Clinical Manifestations of Malignant Struma Ovarii: A Retrospective Case Series in a Tertiary Hospital in Korea.

Background: Malignant struma ovarii (MSO) is a very rare disease in which thyroid cancer originates from the ovary. Because it is rare for endocrinologists to encounter patients with MSO, endocrinologists may have a limited understanding of the disease. Therefore, we analyzed and introduced its incidence and clinical course in a tertiary hospital in Korea. Methods: We retrospectively investigated the clinical data of 170 patients who underwent surgery for struma ovarii at the Department of Obstetrics and Gynecology of Samsung Medical Center from 1994 to May 2023. Results: Among 170 patients with struma ovarii, 15 (8.8%) were diagnosed with MSO. The median age of patients with MSO was 48 years (range, 30 to 74), and the median tumor size was 3.3 cm (range, 0.5 to 11.0). Papillary thyroid carcinoma (46.7%) was the most common subtypes followed by follicular thyroid carcinoma (26.7%). All patients were diagnosed after surgery, with no predictions from preoperative imaging. The surgical extent of gynecological surgery was variable. Four patients (26.7%) underwent thyroidectomy for thyroid cancer, while one underwent total thyroidectomy and radioactive iodine therapy for MSO with peritoneal metastasis. Except for one patient who underwent hemithyroidectomy, thyroid stimulating hormone suppression therapy was performed in four patients. Only 53% of MSO patients were consulted by an endocrinologist. With a median follow-up period of 33 months (range, 4 to 156), 11 patients remained disease-free, one experienced progression with peritoneal seeding, and the remaining one was in treatment. There have been no recurrences or deaths due to MSO. Conclusion: An endocrinologist should be involved in establishing a therapeutic plan for MSO, for which the overall prognosis is generally favorable.

Hippocampal aggregation signatures of pathogenic UBQLN2 in amyotrophic lateral sclerosis and frontotemporal dementia.

Pathogenic variants in the UBQLN2 gene cause X-linked dominant amyotrophic lateral sclerosis and/or frontotemporal dementia characterised by ubiquilin 2 aggregates in neurons of the motor cortex, hippocampus, and spinal cord. However, ubiquilin 2 neuropathology is also seen in sporadic and familial amyotrophic lateral sclerosis and/or frontotemporal dementia cases not caused by UBQLN2 pathogenic variants, particularly C9orf72-linked cases. This makes the mechanistic role of mutant ubiquilin 2 protein and the value of ubiquilin 2 pathology for predicting genotype unclear. Here we examine a cohort of 44 genotypically diverse amyotrophic lateral sclerosis cases with or without frontotemporal dementia, including eight cases with UBQLN2 variants (resulting in p.S222G, p.P497H, p.P506S, p.T487I (two cases), and p.P497L (three cases)). Using multiplexed (5-label) fluorescent immunohistochemistry, we mapped the co-localisation of ubiquilin 2 with phosphorylated TDP-43, dipeptide repeat aggregates, and p62, in the hippocampus of controls (n = 6), or amyotrophic lateral sclerosis with or without frontotemporal dementia in sporadic (n = 20), unknown familial (n = 3), SOD1-linked (n = 1), FUS-linked (n = 1), C9orf72-linked (n = 5), and UBQLN2-linked (n = 8) cases. We differentiate between i) ubiquilin 2 aggregation together with phosphorylated TDP-43 or dipeptide repeat proteins, and ii) ubiquilin 2 self-aggregation promoted by UBQLN2 pathogenic variants that cause amyotrophic lateral sclerosis/and frontotemporal dementia. Overall, we describe a hippocampal protein aggregation signature that fully distinguishes mutant from wildtype ubiquilin 2 in amyotrophic lateral sclerosis with or without frontotemporal dementia, whereby mutant ubiquilin 2 is more prone than wildtype to aggregate independently of driving factors. This neuropathological signature can be used to assess the pathogenicity of UBQLN2 gene variants and to understand the mechanisms of UBQLN2-linked disease.

Toxicity Evaluation of Dose-Escalation in Hypofractionated Regional Nodal Irradiation for Breast Cancer: A Retrospective Study.

