Animal Studies Research Articles

Near-infrared II theranostic agents for the diagnosis and treatment of Alzheimer's disease.

Near-infrared II theranostic agents have gained great momentum in the research field of AD owing tothe appealing advantages. Recently, an array of activatable NIR-II fluorescence probes has been developed tospecifically monitor pathological targets of AD. Furthermore, various NIR-II-mediated nanomaterials with desirablephotothermal and photodynamic properties have demonstrated favorable outcomes in the management of AD. We summerized amounts of references and focused on small-molecule probes, nanomaterials,photothermal therapy, and photodynamic therapy based on NIR-II fluorescent imaging for the diagnosis andtreatment in AD. In addition, design strategies for NIR-II-triggered theranostics targeting AD are presented, andsome prospects are also addressed. NIR-II theranostic agents including small molecular probes and nanoparticles have received theincreasing attention for biomedical applications. Meanwhile, most of the theranostic agents exhibited the promisingresults in animal studies. To our surprise, the multifunctional nanoplatforms also show a great potential in thediagnosis and treatment of AD. Although NIR-II theranostic agents showed the great potential in diagnosis and treatment of AD,there are still many challenges: 1) Faborable NIR-II fluorohpores are still lacking; 2) Biocompatibility, bioseurity anddosage of NIR-II theranostic agents should be further revealed; 3) New equipment and software associated withNIR-II imaging system should be explored.

Technical Advances Targeting Multiday Preservation of Isolated Ex Vivo Lung Perfusion.

Indications for ex vivo lung perfusion (EVLP) have evolved from assessment of questionable donor lungs to treatment of some pathologies and the logistics. Yet up to 3 quarters of donor lungs remain discarded across the globe. Multiday preservation of discarded human lungs on EVLP platforms would improve donor lung utilization rates via application of sophisticated treatment modalities, which could eventually result in zero waitlist mortality. The purpose of this article is to summarize advances made on the technical aspects of the protocols in achieving a stable multiday preservation of isolated EVLP. Based on the evidence derived from large animal and/or human studies, the following advances have been considered important in achieving this goal: ability to reposition donor lungs during EVLP; perfusate adsorption/filtration modalities; perfusate enrichment with plasma and/or donor whole blood, nutrients, vitamins, and amino acids; low-flow, pulsatile, and subnormothermic perfusion; positive outflow pressure; injury specific personalized ventilation strategies; and negative pressure ventilation. Combination of some of these advances in an automatized EVLP device capable of managing perfusate biochemistry and ventilation would likely speed up the processes of achieving multiday preservation of isolated EVLP.

Gap junctions in polycystic ovary syndrome: Implications for follicular arrest.

Gap junctions are specialized intercellular conduits that provide a direct pathway between neighboring cells, which are involved in numerous physiological processes, such as cellular differentiation, cell growth, and metabolic coordination. The effect of gap junctional hemichannels in folliculogenesis is particularly obvious, and the down-regulation of connexins is related to abnormal follicle growth. Polycystic ovary syndrome (PCOS) is a ubiquitous endocrine disorder of the reproductive system, affecting the fertility of adult women due to anovulation. Exciting evidence shows that gap junction is involved in the pathological process related to PCOS and affects the development of follicles in women with PCOS. In this review, we examine the expression of connexins in follicular cells of PCOS and figure out whether such communication could have consequences for PCOS women. While along with results from clinical and related animal studies, we summarize the mechanism of connexins involved in the pathogenesis of PCOS.

