Test-Retest Reliability of a 4-Minute All-Out Critical Force Test in Rock Climbers

International Journal of Exercise Science 16(4): 912-923, 2023. The purpose of this study was to assess the test-retest reliability of a 4-minute all-out critical force test in well-trained rock climbers. Thirteen rock climbers (n=4 females) completed a familiarization session and two all-out critical force tests on different days. During each trial, participants completed 24 repetitions of 7s right-handed, maximal effort hangs from a 20mm edge interspersed with 3 s rest. The end-test force (EF; i.e., critical force), impulse above EF (IEF), and peak force achieved durin g the test were analyzed with paired t-tests to determine differences between trials. Intraclass correlation coefficient (ICC), coefficient of variation (CV), and Bland-Altman analysis were performed to quantify the relative and absolute reliability of the measure, respectively. The level of significance for this study was set at p\u3c0.05. There were no significant differences between trials for any of the reported variables (P≥0.455). For EF, IEF, and peak force, ICC was 0.848, 0.820, and 0.938, respectively; and CV was 21.0%, 13.2%, and 5.6%, respectively. Bland-Altman analyses showed a mean relative bias of -2.3%, -2.8%, and -1.3%, with 95% limits of agreement (LoA) of -62.6% to 58.1%, -40.5% to 30.9%, and -17.2% to 14.6% for EF, IEF, and peak force, respectively, however linear regression revealed a significant proportional bias for EF (p = 0.026, R2 = 0.377). The reliability of this protocol was good to excellent for all parameters; however, there was larger intra-individual variability for EF and IEF. This study suggests that when using the 4-min all-out critical force test in rock climbers, coaches and athletes should be aware that there may be a trade-off between the test’s practicality and the precision of its results

Multi-contrast imaging and digital refocusing on a mobile microscope with a domed LED array

We demonstrate the design and application of an add-on device for improving the diagnostic and research capabilities of CellScope--a low-cost, smartphone-based point-of-care microscope. We replace the single LED illumination of the original CellScope with a programmable domed LED array. By leveraging recent advances in computational illumination, this new device enables simultaneous multi-contrast imaging with brightfield, darkfield, and phase imaging modes. Further, we scan through illumination angles to capture lightfield datasets, which can be used to recover 3D intensity and phase images without any hardware changes. This digital refocusing procedure can be used for either 3D imaging or software-only focus correction, reducing the need for precise mechanical focusing during field experiments. All acquisition and processing is performed on the mobile phone and controlled through a smartphone application, making the computational microscope compact and portable. Using multiple samples and different objective magnifications, we demonstrate that the performance of our device is comparable to that of a commercial microscope. This unique device platform extends the field imaging capabilities of CellScope, opening up new clinical and research possibilities

Investigation of a dual siRNA/chemotherapy delivery system for breast cancer therapy

Multidrug resistance (MDR) is a problem that is often associated with a poor clinical outcome in chemotherapeutic cancer treatment. MDR may potentially be overcome by utilizing synergistic approaches, such as combining siRNA gene therapy and chemotherapy to target different mechanisms of apoptosis. In this study, a strategy is presented for developing multicomponent nanomedicines using orthogonal and compatible chemistries that lead to effective nanotherapeutics. Hyperbranched polymers were used as drug carriers that contained doxorubicin (DOX), attached via a pH-sensitive hydrazone linkage, and ataxia-telangiectasia mutated (ATM) siRNA, attached via a redox-sensitive disulfide group. This nanomedicine also contained cyanine 5 (Cy5) as a diagnostic tracer as well as in-house developed bispecific antibodies that allowed targeting of the epidermal growth factor receptor (EGFR) present on tumor tissue. Highly efficient coupling of siRNA was achieved with 80% of thiol end-groups on the hyperbranched polymer coupling with siRNA. This attachment was reversible, with the majority of siRNA released in vitro under reducing conditions as desired. In cellular studies, the nanomedicine exhibited increased DNA damage and cancer cell inhibition compared to the individual treatments. Moreover, the nanomedicine has great potential to suppress the metabolism of cancer cells including both mitochondrial respiration and glycolytic activity, with enhanced efficacy observed when targeted to the cell surface protein EGFR. Our findings indicated that co-delivery of ATM siRNA and DOX serves as a more efficient therapeutic avenue in cancer treatment than delivery of the single species and offers a potential route for synergistically enhanced gene therapy

