) were the most common diagnoses. The most frequent injury sites were lower and upper extremities accounting for 329,219 (41.1%) and 244,032 (30.5%), whereas 175,645 (21.9%) had head and neck injuries. Musculoskeletal injuries (74%) and concussions (2.6%) were more frequent in adolescents than children (67.6% and 1.6%) and toddlers (56.3% and 1.3%). Internal organ and soft tissue injuries were frequent in toddlers. There were no fatalities reported in the injured patients. Multivariate analysis showed adolescents, female sex, extremity injuries, and musculoskeletal injuries were associated with hospitalization. Injury at a sporting venue was not associated with hospitalization. CONCLUSIONS: Adolescents and girls are at increased risk of trampoline injury, warranting hospitalization. Safety standards may help prevent extremity and musculoskeletal injuries in the pediatric population. Finally, use of trampolines at sporting venues does not appear to be particularly dangerous.

Effect of Intermittent Fasting on Glucose Homeostasis and Bone Remodeling in Glucocorticoid-Induced Osteoporosis Rat Model.

BACKGROUND: The present study examined the effect of intermittent fasting (IF) on bone mineral content (BMC) and bone mineral density (BMD) and the markers of bone remodeling in a glucocorticoid-induced osteoporosis (GIO) rat model. METHODS: Forty male rats were allocated to 4 groups (N=10 per group): control group of normal rats; control+IF group (normal rats subjected to IF for 16-18 hr daily for 90 days); dexamethasone (DEX) group: (DEX [0.5 mg i.p.] for 90 days); and DEX+IF group (DEX and IF for 90 days). By the end of the experiment, BMD and BMC in the right tibia were measured. Serum levels of the following were measured: glucose; insulin; triglycerides (TGs); total cholesterol; parathyroid hormone (PTH); osteoprotegerin (OPG); receptor activator of nuclear factor-κB (RANK); bone-resorbing cytokines, including bone deoxypyridinoline (DPD), N-terminal telopeptide of collagen type I (NTX-1), and tartrate-resistant acid phosphatase 5b (TRAP-5b); and bone-forming cytokines, including alkaline phosphatase (ALP) and osteocalcin (OC). RESULTS: DEX administration for 90 days resulted in significantly increased serum levels of glucose, insulin, TGs, cholesterol, PTH, OPG, DPD, NTX-1, and TRAP-5b and significantly decreased BMD, BMC, and serum levels of RANK, OC, and ALP (all P<0.05). IF for 90 days significantly improved all these parameters (all P<0.05). CONCLUSIONS: IF corrected GIO in rats by inhibiting osteoclastogenesis and PTH secretion and stimulating osteoblast activity.

Association of AIRE (rs2075876), but not CTLA4 (rs231775) polymorphisms with systemic lupus erythematosus.

BACKGROUND: The AIRE (rs2075876) and CTLA4 (rs231775) variants have a crucial function in controlling the negative selection and suppression of T lymphocytes. Numerous reports studied the association of AIRE and CTLA4 variants with different autoimmune disorders, but with inconclusive conclusions. The main purpose of this work is to evaluate the association of these two variants with SLE susceptibility among Egyptian patients. SUBJECTS AND METHODS: A total of 247 participants (100 SLE patients and 147 healthy controls) were enrolled in this case-controlled study. The genomic DNA of these dual variants was genotyped using the TaqMan genotyping method. RESULTS: The AIRE (rs2075876) variant conferred protection against developing SLE disease under allelic [A allele vs. G allele; OR = 0.16, 95%CI = 0.09-0.28], and dominant [GA + AA vs. GG; OR = 0.14, 95%CI = 0.05-0.34] models. Moreover, patients with AIRE rs2075876 (A/A) genotype revealed a statistically significant with lower levels of complement 3 (p-value = 0.007). Nonetheless, the CTLA4 (rs231775) variant was not associated with increased risk of SLE under all genetic association models (p-value > 0.05). However, CTLA4 rs231775 (G/G) genotype observed significant difference with recurrent infection and hematuria. CONCLUSIONS: Our findings indicated that the AIRE (rs2075876) variant conferred protection against developing SLE disease, but not the CTLA4 (rs231775) variant.

The heavy metals lead and cadmium are cytotoxic to human bone osteoblasts via induction of redox stress.

The heavy metals (HMs) lead and cadmium are persistent environmental pollutants capable of inducing ill-health in exposed individuals. One of the primary sites of accumulation and potential damage from HMs is bone, and we therefore examined the acute effects of lead and cadmium on human bone osteoblasts in vitro over a concentration range of 0.1 µM to 1mM, and for 3, 6, 12, 24, and 48 hour exposures. Incubation of osteoblasts with either lead or cadmium reduced cell viability in a concentrations and exposure durations dependent manner, as measured using MTT and LDH assays. Cytotoxicity was significant from 0.1 µM concentrations after 48 hour exposures. Both HMs damaged cellular bioenergetics with reductions of ATP production, mitochondrial complex activities, and aerobic respiration. There was a concomitant elevation of reactive oxygen species, with induction of redox stress measured as increased lipid peroxidation, and depleted cellular redox defense systems via reduced superoxide dismutase and catalase activity and cellular glutathione levels. Both HMs induced nuclear activation of Nrf2, presumably to increase transcription of antioxidant responsive genes to combat oxidative stress. Incubation of osteoblasts with HMs also compromised the secretion of procollagen type 1, osteocalcin, and alkaline phosphatase. Pre-incubation of osteoblasts with reduced glutathione prior to challenge with HMs lessened the cytotoxicity of the HMs, indicative that antioxidants may be a beneficial treatment adjunct in cases of acute lead or cadmium poisoning.