PURPOSE: Regional nodal irradiation (RNI) to the axilla and supraclavicular area presents distinct toxicities, such as lymphedema and shoulder stiffness, compared with whole-breast irradiation. There is insufficient evidence on the safety of dose-escalation in hypofractionated RNI. We aimed to evaluate and compare toxicity rates in patients with breast cancer who received hypofractionated RNI with and without dose-escalation. METHODS AND MATERIALS: We retrospectively analyzed 381 patients with breast cancer treated with hypofractionated RNI between March 2015 and February 2017. Patients received either the standard-dose to the regional nodal area (43.2 Gy/16 fx; 48.7 Gy3.5 equivalent dose [EQD2], 2 Gy equivalent dose with α/ß= 3.5 Gy) or dose-escalation with a median dose of 54.8 Gy3.5 EQD2 (range, 51.7-60.9 Gy3.5 EQD2), depending on clinical and pathologic nodal stage. Toxicity rates of lymphedema and shoulder stiffness were assessed, and statistical analyses were conducted to identify associated factors. RESULTS: The median follow-up time was 32.3 months (5.7-47.0 months). After radiation therapy, 71 (18.6%) patients developed lymphedema, and 48 (12.6%) developed shoulder stiffness. Patients who received dose-escalation exhibited significantly higher rates of lymphedema (32.1% vs 14.8%; odds ratio, 2.72, P = .0004) and shoulder stiffness (23.8% vs 9.4%; odds ratio, 2.01, P = .0205) compared with the standard-dose group. Moreover, dose-escalation showed a tendency to increase the severity of lymphedema and shoulder stiffness. CONCLUSIONS: Patients who received dose-escalation in hypofractionated RNI face a higher risk of developing lymphedema and shoulder stiffness compared with those who received standard-dose hypofractionated RNI. Therefore, it is crucial to implement close and frequent monitoring for early detection, along with timely rehabilitation interventions for these patients.

Comparative analysis of patients with new onset refractory status epilepticus preceded by fever (febrile infection-related epilepsy syndrome) versus without prior fever: An interim analysis.

Febrile infection-related epilepsy syndrome (FIRES) is a subset of new onset refractory status epilepticus (NORSE) that involves a febrile infection prior to the onset of the refractory status epilepticus. It is unclear whether FIRES and non-FIRES NORSE are distinct conditions. Here, we compare 34 patients with FIRES to 30 patients with non-FIRES NORSE for demographics, clinical features, neuroimaging, and outcomes. Because patients with FIRES were younger than patients with non-FIRES NORSE (median = 28 vs. 48 years old, p = .048) and more likely cryptogenic (odds ratio = 6.89), we next ran a regression analysis using age or etiology as a covariate. Respiratory and gastrointestinal prodromes occurred more frequently in FIRES patients, but no difference was found for non-infection-related prodromes. Status epilepticus subtype, cerebrospinal fluid (CSF) and magnetic resonance imaging findings, and outcomes were similar. However, FIRES cases were more frequently cryptogenic; had higher CSF interleukin 6, CSF macrophage inflammatory protein-1 alpha (MIP-1a), and serum chemokine ligand 2 (CCL2) levels; and received more antiseizure medications and immunotherapy. After controlling for age or etiology, no differences were observed in presenting symptoms and signs or inflammatory biomarkers, suggesting that FIRES and non-FIRES NORSE are very similar conditions.

Cisd2 deficiency impairs neutrophil function by regulating calcium homeostasis via Calnexin and SERCA.