Using Gene Expression Signatures to Identify Novel Treatment Strategies in Gulf War Illness

Background Gulf War Illness (GWI) is a complex multi-symptom disorder that affects up to one in three veterans of this 1991 conflict and for which no effective treatment has been found. Discovering novel treatment strategies for such a complex chronic illness is extremely expensive, carries a high probability of failure and a lengthy cycle time. Repurposing Food and Drug Administration approved drugs offers a cost-effective solution with a significantly abbreviated timeline. Methods Here, we explore drug re-purposing opportunities in GWI by combining systems biology and bioinformatics techniques with pharmacogenomic information to find overlapping elements in gene expression linking GWI to successfully treated diseases. Gene modules were defined based on cellular function and their activation estimated from the differential expression of each module’s constituent genes. These gene modules were then cross-referenced with drug atlas and pharmacogenomic databases to identify agents currently used successfully for treatment in other diseases. To explore the clinical use of these drugs in illnesses similar to GWI we compared gene expression patterns in modules that were significantly expressed in GWI with expression patterns in those same modules in other illnesses. Results We found 19 functional modules with significantly altered gene expression patterns in GWI. Within these modules, 45 genes were documented drug targets. Illnesses with highly correlated gene expression patterns overlapping considerably with GWI were found in 18 of the disease conditions studied. Brain, muscular and autoimmune disorders composed the bulk of these. Conclusion Of the associated drugs, immunosuppressants currently used in treating rheumatoid arthritis, and hormone based therapies were identified as the best available candidates for treating GWI symptoms

Confinement of Therapeutic Enzymes in Selectively Permeable Polymer Vesicles by Polymerization-Induced Self-Assembly (PISA) Reduces Antibody Binding and Proteolytic Susceptibility

Covalent PEGylation of biologics has been widely employed to reduce immunogenicity, while improving stability and half-life in vivo. This approach requires covalent protein modification, creating a new entity. An alternative approach is stabilization by encapsulation into polymersomes; however this typically requires multiple steps, and the segregation requires the vesicles to be permeable to retain function. Herein, we demonstrate the one-pot synthesis of therapeutic enzyme-loaded vesicles with size-selective permeability using polymerization-induced self-assembly (PISA) enabling the encapsulated enzyme to function from within a confined domain. This strategy increased the proteolytic stability and reduced antibody recognition compared to the free protein or a PEGylated conjugate, thereby reducing potential dose frequency and the risk of immune response. Finally, the efficacy of encapsulated l-asparaginase (clinically used for leukemia treatment) against a cancer line was demonstrated, and its biodistribution and circulation behavior in vivo was compared to the free enzyme, highlighting this methodology as an attractive alternative to the covalent PEGylation of enzymes

Applicant Reactions to the AAMC Standardized Video Interview During the 2018 Application Cycle

PURPOSE: This study examined applicant reactions to the Association of American Medical Colleges (AAMC) Standardized Video Interview (SVI) during its first year of operational use in emergency medicine (EM) residency program selection in order to identify strategies to improve applicants\u27 SVI experience and attitudes. METHOD: Individuals who self-classified as EM applicants applying in the Electronic Residency Application Service 2018 cycle and completed the SVI in summer 2017 were invited to participate in two surveys. Survey 1, which focused on procedural issues, was administered immediately after SVI completion. Survey 2, which focused on applicants\u27 SVI experience, was administered in fall 2017, after SVI scores were released. RESULTS: The response rates for surveys 1 and 2 were 82.3% (2,906/3,532) and 58.7% (2,074/3,532), respectively. Applicant reactions varied by aspect of the SVI studied and their SVI total scores. Most applicants were satisfied with most procedural aspects of the SVI, but most applicants were not satisfied with the SVI overall or with their total SVI scores. About 20-30% of applicants had neutral opinions about most aspects of the SVI. Negative reactions to the SVI were stronger for applicants who scored lower on the SVI. CONCLUSIONS: Applicants had generally negative reactions to the SVI. Most were skeptical of its ability to assess the target competencies and its potential to add value to the selection process. Applicant acceptance and appreciation of the SVI will be critical to the SVI\u27s acceptance by the graduate medical education community

