Search

Abstract Image-based deformation estimation is an important tool used in a variety of engineering problems, including crack propagation, fracture, and fatigue failure. These tools have been important in biomechanics research where measuring in vitro and in vivo tissue deformations are important for evaluating tissue health and disease progression. However, accurately measuring tissue deformation in vivo is particularly challenging due to limited image signal-to-noise ratio. Therefore, we created a novel deep-learning approach for measuring deformation from a sequence of images collected in vivo called StrainNet. Utilizing a training dataset that incorporates image artifacts, StrainNet was designed to maximize performance in challenging, in vivo settings. Artificially generated image sequences of human flexor tendons undergoing known deformations were used to compare benchmark StrainNet against two conventional image-based strain measurement techniques. StrainNet outperformed the traditional techniques by nearly 90%. High-frequency ultrasound imaging was then used to acquire images of the flexor tendons engaged during contraction. Only StrainNet was able to track tissue deformations under the in vivo test conditions. Findings revealed strong correlations between tendon deformation and applied forces, highlighting the potential for StrainNet to be a valuable tool for assessing rehabilitation strategies or disease progression. Additionally, by using real-world data to train our model, StrainNet was able to generalize and reveal important relationships between the effort exerted by the participant and tendon mechanics. Overall, StrainNet demonstrated the effectiveness of using deep learning for image-based strain analysis in vivo.

Bacterial zoonoses are established causes of severe febrile illness in East Africa. Within a fever etiology study, we applied a high-throughput 16S rRNA metagenomic assay validated for detecting bacterial zoonotic pathogens. We enrolled febrile patients admitted to 2 referral hospitals in Moshi, Tanzania, during September 2007–April 2009. Among 788 participants, median age was 20 (interquartile range 2–38) years. We performed PCR amplification of V1–V2 variable region 16S rRNA on cell pellet DNA, then metagenomic deep-sequencing and pathogenic taxonomic identification. We detected bacterial zoonotic pathogens in 10 (1.3%) samples: 3 with Rickettsia typhi, 1 R. conorii, 2 Bartonella quintana, 2 pathogenic Leptospira spp., and 1 Coxiella burnetii. One other sample had reads matching a Neoerhlichia spp. previously identified in a patient from South Africa. Our findings indicate that targeted 16S metagenomics can identify bacterial zoonotic pathogens causing severe febrile illness in humans, including potential novel agents.

Abstract RNA binding proteins (RBPs) are key regulators of RNA processing and cellular function. Technologies to discover RNA targets of RBPs such as TRIBE (targets of RNA binding proteins identified by editing) and STAMP (surveying targets by APOBEC1 mediated profiling) utilize fusions of RNA base-editors (rBEs) to RBPs to circumvent the limitations of immunoprecipitation (CLIP)-based methods that require enzymatic digestion and large amounts of input material. To broaden the repertoire of rBEs suitable for editing-based RBP-RNA interaction studies, we have devised experimental and computational assays in a framework called PRINTER (protein-RNA interaction-based triaging of enzymes that edit RNA) to assess over thirty A-to-I and C-to-U rBEs, allowing us to identify rBEs that expand the characterization of binding patterns for both sequence-specific and broad-binding RBPs. We also propose specific rBEs suitable for dual-RBP applications. We show that the choice between single or multiple rBEs to fuse with a given RBP or pair of RBPs hinges on the editing biases of the rBEs and the binding preferences of the RBPs themselves. We believe our study streamlines and enhances the selection of rBEs for the next generation of RBP-RNA target discovery.

Salmonella is among the causative agents for diarrhea worldwide, but its risk factors in Tanzanian children are poorly understood. A hospital-based cross-sectional study was conducted in Moshi, Kilimanjaro region, from July 2020 to November 2022 among children under five admitted with diarrhea. A questionnaire was administered to all parents/caretakers of the enrolled children. Logistic regression was utilized to analyze the risk factors, with significance at p < 0.05. A total of 306 children were enrolled in the study. The median age was 13.8 months (IQR 8.4–21.8). The majority (58.5%) were males, and 59.5% were from rural areas. Salmonella was identified in eight (2.6%) stool samples, with a higher prevalence in urban than rural areas (4.8% vs. 1.1%; p-value = 0.044). The significant risk factors associated with Salmonella infection among the children included consuming raw milk (adjusted OR = 30.19; 95% CI: 3.94–231.46), using infant formula (adjusted OR = 15.78; 95% CI: 2.98–83.56), undisclosed household income (adjusted OR = 9.98; 95% CI: 2.46–40.12), purchasing eggs direct from the farms (adjusted OR = 7.58; 95%CI: 1.31–43.96), and contact with chickens (adjusted OR = 6.49; 95%CI: 1.25–33.59). These findings highlight the need for targeted interventions to improve food safety, hygiene practices, and socioeconomic conditions.

Abstract Lumbar intervertebral disc herniation, as a leading cause of low back pain, productivity loss, and disability, is a common musculoskeletal disorder that results in significant socioeconomic burdens. Despite extensive clinical and basic scientific research efforts, herniation etiopathogenesis, particularly its initiation and progression, is not well understood. Understanding herniation etiopathogenesis is essential for developing effective preventive measures and therapeutic interventions. Thus, this review seeks to provide a thorough overview of the advances in herniation‐oriented research, with a discussion on ongoing challenges and potential future directions for clinical, translational, and basic scientific investigations to facilitate innovative interdisciplinary research aimed at understanding herniation etiopathogenesis. Specifically, risk factors for herniation are identified and summarized, including familial predisposition, obesity, diabetes mellitus, smoking tobacco, selected cardiovascular diseases, disc degeneration, and occupational risks. Basic scientific experimental and computational research that aims to understand the link between excessive mechanical load, catabolic tissue remodeling due to inflammation or insufficient nutrient supply, and herniation, are also reviewed. Potential future directions to address the current challenges in herniation‐oriented research are explored by combining known progressive development in existing research techniques with ongoing technological advances. More research on the relationship between occupational risk factors and herniation, as well as the relationship between degeneration and herniation, is needed to develop preventive measures for working‐age individuals. Notably, researchers should explore using or modifying existing degeneration animal models to study herniation etiopathogenesis, as such models may allow for a better understanding of how to prevent mild‐to‐moderately degenerated discs from herniating.