Magnetic resonance evaluation of knee osteoarthritis among the Saudi Population.

BACKGROUND AND OBJECTIVES: Osteoarthritis (OA) is the most prevalent worldwide joint degenerative disorder with high morbidities and disabilities. The current study aimed to investigate the prevalence of knee osteoarthritis (KOA) in Arar by using magnetic resonance imaging (MRI). METHODS: The prevalence of KOA was studied in Arar through MRI evaluation of randomly chosen sample from patients and their relatives attending the Prince Abdul Aziz Bin Mussad Hospital from October 2015 to November 2016. RESULTS: A total of 410 participants were enrolled in the study [328 (80%) male and 82 (20%) females]. After MRI, 163 participants [39.75% (95% CI) = 35.14 - 44.57%)] were diagnosed with KOA. The prevalence of OA was about 25.6% (95% CI = 20.8 - 31.1%) below the age of 40 years, which was found to increase by age in the enrolled volunteers. KOA prevalence was higher in females than males (75.6% and 27.7% respectively). There was a significant association between the age and genders of the participants and the prevalence of OA (p-value < 0.0001 for both variables). There was also a significant association between the age and gender of the participants and the MRI-estimated grading (p-value < 0.0001 and 0.0044 respectively). CONCLUSION: KOA is a common disease among Arar young population, especially females. Its prevalence increases by age with higher grades of severity affecting the elderly.

An active principle of Nigella sativa L., thymoquinone, showing significant antimicrobial activity against anaerobic bacteria.

AIM/BACKGROUND: Thymoquinone (TQ) is the major active principle of Nigella sativa seed (black seed) and is known to control many fungi, bacteria, and some viruses. However, the activity of TQ against anaerobic bacteria is not well demonstrated. Anaerobic bacteria can cause severe infections, including diarrhea, aspiration pneumonia, and brain abscess, particularly in immunodeficient individuals. The present study aimed to investigate the in vitro antimicrobial activity of TQ against some anaerobic pathogens in comparison to metronidazole. METHODS: Standard, ATCC, strains of four anaerobic bacteria (Clostridium difficile, Clostridium perfringens, Bacteroides fragilis, and Bacteroides thetaiotaomicron), were initially isolated on special Brucella agar base (with hemin and vitamin K). Then, minimum inhibitory concentrations (MICs) of TQ and metronidazole were determined against these anaerobes when grown in Brucella agar, using serial agar dilution method according to the recommended guidelines for anaerobic organisms instructed by the Clinical and Laboratory Standards Institute. RESULTS: TQ showed a significant antimicrobial activity against anaerobic bacteria although much weaker than metronidazole. MICs of TQ and metronidazole against various anaerobic human pathogens tested were found to be between 10-160 mg/L and 0.19-6.25 mg/L, respectively. CONCLUSIONS: TQ controlled the anaerobic human pathogenic bacteria, which supports the use of N. sativa in the treatment of diarrhea in folk medicine. Further investigations are in need for determination of the synergistic effect of TQ in combination with metronidazole and the activity of derivatives of TQ against anaerobic infections.

Transient Superficial Peroneal Nerve Palsy After Anterior Cruciate Ligament Reconstruction.

A 19-year-old male subject was diagnosed with medial meniscal, lateral meniscal and anterior cruciate ligament (ACL) tear. The symptoms did not subside after 4 months of physical therapy, and he underwent arthroscopic partial medial and lateral meniscectomy and ACL reconstruction. Immediately after the patient woke up from general anesthesia, he started experience loss of sensation in the area of superficial peroneal nerve with inverted dorsiflexion of foot and ankle. Instantly, the bandage and knee brace was removed and a diagnosis of compartment syndrome was ruled out. After eight hours, post-operatively, the patient started receiving physiotherapy. He complained of numbness and tingling in the same area. After 24 h, post-operatively, the patient started to regain dorsiflexion and eversion gradually. Two days after the surgery, the patient exhibited complete recovery of neurological status.

Students' perspective of bedside teaching: A qualitative study.

OBJECTIVES: To determine students' perception of bedside teaching, to find out barriers in its effective implementation and to suggest strategies to make it an effective learning tool. METHODS: This study was conducted in Faculty of Medicine, Northern Border University Arar, Kingdom of Saudi Arabia between November 2013 and January 2014. The study design was qualitative inductive thematic analysis using transcripts from audio-recorded focus group discussions. Four focused group discussions with medical students of 4(th) and 5(th) year MBBS were conducted. Each 40 to 50 minutes discussion session was audio taped and transcribed verbatim. Thematic analysis extracted key themes pertaining to objectives of the study. RESULTS: A total 75 students of 4(th) and 5(th) year MBBS took part in the study, 48 were female and 27 of them were male. Students believed that bedside teaching is valuable for learning essential clinical skills. They described many barriers in its effective implementation: uncooperative and less number of patients and faculty attitude. Our students suggested various strategies to address these barriers: promotion of awareness among general public about students' learning and its benefits, free medical treatment for expatriates and building of university hospital. CONCLUSION: Bedside teaching is an important learning tool. Its utility can be enhanced by orienting local patients' attitude towards importance of students' learning, by providing free medical treatment to expatriates and by including bedside teaching in faculty development programs.