Quantifying internal intervertebral disc strains to assess nucleus replacement device designs: a digital volume correlation and ultra-high-resolution MRI study.

Introduction: Nucleus replacement has been proposed as a treatment to restore biomechanics and relieve pain in degenerate intervertebral discs (IVDs). Multiple nucleus replacement devices (NRDs) have been developed, however, none are currently used routinely in clinic. A better understanding of the interactions between NRDs and surrounding tissues may provide insight into the causes of implant failure and provide target properties for future NRD designs. The aim of this study was to non-invasively quantify 3D strains within the IVD through three stages of nucleus replacement surgery: intact, post-nuclectomy, and post-treatment. Methods: Digital volume correlation (DVC) combined with 9.4T MRI was used to measure strains in seven human cadaveric specimens (42 ± 18 years) when axially compressed to 1 kN. Nucleus material was removed from each specimen creating a cavity that was filled with a hydrogel-based NRD. Results: Nucleus removal led to loss of disc height (12.6 ± 4.4%, p = 0.004) which was restored post-treatment (within 5.3 ± 3.1% of the intact state, p > 0.05). Nuclectomy led to increased circumferential strains in the lateral annulus region compared to the intact state (-4.0 ± 3.4% vs. 1.7 ± 6.0%, p = 0.013), and increased maximum shear strains in the posterior annulus region (14.6 ± 1.7% vs. 19.4 ± 2.6%, p = 0.021). In both cases, the NRD was able to restore these strain values to their intact levels (p ≥ 0.192). Discussion: The ability of the NRD to restore IVD biomechanics and some strain types to intact state levels supports nucleus replacement surgery as a viable treatment option. The DVC-MRI method used in the present study could serve as a useful tool to assess future NRD designs to help improve performance in future clinical trials.

The use of e-consent in surgery and application to neurosurgery: a systematic review and meta-analysis.

INTRODUCTION: The integration of novel electronic informed consent platforms in healthcare has undergone significant growth over the last decade. Adoption of uniform, accessible, and robust electronic online consenting applications is likely to enhance the informed consent process and improve the patient experience and has the potential to reduce medico-legal ramifications of inadequate consent. A systematic review and meta-analysis was conducted to evaluate the utility of novel electronic means of informed consent in surgical patients and discuss its application to neurosurgical cohorts. METHODS: A review of randomised controlled trials, non-randomised studies of health interventions, and single group pre-post design studies in accordance with the PRISMA statement. Random effects modelling was used to estimate pooled proportions of study outcomes. Patient satisfaction with the informed consent process and patients' gain in knowledge were compared for electronic technologies versus non-electronic instruments. A sub-group analysis was conducted to compare the utility of electronic technologies in neurosurgical cohorts relative to other surgical patients in the context of patient satisfaction and knowledge gain. RESULTS: Of 1042 screened abstracts, 63 studies were included: 44 randomised controlled trials (n = 4985), 4 non-randomised studies of health interventions (n = 387), and 15 single group pre-post design studies (n = 872). Meta-analysis showed that electronic technologies significantly enhanced patient satisfaction with the informed consent process (P < 0.00001) and patients' gain in knowledge (P < 0.00001) compared to standard non-electronic practices. Sub-group analysis demonstrated that neurosurgical patient knowledge was significantly enhanced with electronic technologies when compared to other surgical patients (P = 0.009), but there was no difference in patient satisfaction between neurosurgical cohorts and other surgical patients with respect to electronic technologies (P = 0.78). CONCLUSIONS: Novel electronic technologies can enhance patient satisfaction and increase patients' gain in knowledge of their surgical procedures. Electronic patient education tools can significantly enhance patient knowledge for neurosurgical patients. If used appropriately, these modalities can shorten and/or improve the consent discussion, streamlining the surgical process and improving satisfaction for neurosurgical patients.

An in vitro comparison of three nucleus pulposus removal techniques for partial intervertebral disc replacement: An ultra-high resolution MRI study.

