Single cell RNA-sequencing and RNA-tomography of the avian embryo extending body axis.

Introduction: Vertebrate body axis formation initiates during gastrulation and continues within the tail bud at the posterior end of the embryo. Major structures in the trunk are paired somites, which generate the musculoskeletal system, the spinal cord-forming part of the central nervous system, and the notochord, with important patterning functions. The specification of these different cell lineages by key signalling pathways and transcription factors is essential, however, a global map of cell types and expressed genes in the avian trunk is missing. Methods: Here we use high-throughput sequencing approaches to generate a molecular map of the emerging trunk and tailbud in the chick embryo. Results and Discussion: Single cell RNA-sequencing (scRNA-seq) identifies discrete cell lineages including somites, neural tube, neural crest, lateral plate mesoderm, ectoderm, endothelial and blood progenitors. In addition, RNA-seq of sequential tissue sections (RNA-tomography) provides a spatially resolved, genome-wide expression dataset for the avian tailbud and emerging body, comparable to other model systems. Combining the single cell and RNA-tomography datasets, we identify spatially restricted genes, focusing on somites and early myoblasts. Thus, this high-resolution transcriptome map incorporating cell types in the embryonic trunk can expose molecular pathways involved in body axis development.

Bio-functional properties and phytochemical composition of selected Apis mellifera honey from Africa.

Globally, the demand for natural remedies such as honey to manage ailments has increased. Yet, the health benefits and chemical composition of African honeys are not well understood. Therefore, this study aimed to characterise the bio-functional properties and the phytochemical composition of 18 Apis mellifera honeys from Kenya, Uganda, and Cameroon in comparison to the popular and commercially available Manuka 5+ honey from New Zealand. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay (DPPH-RSA) was used to determine the antioxidant property, whilst the agar well diffusion and broth dilution (Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)) assays were used to determine antimicrobial property. Further, colorimetric methods were used for phytochemical analysis. Our results showed that honeys collected from Rift Valley region of Kenya (e.g. Poi, Salabani and Mbechot) and Western region of Cameron (e.g. Bangoulap) had the highest antioxidant (DPPH RSA of 41.52-43.81%) and antimicrobial (MIC (3.125-6.25% w/v) and MBC (6.25-12.5% w/v)) activities. Additionally, the total flavonoid (770-970 mg QE/100 g), phenol (944.79-1047.53 mg GAE/100 g), terpenoid (239.78-320.89 mg LE/100 g) and alkaloid (119.40-266.57 mg CE/100 g) contents reached the highest levels in these bioactive African honeys, which significantly and positively correlated with their bio-functional properties. The functional and phytochemical composition of these bioactive African honeys were similar to or higher than those of the Manuka 5+ honey. Furthermore, gas chromatography-mass spectrometry analysis of African honeys revealed 10 most prominent volatile organic compounds that contribute to their geographical distinction: triacontane, heptacosane, (Z)-9-tricosene, tetracosane, 6-propyl-2,3-dihydropyran-2,4-dione, octacosane, 1,2,4-trimethylcyclohexane, 1,3-bis(1,1-dimethylethyl) benzene, 2-methylheptane and phytol. Overall, our findings suggest that some of the tested African honeys are natural sources of antimicrobial and antioxidant therapies that can be exploited upon further research and commercialized as high value honey.

Contamination of depressional wetlands in the Mpumalanga Lake District of South Africa near a global emission hotspot.