Efficacy of bone ring grafts for the reconstruction of alveolar ridge deficiencies: a systematic review. Part II: animal trials

Background: Bone ring (BR) grafts have been introduced to reconstruct alveolar ridge defects with simultaneous implant placement, but their clinical effectiveness remains undetermined. The aim of the current systematic review was to critically appraise evidence from animal studies regarding the effectiveness of BR grafts in alveolar ridge reconstruction and their variations under different surgical protocols. Methods: Electronic retrieval of six databases (MEDLINE, Embase, Cochrane Library, ScienceDirect, Web of Science, and Scopus) and citation search until October 11, 2023, for animal studies on bone augmentation employing BR grafts. The outcome variables were total bone area (BA), bone volume (BV), bone-implant contact (BIC), and histology. The protocol was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and prospectively registered with PROSPERO (CRD42023453949). Results: Ten studies were included in the qualitative analysis according to the screening criteria. Two studies demonstrated favorable bone remodeling and osseointegration of the BR with both the implant and pristine bone. A comparative study between autogenous BRs and allogenic BRs reported a higher percentage of BA and BIC at four months of healing, but conflicting data were observed at eight months. Another study indicated a significant advantage of autogenous BRs over bovine and biphasic ceramic BRs in terms of BA and BIC after five weeks. Three studies found that using collagen membranes did not significantly affect BA, BV, or BIC when used simultaneously with autogenous BRs during implant placement. Two studies evaluated one-stage and two-stage implant placement in conjunction with BR grafts, revealing similar levels of BA, BV, and BIC except for differences in total treatment time. Furthermore, one study found that the use of mucogingival junction incision and split-thickness flap significantly reduced the incidence of wound dehiscence compared with conventional incision and flap. Conclusions: Vertical bone augmentation surgery utilizing BR grafts with one-stage implant placement yielded histological and histomorphometric outcomes comparable to those achieved with two-stage implant placement or the additional application of collagen membrane.

Intra-arrest blood-based biomarkers for out-of-hospital cardiac arrest: A scoping review.

Blood-based biomarkers play a central role in the diagnosis and treatment of critically ill patients, yet none are routinely measured during the intra-arrest phase of out-of-hospital cardiac arrest (OHCA). Our objective was to describe methodological aspects, sources of evidence, and gaps in research surrounding intra-arrest blood-based biomarkers for OHCA. We used scoping review methodology to summarize existing literature. The protocol was designed a priori following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews. Inclusion criteria were peer-reviewed scientific studies on OHCA patients with at least one blood draw intra-arrest. We excluded in-hospital cardiac arrest and animal studies. There were no language, date, or study design exclusions. We conducted an electronic literature search using PubMed and Embase and hand-searched secondary literature. Data charting/synthesis were performed in duplicate using standardized data extraction templates. The search strategy identified 11,834 records, with 118 studies evaluating 105 blood-based biomarkers included. Only eight studies (7%) had complete reporting. The median number of studies per biomarker was 2 (interquartile range 1-4). Most studies were conducted in Asia (63 studies, 53%). Only 22 studies (19%) had blood samples collected in the prehospital setting, and only six studies (5%) had samples collected by paramedics. Pediatric patients were included in only three studies (3%). Out of eight predefined biomarker categories of use, only two were routinely assessed: prognostic (97/105, 92%) and diagnostic (61/105, 58%). Despite a large body of literature on intra-arrest blood-based biomarkers for OHCA, gaps in methodology and knowledge are widespread.

Effect of polyphenols against complications of COVID-19: current evidence and potential efficacy.

The COVID-19 pandemic that started in 2019 and resulted in significant morbidity and mortality continues to be a significant global health challenge, characterized by inflammation, oxidative stress, and immune system dysfunction.. Developing therapies for preventing or treating COVID-19 remains an important goal for pharmacology and drug development research. Polyphenols are effective against various viral infections and can be extracted and isolated from plants without losing their therapeutic potential. Researchers have developed methods for separating and isolating polyphenols from complex matrices. Polyphenols are effective in treating common viral infections, including COVID-19, and can also boost immunity. Polyphenolic-based antiviral medications can mitigate SARS-CoV-2 enzymes vital to virus replication and infection. Individual polyphenolic triterpenoids, flavonoids, anthraquinonoids, and tannins may also inhibit the SARS-CoV-2 protease. Polyphenol pharmacophore structures identified to date can explain their action and lead to the design of novel anti-COVID-19 compounds. Polyphenol-containing mixtures offer the advantages of a well-recognized safety profile with few known severe side effects. However, studies to date are limited, and further animal studies and randomized controlled trials are needed in future studies. The purpose of this study was to review and present the latest findings on the therapeutic impact of plant-derived polyphenols on COVID-19 infection and its complications. Exploring alternative approaches to traditional therapies could aid in developing novel drugs and remedies against coronavirus infection.

