Biomaterial-mediated intracellular control of macrophages for cell therapy in pro-inflammatory and pro-fibrotic conditions.

Macrophages are key modulators of all inflammatory diseases and essential for their resolution, making macrophage cell therapy a promising strategy for regenerative medicine. However, since macrophages change rapidly in response to microenvironmental cues, their phenotype must be controlled post-administration. We present a tunable biomaterial-based strategy to control macrophages intracellularly via small molecule-releasing microparticles. Poly(lactic-co-glycolic acid) microparticles encapsulating the anti-inflammatory and anti-fibrotic drug dexamethasone were administered to macrophages in vitro, with uptake rates controlled by different loading regimes. Microparticle dose and dexamethasone content directly affected macrophage phenotype and phagocytic capacity, independent of particle content per cell, leading to an overall pro-reparative, anti-inflammatory, anti-fibrotic phenotype with increased phagocytic and ECM degrading functionality. Intracellularly controlled macrophages partially maintained this phenotype in vivo in a murine pulmonary fibrosis model, with more prominent effects in a pro-fibrotic environment compared to pro-inflammatory. These results suggest that intracellular control using biomaterials has the potential to control macrophage phenotype post-administration, which is essential for successful macrophage cell therapy.

TGF-ßR2 signaling coordinates pulmonary vascular repair after viral injury in mice and human tissue.

Disruption of pulmonary vascular homeostasis is a central feature of viral pneumonia, wherein endothelial cell (EC) death and subsequent angiogenic responses are critical determinants of the outcome of severe lung injury. A more granular understanding of the fundamental mechanisms driving reconstitution of lung endothelium is necessary to facilitate therapeutic vascular repair. Here, we demonstrated that TGF-ß signaling through TGF-ßR2 (transforming growth factor-ß receptor 2) is activated in pulmonary ECs upon influenza infection, and mice deficient in endothelial Tgfbr2 exhibited prolonged injury and diminished vascular repair. Loss of endothelial Tgfbr2 prevented autocrine Vegfa (vascular endothelial growth factor α) expression, reduced endothelial proliferation, and impaired renewal of aerocytes thought to be critical for alveolar gas exchange. Angiogenic responses through TGF-ßR2 were attributable to leucine-rich α-2-glycoprotein 1, a proangiogenic factor that counterbalances canonical angiostatic TGF-ß signaling. Further, we developed a lipid nanoparticle that targets the pulmonary endothelium, Lung-LNP (LuLNP). Delivery of Vegfa mRNA, a critical TGF-ßR2 downstream effector, by LuLNPs improved the impaired regeneration phenotype of EC Tgfbr2 deficiency during influenza injury. These studies defined a role for TGF-ßR2 in lung endothelial repair and demonstrated efficacy of an efficient and safe endothelial-targeted LNP capable of delivering therapeutic mRNA cargo for vascular repair in influenza infection.

Oxidative physiology of two small and highly migratory Arctic seabirds: Arctic terns (Sterna paradisaea) and long-tailed jaegers (Stercorarius longicaudus).

Arctic ecosystems are changing rapidly. The tundra supports nesting migratory seabirds that spend most of their year over the ocean. Migrations are demanding, but it is unclear how physiological capability may equip organisms to respond to their changing environments. For two migratory seabird species nesting in Alaska, USA, the Arctic tern (n = 10) and the long-tailed jaeger (n = 8), we compared oxidative physiology and aerobic capacity measured during incubation and we recorded individual movement paths using electronic tracking tags. Within species, we hypothesized that individuals with longer-distance migrations would show higher oxidative stress and display better aerobic capacity than shorter-distance migrants. We examined blood parameters relative to subsequent fall migration in jaegers and relative to previous spring migration in terns. We present the first measurements of oxidative stress in these species and the first migratory movements of long-tailed jaegers in the Pacific Ocean. Arctic terns displayed positive correlation of oxidative variables, or better integration than jaegers. Relative to physiological sampling, pre-breeding northward migration data were available for terns and post-breeding southward data were available for jaegers. Terns reached a farther maximum distance from the colony than jaegers (16 199 ± 275 km versus 10 947 ± 950 km) and rate of travel northward (447 ± 41.8 km/day) was positively correlated with hematocrit, but we found no other relationships. In jaegers, there were no relationships between individuals' physiology and southward rate of travel (193 ± 52.3 km/day) or migratory distance. While it is not clear whether the much longer migrations of the terns is related to their better integration, or to another factor, our results spark hypotheses that could be evaluated through a controlled phylogenetic study. Species with better integration may be less susceptible to environmental factors that increase oxidative stress, including thermal challenges or changes in prey distribution as the Arctic climate changes rapidly.