The Mpumalanga Lake District (MLD) of South Africa hosts a regionally unique cluster of water bodies of great importance for wetland biodiversity. It is also located close to a global hotspot for coal-fired power station emissions but the local impacts from these sources of pollution are poorly understood. Sediment cores from three contrasting wetlands were 210Pb dated and analysed for a range of contaminants linked to fossil fuel combustion, including trace elements, Hg, sulphur and spheroidal carbonaceous fly-ash particles (SCPs). At the two sites with pre-industrial (1900) baseline sediments, Pb, Zn and especially Cr concentrations and fluxes showed significant increases in the impact period (post-1975). Mercury showed the greatest proportional increase in flux (>4-fold) of all trace metals. Mercury and sulphur concentrations and fluxes showed highly significant correlations with emissions over the corresponding periods, while SCPs in sediments also closely tracked emissions. In a global context, levels of sediment contamination are relatively minor compared with other heavily industrialised regions, with only Cr exceeding the sediment Probable Effects Concentration for biological impact post-1975. Despite the relatively large increases in Hg, concentrations do not reach the Threshold Effects Concentration. The unexpectedly low levels of contamination may be due to i) low levels of many trace contaminants in South African coals compared to global averages, ii) prevailing recirculation patterns which transport pollution away from the study area during the wet season, minimising wet deposition, and iii) pollutant remobilisation through desiccation of wetlands or volatilization. The effects of hydrology and sediment accumulation rates lead to differential transport and preservation of organic-associated and more volatile contaminants (e.g. Hg, S) relative to non-volatile trace elements in wetlands of the MLD. The greatest fluxes of Hg and S are recorded in the site with the highest catchment: lake area ratio, lowest salinity and greatest sediment organic matter content.

Levels of autonomy in FDA-cleared surgical robots: a systematic review.

The integration of robotics in surgery has increased over the past decade, and advances in the autonomous capabilities of surgical robots have paralleled that of assistive and industrial robots. However, classification and regulatory frameworks have not kept pace with the increasing autonomy of surgical robots. There is a need to modernize our classification to understand technological trends and prepare to regulate and streamline surgical practice around these robotic systems. We present a systematic review of all surgical robots cleared by the United States Food and Drug Administration (FDA) from 2015 to 2023, utilizing a classification system that we call Levels of Autonomy in Surgical Robotics (LASR) to categorize each robot's decision-making and action-taking abilities from Level 1 (Robot Assistance) to Level 5 (Full Autonomy). We searched the 510(k), De Novo, and AccessGUDID databases in December 2023 and included all medical devices fitting our definition of a surgical robot. 37,981 records were screened to identify 49 surgical robots. Most surgical robots were at Level 1 (86%) and some reached Level 3 (Conditional Autonomy) (6%). 2 surgical robots were recognized by the FDA to have machine learning-enabled capabilities, while more were reported to have these capabilities in their marketing materials. Most surgical robots were introduced via the 510(k) pathway, but a growing number via the De Novo pathway. This review highlights trends toward greater autonomy in surgical robotics. Implementing regulatory frameworks that acknowledge varying levels of autonomy in surgical robots may help ensure their safe and effective integration into surgical practice.

Identifying Predictors of Initial Surgical Failure during Minimally Invasive Endoscopic Intracerebral Hemorrhage Evacuation.