Background: Nuclectomy, also known as nucleotomy, is a percutaneous surgical procedure performed to remove nucleus material from the center of the disc. Multiple techniques have been considered to perform a nuclectomy, however, the advantages and disadvantages of each are not well understood. Aims: This in vitro biomechanical investigation on human cadaveric specimens aimed to quantitatively compare three nuclectomy techniques performed using an automated shaver, rongeurs, and laser. Material & Methods: Comparisons were made in terms of mass, volume and location of material removal, changes in disc height, and stiffness. Fifteen vertebra-disc-vertebra lumbar specimens were acquired from six donors (40 ± 13 years) and split into three groups. Before and after nucleotomy axial mechanical tests were performed and T2-weighted 9.4T MRIs were acquired for each specimen. Results: When using the automated shaver and rongeurs similar volumes of disc material were removed (2.51 ± 1.10% and 2.76 ± 1.39% of the total disc volume, respectively), while considerably less material was removed using the laser (0.12 ± 0.07%). Nuclectomy using the automated shaver and rongeurs significantly reduced the toe-region stiffness (p = 0.036), while the reduction in the linear region stiffness was significant only for the rongeurs group (p = 0.011). Post-nuclectomy, 60% of the rongeurs group specimens showed changes in the endplate profile while 40% from the laser group showed subchondral marrow changes. Discussion: From the MRIs, homogeneous cavities were seen in the center of the disc when using the automated shaver. When using rongeurs, material was removed non-homogeneously both from the nucleus and annulus regions. Laser ablation formed small and localized cavities suggesting that the technique is not suitable to remove large volumes of material unless it is developed and optimized for this application. Conclusion: The results demonstrate that both rongeurs and automated shavers can be used to remove large volumes of NP material but the reduced risk of collateral damage to surrounding tissues suggests that the automated shaver may be more suitable.

Methods of acoustic gas flux inversion-Investigation into the initial amplitude of bubble excitation.

Passive acoustic inversion techniques for measuring gas flux into the water column have the potential to be a powerful tool for the long-term monitoring and quantification of natural marine seeps and anthropogenic emissions. Prior inversion techniques have had limited precision due to lack of constraints on the initial amplitude of a bubble's excitation following its release into the water column ( R). R is determined by observing the acoustic signal of bubbles released from sediment in a controlled experiment and its use is demonstrated by quantifying the flux from a volcanic CO2 seep offshore Panarea (Italy), improving the precision by 78%.

Does Coronavirus Disease 2019 (COVID-19) Affect Perioperative Morbidity and Mortality for Patients Requiring Emergency Instrumented Spinal Surgery? A Single-Center Cohort Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic sent shockwaves through health services worldwide. Resources were reallocated. Patients with COVID-19 still required instrumented spinal surgery for emergencies. Clinical outcomes for these patients are not known. The objective of this study was to evaluate the effects of COVID-19 on perioperative morbidity and mortality for patients undergoing emergency instrumented spinal surgery and to determine risk factors for increased morbidity/mortality. METHODS: This retrospective cohort study included 11 patients who were negative for COVID-19 and 8 patients who were positive for COVID-19 who underwent emergency instrumented spinal surgery in 1 hospital in the United Kingdom during the pandemic peak. Data collection was performed through case note review. Patients in both treatment groups were comparable for age, sex, body mass index (BMI), comorbidities, surgical indication, and preoperative neurologic status. Predefined perioperative outcomes were recorded within a 30-day postoperative period. Univariable analysis was used to identify risk factors for increased morbidity. RESULTS: There were no mortalities in either treatment group. Four patients positive for COVID-19 (50%) developed a complication compared with 6 (55%) in the COVID-19-negative group (P > 0.05). The commonest complication in both groups was respiratory infection. Three patients positive for COVID-19 (37.5%) required intensive care unit admission, compared with 4 (36%) in the COVID-19-negative group (P > 0.05). The average time between surgery and discharge was 19 and 10 days in COVID-19-positive and -negative groups, respectively (P = 0.02). In the COVID-19 positive group, smoking, abnormal BMI, preoperative oxygen requirement, presence of fever, and oxygen saturations <95% correlated with increased risk of complications. CONCLUSIONS: Emergency instrumented spinal surgery in patients positive for COVID-19 was associated with increased length of hospital stay. There was no difference in occurrence of complications or intensive care unit admission. Risk factors for increased morbidity in patients with COVID-19 included smoking, abnormal BMI, preoperative oxygen requirement, fever and saturations <95%.

