CAnceR IN PreGnancy (CARING) - a retrospective study of cancer diagnosed during pregnancy in the United Kingdom.

BACKGROUND: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population. METHODS: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020). RESULTS: Median age at diagnosis was 33 years, with breast, skin and haematological the most common primary sites. The majority of cases were new diagnoses (109 patients, 91.6%). Most patients were treated with radical intent (96 patients, 80.7%), however, gastrointestinal cancers were associated with a high rate of palliative intent treatment (63.6%). Intervention was commenced during pregnancy in 68 (57.1%) patients; 44 (37%) had surgery and 31 (26.1%) received chemotherapy. Live births occurred in 98 (81.7%) of the cases, with 54 (55.1%) of these delivered by caesarean section. Maternal mortality during the study period was 20.2%. CONCLUSIONS: This is the first pan-tumour report of diagnosis, management and outcomes of cancer diagnosed during pregnancy in the UK. Our findings demonstrate proof of concept that data collection is feasible and highlight the need for further research in this cohort of patients.

Leveraging the Full Continuum of Care to Prevent Opioid Use Disorder.

Substance use disorder prevention programs are most effective when matched appropriately to the baseline risk of the population. Individuals who misuse opioids often have unique risk profiles different from those who use other substances such as alcohol or cannabis. However, most substance use prevention programs are geared toward universal audiences, neglecting key inflection points along the continuum of care. The HEAL Prevention Cooperative (HPC) is a unique cohort of research projects that represents a continuum of care, from community-level universal prevention to indicated prevention among older adolescents and young adults who are currently misusing opioids or other substances. This paper describes the theoretical basis for addressing opioid misuse and opioid use disorder across the prevention continuum, using examples from research projects in the HPC.

Serum persistent organic pollutants and diminished ovarian reserve: a single-exposure and mixture exposure approach from a French case-control study.

STUDY QUESTION: Are persistent organic pollutants (POPs) associated with a diminished ovarian reserve (DOR) in women of reproductive age? SUMMARY ANSWER: Amongst 17 POPs detected in over 20% of serum samples, only p,p'-DDE was significantly associated with an increased risk of DOR, and ß-hexachlorocyclohexane (ß-HCH) was significantly associated with a decreased risk of DOR whilst mixture analyses yielded non-significant associations and did not detect any interactions between POPs. WHAT IS KNOWN ALREADY: Animal studies have shown that several POPs can alter folliculogenesis and increase follicle depletion. However, only a few studies have been conducted in humans, with small sample sizes and inconsistent results. STUDY DESIGN, SIZE, DURATION: Our study included 138 cases and 151 controls from the AROPE case-control study. Study participants were women between 18 and 40 years of age recruited amongst couples consulting for infertility in four fertility centres in western France between 2016 and 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cases of DOR were defined as women with anti-Müllerian hormone (AMH) levels ≤1.1 ng/ml and/or antral follicle count (AFC) <7, and controls were women with AMH levels between 1.1 and 5 ng/ml and AFC ≥ 7, without genital malformations and with a menstrual cycle length between 26 and 35 days. A total of 43 POPs (including 15 organochlorine pesticides, 17 polychlorinated biphenyls, and 9 polybromodiphenylethers) were measured in the serum at inclusion into the study. We conducted logistic regression adjusted for potential confounders using a directed acyclic graph to study the effect of each POP on DOR as single exposures, and used Bayesian kernel machine regression (BKMR) to measure the mixture effect of POPs on DOR. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 43 POPs, 17 were detected in over 20% of the serum samples. In the single-exposure multivariate logistic regressions, p,p'-DDE (median 165.0 IQR 161.0 ng/l in controls) as a continuous exposure was significantly associated with an increased risk of DOR (odds ratio (OR) 1.39, 95% CI 1.10-1.77) and non-significantly associated with an increased risk of DOR for the second and third terciles (OR 1.46, 95% CI 0.74-2.87, and OR 1.72, 95% CI 0.88-3.37, respectively). ß-HCH (median 24.2 IQR 21.5 ng/l in controls) was significantly associated with a decreased risk of DOR when ß-HCH was treated as a continuous exposure (OR 0.63, 95% CI 0.44-0.89) and for the third tercile of exposure (OR 0.43, 95% CI 0.21-0.84) and non-significantly associated with a decreased risk of DOR for the second tercile (OR 0.77, 95% CI 0.42-1.42). All sensitivity analyses confirmed our results. BKMR showed similar associations for single exposures but found no significant associations for the total mixture effect. In addition, the BKMR results did not suggest any interactions between POPs. LIMITATIONS, REASONS FOR CAUTION: Controls were recruited amongst infertile couples and thus may not be representative of all women of reproductive age. However, their POP concentrations were in the same range as in the general French population. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first to examine the associations between serum POPs and DOR. The well-recognized anti-androgenic properties of p,p'-DDE and estrogenic properties of ß-HCH could explain these associations of opposite direction. If these results are replicated elsewhere, this could have an impact on fertility prevention messages and help in understanding the impact of POPs on the female reproductive system. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Fondation de France (grant numbers 2014-50537 and 00110196) and the French Biomedicine Agency (2016). None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Accelerating Solutions for the Overdose Crisis: an Effectiveness-Implementation Hybrid Protocol for the HEAL Prevention Cooperative.

