Role of Systemic Factors in Improving the Prognosis of Diabetic Retinal Disease and Predicting Response to Diabetic Retinopathy Treatment.

Topic: To review clinical evidence on systemic factors that might be relevant to update diabetic retinal disease (DRD) staging systems, including prediction of DRD onset, progression, and response to treatment. Clinical relevance: Systemic factors may improve new staging systems for DRD to better assess risk of disease worsening and predict response to therapy. Methods: The Systemic Health Working Group of the Mary Tyler Moore Vision Initiative reviewed systemic factors individually and in multivariate models for prediction of DRD onset or progression (i.e., prognosis) or response to treatments (prediction). Results: There was consistent evidence for associations of longer diabetes duration, higher glycosylated hemoglobin (HbA1c), and male sex with DRD onset and progression. There is strong trial evidence for the effect of reducing HbA1c and reducing DRD progression. There is strong evidence that higher blood pressure (BP) is a risk factor for DRD incidence and for progression. Pregnancy has been consistently reported to be associated with worsening of DRD but recent studies reflecting modern care standards are lacking. In studies examining multivariate prognostic models of DRD onset, HbA1c and diabetes duration were consistently retained as significant predictors of DRD onset. There was evidence of associations of BP and sex with DRD onset. In multivariate prognostic models examining DRD progression, retinal measures were consistently found to be a significant predictor of DRD with little evidence of any useful marginal increment in prognostic information with the inclusion of systemic risk factor data apart from retinal image data in multivariate models. For predicting the impact of treatment, although there are small studies that quantify prognostic information based on imaging data alone or systemic factors alone, there are currently no large studies that quantify marginal prognostic information within a multivariate model, including both imaging and systemic factors. Conclusion: With standard imaging techniques and ways of processing images rapidly evolving, an international network of centers is needed to routinely capture systemic health factors simultaneously to retinal images so that gains in prediction increment may be precisely quantified to determine the usefulness of various health factors in the prognosis of DRD and prediction of response to treatment. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Glaucoma Prediction Models Based on Ocular and Systemic Findings.

INTRODUCTION: Our aim was to explore the impact of various systemic and ocular findings on predicting the development of glaucoma. METHODS: Medical records of 37,692 consecutive patients examined at a single medical center between 2001 and 2020 were analyzed using machine learning algorithms. Systemic and ocular features were included. Univariate and multivariate analyses followed by CatBoost and Light gradient-boosting machine prediction models were performed. Main outcome measures were systemic and ocular features associated with progression to glaucoma. RESULTS: A total of 7,880 patients (mean age 54.7 ± 12.6 years, 5,520 males [70.1%]) were included in a 3-year prediction model, and 314 patients (3.98%) had a final diagnosis of glaucoma. The combined model included 185 systemic and 42 ocular findings, and reached an ROC AUC of 0.84. The associated features were intraocular pressure (48.6%), cup-to-disk ratio (22.7%), age (8.6%), mean corpuscular volume (MCV) of red blood cell trend (5.2%), urinary system disease (3.3%), MCV (2.6%), creatinine level trend (2.1%), monocyte count trend (1.7%), ergometry metabolic equivalent task score (1.7%), dyslipidemia duration (1.6%), prostate-specific antigen level (1.2%), and musculoskeletal disease duration (0.5%). The ocular prediction model reached an ROC AUC of 0.86. Additional features included were age-related macular degeneration (10.0%), anterior capsular cataract (3.3%), visual acuity (2.0%), and peripapillary atrophy (1.3%). CONCLUSIONS: Ocular and combined systemic-ocular models can strongly predict the development of glaucoma in the forthcoming 3 years. Novel progression indicators may include anterior subcapsular cataracts, urinary disorders, and complete blood test results (mainly increased MCV and monocyte count).

Does HbA1c Level or Glomerular Filtration Rate Affect the Clinical Response to Endothelial Growth Factor Therapy (Ranibizumab or Aflibercept) in Diabetic Macular Edema? A Real-Life Experience.

