Residual Impact of Previous Injury on Musculoskeletal Characteristics in Special Forces Operators

Background: Musculoskeletal injuries are a significant burden to United States Army Special Operations Forces. The advanced tactical skill level and physical training required of Army Special Operators highlights the need to optimize musculoskeletal characteristics to reduce the likelihood of suffering a recurrent injury. Purpose: To identify the residual impact of previous injury on musculoskeletal characteristics. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Isokinetic strength of the knee, shoulder, and back and flexibility of the shoulder and hamstrings were assessed as part of a comprehensive human performance protocol, and self-reported musculoskeletal injury history was obtained. Subjects were stratified based on previous history of low back, knee, or shoulder injury, and within-group and between-group comparisons were made for musculoskeletal variables. Results: Knee injury analysis showed no significant strength or flexibility differences. Shoulder injury analysis found internal rotation strength of the healthy subjects (H) was significantly higher compared with injured (I) and uninjured (U) limbs of the injured group (H, 60.8 ± 11.5 percent body weight [%BW]; I, 54.5 ± 10.5 %BW; U, 55.5 ± 11.3 %BW) (P = .014 [H vs I] and P = .05 [H vs U]). The external rotation/internal rotation strength ratio was significantly lower in the healthy subjects compared with injured and uninjured limbs of the injured group (H, 0.653 ± 0.122; I, 0.724 ± 0.121; U, 0.724 ± 0.124) (P = .026 [H vs I] and P = .018 [H vs U]). Posterior shoulder tightness was significantly different between the injured and uninjured limb of the injured group (I, 111.6° ± 9.4°; U, 114.4° ± 9.3°; P = .008). The back injury analysis found no significant strength differences between the healthy and injured groups. Conclusion: Few physical differences existed between operators with prior knee or back injury. However, operators with a previous history of shoulder injury demonstrated significantly less shoulder strength than uninjured operators as well as decreased shoulder flexibility on the injured side. All operators, regardless of prior injury, must perform the same tasks; therefore, a targeted injury rehabilitation/human performance training specifically focused on internal rotation strength and tightness of the posterior capsule may help reduce the risk for recurrence of injury. Operators presenting with musculoskeletal asymmetries and/or insufficient strength ratios may be predisposed to musculoskeletal injury. Clinical Relevance: Specific fitness programs to compensate for deficiencies in strength and flexibility need to be designed that may reduce the risk of injuries in Special Forces Operators

Normative Data for the NeuroCom Sensory Organization Test in US Military Special Operations Forces.

CONTEXT: Postural stability is the ability to control the center of mass in relation to a person\u27s base of support and can be affected by both musculoskeletal injury and traumatic brain injury. The NeuroCom Sensory Organization Test (SOT) can be used to objectively quantify impairments to postural stability. The ability of postural stability to predict injury and be used as an acute injury-evaluation tool makes it essential to the screening and rehabilitation process. To our knowledge, no published normative data for the SOT from a healthy, highly active population are available for use as a reference for clinical decision making. OBJECTIVE: To present a normative database of SOT scores from a US Military Special Operations population that can be used for future comparison. DESIGN: Cross-sectional study. SETTING: Human performance research laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 542 active military operators from Naval Special Warfare Combatant-Craft Crewmen (n = 149), Naval Special Warfare Command, Sea, Air, and Land (n = 101), US Army Special Operations Command (n = 171), and Air Force Special Operations Command (n = 121). MAIN OUTCOME MEASURE(S): Participants performed each of the 6 SOT conditions 3 times. Scores for each condition, total equilibrium composite score, and ratio scores for the somatosensory, visual, and vestibular systems were recorded. RESULTS: Differences were present across all groups for SOT conditions 1 (P \u3c .001), 2 (P = .001), 4 (P \u3e .001), 5 (P \u3e .001), and 6 (P = .001) and total equilibrium composite (P = .000), visual (P \u3e .001), vestibular (P = .002), and preference (P \u3e .001) NeuroCom scores. CONCLUSIONS: Statistical differences were evident in the distribution of postural stability across US Special Operations Forces personnel. This normative database for postural stability, as assessed by the NeuroCom SOT, can provide context when clinicians assess a Special Operations Forces population or any other groups that maintain a high level of conditioning and training

Partner-Drug Resistance and Population Substructuring of Artemisinin-Resistant Plasmodium falciparum in Cambodia

