Plantar pressure analysis of different orthoses in patients after first metatarsophalangeal joint arthrodesis.

BACKGROUND: There is no gold standard for a walking orthosis after first metatarsophalangeal joint (MTPJ) arthrodesis surgery. Evaluation of plantar pressure measures and patient perceptions for different orthoses may assist surgeons to choose a postsurgery orthotic. The purpose of this study was to measure plantar pressure under the distal first ray during walking and patient perceptions of comfort, stability, and preference with 4 different orthoses in patients with a history of first MTPJ arthrodesis. METHODS: Crossover study in a university laboratory. Eleven patients volunteered (8 female, 3 male, age = 59.4 ± 9.1 years, 21.9 ± 17.5 months since surgery) who had a unilateral first MTPJ arthrodesis procedure more than 6 months before study participation. Four orthosis conditions were evaluated in all participants: patient's shoe, carbon fiber insert, OrthoWedge, and Post-Op Shoe. We analyzed peak plantar pressure and pressure-time integral under the whole foot and the distal first ray as well as recorded subjective rating for comfort and stability. Rank ordered for preferred orthosis. RESULTS: OrthoWedge had significantly lower whole-foot and distal first ray peak pressure than the other conditions. The pressure-time integral for the OrthoWedge was significantly less than the Carbon Fiber Insert and Post-Op Shoe. For stability, comfort, and condition preference, the OrthoWedge was ranked lowest among the 4 conditions. CONCLUSIONS: The OrthoWedge generated the lowest peak plantar pressure but was subjectively ranked as the least preferred orthosis. This discrepancy between objective biomechanical and subjective comfort measures must be weighed as surgeons prescribe an orthosis to patients after first MTPJ arthrodesis.

Positive interplay between FFAR4/GPR120, DPP-IV inhibition and GLP-1 in beta cell proliferation and glucose homeostasis in obese high fat fed mice.

G-protein coupled receptor-120 (GPR120; FFAR4) is a free fatty acid receptor, widely researched for its glucoregulatory and insulin release activities. This study aimed to investigate the metabolic advantage of FFAR4/GPR120 activation using combination therapy. C57BL/6 mice, fed a High Fat Diet (HFD) for 120 days to induce obesity-diabetes, were subsequently treated with a single daily oral dose of FFAR4/GPR120 agonist Compound A (CpdA) (0.1µmol/kg) alone or in combination with sitagliptin (50 mg/kg) for 21 days. After 21-days, glucose homeostasis, islet morphology, plasma hormones and lipids, tissue genes (qPCR) and protein expression (immunocytochemistry) were assessed. Oral administration of CpdA improved glucose tolerance (34% p<0.001) and increased circulating insulin (38% p<0.001). Addition of CpdA with the dipeptidyl peptidase-IV (DPP-IV) inhibitor, sitagliptin, further improved insulin release (44%) compared to sitagliptin alone and reduced fat mass (p<0.05). CpdA alone (50%) and in combination with sitagliptin (89%) induced marked reductions in LDL-cholesterol, with greater effects in combination (p<0.05). All treatment regimens restored pancreatic islet and beta-cell area and mass, complemented with significantly elevated beta-cell proliferation rates. A marked increase in circulating GLP-1 (53%) was observed, with further increases in combination (38%). With treatment, mice presented with increased Gcg (proglucagon) gene expression in the jejunum (130% increase) and ileum (120% increase), indicative of GLP-1 synthesis and secretion. These data highlight the therapeutic promise of FFAR4/GPR120 activation and the potential for combined benefit with incretin enhancing DPP-IV inhibitors in the regulation of beta cell proliferation and diabetes.

Pig fetal skeletal muscle development is associated with genome-wide DNA hypomethylation and corresponding alterations in transcript and microRNA expression.