Vascular Endothelial-derived SPARCL1 Exacerbates Viral Pneumonia Through Pro-Inflammatory Macrophage Activation.

Inflammation upon infectious lung injury is a double-edged sword: while tissue-infiltrating immune cells and cytokines are necessary to control infection, these same factors often aggravate injury. Full appreciation of both the sources and targets of inflammatory mediators is required to facilitate strategies to maintain antimicrobial effects while minimizing off-target epithelial and endothelial damage. Recognizing that the vasculature is centrally involved in tissue responses to injury and infection, we observed that pulmonary capillary endothelial cells (ECs) exhibit dramatic transcriptomic changes upon influenza injury punctuated by profound upregulation of Sparcl1 . Endothelial deletion and overexpression of SPARCL1 implicated this secreted matricellular protein in driving key pathophysiologic symptoms of pneumonia, which we demonstrate result from its effects on macrophage polarization. SPARCL1 induces a shift to a pro-inflammatory "M1-like" phenotype (CD86 + CD206 - ), thereby increasing associated cytokine levels. Mechanistically, SPARCL1 acts directly on macrophages in vitro to induce the pro-inflammatory phenotype via activation of TLR4, and TLR4 inhibition in vivo ameliorates inflammatory exacerbations caused by endothelial Sparcl1 overexpression. Finally, we confirmed significant elevation of SPARCL1 in COVID-19 lung ECs in comparison with those from healthy donors. Survival analysis demonstrated that patients with fatal COVID-19 had higher levels of circulating SPARCL1 protein compared to those who recovered, indicating the potential of SPARCL1 as a biomarker for prognosis of pneumonia and suggesting that personalized medicine approaches might be harnessed to block SPARCL1 and improve outcomes in high-expressing patients.

Robot-assisted Radical Cystectomy Versus Open Radical Cystectomy: A Systematic Review and Meta-analysis of Perioperative, Oncological, and Quality of Life Outcomes Using Randomized Controlled Trials.

CONTEXT: Differences in recovery, oncological, and quality of life (QoL) outcomes between open radical cystectomy (ORC) and robot-assisted radical cystectomy (RARC) for patients with bladder cancer are unclear. OBJECTIVE: This review aims to compare these outcomes within randomized trials of ORC and RARC in this context. The primary outcome was the rate of 90-d perioperative events. The secondary outcomes included operative, pathological, survival, and health-related QoL (HRQoL) measures. EVIDENCE ACQUISITION: Systematic literature searches of MEDLINE, Embase, Web of Science, and clinicaltrials.gov were performed up to May 31, 2022. EVIDENCE SYNTHESIS: Eight trials, reporting 1024 participants, were included. RARC was associated with a shorter hospital length of stay (LOS; mean difference [MD] 0.21, 95% confidence interval [CI] 0.03-0.39, p = 0.02) than and similar complication rates to ORC. ORC was associated with higher thromboembolic events (odds ratio [OR] 1.84, 95% CI 1.02-3.31, p = 0.04). ORC was associated with more blood loss (MD 322 ml, 95% CI 193-450, p < 0.001) and transfusions (OR 2.35, 95% CI 1.65-3.36, p < 0.001), but shorter operative time (MD 76 min, 95% CI 39-112, p < 0.001) than RARC. No differences in lymph node yield (MD 1.07, 95% CI -1.73 to 3.86, p = 0.5) or positive surgical margin rates (OR 0.95, 95% CI 0.54-1.67, p = 0.9) were present. RARC was associated with better physical functioning or well-being (standardized MD 0.47, 95% CI 0.29-0.65, p < 0.001) and role functioning (MD 8.8, 95% CI 2.4-15.1, p = 0.007), but no improvement in overall HRQoL. No differences in progression-free survival or overall survival were seen. Limitations may include a lack of generalization given trial patients. CONCLUSIONS: RARC offers various perioperative benefits over ORC. It may be more suitable in patients wishing to avoid blood transfusion, those wanting a shorter LOS, or those at a high risk of thromboembolic events. PATIENT SUMMARY: This study compares robot-assisted keyhole surgery with open surgery for bladder cancer. The robot-assisted approach offered less blood loss, shorter hospital stays, and fewer blood clots. No other differences were seen.