Given increasing opioid overdose mortality rates in the USA over the past 20 years, accelerating the implementation of prevention interventions found to be effective is critical. The Helping End Addiction Long-Term (HEAL) Prevention Cooperative (HPC) is a consortium of research projects funded to implement and test interventions designed to prevent the onset or escalation of opioid misuse among youth and young adults. The HPC offers a unique opportunity to synthesize and share lessons learned from participating research projects' varied implementation experiences, which can facilitate quicker integration of effective prevention interventions into practice. This protocol paper describes our hybrid approach to collecting and analyzing information about the implementation experiences of nine of the HPC research projects while they maintain their focus on assessing the effectiveness and cost-effectiveness of prevention interventions. To better understand implementation within this context, we will address five research questions: (1) What were the context and approach for implementing the prevention interventions, and how was the overall implementation experience? (2) How representative of the target population are the participants who were enrolled and retained in the research projects' effectiveness trials? (3) For what purposes and how were stakeholders engaged by the research projects? (4) What are the adaptable components of the prevention interventions? And finally, (5) how might implementation of the prevention interventions vary for non-trial implementation? This work will result in intervention-specific and general practical dissemination resources that can help potential adopters and deliverers of opioid misuse prevention make adoption decisions and prepare for successful implementation.

Digital restoration of colour cinematic films using imaging spectroscopy and machine learning.

Digital restoration is a rapidly growing methodology within the field of heritage conservation, especially for early cinematic films which have intrinsically unstable dye colourants that suffer from irreversible colour fading. Although numerous techniques to restore film digitally have emerged recently, complex degradation remains a challenging problem. This paper proposes a novel vector quantization (VQ) algorithm for restoring movie frames based on the acquisition of spectroscopic data with a custom-made push-broom VNIR hyperspectral camera (380-780 nm). The VQ algorithm utilizes what we call a multi-codebook that correlates degraded areas with corresponding non-degraded ones selected from reference frames. The spectral-codebook was compared with a professional commercially available film restoration software (DaVinci Resolve 17) tested both on RGB and on hyperspectral providing better results in terms of colour reconstruction.

Kelp detritus: Unutilized productivity or an unacknowledged trophic resource?

Kelp beds are one of the most productive marine systems and, while little of this production is directly consumed, there is growing evidence that kelp detritus is an essential food source for many detrital and suspension feeders, and forms an important component of offshore sedimentary carbon pools. However, the extent of the contribution of kelp detritus to the nutrition of coastal fauna is not well resolved. In this study, we compare the contribution of phytoplankton, kelp detritus, and waste from fish cages to the diet of a sentinel suspension feeder, the blue mussel (Mytilus edulis) using stable isotopes. We found a significant depletion in both 13C and 15N in kelp tissue with age (distance from stipe to the deteriorating distal end of the kelp frond) which may have biased dietary estimates in previous studies which have applied isotopic source values derived from fresh kelp. Our mixing models indicate that macroalgal detritus formed 59% of the diet of the mussels in Berehaven, Bantry Bay, Ireland. We support the isotopic mixing model results by modelling the relative production of phytoplankton, kelp, and salmon farm waste, and found the supply of C and N from kelp and phytoplankton far exceeded the requirements of the mussels with much less coming from the nearby fish cages. Monthly chlorophyll measurements indicated there was only sufficient phytoplankton density to support mussel growth during the spring and autumn, explaining our observation of patterns in the relative importance of utilization of kelp detritus. Where there is pressure to harvest kelp beds, this study highlights the supporting ecosystem service they provide as an important dietary source in coastal food webs and emphasises the need for appropriate management measures for this resource.