Plasmodium falciparum in western Cambodia has developed resistance to artemisinin and its partner drugs, causing frequent treatment failure. Understanding this evolution can inform the deployment of new therapies. We investigated the genetic architecture of 78 falciparum isolates using whole-genome sequencing, correlating results to in vivo and ex vivo drug resistance and exploring the relationship between population structure, demographic history, and partner drug resistance. Principle component analysis, network analysis and demographic inference identified a diverse central population with three clusters of clonally expanding parasite populations, each associated with specific K13 artemisinin resistance alleles and partner drug resistance profiles which were consistent with the sequential deployment of artemisinin combination therapies in the region. One cluster displayed ex vivo piperaquine resistance and mefloquine sensitivity with a high rate of in vivo failure of dihydroartemisinin-piperaquine. Another cluster displayed ex vivo mefloquine resistance and piperaquine sensitivity with high in vivo efficacy of dihydroartemisinin-piperaquine. The final cluster was clonal and displayed intermediate sensitivity to both drugs. Variations in recently described piperaquine resistance markers did not explain the difference in mean IC90 or clinical failures between the high and intermediate piperaquine resistance groups, suggesting additional loci may be involved in resistance. The results highlight an important role for partner drug resistance in shaping the P. falciparum genetic landscape in Southeast Asia and suggest that further work is needed to evaluate for other mutations that drive piperaquine resistance

An ab initio and AIM investigation into the hydration of 2-thioxanthine

<p>Abstract</p> <p>Background</p> <p>Hydration is a universal phenomenon in nature. The interactions between biomolecules and water of hydration play a pivotal role in molecular biology. 2-Thioxanthine (2TX), a thio-modified nucleic acid base, is of significant interest as a DNA inhibitor yet its interactions with hydration water have not been investigated either computationally or experimentally. Here in, we reported an <it>ab initio </it>study of the hydration of 2TX, revealing water can form seven hydrated complexes.</p> <p>Results</p> <p>Hydrogen-bond (H-bond) interactions in 1:1 complexes of 2TX with water are studied at the MP2/6-311G(d, p) and B3LYP/6-311G(d, p) levels. Seven 2TX^...H₂O hydrogen bonded complexes have been theoretically identified and reported for the first time. The proton affinities (PAs) of the O, S, and N atoms and deprotonantion enthalpies (DPEs) of different N-H bonds in 2TX are calculated, factors surrounding why the seven complexes have different hydrogen bond energies are discussed. The theoretical infrared and NMR spectra of hydrated 2TX complexes are reported to probe the characteristics of the proposed H-bonds. An improper blue-shifting H-bond with a shortened C-H bond was found in one case. NBO and AIM analysis were carried out to explain the formation of improper blue-shifting H-bonds, and the H-bonding characteristics are discussed.</p> <p>Conclusion</p> <p>2TX can interact with water by five different H-bonding regimes, N-H^...O, O-H^...N, O-H^...O, O-H^...S and C-H^...O, all of which are medium strength hydrogen bonds. The most stable H-bond complex has a closed structure with two hydrogen bonds (N(7)-H^...O and O-H^...O), whereas the least stable one has an open structure with one H-bond. The interaction energies of the studied complexes are correlated to the PA and DPE involved in H-bond formation. After formation of H-bonds, the calculated IR and NMR spectra of the 2TX-water complexes change greatly, which serves to identify the hydration of 2TX.</p

Functional annotation of human long noncoding RNAs via molecular phenotyping

Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-todate lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.Peer reviewe

Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants

High-throughput nanopore sequencing of Treponema pallidum tandem repeat genes arp and tp0470 reveals clade-specific patterns and recapitulates global whole genome phylogeny

Sequencing of most Treponema pallidum genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein (arp). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical samples collected from ten countries on six continents. Both tp0470 and arp repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging. The number of tp0470 repeats is on average appears to be higher in Nichols-like clade strains than in SS14-like clade strains. Consistent with previous studies, we found that 14-repeat arp sequences predominate across both major clades, but the combination and order of repeat type varies among subclades, with many arp sequence variants limited to a single subclade. Although strains that were closely related by whole genome sequencing frequently had the same arp repeat length, this was not always the case. Structural modeling of TP0470 suggested that the eight residue repeats form an extended α-helix, predicted to be periplasmic. Modeling of the ARP revealed a C-terminal sporulation-related repeat (SPOR) domain, predicted to bind denuded peptidoglycan, with repeat regions possibly incorporated into a highly charged β-sheet. Outside of the repeats, all TP0470 and ARP amino acid sequences were identical. Together, our data, along with functional considerations, suggests that both TP0470 and ARP proteins may be involved in T. pallidum cell envelope remodeling and homeostasis, with their highly plastic repeat regions playing as-yet-undetermined roles

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant