Category:
Hindfoot; Midfoot/Forefoot
Introduction/ Purpose:
Peritalar subluxation (PTS) is a crucial feature of Progressive Collapsing Foot Deformity (PCFD). Surrounding structures assume distinct ...behaviors, contributing to different disease deformities (classes). One of its most traditional aspects is the midfoot abduction (class B), usually noted by a lateral deviation of distal structures at the talonavicular joint. This finding commonly leads surgeons to perform a lateral column lengthening osteotomy for abduction correction, a complex surgery with potential complications. The first ray's ability to reestablish the tripod and restore the hindfoot by derotating structures under the talus was previously theorized. This study aimed to test the capability of the Lapidus and the Cotton procedures in conjunction with a calcaneus displacement osteotomy (MDCO) to improve midfoot abduction in the setting of a collapsed foot.
Methods:
In this IRB-approved, prospective cohort study, we analyzed patients undergoing medial column instability surgery and evaluated preoperatively with a weight-bearing CT (WBCT). We included individuals receiving a Lapidus bone block procedure or a Cotton for PCFD or Hallux Valgus (HV). Patients having a lateral column lengthening procedure of any type were excluded.
Talonavicular coverage angle (TNCA) was measured as a marker of midfoot abduction. Medial arch collapse and forefoot varus were evaluated by the sagittal talus-first metatarsal angle (TFMA), and the forefoot arch angle (FFA) was measured. Associated procedures and the correction amount (displacement or wedge size) were recorded. Normality was estimated by the Shapiro- Wilk test and comparison among timelines by the one-way ANOVA. A multivariate regression analysis was executed to evaluate which of the measurements influenced abduction improvement. Statistical significance was considered for p-values of less than 0.05.
Results:
A total of 20 patients (age: 43.85 19-72, BMI 30.98 SD: 5.95) were included, 11 PCFD (55%) and 9 HV (45%) with a mean follow-up of 7.5 months (3-12). Bone block Lapidus was performed in most subjects (90%), and the median wedge used was 9mm (5-12mm). MDCO occurred in 55% of patients. All measured variables had improvement with surgery (TNCA: 23.74 to 10.66, p< 0.0001; FFA: 6.27 to 12.67, p< 0.0001; TFMA: 11.73 to 4.22, p=0.0003). A correlation was found between TNCA improvement and FFA improvement (rs=0.46, p=0.0407), but not among TNCA improvement and TFMA improvement (rs=0.43, p=0.06). The size of the wedge did not strongly influence the TNCA correction (R2=0.016, p=0.0036), an improvement moderately explained by the MDCO amount (R2=0.186, p< 0.0001).
Conclusion:
This study demonstrated correction of midfoot abduction, translated by the TNCA, in the absence of lateral column lengthening procedures. When evaluating patients submitted to first ray procedures (bone block Lapidus and Cotton) in conjunction with MDCO, an enhancement on the talar head coverage was noted. Variables associated with arch height and forefoot varus (FFA and TFMA) were correlated with the TNCA improvement. Nevertheless, only the MDCO displacement amount and not the size of the used allograft wedge could explain changes in TNCA. The provided data might support surgeons when planning treatment in the PCFD scenario.
Liver fluke infection causes serious disease (fasciolosis) in cattle and sheep in many regions of the world, resulting in production losses and additional economic consequences due to condemnation of ...the liver at slaughter. Liver fluke depends on mud snails as an intermediate host and infect livestock when ingested through grazing. Therefore, environmental factors play important roles in infection risk and climate change is likely to modify this. Here, we demonstrate how slaughterhouse data can be integrated with other data, including animal movement and climate variables to identify environmental risk factors for liver fluke in cattle in Scotland. We fitted a generalized linear mixed model to the data, with exposure-weighted random and fixed effects, an approach which takes into account the amount of time cattle spent at different locations, exposed to different levels of risk. This enabled us to identify an increased risk of liver fluke with increased animal age, rainfall, and temperature and for farms located further to the West, in excess of the risk associated with a warmer, wetter climate. This model explained 45% of the variability in liver fluke between farms, suggesting that the unexplained 55% was due to factors not included in the model, such as differences in on-farm management and presence of wet habitats. This approach demonstrates the value of statistically integrating routinely recorded slaughterhouse data with other pre-existing data, creating a powerful approach to quantify disease risks in production animals. Furthermore, this approach can be used to better quantify the impact of projected climate change on liver fluke risk for future studies.
