The Norwegian registry for spine surgery (NORspine): cohort profile.

PURPOSE: To review and describe the development, methods and cohort of the lumbosacral part of the Norwegian registry for spine surgery (NORspine). METHODS: NORspine was established in 2007. It is government funded, covers all providers and captures consecutive cases undergoing operations for degenerative disorders. Patients' participation is voluntary and requires informed consent. A set of baseline-, process- and outcome-variables (3 and 12 months) recommended by the International Consortium for Health Outcome Measurement is reported by surgeons and patients. The main outcome is the Oswestry disability index (ODI) at 12 months. RESULTS: We show satisfactory data quality assessed by completeness, timeliness, accuracy, relevance and comparability. The coverage rate has been 100% since 2016 and the capture rate has increased to 74% in 2021. The cohort consists of 60,647 (47.6% women) cases with mean age 55.7 years, registered during the years 2007 through 2021. The proportions > 70 years and with an American Society of Anaesthesiologists' Physical Classification System (ASA) score > II has increased gradually to 26.1% and 19.3%, respectively. Mean ODI at baseline was 43.0 (standard deviation 17.3). Most cases were operated with decompression for disc herniation (n = 26,557, 43.8%) or spinal stenosis (n = 26,545, 43.8%), and 7417 (12.2%) with additional or primary fusion. The response rate at 12 months follow-up was 71.6%. CONCLUSION: NORspine is a well-designed population-based comprehensive national clinical quality registry. The register's methods ensure appropriate data for quality surveillance and improvement, and research.

Association between periodontitis and disc structural failure in older adults with lumbar degenerative disorders: A prospective cohort study.

BACKGROUND: Bacterial microbiome as a putative trigger of inflammation might indicate the cascade of mouth-gut-disc axis for causing intervertebral disc (IVD) structural failures (such as IVD degeneration and endplate change) processed. However, direct evidence for the mouth-gut-disc axis still unclear. Therefore, it is interesting to explore periodontal inflammation related to IVD structural failures and clinical outcomes. METHODS: This prospective cohort study enrolled older adults (aged ≥ 75 years) who scheduled to undergo elective open lumbar spine surgery. Demographic, radiological, clinical, and periodontal parameters were recorded. Independent samples t-test and Pearson's correlation analysis were calculated. RESULTS: A total of 141 patients with lumbar degenerative disorders (56 males and 85 females; age 79.73 ± 3.34 years) were divided into edentulous group (19 patients), No/Mild group (84 patients), and Moderate/Severe group (38 patients). The incidence rates of IVD degeneration in each lumbar segmental level based on Pfirrmann grade and endplate change in the fourth and fifth lumbar vertebrae, and Visual Analogue Scale (VAS) low back pain (LBP) and leg pain of patients at preoperative in dentate group was significantly higher compared with edentulous group, especially the comparisons between Moderate/Severe and edentulous groups. There were no significant differences in the range of motion, lumbar lordosis, pelvic incidence, pelvic tilt, sacral slope, and disc height between dentate and edentulous groups. There was a positive association between plaque index (PLI) and pain scores (VAS LBP: r = 0.215, P = 0.030 and VAS leg pain: r = 0.309, P = 0.005), but no significant difference in Oswestry disability index (ODI) score. CONCLUSION: Results show that the severity of periodontitis is associated with higher incidence rates of IVD degeneration and endplate change and clinical outcomes in older adults with lumbar degenerative disorders. Furthermore, the discovery of these relationships unveils a novel mechanism through which the alterations in oral microbiome composition potentially promote IVD degeneration and pain.

Six generations of CHMP2B-mediated Frontotemporal Dementia: Clinical features, predictive testing, progression, and survival.

