Functionality of arbuscular mycorrhizal fungi varies across different growth stages of maize under drought conditions.

Physio-biochemical regulations governing crop growth period are pivotal for drought adaptation. Yet, the extent to which functionality of arbuscular mycorrhizal fungi (AM fungi) varies across different stages of maize growth under drought conditions remains uncertain. Therefore, periodic functionality of two different AM fungi i.e., Rhizophagus irregularis SUN16 and Glomus monosporum WUM11 were assessed at jointing, silking, and pre-harvest stages of maize subjected to different soil moisture gradients i.e., well-watered (80% SMC (soil moisture contents)), moderate drought (60% SMC), and severe drought (40% SMC). The study found that AM fungi significantly (p < 0.05) affected various morpho-physiological and biochemical parameters at different growth stages of maize under drought. As the plants matured, AM fungi enhanced root colonization, glomalin contents, and microbial biomass, leading to increased nutrient uptake and antioxidant activity. This boosted AM fungal activity ultimately improved photosynthetic efficiency, evident in increased photosynthetic pigments and photosynthesis. Notably, R. irregularis and G. monosporum improved water use efficiency and mycorrhizal dependency at critical growth stages like silking and pre-harvest, indicating their potential for drought resilience to stabilize yield. The principal component analysis highlighted distinct plant responses to drought across growth stages and AM fungi, emphasizing the importance of early-stage sensitivity. These findings underscore the potential of incorporating AM fungi into agricultural management practices to enhance physiological and biochemical responses, ultimately improving drought tolerance and yield in dryland maize cultivation.

Adipose-derived regenerative therapies for the treatment of knee osteoarthritis.

Knee osteoarthritis is a degenerative condition with a significant disease burden and no disease-modifying therapy. Definitive treatment ultimately requires joint replacement. Therapies capable of regenerating cartilage could significantly reduce financial and clinical costs. The regenerative potential of mesenchymal stromal cells (MSCs) has been extensively studied in the context of knee osteoarthritis. This has yielded promising results in human studies, and is likely a product of immunomodulatory and chondroprotective biomolecules produced by MSCs in response to inflammation. Adipose-derived MSCs (ASCs) are becoming increasingly popular owing to their relative ease of isolation and high proliferative capacity. Stromal vascular fraction (SVF) and micro-fragmented adipose tissue (MFAT) are produced by the enzymatic and mechanical disruption of adipose tissue, respectively. This avoids expansion of isolated ASCs ex vivo and their composition of heterogeneous cell populations, including immune cells, may potentiate the reparative function of ASCs. In this editorial, we comment on a multicenter randomized trial regarding the efficacy of MFAT in treating knee osteoarthritis. We discuss the study's findings in the context of emerging evidence regarding adipose-derived regenerative therapies. An underlying mechanism of action of ASCs is proposed while drawing important distinctions between the properties of isolated ASCs, SVF, and MFAT.

Comparison of Laparoscopic Intraperitoneal Onlay Mesh (IPOM) Hernioplasty With Laparoscopic IPOM-Plus: Our Initial Experience in Pakistan.

Objectives Laparoscopic intraperitoneal onlay mesh hernioplasty (IPOM) for ventral hernias has been used for a long time. However, there have been some issues associated with it, thereby leading to the introduction of a new technique that involves laparoscopic closure of the fascial defect with suture followed by intraperitoneal onlay mesh placement (IPOM-Plus). We carried out this study to compare the outcome of laparoscopic IPOM with fascial defect closure versus without defect closure in midline ventral hernia repair in terms of recurrence. Methodology This comparative study was carried out in the Department of Surgery, Services Hospital, Lahore, from October 16, 2020, to April 15, 2022. A total of 84 patients of both genders, aged between 18 and 70 years, presenting with midline ventral hernia were included in the study. Patients with recurrent hernia, unstable cardiopulmonary conditions, neurological or psychiatric diseases, chronic renal disease, congestive cardiac failure, and chronic obstructive pulmonary disease (COPD) were excluded from the study. Patients were assigned to two groups. Group 1 underwent IPOM with the closure of the defect, and Group 2 underwent IPOM without the closure of the defect. Patients were observed for immediate postoperative complications. Patients were monitored for one year to assess recurrence through clinical evaluation and ultrasonography. Results In this study, seroma formation was found in 3 (7.14%) patients for laparoscopic IPOM with fascial defect closure and 10 (23.81%) in those undergoing laparoscopic IPOM without defect closure (P-value = 0.035). Recurrence was identified in 2 (4.76%) patients undergoing laparoscopic IPOM with fascial defect closure and 9 (21.43%) in those undergoing laparoscopic IPOM without defect closure (P-value = 0.024). Conclusions This study concluded that the frequency of recurrence is less after laparoscopic IPOM with fascial defect closure in midline ventral hernia repair than after laparoscopic IPOM without fascial defect closure.