Background and Purpose: Intracerebral hemorrhage (ICH) is a common and severe disease with high rates of morbidity and mortality; however, minimally invasive surgical (MIS) hematoma evacuation represents a promising avenue for treatment. In February of 2019, the MISTIE III study found that stereotactic thrombolysis with catheter drainage did not benefit patients with supratentorial spontaneous ICH but that a clinical benefit may be present when no more than 15 mL of hematoma remains at the end of treatment. Intraoperative CT (iCT) imaging has the ability to assess whether or not this surgical goal has been met in real time, allowing for operations to add additional CT-informed 'evacuation periods' (EPs) to achieve the surgical goal. Here, we report on the frequency and predictors of initial surgical failure on at least one iCT requiring additional EPs in a large cohort of patients undergoing endoscopic minimally invasive ICH evacuation with the SCUBA technique. Methods: All patients who underwent minimally invasive endoscopic evacuation of supratentorial spontaneous ICH in a major health system between December 2015 and October 2018 were included in this study. Patient demographics, clinical and radiographic features, procedural details, and outcomes were analyzed retrospectively from a prospectively collected database. Procedures were characterized as initially successful when the first iCT demonstrated that surgical success had been achieved and initially unsuccessful when the surgical goal was not achieved, and additional EPs were performed. The surgical goal was prospectively identified in December of 2015 as leaving no more than 20% of the preoperative hematoma volume at the end of the procedure. Descriptive statistics and regression analyses were performed to identify predictors of initial failure and secondary rescue. Results: Patients (100) underwent minimally invasive endoscopic ICH evacuation in the angiography suite during the study time period. In 14 cases, the surgical goal was not met on the first iCT and multiple Eps were performed; in 10 cases the surgical goal was not met, and no additional EPs were performed. In 14 cases, the surgical goal was never achieved. When additional EPs were performed, a rescue rate of 71.4% (10/14) was seen, bringing the total percentage of cases meeting the surgical goal to 86% across the entire cohort. Cases in which the surgical goal was not achieved were significantly associated with older patients (68 years vs. 60 years; p = 0.0197) and higher rates of intraventricular hemorrhage (34.2% vs. 70.8%; p = 0.0021). Cases in which the surgical goal was rescued from initial failure had similar levels of IVH, suggesting that these additional complexities can be overcome with the use of additional iCT-informed EPs. Conclusions: Initial and ultimate surgical failure occurs in a small percentage of patients undergoing minimally invasive endoscopic ICH evacuation. The use of intraoperative imaging provides an opportunity to evaluate whether or not the surgical goal has been achieved, and to continue the procedure if the surgeon feels that more evacuation is achievable. Now that level-one evidence exists to target a surgical evacuation goal during minimally invasive ICH evacuation, intraoperative imaging, such as iCT, plays an important role in aiding the surgical team to achieve the surgical goal.

Bone Cements Used in Vertebral Augmentation: A State-of-the-art Narrative Review.

Vertebral compression fractures (VCFs) are common in osteoporotic patients, with a frequency projected to increase alongside a growing geriatric population. VCFs often result in debilitating back pain and decreased mobility. Cement augmentation, a minimally invasive surgical technique, is widely used to stabilize fractures and restore vertebral height. Acrylic-based cements and calcium phosphate cements are currently the two primary fill materials utilized for these procedures. Despite their effectiveness, acrylic bone cements and calcium phosphate cements have been associated with various intraoperative and postoperative incidents impacting VCF treatment. Over the past decade, discoveries in the field of biomedical engineering and material science have shown advancements toward addressing these limitations. This narrative review aims to assess the potential pitfalls and barriers of the various types of bone cements.

Modeling daily yields of milk, fat, protein, and lactose of New Zealand dairy goats undergoing standard and extended lactations.

This study aimed to assess the milk production data for New Zealand dairy goats in either a standard lactation (SL; ≤305 d in milk [DIM]) or extended lactation (EL; >305 and ≤670 DIM) using a random regression (RR) with third- and fifth-order Legendre polynomials, respectively. Persistency of EL was defined as (B/A) × 100, where A was the accumulated yield from d 1 to 305, and B was the accumulated yield from d 366 to 670. On average, goats in SL produced 1,183 kg of milk, 37 kg of fat, 37 kg of protein, and 54 kg of lactose. The average production of milk, fat, protein, and lactose in EL were 2,473 kg, 78 kg, 79 kg, and 112 kg, respectively. The average persistences for milk, fat, protein, and lactose yields during EL were 98%, 98%, 102%, and 96%, respectively. The relative prediction errors were close to 10% and the concordance correlation coefficients >0.92, indicating that the RR model with Legendre polynomials is adequate for modeling lactation curves for both SL and EL. Total yields and persistency were analyzed with a mixed model that included the fixed effects (year, month of kidding, parity, and proportion of Saanen) as covariates and the random effects of animal and residual errors. Effects of year, month of kidding, and parity were significant on the total yields of milk, fat, protein, and lactose for both SL and EL. The total milk yield of first-parity goats with SL was 946 kg and the total milk yield of second-parity goats with SL was 1,284 kg, making a total of 2,230 kg over 2 years. The total milk yield of a first-parity goat with EL was 2,140 kg. Thus, on average, a goat with SL for the first and second parity produced 90 kg more milk than a first-parity goat subjected to EL. However, a second-parity goat subjected to EL produced 43 kg more milk (2,639 kg) than a goat with SL following the second and third parity (1,284 kg + 1,312 kg). These data, along with the various other benefits of EL (e.g., fewer offspring born and reduced risk of mastitis, lameness, and metabolic problems in early lactation), indicate that EL as a management strategy holds the potential to improve dairy goat longevity and lifetime efficiency without compromising milk production.