Faunal mediated carbon export from mangroves in an arid area.

The outwelling paradigm argues that mangrove and saltmarsh wetlands export much excess production to downstream marine systems. However, outwelling is difficult to quantify and currently 40-50% of fixed carbon is unaccounted for. Some carbon is thought outwelled through mobile fauna, including fish, which visit and feed on mangrove produce during tidal inundation or early life stages before moving offshore, yet this pathway for carbon outwelling has never been quantified. We studied faunal carbon outwelling in three arid mangroves, where sharp isotopic gradients across the boundary between mangroves and down-stream systems permitted spatial differentiation of source of carbon in animal tissue. Stable isotope analysis (C, N, S) revealed 22-56% of the tissue of tidally migrating fauna was mangrove derived. Estimated consumption rates showed that 1.4% (38 kg C ha-1 yr-1) of annual mangrove litter production was directly consumed by migratory fauna, with <1% potentially exported. We predict that the amount of faunally-outwelled carbon is likely to be highly correlated with biomass of migratory fauna. While this may vary globally, the measured migratory fauna biomass in these arid mangroves was within the range of observations for mangroves across diverse biogeographic ranges and environmental settings. Hence, this study provides a generalized prediction of the relatively weak contribution of faunal migration to carbon outwelling from mangroves and the current proposition, that the unaccounted-for 40-50% of mangrove C is exported as dissolved inorganic carbon, remains plausible.

A humeral intracondylar repair system for the management of humeral intracondylar fissure and humeral condylar fracture.

OBJECTIVES: To report complications, clinical outcomes and CT-imaging outcomes of a surgical system designed for the management of humeral intracondylar fissures and humeral condylar fractures. MATERIALS AND METHODS: Retrospective review of fracture healing from medical records, direct owner contact and an online data-submission service. Follow-up included CT scans and a calculated "bone-opacity continuity index" to quantify bone healing. RESULTS: There was one major surgical complication and one major medical complication out of 34 fissure cases, and two major surgical and one major medical complication out of 14 fractures. Follow-up times ranged from 29 to 1268 days. All cases with CT follow-up had some continuity of bone opacity across the condyle. CLINICAL SIGNIFICANCE: In the cases included in this study, this repair system was associated with low complication rates and favourable healing rates, particularly for humeral intracondylar fissure.

How close is the axillary nerve to the inferior glenoid? A magnetic resonance study of normal and arthritic shoulders.

INTRODUCTION: Axillary nerve injury is a major complication of shoulder surgery during glenoid exposure. The aim of this study was to measure the mean distance between the inferior glenoid and the axillary nerve in healthy shoulders and then to compare this distance between osteoarthritic and rotator cuff deficient glenohumeral joints. METHODS: The magnetic resonance images of 50 patients with normal glenohumeral joints were reviewed. The infra-glenoid tubercle was determined as a fixed point and the distance to the axillary nerve was measured. Two separate assessors measured on the same sagittal sections. With a study power of 80%, the sample needed in each comparison group was 28 patients. Measurements were then performed on scans in patients with osteoarthritis and cuff tear arthropathy. The mean distance was compared between groups. RESULTS: The mean distance between the infra-glenoid tubercle and axillary nerve was 12mm (standard deviation, SD, 5.6mm) in normal shoulders, 10.6mm (SD 5.4mm) in shoulders with osteoarthritis and 9.7mm (SD 3.7mm) in those with cuff tear arthropathy. For this sample size of 50 patients with a confidence interval of 95%, the mean range is 12mm (95% CI 10.4-13.6). A comparison between normal shoulder and osteoarthritis showed a p-value of 0.3, and between normal and cuff tear arthropathy a p-value of 0.06. This was not statistically significant. CONCLUSIONS: The axillary nerve lies on average 12mm from the infra-glenoid tubercle. The presence of inferior osteophytes in glenohumeral osteoarthritis and the proximal migration of humeral head in cuff tear arthropathy does not seem to alter the course of the nerve significantly in relation to the inferior glenoid tubercle.