OBJECTIVES: Chromosome 3-linked frontotemporal dementia (FTD-3) is caused by a c.532-1G > C mutation in the CHMP2B gene. It is extensively studied in a Danish family comprising one of the largest families with an autosomal dominantly inherited frontotemporal dementia (FTD). This retrospective cohort study utilizes demographics to identify risk factors for onset, progression, life expectancy, and death in CHMP2B-mediated FTD. The pedigree of 528 individuals in six generations is provided, and clinical descriptions are presented. Choices of genetic testing are evaluated. MATERIALS AND METHODS: Demographic and lifestyle factors were assessed in survival analysis in all identified CHMP2B mutation carriers (44 clinically affected FTD-3 patients and 16 presymptomatic CHMP2B mutation carriers). Predictors of onset and progression included sex, parental disease course, education, and vascular risk factors. Life expectancy was established by matching CHMP2B mutation carriers with average life expectancies in Denmark. RESULTS: Disease course was not correlated to parental disease course and seemed unmodified by lifestyle factors. Diagnosis was recognized at an earlier age in members with higher levels of education, probably reflecting an early dysexecutive syndrome, unmasked earlier in people with higher work-related requirements. Carriers of the CHMP2B mutation had a significant reduction in life expectancy of 13 years. Predictive genetic testing was chosen by 20% of at-risk family members. CONCLUSIONS: CHMP2B-mediated FTD is substantiated as an autosomal dominantly inherited disease of complete penetrance. The clinical phenotype is a behavioral variant FTD. The disease course is unpredictable, and life expectancy is reduced. The findings may be applicable to other genetic FTD subtypes.

Optogenetic control of neural differentiation in Opto-mGluR6 engineered retinal pigment epithelial cell line and mesenchymal stem cells.

In retinal degenerative disorders, when neural retinal cells are damaged, cell transplantation is one of the most promising therapeutic approaches. Optogenetic technology plays an essential role in the neural differentiation of stem cells via membrane depolarization. This study explored the efficacy of blue light stimulation in neuroretinal differentiation of Opto-mGluR6-engineered mouse retinal pigment epithelium (mRPE) and bone marrow mesenchymal stem cells (BMSCs). mRPE and BMSCs were selected for optogenetic study due to their capability to differentiate into retinal-specific neurons. BMSCs were isolated and phenotypically characterized by the expression of mesenchymal stem cell-specific markers, CD44 (99%) and CD105 (98.8%). mRPE culture identity was confirmed by expression of RPE-specific marker, RPE65, and epithelial cell marker, ZO-1. mRPE cells and BMSCs were transduced with AAV-MCS-IRES-EGFP-Opto-mGluR6 viral vector and stimulated for 5 days with blue light (470 nm). RNA and protein expression of Opto-mGluR6 were verified. Optogenetic stimulation-induced elevated intracellular Ca2+ levels in mRPE- and BMS-treated cells. Significant increase in cell growth rate and G1/S phase transition were detected in mRPE- and BMSCs-treated cultures. Pou4f1, Dlx2, Eomes, Barlh2, Neurod2, Neurod6, Rorb, Rxrg, Nr2f2, Ascl1, Hes5, and Sox8 were overexpressed in treated BMSCs and Barlh2, Rorb, and Sox8 were overexpressed in treated mRPE cells. Expression of Rho, Thy1, OPN1MW, Recoverin, and CRABP, as retinal-specific neuron markers, in mRPE and BMS cell cultures were demonstrated. Differentiation of ganglion, amacrine, photoreceptor cells, and bipolar and Muller precursors were determined in BMSCs-treated culture and were compared with mRPE. mRPE cells represented more abundant terminal Muller glial differentiation compared with BMSCs. Our results also demonstrated that optical stimulation increased the intracellular Ca2+ level and proliferation and differentiation of Opto-mGluR6-engineered BMSCs. It seems that optogenetic stimulation of mRPE- and BMSCs-engineered cells would be a potential therapeutic approach for retinal degenerative disorders.

Neuro-regenerative potential of dental stem cells: a concise review.

This review will summarize the research information regarding the regenerative potential of dental stem cells for the treatment of neurodegenerative disorders. As compared to existing treatment modalities, the stem cell therapy seems promising, and accumulating evidences about the differentiation of stem cells into various lineages are proving it. The incidence of neurodegenerative diseases such as Alzheimer's, Parkinson's, stroke, and peripheral neuropathy is increasing due to the rise in life expectancies of people which have put a huge burden on economies. Finding a promising treatment could benefit not only the patients but also the communities. Dental stem cells hold a great potential to differentiate into neuronal cells. Many studies have reported the differentiation potential of the dental stem cells with the presence of neuronal lineage markers. In this review, we conferred how the use of dental stem cells can benefit the above-mentioned bedridden diseases.