1 Department of Medicine, Washington University
School of Medicine, St. Louis 63110; and 2 Departments
of Physiology and Internal Medicine and Diabetes and Cardiovascular
Biology Program, School of ...Medicine, University of Missouri, Columbia,
Missouri 65212
There
is evidence suggesting that adaptive increases in GLUT4 and
mitochondria in skeletal muscle occur in parallel. It has been reported
that raising cytosolic Ca 2+ in myocytes induces increases
in mitochondrial enzymes. In this study, we tested the hypothesis that
an increase in cytosolic Ca 2+ induces an increase in GLUT4.
We found that raising cytosolic Ca 2+ by exposing L6
myotubes to 5 mM caffeine for 3 h/day for 5 days induced increases in
GLUT4 protein and in myocyte enhancer factor (MEF)2A and MEF2D, which
are transcription factors involved in regulating GLUT4 expression. The
caffeine-induced increases in GLUT4 and MEF2A and MEF2D were partially
blocked by dantrolene, an inhibitor of sarcoplasmic reticulum
Ca 2+ release, and completely blocked by KN93, an inhibitor
of Ca 2+ -calmodulin-dependent protein kinase (CAMK).
Caffeine also induced increases in MEF2A, MEF2D, and GLUT4 in rat
epitrochlearis muscles incubated with caffeine in culture medium.
5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR), which activates
AMP-activated protein kinase (AMPK), also induced approximately
twofold increases in GLUT4, MEF2A, and MEF2D in L6 myocytes. Our
results provide evidence that increases in cytosolic Ca 2+
and activation of AMPK, both of which occur in exercising muscle, increase GLUT4 protein in myocytes and skeletal muscle. The data suggest that this effect of Ca 2+ is mediated by activation
of CAMK and indicate that MEF2A and MEF2D are involved in this adaptive response.
5'-adenosine monophosphate-activated protein kinase; gene
expression; skeletal muscle; tissue culture; myocyte enhancer factor 2; Ca 2+ -calmodulin-dependent protein kinase
The optimization of multistep chemical syntheses is critical for the rapid development of new pharmaceuticals. However, concatenating individually optimized reactions can lead to inefficient ...multistep syntheses, owing to chemical interdependencies between the steps. Herein, we develop an automated continuous flow platform for the simultaneous optimization of telescoped reactions. Our approach is applied to a Heck cyclization‐deprotection reaction sequence, used in the synthesis of a precursor for 1‐methyltetrahydroisoquinoline C5 functionalization. A simple method for multipoint sampling with a single online HPLC instrument was designed, enabling accurate quantification of each reaction, and an in‐depth understanding of the reaction pathways. Notably, integration of Bayesian optimization techniques identified an 81 % overall yield in just 14 h, and revealed a favorable competing pathway for formation of the desired product.
An autonomous continuous flow platform for the rapid development of multistep synthetic pathways is reported. New multipoint sampling and Bayesian optimization techniques were combined, enabling simultaneous identification of optimum reaction conditions within a pharmaceutical process. The short optimization times achieved are promising for development of telescoped reactions in the future.
There is evidence suggesting that adaptive increases in GLUT4 and mitochondria in skeletal muscle occur in parallel. It has been reported that raising cytosolic Ca(2+) in myocytes induces increases ...in mitochondrial enzymes. In this study, we tested the hypothesis that an increase in cytosolic Ca(2+) induces an increase in GLUT4. We found that raising cytosolic Ca(2+) by exposing L6 myotubes to 5 mM caffeine for 3 h/day for 5 days induced increases in GLUT4 protein and in myocyte enhancer factor (MEF)2A and MEF2D, which are transcription factors involved in regulating GLUT4 expression. The caffeine-induced increases in GLUT4 and MEF2A and MEF2D were partially blocked by dantrolene, an inhibitor of sarcoplasmic reticulum Ca(2+) release, and completely blocked by KN93, an inhibitor of Ca(2+)-calmodulin-dependent protein kinase (CAMK). Caffeine also induced increases in MEF2A, MEF2D, and GLUT4 in rat epitrochlearis muscles incubated with caffeine in culture medium. 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR), which activates AMP-activated protein kinase (AMPK), also induced approximately twofold increases in GLUT4, MEF2A, and MEF2D in L6 myocytes. Our results provide evidence that increases in cytosolic Ca(2+) and activation of AMPK, both of which occur in exercising muscle, increase GLUT4 protein in myocytes and skeletal muscle. The data suggest that this effect of Ca(2+) is mediated by activation of CAMK and indicate that MEF2A and MEF2D are involved in this adaptive response.