Maternal high-fat diet during lactation reprograms the dopaminergic circuitry in mice.

The maternal perinatal environment modulates brain formation, and altered maternal nutrition has been linked to the development of metabolic and psychiatric disorders in the offspring. Here, we showed that maternal high-fat diet (HFD) feeding during lactation in mice elicits long-lasting changes in gene expression in the offspring's dopaminergic circuitry. This translated into silencing of dopaminergic midbrain neurons, reduced connectivity to their downstream targets, and reduced stimulus-evoked dopamine (DA) release in the striatum. Despite the attenuated activity of DA midbrain neurons, offspring from mothers exposed to HFD feeding exhibited a sexually dimorphic expression of DA-related phenotypes, i.e., hyperlocomotion in males and increased intake of palatable food and sucrose in females. These phenotypes arose from concomitantly increased spontaneous activity of D1 medium spiny neurons (MSNs) and profoundly decreased D2 MSN projections. Overall, we have unraveled a fundamental restructuring of dopaminergic circuitries upon time-restricted altered maternal nutrition to induce persistent behavioral changes in the offspring.

Considerations for development of an evidence dossier to support the use of mobile sensor technology for clinical outcome assessments in clinical trials.

BACKGROUND: Mobile sensors offer enormous potential for the collection of informative clinical endpoints in clinical trials to support regulatory decision making and product labelling. There are currently no specific guidelines on the information needed to enable regulators to review and accept proposed endpoints derived from mobile sensors for use in drug development trials. OBJECTIVE: The purpose of this working group report is to recommend the structure and content of an evidence dossier intended to support whether a clinical endpoint derived from mobile sensor data is fit-for-purpose for use in regulatory submissions for drug approvals. EVIDENCE DOSSIER: The structure and content of a dossier to provide evidence supporting the use of a sensor-derived clinical endpoint is described. Sections include clinical endpoint definition and positioning, the concept of interest, the context of use, clinical validation and interpretation, study implementation, and analytical validity with sensor performance verification in support of the selected sensor. CONCLUSIONS: In the absence of definitive regulatory guidance, this report provides a considered approach to compiling a comprehensive body of evidence to justify acceptance of mobile sensors for support of new drug applications.

Decision-making by the NICE Interventional Procedures Advisory Committee.

BACKGROUND: This study explored the evidence base for recommendations by the National Institute of Health and Care Excellence (NICE) Interventional Procedures Advisory Committee, the only NICE committee not to consider cost. The four potential recommendations are: Standard Arrangements (can be performed as routine practice in the NHS); Special Arrangements (can be done under certain conditions); Research Only; and Do Not Do. METHODS: Quantitative content analysis of data extracted from all published Interventional Procedure Guidance (IPG) for 2003-2018 (n = 496) was undertaken. All data were extracted independently by two researchers; disagreements were clarified by consensus. Data were tabulated, descriptive statistics produced, and regression analyses performed. RESULTS: The proportion of IPGs by recommendation was: 50·0 per cent Standard Arrangements; 37·2 per cent Special Arrangements; 11·1 per cent Research Only; and 1·6 per cent Do Not Do. There was a clear trend over time: the proportion of recommendations for Standard Arrangements decreased, whereas the evidence threshold increased. Adjusted mean numbers of patients in the evidence base by recommendation type were: Standard, 4867; Special, 709; Research Only, 386. Regression analyses confirmed that the year of recommendation, numbers of patients and levels of evidence all affected the likely recommendation. CONCLUSION: This study suggests that the likelihood of achieving the most positive recommendation (Standard Arrangements) is decreasing, and that this is most likely due to evidential requirements becoming more demanding. These findings are distinct from those reported for other NICE committees, for which the cost and statistical superiority of new therapies are among the drivers of recommendations.