Diagnostic validation of vertebral heart score machine learning algorithm for canine lateral chest radiographs.

OBJECTIVES: The vertebral heart score is a measurement used to index heart size relative to thoracic vertebra. Vertebral heart score can be a useful tool for identifying and staging heart disease and providing prognostic information. The purpose of this study is to validate the use of a vertebral heart score algorithm compared to manual vertebral heart scoring by three board-certified veterinary cardiologists. MATERIALS AND METHODS: A convolutional neural network centred around semantic segmentation of relevant anatomical features was developed to predict heart size and vertebral bodies. These predictions were used to calculate the vertebral heart score. An external validation study consisting of 1200 canine lateral radiographs was randomly selected to match the underlying distribution of vertebral heart scores. Three American College of Veterinary Internal Medicine board-certified cardiologists were enrolled to manually score 400 images each using the traditional Buchanan method. Post-scoring, the cardiologists evaluated the algorithm for misaligned anatomic landmarks and overall image quality. RESULTS: The 95th percentile absolute difference between the cardiologist vertebral heart score and the algorithm vertebral heart score was 1.05 vertebrae (95% confidence interval: 0.97 to 1.20 vertebrae) with a mean bias of -0.09 vertebrae (95% confidence interval: -0.12 to -0.05 vertebrae). In addition, the model was observed to be well calibrated across the predictive range. CLINICAL SIGNIFICANCE: We have found the performance of the vertebral heart score algorithm comparable to three board-certified cardiologists. While validation of this vertebral heart score algorithm has shown strong performance compared to veterinarians, further external validation in other clinical settings is warranted before use in those settings.

Investigating the use of local nerve blocks and general anaesthesia in reducing pain during and after disbudding procedure in goat kids.

The aim of this study was to compare the pain responses (as measured by noise and movement) during administration of local anaesthetic and during and after disbudding in goat kids. Eighty, seven- to ten-day-old, Saanen goat kids from one farm were enrolled and randomly assigned to one of four different methods of pain relief. Twenty kids had local anaesthetic (LA) applied at two sites per horn bud (LA group), 20 kids had LA applied to the two locations using a jet injector (JI group) and 20 kids were given a general anaesthetic (GA) using a combination of 0.02 mg/kg medetomidine and 2 mg/kg ketamine followed by a horn bud block applied as per the LA group (GA group). The remaining 20 kids had no treatment other than meloxicam (control group). Although responses between goat kids and at different time periods were variable, in comparison to the control group, GA eliminated the responses associated with injection of lignocaine and the responses during the period of disbudding, and provided a reduction in head scratches and shakes across multiple time periods.

A healthy but depleted herd: Predators decrease prey disease and density.

The healthy herds hypothesis proposes that predators can reduce parasite prevalence and thereby increase the density of their prey. However, evidence for such predator-driven reductions in the prevalence of prey remains mixed. Furthermore, even less evidence supports increases in prey density during epidemics. Here, we used a planktonic predator-prey-parasite system to experimentally test the healthy herds hypothesis. We manipulated density of a predator (the phantom midge, Chaoborus punctipennis) and parasitism (the virulent fungus Metschnikowia bicuspidata) in experimental assemblages. Because we know natural populations of the prey (Daphnia dentifera) vary in susceptibility to both predator and parasite, we stocked experimental populations with nine genotypes spanning a broad range of susceptibility to both enemies. Predation significantly reduced infection prevalence, eliminating infection at the highest predation level. However, lower parasitism did not increase densities of prey; instead, prey density decreased substantially at the highest predation levels (a major density cost of healthy herds predation). This density result was predicted by a model parameterized for this system. The model specifies three conditions for predation to increase prey density during epidemics: (i) predators selectively feed on infected prey, (ii) consumed infected prey release fewer infectious propagules than unconsumed prey, and (iii) sufficiently low infection prevalence. While the system satisfied the first two conditions, prevalence remained too high to see an increase in prey density with predation. Low prey densities caused by high predation drove increases in algal resources of the prey, fueling greater reproduction, indicating that consumer-resource interactions can complicate predator-prey-parasite dynamics. Overall, in our experiment, predation reduced the prevalence of a virulent parasite but, at the highest levels, also reduced prey density. Hence, while healthy herds predation is possible under some conditions, our empirical results make it clear that the manipulation of predators to reduce parasite prevalence may harm prey density.