Advantages of determining the fertile window with the individualised Natural Cycles algorithm over calendar-based methods.

Purpose: This study aims to compare the accuracy of fertile window identification with the contraceptive app Natural Cycles against the Rhythm Method and Standard Days Method (SDM).Materials and methods: Menstruation dates, basal body temperature (BBT), and luteinising hormone (LH) test results were collected anonymously from Natural Cycles app users. The fraction of green days (GDs) and wrong green days (WGDs) allocated by the various algorithms was determined over 12 cycles. For comparison of Natural Cycles and the Rhythm Method, 26,626 cycles were analysed.Results: Natural Cycles' algorithms allocated 59% GDs (LH, BBT) in cycle 12, while the fraction of WGDs averaged 0.08%. The Rhythm Method requires monitoring of six cycles, resulting in no GDs or WGDs in cycle 1-6. In cycle 7, 49% GDs and 0.26% WGDs were allocated. GDs and WGDs decreased to 43% and 0.08% in cycle 12. The probabilities of WGDs on the day before ovulation with Natural Cycles were 0.31% (BBT) and 0% (LH, BBT), and 0.80% with the Rhythm Method. The probability of WGDs on the day before ovulation was 6.90% with the SDM.Conclusions: This study highlights that individualised algorithms are advantageous for accurate determination of the fertile window and that static algorithms are more likely to fail during the most fertile days.

Real-world menstrual cycle characteristics of more than 600,000 menstrual cycles.

The use of apps that record detailed menstrual cycle data presents a new opportunity to study the menstrual cycle. The aim of this study is to describe menstrual cycle characteristics observed from a large database of cycles collected through an app and investigate associations of menstrual cycle characteristics with cycle length, age and body mass index (BMI). Menstrual cycle parameters, including menstruation, basal body temperature (BBT) and luteinising hormone (LH) tests as well as age and BMI were collected anonymously from real-world users of the Natural Cycles app. We analysed 612,613 ovulatory cycles with a mean length of 29.3 days from 124,648 users. The mean follicular phase length was 16.9 days (95% CI: 10-30) and mean luteal phase length was 12.4 days (95% CI: 7-17). Mean cycle length decreased by 0.18 days (95% CI: 0.17-0.18, R 2 = 0.99) and mean follicular phase length decreased by 0.19 days (95% CI: 0.19-0.20, R 2 = 0.99) per year of age from 25 to 45 years. Mean variation of cycle length per woman was 0.4 days or 14% higher in women with a BMI of over 35 relative to women with a BMI of 18.5-25. This analysis details variations in menstrual cycle characteristics that are not widely known yet have significant implications for health and well-being. Clinically, women who wish to plan a pregnancy need to have intercourse on their fertile days. In order to identify the fertile period it is important to track physiological parameters such as basal body temperature and not just cycle length.

Typical use effectiveness of Natural Cycles: postmarket surveillance study investigating the impact of previous contraceptive choice on the risk of unintended pregnancy.