Non-medical factors significantly influence the length of hospital stay after surgery for degenerative spine disorders.

BACKGROUND: Unnecessarily long hospital stays are costly and inefficient. Studies have shown that the length of hospital stay (LOS) for spine surgical procedures is influenced by various disease-related or medical factors, but few have examined the role of socio-demographic/socio-economic (SDE) factors. METHODS: This was a retrospective analysis of data from 10,770 patients (5056 men, 5714 women; 62 ± 15 years) with degenerative spinal disorders, collected prospectively in an in-house database within the framework of EUROSPINE's Spine Tango Registry. Surgeons completed the Tango surgery form (clinical history, demographics, surgical measures, complications), and patients, a baseline Core Outcome Measures Index. Stepwise linear regression analyses examined SDE predictors of LOS, controlling for potential medical/biological factors. RESULTS: The mean LOS was 7.9 ± 5.2 days. The final model accounted for 42% of variance in LOS, with SDE variables explaining 13% variance and medical/surgical predictors, 29%. In the final model, the SDE factors age and being female were significant independent predictors of LOS, whereas others were either non-significant (insurance status, being of Swiss nationality, being a smoker) or reached only borderline significance (p < 0.1) (BMI). Controlling for all other SDE and medical/surgical confounders, being female was associated with 1.11-day longer LOS (95% CI 0.96-1.27; p < 0.0001). CONCLUSIONS: Patients of advanced age and female gender are at increased risk of longer hospital stay after surgery for degenerative spinal disorders. Further studies should seek to understand the reasoning behind the gender disparity, in order to minimise potentially unnecessary costs of prolonged LOS. Targeted preoperative discharge planning may improve the utilisation of hospital resources. These slides can be retrieved under Electronic Supplementary Material.

Harnessing ionic mechanisms to achieve disease modification in neurodegenerative disorders.

Progressive neuronal death is the key pathogenic event leading to clinical symptoms in neurodegenerative disorders (NDDs). Neuroprotective treatments are virtually unavailable, partly because of the marked internal heterogeneity of the mechanisms underlying pathology. Targeted neuroprotection would require deep mechanistic knowledge across the entire aetiological spectrum of each NDD and the development of tailored treatments. Although ideal, this strategy appears challenging, as it would require a degree of characterization of both the disease and the patient that is currently unavailable. The alternate strategy is to search for commonalities across molecularly distinct NDD forms and exploit these for the development of drugs with broad-spectrum efficacy. In this view, mounting evidence points to ionic mechanisms (IMs) as targets with potential therapeutic efficacy across distinct NDD subtypes. The scope of this review is to present clinical and preclinical evidence supporting the link between disruption of IMs and neuronal death in specific NDDs and to critically revise past and ongoing attempts of harnessing IMs for the development of neuroprotective treatments.

Magnetic resonance evaluation of knee osteoarthritis among the Saudi Population.

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

Structural Brain Correlations of Visuospatial and Visuoperceptual Tests in Parkinson's Disease.

BACKGROUND: Diagnosis of mild cognitive impairment in Parkinson's disease (PD) is relevant because it is a marker for evolution to dementia. However, the selection of suitable tests to evaluate separate cognitive domains in mild cognitive impairment related to PD remains an open question. The current work aims to investigate the neuroanatomical correlates of several visuospatial/visuoperceptual tests using the same sample and a multimodal MRI approach. METHODS: The study included 36 PD patients and 20 healthy subjects matched for age, sex, and education. The visuospatial/visuoperceptual tests selected were: Pentagon Copying Test (PCT), Judgment of Line Orientation Test (JLOT), Visual Form Discrimination Test (VFDT), Facial Recognition Test (FRT), Symbol Digit Modalities Test (SMDT), and clock copying task (CLOX2). FreeSurfer was used to assess cortical thickness, and tract-based spatial statistics was used for fractional anisotropy analysis. RESULTS: Lower performance in the PCT, JLOT, and SDMT was associated with extensive cortical thickness reductions in lateral parietal and temporal regions. VFDT and CLOX2 did not show this common pattern and correlated with more limited medial occipito-temporal and occipito-parietal regions. Performance in all visuospatial/visuoperceptual tests correlated with fractional anisotropy in the corpus callosum. CONCLUSIONS: Our findings show that JLOT, SDMT, and PCT, in addition to differentiating patients from controls, are suitable visuospatial/visuoperceptual tests to reflect cortical thinning in lateral temporo-parietal regions in PD patients. We did not observe the dissociation between dorsal and ventral streams that was expected according to the neuropsychological classification of visuospatial and visuoperceptual tests. (JINS, 2018, 24, 33-44).