First evidence of industrial fly-ash in an Antarctic ice core.

Spheroidal carbonaceous particles (SCPs) are a component of fly-ash, the particulate by-product of industrial high temperature combustion of fuel-oil and coal-series fuels. We provide the first evidence that these indelible markers of industrialisation have been deposited in Antarctic ice, thousands of kilometres from any potential source. The earliest observed particle was deposited in an ice layer from 1936 CE. While depositional fluxes are low, chemical analysis of individual SCPs indicates a coal combustion origin.

Consensus recommendations on therapeutic hypothermia after minimally invasive intracerebral hemorrhage evacuation from the hypothermia for intracerebral hemorrhage (HICH) working group.

Background and purpose: Therapeutic hypothermia (TH), or targeted temperature management (TTM), is a classic treatment option for reducing inflammation and potentially other destructive processes across a wide range of pathologies, and has been successfully used in numerous disease states. The ability for TH to improve neurological outcomes seems promising for inflammatory injuries but has yet to demonstrate clinical benefit in the intracerebral hemorrhage (ICH) patient population. Minimally invasive ICH evacuation also presents a promising option for ICH treatment with strong preclinical data but has yet to demonstrate functional improvement in large randomized trials. The biochemical mechanisms of action of ICH evacuation and TH appear to be synergistic, and thus combining hematoma evacuation with cooling therapy could provide synergistic benefits. The purpose of this working group was to develop consensus recommendations on optimal clinical trial design and outcomes for the use of therapeutic hypothermia in ICH in conjunction with minimally invasive ICH evacuation. Methods: An international panel of experts on the intersection of critical-care TH and ICH was convened to analyze available evidence and form a consensus on critical elements of a focal cooling protocol and clinical trial design. Three focused sessions and three full-group meetings were held virtually from December 2020 to February 2021. Each meeting focused on a specific subtopic, allowing for guided, open discussion. Results: These recommendations detail key elements of a clinical cooling protocol and an outline for the roll-out of clinical trials to test and validate the use of TH in conjunction with hematoma evacuation as well as late-stage protocols to improve the cooling approach. The combined use of systemic normothermia and localized moderate (33.5°C) hypothermia was identified as the most promising treatment strategy. Conclusions: These recommendations provide a general outline for the use of TH after minimally invasive ICH evacuation. More research is needed to further refine the use and combination of these promising treatment paradigms for this patient population.

Comparison of Three Anaesthetic Options to Reduce Acute Pain Response in Kid Goats.

Three options for anesthetizing the skin around the horn bud of dairy goat kids were explored. Forty-five <10-day-old Saanen goat kids from were randomly split into five treatment groups (topical anesthetic cream (TA), vapocoolant spray (VS), local anesthetic applied by jet injector (JI), control - no treatment but painful stimulus applied (C), sham - no treatment and touching sites with a finger. The painful stimulus was multiple needle pricks on the skin around the horn bud. The outcome variables measured were heart rate movement, and vocalization during treatment application and administration of a painful stimulus around the horn bud. Heart rates were greater during application of a VS compared to TA.Neither the TA nor the VS appeared to have any effect on the response to the painful stimulus. Kids in the JI group had a 96% reduced odds of expressing a marked pain response in comparison to TA group and an 83% reduction in the odds of a high movement grade during a painful procedure in comparison to the combined results of the other three treatment groups.

Pathogens and predators: examining the separate and combined effects of natural enemies on assemblage structure.