Association between proximity to COVID-19 and the quality of life of healthcare workers.

BACKGROUND: The coronavirus disease 2019 (COVID-19) affects almost all countries in the world and it impacts every aspect of people's life-physically, mentally, and socio-economically. There are several research studies examining the impact of this pandemic on health, however, very few studies examining the impact of this pandemic on quality of life. This study aimed to investigate the association between proximity to the COVID-19 and quality of life of healthcare workers and identify factors influencing quality of life. METHODS: A cross-sectional study was conducted among hospital staff in a tertiary hospital in Singapore. Data on demographic, medical history, lifestyle factors, psychosocial factors, and quality of life were collected using online self-administered questionnaire. Quality of life (QoL) was measured by the WHOQOL-BREF questionnaire. Robust linear regression was used to determine factors associated with quality of life. RESULTS: A total of 1911 participants were included in the analysis. The average age of participants was 38.25 (SD = 11.28) years old. 26.90% of participants had been quarantined, hospitalised, being suspected or diagnosed of having COVID-19 infection and they were found to have the lowest levels of QoL across all four domains (physical, psychological, social, and environmental domains). Participants who were singles or nurses, worked in shifts or worked longer hours, had chronic diseases were likely to have lower QoL scores compared to participants in other categories. Healthy lifestyle, social connectivity, resilience, social and workplace support were associated with higher QoL scores. CONCLUSIONS: In planning of measures which aim to improve QoL of healthcare workers, priority should be given to individuals who have been quarantined, hospitalised, being suspected, or diagnosed of having COVID-19 infection. In addition to the proximity of the COVID, lifestyle and psychosocial factors contribute to QoL of healthcare workers. Hence, multifaceted interventions are needed to improve QoL of healthcare workers.

ΔNp63 drives dysplastic alveolar remodeling and restricts epithelial plasticity upon severe lung injury.

The lung exhibits a robust, multifaceted regenerative response to severe injuries such as influenza infection, during which quiescent lung-resident epithelial progenitors participate in two distinct reparative pathways: functionally beneficial regeneration via alveolar type 2 (AT2) cell proliferation and differentiation, and dysplastic tissue remodeling via intrapulmonary airway-resident basal p63+ progenitors. Here we show that the basal cell transcription factor ΔNp63 is required for intrapulmonary basal progenitors to participate in dysplastic alveolar remodeling following injury. We find that ΔNp63 restricts the plasticity of intrapulmonary basal progenitors by maintaining either active or repressive histone modifications at key differentiation gene loci. Following loss of ΔNp63, intrapulmonary basal progenitors are capable of either airway or alveolar differentiation depending on their surrounding environment both in vitro and in vivo. Uncovering these regulatory mechanisms of dysplastic repair and lung basal cell fate choice highlight potential therapeutic targets to promote functional alveolar regeneration following severe lung injuries.

The impact of preoperative glycated hemoglobin (HbA1c) on postoperative complications after elective major abdominal surgery: a meta-analysis.

BACKGROUND: Diabetes is a risk factor for postoperative complications. Previous meta-analyses have shown that elevated glycated hemoglobin (HbA1c) levels are associated with postoperative complications in various surgical populations. However, this is the first meta-analysis to investigate the association between preoperative HbA1c levels and postoperative complications in patients undergoing elective major abdominal surgery. METHODS: PRISMA guidelines were adhered to for this study. Six databases were searched up to April 1, 2020. Primary studies investigating the effect of HbA1c levels on postoperative complications after elective major abdominal surgery were included. Risk of bias and quality of evidence assessments were performed. Data were pooled using a random effects model. Meta-regression was performed to evaluate different HbA1c cut-off values. RESULTS: Twelve observational studies (25,036 patients) were included. Most studies received a 'good' and 'moderate quality' score using the NOS and GRADE, respectively. Patients with a high HbA1c had a greater risk of anastomotic leaks (odds ratio [OR]: 2.80, 95% CI [1.63, 4.83], P < 0.001), wound infections (OR: 1.21, 95% CI [1.08, 1.36], P = 0.001), major complications defined as Clavien-Dindo [CD] 3-5 (OR: 2.16, 95% CI [1.54, 3.01], P < 0.001), and overall complications defined as CD 1-5 (OR: 2.12, 95% CI [1.48, 3.04], P < 0.001). CONCLUSIONS: An HbA1c between 6% and 7% is associated with higher risks of anastomotic leaks, wound infections, major complications, and overall postoperative complications. Therefore, guidelines with an HbA1c threshold > 7% may be putting pre-optimized patients at risk. Future randomized controlled trials are needed to explore causation before policy changes are made.