How does patient-rated outcome change over time following the surgical treatment of degenerative disorders of the thoracolumbar spine?

PURPOSE: Patient-rated measures are considered the gold standard for assessing the outcome of spine surgery, but there is no consensus on the appropriate timing of follow-up. Journals often demand a minimum 2-year follow-up, but the indiscriminate application of this principle may not be warranted. We examined the course of change in patient outcomes up to 5 years after surgery for degenerative spinal disorders. METHODS: The data were evaluated from 4287 consecutive patients (2287 women, 2000 men; aged 62 ± 15 years) with degenerative disorders of the thoracolumbar spine, undergoing first-time surgery at the given level between 01/01/2005 and 31/12/2011. The Core Outcome Measures Index (COMI; scored 0-10) was completed by 4012 (94%) patients preoperatively, 4008 (93%) at 3-month follow-up, 3897 (91%) at 1-year follow-up, 3736 (87%) at 2-year follow-up, and 3387 (79%) at 5-year follow-up. 2959 (69%) completed the COMI at all five time-points. RESULTS: The individual COMI change scores from preoperatively to the various follow-up time-points showed significant correlations ranging from r = 0.50 (for change scores at the earliest vs the latest follow-up) to r = 0.75 (for change scores after 12- vs 24-month follow-up). Concordance with respect to whether the minimum clinically important change score was achieved at consecutive time-points was also good (70-82%). COMI decreased significantly (p < 0.05) from preop to 3 months (by 3.6 ± 2.8 points) and from 3 to 12 months (by 0.3 ± 2.4 points), then levelled off up to 5 years (0.04-0.05 point change; p > 0.05). The course of change up to 12 months differed slightly (p < 0.05) depending on pathology/whether fusion was carried out. For patients undergoing simple decompression, 3-month follow-up was sufficient; those undergoing fusion continued to show further slight but significant change up to 12 months. CONCLUSIONS: Stable group mean COMI scores were observed for all patients from 12 months postoperatively onwards. The early postoperative results appeared to herald the longer term outcome. As such, a 'wait and see policy' in patients with a poor initial outcome at 3 months is not advocated. The insistence on a 2-year follow-up could result in a failure to intervene early to achieve better long-term outcomes.

Development of the Japanese Core Outcome Measures Index (COMI): cross-cultural adaptation and psychometric validation.

BACKGROUND: The patient-rated Core Outcome Measures Index (COMI) assesses the multidimensional impact of back problems on the sufferer. The brevity and comprehensibility of the tool make it practical for use in clinical and research settings. Although the COMI has been cross-culturally adapted in various languages worldwide, there is currently no Japanese version. The aim of this study was to develop a Japanese version of the COMI by: (1) performing a cross-cultural adaptation of the English version and (2) evaluating the psychometric properties of the Japanese version of the COMI in Japanese volunteers with chronic back problems. METHODS: The English version of the COMI was cross-culturally adapted for the Japanese language using established guidelines. The pre-final version was pilot-tested in five Japanese-speaking patients with low back pain (LBP) and a history of spine surgery. The psychometric properties of the Japanese COMI were tested in a group of 1052 individuals with chronic LBP (LBP ≥3 months), aged 20-69 years, who were recruited through a web-based survey. The psychometric properties that were evaluated included convergent and known-group validity, using the following reference questionnaires: EuroQol 5 Dimension, Roland Morris Disability Questionnaire, Short Form 8™ Health Survey, and the Keele STarT Back Screening Tool. RESULTS: The pre-final version of the cross-culturally adapted Japanese COMI was completed without any major problems of understanding or acceptability. For the evaluation of its psychometric properties, tests for convergent validity showed moderate correlations between COMI items and the respective reference questionnaires for symptom-specific well-being [- 0.33--0.48] and disability domains [0.48] and strong correlations (> 0.5) for the other domains and the COMI summary score. The analysis of known-group validity showed a linear trend for the COMI score in relation to prognostic risk (P < 0.001). CONCLUSIONS: The Japanese COMI retained conceptual equivalence to the original using comprehensible and acceptable Japanese expressions. We developed a Japanese version of the COMI that displayed qualities that support its convergent and known-group validity. The availability of a Japanese version of the COMI should allow for improved documentation of the care provided to patients with back problems.