ANTECEDENTES: Este estudio analiza los niveles de evidencia de las recomendaciones propuestas por el Interventional Procedures Advisory Committee del National Institute of Health and Care Excellence (NICE), el único comité NICE que no tiene en consideración los costes en la guía para los procedimientos de intervención. Las cuatro recomendaciones potenciales son: disposiciones estándar (se pueden efectuar sin restricciones en el marco del NHS); disposiciones especiales (se pueden efectuar bajo ciertas condiciones), en el ámbito de la investigación solo; y no intervenir. MÉTODOS: Se realizó un análisis cuantitativo del contenido de todas las Interventional Procedure Guidance (IPG) publicadas entre 2003-2018 (n = 496). Se obtuvieron todos los datos de forma independiente por dos investigadores y los desacuerdos entre ellos se decidieron por consenso. Se tabularon los datos y se realizaron estadísticas descriptivas y análisis de regresión. RESULTADOS: La proporción de las IPG según el tipo de recomendación eran estándar en el 50% de los casos, especial en el 37%, solo investigación en el 11% y no intervenir en el 2%. Se observó una clara tendencia a lo largo del tiempo: la proporción de recomendaciones del tipo de disposiciones estándar disminuía, mientras que el umbral para la evidencia aumentaba. La media ajustada del número de pacientes para cada tipo de recomendación (estándar, específica y solo investigación) fue de 4.867, 709 y 386, respectivamente. Los análisis de regresión confirmaron que el año de la recomendación, el número de pacientes y los niveles de evidencia afectaban el tipo de recomendación. Estos resultados son diferentes a los relativos a otros comités de NICE, en los que el coste y la superioridad estadística de las nuevas terapias son los motores de las recomendaciones. CONCLUSIÓN: Este estudio sugiere que la probabilidad de lograr la recomendación más positiva (disposición estándar) está disminuyendo, y ello con toda probabilidad es debido a que los requerimientos relacionados con la evidencia son cada vez más exigentes.

A Review of Issues Affecting the Efficiency of Decision Making in the NICE Single Technology Appraisal Process.

BACKGROUND: Escalating demands upon the National Institute for Health and Care Excellence's (NICE's) Single Technology Appraisal (STA) programme require a 2.5-times increase upon 2015 capacity by 2020. This additional strain on committee resources threatens to compromise the rigour of the STA process. In 2018, NICE introduced changes to the appraisal process, aiming to expedite final decisions, including consultation opportunities prior to the company's evidence submission, a 'Technical Engagement' stage prior to the first committee meeting, and powers for committee chairs to recommend technologies without a second formal meeting. OBJECTIVE: This study reviews recent STAs and aims to understand why appraisals require multiple meetings, and whether recent reforms can address the underlying issues. METHODS: NICE STAs published between January 2010 and January 2018 were reviewed, excluding updates or re-considerations. Data on cost, clinical, and decision-making outcomes from 146 appraisals were extracted and analysed thematically. RESULTS: Drugs for advanced cancers were least likely to be recommended (28/43 [65.1%] vs 71/74 [96%] for non-cancer) and took longer (2.36 meetings for a final decision vs 1.97 for non-cancer). The academic review increased upon the company's base-case incremental cost-effectiveness ratio by a median of 32.7%. Eighty-four technologies (57.5%) received a negative preliminary recommendation, deferring a final decision by an average of 142 days. Of these, 85.1% were not considered cost-effective. Uncertainty in economic (34.3%) and clinical (22.3%) data also prevented a positive decision. The majority (72.6% [61/84]) of negative preliminary decisions were overturned following further committee discussion; important considerations were Patient Access Schemes, decision optimisation, and the Cancer Drugs Fund. CONCLUSIONS: Value considerations are the primary driver of negative preliminary recommendations. It is unclear if new opportunities for additional interaction between NICE, review groups, and manufacturers will meaningfully improve the efficiency of the appraisal process, particularly given the proportion of technologies requiring further committee discussion for decision optimisation or admission into the CDF.

Reconstruction of the glenoid using autologous bone-graft and the SMR Axioma TT metal-backed prosthesis: the first 45 sequential cases at a minimum of two years' follow-up.