Objective. To compare resource utilization and costs associated with 3 alternative screening approaches to identify early-onset sepsis (EOS) in infants born at ≥35 wk of gestational age, as recommended by the American Academy of Pediatrics (AAP) in 2018. Study Design. Decision tree–based cost analysis of the 3 AAP-recommended approaches: 1) categorical risk assessment (categorization by chorioamnionitis exposure status), 2) neonatal sepsis calculator (a multivariate prediction model based on perinatal risk factors), and 3) enhanced clinical observation (assessment based on serial clinical examinations). We evaluated resource utilization and direct costs (2022 US dollars) to the health system. Results. Categorical risk assessment led to the greatest neonatal intensive care unit usage (210 d per 1,000 live births) and antibiotic exposure (6.8%) compared with the neonatal sepsis calculator (112 d per 1,000 live births and 3.6%) and enhanced clinical observation (99 d per 1,000 live births and 3.1%). While the per-live birth hospital costs of the 3 approaches were similar—categorical risk assessment cost $1,360, the neonatal sepsis calculator cost $1,317, and enhanced clinical observation cost $1,310—the cost of infants receiving intervention under categorical risk assessment was approximately twice that of the other 2 strategies. Results were robust to variations in data parameters. Conclusion. The neonatal sepsis calculator and enhanced clinical observation approaches may be preferred to categorical risk assessment as they reduce the number of infants receiving intervention and thus antibiotic exposure and associated costs. All 3 approaches have similar costs over all live births, and prior literature has indicated similar health outcomes. Inclusion of downstream effects of antibiotic exposure in the neonatal period should be evaluated within a cost-effectiveness analysis. Highlights Of the 3 approaches recommended by the American Academy of Pediatrics in 2018 to identify early-onset sepsis in infants born at ≥35 weeks, the categorical risk assessment approach leads to about twice as many infants receiving evaluation to rule out early-onset sepsis compared with the neonatal sepsis calculator and enhanced clinical observation approaches. While the hospital costs of the 3 approaches were similar over the entire population of live births, the neonatal sepsis calculator and enhanced clinical observation approaches reduce antibiotic exposure, neonatal intensive care unit admission, and hospital costs associated with interventions as part of the screening approach compared with the categorical risk assessment approach.

Abstract Background Cryptococcosis is an increasingly common infection given the growing immunocompromised population worldwide. Cryptococcal antigen (CrAg) testing demonstrates excellent sensitivity and specificity and is the mainstay of diagnosis. However, there may be rare instances in which false-negative CrAg results can delay diagnosis and early treatment, which are critical to ensure positive outcomes. Case presentation A 31-year-old man living with HIV/AIDS who was not taking antiretroviral therapy was hospitalized with fever, diarrhea, and headaches. CD4 count on presentation was 71 cells/uL, and HIV viral load was 3,194,949 copies/mL. Serum CrAg testing was initially negative, however CSF CrAg performed several days later was positive at 1:40 and blood and CSF cultures grew Cryptococcus neoformans. Colonoscopy revealed mucosal papules throughout the sigmoid colon, and tissue biopsy showed yeast within the lamina propria consistent with GI cryptococcosis. Given the high burden of disease, the original serum CrAg specimen was serially diluted and subsequently found to be positive at 1:2,560, confirming the postzone phenomenon. Conclusion Cryptococcosis has a wide array of presentations including intraluminal GI disease, as seen in this patient. While serum CrAg testing displays excellent test characteristics, it is important for clinicians to be aware of the rare instances in which false-negative results may occur in the presence of excess antigen, as in this case.

Aromatic amino acids in proteins support ligand binding and protein stability. To parse the physiocochemical roles of aromatic interactions, here Galles, Infield and co-authors identify pyrrolysine-based aminoacyl-tRNA synthetases that enable the encoding of fluorinated phenylalanine amino acids.

Background: Several reports have shown that shoulder stabilizing procedures lead to postoperative external rotation (ER) deficits. However, no study on arthroscopic Latarjet procedures has investigated the effect on ER when the arm is abducted at 0° (ER0) and 90° (ER90). This study examined the relationship between the arthroscopic Latarjet procedure and the subsequent effect on ER0 and ER90. Methods: Patients who underwent an arthroscopic Latarjet procedure from December 2015 to April 2021 were retrospectively evaluated. Preoperative ER0 and ER90 values were obtained from the contralateral shoulder. ER0 and ER90 values from the operative side were collected at both 3 and 6 months postoperatively. A repeated measures ANOVA was performed to assess the mean preoperative and postoperative values. Results: Forty-six patients met the inclusion criteria. Mean ER0 for the 3- and 6-month time frames measured 44.2° and 54.6°, respectively. Mean ER90 for the 3- and 6-month time frames measured 78.4° and 90.4°, respectively. Comparison to the contralateral arm at the 3-month follow-up period showed a deficit of 14.9° (P = .0001) and 17.2° (P = .0001) for ER0 and ER90, respectively. At the 6-month follow-up period, patients demonstrated an average decline in ER0 and ER90 of 4.57° (P = .063) and 5.11° (P = .008), respectively. Conclusion: A nominal deficit in ER occurred for both ER0 and ER90 status post arthroscopic Latarjet procedure. Despite loss of ER90 at 6 months achieving statistical significance, the clinical impact is arguably inconsequential. Such limited loss of ER provides more information regarding bony procedures being a more definitive treatment for glenohumeral instability and the ability to restore native motion.

Abstract Sea level rise (SLR) and saltwater intrusion are driving inland shifts in coastal ecosystems. Here, we make high‐resolution (1 m) predictions of land conversion under future SLR scenarios in 81 watersheds surrounding Chesapeake Bay, United States, a hotspot for accelerated SLR and saltwater intrusion. We find that 1050–3748 km2 of marsh could be created by 2100, largely at the expense of forested wetlands. Predicted marsh migration exceeds total current tidal marsh area and is ~ 4× greater than historical observations. Anthropogenic land use in marsh migration areas is concentrated within a few watersheds and minimally impacts calculated metrics of marsh resilience. Despite regional marsh area maintenance, local ecosystem service replacement within vulnerable watersheds remains uncertain. However, our work suggests that topography rather than land use drives spatial variability in wetland vulnerability regionally, and that rural land conversion is needed to compensate for extensive areal losses on heavily developed coasts globally.

