Electrosynthetic C-F bond cleavage.

Fluorinated organic compounds are common among pharmaceuticals, agrochemicals and materials. The significant strength of the C-F bond results in chemical inertness that, depending on the context, is beneficial, problematic or simply a formidable synthetic challenge. Electrosynthesis is a rapidly expanding methodology that can enable new reactivity and selectivity for cleavage and formation of chemical bonds. Here, a comprehensive overview of synthetically relevant electrochemically driven protocols for C-F bond activation and functionalization is presented, including photoelectrochemical strategies.

Characterization of cerebrospinal fluid biomarkers associated with neurodegenerative diseases in healthy cynomolgus and rhesus macaque monkeys.

Monkeys are becoming important translational models of neurodegenerative disease. To facilitate model development, we measured cerebrospinal fluid (CSF) concentrations of key biomarkers in healthy male and female cynomolgus and rhesus macaques. Amyloid beta (Aß40, Aß42), tau (total tau [t-tau], phosphorylated tau [pThr181]), and neurofilament light (NfL) concentrations were measured in CSF of 82 laboratory-housed, experimentally naïve cynomolgus (n = 33) and rhesus (n = 49) macaques. Aß40 and Aß42 were significantly higher in rhesus, and female rhesus were higher than males. NfL and t-tau were higher in males, and NfL was higher in rhesus macaques. p-tau was not affected by species or sex. We also examined whether sample location (lumbar or cisterna puncture) affected concentrations. Sample acquisition site only affected NfL, which was higher in CSF from lumbar puncture compared to cisterna magna puncture. Establishing normative biomarker values for laboratory-housed macaque monkeys provides an important resource by which to compare to monkey models of neurodegenerative diseases.

Osteoarthritic and non-osteoarthritic patients show comparable coronal knee joint line orientations in a cross-sectional study based on 3D reconstructed CT images.

PURPOSE: Recently introduced total knee arthroplasty (TKA) alignment strategies aim to restore the pre-arthritic alignment of an individual patient. The native alignment of a patient can only be restored with detailed knowledge about the native and osteoarthritic alignment as well as differences between them. The first aim of this study was to assess the alignment of a large series of osteoarthritic (OA) knees and investigate whether femoral and tibial joint lines vary within patients with the same overall lower limb alignment. The secondary aim was to compare the alignment of OA patients to the previously published data of non-OA patients. This information could be useful for surgeons considering implementing one of the new alignment concepts. MATERIAL: Coronal alignment parameters of 2692 knee OA patients were measured based on 3D reconstructed CT data using a validated planning software (Knee-PLAN®, Symbios, Yverdon les Bains, Switzerland). Based on these measurements, patients' coronal alignment was phenotyped according to the functional knee phenotype concept. These phenotypes represent an alignment variation of either the overall alignment, the femoral joint line orientation or the tibial joint line orientation. Each phenotype is defined by a specific mean and covers a range of ± 1.5° from this mean. Mean values and distribution among the phenotypes are presented and compared between two populations (OA patients of this study and non-OA patients of a previously published study) as well as between HKA subgroups (varus, valgus and neutral) using t tests and Chi-square tests (p < 0.05). RESULTS: Femoral and tibial joint lines varied within patients with the same overall lower limb alignment. A total of 162 functional knee phenotypes were found (119 males, 136 females and 94 mutual phenotypes). Mean values differed between the OA and non-OA population, but differences were small (< 2°) except for the overall alignment (e.g. HKA). The distribution of OA and non-OA patients among the phenotypes differed significantly, especially among the limb phenotypes. CONCLUSION: Differences between OA and non-OA knees are small regarding coronal femoral and tibial joint line orientation. Femoral and tibial joint line orientation of osteoarthritic patients can, therefore, be used to estimate their native coronal alignment and plan an individualized knee alignment. LEVEL OF CLINICAL EVIDENCE: III.

A comparison of femoral component rotation after total knee arthroplasty in Kanekasu radiographs, axial CT slices and 3D reconstructed images.