Fetal myogenesis represents a critical period of porcine skeletal muscle development and requires coordinated expression of thousands of genes. Epigenetic mechanisms, including DNA methylation, drive transcriptional regulation during development; however, these processes are understudied in developing porcine tissues. We performed bisulfite sequencing to assess DNA methylation in pig longissimus dorsi muscle at 41- and 70-days gestation (dg), as well as RNA- and small RNA-sequencing to identify coordinated changes in methylation and expression between myogenic stages. We identified 45 739 differentially methylated regions (DMRs) between stages, and the majority (N = 34 232) were hypomethylated at 70 versus 41 dg. Integration of methylation and transcriptomic data revealed strong associations between differential gene methylation and expression. Differential miRNA methylation was significantly negatively correlated with abundance, and dynamic expression of assayed miRNAs persisted postnatally. Motif analysis revealed significant enrichment of myogenic regulatory factor motifs among hypomethylated regions, suggesting that DNA hypomethylation may function to increase accessibility of muscle-specific transcription factors. We show that developmental DMRs are enriched for GWAS SNPs for muscle- and meat-related traits, demonstrating the potential for epigenetic processes to influence phenotypic diversity. Our results enhance understanding of DNA methylation dynamics of porcine myogenesis and reveal putative cis-regulatory elements governed by epigenetic processes.

Immune Activation following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study.

Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual's cancer that may be most effectively targeted. Informed using WGTA, a patient with advanced mismatch repair-deficient colorectal cancer was treated with the antihypertensive drug irbesartan and experienced a profound and durable response. We describe the subsequent relapse of this patient and potential mechanisms of response using WGTA and multiplex immunohistochemistry (m-IHC) profiling of biopsies before and after treatment from the same metastatic site of the L3 spine. We did not observe marked differences in the genomic landscape before and after treatment. Analyses revealed an increase in immune signalling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumour. These results indicate that the observed anti-tumour response to irbesartan may have been due to an activated immune response. Determining whether there may be other cancer contexts in which irbesartan may be similarly valuable will require additional studies.

The Epidemiology of Ankle Sprains in US High School Sports, 2011-2012 to 2018-2019 Academic Years.

CONTEXT: Continued monitoring of ankle sprain rates and distributions is needed to assess temporal patterns and gauge how changes in incidence may be associated with prevention efforts. OBJECTIVE: To describe the epidemiology of ankle sprains in 16 US high school sports during the 2011-2012 to 2018-2019 school years. DESIGN: Descriptive epidemiology study. SETTING: Online injury surveillance from high school sports. PATIENTS OR OTHER PARTICIPANTS: High school athletes who participated in practices and competitions during the 2011-2012 to 2018-2019 school years. MAIN OUTCOME MEASURE(S): A convenience sample of high school athletic trainers provided injury and athlete-exposure (AE) data to the National High School Sports-Related Injury Surveillance Study (data provided by High School Reporting Information Online [HS RIO]). Ankle sprain rates per 10 000 AEs with 95% CIs and distributions were calculated. Yearly rates were examined overall and by event type, injury mechanism, and recurrence. RESULTS: Overall, 9320 ankle sprains were reported (overall rate = 2.95/10 000 AEs; 95% CI = 2.89, 3.01). The highest sport-specific rates were reported in girls' basketball (5.32/10 000 AEs), boys' basketball (5.13/10 000 AEs), girls' soccer (4.96/10 000 AEs), and boys' football (4.55/10 000 AEs). Most ankle sprains occurred during competition (54.3%) and were due to contact with another person (39.5%) or noncontact (35.0%). Also, 14.5% of injuries were recurrent. Across the included academic years, ankle sprain rates generally increased. Compared with the 2011-2012 academic year, rates in the 2018-2019 academic year overall were 22% higher; noncontact-related and recurrent ankle sprain rates also generally increased by 91% and 29%, respectively. CONCLUSIONS: Time trends suggested that ankle sprain rates have increased across the past decade, particularly among those with noncontact-related mechanisms, contrasting with previous research that indicated decreases in incidence. These findings may pinpoint specific etiologic factors that should direct prevention efforts, including considering both person-contact and noncontact mechanisms by mitigating illegal contact through rule changes and enforcement, as well as bracing and proprioceptive and balance-training programs.

Motion Artifacts and Correction in Multipulse High-Frame Rate Contrast-Enhanced Ultrasound.

High-frame-rate (HFR) ultrasound (US) imaging and contrast-enhanced US (CEUS) are often implemented using multipulse transmissions, to enhance image quality. Multipulse approaches, however, suffer from degradation in the presence of motion, especially when coherent compounding and CEUS are combined. In this paper, we investigate this effect on the intensity of HFR CEUS in deep tissue imaging using simulations and in vivo contrast echocardiography (CE). The simulation results show that the motion artifact is much higher when the flow is in an axial direction than a lateral direction. Using a pulse repetition frequency suitable for cardiac imaging, a motion of 35 cm/s can cause as much as 28.5 dB decrease in image intensity, where compounding can contribute up to 18.7 dB of intensity decrease (11 angles). These motion effects are also demonstrated for in vivo cardiac HFR CE, where the large velocities of both the myocardium and the blood are present. Intensity reductions of 10.4 dB are readily visible in the chamber. Finally, we demonstrate how performing motion-correction before pulse inversion compounding greatly reduces such motion artifact and improve image signal-to-noise ratio and contrast.