Introduction: Social insecurity, a form of deprivation of social amenities, if present among patients presenting in a rural emergency department (ED) can be a source of medical burden and poor health outcomes. Although knowledge and understanding of the insecurity profile of such patients is necessary for targeted care that improves their health outcomes, the concept has not been comprehensively quantified. In this study we explored, characterized, and quantified the social insecurity profile of ED patients at a rural teaching hospital in southeastern North Carolina with a large Native American population. Methods: A paper survey questionnaire was administered by trained research assistants between May–June 2018 to patients who presented to the ED and consented to participate in this cross-sectional, single-center study. The survey was anonymous with no identifying information collected on the respondents. A general demographic section and questions derived from the literature capturing sub-constructs of social insecurity—communication access, access to transportation, housing insecurity and home environment, food insecurity, and exposure to violence–were captured in the survey. We assessed the factors included in the index of social insecurity based on a rank ordering using the magnitude of their coefficient of variation and the Cronbach’s alpha reliability index of the constituent items. Results: Overall, we collected 312 surveys from the approximately 445 administered and included them in the analysis, representing a response rate of about 70%. The average age of the 312 respondents was 45.1 (±17.7) years with a range of 18.0–96.0. More females (54.2%) than males participated in the survey. Native Americans (34.3%), Blacks (33.7%), and Whites (27.6%) comprised the three major racial/ethnicity groups of the sample, which are representative of the study area’s population distribution. Social insecurity was observed among this population regarding all the subdomains and an overall measure (P

The study aimed to evaluate the implementation, and problems encountered in the implementation of Philippine National Police Electronic – Project Systems in Lipa City Batangas. The descriptive research design was used employing a self-made survey questionnaire distributed purposively to 120 internal stakeholders as the respondents of the study. The basic statistical tools were used to interpret and analysed the data gathered. The study revealed that e-Subpoena, e-Gallery, e-Warrant System, and e-Blotter Report are implemented in Lipa City, Batangas within the indicators of an effective implementation plan. However, the study also revealed that the stakeholders encountered serious problems in the implementation of PNP’s e-Project Systems within the bounds of the criteria used. This study asserts that although the PNP’s e-Project Systems in Lipa City Batangas are implemented, the regular conduct of capability building is necessary for the monitoring, supervision and management of the project.

The “job talk” is a standard element of faculty recruiting. How audiences treat candidates for faculty positions during job talks could have disparate impact on protected groups, including women. We annotated 156 job talks from five engineering and science departments for 13 categories of questions and comments. All departments were ranked in the top 10 by US News & World Report. We find that differences in the number, nature, and total duration of audience questions and comments are neither material nor statistically significant. For instance, the median difference (by gender) in the duration of questioning ranges from zero to less than two minutes in the five departments. Moreover, in some departments, candidates who were interrupted more often were more likely to be offered a position, challenging the premise that interruptions are necessarily prejudicial. These results are specific to the departments and years covered by the data, but they are broadly consistent with previous research, which found differences comparable in magnitude. However, those studies concluded that the (small) differences were statistically significant. We present evidence that the nominal statistical significance is an artifact of using inappropriate hypothesis tests. We show that it is possible to calibrate those tests to obtain a proper P -value using randomization.

Abstract Introduction Despite prioritization, routine antenatal influenza vaccine coverage is 35 years were less likely to be vaccinated than women aged 18—24 years (OR = 0.9 p = 0.053; OR = 0.9 p

Abstract Mechanical testing is a valuable tool for assessing intervertebral disc health, but the wide range of testing protocols makes it difficult to compare results from different studies. Normalizing mechanical properties by disc geometry allows for such comparisons, but there is little consistency in the methods by which disc geometry is measured. As such, we hypothesized that methods used to measure disc geometry would impact reported mechanical properties. Disc height and area were measured using computed tomography (CT), digital calipers, and ImageJ to yield three different measurements for disc height and six for disc area. Disc heights measured by digital calipers ex situ were >30% less than disc heights measured in situ by CT, and disc areas measured ex situ using ImageJ were >30% larger than those measured by CT. This significantly affected reported mechanical properties, leading to a 65% reduction in normalized compressive stiffness in the most extreme case. Though we cannot quantitatively correct between methods, results presented in this study suggest that disc geometry measurement methods have a significant impact on normalized mechanical properties and should be accounted for when comparing results.

Abstract Background Aberrant lipogenicity and deregulated autophagy are common in most advanced human cancer and therapeutic strategies to exploit these pathways are currently under consideration. Group III Phospholipase A2 (sPLA2-III/PLA2G3), an atypical secretory PLA2, is recognized as a regulator of lipid metabolism associated with oncogenesis. Though recent studies reveal that high PLA2G3 expression significantly correlates with poor prognosis in several cancers, however, role of PLA2G3 in ovarian cancer (OC) pathogenesis is still undetermined. Methods CRISPR-Cas9 and shRNA mediated knockout and knockdown of PLA2G3 in OC cells were used to evaluate lipid droplet (LD) biogenesis by confocal and Transmission electron microscopy analysis, and the cell viability and sensitization of the cells to platinum-mediated cytotoxicity by MTT assay. Regulation of primary ciliation by PLA2G3 downregulation both genetically and by metabolic inhibitor PFK-158 induced autophagy was assessed by immunofluorescence-based confocal analysis and immunoblot. Transient transfection with GFP-RFP-LC3B and confocal analysis was used to assess the autophagic flux in OC cells. PLA2G3 knockout OVCAR5 xenograft in combination with carboplatin on tumor growth and metastasis was assessed in vivo. Efficacy of PFK158 alone and with platinum drugs was determined in patient-derived primary ascites cultures expressing PLA2G3 by MTT assay and immunoblot analysis. Results Downregulation of PLA2G3 in OVCAR8 and 5 cells inhibited LD biogenesis, decreased growth and sensitized cells to platinum drug mediated cytotoxicity in vitro and in in vivo OVCAR5 xenograft. PLA2G3 knockdown in HeyA8MDR-resistant cells showed sensitivity to carboplatin treatment. We found that both PFK158 inhibitor-mediated and genetic downregulation of PLA2G3 resulted in increased number of percent ciliated cells and inhibited cancer progression. Mechanistically, we found that PFK158-induced autophagy targeted PLA2G3 to restore primary cilia in OC cells. Of clinical relevance, PFK158 also induces percent ciliated cells in human-derived primary ascites cells and reduces cell viability with sensitization to chemotherapy. Conclusions Taken together, our study for the first time emphasizes the role of PLA2G3 in regulating the OC metastasis. This study further suggests the therapeutic potential of targeting phospholipases and/or restoration of PC for future OC treatment and the critical role of PLA2G3 in regulating ciliary function by coordinating interface between lipogenesis and metastasis.