In the context of aging, the susceptibility to infectious diseases increases, leading to heightened morbidity and mortality. This phenomenon, termed immunosenescence, is characterized by dysregulation in the aging immune system, including abnormal alterations in lymphocyte composition, elevated basal inflammation, and the accumulation of senescent T cells. Such changes contribute to increased autoimmune diseases, enhanced infection severity, and reduced responsiveness to vaccines. Utilizing aging animal models becomes imperative for a comprehensive understanding of immunosenescence, given the complexity of aging as a physiological process in living organisms. Our investigation focuses on Cisd2, a causative gene for Wolfram syndrome, to elucidate on immunosenescence. Cisd2 knockout (KO) mice, serving as a model for premature aging, exhibit a shortened lifespan with early onset of aging-related features, such as decreased bone density, hair loss, depigmentation, and optic nerve degeneration. Intriguingly, we found that the Cisd2 KO mice present a higher number of neutrophils in the blood; however, isolated neutrophils from these mice display functional defects. Through mass spectrometry analysis, we identified an interaction between Cisd2 and Calnexin, a protein known for its role in protein quality control. Beyond this function, Calnexin also regulates calcium homeostasis through interaction with sarcoendoplasmic reticulum calcium transport ATPase (SERCA). Our study proposes that Cisd2 modulates calcium homeostasis via its interaction with Calnexin and SERCA, consequently influencing neutrophil functions.

AraDQ: an automated digital phenotyping software for quantifying disease symptoms of flood-inoculated Arabidopsis seedlings.

BACKGROUND: Plant scientists have largely relied on pathogen growth assays and/or transcript analysis of stress-responsive genes for quantification of disease severity and susceptibility. These methods are destructive to plants, labor-intensive, and time-consuming, thereby limiting their application in real-time, large-scale studies. Image-based plant phenotyping is an alternative approach that enables automated measurement of various symptoms. However, most of the currently available plant image analysis tools require specific hardware platform and vendor specific software packages, and thus, are not suited for researchers who are not primarily focused on plant phenotyping. In this study, we aimed to develop a digital phenotyping tool to enhance the speed, accuracy, and reliability of disease quantification in Arabidopsis. RESULTS: Here, we present the Arabidopsis Disease Quantification (AraDQ) image analysis tool for examination of flood-inoculated Arabidopsis seedlings grown on plates containing plant growth media. It is a cross-platform application program with a user-friendly graphical interface that contains highly accurate deep neural networks for object detection and segmentation. The only prerequisite is that the input image should contain a fixed-sized 24-color balance card placed next to the objects of interest on a white background to ensure reliable and reproducible results, regardless of the image acquisition method. The image processing pipeline automatically calculates 10 different colors and morphological parameters for individual seedlings in the given image, and disease-associated phenotypic changes can be easily assessed by comparing plant images captured before and after infection. We conducted two case studies involving bacterial and plant mutants with reduced virulence and disease resistance capabilities, respectively, and thereby demonstrated that AraDQ can capture subtle changes in plant color and morphology with a high level of sensitivity. CONCLUSIONS: AraDQ offers a simple, fast, and accurate approach for image-based quantification of plant disease symptoms using various parameters. Its fully automated pipeline neither requires prior image processing nor costly hardware setups, allowing easy implementation of the software by researchers interested in digital phenotyping of diseased plants.

Provider Experience With the Use of Ketamine for Refractory Status Epilepticus.

OBJECTIVE: Refractory status epilepticus (RSE) treated with anesthetic agents can be associated with complications including respiratory depression and hypotension. Ketamine is an emerging RSE treatment, but optimal dosing and timing are unknown. We studied provider attitudes and practices regarding the use of ketamine for RSE. METHODS: A literature review informed the creation of the survey, developed by professionals in epilepsy, pharmacy, and neurocritical care. The survey was distributed to members of the Critical Care EEG Monitoring and Research Consortium, Neurocritical Care Society, American Academy of Neurology Synapse community, American Epilepsy Society, and the Canadian League Against Epilepsy. Descriptive statistics were calculated. RESULTS: There were 109 respondents. First-line agents for RSE were midazolam (53%), propofol (42%), pentobarbital (2%), and ketamine (1%). Reasons for ketamine use included failure of midazolam/propofol to control seizures (81%) or hypotension on another anesthetic (35%). Perceived contraindications included hypertension (37%), elevated intracranial pressure (24%), and heart failure (18%). Perceived benefits included decreased use of vasopressors (53%) and more rapid RSE control when used adjunctively (49%). Routine ketamine users often treated more than 10 RSE cases per year, worked as intensivists or at academic institutions. Of the respondents, 59% found ketamine useful for RSE and 94% were interested in learning more about its use. CONCLUSIONS: Although most participants found ketamine helpful for RSE, it is mainly used as a second-line agent adjunctively with midazolam or propofol. Perceived ketamine benefits included decreased need for hemodynamic support and more rapid seizure control when used in conjunction with other anesthetics. Perceived contraindications centered on cardiac and intracranial pressure concerns.