MicroRNA Signatures of the Developing Primate Fovea.

Rod and cone photoreceptors differ in their shape, photopigment expression, synaptic connection patterns, light sensitivity, and distribution across the retina. Although rods greatly outnumber cones, human vision is mostly dependent on cone photoreceptors since cones are essential for our sharp visual acuity and color discrimination. In humans and other primates, the fovea centralis (fovea), a specialized region of the central retina, contains the highest density of cones. Despite the vast importance of the fovea for human vision, the molecular mechanisms guiding the development of this region are largely unknown. MicroRNAs (miRNAs) are small post-transcriptional regulators known to orchestrate developmental transitions and cell fate specification in the retina. Here, we have characterized the transcriptional landscape of the developing rhesus monkey retina. Our data indicates that non-human primate fovea development is significantly accelerated compared to the equivalent retinal region at the other side of the optic nerve head, as described previously. Notably, we also identify several miRNAs differentially expressed in the presumptive fovea, including miR-15b-5p, miR-342-5p, miR-30b-5p, miR-103-3p, miR-93-5p as well as the miRNA cluster miR-183/-96/-182. Interestingly, miR-342-5p is enriched in the nasal primate retina and in the peripheral developing mouse retina, while miR-15b is enriched in the temporal primate retina and increases over time in the mouse retina in a central-to-periphery gradient. Together our data constitutes the first characterization of the developing rhesus monkey retinal miRNome and provides novel datasets to attain a more comprehensive understanding of foveal development.

A review of preclinical absorbable inferior vena cava filters.

OBJECTIVE: Absorbable inferior vena cava filters (IVCFs) could be more effective and safer than standard IVCFs in theory, as they will self-resorb over time, thus rendering the need for filter retrieval and the risks associated with it unnecessary. This scoping review aims to evaluate the design of current absorbable IVCFs, review the development phase of the absorbable IVCFs, assess the efficacy of the absorbable IVCFs and their complications, and discuss the limitations and areas for future research. METHODS: MEDLINE, PubMed, and Embase databases were electronically searched and citations of relevant studies manually searched. Study selection and data extraction were performed by two independent reviewers using predetermined criteria and stored on premade proforma, respectively. The risk of bias (RoB) for both in vitro and in vivo studies were performed using established RoB tools. RESULTS: Eight studies were suitable for inclusion in this scoping review; five were in vivo and three were in vitro studies. No clinical trials were found. The RoB varied from moderate to high for in vivo studies and from low to moderate for in vitro studies. Overall, there was evidence from both in vivo and in vitro studies that absorbable IVCFs were effective in clot capturing and self-resorption and could decrease complications associated with standard IVCFs. However, there was a broad lack of statistical analyses and control groups to determine the significance of these findings. CONCLUSIONS: Absorbable IVCFs have shown promising features and results in preclinical models. However, significant research needs to be further performed to achieve the ideal characteristics of an absorbable IVCF before the first human trial can be conducted safely.

Impact of preoperative HbA1c on postoperative complications after elective major abdominal surgery: a systematic review protocol.

INTRODUCTION: Diabetes has an increasing worldwide prevalence. It is known to be a predisposing factor for postoperative complications. Preoperative glycaemic control strategies should be pursued as glycaemic control could serve as a modifiable risk factor. Glycated haemoglobin (HbA1c), a marker of 3-month average glycaemic control, has been shown in meta-analyses to predict postoperative complications in cardiothoracic, bariatric and orthopaedic surgery. However, there is no meta-analysis in the major abdominal surgery population, in whom morbidity may be higher due to the nature of the surgery. Understanding the association between HbA1c and postoperative complications could help in preoperative risk prognostication, counselling and glycaemic target selection. The aim of this systematic review and meta-analysis is to evaluate all evidence on the association between preoperative HbA1c and postoperative complications in elective major abdominal surgery, and to investigate the threshold HbA1c level before postoperative complication rates increase. METHODS AND ANALYSIS: This review will be performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. PubMed, Embase, Cochrane Central Register of Controlled Trials, Google Scholar and China National Knowledge Infrastructure will be searched for all original studies. Study selection, data extraction, risk of bias and quality assessment will be conducted by two independent reviewers. The primary outcome is the association between preoperative HbA1c and major postoperative complications (Clavien Dindo 3-5), and the secondary outcome is the association between HbA1c and overall postoperative complications. Data management and synthesis will be performed using Microsoft Excel and Stata to derive pool estimates. ETHICS AND DISSEMINATION: No ethics approval is required as only secondary data will be used. Findings will be disseminated through peer-reviewed journals and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42020167347.