Expression of inflammatory markers in women with perinatal depressive symptoms.

Perinatal depression affects 10-20% of women and is associated with poor outcomes for mother and child. Inflammation is associated with depression in non-pregnant adults. Perinatal depression and inflammation in pregnancy are independently associated with morbidities including obesity, gestational diabetes, preeclampsia, and preterm birth. The role of inflammation in perinatal depression has received little attention. We hypothesized an association between self-reported perinatal depressive symptoms and serum inflammatory biomarkers TNF-α, IL-6, IL-1ß, and CRP. 110 healthy gravidas were recruited in third trimester from an academic medical center, with a baseline study visit at a mean of 32.5 (SD ± 1.8) weeks gestational age. Sixty-three participants completed the Edinburgh Postnatal Depression Scale (EPDS) and provided demographic information and serum samples upon enrollment and at 3 and 6 months postpartum. Serum inflammatory markers were quantified by multiplex array. Multiple linear mixed effects models were used to evaluate trends of biomarkers with the EPDS score in the third trimester of pregnancy and the postpartum period. Elevated serum TNF-α was associated with lower EPDS total score (ß = - 0.90, p = 0.046) after adjusting for demographics and medication use. In contrast, IL-6, CRP, and IL-1ß did not demonstrate statistically significant associations with depressive symptoms by the EPDS in either crude or adjusted models. Study findings showed no association or an inverse (TNF-α) association between inflammatory markers and perinatal depressive symptoms. Relevant literature evaluating a role for inflammation in depression in the unique context of pregnancy is both limited and inconsistent, and further exploration is merited.

The Effect of Arterial Curvature on Blood Flow in Arterio-Venous Fistulae: Realistic Geometries and Pulsatile Flow.

Arterio-Venous Fistulae (AVF) are regarded as the "gold standard" method of vascular access for patients with End-Stage Renal Disease (ESRD) who require haemodialysis. However, up to 60% of AVF do not mature, and hence fail, as a result of Intimal Hyperplasia (IH). Unphysiological flow and oxygen transport patterns, associated with the unnatural and often complex geometries of AVF, are believed to be implicated in the development of IH. Previous studies have investigated the effect of arterial curvature on blood flow in AVF using idealized planar AVF configurations and non-pulsatile inflow conditions. The present study takes an important step forwards by extending this work to more realistic non-planar brachiocephalic AVF configurations with pulsatile inflow conditions. Results show that forming an AVF by connecting a vein onto the outer curvature of an arterial bend does not, necessarily, suppress unsteady flow in the artery. This finding is converse to results from a previous more idealized study. However, results also show that forming an AVF by connecting a vein onto the inner curvature of an arterial bend can suppress exposure to regions of low wall shear stress and hypoxia in the artery. This finding is in agreement with results from a previous more idealized study. Finally, results show that forming an AVF by connecting a vein onto the inner curvature of an arterial bend can significantly reduce exposure to high WSS in the vein. The results are important, as they demonstrate that in realistic scenarios arterial curvature can be leveraged to reduce exposure to excessively low/high levels of WSS and regions of hypoxia in AVF. This may in turn reduce rates of IH and hence AVF failure.

The effect of in-plane arterial curvature on blood flow and oxygen transport in arterio-venous fistulae.

Arterio-Venous Fistulae (AVF) are the preferred method of vascular access for patients with end stage renal disease who need hemodialysis. In this study, simulations of blood flow and oxygen transport were undertaken in various idealized AVF configurations. The objective of the study was to understand how arterial curvature affects blood flow and oxygen transport patterns within AVF, with a focus on how curvature alters metrics known to correlate with vascular pathology such as Intimal Hyperplasia (IH). If one subscribes to the hypothesis that unsteady flow causes IH within AVF, then the results suggest that in order to avoid IH, AVF should be formed via a vein graft onto the outer-curvature of a curved artery. However, if one subscribes to the hypothesis that low wall shear stress and/or low lumen-to-wall oxygen flux (leading to wall hypoxia) cause IH within AVF, then the results suggest that in order to avoid IH, AVF should be formed via a vein graft onto a straight artery, or the inner-curvature of a curved artery. We note that the recommendations are incompatible-highlighting the importance of ascertaining the exact mechanisms underlying development of IH in AVF. Nonetheless, the results clearly illustrate the important role played by arterial curvature in determining AVF hemodynamics, which to our knowledge has been overlooked in all previous studies.