Identification of kidney stones in KUB X-ray images using VGG16 empowered with explainable artificial intelligence.

A kidney stone is a solid formation that can lead to kidney failure, severe pain, and reduced quality of life from urinary system blockages. While medical experts can interpret kidney-ureter-bladder (KUB) X-ray images, specific images pose challenges for human detection, requiring significant analysis time. Consequently, developing a detection system becomes crucial for accurately classifying KUB X-ray images. This article applies a transfer learning (TL) model with a pre-trained VGG16 empowered with explainable artificial intelligence (XAI) to establish a system that takes KUB X-ray images and accurately categorizes them as kidney stones or normal cases. The findings demonstrate that the model achieves a testing accuracy of 97.41% in identifying kidney stones or normal KUB X-rays in the dataset used. VGG16 model delivers highly accurate predictions but lacks fairness and explainability in their decision-making process. This study incorporates the Layer-Wise Relevance Propagation (LRP) technique, an explainable artificial intelligence (XAI) technique, to enhance the transparency and effectiveness of the model to address this concern. The XAI technique, specifically LRP, increases the model's fairness and transparency, facilitating human comprehension of the predictions. Consequently, XAI can play an important role in assisting doctors with the accurate identification of kidney stones, thereby facilitating the execution of effective treatment strategies.

In vivo microstructural heterogeneity of white matter and cognitive correlates in aging using tissue compositional analysis of diffusion magnetic resonance imaging.

BACKGROUND: Age-related cognitive decline is linked to changes in the brain, particularly the deterioration of white matter (WM) microstructure that accelerates after the age of 60. WM deterioration is associated with mild cognitive impairment and dementia, but the origin and role of white matter signal abnormalities (WMSA) seen in standard MRI remain debated due to their heterogeneity. This study explores the potential of single-shell 3-tissue constrained spherical deconvolution (SS3T-CSD), a novel technique that models diffusion data in terms of gray matter (TG ), white matter (Tw ), and cerebrospinal fluid (TC ), to differentiate WMSA from normal-appearing white matter and better understand the interplay between changes in WM microstructure and decline in cognition. METHODS: A total of 189 individuals from the GENIC cohort were included. MRI data, including T1-weighted and diffusion images, were obtained. Preprocessing steps were performed on the diffusion MRI data, followed by the SS3T-CSD. WMSA were segmented using FreeSurfer. Statistical analyses were conducted to assess the association between age, WMSA volume, 3-tissue signal fractions (Tw , TG , and TC ), and neuropsychological variables. RESULTS: Participants above 60 years old showed worse cognitive performance and processing speed compared to those below 60 (p < .001). Age was negatively associated with Tw in normal-appearing white matter (p < .001) and positively associated with TG in both WMSA (p < .01) and normal-appearing white matter (p < .001). Age was also significantly associated with WMSA volume (p < .001). Higher processing speed was associated with lower Tw and higher TG , in normal-appearing white matter (p < .01 and p < .001, respectively), as well as increased WMSA volume (p < .001). Similarly, lower MMSE scores correlated with lower Tw and higher TG in normal-appearing white matter (p < .05). High cholesterol and hypertension were associated with higher WMSA volume (p < .05). CONCLUSION: The microstructural heterogeneity within normal-appearing white matter and WMSA is associated with increasing age and cognitive variation, in cognitively unimpaired individuals. Furthermore, the 3-tissue signal fractions are more specific to potential white matter alterations than conventional MRI measures such as WMSA volume. These findings also support the view that the WMSA volumes may be more influenced by vascular risk factors than the 3-tissue metrics. Finally, the 3-tissue metrics were able to capture associations with cognitive tests and therefore capable of capturing subtle pathological changes in the brain in individuals who are still within the normal range of cognitive performance.