OBJECTIVE: To investigate the association between contraceptive effectiveness of Natural Cycles and users' previous choice of contraceptive, and to evaluate the impact of shifting from other methods to Natural Cycles on the risk of unintended pregnancy. SETTING: Natural Cycles mobile application. PARTICIPANTS: 16 331 Natural Cycles users in Sweden for the prevention of pregnancy. OUTCOME MEASURES: Risk of unintended pregnancy. STUDY DESIGN: Real world evidence was collected from Natural Cycles users regarding contraceptive use prior to using Natural Cycles and sexual activity while using Natural Cycles. We calculated the typical use 1-year Pearl Index (PI) and 13-cycle failure rate of Natural Cycles for each cohort. The PI was compared with the population PI of their stated previous methods. RESULTS: For women who had used condoms before, the PI of Natural Cycles was the lowest at 3.5±0.5. For women who had used the pill before, the PI of Natural Cycles was the highest at 8.1±0.6. The frequency of unprotected sex on fertile days partially explained some of the observed variation in PI between cohorts. 89% of users switched to Natural Cycles from methods with higher or similar reported PIs. CONCLUSION: The effectiveness of Natural Cycles is influenced by previous contraceptive choice and this should be considered when evaluating the suitability of the method for the individual. We estimate that Natural Cycles usage can reduce the overall likelihood of having an unintended pregnancy by shifting usage from less effective methods.

The spectrum of traumatic injuries at the craniocervical junction: a review of imaging findings and management.

The craniocervical junction is an area with unique biomechanical properties and injuries conferred often represent high-impact trauma. The vital structures traversing this region are susceptible to injury with frequent, only subtle findings identified on unenhanced CT, with MRI and CT angiography often revealing the full extent of injuries. This article reviews the osseous and ligamentous anatomy of the region and common injury patterns. Endovascular and neurosurgical management will also be discussed.

A 500 year sediment lake record of anthropogenic and natural inputs to Windermere (English Lake District) using double-spike lead isotopes, radiochronology, and sediment microanalysis.

A high-resolution record of pollution is preserved in recent sediments from Windermere, the largest lake in the English Lake District. Data derived from X-ray core scanning (validated against wavelength dispersive X-ray fluorescence), radiochronological techniques ((210)Pb and (137)Cs) and ultrahigh precision, double-spike mass spectrometry for lead isotopes are combined to decipher the anthropogenic inputs to the lake. The sediment record suggests that while most element concentrations have been stable, there has been a significant increase in lead, zinc, and copper concentrations since the 1930s. Lead isotope down-core variations identify three major contributory sources of anthropogenic (industrial) lead, comprising gasoline lead, coal combustion lead (most likely source is coal-fired steam ships), and lead derived from Carboniferous Pb-Zn mineralization (mining activities). Periods of metal workings do not correlate with peaks in heavy metals due to the trapping efficiency of up-system lakes in the catchment. Heavy metal increases could be due to flood-induced metal inwash after the cessation of mining and the weathering of bedrock in the catchment. The combination of sediment analysis techniques used provides new insights into the pollutant depositional history of Windermere and could be similarly applied to other lake systems to determine the timing and scale of anthropogenic inputs.

Rigid occipitocervical fixation: indications, outcomes, and complications in the modern era.

OBJECT: Over the past 40 years, various methods and instrumentation types have been developed for occipitocervical fixation (OCF) in the management of occipitocervical instability. This study reports indications, outcomes, and complications with rigid OCF using screw-rod and screw-plate instrumentation, which has comparatively less long-term data. METHODS: A prospectively maintained database identified 100 consecutive patients who underwent rigid OCF in a single unit over a period of 13 years. Patient demographics, clinical indications, pre- and postoperative radiographic findings, neck disability indices (NDIs), myelopathy disability indices (MDIs), visual analog scale (VAS) scores, and Ranawat scores were recorded. Complications including instrumentation failure were also documented. RESULTS: Underlying etiologies included rheumatoid arthritis (RA; 41%), tumor (16%), trauma (15%), congenital etiologies (14%), metabolic (6%) and inflammatory (6%) conditions, and infection (2%). The pre- and postoperative MDI and VAS scores for neck pain showed significant improvements in the RA group (MDI 64.5% vs 42.5%, p = 0.02; mean VAS 7.5 of 10 vs 3.7 of 10, p < 0.001). Improvements in MDI and NDI outcome measures were also seen in the trauma and tumor categories. Overall, there were 4 cases of instrumentation failure; all included broken rods in the stress riser region of occipitocervical rod curvature, and 1 patient also had occipital plate screw pullout. Other complications included 5 wound infections requiring wound washout, 1 vertebral artery injury (no clinical sequelae), and 1 perioperative death due to myocardial infarction. CONCLUSIONS: Rigid OCF is a safe and effective method of managing occipitocervical instability due to a variety of causes. Outcome measures are favorable, and patients with chronically debilitating diseases such as RA may benefit in terms of improvements in neurological deficit and neck pain. The complication profile is comparable to that reported in other series of OCF in the literature, as well as to the previously used semirigid type of rod/sublaminar wire fixation.