AIMS: We present our experience of using a metal-backed prosthesis and autologous bone graft to treat gross glenoid bone deficiency. PATIENTS AND METHODS: A prospective cohort study of the first 45 shoulder arthroplasties using the SMR Axioma Trabecular Titanium (TT) metal-backed glenoid with autologous bone graft. Between May 2013 and December 2014, 45 shoulder arthroplasties were carried out in 44 patients with a mean age of 64 years (35 to 89). The indications were 23 complex primary arthroplasties, 12 to revise a hemiarthroplasty or resurfacing, five for aseptic loosening of the glenoid, and five for infection. RESULTS: Of the 45 patients, 16 had anatomical shoulder arthroplasties (ASA) and 29 had reverse shoulder arthroplasties (RSA). Postoperatively, 43/45 patients had a CT scan. In 41 of 43 patients (95%), the glenoid peg achieved > 50% integration. In 40 of 43 cases (93%), the graft was fully or partially integrated. There were seven revisions (16%) but only four (9%) required a change of baseplate. Four (25%) of the 16 ASAs were revised for instability or cuff failure. At two-year radiological follow-up, five of the 41 cases (11%) showed some evidence of lucent lines. CONCLUSION: The use of a metal baseplate with a trabecular titanium surface in conjunction with autologous bone graft is a reliable method of addressing glenoid bone defects in primary and revision RSA setting in the short term. ASAs have a higher rate of complications with this technique.

Subpectoral biceps tenodesis using a novel anterior cortical button technique.

BACKGROUND: Various surgical treatments are described in the literature for biceps pathology. METHOD: The techniques currently described for subpectoral tenodesis involve the use of suture anchors, interference screws, bicortical suture buttons or unicortical suture buttons. RESULTS: A review of 31 patients with a subpectoral biceps tenodesis using the anterior cortical button technique is presented. CONCLUSIONS: We describe a novel technique, which provides an opportunity to obtain a robust cortical and intramedullary tenodesis, performed under direct vision without the risk of drilling the far cortex and therefore avoiding any potential for neurological injury. There is no cortical implant, which may lead to a diaphyseal stress riser and subsequent fracture risk.

Revealing the biography of a hidden medieval manuscript using synchrotron and conventional imaging techniques.

Reading the content of hidden texts from ancient manuscripts has become an increasingly important endeavor thanks to the variety of non-destructive analytical tools and image processing routines available for this task. In this study, portable macro X-Ray Fluorescence (MA-XRF-tube), Visible Hyperspectral Imaging (HSI) together with Synchrotron based macro X-Ray Fluorescence (MA-XRF-SR) are combined with signal processing methods to reveal the biography of a degraded manuscript recycled as binding material for a 16th century printed edition of Hesiod's Works and Days. The analytical techniques allow visualizing the hidden text, revealing passages from the Institutes Justinian, a 6th century A.D codification of the Roman Law, with further marginal comments on medieval Canon Law. In addition, the identification of the materials (e.g. pigments, inks) part of the original manuscript together with their sequence of use are revealed: i) the preparation of the parchment using a Ca-based preparation layer, ii) drawing of ruled guide lines, using a Pb-based pen or ink, iii) writing of the main text using a rich Fe-gall ink with modulating color pigments (Hg-, Cu- and Pb- based) and iv) addition of two types of comments to the main text, one of the ink used for the comments being a Fe-gall ink rich in Cu.

Intergenerational impact of maternal overnutrition and obesity throughout pregnancy in sheep on metabolic syndrome in grandsons and granddaughters.