Above-and below-ground feedback loop of maize is jointly enhanced by plant growth-promoting rhizobacteria and arbuscular mycorrhizal fungi in drier soil.

Drought is a potent abiotic stressor that arrests crop growth, significantly affecting crop health and yields. The arbuscular mycorrhizal fungi (AMF), and plant growth-promoting rhizobacteria (PGPR) can offer to protect plants from stressful environments through improving water, and nutrient use efficiency by strengthening plant root structure and harnessing favorable rhizosphere environments. When Acaulospora laevis (AMF) and Bacillus subtilus (PGPR) are introduced in combination, enhanced root growth and beneficial microbial colonization can mitigate drought stress. To assess this potential, a pot experiment was done with maize (Zea mays L.) to explore the effects of A. laevis and B. subtilus under different water levels (well-watered = 80 %; moderate water stress = 55 %; and severe water stress = 35 %) on maize yield, soil microbial activities, nutrients contents, root, and leaf functioning. Plants exposed to severe drought stress hampered their root and leaf functioning, and reduced grain yield compared with control plants. Combined use of AMF and PGPR increased root colonization (104.6 %-113.2 %) and microbial biomass carbon (36.38 %-40.23 %) under moderate to severe drought conditions over control. Higher root colonization was strongly linked with elevated ACC (aminocyclopropane-1-carboxylic acid) production, subsequently enhancing water use efficiency (21.62 %-12.77 %), root hydraulic conductivity (1.9 %-1.4 %) and root nutrient uptake under moderate to severe drought conditions. Enhanced nutrient uptake further promoted leaf photosynthetic rate by 27.3 %-29.8 % under moderate and severe drought stress. Improving leaf and root physiological functioning enhanced maize grain yield under stressful environments. Furthermore, co-inoculation with AMF-PGPR reduced cellular damage by lowering oxidative enzyme levels and increasing antioxidative enzyme activities, improving plant performance and grain yield under stressful environments. Conclusively, the synergistic interaction of AMF with PGPR ensured plant stress tolerance by reducing cellular injury, facilitating root-leaf functioning, enhancing nutrient-water-use-efficiencies, and increasing yield under drought stress.

The Effects of Chronological Age on the Chondrogenic Potential of Mesenchymal Stromal Cells: A Systematic Review.

Tissue engineering and cell therapy for regenerative medicine have great potential to treat chronic disorders. In musculoskeletal disorders, mesenchymal stromal cells (MSCs) have been identified as a relevant cell type in cell and regenerative strategies due to their multi-lineage potential, although this is likely to be a result of their trophic and immunomodulatory effects on other cells. This PRISMA systematic review aims to assess whether the age of the patient influences the chondrogenic potential of MSCs in regenerative therapy. We identified a total of 3027 studies after performing a search of four databases, including Cochrane, Web of Science, Medline, and PubMed. After applying inclusion and exclusion criteria, a total of 14 papers were identified that were reviewed, assessed, and reported. Cell surface characterization and proliferation, as well as the osteogenic, adipogenic, and chondrogenic differentiation, were investigated as part of the analysis of these studies. Most included studies suggest a clear link between aged donor MSCs and diminished clonogenic and proliferative potential. Our study reveals a heterogeneous and conflicting range of outcomes concerning the chondrogenic, osteogenic, and adipogenic potential of MSCs in relation to age. Further investigations on the in vitro effects of chronological age on the chondrogenic potential of MSCs should follow the outcomes of this systematic review, shedding more light on this complex relationship.