INTRODUCTION: Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for diabetic macular edema (DME). We investigated the effect of initial glycosylated hemoglobin (HbA1c) level and glomerular filtration rate (GFR) on treatment outcomes in patients with DME receiving anti-VEGF injections in routine clinical practice. METHODS: A retrospective analysis of data from the prospective, multi-center, observational Fight Retinal Blindness! registry was performed. A total of 178 eyes with DME treated with anti-VEGF agents (ranibizumab or aflibercept) from 1 January 2010 to 31 March 2019 were enrolled in the analysis, with the long study period to allow for up to 24 months of follow-up. Data for eyes were tracked in the Fight Retinal Blindness! registry, and clinical parameters were collected by using local software. Changes in visual (best-corrected visual acuity [BCVA], in letters) and anatomic outcomes (central subfield thickness [CST], in microns) between subgroups of patients according to baseline HbA1c level (≤ 7% vs. > 7%) and GFR (> vs. ≤ 60 ml/min/m2 at 24 months were assessed. RESULTS: The multivariate adjusted mean improvement in BCVA at 24 months of treatment was + 5.2 and + 6.8 letters in subgroups with baseline HbA1c level ≤ 7% and > 7%, respectively (p = 0.541), and + 6.9 and + 6.4 letters in subgroups with GFR > 60 and < 60 ml/min/1.73 m2, respectively (p = 0.852). The multivariate adjusted mean CST reduction was - 89.9 and - 76.4 µm in subgroups with baseline HbA1c level ≤ 7% and > 7%, respectively (p = 0.505), and - 85 and - 115 µm in subgroups with baseline GFR > 60 and ≤ 60 ml/min/1.73 m2, respectively (p = 0.130). CONCLUSION: These results seem to indicate that visual and anatomical improvement in patients receiving intravitreal VEGF inhibitors for DME are independent of baseline HbA1c level and GFR, leading to the conclusion that high HbA1c levels or low GFR should not dictate injection timing in routine clinical practice. This study offers valuable insights for ophthalmologists, enabling a personalized treatment approach and optimizing DME patient outcomes.

Our study investigated how initial levels of glycosylated hemoglobin (HbA1c) and glomerular filtration rate (GFR) influence the treatment outcomes of diabetic macular edema (DME). DME is a complication of diabetes characterized by retinal swelling and vision problems. We analyzed data from a registry of DME patients who received intravitreal injections of medication to reduce swelling. Our study included 178 eyes receiving anti-vascular endothelial growth factor (anti-VEGF) injections in routine clinical practice. The results indicated that the initial HbA1c levels and GFR at baseline did not demonstrate a significant influence on the visual and anatomical improvements observed in patients with DME after 24 months of treatment, suggesting that HbA1c levels and kidney function should not be the primary factors taken into consideration in determining the timing of injections in routine clinical practice. These findings emphasize the importance of a personalized treatment approach that considers individual patient factors beyond HbA1c levels and kidney function to optimize outcomes for DME patients. This information can guide ophthalmologists in making informed decisions on the timing and frequency of injections for their patients with DME.

Age-associated systemic factors change central and peripheral immunity in adult male mice.

Aging coincides with major changes in brain immunity that aid in a decline in neuronal function. Here, we postulate that systemic, pro-aging factors contribute to immunological changes that occur within the brain during aging. To investigate this hypothesis, we comprehensively characterized the central and peripheral immune landscape of 20-month-old male mice using cytometry by time-of-flight (CyTOF) and investigated the role of age-associated circulating factors. We found that CD8+ T cells expressing programmed cell death protein 1 (PD1) and tissue-resident memory CD8+ T cells accumulated in the aged brain while levels of memory T cells rose in the periphery. Injections of plasma derived from 20-month-old mice into 5-month-old receiving mice decreased the frequency of splenic and circulating naïve T cells, increased memory CD8+ T cells, and non-classical, patrolling monocytes in the spleen, and elevated levels of regulatory T cells and non-classical monocytes in the blood. Notably, CD8+ T cells accumulated within white matter areas of plasma-treated mice, which coincided with the expression of vascular cell adhesion molecule 1 (VCAM-1), a mediator of immune cell trafficking, on the brain vasculature. Taken together, we here describe age-related immune cell changes in the mouse brain and circulation and show that age-associated systemic factors induce the expansion of CD8+ T cells in the aged brain.