In this paper, we focus on the impact on soil organic carbon (SOC) of two dedicated energy crops: perennial grass Miscanthus x Giganteus (Miscanthus) and short rotation coppice (SRC)‐willow. The ...amount of SOC sequestered in the soil is a function of site‐specific factors including soil texture, management practices, initial SOC levels and climate; for these reasons, both losses and gains in SOC were observed in previous Miscanthus and SRC‐willow studies. The ECOSSE model was developed to simulate soil C dynamics and greenhouse gas emissions in mineral and organic soils. The performance of ECOSSE has already been tested at site level to simulate the impacts of land‐use change to short rotation forestry (SRF) on SOC. However, it has not been extensively evaluated under other bioenergy plantations, such as Miscanthus and SRC‐willow. Twenty‐nine locations in the United Kingdom, comprising 19 paired transitions to SRC‐willow and 20 paired transitions to Miscanthus, were selected to evaluate the performance of ECOSSE in predicting SOC and SOC change from conventional systems (arable and grassland) to these selected bioenergy crops. The results of the present work revealed a strong correlation between modelled and measured SOC and SOC change after transition to Miscanthus and SRC‐willow plantations, at two soil depths (0–30 and 0–100 cm), as well as the absence of significant bias in the model. Moreover, model error was within (i.e. not significantly larger than) the measurement error. The high degrees of association and coincidence with measured SOC under Miscanthus and SRC‐willow plantations in the United Kingdom, provide confidence in using this process‐based model for quantitatively predicting the impacts of future land use on SOC, at site level as well as at national level.
Fetal alcohol spectrum disorder (FASD), a life-long condition resulting from prenatal alcohol exposure (PAE), is associated with structural brain anomalies and neurobehavioral differences. Evidence ...from longitudinal neuroimaging suggest trajectories of white matter microstructure maturation are atypical in PAE. We aimed to further characterize longitudinal trajectories of developmental white matter microstructure change in children and adolescents with PAE compared to typically-developing Controls using diffusion-weighted Neurite Orientation Dispersion and Density Imaging (NODDI).
Participants: Youth with PAE (
= 34) and typically-developing Controls (
= 31) ages 8-17 years at enrollment. Participants underwent formal evaluation of growth and facial dysmorphology. Participants also completed two study visits (17 months apart on average), both of which involved cognitive testing and an MRI scan (data collected on a Siemens Prisma 3 T scanner). Age-related changes in the orientation dispersion index (ODI) and the neurite density index (NDI) were examined across five corpus callosum (CC) regions defined by tractography.
While linear trajectories suggested similar overall microstructural integrity in PAE and Controls, analyses of symmetrized percent change (SPC) indicated group differences in the timing and magnitude of age-related increases in ODI (indexing the bending and fanning of axons) in the central region of the CC, with PAE participants demonstrating atypically steep increases in dispersion with age compared to Controls. Participants with PAE also demonstrated greater increases in ODI in the mid posterior CC (trend-level group difference). In addition, SPC in ODI and NDI was differentially correlated with executive function performance for PAE participants and Controls, suggesting an atypical relationship between white matter microstructure maturation and cognitive function in PAE.
Preliminary findings suggest subtle atypicality in the timing and magnitude of age-related white matter microstructure maturation in PAE compared to typically-developing Controls. These findings add to the existing literature on neurodevelopmental trajectories in PAE and suggest that advanced biophysical diffusion modeling (NODDI) may be sensitive to biologically-meaningful microstructural changes in the CC that are disrupted by PAE. Findings of atypical brain maturation-behavior relationships in PAE highlight the need for further study. Further longitudinal research aimed at characterizing white matter neurodevelopmental trajectories in PAE will be important.
Background
Influenza epidemiology in Africa is generally not well understood. Using syndrome definitions to screen patients for laboratory confirmation of infection is an established means to ...effectively conduct influenza surveillance.