Growing evidence suggests considerable variation in endemic typhoid fever incidence at some locations over time, yet few settings have multi-year incidence estimates to inform typhoid control measures. We sought to describe a decade of typhoid fever incidence in the Kilimanjaro Region of Tanzania. Cases of blood culture confirmed typhoid were identified among febrile patients at two sentinel hospitals during three study periods: 2007-08, 2011-14, and 2016-18. To account for under-ascertainment at sentinel facilities, we derived adjustment multipliers from healthcare utilization surveys done in the hospital catchment area. Incidence estimates and credible intervals (CrI) were derived using a Bayesian hierarchical incidence model that incorporated uncertainty of our observed typhoid fever prevalence, of healthcare seeking adjustment multipliers, and of blood culture diagnostic sensitivity. Among 3,556 total participants, 50 typhoid fever cases were identified. Of typhoid cases, 26 (52%) were male and the median (range) age was 22 (

Abstract Changes in brain resting-state functional connectivity (rsFC) were investigated using a longitudinal design by following a 2-month focused attention meditation (FAM) practice and analyzing their association with FAM practice time. Ten novice meditators were recruited from a university meditation course. Participants were scanned with a resting-state fMRI sequence with multi-echo EPI acquisition at baseline and at the 2-month follow-up. Total FAM practice time was calculated from the daily log of the participants. We observed significantly increased rsFC between the posterior cingulate cortex (PCC) and dorsal attention network (DAN), the right middle temporal (RMT) region and default mode network (DMN), the left and right superior parietal lobules (LSPL/RSPL) and DMN, and the LSPL/RSPL and DAN. Furthermore, the rsFC between the LSPL and medial prefrontal cortex was significantly associated with the FAM practice time. These results demonstrate increased connectivity within the DAN, between the DMN and DAN, and between the DMN and visual cortex. These findings demonstrate that FAM can enhance the brain connection among and within brain networks, especially DMN and DAN, indicating potential effect of FAM on fast switching between mind wandering and focused attention and maintaining attention once in the attentive state.

This essay examines how Black girl narratives are finding and making space and place in the arena of comic books and television. With the rise in Black girl (super)hero protagonists on the comic book pages and adapted television shows, it is essential to explore the significance of their rising inclusion, visibility, and popularity and understand how they contribute to the discourse surrounding the next generation of heroes. Guided by an Afrofuturist, Black feminist, and intersectional framework, I discuss the progressive possibilities of popular media culture in depicting Black girlhood and adolescence. In Marvel Comics’ “RiRi Williams/Ironheart”, DC Comics’ “Naomi McDuffie”, and Boom! Studios’ “Eve”, these possibilities are evident. Blending aspects of adventure, fantasy, sci-fi, and STEM, each character offers fictional insight into the lived experiences of Black girl youth from historical, aesthetic, and expressive perspectives. Moreover, as talented and adventurous characters, their storylines, whether on the comic book pages or the television screen, reveal a necessary change to the landscape of popular media culture.

The Open Science (OS) movement is rapidly gaining traction among policy-makers, research funders, scientific journals and individual scientists. Despite these tendencies, the pace of implementing OS throughout the scientific process and across the scientific community remains slow. Thus, a better understanding of the conditions that affect OS engagement, and in particular, of how practitioners learn, use, conduct and share research openly can guide those seeking to implement OS more broadly. We surveyed participants at an OS workshop hosted by the Living Norway Ecological Data Network in 2020 to learn how they perceived OS and its importance in their research, supervision and teaching. Further, we wanted to know what OS practices they had encountered in their education and what they saw as hindering or helping their engagement with OS. The survey contained scaled-response and open-ended questions, allowing for a mixed-methods approach. We obtained survey responses from 60 out of 128 workshop participants (47%). Responses indicated that usage and sharing of open data and code, as well as open access publication, were the most frequent OS practices. Only a minority of respondents reported having encountered OS in their formal education. A majority also viewed OS as less important in their teaching than in their research and supervisory roles. The respondents' suggestions for what would facilitate greater OS engagement in the future included knowledge, guidelines, and resources, but also social and structural support. These are aspects that could be strengthened by promoting explicit implementation of OS practices in higher education and by nurturing a more inclusive and equitable OS culture. We argue that incorporating OS in teaching and learning of science can yield substantial benefits to the research community, student learning, and ultimately, to the wider societal objectives of science and higher education.

Inguinoscrotal herniation of the bladder is a rare presentation of inguinal hernia that can result in significant complications if untreated. We describe a case of an elderly male with a delayed presentation of bladder herniation resulting in severe acute kidney injury requiring urgent placement of nephrostomy tubes. Ultimately surgery is required for definitive management.