The association between retinal microvasculature derived from optical coherence tomography angiography and systemic factors in type 2 diabetics.

Aims: To investigate the correlation between the retinal microvasculature using optical coherence tomography angiography (OCTA) and systemic factors in type 2 diabetes mellitus (T2DM) patients. Methods: This cross-sectional study obtained OCTA data from patients with T2DM administered at hospital and referred to ophthalmic services. Patient data about demographics, comorbid conditions, and blood biomarkers were extracted from electronic medical records. Data from OCTA scans obtained by CIRRUS HD-OCT Model 5,000 were obtained. Vessel density (VD) and perfusion density (PD) within the superficial capillary plexus, and foveal avascular zone (FAZ) area were automatically segmented. These parameters were tested for their correlations with systemic factors by univariate and multivariable linear regression analyses. Results: A total of 144 T2DM patients (236 eyes) were available for analysis, with mean age of 53.6 (SD = 10.34) and 56.9% were male. Chronic kidney disease, cardiovascular disease, increased serum creatinine (Scr), red blood cell count (RBC), platelets (PLT), apolipoprotein B (APOB), and decreased urine albumin to creatinine ratio (UACR) were significantly associated with lower VD and PD (all p < 0.013). UACR and triglyceride (TRIG) were significantly correlated with FAZ area (all p < 0.017). In multivariate analyses, PLT, eGFR, and APOB were independent risk factors for retinal rarefaction, and UACR was a significant predictor of FAZ area. Conclusion: We found several systemic risk factors, such as PLT, renal function and lipid profiles were associated with PD, VD, and FAZ area among Chinese T2DM patients.

Systemic Factors in Temporomandibular Disorder Pain.

The science of temporomandibular disorder (TMD) pain and its management has gone through significant changes during the last several decades. The authors strongly feel that the effect of systemic factors influencing TMD pain has been largely overlooked and poorly accounted for, even in established pain-management programs and protocols. The hope is that this article will act as a wake-up call for the pain management community to consider the importance of adequate knowledge of the systemic factors that affect the experience of TMD pain by the patient.

Analysis of ganglion cell-inner plexiform layer thickness in retinal vein occlusion with resolved macular edema.

PURPOSE: To analyze the retinal ganglion cell-inner plexiform layer (GCIPL) changes in retinal vein occlusion (RVO) eyes with resolved macular edema using optical coherence tomography. METHODS: We compared the average and minimum GCIPL thickness in RVO eyes with fellow eyes and healthy controls including 40 unilateral RVO patients and 48 healthy subjects. The average GCIPL thickness in BRVO eyes was segmented into the affected and opposite area according to the site of lesion, comparing them with corresponding areas in fellow eyes. Furthermore, maximum central macular thickness (CMT), visual acuity (VA), and intravitreal injection times were recorded to investigate their relationship with the GCIPL thickness. RESULTS: Despite no significant difference in CMT (P = 0.96), the average (P = 0.02 and P < 0.001, respectively) and minimum (both P < 0.001) GCIPL thicknesses were decreased in RVO eyes with resolved macular edema after treatment in comparison to fellow eyes and healthy eyes. Maximum CMT thickness was negatively correlated with the minimum GCIPL thickness (r = - 0.47, P = 0.003). VA and average GCIPL thickness were associated (rs = - 0.49, P = 0.002). In a subgroup analysis that only included BRVO patients, the opposite area revealed no significant difference between two eyes (P = 0.91) although the affected area in BRVO eyes was decreased (P < 0.001). CONCLUSIONS: A decrease of GCIPL thickness in RVO was observed even after anatomic restoration and associated with VA prognosis. These GCIPL defects could be attributable to systemic risks and RVO itself, not anti-VEGF effects.