Effect of Injectable Acellular Adipose Matrix on Soft Tissue Reconstruction in a Murine Model.

The extracellular matrix isolated from adipose tissue, known as acellular adipose matrix (AAM), represents a novel biomaterial. AAM functions as a scaffold that not only supports stem cell proliferation and differentiation but also induces adipogenesis and angiogenesis. This study aims to investigate the volumetric effects and microenvironmental changes associated with injectable AAM in comparison to conventional fat grafting. AAM was manufactured from fresh human abdominoplasty fat using a mechanically modified method and then transformed into an injectable form. Lipoaspirate was harvested employing the Coleman technique. A weight and volume study was conducted on athymic nude mice by injecting either injectable AAM or lipoaspirate into the scalp (n=6 per group). After eight weeks, graft retention was assessed through weight measurement and volumetric analysis using micro-computed tomography (micro-CT) scanning. Histological analysis was performed using immunofluorescence staining for perilipin and CD31. Injectable AAM exhibited similar weight and volume effects in murine models. Histological analysis revealed comparable inflammatory cell presence with minimal capsule formation when compared to conventional fat grafts. Adipogenesis occurred in both AAM-injected and conventional fat graft models, with no significant difference in the blood vessel area (%) between the two. In summary, injectable AAM demonstrates effectiveness comparable to conventional fat grafting concerning volume effects and tissue regeneration in soft tissue reconstruction. This promising allogeneic injectable holds the potential to serve as a safe and effective "Off-the-Shelf" alternative in both aesthetic and reconstructive clinical practices. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

How Reliable Is Endoscopic Scoring of Postoperative Recurrence in Crohn Disease?: A Systematic Review and Meta-Analysis

Objective: Guidelines advise to perform endoscopic surveillance following ileocolic resection (ICR) in Crohn disease (CD) for timely diagnosis of recurrence. This study aims to assess the variation in endoscopic recurrence (ER) rates in patients after ICR for CD using the most commonly used classification systems, the Rutgeerts score (RS) and modified Rutgeerts score (mRS) classifications. Methods: A systematic literature search using MEDLINE, Embase, and the Cochrane Library was performed. Randomized controlled trials and cohort studies describing ER < 12 months after an ICR for CD were included. Animal studies, reviews, case reports (<30 included patients), pediatric studies, and letters were excluded. The Newcastle–Ottawa Quality Assessment Scale and Cochrane Collaboration’s tool were used to assess risk of bias. Main outcome was the range of ER rates within 12 months postoperatively, defined as RS ≥ i2 and/or mRS ≥ i2b. A proportional meta-analysis was performed. The final search was performed on January 4, 2022. The study was registered at PROSPERO, CRD42022363208. Results: Seventy-six studies comprising 7751 patients were included. The weighted mean of ER rates in all included studies was 44.0% (95% confidence interval, 43.56–44.43). The overall range was 5.0% to 93.0% [interquartile range (IQR), 29.2–59.0]. The weighted means for RS and mRS were 44.0% and 41.1%, respectively. The variation in ER rates for RS and mRS were 5.0% to 93.0% (IQR, 29.0–59.5) and 19.8% to 62.9% (IQR, 37.3–46.5), respectively. Within studies reporting both RS and mRS, the weighted means for ER were 61.3% and 40.6%, respectively. Conclusions: This study demonstrates a major variation in ER rates after ICR for CD, suggesting a high likelihood of inadequate diagnosis of disease recurrence, with potentially impact on quality of life and health care consumption. Therefore, there is an important need to improve endoscopic scoring of recurrent disease.