We previously reported that maternal overnutrition and obesity (MO) throughout pregnancy and lactation in sheep (MOF0) decreases term fetal pancreatic ß-cell numbers and increases perirenal adiposity producing hyperphagia, increased adiposity and insulin resistance in adult female offspring (MOF1) fed ad libitum. Pregnant female MOF1 exhibited increased blood glucose from mid to late gestation vs control F1 (CTRF1) though both groups ate only to NRC recommendations. MOF1 ewes delivered female offspring (F2) who like their MOF1 mothers exhibited increased abdominal adiposity and absent neonatal leptin surge. In the current work, we determined if adult MOF2 exhibited metabolic syndrome components when fed ad libitum. After weaning, MOF2 males (n = 5), MOF2 females (n = 6), CTRF2 males (n = 5), and CTRF2 females (n = 6) were fed to NRC requirements until 19 mo followed by 12-wk ad libitum feeding. Body weight and % fat increased (P < 0.01) in all F2 during this feeding trial. MOF2 males were heavier (P < 0.01) than CTRF2 males and females, and MOF2 females throughout the trial. By wk 8, baseline blood glucose concentrations increased (P < 0.001) in MOF2 females, but not other groups, remaining elevated throughout the trial. Baseline insulin was similar through wk 6, increasing (P < 0.05) at wk 8 in MOF2 females only. MOF2 female insulin returned to CTRF2 female levels during wk 10 and 12. The progressive increase of plasma glucose on wk 8 in association with increased insulin in MOF2 females but not other groups demonstrated a diet-induced increase (P < 0.001) in MOF2 female insulin resistance. The subsequent decline in insulin during wk 10 and 12 despite elevated glucose in MOF2 females is consistent with a decrease in glucose-stimulated pancreatic ß-cell function. These data indicate that ad libitum feeding exceeds the pancreatic secretory response predisposing MOF2 females to hyperglycemia. Furthermore, there was a sex difference where MOF2 males increased body mass and MOF2 females displayed insulin/glucose dysregulation.

The development of confocal arthroscopy as optical histology for rotator cuff tendinopathy.

MRI, ultrasound and video arthroscopy are traditional imaging technologies for noninvasive or minimal invasive assessment of the rotator cuff tendon pathology. However, these imaging modalities do not have sufficient resolution to demonstrate the pathology of rotator cuff tendons at a microstructural level. Therefore, they are insensitive to low-level tendon diseases. Although traditional histology can be used to analyze the physiology of rotator cuff tendons, it requires biopsy that traumatizes the rotator cuff, thus, potentially comprising the mechanical properties of tendons. Besides, it cannot offer real-time histological information. Confocal endoscopy offers a way to assess the microstructural disorder in tissues without biopsy. However, the application of this useful technique for detecting low-level tendon diseases has been restricted by using clinical grade fluorescent contrast agent to acquire high-resolution microstructural images of tendons. In this study, using a clinical grade sodium fluorescein contrast agent, we have reported the development of confocal arthroscopy for optical histological assessment without biopsy. The confocal arthroscopic technique was able to demonstrate rotator cuff tendinopathy in human cadavers, which appeared macroscopically normal under video arthroscopic examinations. The tendinopathy status of the rotator cuff tendons was confirmed by corresponding traditional histology. The development of confocal arthroscopy may provide a minimally invasive imaging technique for real-time histology of rotator cuff without the need for tissue biopsy. This technique has the potential for surgeons to gain in real time the histological information of rotator cuff tendons, which may assist planning repair strategies and potentially improve intervention outcomes.

Mechanical performance in axial compression of a titanium polyaxial locking plate system in a fracture gap model.

OBJECTIVE: To evaluate the bending strength of the VetLOX® polyaxial locking plate system. MATERIALS AND METHODS: Thirty-five 3.5 mm 12-hole titanium VetLOX® plates were used to stabilize seven different construct designs in a 1 cm fracture gap simulation model. Each construct was subjected to axial compression. Mean bending stiffness (BS) and yield load (YL) of each construct design were analysed using a one-way ANOVA and Tukey post-hoc analysis. Screw angulation was measured on reconstructed computed tomography (CT) images. RESULTS: Reducing plate working length for fixed-angle constructs significantly increased BS (p <0.01) and YL (p <0.01). For a constant plate working length, increasing screw number did not significantly affect BS (p = 1.0) or YL (p = 0.86). Screw angulation measurement technique was validated by intra-class correlation coefficients (ICC) (ICC >0.9 for inter- and intra-observer measurements). An average screw angle of 13.2° did not significantly affect mechanical performance although incomplete screw head-plate engagement was noted on some reconstructed CT images when angulation exceeded 10°. Prefabricated screw-head inserts did not significantly increase mechanical performance. A 4 mm bone-plate stand-off distance significantly reduced BS and YL by 63% and 69% respectively. CLINICAL RELEVANCE: The VetLOX® system allows the benefits of polyaxial screw insertion whilst maintaining comparable bending properties to fixed angle insertion. The authors recommend accurate plate contouring to reduce the risk of plate bending.