Natural enemy ecology strives to unify predator-prey and host-pathogen interactions under a common framework to gain insights into community- and ecosystem-level processes. To address this goal, ecologists need a greater emphasis on: (1) quantifying pathogen-mediated effects on community structure to enable comparisons with predator-mediated effects and (2) determining the interactive effects of combined natural enemies on communities. We conducted a mesocosm experiment to assess the individual and combined effects of predators (dragonfly larvae and adult water bugs) and a pathogen (ranavirus) on the abundance and composition of a larval amphibian assemblage. We found that our three natural enemies structured victim assemblages in unique ways, producing distinct assemblages. Additionally, we found that in combination treatments, predators mainly drove assemblage structure such that the assemblages most closely resembled their respective predator treatments. We also found that predators reduced infection prevalence in combination treatments, and that the magnitude of this effect was dependent on predator identity. Compared to virus-alone treatments, the presence of dragonflies and water bugs reduced infection prevalence by 79% and 63%, respectively. Additionally, the presence of dragonflies eliminated ranavirus infection in two species, which demonstrates the prominent role of predators in disease dynamics in this system. Overall, this work demonstrates the importance of considering natural enemies in community ecology, as each enemy can elicit a unique structural change. Additionally, this study provides a unique empirical test of the healthy herds hypothesis for multi-species assemblages and underscores the importance of advancing our understanding of multi-enemy interactions within communities.

PDGFRß promotes oncogenic progression via STAT3/STAT5 hyperactivation in anaplastic large cell lymphoma.

BACKGROUND: Anaplastic large cell lymphoma (ALCL) is an aggressive non-Hodgkin T cell lymphoma commonly driven by NPM-ALK. AP-1 transcription factors, cJUN and JUNb, act as downstream effectors of NPM-ALK and transcriptionally regulate PDGFRß. Blocking PDGFRß kinase activity with imatinib effectively reduces tumor burden and prolongs survival, although the downstream molecular mechanisms remain elusive. METHODS AND RESULTS: In a transgenic mouse model that mimics PDGFRß-driven human ALCL in vivo, we identify PDGFRß as a driver of aggressive tumor growth. Mechanistically, PDGFRß induces the pro-survival factor Bcl-xL and the growth-enhancing cytokine IL-10 via STAT5 activation. CRISPR/Cas9 deletion of both STAT5 gene products, STAT5A and STAT5B, results in the significant impairment of cell viability compared to deletion of STAT5A, STAT5B or STAT3 alone. Moreover, combined blockade of STAT3/5 activity with a selective SH2 domain inhibitor, AC-4-130, effectively obstructs tumor development in vivo. CONCLUSIONS: We therefore propose PDGFRß as a novel biomarker and introduce PDGFRß-STAT3/5 signaling as an important axis in aggressive ALCL. Furthermore, we suggest that inhibition of PDGFRß or STAT3/5 improve existing therapies for both previously untreated and relapsed/refractory ALK+ ALCL patients.

Development and Clinical Validation of a Finite Element Method Model Mapping Focal Intracranial Cooling.

Therapeutic hypothermia (TH) is a common and effective technique to reduce inflammation and induce neuroprotection across a variety of diseases. Focal TH of the brain can avoid the side effects of systemic cooling. The degree and extent of focal TH are a function of cooling probe design and local brain thermoregulation processes. To refine focal TH probe design, with application-specific optimization, we develop precise computational models of brain thermodynamics under intense local cooling. Here, we present a novel multiphysics in silico model that can accurately predict brain response to focal cooling. The model was parameterized from previously described values of metabolic activity, thermal conductivity, and temperature-dependent cerebral perfusion. The model was validated experimentally using data from clinical cases where local cooling was induced intracranially and brain temperatures monitored in real-time with MR thermometry. The validated model was then used to identify optimal design probe parameters to maximize volumetric TH, including considering three stratifications of cooling (mild, moderate, and profound) to produce Volume of Tissue Cooled (VOTC) maps. We report cooling radius increases in a nearly linear fashion with probe length and decreasing probe surface temperature.