Clinical practice guidelines for cervical cancer: the Korean Society of Gynecologic Oncology guidelines.

This fifth revised version of the Korean Society of Gynecologic Oncology practice guidelines for the management of cervical cancer incorporates recent research findings and changes in treatment strategies based on version 4.0 released in 2020. Each key question was developed by focusing on recent notable insights and crucial contemporary issues in the field of cervical cancer. These questions were evaluated for their significance and impact on the current treatment and were finalized through voting by the development committee. The selected key questions were as follows: the efficacy and safety of immune checkpoint inhibitors as first- or second-line treatment for recurrent or metastatic cervical cancer; the oncologic safety of minimally invasive radical hysterectomy in early stage cervical cancer; the efficacy and safety of adjuvant systemic treatment after concurrent chemoradiotherapy in locally advanced cervical cancer; and the oncologic safety of sentinel lymph node mapping compared to pelvic lymph node dissection. The recommendations, directions, and strengths of this guideline were based on systematic reviews and meta-analyses, and were finally confirmed through public hearings and external reviews. In this study, we describe the revised practice guidelines for the management of cervical cancer.

Elevated phase amplitude coupling as a depression biomarker in epilepsy.

Depression is prevalent in epilepsy patients and their intracranial brain activity recordings can be used to determine the types of brain activity that are associated with comorbid depression. We performed case-control comparison of spectral power and phase amplitude coupling (PAC) in 34 invasively monitored drug resistant epilepsy patients' brain recordings. The values of spectral power and PAC for one-minute segments out of every hour in a patient's study were correlated with pre-operative assessment of depressive symptoms by Beck Depression Inventory-II (BDI). We identified an elevated PAC signal (theta-alpha-beta phase (5-25 Hz)/gamma frequency (80-100 Hz) band) that is present in high BDI scores but not low BDI scores adult epilepsy patients in brain regions implicated in primary depression, including anterior cingulate cortex, amygdala and orbitofrontal cortex. Our results showed the application of PAC as a network-specific, electrophysiologic biomarker candidate for comorbid depression and its potential as treatment target for neuromodulation.

The effect of ulinastatin on acute kidney injury in patients undergoing off-pump cardiac bypass surgery.

BACKGROUND: Ulinastatin, an anti-inflammatory and antioxidant trypsin inhibitor, has shown potential in mitigating acute kidney injury (AKI) and reducing serum creatinine levels after various surgeries. This retrospective study aimed to evaluate the effects of ulinastatin on AKI in patients undergoing off-pump coronary artery bypass (OPCAB) surgery. METHODS: We hypothesized that the administration of ulinastatin could prevent AKI in OPCAB. Electrical medical records were reviewed to identify OPCAB patients between January 2015 and June 2020. The utilization of ulinastatin was randomly determined and applied during this period. Acute kidney injury was defined according to the KDIGO guideline, and its incidence was compared between the ulinastatin administration group and the control group. To investigate the effect of ulinastatin on renal function, multivariate logistic regression analysis was used to calculate propensity scores for each group. RESULTS: A total 454 OPCAB were performed, and after following inclusion and exclusion process, 100 patients were identified in the ulinastatin group and 303 patients in the control group. Using 1:2 propensity score matching, we analyzed 100 and 200 patients in the ulinastatin and control groups. The incidence of AKI was similar between the groups (2.5% for the control group, 2.0% for the ulinastatin group, p > 0.999). However, the serum creatinine value on the first post-operative day were significantly lower in the ulinastatin group compared to the control group (0.774 ± 0.179 mg/dL vs 0.823 ± 0.216 mg/dL, P = 0.040), while no significant differences were observed for the other time points (P > 0.05). The length of ICU stay day was significantly shorter in the ulinastatin group (2.91 ± 2.81 day vs 5.22 ± 7.45 day, respectively, P < 0.001). CONCLUSIONS: Ulinastatin did not have a significant effect on the incidence of AKI; it demonstrated the ability to reduce post-operative serum creatine levels at first post-operative day and shorten the length of ICU stay.