An hour of bright white light in the early morning improves performance and advances sleep and circadian phase during the Antarctic winter.

Previous work has demonstrated that exposure to an hour of bright light in the morning and the evening during the Polar winter has beneficial effects on circadian phase. This study investigated the effect of a single hour of bright white morning light on circadian phase, sleep, alertness and cognitive performance. Nine individuals (eight male, one female, median age 30 years), wintering at Halley Research Station (75°S), Antarctica from 7th May until 6th August 2007, were exposed to bright white light for a fortnight from 08:30 to 09:30 h, with two fortnight control periods on either side. This sequence was performed twice, before and following Midwinter. Light exposure, sleep and alertness were assessed daily by actigraphy, sleep diaries and subjective visual analogue scales. Circadian phase (assessed by urinary 6-sulphatoxymelatonin rhythm) and cognitive performance were evaluated at the end of each fortnight. During light exposure circadian phase was advanced from 4.97 ± 0.96 decimal hours (dh) (mean ± SD) to 4.08 ± 0.68 dh (p = 0.003). Wake-up time was shifted by a similar margin from 8.45 ± 1.83 dh to 7.59 ± 0.78 dh (p < 0.001). Sleep start time was also advanced (p = 0.047) but by a lesser amount, consequently, actual sleep time was slightly reduced. There was no change in objective or subjective measures of sleep quality or subjective measures of alertness. An improvement in cognitive performance was found with both the Single Letter Cancellation Test (p < 0.001) and the Digit Symbol Substitution Test (p = 0.026) with preserved circadian variation. These beneficial effects of a single short duration light treatment may have implications not only for the Antarctic but other remote environments where access to natural light and delayed circadian phase, is problematic. These results require validation in larger studies at varying locations.

Synthetic approaches to a chiral 4-amino-3-hydroxy piperidine with pharmaceutical relevance.

Four synthetic strategies were evaluated towards the preparation of (-)-(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol (1), which was constructed with control over the relative and absolute stereochemistry of the 4,3-amino alcohol moiety. The first strategy employed a novel Rh(I) catalyzed asymmetric hydrogenation, while two other strategies exploited the existing stereochemistry in 2-deoxy-D-ribose, and the fourth explored both biocatalytic and classical resolution techniques as a means to impart enantioenrichment to racemic intermediates en route to targeted structure (-)-1.

High performance gel imaging with a commercial single lens reflex camera.

A high performance gel imaging system was constructed using a digital single lens reflex camera with epi-illumination to image 19 × 23 cm agarose gels with up to 10,000 DNA bands each. It was found to give equivalent performance to a laser scanner in this high throughput DNA fingerprinting application using the fluorophore SYBR Green(®). The specificity and sensitivity of the imager and scanner were within 1% using the same band identification software. Low and high cost color filters were also compared and it was found that with care, good results could be obtained with inexpensive dyed acrylic filters in combination with more costly dielectric interference filters, but that very poor combinations were also possible. Methods for determining resolution, dynamic range, and optical efficiency for imagers are also proposed to facilitate comparison between systems.

Diagnosis of distal 22q11.2 deletion syndrome in a patient with a teratoid/rhabdoid tumour.

We report an 18 year old patient with mild intellectual disability who was diagnosed with a late onset teratoid/rhabdoid tumour by histological and immunohistochemical studies. Array-CGH studies, performed on a peripheral blood sample, showed a 3.4Mb deletion of chromosome 22q11.2, distal to the common DiGeorge syndrome (DGS) or Velocardiofacial syndrome (VCFs) region. This deletion is consistent with a diagnosis of distal 22q11.2 deletion syndrome. The deletion encompasses the INI1/SMARCB1 tumour suppressor gene. Biallelic inactivation of this gene is characteristic of atypical teratoid/rhabdoid tumours. Although several constitutional chromosome conditions are known to have increased susceptibility to various forms of cancer, very little is known regarding the magnitude of risk for malignancy associated with distal 22q11.2 deletion syndrome. In view of this finding we suggest that patients diagnosed with distal 22q11.2 deletion syndrome undergo careful prolonged monitoring for this type of tumour. This case demonstrates the need to carefully assess regions found to be deleted in individuals, referred for dysmorphia and/or developments delay, by array-CGH for the presence of genes known to be implicated in malignancy.