Implant Stability and Histomorphometric Analysis Comparing Two Different Implant Macrogeometries Placed in Fresh Sockets: An Experimental Study in Sheep.

The aim of the present animal study was to examine the impact of two implant designs that promote different insertion torque values on implant stability and evaluate, histomorphometrically, the bone healing for immediate implant placement in fresh sockets. Twelve female sheep (35.0±5.0kg) and 48 conical Morse-taper dental implants divided into two groups (n = 24 per group): G1 group, where the implants present a design that can provide high insertion torque values; and G2 group, where the implants present a design that can provide low insertion torque values. Both had the same surface treatment, and dimensions (4.0 mm in diameter and 10 mm in length). The first two posterior teeth (both sides) were extracted carefully. Sequentially, there were osteotomies in the mesial socket of each molar tooth. The final implant position was 2 mm below the buccal bone crest level. On the right side, implants of the G1 were placed anteriorly, followed by implants of the G2; and, on the left side, it was the reverse. A digital torquemeter was used to measure the maximum final insertion torque value (f-IT). The initial implant stability quotient (ISQ) was measured immediately after the implant insertion (T0) and immediately after the euthanasia and removing the mandibles with the implants. The animals were euthanized (n=6 animals/ time) at 21 days (T1) and 35 days (T2). The t-test was used to compare statistical differences for each intragroup parameter analyzed. Pearson's correlation was used to analyze possible correlations: f-IT and BIC%, f-IT and ISQ, and ISQ and %BIC. Regarding the insertion torque, the G1 presented higher values than the G2, with a statistically significant difference (p<0.0001). The ISQ mean values were higher in the B-L direction than those obtained for M-D for both groups. %BIC measurements showed higher values in samples from G2 than G1 at both times and in both directions. New bone, medullary spaces, and collagen matrix had statistical differences between the groups at each evaluation time. Using implants with a modified macrogeometry plays a significant role in implant stability and the healing process of bone tissue around the implant. It is important for clinicians to carefully consider implant macrogeometry when planning dental implant surgery to achieve optimal implant stability and successful osseointegration, mainly in cases of immediate implant placement.

Shark Dive and Hologram Zoo: Two Case Studies of Virtual Animal Encounters as Possible Models for Sustainable Wildlife Tourism.

Wildlife tourism is commonly argued to positively contribute to nature conservation by providing humans with educational and meaningful first-hand experiences with animals. However, concern for the sustainability of nature due to the negative impacts of wildlife tourism on animals and the environment invites alternative virtual opportunities for close encounters. Participant Observation framed by an Animal Studies perspective is employed to interpret two contemporary Australian family entertainments, Shark Dive and Hologram Zoo, centred on providing people with wild animal interactions but without real animals present. Shark Dive is a theatrical puppetry production replicating a real shark dive, and Hologram Zoo is an augmented reality experience that displays a variety of animals in 3D. The content of both is examined to understand how the animals are imagined, experienced, and given significance to determine whether they offer viable alternatives or complementary additions to in situ wildlife tourism. Findings reveal both hold potential for virtual wildlife tourism. Shark Dive provides a positive representation of marine life, generating awareness about conservation and encouraging self-reflection. Hologram Zoo's depiction of wild animals is impressive, but to more closely align with contemporary wildlife tourism ideals, the experience could enhance its conservation messaging and positive human-animal interactions.

Torsion constants and virtual mechanical tests are valid image-based surrogate measures of ovine fracture healing.