Tongue Metastasis From Renal Cell Carcinoma: A Rare Case Presentation.

Renal cell carcinoma (RCC) is characterized by a marked metastatic potential and is the third most common cancer of metastasis to the head and neck, following breast and lung cancer. We report a rare case of a patient with RCC with metastasis to the tongue. A 72-year-old man visited our otorhinolaryngology clinic complaining of tongue pain and ulcerative lesions which occurred 3 weeks before. The patient had been diagnosed with RCC and received a right radical nephrectomy 3 years previously. Because the lesion was suspected to be malignant, a hemiglossectomy was planned. However, metastatic lesions were suspected on the left upper lung and the left 10th ribs in imaging studies and the result of an incisional biopsy revealed tongue metastasis of RCC. RCC metastasis to the tongue is extremely rare. Only 51 cases were reported worldwide from 1911 to 2017. According to the literature, no case of RCC metastasis to the tongue has been reported to date in Korea. Therefore, we report this case along with a review of the literature.

Estimating motor progression trajectory pursuant to temporal dynamic status of cardiac denervation in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a multifaceted disease that encompasses diverse clinical phenotypes. The diversity of PD could be subtyped based on the temporal dynamic status of cardiac sympathetic innervation; (1) initially, denervated myocardium (peripheral nervous system-predominant; PNS-predominant), (2) preserved myocardium (central nervous system-predominant; CNS-predominant), and (3) preserved myocardium who developed cardiac sympathetic denervation (CSD) on the subsequent imaging (Converter; delayed cardiac denervation). This study assessed how the cardiac denervation could reflect the pathobiology. We investigated whether this phenotyping could help predict the motor progression trajectory of PD. METHODS: Cardiac sympathetic innervation was evaluated using initial and sequential 123I-meta-iodobenzylguanidine myocardial scintigraphy and patients were stratified into three groups as above. Motor severity and progression were evaluated in each patient. The association between subtypes and dopaminergic nigrostriatal degeneration was analyzed. The influence of cardiac denervation on motor progression was also investigated. RESULTS: Among the enrolled 195 patients, 144 PD subjects were defined as PNS-predominant, 16 as Converter, and 35 as CNS-predominant. The most severe nigrostriatal degeneration was observed in the PNS-predominant group and the dopaminergic degeneration was the most asymmetric in the CNS-predominant group. Positive linear trends of nigrostriatal degeneration and its asymmetric degeneration of striatum and globus pallidus were found across the patterns of cardiac sympathetic innervation (PNS-predominant vs. Converter vs. CNS-predominant). It indicated an increasing degree of asymmetric degeneration among the groups. A longitudinal estimation of motor progression revealed distinct cardiac denervation trajectories for each subtype. CONCLUSIONS: These results implicated that the subtypes of CSD might indicate a predominant origin and spreading pattern of pathobiology.