ABSTRACT Humans are exposed to ionizing radiation via spaceflight or cancer radiotherapy, and exposure from radiotherapy is known to increase risk of skeletal fractures. Although irradiation can reduce trabecular bone mass, alter trabecular microarchitecture, and increase collagen cross‐linking, the relative contributions of these effects to any loss of mechanical integrity remain unclear. To provide insight, while addressing both the monotonic strength and cyclic‐loading fatigue life, we conducted total‐body, acute, gamma‐irradiation experiments on skeletally mature (17‐week‐old) C57BL/6J male mice (n = 84). Mice were administered doses of either 0 Gy (sham), 1 Gy (motivated by cumulative exposures from a Mars mission), or 5 Gy (motivated by clinical therapy regimens) with retrieval of the lumbar vertebrae at either a short‐term (11‐day) or long‐term (12‐week) time point after exposure. Micro‐computed tomography was used to assess trabecular and cortical quantity and architecture, biochemical composition assays were used to assess collagen quality, and mechanical testing was performed to evaluate vertebral compressive strength and fatigue life. At 11 days post‐exposure, 5 Gy irradiation significantly reduced trabecular mass (p

A comprehensive understanding of multiscale and multiphasic intervertebral disc mechanics is crucial for designing advanced tissue engineered structures aiming to recapitulate native tissue behavior. The bovine caudal disc is a commonly used human disc analog due to its availability, large disc height and area, and similarities in biochemical and mechanical properties to the human disc. Because of challenges in directly measuring subtissue-level mechanics, such as in situ fiber mechanics, finite element models have been widely employed in spinal biomechanics research. However, many previous models use homogenization theory and describe each model element as a homogenized combination of fibers and the extrafibrillar matrix while ignoring the role of water content or osmotic behavior. Thus, these models are limited in their ability in investigating subtissue-level mechanics and stress-bearing mechanisms through fluid pressure. The objective of this study was to develop and validate a structure-based bovine caudal disc model, and to evaluate multiscale and multiphasic intervertebral disc mechanics under different loading conditions and with degeneration. The structure-based model was developed based on native disc structure, where fibers and matrix in the annulus fibrosus were described as distinct materials occupying separate volumes. Model parameters were directly obtained from experimental studies without calibration. Under the multiscale validation framework, the model was validated across the joint-, tissue-, and subtissue-levels. Our model accurately predicted multiscale disc responses for 15 of 16 cases, emphasizing the accuracy of the model, as well as the effectiveness and robustness of the multiscale structure-based modeling-validation framework. The model also demonstrated the rim as a weak link for disc failure, highlighting the importance of keeping the cartilage endplate intact when evaluating disc failure mechanisms in vitro. Importantly, results from this study elucidated important fluid-based load-bearing mechanisms and fiber-matrix interactions that are important for understanding disease progression and regeneration in intervertebral discs. In conclusion, the methods presented in this study can be used in conjunction with experimental work to simultaneously investigate disc joint-, tissue-, and subtissue-level mechanics with degeneration, disease, and injury.

One potentially important bone quality characteristic is the response of bone to cyclic (repetitive) mechanical loading. In small animals, such as in rats and mice, cyclic loading experiments are particularly challenging to perform in a precise manner due to the small size of the bones and difficult-to-eliminate machine compliance. Addressing this issue, we developed a precise method for ex vivo cyclic compressive loading of isolated mouse vertebral bodies. The method has three key characteristics: 3D-printed support jigs for machining plano-parallel surfaces of the tiny vertebrae; pivotable loading platens to ensure uniform contact and loading of specimen surfaces; and specimen-specific micro-CT-based finite element analysis to measure stiffness to prescribe force levels that produce the same specified level of strain for all test specimens. To demonstrate utility, we measured fatigue life for three groups (n = 5–6 per group) of L5 vertebrae of C57BL/6J male mice, comparing our new method against two methods commonly used in the literature. We found reduced scatter of the mechanical behavior for this new method compared to the literature methods. In particular, for a controlled level of strain, the standard deviation of the measured fatigue life was up to 5-fold lower for the new method (F-ratio = 4.9; p

Coastal salt marshes, which provide valuable ecosystem services such as flood mitigation and carbon sequestration, are threatened by rising sea level. In response, these ecosystems migrate landward, converting available upland into salt marsh. In the coastal-plain surrounding Chesapeake Bay, United States, conversion of coastal forest to salt marsh is well-documented and may offset salt marsh loss due to sea level rise, sediment deficits, and wave erosion. Land slope at the marsh-forest boundary is an important factor determining migration likelihood, however, the standard method of using field measurements to assess slope across the marsh-forest boundary is impractical on the scale of an estuary. Therefore, we developed a general slope quantification method that uses high resolution elevation data and a repurposed shoreline analysis tool to determine slope along the marsh-forest boundary for the entire Chesapeake Bay coastal-plain and find that less than 3% of transects have a slope value less than 1%; these low slope environments offer more favorable conditions for forest to marsh conversion. Then, we combine the bay-wide slope and elevation data with inundation modeling from Hurricane Isabel to determine likelihood of coastal forest conversion to salt marsh. This method can be applied to local and estuary-scale research to support management decisions regarding which upland forested areas are more critical to preserve as available space for marsh migration.

Abstract Biomechanical testing methodologies for the spine have developed over the past 50 years. During that time, there have been several paradigm shifts with respect to techniques. These techniques evolved by incorporating state‐of‐the‐art engineering principles, in vivo measurements, anatomical structure‐function relationships, and the scientific method. Multiple parametric studies have focused on the effects that the experimental technique has on outcomes. As a result, testing methodologies have evolved, but there are no standard testing protocols, which makes the comparison of findings between experiments difficult and conclusions about in vivo performance challenging. In 2019, the international spine research community was surveyed to determine the consensus on spine biomechanical testing and if the consensus opinion was consistent with the scientific evidence. More than 80 responses to the survey were received. The findings of this survey confirmed that while some methods have been commonly adopted, not all are consistent with the scientific evidence. This review summarizes the scientific literature, the current consensus, and the authors' recommendations on best practices based on the compendium of available evidence.

Infection is a rare cause of orbital apex syndrome (OAS) and most commonly occurs in immunocompromised hosts. We report a case of OAS in an elderly immunocompetent female due to invasive aspergillosis and Staphylococcus aureus co-infection. The patient required both surgical debridement and prolonged courses of antibiotic and antifungal therapy. Invasive fungal disease must be considered in cases of OAS, even in patients without classic risk factors.

Zhou and colleagues are commended for their innovative research on the tolerability of “low-viscosity” fibre supplements in symptomatic diabetic gastroparesis patients [...]

