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Rudolf C - Through Fusion _BEST_
Surgical treatment options for SI joint disorders have been unattractive until relatively recently. Open arthrodesis, commonly performed throughout the 1900s, is now reserved primarily for traumatic pelvic ring fractures due to the invasiveness of the procedure, coupled with a high morbidity rate [14-16]. In recent years, several minimally invasive techniques for fusing the SI joint have been introduced into the surgical repertoire [17-21]. MIS SI joint fusion for certain SI joint disorders (degenerative sacroiliitis and SI joint disruptions), specifically using a series of triangular titanium implants, has been shown to result in lower morbidity, including shorter operating times and hospital stays, fewer complications, a lower reoperation rate, and higher gains in patient quality of life compared to the open surgical method, as evidenced by a recent comparative cohort study [22].
Rudolf C - Through Fusion
Demographic variables were tabulated and expressed as frequency and means with standard deviation, where appropriate. A repeated measures analysis of variance (ANOVA) was used to compare VAS pain scores from baseline to all postoperative time points. A paired t-test was used to assess improvement from baseline to the 60-month time point on the SI joint survey. An unpaired t-test was performed to assess the effect of sex and history of prior lumbar spinal fusion on outcomes. Statistical analyses were performed using R software [26]. Clinical improvement was defined using previously validated minimum clinically important difference (MCID) and substantial clinical benefit (SCB) values for back pain on VAS. MCID is defined as a change of >2.0 points and SCB is defined as a 2.5-point decrease or a raw score of
Subject 1013 is a 50-year old female who presented to the clinic post L4-S1 arthrodesis with complex pain syndrome and concomitant chronic conditions requiring multiple medications to manage her pain. Furthermore, due to her diminished ambulatory capability, she required assistance in performing activities of daily living. Subject symptoms and findings on physical exam suggested degenerative sacroiliitis. The SI joint as a pain generator was confirmed by intra-articular SI joint injection. The subject underwent a single-side SI joint fusion. She experienced good pain improvement on the operative side, prompting her to undergo diagnostic testing on the contralateral side followed by SI joint fusion. Postoperatively, she experienced significant improvement in ambulation and capacity for activities of daily living and near complete resolution of her bilateral SI joint pain. One year later, her degenerative hip joint disease had progressed, resulting in a left-sided total hip replacement. This subject declined to participate in the imaging component of the study. The degradation of function and high ODI score at the 5-year assessment seems associated with recurrent spine-related low back pain.
Positive clinical outcomes are based on accurate diagnosis and assessment of all potential pain generators in the lumbar spine, SI joint and hip. Correctly diagnosing SI joint disorders requires a rigorous approach to arrive at an accurate diagnosis. A detailed history, comprehensive physical examination, and an index of suspicion are required to formulate a differential diagnosis. The practitioner utilizes imaging and diagnostic testing for the process of inclusion/exclusion of the different diagnostic possibilities. Several pathophysiologic conditions that affect the lumbar spine-SI joint-hip axis can present similarly and typically low back pain patients have multiple pain generators. Biomechanical studies clearly show an interdependent kinematic relationship within the lumbopelvic hip complex, with changes in one structure affecting degree of motion and load within the entire complex [32]. Therefore, the SI joint should be evaluated as a potential pain generator in patients who fail to improve or experience late non-mechanical failures after lumbar arthrodesis. Pain and degeneration in the SI joint after lumbar arthrodesis has been reported to range between 43 and 75% [6, 30, 33, 34]. The relatively low success rate of spinal fusion, combined with the high incidence of diagnosable SI joint disorders in patients presenting with low back pain strongly suggests that the SI joint is often overlooked as a PG in this population [3]. An accurate diagnosis requires not only a ruling out or downgrading of other conditions, but also a thorough evaluation of the lumbar spine and hip, as well as a physical exam that includes maneuvers that stress the SI joint and a series of image-guided intra-articular diagnostic injections.