Methane Decomposition to Hydrogen Over Zirconia-Supported Fe Catalysts-Effects of the Modified Support.

Methane decomposition is a promising route to synthesize COx -free hydrogen and carbon nanomaterials (CNMs ). In this work, the impregnation method was employed for the preparation of the catalysts. Systematic investigations on the activity and stability of Fe-based catalysts were carried out in a packed-bed micro-activity reactor at 800 °C with a feed gas flow rate of 18 mL/min. The effect of doping Y2 O3 , MgO, SiO2 and TiO2 over ZrO2 on the catalytic performance was also studied. BET revealed that the specific surface areas and pore volumes are increased after SiO2 , TiO2 , and Y2 O3 are added to ZrO2 while MgO had a negative impact and hence a little decrease in specific surface area is observed. The catalytic activity results showed that the Fe-based catalyst supported over TiO2 -doped ZrO2 that is, Fe-TiZr, demonstrated the highest activity and stability, with a maximum methane conversion of 81.3 % during 180 min time-on-stream. At 800 °C, a maximum initial methane conversion of 73 %, 38 %, 64 %, and 69 % and a final carbon yield of 121 wt. %, 55 wt. %, 354 wt. %, and 174 wt. % was achieved using Fe-MgZr, Fe-SiZr, Fe-TiZr and Fe-YZr catalysts, respectively. Moreover, bulk deposition of uniform carbon nanotubes with a high degree of graphitization and different diameters was observed over the catalysts.

Alternating Direction Method of Multipliers-Based Constant Modulus Waveform Design for Dual-Function Radar-Communication Systems.

In this paper, we design constant modulus waveforms for dual-function radar-communication (DFRC) systems based on a multi-input multi-output (MIMO) configuration of sensors for a far-field scenario. At first, we formulate a non-convex optimization problem subject to waveform synthesis for minimizing the interference power while maintaining a constant modulus constraint. Next, we solve this non-convex problem, iteratively, using the alternating direction method of multipliers (ADMM) algorithm. Importantly, the designed waveforms approximate a desired beampattern in terms of a high-gain radar beam and a slightly high gain communication beam while maintaining a desired low sidelobe level. The designed waveforms ensure an improved detection probability and an improved bit error rate (BER) for radar and communications parts, respectively. Finally, we demonstrate the effectiveness of the proposed method through simulation results.

Hybrid FSK-FDM Scheme for Data Rate Enhancement in Dual-Function Radar and Communication.

In this paper, we present a hybrid frequency shift keying and frequency division multiplexing (i.e., FSK-FDM) approach for information embedding in dual-function radar and communication (DFRC) design to achieve an improved communication data rate. Since most of the existing works focus on merely two-bit transmission in each pulse repetition interval (PRI) using different amplitude modulation (AM)- and phased modulation (PM)-based techniques, this paper proposes a new technique that doubles the data rate by using a hybrid FSK-FDM technique. Note that the AM-based techniques are used when the communication receiver resides in the side lobe region of the radar. In contrast, the PM-based techniques perform better if the communication receiver is in the main lobe region. However, the proposed design facilitates the delivery of information bits to the communication receivers with an improved bit rate (BR) and bit error rate (BER) regardless of their locations in the radar's main lobe or side lobe regions. That is, the proposed scheme enables information encoding according to the transmitted waveforms and frequencies using FSK modulation. Next, the modulated symbols are added together to achieve a double data rate using the FDM technique. Finally, each transmitted composite symbol contains multiple FSK-modulated symbols, resulting in an increased data rate for the communication receiver. Numerous simulation results are presented to validate the effectiveness of the proposed technique.

Genome Editing Technology: A New Frontier for the Treatment and Prevention of Cardiovascular Diseases.