Abstract In vitro mechanical testing of intervertebral discs is crucial for basic science and pre‐clinical testing. Generally, these tests aim to replicate in vivo conditions, but simplifications are necessary in specimen preparation and mechanical testing due to complexities in both structure and the loading conditions required to replicate in vivo conditions. There has been a growing interest in developing a consensus of testing protocols within the spine community to improve comparison of results between studies. The objective of this study was to perform axial compression experiments on bovine bone‐disc‐bone specimens at three institutions. No differences were observed between testing environment being air, with PBS soaked gauze, or a PBS bath (P > .206). A 100‐fold increase in loading rate resulted in a small (2%) but significant increase in compressive mechanics (P

The objective of this study was to investigate the effect of okra pectin as a stabilizer and a texturizer on the quality and consumer acceptability of tigernut milk and fried yam, respectively. Okra pectin concentrations 0% (control), 0.2%, 0.4% and 0.6% were used in the preparation of tigernut milk as well as to pretreat yam slices before deep frying. The viscosity and microbial quality of the tigernut milk samples were evaluated, whilst the moisture content, oil uptake and colour of fried yam were also determined. Consumer acceptability test was conducted on both the tigernut milk and fried yam using 50 semi-trained panelists. The viscosity of the tigernut milk samples which ranged from 4.67 cP to 10.50 cP increased with increasing concentrations of okra pectin. The microbial load of all tigernut milk samples were within the acceptable limits. With the exception of sample appearance, okra pectin also had no significant effect (p > 0.05) on the sensory quality of tigernut milk. On the other hand, okra pectin treatment in the fried yam samples resulted in significantly different moisture (54.33–56.71%), oil uptake/fat content (4.00–5.50%) and colour (L*a*b*) values. Results showed that okra pectin had no significant effect (p > 0.05) on all sensory quality parameters of fried yam samples though 0.2% okra pectin treated yam had the highest mean overall acceptability. The findings suggest that treatment with okra pectin can be exploited to make appreciable impact on the quality and consumer acceptability of fried yam.

Tissue engineering strategies show great potential for repairing osteochondral defects in osteoarthritic joints; however, these approaches often rely on passaging cells multiple times to obtain enough cells to produce functional tissue. Unfortunately, monolayer expansion culture causes chondrocyte dedifferentiation, which is accompanied by a phenotypical and morphological shift in chondrocyte properties that leads to a reduction in the quality of de novo cartilage produced. Thus, the objective of this study was to evaluate transcriptional variations during in vitro expansion culture and determine how differences in cell phenotype from monolayer expansion alter development of functional engineered cartilage. We used an unbiased approach to explore genome-wide transcriptional differences in chondrocyte phenotype at passage 1 (P1), P3, and P5, and then seeded cells into hydrogel scaffolds at P3 and P5 to assess cells' abilities to produce cartilaginous extracellular matrix in three dimensional (3D). We identified distinct phenotypic differences, specifically for genes related to extracellular organization and cartilage development. Both P3 and P5 chondrocytes were able to produce chondrogenic tissue in 3D, with P3 cells producing matrix with greater compressive properties and P5 cells secreting matrix with higher glycosaminoglycan/DNA and collagen/DNA ratios. Furthermore, we identified 24 genes that were differentially expressed with passaging and enriched in human osteoarthritis (OA) genome-wide association studies, thereby prioritizing them as functionally relevant targets to improve protocols that recapitulate functional healthy cartilage with cells from adult donors. Specifically, we identified novel genes, such as TMEM190 and RAB11FIP4, which were enriched with human hip OA and may play a role in chondrocyte dedifferentiation. This work lays the foundation for several pathways and genes that could be modulated to enhance the efficacy for chondrocyte culture for tissue regeneration, which could have transformative impacts for cell-based cartilage repair strategies.

Lower back pain continues to be a global epidemic, limiting quality of life and ability to work, due in large part to symptomatic disc degeneration. Development of more effective and less invasive biological strategies are needed to treat disc degeneration. In vitro models such as macro- or micro-bioreactors or mechanically active organ-chips hold great promise in reducing the need for animal studies that may have limited clinical translatability, due to harsher and more complex mechanical loading environments in human discs than in most animal models. This review highlights the complex loading conditions of the disc in situ, evaluates state-of-the-art designs for applying such complex loads across multiple length scales, from macro-bioreactors that load whole discs to organ-chips that aim to replicate cellular or engineered tissue loading. Emphasis was placed on the rapidly evolving more customizable organ-chips, given their greater potential for studying the progression and treatment of symptomatic disc degeneration. Lastly, this review identifies new trends and challenges for using organ-chips to assess therapeutic strategies.

Many workers who engage in manual material handling (MMH) jobs experience high physical demands that are associated with work-related musculoskeletal disorders (WMSDs). Quantifying the physical demands of a job is important for identifying high risk jobs and is a legal requirement in the United States for hiring and return to work following injury. Currently, most physical demand analyses (PDAs) are performed by experts using observational and semi-quantitative methods. The lack of accuracy and reliability of these methods can be problematic, particularly when identifying restrictions during the return-to-work process. Further, when a worker does return-to-work on modified duty, there is no way to track compliance to work restrictions conflating the effectiveness of the work restrictions versus adherence to them. To address this, we applied a deep learning model to data from eight inertial measurement units (IMUs) to predict 15 occupational physical activities. Overall, a 95% accuracy was reached for predicting isolated occupational physical activities. However, when applied to more complex tasks that combined occupational physical activities (OPAs), accuracy varied widely (0–95%). More work is needed to accurately predict OPAs when combined into simulated work tasks.

Abstract Bovine caudal discs have been widely used in spine research due to their increased availability, large size, and mechanical and biochemical properties that are comparable to healthy human discs. However, despite their extensive use, the radial variations in bovine disc composition have not yet been rigorously quantified with high spatial resolution. Previous studies were limited to qualitative analyses or provided limited spatial resolution in biochemical properties. Thus, the main objective of this study was to provide quantitative measurements of biochemical composition with higher spatial resolution than previous studies that employed traditional biochemical techniques. Specifically, traditional biochemical analyses were used to measure water, sulfated glycosaminoglycan, collagen, and DNA contents. Gravimetric water content was compared to data obtained through Raman spectroscopy and differential scanning calorimetry. Additionally, spatial distribution of lipids in the disc's collagen network was visualized and quantified, for the first time, using multi‐modal second harmonic generation (SHG) and Coherent anti‐Stokes Raman (CARS) microscopy. Some heterogeneity was observed in the nucleus pulposus, where the water content and water‐to‐protein ratio of the inner nucleus were greater than the outer nucleus. In contrast, the bovine annulus fibrosus exhibited a more heterogeneous distribution of biochemical properties. Comparable results between orthohydroxyproline assay and SHG imaging highlight the potential benefit of using SHG microscopy as a less destructive method for measuring collagen content, particularly when relative changes are of interest. CARS images showed that lipid deposits were distributed equally throughout the disc and appeared either as individual droplets or as clusters of small droplets. In conclusion, this study provided a more comprehensive assessment of spatial variations in biochemical composition of the bovine caudal disc.