Methods
To compare influenza‐related epidemiologic data, from October 2010 through March 2013, we enrolled hospitalized severe acute respiratory infection (SARI; fever with respiratory symptoms) and acute febrile illness (AFI; fever without respiratory or other localizing symptoms) patients from three referral hospitals in Ghana. Demographic and epidemiologic data were obtained from enrolled patients after which nasopharyngeal and oropharyngeal swabs were collected, and processed by molecular methods for the presence of influenza viruses.
Results
Of 730 SARI patients, 59 (8%) were influenza positive; of 543 AFI patients, 34 (6%) were positive for influenza. Both SARI and AFI surveillance yielded influenza A(H3N2) (3% versus 1%), A(H1N1)pdm09 (2% versus 1%), and influenza B (3% versus 4%) in similar proportions. Data from both syndromes show year‐round influenza transmission but with increased caseloads associated with the rainy seasons.
Conclusions
As an appreciable percentage of influenza cases (37%) presented without defined respiratory symptoms, and thus met the AFI but not the SARI definition, it is important to consider broader screening criteria (i.e., AFI) to identify all laboratory‐confirmed influenza. The identified influenza transmission seasonality has important implications for the timing of related public health interventions.
ABSTRACT
Nuclear respiratory factor 1 (NRF‐1) is a transcriptional activator of nuclear genes that encode a range of mitochondrial proteins including cytochrome c, various other respiratory chain ...subunits, and δ‐aminolevulinate synthase. Activation of NRF‐1 in fibroblasts has been shown to induce increases in cytochrome c expression and mitochondrial respiratory capacity. To further evaluate the role of NRF‐1 in the regulation of mitochondrial biogenesis and respiratory capacity, we generated transgenic mice overexpressing NRF‐1 in skeletal muscle. Cytochrome c expression was increased ∼twofold and δ‐aminolevulinate synthase was increased ∼50% in NRF‐1 transgenic muscle. The levels of some mitochondrial proteins were increased 50–60%, while others were unchanged. Muscle respiratory capacity was not increased in the NRF‐1 transgenic mice. A finding that provides new insight regarding the role of NRF‐1 was that expression of MEF2A and GLUT4 was increased in NRF‐1 transgenic muscle. The increase in GLUT4 was associated with a proportional increase in insulin‐stimulated glucose transport. These results show that an isolated increase in NRF‐1 is not sufficient to bring about a coordinated increase in expression of all of the proteins necessary for assembly of functional mitochondria. They also provide the new information that NRF‐1 overexpression results in increased expression of GLUT4.—Baar, K., Song, Z., Semenkovich, C. F., Jones, T. E,. Han, D.‐H., Nolte, L. A., Ojuka, E. O., Chen, M., Holloszy, J. O. Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity. FASEB J. 17, 1666–1673 (2003)
Lambs routinely undergo painful husbandry procedures including ear tagging, tail docking and castration. Pain early in life is important because it can compromise lamb welfare. Studies of altricial ...species, such as rodents and humans, suggest that baseline pain sensitivity varies with age and sex. While age effects on behavioural or physiological responses to pain induced by injury have been assessed in lambs, the effects of age and sex on baseline pain sensitivity have not. The aim of this study was to investigate the effects of age and sex on baseline pain sensitivity in lambs using a remote laser thermal stimulus. Thermal nociceptive thresholds were measured in male and female lambs aged between one and 12
days old. There was no main effect of sex or age on lambs’ latency to respond to the thermal stimulus. However, there was a significant interaction effect of sex and age, with male and female pain sensitivity diverging with increasing age. The latency to respond increased with age in males but did not change significantly with age in females. This suggests that older males were less sensitive to thermal pain than younger males. The ontogeny of pain processing appears to differ between male and female lambs. This may be explained by sex-specific changes in peripheral components of the pain processing system (e.g. population, distribution or sensitivity of receptors) or in central integration of nociceptive signals. Alternatively, there may be sex-specific changes with age in other physiological processes relevant to thermal nociception, e.g. peripheral thermoregulation. Future research should look beyond 12
days of age to see whether sex differences in pain sensitivity persist, thus providing a more complete picture of the ontogeny of pain processing development in precocial species.
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