The management and referral of iliofemoral deep venous thrombosis in North West London.

BACKGROUND: Post-thrombotic syndrome is a common complication of iliofemoral deep venous thrombosis (IFDVT). Existing evidence and National Institute for Health and Care Excellence guidelines suggest that this can be reduced by prompt thrombolytic therapy or thrombectomy. We aimed to evaluate the characteristics of IFDVT patients and to identify whether patients are being offered the recommended treatment pathway. METHODS: A multicenter cross-sectional study was conducted across eight hospital sites in the North West London region, of which two were hub hospitals in their local vascular service networks. Patients with proximal DVT were identified using International Classification of Diseases, Tenth Revision coding during a 1-year period. Data on demographics, diagnostic methods used, interventions, and referrals were extracted from electronic and paper medical records. RESULTS: During the study period, 132 patients with IFDVT were identified (mean age, 59.4 years; 55% female); 75% of these patients had an IFDVT. In this cohort, the biggest predisposing factors were previous DVT (n = 35), malignant disease (n = 35), and immobility (n = 20). In total, 104 patients were administered anticoagulation, and 88 of these patients received anticoagulation within 24 hours. The cases of 45 patients were either discussed with or promptly referred to a vascular service, after which 20 patients were treated solely with anticoagulation, whereas 20 patients received thrombolysis of varying methods. CONCLUSIONS: A significant proportion (56%) of symptomatic IFDVT patients are not being appropriately referred to or discussed with vascular services. Of these, 43% would have been eligible for consideration of early thrombus removal. Adherence to the National Institute for Health and Care Excellence guidelines could be improved by increasing awareness among emergency department colleagues.

Let-7 regulates cell cycle dynamics in the developing cerebral cortex and retina.

In the neural progenitors of the developing central nervous system (CNS), cell proliferation is tightly controlled and coordinated with cell fate decisions. Progenitors divide rapidly during early development and their cell cycle lengthens progressively as development advances to eventually give rise to a tissue of the correct size and cellular composition. However, our understanding of the molecules linking cell cycle progression to developmental time is incomplete. Here, we show that the microRNA (miRNA) let-7 accumulates in neural progenitors over time throughout the developing CNS. Intriguingly, we find that the level and activity of let-7 oscillate as neural progenitors progress through the cell cycle by in situ hybridization and fluorescent miRNA sensor analyses. We also show that let-7 mediates cell cycle dynamics: increasing the level of let-7 promotes cell cycle exit and lengthens the S/G2 phase of the cell cycle, while let-7 knock down shortens the cell cycle in neural progenitors. Together, our findings suggest that let-7 may link cell proliferation to developmental time and regulate the progressive cell cycle lengthening that occurs during development.

Human Adipose-Derived Stem Cells with Great Therapeutic Potential.

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift in regenerative medicine. The use of either embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically highly beneficial. While clinically, adipose-derived stem cells (ADSCs) are one of the most widely used types of stem cells used more than five years in clinically setting. It has many advantages including; yields a high number of ADSCs per volume of tissue, high rate of proliferation, anti-fibrotic, anti-apoptotic, anti-inflammation, immunomodulation, and paracrine mechanisms have been demonstrated in various preclinical studies. It is much easier to harvest compared with bone marrow stem cells. Results of clinical studies have demonstrated the potentials of ADSCs for stem cells therapy for a number of clinical disorders. The aim of this paper was to provide an update on the most recent developments of ADSCs, by highlighting the properties and features of ADSCs, critically discussing its clinical benefit and its clinical trials in treatment and regeneration. This is a multi-billion dollars industry with huge interest to clinician, academia and industries.

Habitat structure changes the relationships between predator behavior, prey behavior, and prey survival rates.