Introduction: Emergency department (ED) visits for mental health and substance use disorders have been on the rise, with substance use disorders frequently coexisting with mental health disorders. This study evaluated substances commonly used/abused by patients presenting to the ED of a rural, regional medical center with subsequent admission for mental health treatment in Robeson County, North Carolina. Methods: This retrospective, single-center study was approved by the Southeastern Health Institutional Review Board. We reviewed medical records of psychiatric patients presenting to the ED with ultimate admission to the inpatient psychiatric unit between January 1, 2016, and June 30, 2016. Frequencies of controlled substances testing positive on urine drug and alcohol screenings in admitted patients were obtained and analyzed. We also made ethnic and gender comparisons. Results: A total of 477 patients met inclusion criteria. The percentage of patients testing positive were as follows: tetrahydrocannabinol (THC) (40%); cocaine (28.7%); alcohol (15.1%); benzodiazepines (13%); opiates (9.6%); amphetamines (2.9%); barbiturates (2.3%); and methadone (0.8%). A relatively higher proportion of patients tested positive for THC than any other substance ( p≤.0002). We found statistically significant differences for gender ( p=.0004) and ethnicity ( p

Bacterial zoonoses cause severe febrile illness in East Africa (2). Patients with bacterial zoonotic diseases can have nonspecific febrile illnesses that are difficult to diagnose clinically or in the laboratory [...]

RNA binding proteins (RBPs) are key regulators of RNA processing and cellular function. Technologies to discover RNA targets of RBPs such as TRIBE (targets of RNA binding proteins identified by editing) and STAMP (surveying targets by APOBEC1 mediated profiling) utilize fusions of RNA base-editors (rBEs) to RBPs to circumvent the limitations of immunoprecipitation (CLIP)-based methods that require enzymatic digestion and large amounts of input material. To broaden the repertoire of rBEs suitable for editing-based RBP-RNA interaction studies, we have devised experimental and computational assays in a framework called PRINTER (protein-RNA interaction-based triaging of enzymes that edit RNA) to assess over thirty A-to-I and C-to-U rBEs, allowing us to identify rBEs that expand the characterization of binding patterns for both sequence-specific and broad-binding RBPs. We also propose specific rBEs suitable for dual-RBP applications. We show that the choice between single or multiple rBEs to fuse with a given RBP or pair of RBPs hinges on the editing biases of the rBEs and the binding preferences of the RBPs themselves. We believe our study streamlines and enhances the selection of rBEs for the next generation of RBP-RNA target discovery.

The “job talk” is a standard element of faculty recruiting. How audiences treat candidates for faculty positions during job talks could have disparate impact on protected groups, including women. We annotated 156 job talks from five engineering and science departments for 13 categories of questions and comments. All departments were ranked in the top 10 by US News & World Report. We find that differences in the number, nature, and total duration of audience questions and comments are neither material nor statistically significant. For instance, the median difference (by gender) in the duration of questioning ranges from zero to less than two minutes in the five departments. Moreover, in some departments, candidates who were interrupted more often were more likely to be offered a position, challenging the premise that interruptions are necessarily prejudicial. These results are specific to the departments and years covered by the data, but they are broadly consistent with previous research, which found differences comparable in magnitude. However, those studies concluded that the (small) differences were statistically significant. We present evidence that the nominal statistical significance is an artifact of using inappropriate hypothesis tests. We show that it is possible to calibrate those tests to obtain a proper P-value using randomization.

ObjectiveCartilage tissue engineering strategies that use autologous chondrocytes require in vitro expansion of cells to obtain enough cells to produce functional engineered tissue. However, chondrocytes dedifferentiate during expansion culture, limiting their ability to produce chondrogenic tissue and their utility for cell-based cartilage repair strategies. The current study identified conditions that favor cartilage production and the mechanobiological mechanisms responsible for these benefits.DesignChondrocytes were isolated from juvenile bovine knee joints and cultured with (primed) or without (unprimed) a growth factor cocktail. Gene expression, cell morphology, cell adhesion, cytoskeletal protein distribution, and cell mechanics were assessed. Following passage 5, cells were embedded into agarose hydrogels to evaluate functional properties of engineered cartilage.ResultsPriming cells during expansion culture altered cell phenotype and chondrogenic tissue production. Unbiased RNA-sequencing analysis suggested, and experimental studies confirmed, that growth factor priming delays dedifferentiation associated changes in cell adhesion and cytoskeletal organization. Priming also overrode mechanobiological pathways to prevent chondrocytes from remodeling their cytoskeleton to accommodate the stiff, monolayer microenvironment. Passage 1 primed cells deformed less and had lower YAP1 activity than unprimed cells. Differences in cell adhesion, morphology, and cell mechanics between primed and unprimed cells were mitigated by passage 5.ConclusionsPriming suppresses mechanobiologic cytoskeletal remodeling to prevent chondrocyte dedifferentiation, resulting in more cartilage-like tissue-engineered constructs.