The mitochondrial protein OPA1 regulates the quiescent state of adult muscle stem cells.

Quiescence regulation is essential for adult stem cell maintenance and sustained regeneration. Our studies uncovered that physiological changes in mitochondrial shape regulate the quiescent state of adult muscle stem cells (MuSCs). We show that MuSC mitochondria rapidly fragment upon an activation stimulus, via systemic HGF/mTOR, to drive the exit from deep quiescence. Deletion of the mitochondrial fusion protein OPA1 and mitochondrial fragmentation transitions MuSCs into G-alert quiescence, causing premature activation and depletion upon a stimulus. OPA1 loss activates a glutathione (GSH)-redox signaling pathway promoting cell-cycle progression, myogenic gene expression, and commitment. MuSCs with chronic OPA1 loss, leading to mitochondrial dysfunction, continue to reside in G-alert but acquire severe cell-cycle defects. Additionally, we provide evidence that OPA1 decline and impaired mitochondrial dynamics contribute to age-related MuSC dysfunction. These findings reveal a fundamental role for OPA1 and mitochondrial dynamics in establishing the quiescent state and activation potential of adult stem cells.

Central nervous system regeneration: the roles of glial cells in the potential molecular mechanism underlying remyelination.

Glial cells play crucial roles in brain homeostasis and pathogenesis of central nervous system (CNS) injuries and diseases. However, the roles of these cells and the molecular mechanisms toward regeneration in the CNS have not been fully understood, especially the capacity of them toward demyelinating diseases. Therefore, there are still very limited therapeutic strategies to restore the function of adult CNS in diseases such as multiple sclerosis (MS). Remyelination, a spontaneous regeneration process in the CNS, requires the involvement of multiple cellular and extracellular components. Promoting remyelination by therapeutic interventions is a promising novel approach to restore the CNS function. Herein, we review the role of glial cells in CNS diseases and injuries. Particularly, we discuss the roles of glia and their functional interactions and regulatory mechanisms in remyelination, as well as the current therapeutic strategies for MS.

THE EFFECT OF LOCAL AND SYSTEMIC FACTORS ON DENTAL IMPLANT FAILURE - ANALYSIS OF 670 PATIENTS WITH 1260 IMPLANTS.

The etiopathogenesis of dental implant failure is multifactorial and may include numerous local and systemic factors, however, studies including both local and systemic factors are still lacking. Therefore, the aim of this study was to evaluate whether periodontal disease, oral hygiene index, i.e. bleeding on probing (BOP), full mouth plaque index (FMPI), smoking, systemic diseases, as well as implant characteristics (length and diameter) affect failure of implant-prosthodontic therapy. Data on 670 patients were retrieved in whom 1260 dental implants had been placed and followed-up for at least five to ten years. Categorical data were analyzed by the χ2-test, whereas Mann-Whitney test was used for continuous variables (age, BOP and FMPI). The values of p<0.05 were considered significant. The effect of local and systemic factors on the success of implant-prosthodontic therapy was assessed by multiple logistic regression analysis. Forty-five (6.7%) patients had systemic diseases, of which diabetes mellitus was most common, followed by atherosclerosis, diabetes and atherosclerosis, diabetes mellitus type 1, lymphoma, and hepatitis C. One-third (33.4%) of the patients were smokers. Periodontal disease was present in 170 patients, while 500 patients were without periodontal disease. Nine implants were lost during the period of five years. There were no differences regarding the type of implant or type of connection to the prosthetic suprastructure. However, most of these patients had a periodontal disease. There were no significant differences in dental implant failure rates between smokers and non-smokers or between patients with and without systemic diseases. Furthermore, the results of this study showed that implant type (straight vs. tapered) and type of connection with prosthodontic appliance (cemented or screw retained) did not affect BOP and FMPI. In smokers, significant improvement of BOP and FMPI was noticed. Initially, smokers had a significantly worse BOP (0.0037) when compared to non-smokers; however, there were no differences regarding FMPI (p=0.4218) between the two groups. In patients with periodontal disease, improvement of BOP and FMPI was seen at 5-year follow-up and no significant differences were found when compared to patients without periodontal disease. There were no significant differences in BOP and FMPI between patients with and without diabetes at 5-year follow-up. Atherosclerosis had a significant negative effect on BOP, but not on FMPI at 5-year follow-up. It is concluded that periodontal disease had a significant impact on the implant-prosthodontic therapy.