The individual behavioral traits of predators and prey sometimes determine the outcome of their interactions. Here, we examine whether changes to habitat complexity alter the effects of predator and prey behavior on their survival rates. Specifically, we test whether behavioral traits (activity level, boldness, and perch height) measured in predators and prey or multivariate behavioral volumes best predict the survival rates of both trophic levels in staged mesocosms with contrasting structural complexity. Behavioral volumes and hypervolumes are a composite group-level behavioral diversity metric built from the individual-level behavioral traits we measured in predators and prey. We stocked mesocosms with a host plant and groups of cannibalistic predators (n = 5 mantises/mesocosm) and their prey (n = 15 katydids/mesocosm), and mesocosms varied in the presence/absence of additional non-living climbing structures. We found that mantis survival rates were unrelated to any behavioral metric considered here, but were higher in structurally complex mesocosms. Unexpectedly, katydids were more likely to survive when mantis groups occupied larger behavioral volumes, indicating that more behaviorally diverse predator groups are less lethal. Katydid mortality was also increased when both predators and prey exhibited higher average perch heights, but this effect was increased by the addition of supplemental structure. This is consistent with the expectation that structural complexity increases the effect of intraspecific behavioral variation on prey survival rates. Collectively, these results convey that the effects of predator and prey behavior on prey survival could depend highly on the environment in which they are evaluated.

Can activity monitors predict outcomes in patients with heart failure? A systematic review.

Actigraphy is increasingly incorporated into clinical practice to monitor intervention effectiveness and patient health in congestive heart failure (CHF). We explored the prognostic impact of actigraphy-quantified physical activity (AQPA) on CHF outcomes. PubMed and Medline databases were systematically searched for cross-sectional studies, cohort studies or randomised controlled trials from January 2007 to December 2017. We included studies that used validated actigraphs to predict outcomes in adult HF patients. Study selection and data extraction were performed by two independent reviewers. A total of 17 studies (15 cohort, 1 cross-sectional, 1 randomised controlled trial) were included, reporting on 2,759 CHF patients (22-89 years, 27.7% female). Overall, AQPA showed a strong inverse relationship with mortality and predictive utility when combined with established risk scores, and prognostic roles in morbidity, predicting cognitive function, New York Heart Association functional class and intercurrent events (e.g. hospitalisation), but weak relationships with health-related quality of life scores. Studies lacked consensus regarding device choice, time points and thresholds of PA measurement, which rendered quantitative comparisons between studies difficult. AQPA has a strong prognostic role in CHF. Multiple sampling time points would allow calculation of AQPA changes for incorporation into risk models. Consensus is needed regarding device choice and AQPA thresholds, while data management strategies are required to fully utilise generated data. Big data and machine learning strategies will potentially yield better predictive value of AQPA in CHF patients.

Spatiotemporal gait changes in healthy pregnant women and women with pelvic girdle pain: A systematic review.

INTRODUCTION: Gait is affected in women with pelvic girdle pain (PGP), a musculoskeletal condition affecting 20% of pregnant women. Whilst there is evidence of spatiotemporal changes in gait during healthy pregnancy, less is known in relation to women with PGP. Appreciating gait characteristics during healthy pregnancy could inform our understanding of the role of gait in PGP. PURPOSE: The purpose of this review was to systematically analyse differences in the spatiotemporal parameters of gait in healthy pregnant women and those with PGP, and to make recommendations to improve research methods in investigating gait in PGP women. METHODS: The review was undertaken following the PRISMA guidelines. Three databases and pre-existing literature were electronically and manually searched. Study selection and data extraction were conducted by two reviewers. Quality assessment was performed using the NHLBI tool for Observational Cohort and Cross-sectional Studies. RESULTS: The search returned 2925 results. Fourteen studies were selected for data extraction. Twelve studies investigated gait in healthy pregnant women and two in PGP women. Studies employed either a cohort or cross-sectional design and used various methods to assess gait. Three, nine and two studies were high, medium and low in quality, respectively. Direct comparisons between studies were impeded due to incomparable gestational time-points investigated, in addition to variations in gait parameters and definitions used. CONCLUSION: Evidence from studies on healthy pregnant women could inform future research on PGP women, for which current evidence is scarce. We recommend the standardisation of critical factors to allow inter-study comparisons for a meta-analysis.

Emerging In Vitro 3D Tumour Models in Nanoparticle-Based Gene and Drug Therapy.

3D models are emerging as valuable tools for personalised nanoparticle-based cancer treatments. 3D models represent in vivo cancers more realistically than 2D patterns that are grown in Petri dishes. However, creating a 3D cancer model that mimics the complexity and heterogeneity of cancers in vivo remains difficult.