Influence of previous surgery on patient-rated outcome after surgery for degenerative disorders of the lumbar spine.

PURPOSE: Few studies have used multivariate models to quantify the effect of multiple previous spine surgeries on patient-oriented outcome after spine surgery. This study sought to quantify the effect of prior spine surgery on 12-month postoperative outcomes in patients undergoing surgery for different degenerative disorders of the lumbar spine. METHODS: The study included 4940 patients with lumbar degenerative disease documented in the Spine Tango Registry of EUROSPINE, the Spine Society of Europe, from 2004 to 2015. Preoperatively and 12 months postoperatively, patients completed the multidimensional Core Outcome Measures Index (COMI; 0-10 scale). Patients' medical history and surgical details were recorded using the Spine Tango Surgery 2006 and 2011 forms. Multiple linear regression models were used to investigate the relationship between the number of previous surgeries and the 12-month postoperative COMI score, controlling for the baseline COMI score and other potential confounders. RESULTS: In the adjusted model including all cases, the 12-month COMI score showed a 0.37-point worse value [95 % confidence intervals (95 % CI) 0.29-0.45; p < 0.001] for each additional prior spine surgery. In the subgroup of patients with lumbar disc herniation, the corresponding effect was 0.52 points (95 % CI 0.27-0.77; p < 0.001) and in lumbar degenerative spondylolisthesis, 0.40 points (95 % CI 0.17-0.64; p = 0.001). CONCLUSIONS: We were able to demonstrate a clear "dose-response" effect for previous surgery: the greater the number of prior spine surgeries, the systematically worse the outcome at 12 months' follow-up. The results of this study can be used when considering or consenting a patient for further surgery, to better inform the patient of the likely outcome and to set realistic expectations.

Structure and function of the interphotoreceptor matrix surrounding retinal photoreceptor cells.

The interphotoreceptor matrix (IPM) is a highly organized structure with interconnected domains surrounding cone and rod photoreceptor cells and extends throughout the subretinal space. Based on known roles of the extracellular matrix in other tissues, the IPM is thought to have several prominent functions including serving as a receptor for growth factors, regulating retinoid transport, participating in cytoskeletal organization in surrounding cells, and regulation of oxygen and nutrient transport. In addition, a number of studies suggest that the IPM also may play a significant role in the etiology of retinal degenerative disorders. In this review, we describe the present knowledge concerning the structure and function of the IPM under physiological and pathological conditions.

Hypoxia-Inducible Factor and Oxidative Stress in Tendon Degeneration: A Molecular Perspective.

Tendinopathy is a debilitating condition marked by degenerative changes in the tendons. Its complex pathophysiology involves intrinsic, extrinsic, and physiological factors. While its intrinsic and extrinsic factors have been extensively studied, the role of physiological factors, such as hypoxia and oxidative stress, remains largely unexplored. This review article delves into the contribution of hypoxia-associated genes and oxidative-stress-related factors to tendon degeneration, offering insights into potential therapeutic strategies. The unique aspect of this study lies in its pathway-based evidence, which sheds light on how these factors can be targeted to enhance overall tendon health.

Sensing the future: A review on emerging technologies for assessing and monitoring bone health.