In large animal studies, the mechanical reintegration of the bone fragments is measured using postmortem physical testing, but these assessments can only be performed once, after sacrifice. Image-based virtual mechanical testing is an attractive alternative because it could be used to monitor healing longitudinally. However, the procedures and software required to perform finite element analysis (FEA) on subject-specific models for virtual mechanical testing can be time consuming and costly. Accordingly, the goal of this study was to determine whether a simpler image-based geometric measure-the torsion constant, sometimes known as polar moment of inertia-can be reliably used as a surrogate measure of bone healing in large animals. To achieve this, postmortem biomechanical testing and microCT scans were analyzed for a total of 33 operated and 20 intact ovine tibiae. An image-processing procedure to compute the attenuation-weighted torsion constant from the microCT scans was developed in MATLAB and this code has been made freely available. Linear regression analysis was performed between the postmortem biomechanical data, the results of virtual mechanical testing using FEA, and the torsion constants measured from the scans. The results showed that virtual mechanical testing is the most reliable surrogate measure of postmortem torsional rigidity, having strong correlations and high absolute agreement. However, when FEA is not practical, the torsion constant is a viable alternative surrogate measure that is moderately correlated with postmortem torsional rigidity and can be readily calculated.

Tinnitus-related increases in single-unit activity in awake rat auditory cortex correlate with tinnitus behavior

Tinnitus is known to affect 10–15 % of the population, severely impacting 1–2 % of those afflicted. Canonically, tinnitus is generally a consequence of peripheral auditory damage resulting in maladaptive plastic changes in excitatory/inhibitory homeostasis at multiple levels of the central auditory pathway as well as changes in diverse nonauditory structures. Animal studies of primary auditory cortex (A1) generally find tinnitus-related changes in excitability across A1 layers and differences between inhibitory neuronal subtypes. Changes due to sound-exposure include changes in spontaneous activity, cross-columnar synchrony, bursting and tonotopic organization. Few studies in A1 directly correlate tinnitus-related changes in neural activity to an individual animal's behavioral evidence of tinnitus. The present study used an established condition-suppression sound-exposure model of chronic tinnitus and recorded spontaneous and driven single-unit responses from A1 layers 5 and 6 of awake Long-Evans rats. A1 units recorded from animals with behavioral evidence of tinnitus showed significant increases in spontaneous and sound-evoked activity which directly correlated to the animal's tinnitus score. Significant increases in the number of bursting units, the number of bursts/minute and burst duration were seen for A1 units recorded from animals with behavioral evidence of tinnitus. The present A1 findings support prior unit recording studies in auditory thalamus and recent in vitro findings in this same animal model. The present findings are consistent with sensory cortical studies showing tinnitus- and neuropathic pain-related down-regulation of inhibition and increased excitation based on plastic neurotransmitter and potassium channel changes. Reducing A1 deep-layer tinnitus-related hyperactivity is a potential target for tinnitus pharmacotherapy.

Brain-Derived Neurotrophic Factor (BDNF) Enhances Osteogenesis and May Improve Bone Microarchitecture in an Ovariectomized Rat Model.

Brain-derived neurotrophic factor (BDNF) has gained attention as a therapeutic agent due to its potential biological activities, including osteogenesis. However, the molecular mechanisms involved in the osteogenic activity of BDNF have not been fully understood. This study aimed to investigate the action of BDNF on the osteoblast differentiation in bone marrow stromal cells, and its influence on signaling pathways. In addition, to evaluate the clinical efficacy, an in vivo animal study was performed. Preosteoblast cells (MC3T3-E1), bone marrow-derived stromal cells (ST2), and a direct 2D co-culture system were treated with BDNF. The effect of BDNF on cell proliferation was determined using the CCK-8 assay. Osteoblast differentiation was assessed based on alkaline phosphatase (ALP) activity and staining and the protein expression of multiple osteoblast markers. Calcium accumulation was examined by Alizarin red S staining. For the animal study, we used ovariectomized Sprague-Dawley rats and divided them into BDNF and normal saline injection groups. MicroCT, hematoxylin and eosin (H&E), and tartrate-resistant acid phosphatase (TRAP) stain were performed for analysis. BDNF significantly increased ALP activity, calcium deposition, and the expression of osteoblast differentiation-related proteins, such as ALP, osteopontin, etc., in both ST-2 and the MC3T3-E1 and ST-2 co-culture systems. Moreover, the effect of BDNF on osteogenic differentiation was diminished by blocking tropomyosin receptor kinase B, as well as inhibiting c-Jun N-terminal kinase and p38 MAPK signals. Although the animal study results including bone density and histology showed increased osteoblastic and decreased osteoclastic activity, only a portion of parameters reached statistical significance. Our study results showed that BDNF affects osteoblast differentiation through TrkB receptor, and JNK and p38 MAPK signal pathways. Although not statistically significant, the trend of such effects was observed in the animal experiment.