Discrimination of paediatric brain tumours using apparent diffusion coefficient histograms.

OBJECTIVE: To determine if histograms of apparent diffusion coefficients (ADC) can be used to differentiate paediatric brain tumours. METHODS: Imaging of histologically confirmed tumours with pre-operative ADC maps were reviewed (54 cases, 32 male, mean age 6.1 years; range 0.1-15.8 years) comprising 6 groups. Whole tumour ADC histograms were calculated; normalised for volume. Stepwise logistic regression analysis was used to differentiate tumour types using histogram metrics, initially for all groups and then for specific subsets. RESULTS: All 6 groups (5 dysembryoplastic neuroectodermal tumours, 22 primitive neuroectodermal tumours (PNET), 5 ependymomas, 7 choroid plexus papillomas, 4 atypical teratoid rhabdoid tumours (ATRT) and 9 juvenile pilocytic astrocytomas (JPA)) were compared. 74% (40/54) were correctly classified using logistic regression of ADC histogram parameters. In the analysis of posterior fossa tumours, 80% of ependymomas, 100% of astrocytomas and 94% of PNET-medulloblastoma were classified correctly. All PNETs were discriminated from ATRTs (22 PNET and 4 supratentorial ATRTs) (100%). CONCLUSIONS: ADC histograms are useful in differentiating paediatric brain tumours, in particular, the common posterior fossa tumours of childhood. PNETs were differentiated from supratentorial ATRTs, in all cases, which has important implications in terms of clinical management. Key Points • MR based apparent diffusion coefficient histograms can help differentiate paediatric brain tumours • ADC histogram parameters correctly classified the great majority of posterior fossa tumours.

Contrasting décollement and prism properties over the Sumatra 2004-2005 earthquake rupture boundary.

Styles of subduction zone deformation and earthquake rupture dynamics are strongly linked, jointly influencing hazard potential. Seismic reflection profiles across the trench west of Sumatra, Indonesia, show differences across the boundary between the major 2004 and 2005 plate interface earthquakes, which exhibited contrasting earthquake rupture and tsunami generation. In the southern part of the 2004 rupture, we interpret a negative-polarity sedimentary reflector approximately 500 meters above the subducting oceanic basement as the seaward extension of the plate interface. This predécollement reflector corresponds to unusual prism structure, morphology, and seismogenic behavior that are absent along the 2005 rupture zone. Although margins like the 2004 rupture zone are globally rare, our results suggest that sediment properties influence earthquake rupture, tsunami hazard, and prism development at subducting plate boundaries.

Expression of lipogenic factors galectin-12, resistin, SREBP-1, and SCD in human sebaceous glands and cultured sebocytes.