Background/Objective: Whole organ in vitro intervertebral disc models have been associated with poor maintenance of cell viability. No previous studies have used a rotating wall vessel bioreactor for intervertebral disc explants culture. The purpose of this study was to develop and validate an in vitro model for the assessment of biological and biomechanical measures of intervertebral disc health and disease. Methods: To this end, endplate-intervertebral disc-endplate whole organ explants were harvested from the tails of rats. For the injured group, the annulus fibrosus was penetrated with a 20G needle to the nucleus pulposus and aspirated. Explants were cultured in a rotating wall vessel bioreactor for 14 days. Results: Cell viability and histologic assessments were performed at Day 0, Day 1, Day 7, and Day 14. Compressive mechanical properties of the intervertebral disc were assessed at Day 0 and Day 14. In the annulus fibrosus and nucleus pulposus cells, the uninjured group maintained high viability through 14 days of culture, whereas cell viability in annulus fibrosus and nucleus pulposus of the injured intervertebral discs was markedly lower at Day 7 and Day 14. Histologically, the uninjured intervertebral discs maintained cell viability and tissue morphology and architecture through 14 days, whereas the injured intervertebral discs showed areas of cell death, loss of extracellular matrix integrity, and architecture by Day 14. Stiffness values for uninjured intervertebral discs were similar at Day 0 and Day 14, whereas the stiffness for the injured intervertebral discs was approximately 2.5 times greater at Day 14. Conclusion: These results suggest that whole organ intervertebral discs explants can be successfully cultured in a rotating wall vessel bioreactor to maintain cell viability and tissue architecture in both annulus fibrosus and nucleus pulposus for at least 14 days. In addition, the injury used produced pathologic changes consistent with those seen in degenerative intervertebral disc disease in humans. This model will permit further study into potential future treatments and other mechanisms of addressing intervertebral disc disease.

The recent global pandemic necessitated a shift which compelled educators to embrace online modalities. The authors examined the preparedness of teachers for this transition in three key domains: material readiness, home environment readiness and psychological disposition readiness. Survey data, gathered from 219 Filipino educators via an online questionnaire, revealed noteworthy insights. Most respondents registered a lack of confidence in internet connectivity and admitted not having household surroundings conducive to work-from-home arrangements. Despite some educators expressing readiness for online instruction, a prevalent theme emerged wherein a majority demonstrated unwillingness to assume the role of 'digital teachers'. This study posits that while transitioning to non-traditional spaces like the online platform is imperative in times of global pandemic, being mindful of the myriad of readiness issues faced by educators is equally important to ensure a truly meaningful and effective online teaching experience.

Multiple sclerosis (MS) is a major cause of disability and poor quality of life (QOL). Previous studies have shown differences in MS health outcomes between countries. This study aimed to examine the associations between international regions and health outcomes in people with MS. Self-reported data were taken from the Health Outcomes and Lifestyle In a Sample of people with Multiple Sclerosis online survey collected in 2012. The 2,401 participants from 37 countries were categorized into three regions: Australasia, Europe, and North America. Differences were observed between regions in disability, physical and mental health QOL, fatigue, and depression, but most of these disappeared after adjusting for sociodemographic, disease, and lifestyle factors in multivariable regression models. However, adjusted odds for disability were higher in Europe [odds ratio (OR): 2.17, 95% confidence interval (CI): 1.28 to 3.67] and North America (OR: 1.79, 95% CI: 1.28 to 2.51) compared to Australasia. There may be other unmeasured factors that vary between regions, including differences in access and quality of healthcare services, determining disability in MS. When assessing differences in MS health outcomes, lifestyle factors and medication use should be taken into consideration.

Functionally gradient materials, characterized by a smooth compositional change over space, have gained attention in recent years due to their tunable properties and ability to reduce mechanical stress concentrations. Specifically, attaining high stiffness without compromising toughness is a challenge, as the properties are inversely related. Varying moduli gradients, as seen abundantly in biological materials, do not present this trade-off, facilitating increased rigidity without altering maximum elongation. Herein, the application of stiffness gradients in porous structures is investigated through compressive mechanical testing, computerized tomography imaging, and finite element modeling. Gradients are compared to several alternative designs to investigate the importance of a smooth material transition and increased radial stiffness. All groups are compressed to 50% strain and the pre- and postpore closure modulus, toughness, and dimensional change in the transverse and radial directions are measured. The findings indicate that a mechanical gradient with increasing radial stiffness allows for balance of mechanical integrity and favorable recovery characteristics, crucial for long-lasting performance. Furthermore, the structures with an increasing radial stiffness outperform those with a decreasing radial stiffness in all aspects. The results emphasize the mechanical advantages and optimization potential of a radial stiffness gradient for a wide range of load-bearing applications.

Growing clinical evidence suggests a correlation between diabetes and more frequent and severe intervertebral disc failure, partially attributed to accelerated advanced glycation end-products (AGE) accumulation in the annulus fibrosus (AF) through non-enzymatic glycation. However, in vitro glycation (i.e., crosslinking) reportedly improved AF uniaxial tensile mechanical properties, contradicting clinical observations. Thus, this study used a combined experimental-computational approach to evaluate the effect of AGEs on anisotropic AF tensile mechanics, applying finite element models (FEMs) to complement experimental testing and examine difficult-to-measure subtissue-level mechanics. Methylglyoxal-based treatments were applied to induce three physiologically relevant AGE levels in vitro. Models incorporated crosslinks by adapting our previously validated structure-based FEM framework. Experimental results showed that a threefold increase in AGE content resulted in a ∼55% increase in AF circumferential-radial tensile modulus and failure stress and a 40% increase in radial failure stress. Failure strain was unaffected by non-enzymatic glycation. Adapted FEMs accurately predicted experimental AF mechanics with glycation. Model predictions showed that glycation increased stresses in the extrafibrillar matrix under physiologic deformations, which may increase tissue mechanical failure or trigger catabolic remodeling, providing insight into the relationship between AGE accumulation and increased tissue failure. Our findings also added to the existing literature regarding crosslinking structures, indicating that AGEs had a greater effect along the fiber direction, while interlamellar radial crosslinks were improbable in the AF. In summary, the combined approach presented a powerful tool for examining multiscale structure-function relationships with disease progression in fiber-reinforced soft tissues, which is essential for developing effective therapeutic measures. STATEMENT OF SIGNIFICANCE: Increasing clinical evidence correlates diabetes with premature intervertebral disc failure, likely due to advanced glycation end-products (AGE) accumulation in the annulus fibrosus (AF). However, in vitro glycation reportedly increases AF tensile stiffness and toughness, contradicting clinical observations. Using a combined experimental-computational approach, our work shows that increases in AF bulk tensile mechanical properties with glycation are achieved at the risk of exposing the extrafibrillar matrix to increased stresses under physiologic deformations, which may increase tissue mechanical failure or trigger catabolic remodeling. Computational results indicate that crosslinks along the fiber direction account for 90% of the increased tissue stiffness with glycation, adding to the existing literature. These findings provide insight into the multiscale structure-function relationship between AGE accumulation and tissue failure.