Role of Treg cell subsets in cardiovascular disease pathogenesis and potential therapeutic targets.

In the genesis and progression of cardiovascular diseases involving both innate and adaptive immune responses, inflammation plays a pivotal and dual role. Studies in experimental animals indicate that certain immune responses are protective, while others exacerbate the disease. T-helper (Th) 1 cell immune responses are recognized as key drivers of inflammatory progression in cardiovascular diseases. Consequently, the CD4+CD25+FOXP3+ regulatory T cells (Tregs) are gaining increasing attention for their roles in inflammation and immune regulation. Given the critical role of Tregs in maintaining immune-inflammatory balance and homeostasis, abnormalities in their generation or function might lead to aberrant immune responses, thereby initiating pathological changes. Numerous preclinical studies and clinical trials have unveiled the central role of Tregs in cardiovascular diseases, such as atherosclerosis. Here, we review the roles and mechanisms of Treg subsets in cardiovascular conditions like atherosclerosis, hypertension, myocardial infarction and remodeling, myocarditis, dilated cardiomyopathy, and heart failure. While the precise molecular mechanisms of Tregs in cardiac protection remain elusive, therapeutic strategies targeting Tregs present a promising new direction for the prevention and treatment of cardiovascular diseases.

Animal models of Klebsiella pneumoniae mucosal infections.

Klebsiella pneumoniae is among the most relevant pathogens worldwide, causing high morbidity and mortality, which is worsened by the increasing rates of antibiotic resistance. It is a constituent of the host microbiota of different mucosa, that can invade and cause infections in many different sites. The development of new treatments and prophylaxis against this pathogen rely on animal models to identify potential targets and evaluate the efficacy and possible side effects of therapeutic agents or vaccines. However, the validity of data generated is highly dependable on choosing models that can adequately reproduce the hallmarks of human diseases. The present review summarizes the current knowledge on animal models used to investigate K. pneumoniae infections, with a focus on mucosal sites. The advantages and limitations of each model are discussed and compared; the applications, extrapolations to human subjects and future modifications that can improve the current techniques are also presented. While mice are the most widely used species in K. pneumoniae animal studies, they present limitations such as the natural resistance to the pathogen and difficulties in reproducing the main steps of human mucosal infections. Other models, such as Drosophila melanogaster (fruit fly), Caenorhabditis elegans, Galleria mellonella and Danio rerio (zebrafish), contribute to understanding specific aspects of the infection process, such as bacterial lethality and colonization and innate immune system response, however, they but do not present the immunological complexity of mammals. In conclusion, the choice of the animal model of K. pneumoniae infection will depend mainly on the questions being addressed by the study, while a better understanding of the interplay between bacterial virulence factors and animal host responses will provide a deeper comprehension of the disease process and aid in the development of effective preventive/therapeutic strategies.