The transcription factors CCAAT enhancer-binding protein alpha, beta, and delta, and peroxisome proliferator-activated receptor gamma are known to be crucial to the differentiation of adipocytes and are expressed in sebaceous gland cells. As lipogenesis is key to both adipocyte and sebocyte differentiation we hypothesize that sebocytes follow a similar program of differentiation to adipocytes. We have investigated the expression of known adipogenic factors resistin, galectin-12, sterol response-element-binding protein-1 (SREBP-1) and stearoyl-CoA desaturase in the immortalized sebaceous gland cell line SZ95 and whole skin. Reverse transcriptase-PCR analysis showed the expression of galectin-12, resistin, SREBP-1, and stearoyl-CoA desaturase mRNAs in SZ95 sebocytes. Immunoreactivity was observed for galectin-12 and SREBP-1 in the nuclei and resistin in the cytoplasm of basal sebocytes, and stearoyl CoA desaturase in the cytoplasm of basal and luminal sebocytes of human scalp skin. Expression of galectin-12, resistin, and SREBP-1 in SZ95 sebocytes was confirmed by Western blot analysis. These data provide further evidence that pathways of differentiation in adipocytes and sebocytes could be similar and therefore further understanding of sebaceous gland differentiation and lipogenesis and potential therapies for sebaceous gland disorders may be obtained from our knowledge of adipocyte differentiation.

Selective ablation of retinoblastoma protein function by the RET finger protein.

The retinoblastoma tumor suppressor protein (Rb) affects gene transcription both negatively and positively and through this regulates distinct cellular responses. Although cell cycle regulation requires gene repression, Rb's ability to promote differentiation and part of its antiproliferative activity appears to rely on the activation of gene transcription. We present evidence here that the RET finger protein (RFP)/tripartite motif protein 27 (TRIM 27) inhibits gene transcription activation by Rb but does not affect gene repression. RFP binds to Rb and prevents the degradation of the EID-1 inhibitor of histone acetylation and differentiation. Furthermore, ablation of RFP in U2OS osteosarcoma cells augments a transcriptional program indicative of lineage-specific differentiation in response to Rb. These findings provide precedent for a regulatory pathway that uncouples different Rb-dependent activities and thus silences specific cellular responses to Rb in a selective way.

Contrasting expression patterns of CCAAT/enhancer-binding protein transcription factors in the hair follicle and at different stages of the hair growth cycle.

Hair follicles undergo repeated cycles of growth and regression, throughout the entire life of the organism. These dynamic changes require closely co-ordinated regulation of gene expression. The CCAAT/enhancer-binding proteins are a family of basic region/leucine zipper transcription factors that regulate gene transcription in various tissues. They have been implicated in epidermal differentiation and may therefore play an important role in the hair follicle. We have investigated the localization of four members of this family--CCAAT/enhancer-binding protein-alpha, -beta, and -delta, and Gadd153--in both human and murine hair follicles by immunohistochemistry. Furthermore, we examined CCAAT/enhancer-binding protein-alpha, -beta, and -delta immunoreactivity at different stages of the depilation-induced murine hair growth cycle. Distinct immunoreactivity patterns for CCAAT/enhancer-binding protein-alpha, -beta, and -delta, and Gadd153 were observed in the outer root sheath, sebaceous gland, dermal papilla, and connective tissue sheath of human anagen hair follicles. In murine follicles, CCAAT/enhancer-binding protein-alpha was expressed in the outer root sheath, sebaceous gland, and dermal papilla, whereas CCAAT/enhancer-binding protein-beta expression was confined to the matrix, sebaceous gland, and inner and outer root sheaths. Both CCAAT/enhancer-binding protein-alpha and -beta were upregulated during anagen, then downregulated in catagen follicles. In contrast, CCAAT/enhancer-binding protein-delta showed no hair cycle-dependent variation in immunoreactivity. These data suggests that the expression of CCAAT/enhancer-binding protein-alpha and -beta may, in turn, play a part in regulating hair cycle-dependent gene expression. Moreover, as CCAAT/enhancer-binding protein-alpha, -beta, and -delta are crucial in the regulation of adipocyte differentiation and lipid metabolism, their expression in sebocytes suggests they may also play a similar role in differentiation and lipid metabolism of the sebaceous gland.