Dapagliflozin Does Not Protect against Adriamycin-Induced Kidney Injury in Mice.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors target SGLT2 in renal proximal tubules and promote glycosuria in type 2 diabetes mellitus in humans and animal models, resulting in reduced blood glucose levels. Although clinical trials have shown that SGLT2 inhibitors attenuate the progression of chronic kidney disease, there have been concerns regarding SGLT2-induced acute kidney injury. In this study, we investigated the effect of SGLT2 inhibitors on adriamycin-induced kidney injury in mice. METHODS: Seven-week-old balb/c mice were injected with adriamycin 11.5 mg/kg via the tail vein. Additionally, dapagliflozin was administered via gavage for 2 weeks. The mice were divided into five groups: vehicle, dapagliflozin 3 mg/kg, adriamycin, adriamycin plus dapagliflozin 1 mg/kg, and adriamycin plus dapagliflozin 3 mg/kg. RESULTS: Adriamycin injection reduced the body weight and food and water intakes. Dapagliflozin also decreased the body weight and food and water intakes. Fasting blood glucose and urine volume were not altered by either adriamycin or dapagliflozin. Once adriamycin-induced kidney injury had developed, there were no differences in systolic blood pressure among the groups. Dapagliflozin did not alleviate proteinuria in adriamycin-induced kidney injury. Adriamycin induced significant glomerular and interstitial injury, but dapagliflozin did not attenuate these changes in renal injury. Interestingly, SGLT2 expressions were different between the cortex and medulla of kidneys by dapagliflozin treatment. Dapagliflozin increased SGLT2 expression in medulla, not in cortex. CONCLUSION: Dapagliflozin had no effect on proteinuria or inflammatory changes such as glomerular and tubular damages in adriamycin-induced kidney injury. Our study suggests that dapagliflozin does not protect against adriamycin-induced kidney injury. More experimental studies regarding the effects of SGLT2 inhibitors on various kidney diseases are needed to clarify the underlying mechanisms.

Responsive Neurostimulation for People With Drug-Resistant Epilepsy and Autism Spectrum Disorder.

PURPOSE: Individuals with autism spectrum disorder (ASD) have comorbid epilepsy at much higher rates than the general population, and about 30% will be refractory to medication. Patients with drug-resistant epilepsy (DRE) should be referred for surgical evaluation, yet many with ASD and DRE are not resective surgical candidates. The aim of this study was to examine the response of this population to the responsive neurostimulator (RNS) System. METHODS: This multicenter study evaluated patients with ASD and DRE who underwent RNS System placement. Patients were included if they had the RNS System placed for 1 year or more. Seizure reduction and behavioral outcomes were reported. Descriptive statistics were used for analysis. RESULTS: Nineteen patients with ASD and DRE had the RNS System placed at 5 centers. Patients were between the ages of 11 and 29 (median 20) years. Fourteen patients were male, whereas five were female. The device was implanted from 1 to 5 years. Sixty-three percent of all patients experienced a >50% seizure reduction, with 21% of those patients being classified as super responders (seizure reduction >90%). For the super responders, two of the four patients had the device implanted for >2 years. The response rate was 70% for those in whom the device was implanted for >2 years. Improvements in behaviors as measured by the Clinical Global Impression Scale-Improvement scale were noted in 79%. No complications from the surgery were reported. CONCLUSIONS: Based on the authors' experience in this small cohort of patients, the RNS System seems to be a promising surgical option in people with ASD-DRE.

Cellular Stress Responses against Coronavirus Infection: A Means of the Innate Antiviral Defense.

Cellular stress responses are crucial for maintaining cellular homeostasis. Stress granules (SGs), activated by eIF2α kinases in response to various stimuli, play a pivotal role in dealing with diverse stress conditions. Viral infection, as one kind of cellular stress, triggers specific cellular programs aimed at overcoming virus-induced stresses. Recent studies have revealed that virus-derived stress responses are tightly linked to the host's antiviral innate immunity. Virus infection-induced SGs act as platforms for antiviral sensors, facilitating the initiation of protective antiviral responses called "antiviral stress granules" (avSGs). However, many viruses, including coronaviruses, have evolved strategies to suppress avSG formation, thereby counteracting the host's immune responses. This review discusses the intricate relationship between cellular stress responses and antiviral innate immunity, with a specific focus on coronaviruses. Furthermore, the diverse mechanisms employed by viruses to counteract avSGs are described.

Systematic review of multiple versus single device closure of Secundum atrial septal defects in adults.