Bone health is crucial at all stages of life. Several medical conditions and changes in lifestyle affect the growth, structure, and functions of bones. This may lead to the development of bone degenerative disorders, such as osteoporosis, osteoarthritis, rheumatoid arthritis, etc., which are major public health concerns worldwide. Accurate and reliable measurement and monitoring of bone health are important aspects for early diagnosis and interventions to prevent such disorders. Significant progress has recently been made in developing new sensing technologies that offer non-invasive, low-cost, and accurate measurements of bone health. In this review, we have described bone remodeling processes and common bone disorders. We have also compiled information on the bone turnover markers for their use as biomarkers in biosensing devices to monitor bone health. Second, this review details biosensing technology for bone health assessment, including the latest developments in various non-invasive techniques, including dual-energy X-ray absorptiometry, magnetic resonance imaging, computed tomography, and biosensors. Further, we have also discussed the potential of emerging technologies, such as biosensors based on nano- and micro-electromechanical systems and application of artificial intelligence in non-invasive techniques for improving bone health assessment. Finally, we have summarized the advantages and limitations of each technology and described clinical applications for detecting bone disorders and monitoring treatment outcomes. Overall, this review highlights the potential of emerging technologies for improving bone health assessment with the potential to revolutionize clinical practice and improve patient outcomes. The review highlights key challenges and future directions for biosensor research that pave the way for continued innovations to improve diagnosis, monitoring, and treatment of bone-related diseases.

Neuroprotective potentials of Lead phytochemicals against Alzheimer's disease with focus on oxidative stress-mediated signaling pathways: Pharmacokinetic challenges, target specificity, clinical trials and future perspectives.

BACKGROUND: Alzheimer's diseases (AD) and dementia are among the highly prevalent neurological disorders characterized by deposition of beta amyloid (Aß) plaques, dense deposits of highly phosphorylated tau proteins, insufficiency of acetylcholine (ACh) and imbalance in glutamatergic system. Patients typically experience cognitive, behavioral alterations and are unable to perform their routine activities. Evidence also suggests that inflammatory processes including excessive microglia activation, high expression of inflammatory cytokines and release of free radicals. Thus, targeting inflammatory pathways beside other targets might be the key factors to control- disease symptoms and progression. PURPOSE: This review is aimed to highlight the mechanisms and pathways involved in the neuroprotective potentials of lead phytochemicals. Further to provide updates regarding challenges associated with their use and their progress into clinical trials as potential lead compounds. METHODS: Most recent scientific literature on pre-clinical and clinical data published in quality journals especially on the lead phytochemicals including curcumin, catechins, quercetin, resveratrol, genistein and apigenin was collected using SciFinder, PubMed, Google Scholar, Web of Science, JSTOR, EBSCO, Scopus and other related web sources. RESULTS: Literature review indicated that the drug discovery against AD is insufficient and only few drugs are clinically approved which have limited efficacy. Among the therapeutic options, natural products have got tremendous attraction owing to their molecular diversity, their safety and efficacy. Research suggest that natural products can delay the disease onset, reduce its progression and regenerate the damage via their anti-amyloid, anti-inflammatory and antioxidant potentials. These agents regulate the pathways involved in the release of neurotrophins which are implicated in neuronal survival and function. Highly potential lead phytochemicals including curcumin, catechins, quercetin, resveratrol, genistein and apigenin regulate neuroprotective signaling pathways implicated in neurotrophins-mediated activation of tropomyosin receptor kinase (Trk) and p75 neurotrophins receptor (p75NTR) family receptors. CONCLUSIONS: Phytochemicals especially phenolic compounds were identified as highly potential molecules which ameliorate oxidative stress induced neurodegeneration, reduce Aß load and inhibit vital enzymes. Yet their clinical efficacy and bioavailability are the major challenges which need further interventions for more effective therapeutic outcomes.

Transcriptome dataset of light-dependent expression in the early onset retinal degeneration model, Mcoln1-/- mouse.

Retinal degenerative diseases (RDDs) are a diverse group of retinal disorders that cause visual impairment. While RDD prevalence is high, little is known about the molecular mechanisms underlying the pathogenesis within many of these disorders. Here we use transcriptome analysis to elucidate the molecular mechanisms that drive early onset photoreceptor neuron function loss in the mouse model of the RDD Mucolipidosis type IV (MLIV). MLIV is a lysosomal storage disorder resulting from loss of function mutations in the MCOLN1 gene. MCOLN1 encodes a lysosomal cation channel, the transient receptor potential channel mucolipin 1 (Trpml1). To identify changes in gene expression during onset in MLIV we used a genetic mouse model (Mcoln1-/-) which recapitulates clinical attributes of the human disease. We conducted transcriptome analysis in 6-week old control and Mcoln1-/- mice under normal 12:12 light cycle as well as low and high light stress conditions. These data will be valuable to the vision research community for identifying differentially expressed in early onset MLIV potentially leading to new insights into the pathophysiology of this RDD. Raw FASTQ files and processed counts files for the RNA-seq libraries are deposited in the NCBI Sequence Read Archive (SRA) and have been assigned BioProject accession PRJNA1002601 [1].