Over the past 2 decades, genome-editing technique has proven to be a robust editing method that revolutionizes the field of biomedicine. At the genetic level, it can be efficiently utilized to generate various disease-resistance models to elucidate the mechanism of human diseases. It also develops an outstanding tool and enables the generation of genetically modified organisms for the treatment and prevention of various diseases. The versatile and novel clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) system mitigates the challenges of various genome editing techniques such as zinc-finger nucleases, and transcription activator-like effector nucleases. For this reason, it has become a ground-breaking technology potentially employed to manipulate the desired gene of interest. Interestingly, this system has been broadly utilized due to its tremendous applications for treating and preventing tumors and various rare disorders; however, its applications for treating cardiovascular diseases (CVDs) remain in infancy. More recently, 2 newly developed genome editing techniques, such as base editing and prime editing, have further broadened the accuracy range to treat CVDs under consideration. Furthermore, recently emerged CRISPR tools have been potentially applied in vivo and in vitro to treat CVDs. To the best of our knowledge, we strongly enlightened the applications of the CRISPR/Cas9 system that opened a new window in the field of cardiovascular research and, in detail, discussed the challenges and limitations of CVDs.

High biocompatible nitrogen and sulfur Co-doped carbon dots for Hg(II) detection and their long-term biological stability in living cells.

Fluorescent carbon dots have been highly reported nanomaterials in recent times because of their excellent physio-chemical properties and various field of applications. Herein, a one-step hydrothermal approach was used to synthesize high biocompatible nitrogen and sulfur co-doped carbon dots, and examined their chemical sensing (Hg2+) and biological imaging properties. The N,S-CDs exhibited blue light, demonstrating a high quantum yield of up to 44.5% and excitation-independent fluorescent characteristics. Cytotoxicity was observed by CCK-8 assay using T-ca cells as a target source. Cell viability was recorded over 80% even after 7 days of treatment with a concentration up to 400 µg/mL, indicating low-toxicity of N,S-CDs. Notably, the bright blue fluorescence of N,S-CDs was quenched by introducing toxic Hg2+ ions into the solution. The detection limit was calculated to be about ∼3.5 nM, which is quite impressive compared to previous reports. Because of their low-toxicity, nano-size, and environment friendly properties, N,S-CDs could be excellent fluorescent agents for bio-imaging applications. The biological stability of fluorescent N,S-CDs was tested over time, and the findings were significant even after 8 days of incubation with T-ca cells. Because of good biocompatibility and bright fluorescence, N,S-CDs were suitable for in vivo imaging.

Dual Mobility Total Hip Replacements in Young Patients- A Systematic Review.

Background: There is little consensus on outcomes of dual Mobility total hip replacement (DM-THR) in younger patients. We performed a systematic review to examine this. Methods: A systematic review of all observational studies and randomised controlled trials of patients under 70 with primary DM-THR in MEDLINE, EMBASE, Pubmed, Cochrane was performed according to PRISMA guidelines. Collected data included demographics, revision, dislocation and infection rates and functional scores. Results: Twelve papers studying 738 DM-THR in 664 patients were included. The mean patient age was 46.9 years (13.5-69.0), with 319 (48.0%) being female and 419 (52.0%) being male. After an average follow-up of 90.0 months (1-371 months), the revision rate was 12.7% (84 hips), 0 dislocations were reported but 2.5% (15 hips) underwent intra-prosthetic dislocation. 32.1% hip revisions were due to aseptic loosening. Conclusion: Limited literature surrounding the use of DM-THR suggests favourable stability but higher revision rates than conventional THR.

Bone Marrow-Derived Mesenchymal Stem Cell Implants for the Treatment of Focal Chondral Defects of the Knee in Animal Models: A Systematic Review and Meta-Analysis.