The AAMC Standardized Video Interview: Reactions and Use by Residency Programs During the 2018 Application Cycle

PURPOSE: To evaluate how emergency medicine (EM) residency programs perceived and used Association of American Medical Colleges (AAMC) SVI total scores and videos during the Electronic Residency Application Service (ERAS) 2018 cycle. METHOD: Study 1 (November 2017) used a program director survey to evaluate user reactions to the SVI following the first year of operational use. Study 2 (January 2018) analyzed program usage of SVI video responses using data collected through the AAMC Program Director\u27s Workstation. RESULTS: Results from the survey (125/175 programs, 71% response rate) and video usage analysis suggested programs viewed videos out of curiosity and to understand the range of SVI total scores. Programs were more likely to view videos for attendees of U.S. MD-granting medical schools and applicants with higher United States Medical Licensing Examination Step 1 scores, but there were no differences by gender or race/ethnicity. More than half of programs that did not use SVI total scores in their selection processes were unsure of how to incorporate them (36/58, 62%) and wanted additional research on utility (33/58, 57%). More than half of programs indicated being at least somewhat likely to use SVI total scores (55/97; 57%) and videos (52/99; 53%) in the future. CONCLUSIONS: Program reactions on the utility and ease of use of SVI total scores were mixed. Survey results indicate programs used the SVI cautiously in their selection processes, consistent with AAMC recommendations. Future surveys of SVI users will help the AAMC gauge improvements in user acceptance and familiarity with the SVI

No pain, no gain? The effects of pain-promoting neuropeptides and neurotrophins on fracture healing

Neuropeptides and neurotrophins are key regulators of peripheral nociceptive nerves and contribute to the induction, sensitization, and maintenance of pain. It is now known that these peptides also regulate non-neuronal tissues, including bone. Here, we review the effects of numerous neuropeptides and neurotrophins on fracture healing. The neuropeptides calcitonin-gene related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating peptide (PACAP) have varying effects on osteoclastic and osteoblastic activity. Ultimately, CGRP and SP both accelerate fracture healing, while VIP and PACAP seem to negatively impact healing. Unlike the aforementioned neuropeptides, the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have more uniform effects. Both factors upregulate osteoblastic activity, osteoclastic activity, and, in vivo, stimulate osteogenesis to promote fracture healing. Future research will need to clarify the exact mechanism by which the neuropeptides and neurotrophins influence fracture healing. Specifically, understanding the optimal expression patterns for these proteins in the fracture healing process may lead to therapies that can maximize their bone-healing capabilities and minimize their pain-promoting effects. Finally, further examination of protein-sequestering antibodies and/or small molecule agonists and antagonists may lead to new therapies that can decrease the rate of delayed union/nonunion outcomes and fracture-associated pain

Dynamic edge effects in small mammal communities across a conservation-agricultural interface in Swaziland

Across the planet, high-intensity farming has transformed native vegetation into monocultures, decreasing biodiversity on a landscape scale. Yet landscape-scale changes to biodiversity and community structure often emerge from processes operating at local scales. One common process that can explain changes in biodiversity and community structure is the creation of abrupt habitat edges, which, in turn, generate edge effects. Such effects, while incredibly common, can be highly variable across space and time; however, we currently lack a general analytical framework that can adequately capture such spatio-temporal variability. We extend previous approaches for estimating edge effects to a non-linear mixed modeling framework that captures such spatio-temporal heterogeneity and apply it to understand how agricultural land-uses alter wildlife communities. We trapped small mammals along a conservation-agriculture land-use interface extending 375 m into sugarcane plantations and conservation land-uses at three sites during dry and wet seasons in Swaziland, Africa. Sugarcane plantations had significant reductions in species richness and heterogeneity, and showed an increase in community similarity, suggesting a more homogenized small mammal community. Furthermore, our modeling framework identified strong variation in edge effects on communities across sites and seasons. Using small mammals as an indicator, intensive agricultural practices appear to create high-density communities of generalist species while isolating interior species in less than 225 m. These results illustrate how agricultural land-use can reduce diversity across the landscape and that effects can be masked or magnified, depending on local conditions. Taken together, our results emphasize the need to create or retain natural habitat features in agricultural mosaics.Texas A&M Agrilife Researchhttp://www.plosone.orgam2013Zoology and EntomologyMammal Research Institut