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Abstract Background This retrospective analysis aimed to comprehensively review the design and regulatory aspects of bioequivalence trials submitted to the Saudi Food and Drug Authority (SFDA) since 2017. Methods This was a retrospective, comprehensive analysis study. The Data extracted from the SFDA bioequivalence assessment reports were analyzed for reviewing the overall design and regulatory aspects of the successful bioequivalence trials, exploring the impact of the coefficient of variation of within-subject variability (CVw) on some design aspects, and providing an in-depth assessment of bioequivalence trial submissions that were deemed insufficient in demonstrating bioequivalence. Results A total of 590 bioequivalence trials were included of which 521 demonstrated bioequivalence (440 single active pharmaceutical ingredients [APIs] and 81 fixed combinations). Most of the successful trials were for cardiovascular drugs (84 out of 521 [16.1%]), and the 2 × 2 crossover design was used in 455 (87.3%) trials. The sample size tended to increase with the increase in the CVw in trials of single APIs. Biopharmaceutics Classification System Class II and IV drugs accounted for the majority of highly variable drugs (58 out of 82 [70.7%]) in the study. Most of the 51 rejected trials were rejected due to concerns related to the study center (n = 21 [41.2%]). Conclusion This comprehensive analysis provides valuable insights into the regulatory and design aspects of bioequivalence trials and can inform future research and assist in identifying opportunities for improvement in conducting bioequivalence trials in Saudi Arabia.

Bone specimens obtained for biomechanical experiments are fresh-frozen for storage to slow down tissue degradation and autolysis in long-term storage. Alternatively, due to infectious risks related to the fresh tissues, fixative agents are commonly used. However, fixatives will likely change the mechanical properties of bone. Existing studies on this issue gave controversial results that are hardly comparable due to a variety of measurement approaches. For this reason, the influence of ethanol and a formalin-based fixative agent was evaluated on the mechanical properties of human cortical bone specimens by means of four-point-bending tests. 127 prismatic specimens with rectangular cross sections (2.5 x 2.5 x 20 mm3) were obtained from different regions of two fresh human femora (medial, lateral, dorsal, ventral). Specimens were either fixed in ethanol or in a mixed formalin solution or frozen following a given scheme. After two weeks of storage the samples were re-hydrated in isotonic saline and subsequently tested mechanically. The elastic bending modulus and ultimate bending strength were computed considering the actual dimensions of each specific specimen. For statistical analysis a one-way-ANOVA and an LSD post-hoc-test were performed. For ultimate bending strength no significant differences due to formalin or ethanol fixation, as compared to unfixed-fresh bone specimens could be found. And only for few cases significant differences in elastic bending modulus were observed when the two bones were evaluated separately. Since more differences of significant level due to the anatomical region of the samples were determined, the original location seems to have more influence on the evaluated mechanical properties than the method of (chemical) fixation. Consequently, ethanol and the mixed formalin solution can be recommended as a fixation agent for samples in biomechanical testing, if these samples are rinsed in isotonic saline prior to static mechanical testing.

Inflammatory reactions associated with osteolysis and implant loosening can be the result of generated CoCr particles and the simultaneous release of ions, which are the consequence of wear at the articulating surfaces of metallic implants. By now, there is little knowledge about the influence of CoCr ions on the viability of human osteoblasts (hOB).

The medial patellofemoral ligament (MPFL) is a key structure in the treatment of habitual and traumatic patellofemoral instability. However, there exists little knowledge about its behaviour during deep knee flexion after femoral refixation. Since improper femoral attachment sites may lead to unnatural length change patterns in the ligament and consequently to osteoarthritis due to pathological femoro-patellar contact pressure, the understanding of the patella kinematics and MPFL behaviour is crucial.

This study aimed to identify the effect of using computerized program on the level of technical and cognitive performance in basketball amongst female in the faculty of physical education at An-najah National University. The sample of the study consisted of (40) students, from basketball course, were divided equally among experimental and control groups. The Computerized Program (CP) was on the experimental group for 8-weeks, three times a week, and 50 minut for each class, while the traditional program was under the control group for the same duration. T-test were used for analyzing, means, standard deviation. The results of the study revealed a positive effect of using computerized program on the level of technical and cognitive performance in basketball .Also, the results indicated significant differences between experimental and control groups in the level of basketball performance as well as in knowledge domain of the course in favor of experimental group. Based on the findings of the study the researcher recommended the use of educational technology in teaching practical courses for physical education students.