Survival and replication of Mycoplasma species in recycled bedding sand and association with mastitis on dairy farms in Utah.

Mycoplasma spp., usually Mycoplasma bovis, are important bovine pathogens that can cause mastitis, metritis, pneumonia, and arthritis. The currently documented routes of transmission of Mycoplasma spp. are through contaminated milking equipment and by direct animal contact. The existence of environmental sources for Mycoplasma spp. and their role in transmission and clinical disease is poorly characterized. Mycoplasma spp. (confirmed as M. bovis in 2 of 4 samples tested using PCR) was found in recycled bedding sand originating from a dairy experiencing an outbreak of clinical mycoplasma mastitis. Mycoplasma spp. were subsequently found in bedding sand from 2 other dairies whose bulk-tank milk was mycoplasma-positive. The association between the occurrence of Mycoplasma spp. in recycled bedding sand and mycoplasma mastitis in cows was further investigated using a pile of recycled sand from dairy 1. Study objectives included the determination of factors associated with the concentration of Mycoplasma spp. in recycled bedding sand and the duration of survival of mycoplasmas in the sand. We also evaluated the efficacy of 2 disinfectants at 2 different concentrations each for the elimination of Mycoplasma spp. from contaminated sand. Mycoplasma spp. survived in the sand pile for 8 mo. The concentration of Mycoplasma spp. within the sand pile was directly related to temperature and precipitation. It was also positively associated with the growth of gram-negative microorganisms, suggesting the possibility of the formation of a biofilm. Ideal temperatures for replication of Mycoplasma spp. occurred between 15 and 20 degrees C. Moisture in the sand and movement of the sand pile also appeared to play a role in replication of mycoplasmas. We found that 0.5% sodium hypochlorite or 2% chlorhexidine were efficacious in eliminating Mycoplasma spp. from contaminated bedding sand. Recycled bedding sand could be an environmental source of Mycoplasma spp., including M. bovis, infections in dairy cows. Future studies should investigate the contribution of this environmental source to the epidemiology of mycoplasma infections in dairy cattle.

Ethical issues, justification, referral criteria for budget limited and high-dose procedures.

This paper reviews some of the issues connected with questions of ethics, health economics, radiation dose and referral criteria arising from a workshop held under the auspices of the Sentinel Research Program FP6-012909. An extensive bibliography of further reading is included.

Effects of planting date on fiber digestibility of whole-crop barley and productivity of lactating dairy cows.

Objectives of the study were to evaluate the effect of planting date on in vitro neutral detergent fiber digestibility (IVFD) of whole-crop barley (Hordeum vulgare) and its effects on productivity of lactating dairy cows. Two cultivars of barley were planted on May 5 (BM) and June 7 (BJ), 2005 at the Edmonton Research Station, University of Alberta. They were harvested at late-dough stage on July 26 and August 25, respectively, for BM and BJ and ensiled. The BJ had greater 30-h IVFD (61.2 vs. 51.9%) and crude protein concentration (12.4 vs. 8.7%) at harvest compared with BM. Thirty lactating cows, including 6 ruminally cannulated cows, in mid to late lactation (183 +/- 71.7 d in milk; mean +/- standard deviation) were fed diets containing BM or BJ at 58.5% of dietary DM in a crossover design with 19-d periods. The dietary neutral detergent fiber concentration was 30.6 and 28.8% for BM and BJ diets, respectively. Dry matter intake and milk yield were not affected by treatment and averaged 20.2 and 27.2 kg/ d, respectively. The lack of responses could have been attributed to the low-energy demands for cows used in this experiment; ruminal physical fill might not have limited dry matter intake. However, cows fed BJ had greater total tract dry matter digestibility (68.9 vs. 66.1%) and tended to increase body weight gain (864 vs. 504 g/d) compared with those fed BM. Delaying the planting date of barley altered its growing environment and affected nutrient composition and IVFD of whole-crop barley and energy availability to animals. Further research is needed to confirm if the planting date consistently affects nutrient composition and IVFD of barley at harvest.