An invitation to bring animals into feminist and queer sociology

AbstractThis paper presents an invitation to feminist and queer sociology to engage more frequently, enthusiastically, and deeply with animals. Feminist and queer sociology that attend to animals and animality stand to develop better knowledge for animals and animal studies and for women, queers, and feminist and queer sociology. Sociologists working from feminist and queer perspectives are also particularly well‐positioned within the discipline of sociology to contribute to and take advantage of the insights of the field of feminist animal studies. After a brief review of what feminist animal studies is, I proceed through three steps to elaborate the imperative for feminist and queer sociology to consider animals. First, I show how feminist animal studies as a theoretical perspective engages with issues that are core to feminist and queer sociology. Second, I center intersectional feminism and lay out how incorporating species can and does enhance our understanding of intersectional processes. Third, I present an ethical call, grounded in the traditions of feminist ethics and ecofeminism, to attend to species in feminist and queer sociology.

Identifying the Cerebral Physiologic Response to Aerobic Exercise Following Concussion: A Scoping Review.

The purpose of this study was to identify the cerebral physiologic response to aerobic exercise in individuals with a symptomatic concussion, highlighting available knowledge and knowledge gaps in the literature. A systematic scoping review was conducted and reported in keeping with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. A search of EMBASE, MEDLINE, SCOPUS, BIOSIS, and Cochrane libraries was conducted on June 15, 2023 (from database inception). An online systematic/scoping review management system was used to remove duplicates, and the remaining articles were screened for inclusion by 2 researchers. Inclusion criteria required articles to be original research published in peer-reviewed journals. Additionally, studies were required to have an aerobic exercise component, include a measure of cerebral physiology during a bout of aerobic exercise, exclude moderate and/or severe traumatic brain injury (TBI) populations, and be in the English language. Both human and animal studies were included, with participants of any age who were diagnosed with a mild TBI/concussion only (ie, Glasgow Coma Scale score ≥ 13). Studies could be of any design as long as a measure of cerebral physiologic response to a bout of aerobic exercise was included. The search resulted in 1773 articles to be screened and data from 3 eligible studies were extracted. There are currently too few studies investigating the cerebral physiologic response to aerobic exercise following concussion or mild TBI to draw definitive conclusions. Further research on this topic is necessary since understanding the cerebral physiologic response to aerobic exercise in the concussion and mild TBI populations could assist in optimizing exercise-based treatment prescription and identifying other targeted therapies.

Incidence, Prevalence, Risk Factors, and Clinical Treatment for Children with Developmental Dysplasia of the Hip in Saudi Arabia. A Systematic Review.

Developmental dysplasia of the hip (DDH) leads to pain, joint instability, and early degenerative joint disease. Incidence, prevalence, and management strategies of DDH have been well-documented in several countries, but not in Saudi Arabia. We synthesized the current evidence regarding incidence, prevalence, risk factors, and clinical treatment for children with DDH in Saudi Arabia. We searched 3 databases to locate studies. Studies that included children with DDH in Saudi Arabia; reported either incidence rate, prevalence, risk factors, and/or clinical practice; and were available in English or Arabic were included. We excluded reviews, case studies, or animal studies. Two independent authors reviewed potential studies and assessed study's quality. Our search yielded 67 potential studies, of which 16 studies were included (total DDH sample = 3,127; age range = 2.5 to 86.4 months). Three studies reported incidence rates ranging from 3.1 to 4.9 per 1000 births, and 3 studies reported prevalence ranging from 6 to 78%. Nine studies reported that female sex, breech position, family history, and age less than 3 years were risk factors associated with DDH. Four studies reported that brace applications and closed reduction were conservative treatments, and 9 studies reported that open hip reduction, adductor tenotomy, and/or pelvic osteotomy were surgical approaches to treat DDH. In Saudi Arabia, the Incidence and prevalence rates of DDH are 3.1 to 4.9 per 1,000 births, and 6-78%, respectively (differ from what has been reported in other countries), but the risk factors of DDH in Saudi Arabia appear to be similar in comparison to other countries (female, breech presentation, family history of DDH).