The anti-human IgM single-domain antibody is an in-house developed camelid sdAb that specifically recognizes human IgM. It has no cross-reactivity with human IgG molecules. This product can be fully customized to meet your needs, for example, sdAb anti-human IgM is also available as MBP (maltose-binding protein) fusion protein to increase its size, ideal for immobilizing it in lateral flow assays.
mtDNA is organized in nucleoids carrying approximately a thousand molecules of the packaging protein TFAM/mtDNA and the replisome machinery (POLG, TWINKLE, and mtSSBP1, among others). When OMM fusion machinery (MFN1 and MFN2) is mutated, losing its function, mtDNA clusters with reduced levels of POLG and mtSSBP1 and increased levels of TWINKLE, causing a replication rate decline and mtDNA depletion. The IMM fusion protein OPA1 is facing to the IMS and seems to not be involved in mtDNA clustering but is, as MFNs, required to maintain the replicative capacity of mtDNA [8]. IMM, inner mitochondrial membrane; IMS, intermembrane space; KO, knock-out; MFN, mitofusin; mtDNA, mitochondrial DNA; mtSSBP1, mitochondrial single-stranded binding protein; OMM, outer mitochondrial membrane; OPA1, optic atrophy 1; POLG, DNA polymerase gamma; TFAM, transcription factor A, mitochondrial; TWINKLE, mitochondrial helicase.
In the present work, Silva Ramos and colleagues [8] show for the first time a direct link between the dynamics machinery and mtDNA copy number. Using a battery of techniques in cardiomyocytes and immortalized MEFs (mouse embryonic fibroblasts), the authors link replication of mtDNA to the outer (MFN1 and MFN2) and inner (OPA1) membrane fusion proteins, but surprisingly, they show that nucleoid distribution only relies on the outer membrane fusion and fission proteins (Fig 1).
Traditionally, mtDNA depletion affecting the fusion machinery was related to increased mtDNA mutation rates [11]. However, when absolute levels were measured, very few molecules with deletions and point mutations were found, ruling out this as causative for depletion. On the other hand, mitochondrial dysfunction might cause an imbalance in important intermediate metabolites, especially the synthesis of pyrimidine nucleotides, which are necessary to make new mtDNA molecules, at the end causing mtDNA depletion. Here, the authors exclude both possibilities, despite some differences depending on the models they analyzed, but find an imbalance of components of the mtDNA replisome machinery when mitochondrial fusion is abolished.
Additionally, the authors further establish the outer mitochondrial membrane (OMM) as a key component for the distribution of mtDNA (Fig 1). Using superresolution microscopy, the authors show impressive clustering of nucleoids containing several molecules of mtDNA in the absence of outer membrane fusion, which could not have been resolved using conventional confocal microscopy. This aberrant aggregation, however, neither affects mitochondrial transcription activity nor is linked to the altered replisome composition.
The authors also show in a series of experiments the physiological relevance of these findings. The mixing of matrix components through IMM and OMM fusion is indispensable to keep mtDNA replicative rates high. Mitochondria, as a central hub in many metabolic pathways, need to be able to adapt, e.g., to changes in carbon source supply, and this is reflected in morphological changes [15, 16]. Beyond modulating mitochondrial network morphology during stress or in response to a changing metabolic environment, this work shows that mitochondrial fusion and fission also ensure proper content mixing required in order to maintain high mtDNA replicative capacity. The results the authors present suggest that mitochondrial content mixing induced by mitochondrial dynamics is necessary to maintain the delicate protein composition balance of the mitochondrial replisome. How mitochondrial outer and inner membrane fusion proteins affect replisome composition and why outer and not inner membrane fusion controls nucleoid distribution remains to be solved.
When he was nine years old, Steiner believed that he saw the spirit of an aunt who had died in a far-off town, asking him to help her at a time when neither he nor his family knew of the woman's death.[37] Steiner later related that as a child, he felt "that one must carry the knowledge of the spiritual world within oneself after the fashion of geometry ... [for here] one is permitted to know something which the mind alone, through its own power, experiences. In this feeling I found the justification for the spiritual world that I experienced ... I confirmed for myself by means of geometry the feeling that I must speak of a world 'which is not seen'."[2]
Steiner became a well-known and controversial public figure during and after World War I. In response to the catastrophic situation in post-war Germany, he proposed extensive social reforms through the establishment of a Threefold Social Order in which the cultural, political and economic realms would be largely independent. Steiner argued that a fusion of the three realms had created the inflexibility that had led to catastrophes such as World War I. In connection with this, he promoted a radical solution in the disputed area of Upper Silesia, claimed by both Poland and Germany. His suggestion that this area be granted at least provisional independence led to his being publicly accused of being a traitor to Germany.[60] 041b061a72