Differentiating distinct and converging neural correlates of types of systemic environmental exposures.

Systemic environmental disadvantage relates to a host of health and functional outcomes. Specific structural factors have seldom been linked to neural structure, however, clouding understanding of putative mechanisms. Examining relations during childhood/preadolescence, a dynamic period of neurodevelopment, could aid bridge this gap. A total of 10,213 youth were recruited from the Adolescent Brain and Cognitive Development study. Self-report and objective measures (Census and Federal bureau of investigation metrics extracted using geocoding) of environmental exposures were used, including stimulation indexing lack of safety and high attentional demands, discrepancy indexing social exclusion/lack of belonging, and deprivation indexing lack of environmental enrichment. Environmental measures were related to cortical thickness, surface area, and subcortical volume regions, controlling for other environmental exposures and accounting for other brain regions. Self-report (|ß| = .04-.09) and objective (|ß| = .02-.06) environmental domains related to area/thickness in overlapping (e.g., insula, caudal anterior cingulate), and unique regions (e.g., for discrepancy, rostral anterior and isthmus cingulate, implicated in socioemotional functions; for stimulation, precuneus, critical for cue reactivity and integration of environmental cues; and for deprivation, superior frontal, integral to executive functioning). For stimulation and discrepancy exposures, self-report and objective measures showed similarities in correlate regions, while deprivation exposures evidenced distinct correlates for self-report and objective measures. Results represent a necessary step toward broader work aimed at establishing mechanisms and correlates of structural disadvantage, highlighting the relevance of going beyond aggregate models by considering types of environmental factors, and the need to incorporate both subjective and objective measurements in these efforts.

Attenuation of age-elevated blood factors by repositioning plasmapheresis: A novel perspective and approach.

Aging is associated with the impairment of stem cell activation, leading to the functional decline of tissues and increasing the risk for age-associated diseases. The old, damaged or unrepaired tissues disturb distant tissue homeostasis by secreting factors into the circulation, which may not only serve as biomarkers for specific age-associated pathologies but also induce a variety of degenerative phenotypes. In this review, we summarize and discuss systemic determinants that perpetuate age-related tissue dysfunction. We further elaborate on the effects of attenuating these circulating factors by highlighting recent advances which utilize plasmapheresis in a pre-clinical or clinical setting. Overall, we postulate that repositioning therapeutic plasma exchange (TPE) to dilute the systemic factors, which become deleterious at their age-elevated levels, could be a rapidly effective rejuvenation therapy that recalibrates crucial signaling pathways to a youthful state.

Acute spinal cord injury: Pathophysiology and pharmacological intervention (Review).

Spinal cord injury (SCI) is one of the most debilitating of all the traumatic conditions that afflict individuals. For a number of years, extensive studies have been conducted to clarify the molecular mechanisms of SCI. Experimental and clinical studies have indicated that two phases, primary damage and secondary damage, are involved in SCI. The initial mechanical damage is caused by local impairment of the spinal cord. In addition, the fundamental mechanisms are associated with hyperflexion, hyperextension, axial loading and rotation. By contrast, secondary injury mechanisms are led by systemic and cellular factors, which may also be initiated by the primary injury. Although significant advances in supportive care have improved clinical outcomes in recent years, a number of studies continue to explore specific pharmacological therapies to minimize SCI. The present review summarized some important pathophysiologic mechanisms that are involved in SCI and focused on several pharmacological and non­pharmacological therapies, which have either been previously investigated or have a potential in the management of this debilitating injury in the near future.

[The verification of systemic factors of oncology care organization in the Saratov oblast].