Juliane Pasold,1 Kathleen Zander,1 Benjamin Heskamp,1 Cordula Grüttner,2 Frank Lüthen,3 Thomas Tischer,1 Anika Jonitz-Heincke,1 Rainer Bader1 1Department of Orthopaedics, Biomechanics and Implant Technology Laboratory, University Medicine Rostock, Rostock, Germany; 2Micromod Particletechnology GmbH, Rostock, Germany; 3Institute of Cell Biology, University Medicine Rostock, Rostock, Germany Purpose: In the present study, silica nanoparticles (sNP) coupled with insulin-like growth factor 1 (IGF-1) were loaded on a collagen-based scaffold intended for cartilage repair, and the influence on the viability, proliferation, and differentiation potential of human primary articular chondrocytes was examined. Methods: Human chondrocytes were isolated from the hyaline cartilage of patients (n=4, female, mean age: 73±5.1 years) undergoing primary total knee joint replacement. Cells were dedifferentiated and then cultivated on a bioresorbable collagen matrix supplemented with fluorescent sNP coupled with IGF-1 (sNP–IGF-1). After 3, 7, and 14 days of cultivation, cell viability and integrity into the collagen scaffold as well as metabolic cell activity and synthesis rate of matrix proteins (collagen type I and II) were analyzed. Results: The number of vital cells increased over 14 days of cultivation, and the cells were able to infiltrate the collagen matrix (up to 120 µm by day 7). Chondrocytes cultured on the collagen scaffold supplemented with sNP–IGF-1 showed an increase in metabolic activity (5.98-fold), and reduced collagen type I (1.58-fold), but significantly increased collagen type II expression levels (1.53-fold; P=0.02) after 7 days of cultivation compared to 3 days. In contrast, chondrocytes grown in a monolayer on plastic supplemented with sNP-IGF-1 had significantly lower metabolic activity (1.32-fold; P=0.007), a consistent amount of collagen type I, and significantly reduced collagen type II protein expression (1.86-fold; P=0.001) after 7 days compared to 3 days. Conclusion: Collagen-based scaffolds enriched with growth factors, such as IGF-1 coupled to nanoparticles, represent an improved therapeutic intervention for the targeted and controlled treatment of articular cartilage lesions. Keywords: chondrogenic differentiation, silica nanoparticles, growth factor, 3D-matrix, cartilage repair

Aim: Colorectal cancer resection in the elderly may be associated with significant morbidity. This study aimed to assess perioperative morbidity in elderly patients undergoing colorectal cancer resection and to investigate risk factors for postoperative complications. Materials and Methods: Consecutive patients aged ≥ 75 years undergoing colorectal cancer resection with curative intent between January 2014 and December 2021 at our institution were included. We evaluated risk factors for postoperative complications, length of hospital stays (LOS), 30-day readmission, and 90-day mortality rates. Results: A total of 843 patients underwent colorectal cancer resection during the study period, of whom 202 patients were 75 years or older. Advanced age was associated with postoperative complications (Clavien–Dindo score > 3b, p = 0.001). Sarcopenia, preoperative plasma albumin < 3.5 g/dL, and open and urgent surgery were significantly correlated with major complications (p = 0.015, p = 0.022, p = 0.003, and p < 0.001, respectively). LOS was longer in elderly patients with a modified 5-item Frailty Index (5-mFI) ≥ 2 and low preoperative serum albumin levels, as well as following open surgery (p = 0.006, p = 0.001 and p < 0.001, respectively). Sarcopenia and preoperative plasma albumin < 3.5 g/dL were predictors for 90-day mortality (p = 0.004 and p > 0.001). Conclusion: Advanced age, sarcopenia, preoperative hypoalbuminemia, 5-mFI ≥ 2, and open or urgent surgery may serve as predictors for postoperative morbidity in the elderly population. [ABSTRACT FROM AUTHOR]

A nonlinear-dynamical algorithm for city planning is proposed as an impulse pattern formulation (IPF) for predicting relevant parameters such as health, artistic freedom, or financial developments of different social or political stakeholders over the cause of a planning process. The IPF has already shown high predictive precision at low computational cost in musical instrument simulations, brain dynamics, and human–human interactions. The social and political IPF consists of three basic equations of system state developments, self-adaptation of stakeholders, two adaptive interactions, and external impact terms suitable for respective planning situations. Typical scenarios of stakeholder interactions and developments are modeled by adjusting a set of system parameters. These include stakeholder reaction to external input, enhanced system stability through self-adaptation, stakeholder convergence due to adaptive interaction, as well as complex dynamics in terms of fixed stakeholder impacts. A workflow for implementing the algorithm in real city planning scenarios is outlined. This workflow includes machine learning of a suitable set of parameters suggesting best-practice planning to aim at the desired development of the planning process and its output. [ABSTRACT FROM AUTHOR]

Background: Obsessive-Compulsive Disorder (OCD) is a debilitating condition marked by the presence of intrusive obsessions and repetitive compulsions. The primary care setting often serves as the first line of contact for individuals grappling with mental health issues, making it a crucial frontier in the early detection and management of OCD. Therefore, the accurate diagnosis of OCD in such settings is essential for effective management. Objective: This review article aims to provide a comprehensive overview of the diagnostic process for OCD, emphasizing the clinical presentation, differential diagnosis, and various diagnostic tools available. Additionally, it explores current strategies for managing OCD, including pharmacological and psychotherapeutic interventions. Methodology: For this review, a comprehensive literature search was conducted using Google Scholar and PubMed databases. Keywords such as "Diagnosis," "obsessive compulsive disorder," and "management" were employed to narrow down relevant studies. Both qualitative and quantitative research papers were included, while non-English publications and those lacking peer-review were excluded. Results: Core symptoms of OCD include obsessions and compulsions, with the Y-BOCS being a standard measure for diagnosis. Differential diagnosis is essential to distinguish OCD from other conditions. SSRIs have been recognized as first-line pharmacological treatments. CBT, particularly Exposure and Response Prevention, remains a potent psychotherapeutic intervention. Emerging treatments like DBS and TMS offer hope for those unresponsive to conventional treatments. Combination therapies have shown enhanced efficacy in certain cases. Conclusion: The meticulous diagnosis of OCD requires recognizing its core symptoms, ruling out other conditions, and leveraging validated clinical tools. A multi-faceted management approach combining pharmacological and psychological treatments ensures optimal patient outcomes, with ongoing research introducing promising new interventions. [ABSTRACT FROM AUTHOR]