INTRODUCTION: Multiple device closure (MDC) strategy has been used in treating of complex Atrial septal defects (ASDs) in adults. The safety profile of MDC compared to conventional single device closure (SDC) is unknown in this population. This report represents the first review examining the outcomes of single versus multiple device ASD closure in adults with ostium secundum defects. METHODS: Literature databases and manual search from their inception until June 30th, 2017 followed the Preferred Reporting Items of Systemic Review and Meta-Analysis (PRISMA) guideline. Main outcomes are 1) overall complication incidence, 2) arrhythmia incidence, 3) residual shunt rate. Each outcome profile was pooled by MDC and SDC, respectively and chi-square analysis was applied to examine statistical significance between MDC and SDC strategies (two-sided and p < .050). RESULTS: A total of 1806 + studies were initially screened, and 20 studies were finally selected (MDC group, 147 patients; SDC group, 1706 patients). There was no difference in overall complication incidence (χ2 = 1.269; p = .259) and arrhythmia incidence (χ2 = 0.325; p = .568) between MDC and SDC. There was no difference in residual shunt rate between the SDC (4.10 %; 70/1706) and MDC groups (6.80 %; 10/147; χ2 = 2.387; p = .122). CONCLUSIONS: The outcomes of percutaneous multiple ASD closure (MDC) seem to be safe and effective as compared to conventional single ASD (SDC) closure in terms of device - related complications and technical success of the procedure. Prospective registry data and randomized trials are needed to determine the long-term outcomes of percutaneous ASD closure using MDC.

Atelocollagen Scaffold Enhances Cartilage Regeneration in Osteochondral Defects: A Study in Rabbits.

BACKGROUND: To enhance articular cartilage healing, microfractures (Mfx) and bone marrow aspirate concentrate (BMAC) are commonly used, and some form of scaffold is often used together to increase its efficacy. Herein, we compared the efficacy of atelocollagen scaffold to that of collagen scaffold when used with Mfx or BMAC on osteochondral defect of animal. METHODS: This experiment was designed in two stages, and therapeutic effects of Mfx and BMAC were respectively evaluated when used with atelocollagen or collagen scaffold. Femoral condyle defects were artificially created in male New Zealand White rabbits, and in each stage, 12 rabbits were randomly allocated into three treatment groups: test group with additional atelocollagen scaffold, the positive control group with collagen scaffold, and the negative control group. Then, for 12 weeks, macroscopic and histological evaluations were performed. RESULTS: At 12 weeks, defects in the test group were fully regenerated with normal cartilage-like tissue, and were well integrated with the surrounding cartilage at both stages experiment, whereas defects in the control groups were not fully filled with regenerated tissue, and the tissue appeared as fibrous tissue. Histologically, the regenerated tissue in the test group showed a statistically significant improvement compared to the positive and negative control groups, achieving a similar structure as normal articular cartilage. CONCLUSION: The results showed that implantation of the atelocollagen scaffold enhanced cartilage regeneration following osteochondral defects in rabbits. This suggests that the atelocollagen scaffold can be used with Mfx or BMAC for effective regeneration of osteochondral defects.

Cardiac sympathetic "morbidity" might reflect the neurobiology of early Parkinson's disease.

BACKGROUND: An appropriate extracranial biomarker that delineates endophenotypes of Parkinson's disease (PD) at an early stage and reflects the neurodegenerative process is lacking. An evaluation of myocardial sympathetic nerve terminals could be a good candidate. This study aimed to explore subtypes of PD patients that showed cardiac catecholaminergic vesicular defect and their characteristics. METHODS: This study included 122 early drug-naïve PD patients who were followed for approximately 4-5 years. All patients were examined with 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane positron-emission tomography and 123I-meta-iodobenzylguanidine myocardial scintigraphy. Cardiac scans were reexamined two or three times. Patients were subgrouped into the sympathetic denervated group at the initial scan, those without evidence of denervated myocardium in the first and subsequent scans, and the converters whose myocardium was initially normal but became impaired in the subsequent scans. Cognition in 99 patients was initially assessed with neuropsychological tests. Any associations between cardiac denervation subtypes and presynaptic dopamine transporter densities were investigated. Cognitive status relevant to cardiac sympathetic denervation status was evaluated. RESULTS: This study found that cross-sectional comparisons of presynaptic monoamine transporter availability with a predefined order of cardiac denervation groups revealed parallel degeneration. A quadratic correlation between cardiac catecholamine capacity and cognition was observed. This association was interpreted to reflect the early neurobiology of PD. CONCLUSION: An observed cardiac catecholaminergic gradient was to mirror the central neurobiology of early PD.