In Russia, the oncological diseases significantly impact public health. The study of oncological medical care organization in the Saratov Oblast, that has a number of territorial demographic and medical social characteristics, affecting oncological situation, was carried out. The purpose of the study is to verify systemic factors determining specific characteristics of the oncological medical care organization in the Saratov Oblast. MATERIALS AND METHODS: To elaborate objective comprehension of specific characteristics of the oncological medical care organization in the Saratov Oblast medical and sociological focus groups study was carried out, involving sampling of 12 experts oncologists and health care organizers. THE RESULTS: The original guide scenario developed for the focus group study included expert discussion on trends in oncological medical care organization at the Oblast level and directions of improving continuum of oncological care. The study data analysis was implemented in accordance with specified scenario. CONCLUSION: The focus group study elaborated objective understanding of the specific characteristics of oncological medical care organization in the Oblast and predetermined verification and ranking of systemic factors that significantly impact the continuum of oncological care.

Factors Affecting a Short-Term Response to Anti-VEGF Therapy in Diabetic Macular Edema.

Diabetic macular edema (DME) is a common cause of visual impairment in patients with diabetes. Although intravitreal anti-vascular endothelial growth factor (VEGF) injections were efficacious in clinical trials, several patients exhibited a poor response. This study aimed to compare clinical features between patients who were susceptible to intravitreal anti-VEGF injections for DME and those who were not. A single-center, retrospective study of 102 such patients was conducted (123 eyes; mean ± standard deviation age, 63.4 ± 10.8 years; 57.8% males). Systemic and ocular data, assessed at baseline and after a month, were compared between good (>20% decrease in central macular thickness (CMT)) and poor (≤20% decrease in CMT) responders using the Mann-Whitney U test/Fisher's exact test. Eighty-one eyes (65.9%) were good responders. The glycosylated hemoglobin level was higher (p = 0.011) in poor (7.5% ± 0.94%) than in good (7.04% ± 1.19%) responders. The foveal avascular zone was larger (p = 0.0003) in poor (0.67 ± 0.33 µm2) than in good (0.47 ± 0.23 µm2) responders. The number of microaneurysms in the pericapillary network was higher (p = 0.0007) in poor (2.7 ± 2.2) than in good (1.4 ± 2.0) responders. Baseline glycemic control and macular ischemia may be associated with the short-term response to intravitreal anti-VEGF injections.

Hyperdipsia in sheep bearing lesions in the medial septal nucleus.

Previous experiments in rodents showed that ablation of the septal brain region caused hyperdipsia. We investigated which part of the septal region needs ablation to produce hyperdipsia in sheep, and whether increased drinking was a primary hyperdipsia. Following ablation of the medial septal region (n = 5), but not parts of the lateral septal region (n = 4), daily water intake increased from ~2.5-5 L/day up to 10 L/day for up to 3 months post-lesion. In hyperdipsic sheep, plasma osmolality increased on the first day post-lesion and body weight fell, suggesting that initial hyperdipsia was secondary to fluid loss. However hyperosmolality was not sustained long-term and plasma hypo-osmolality persisted from 0.5 to 3 months post-lesion. Acute dipsogenic responses to intravenous hypertonic saline, intravenous or intracerebroventricular angiotensin II, water deprivation for 2 days, or feeding over 5 h were not potentiated by medial septal lesions, showing that the rapid pre-systemic inhibitory influences that cause satiation of thirst upon the act of drinking were intact. However, hyperdipsic sheep continued to ingest water when hyponatremic (plasma [Na] was 127-132 mmol/l) and plasma osmolality was 262-268 mosmol/kg due to retention of ingested fluid resulting from intravenous infusion of vasopressin administered to maintain a basal blood level of antidiuretic hormone. The results show that septal lesion-induced hyperdipsia is not due to disruption of acute pre-systemic influences associated with drinking water that initiates rapid satiation of thirst. Rather, inhibitory influences of hyponatremia, hypo-osmolality or hypervolemia on drinking appear to be disrupted by medial septal lesions.