Secretome-based acellular therapy of bone marrow-derived mesenchymal stem cells in degenerative and immunological disorders: A narrative review.

The bone marrow (BM) plays a pivotal role in homeostasis by supporting hematopoiesis and immune cells' activation, maturation, interaction, and deployment. "BMSC-derived secretome" refers to the complete repertoire of secreted molecules, including nucleic acids, chemokines, growth factors, cytokines, and lipids from BM-derived mesenchymal stem cells (BMSCs). BMSC-derived secretomes are the current molecular platform for acellular therapy. Secretomes are highly manipulable and can be synthesised in vast quantities using commercially accessible cell lines in the laboratory. Secretomes are less likely to elicit an immunological response because they contain fewer surface proteins. Moreover, the delivery of BMSC-derived secretomes has been shown in numerous studies to be an effective, cell-free therapy method for alleviating the symptoms of inflammatory and degenerative diseases. As a result, secretome delivery from BMSCs has the same therapeutic effects as BMSCs transplantation but may have fewer adverse effects. Additionally, BMSCs' secretome has therapeutic promise for organoids and parabiosis studies. This review focuses on recent advances in secretome-based cell-free therapy, including its manipulation, isolation, characterisation, and delivery systems. The diverse bioactive molecules of secretomes that successfully treat inflammatory and degenerative diseases of the musculoskeletal, cardiovascular, nervous, respiratory, reproductive, gastrointestinal, and anti-ageing systems were also examined in this review. However, secretome-based therapy has some unfavourable side effects that may restrict its uses. Some of the adverse effects of this modal therapy were briefly mentioned in this review.

Safety and Efficacy of Cortical Bone Trajectory Screw Fixation Combined with Facet Fusion for the Treatment of Lumbar Degenerative Disease.

OBJECTIVE: The mainstream lumbar fusion surgeries have various shortcomings, such as complex operation, much invasion, and loss of lumbar function. How to minimize the surgical injury and to achieve better therapeutic effects has become the goal pursued by spine surgeons. This study introduces a cortical bone trajectory (CBT) screw fixation combined with facet fusion (FF), evaluates its safety and efficacy, and explores its advantages, in order to provide a reference for treatment of patients with single-level lumbar stenosis or grade I degenerative spondylolisthesis. METHODS: We retrospectively analyzed the clinical, radiological, and operative data of 167 patients with single-level lumbar stenosis or grade I degenerative spondylolisthesis who underwent FF or transforaminal lumbar interbody fusion (TLIF) from January 2013 to September 2019 in the spine surgery department of the Second Hospital of Shandong University. Patients were divided into four groups according to surgical method: group CBT-FF, CBT screw combined with FF; group PS-FF, pedicle screw (PS) combined with FF; group CBT-TLIF, CBT screw combined with TLIF; and group PS-TLIF, PS combined with TLIF. The operation time, estimated intraoperative blood loss, complications after surgery, visual analog scale (VAS), and Oswestry disability index (ODI) of the four groups were compared. The fusion was evaluated by anteroposterior and lateral X-ray, CT scan, and three-dimensional reconstruction. RESULTS: Twelve months after surgery, the fusion rate of four groups had no significantly statistical differences (p = 0.914). VAS and ODI scores were lower after surgery than before. Low back pain VAS scores 1 week after surgery in group CBT-FF and group CBT-TLIF were significantly lower than those in group PS-FF and group PS-TLIF (pCF/PF = 0.001, pCF/PT = 0.000, pPF/CT = 0.049, pCT/PT = 0.000). Low back pain VAS score 3 months after surgery was significantly lower in group CBT-FF than group PS-FF and group PS-TLIF (pCF/PF = 0.045, pCF/PT = 0.008). ODI score 1 week after surgery was significantly lower in group CBT-FF than group PS-FF, group CBT-TLIF, and group PS-TLIF (pCF/PF = 0.000, pCF/CT = 0.005, pCF/PT = 0.000, pCT/PT = 0.015). ODI score 3 months after surgery was significantly lower in group CBT-FF than group PS-FF, group CBT-TLIF, and group PS-TLIF (pCF/PF = 0.001, pCF/CT = 0.002, pCF/PT = 0.000). Incidence of complications did not significantly differ among the groups. CONCLUSION: CBT screw fixation combined with FF is a safe and efficacious procedure for patients with single-level lumbar stenosis or grade I degenerative spondylolisthesis. This minimally invasive approach of lumbar fusion can be simply and easily performed. Patients who undergo CBT screw fixation combined with FF recovered faster than TLIF.