Osteoarthritis remains an unfortunate long-term consequence of focal cartilage defects of the knee. Associated with functional loss and pain, it has necessitated the exploration of new therapies to regenerate cartilage before significant deterioration and subsequent joint replacement take place. Recent studies have investigated a multitude of mesenchymal stem cell (MSC) sources and polymer scaffold compositions. It is uncertain how different combinations affect the extent of integration of native and implant cartilage and the quality of new cartilage formed. Implants seeded with bone marrow-derived MSCs (BMSCs) have demonstrated promising results in restoring these defects, largely through in vitro and animal studies. A PRISMA systematic review and meta-analysis was conducted using five databases (PubMed, MEDLINE, EMBASE, Web of Science, and CINAHL) to identify studies using BMSC-seeded implants in animal models of focal cartilage defects of the knee. Quantitative results from the histological assessment of integration quality were extracted. Repair cartilage morphology and staining characteristics were also recorded. Meta-analysis demonstrated that high-quality integration was achieved, exceeding that of cell-free comparators and control groups. This was associated with repair tissue morphology and staining properties which resembled those of native cartilage. Subgroup analysis showed better integration outcomes for studies using poly-glycolic acid-based scaffolds. In conclusion, BMSC-seeded implants represent promising strategies for the advancement of focal cartilage defect repair. While a greater number of studies treating human patients is necessary to realize the full clinical potential of BMSC therapy, high-quality integration scores suggest that these implants could generate repair cartilage of substantial longevity.

Changes in White Matter Microstructure Over 3 Years in People With and Without Stroke.

BACKGROUND AND OBJECTIVES: Cerebral white matter health can be estimated by MRI-derived indices of microstructure. White matter dysfunction is increasingly recognized as a contributor to neurodegenerative disorders affecting cognition and to functional outcomes after stroke. Reduced indices of white matter microstructure have been demonstrated cross-sectionally in stroke survivors compared with stroke-free participants, but longitudinal changes in the structure of white matter after stroke remain largely unexplored. We aimed to characterize white matter micro- and macrostructure over 3 years after stroke and study associations with white matter metrics and cognitive functions. METHODS: Patients with first-ever or recurrent ischemic stroke of any etiology in any vascular territory were compared with stroke-free age- and sex-matched controls. Those diagnosed with hemorrhagic stroke, TIA, venous infarction, or significant medical comorbidities, psychiatric and neurodegenerative disorders, substance abuse, or history of dementia were excluded. Diffusion-weighted MRI data at 3, 12, and 36 months were analyzed using a longitudinal fixel-based analysis, sensitive to fiber tract-specific differences within a voxel. It was used to examine whole-brain white matter degeneration in stroke compared with control participants. We studied microstructural differences in fiber density and macrostructural changes in fiber-bundle cross-section, in relation to cognitive performance. Analyses were performed controlling for age, intracranial volume, and education (family-wise error-corrected p < 0.05, nonparametric testing over 5,000 permutations). RESULTS: We included 71 participants with stroke (age 66 ± 12 years, 22 women) and 36 controls (age 69 ± 5 years, 13 women). We observed extensive white matter structural degeneration across the whole brain, particularly affecting the thalamic, cerebellar, striatal, and superior longitudinal tracts and corpus callosum. Importantly, follow-up regression analyses in 72 predefined tracts showed that the decline in fiber density and cross-section from 3 months to 3 years was associated with worse cognitive performance at 3 years after stroke, especially affecting visuospatial processing, processing speed, language, and recognition memory. DISCUSSION: We conclude that white matter neurodegeneration in ipsi- and contralesional thalamic, striatal, and cerebellar tracts continues to be greater in stroke survivors compared with stroke-free controls. White matter degeneration persists even years after stroke and is associated with poststroke cognitive impairment. TRIAL REGISTRATION INFORMATION: ClinicalTrails.gov NCT02205424.

Recent Advances in Transition Metal-Based Catalysts for Ethylene Copolymerization with Polar Comonomer.