Linking contemporary river restoration to economics, technology, politics, and society: Perspectives from a historical case study of the Po River Basin, Italy.

River restoration is a novel paradigm of 'mirescape' (land-and-water-scape) management that developed along with the emergence of aquatic ecology. River restoration can be seen as the application of an ecological perspective to return rivers to nature. However, the river restoration paradigm is also the contemporary iteration of historical phases of mirescape management. We review the long and varied recorded history of the Po River in northern Italy as a case study to illustrate the transformations and common themes of mirescape management. We find, first, that significant changes in mirescape management and river condition only occur in the context of larger social, political, technological and economic transformations. Second, we show how particular cultural understandings, economic interests, technological innovations and political powers have driven particular paradigms of mirescape management. These have tended towards increasing territorial separation of wet and dry. We find, third, that these separations lead not only to increasing economic precariousness for many, but also to increasingly severe disasters. We conclude that river restoration faces social and political challenges to becoming relevant at a mirescape scale, due to its lack of integration with land management, or with current social, political, technological and economic transformations. To act on this conclusion, we suggest philosophically aligned social movements that river restoration could work with to improve impact and uptake.

Influences of circulatory factors on intervertebral disc aging phenotype.

Whether disc aging is influenced by factors beyond its local environment is an important unresolved question. Here we performed heterochronic parabiosis in mice to study the effects of circulating factors in young and old blood on age-associated intervertebral disc degeneration. Compared to young isochronic pairs (Y-Y), young mice paired with old mice (Y-O) showed significant increases in levels of disc MMP-13 and ADAMTS4, aggrecan fragmentation, and histologic tissue degeneration, but negligible changes in cellular senescence markers (p16INK4a, p21Cip1). Compared to old isochronic pairs (O-O), old mice paired with young mice (O-Y) exhibited a significant decrease in expression of cellular senescence markers (p16, p21, p53), but only marginal decreases in the levels of disc MMP-13 and ADAMTS4, aggrecan fragmentation, and histologic degeneration. Thus, exposing old mice to young blood circulation greatly suppressed disc cellular senescence, but only slightly decreased disc matrix imbalance and degeneration. Conversely, exposing young mice to old blood accelerated their disc matrix imbalance and tissue degeneration, with little effects on disc cellular senescence. Thus, non-cell autonomous effects of circulating factors on disc cellular senescence and matrix homeostasis are complex and suggest that disc matrix homeostasis is modulated by systemic factors and not solely through local disc cellular senescence.

Local and systemic factors associated with marginal bone loss around dental implants: a retrospective clinical study.

OBJECTIVES: The aim of this study was to determine the influence of patient-related systemic factors, local bone and intraoral factors, and implant-related factors on peri-implant marginal bone loss (MBL). METHOD AND MATERIALS: The following data were collected from patients who received dental implants and were recalled for examinations at least 3 years after treatment completion: medical history, age, sex, habits, periodontal health, implant size and surface, surgical procedure, prosthesis type, implant failure, Plaque Index, and oral hygiene. MBL was investigated using both baseline and follow-up panoramic radiographs. RESULTS: The study included 1,126 dental implants placed in 304 patients (185 [60.9%] women and 119 [39.1%] men). The mean age was 54.30 ± 13.52 years (range 22 to 83 years). The mean follow-up period was 58.8 ± 11.2 months. The MBL was observed in 271 (24.1%) implants, of which 160 (14.2%) were ≤ 2 mm and 111 (9.9%) were > 2 mm. Respective mean MBL values on mesial and distal sides were 0.42 ± 1.03 mm and 0.42 ± 1.02 mm. Of the implants, 19 (1.7%) were lost, leading to an implant success rate of 98.3%. Age, history of hysterectomy, history of periodontitis, oral hygiene, abrasions, smoking, implant location, implant surface, implant length, surgical procedure type, and prosthesis type were all found to be statistically significant for MBL (P < .05). Certain combinations of these factors resulted in increased MBL. CONCLUSION: In the present study, local factors had more significant effects on MBL than did systemic factors, and combinations of these factors had greater effects on MBL.