OBJECTIVE: To compare the posterior condylar angle measured with Kanekasu radiograph and 2D-CT with the gold standard 3D-CT following primary total knee arthroplasty (TKA). METHODS: Eighty-two knees with pain following TKA were included in this retrospective study. Two independent raters measured the anatomical and surgical posterior condylar angles twice on each Kanekasu radiograph and 2D-CT. These measurements were compared against the 3D-CT measurement. The intra- and interrater reliability of the Kanekasu radiograph and 2D-CT and the correlation with 3D-CT were calculated. RESULTS: The intra- and interrater reliability for measurements of the anatomical posterior condyle angle for the Kanekasu radiograph and the 2D-CT were excellent for both raters (0.85-0.92). For the less experienced rater 1, the intrarater reliability was significantly better for 2D-CT than Kanekasu radiograph for measuring both the surgical (p < 0.01) and anatomical posterior condyle angles (p < 0.05). For the experienced rater 2, the intrarater reliability was significantly better for Kanekasu radiograph than 2D-CT for measurement of the surgical posterior condyle angle (p < 0.05). The correlation with 3D-CT is higher in 2D-CT than in Kanekasu radiograph (p < 0.01). While the Kanekasu radiograph predicts the 3D-CT angle with 65.9%, 2D-CT can measure the true angle with 82.9% certainty. CONCLUSION: Measurements using the anatomical transepicondylar axis are easier to replicate compared to the surgical transepicondylar axis. In comparison with the gold standard 3D-CT, 2D-CT showed a significantly higher correlation with 3D-CT than the Kanekasu measurements. If 3D-CT is available, it should be preferred over 2D-CT and Kanekasu view radiograph for femoral component rotation measurements.

Typical MRI-pattern suggests peak maturation of the ACI graft 2 years after third-generation ACI: a systematic review.

PURPOSE: The purpose of the present article was (1) to systematically review the current literature and (2) to collect data regarding the postoperative magnetic resonance imaging (MRI) appearance of third-generation autologous chondrocyte implantation (ACI) grafts and (3) to provide an overview of imaging findings at various postoperative time points. METHODS: A systematic review of the literature in Medline (Pubmed) and Embase was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Articles which reported the post-operative MRI morphological outcomes following the use of third-generation ACI for treatment of knee cartilage lesions were included. All MRI results were allocated to six different time intervals: ≤ 3 months, > 3-6 months, > 6 months-1 year, > 1 year-2 years, > 2-5 years and > 5 years after surgery. RESULTS: A total of 22 studies were included and the study populations ranged from 13 to 180 patients adding up to a total of 951 patients. Parameters such as defect fill, border integration, surface contour, graft morphology and integrity of the subchondral lamina all improve gradually with a peak two years following surgery suggesting complete graft maturation at this time point. After this peak, a statistically insignificant decline is noted for most of the parameters. Signal intensity was found to gradually shift from hyperintense to isointense in the first 36 months and to hypointense later on. Contrarily, subchondral bone edema is not only a postoperative feature of the procedure but also can reappear or persist up to ten years after surgery. As graft failures can appear after two years, consequently, the MRI composite score is also affected. CONCLUSION: Recurring patterns in postoperative MRI appearance were observed in certain parameters including defect filling, graft signal intensity and structure, border integration of the graft while parameters like subchondral bone tend to be unpredictable. Given the heterogenous findings in terms of clinical correlation, and relating that aspect to the patterns found in this review, an MRI is justified at three months, one year, two years and five years after surgery, unless the clinical symptomatology and individual patient needs dictate otherwise. LEVEL OF EVIDENCE: IV.

The effect of lumbar puncture on the neurodegeneration biomarker neurofilament light in macaque monkeys.

INTRODUCTION: Neurofilament light (NFL) in cerebrospinal fluid (CSF) is elevated in neurodegenerative disease patients, and may track disease progression and treatment. Macaque monkeys are emerging as important translational models of neurodegeneration, and NFL may be a useful biomarker. METHODS: To determine the influence of a previous lumbar puncture (LP) on NFL, we collected CSF at multiple time points in macaque monkeys via LP or cisterna magna puncture. NFL, amyloid beta (Aß40, Aß42), and tau (tTau, pTau) in CSF were measured by standard enzyme-linked immunosorbent assay and multiplex. RESULTS: NFL was significantly elevated at 14 to 23 days after an LP (median increase: 162%). Aß and tau biomarkers remained stable. NFL peaked and decayed over 1 to 2 months after LP. NFL was not elevated after cisterna magna puncture. DISCUSSION: Results suggest damage of the cauda equina during LP may increase NFL. Caution should be taken in interpreting NFL concentration in studies in which repeat LPs are performed.