Comparison between Three-Dimensional Printed Titanium and PEEK Cages for Cervical and Lumbar Interbody Fusion: A Prospective Controlled Trial.

OBJECTIVES: The three-dimensional printing titanium (3DPT) cage with excellent biomechanical properties and osseointegration capabilities has been initially used in spinal fusion, while the polyetheretherketone (PEEK) cage, a bioinert material device, has been a widely used for decades with relatively excellent clinical outcomes. This study was performed to investigate the early radiographic and clinical outcomes of 3DPT cage versus PEEK cage in patients undergoing anterior cervical discectomy and fusion (ACDF) and transforaminal lumbar interbody fusion (TLIF). METHODS: This prospective controlled trial, from December 2019 to June 2022, included patients undergoing ACDF and TLIF with 3DPT cages and compared them to patients using PEEK cages for treating spinal degenerative disorders. The outcome measures included radiographic parameters (intervertebral height [IH], subsidence, fusion status, and bone-cage interface contact) and clinical outcomes (Japanese Orthopaedic Association [JOA], Neck Disability Index [NDI], Oswestry Disability Index [ODI], Short Form 12-Item Survey [SF-12], Visual Analog Scale [VAS], and Odom's criteria). Student's independent samples t test and Pearson's chi-square test were used to compare the outcome measures between the two groups before surgery and at 1 week, 3 and 6 months after surgery. RESULTS: For the patients undergoing ACDF, the 3DPT (18 patients/[26 segments]) and PEEK groups (18 patients/[26 segments]) had similar fusion rates at 3 months and 6 months follow-up (3 months: 96.2% vs. 83.3%, p = 0.182; 6 months: 100% vs. 91.7%, p = 0.225). The subsidence in the 3DPT group was significantly lower than that in the PEEK group (3 months: 0.4 ± 0.2 mm vs. 0.9 ± 0.7 mm p = 0.004; 6 months: 0.7 ± 0.3 mm vs. 1.5 ± 0.8 mm, p < 0.001). 3DPT and PEEK cage all achieved sufficient contact with the cervical endplates. For the patients undergoing TLIF, the 3DPT (20 patients/[26 segments]) and PEEK groups (20 patients/[24 segments]) had no statistical difference in fusion rate (3 months: 84.6% vs. 58.3%, p = 0.059; 6 months: 92.3% vs. 75%, p = 0.132). The subsidence was lower than that in the PEEK group without significantly difference (3 months: 0.9 ± 0.7 mm vs.1.2 ± 0.9 mm p = 0.136; 6 months: 1.6 ± 1.0 mm vs. 2.0 ± 1.0 mm, p = 0.200). At the 3-month follow-up, the bone-cage interface contact of the 3DPT cage was significantly better than that of the PEEK cage (poor contact: 15.4% vs. 75%, p < 0.001). The values of UAR were higher in the 3DPT group than in the PEEK group during the follow-up in cervical and lumbar fusion, there were more statistical differences in lumbar fusion. There were no significant differences in the clinical assessment between 3DPT or PEEK cage in spinal fusion. CONCLUSION: The 3DPT cage and PEEK cage can achieve excellent clinical outcomes in cervical and lumbar fusion. The 3DPT cage has advantage in fusion quality, subsidence severity, and bone-cage interface contact than PEEK cage.