Associations between peripartum lying and activity behaviour and blood non-esterified fatty acids and ß-hydroxybutyrate in grazing dairy cows.

During early lactation, most dairy cows experience negative energy balance (NEB). Failure to cope with this NEB, however, can place cows at greater risk of developing metabolic disease. Our objective was to characterise, retrospectively, lying behaviour and activity of grazing dairy cows grouped according to blood non-esterified fatty acids (NEFAs) and ß-hydroxybutyrate (BHB) as indicators of postpartum metabolic state. Blood was sampled weekly for up to 4 weeks precalving, on the day of calving (day 0), daily between 1 and 4 days postcalving, and then at least weekly between week 1 and week 5 postcalving for analysis of plasma NEFAs and BHB concentrations. Two hundred and forty-four multiparous Holstein-Friesian and Holstein-Friesian × Jersey cows were classified into one of three metabolic status groups based on maximum blood NEFAs and BHB concentrations during week 1 and 2 postcalving. A cow was classified as having either: (1) low NEFAs and low BHB (Lo-Lo; n = 78), when all blood samples were <1.0 mmol/L for NEFAs and ≤1.0 mmol/L for BHB during the first 2 weeks postcalving; (2) high NEFAs and low BHB (Hi-Lo; n = 134), when blood NEFAs were ≥1.0 mmol/L and blood BHB was ≤1.0 mmol/L at the same sampling time point during the first 2 weeks postcalving; or (3) high NEFAs and high BHB (Hi-Hi; n = 32), when blood NEFAs were ≥1.0 mmol/L and blood BHB was ≥1.2 mmol/L at the same sampling time point during the first 2 weeks postcalving. Accelerometers (IceTag or IceQube devices; IceRobotics Ltd.) were used to monitor lying and activity behaviours peripartum (-21 to +35 days relative to calving). Changes in lying behaviour and activity occurred before the mean day that cows were classified Hi-Hi and Hi-Lo (2.2 and 3.5 d postcalving, respectively). Up to 3 weeks preceding calving, Hi-Hi cows were more active, had fewer daily lying bouts (LBs), and spent less time lying than Lo-Lo cows. In addition, Hi-Hi cows had fewer daily LBs and were less active up to 4 weeks postcalving than Lo-Lo cows, but these differences were biologically small. Groups of grazing cows classified as experiencing a more severe metabolic challenge behave differently up to 3 weeks precalving than their herdmates with lower blood NEFAs and BHB postcalving. These altered behaviours may allow identification of individual cows at risk of a metabolic challenge, but further research is required.

Telehealth treatment for nonspecific low back pain: A review of the current state in mobile health.

INTRODUCTION: Nonspecific low back pain (LBP) is an idiopathic musculoskeletal condition that affects four of five individuals in their lifetime and is the leading cause of job-related disability in the United States. The interest in interactive and dynamic telehealth treatments for LBP continues to grow, and it is important for the medical community to remain up-to-date on the state of the science. LITERATURE SURVEY: Relevant studies published from March 2016 until March 2021 were identified through a systematic search of EMBASE, MedLine, and Web of Science. The search strategy combined the concepts of back pain, telehealth, and mobile applications. METHODOLOGY: Titles and abstracts were screened to select full-text randomized controlled trials or protocols, and methodological quality and risk of bias was assessed using the Cochrane risk-of-bias tool. Data were synthesized narratively. SYNTHESIS: We included seven concluded randomized-controlled trials and two study protocols reporting mobile health (mHealth) solutions for LBP. Six of the seven concluded trials found a significant improvement in self-reported numerical pain rating scale compared to the control group. A single trial compared a mHealth solution to physical therapy, with the majority of studies comparing interventions to "usual care." Substantial heterogeneity in reporting of sample characteristics was found, indicating a lack of standardization through the field. CONCLUSIONS: mHealth solutions may positively impact people with LBP. Larger trials should be encouraged and the field should coalesce around a set of baseline variables for collection and reporting. Because many interventions involve patient engagement, future trials should aim to further quantify adherence levels and begin to define telehealth "doses" associated with better outcomes.