The synthesis of polar functionalized polyolefin (PFP) offers improvement in mixing properties, polymer surface, and rheological properties with the potential of upgraded polyolefins for modern and ingenious applications. The synthesis of PFP from metal-based catalyzed olefin (non-polar in nature) copolymerization with polar comonomers embodies energy-efficient, atom-efficient, and apparently an upfront methodology. Despite their outstanding success during conventional polymerization of olefin, 3rd and 4th group (early transition metal)-based catalysts, owing to their electrophilic nature, face challenges mainly due to Lewis basic sites of the polar monomers. On the contrary, late transition metal-based catalysts have also made progress, in recent years, for PFP synthesis. The recent past has also witnessed several advancements in the development of dominating palladium-based catalysts while their lower resistance towards ligand functional groups has limited the practical application of abundant and cheaper nickel-based catalysts. However, the relentless efforts of the scientific community, during the past half-decade, have indicated rigorous progress in the development of nickel-based catalysts for PFP synthesis. In this review, we have abridged the recent research trends in both early as well as late transition metal-based catalyst development. Furthermore, we have highlighted the role of transition metal-based catalysts in influencing the polymer properties.

Principles of management of hand fractures.

The optimal management of hand fractures requires a multidisciplinary approach. Initial assessment should include a thorough medical history and clinical examination, followed by appropriate radiological imaging. These are crucial in determining the appropriate management. Following joint stabilisation to allow fractures to unite, early mobilisation is needed to maximise the functional restoration of the hand. In this review, the principles of operative and non-operative management of these injuries are discussed.

Evaluating the Effect of Hypoxia on Human Adult Mesenchymal Stromal Cell Chondrogenesis In Vitro: A Systematic Review.

Human adult mesenchymal stromal cells (MSCs) from a variety of sources may be used to repair defects in articular cartilage by inducing them into chondrogenic differentiation. The conditions in which optimal chondrogenic differentiation takes place are an area of interest in the field of tissue engineering. Chondrocytes exist in vivo in a normally hypoxic environment and thus it has been suggested that exposing MSCs to hypoxia may also contribute to a beneficial effect on their differentiation. There are two main stages in which MSCs can be exposed to hypoxia, the expansion phase when cells are cultured, and the differentiation phase when cells are induced with a chondrogenic medium. This systematic review sought to explore the effect of hypoxia at these two stages on human adult MSC chondrogenesis in vitro. A literature search was performed on PubMed, EMBASE, Medline via Ovid, and Cochrane, and 24 studies were ultimately included. The majority of these studies showed that hypoxia during the expansion phase or the differentiation phase enhances at least some markers of chondrogenic differentiation in adult MSCs. These results were not always demonstrated at the protein level and there were also conflicting reports. Studies evaluating continuous exposure to hypoxia during the expansion and differentiation phases also had mixed results. These inconsistent results can be explained by the heterogeneity of studies, including factors such as different sources of MSCs used, donor variability, level of hypoxia used in each study, time exposed to hypoxia, and differences in culture methodology.

Mendelian Randomization Studies of Lifestyle-Related Risk Factors for Osteoarthritis: A PRISMA Review and Meta-Analysis.

Risk factors for osteoarthritis (OA) often exert effects over protracted time-courses. Mendelian randomization (MR) studies therefore have an advantage over conventional observational studies when studying the causal effect of long-term lifestyle-related risk factors on OA. However, given the heterogeneous design of existing MR studies on OA, the reported causal estimates of these effects remain inconsistent, thus obscuring the true extent of the biological effects of OA lifestyle-risk factors. We conducted a PRISMA systematic review and specifically included MR studies that investigated the causal effect between lifestyle-related risk factors and OA, where causal estimates for various lifestyle factors were pooled for meta-analysis. Quality of studies was assessed according to STROBE-MR guidelines. A total of 1576 studies were evaluated and 23 were included. Overall, the studies included were of high quality and had a low risk of bias. Our meta-analysis demonstrates the positive causal effect of BMI (ORIVW-random effects 1.49 [1.23-1.80]) and negative causal effects of serum calcium (ORIVW-random effects 0.69 [0.57-0.83]) and LDL levels (ORIVW-random effects 0.93 [0.90-0.96]) on OA. Despite the heterogeneous designs and estimates of causal effects provided by various MR studies, our meta-analysis suggests that lifestyle-related risk factors in the form of BMI, serum calcium, and LDL have true biological effects on the development of OA.