Discovering single cannabidiol or synergistic antitumor effects of cannabidiol and cytokine-induced killer cells on non-small cell lung cancer cells.

A multitude of findings from cell cultures and animal studies are available to support the anti-cancer properties of cannabidiol (CBD). Since CBD acts on multiple molecular targets, its clinical adaptation, especially in combination with cancer immunotherapy regimen remains a serious concern. Considering this, we extensively studied the effect of CBD on the cytokine-induced killer (CIK) cell immunotherapy approach using multiple non-small cell lung cancer (NSCLC) cells harboring diverse genotypes. Our analysis showed that, a) The Transient Receptor Potential Cation Channel Subfamily V Member 2 (TRPV2) channel was intracellularly expressed both in NSCLC cells and CIK cells. b) A synergistic effect of CIK combined with CBD, resulted in a significant increase in tumor lysis and Interferon gamma (IFN-g) production. c) CBD had a preference to elevate the CD25+CD69+ population and the CD62L_CD45RA+terminal effector memory (EMRA) population in NKT-CIK cells, suggesting early-stage activation and effector memory differentiation in CD3+CD56+ CIK cells. Of interest, we observed that CBD enhanced the calcium influx, which was mediated by the TRPV2 channel and elevated phosphor-Extracellular signal-Regulated Kinase (p-ERK) expression directly in CIK cells, whereas ERK selective inhibitor FR180204 inhibited the increasing cytotoxic CIK ability induced by CBD. Further examinations revealed that CBD induced DNA double-strand breaks via upregulation of histone H2AX phosphorylation in NSCLC cells and the migration and invasion ability of NSCLC cells suppressed by CBD were rescued using the TRPV2 antagonist (Tranilast) in the absence of CIK cells. We further investigated the epigenetic effects of this synergy and found that adding CBD to CIK cells decreased the Long Interspersed Nuclear Element-1 (LINE-1) mRNA expression and the global DNA methylation level in NSCLC cells carrying KRAS mutation. We further investigated the epigenetic effects of this synergy and found that adding CBD to CIK cells decreased the Long Interspersed Nuclear Element-1 (LINE-1) mRNA expression and the global DNA methylation level in NSCLC cells carrying KRAS mutation. Taken together, CBD holds a great potential for treating NSCLC with CIK cell immunotherapy. In addition, we utilized NSCLC with different driver mutations to investigate the efficacy of CBD. Our findings might provide evidence for CBD-personized treatment with NSCLC patients.

Antimicrobial prophylaxis in companion animal surgery: A scoping review for European Network for Optimization of Antimicrobial Therapy (ENOVAT) guidelines

Surgical antimicrobial prophylaxis (SAP) is widely used to reduce the risk of surgical site infections (SSI), but there is uncertainty as to what the proportion of SSI reduction is. Therefore, it is difficult for surgeons to properly weigh the costs, risks and benefits for individual patients when deciding on the use of SAP, making it challenging to promote antimicrobial stewardship in primary practice settings. The objective of this study was to map the veterinary evidence focused on assessing the effect of SAP on SSI development and in order to identify surgical procedures with some research evidence and possible knowledge gaps. In October 2021 and December 2022, Scopus, CAB Abstracts, Web of Science Core Collection, Embase and MEDLINE were systematically searched. Double blinded screening of records was performed to identify studies in companion animals that reported on the use of SAP and SSI rates. Comparative data were available from 34 out of 39123 records screened including: eight randomised controlled trials (RCT), 23 cohort studies (seven prospective and 16 retrospective) and three retrospective case series representing 12476 dogs and cats in total. Extracted data described peri- or post-operative SAP in nine, and 25 studies, respectively. In the eight RCTs evaluating SAP in companion animals, surgical procedure coverage was skewed towards orthopaedic stifle surgeries in referral settings and there was large variation in SAP protocols, SSI definitions and follow-up periods. More standardized data collection and agreement of SSI definitions is needed to build stronger evidence for optimized patient care.