Telehealth for a better service delivery in orthopaedic surgery.

Telehealth has the potential to change the way we approach patient care. From virtual consenting to reducing carbon emissions, costs, and waiting times, it is a powerful tool in our clinical armamentarium. There is mounting evidence that remote diagnostic evaluation and decision-making have reached an acceptable level of accuracy and can safely be adopted in orthopaedic surgery. Furthermore, patients' and surgeons' satisfaction with virtual appointments are comparable to in-person consultations. Challenges to the widespread use of telehealth should, however, be acknowledged and include the cost of installation, training, maintenance, and accessibility. It is also vital that clinicians are conscious of the medicolegal and ethical considerations surrounding the medium and adhere strictly to the relevant data protection legislation and storage framework. It remains to be seen how organizations harness the full spectrum of the technology to facilitate effective patient care.

The impact of the menstrual cycle on orthopaedic sports injuries in female athletes.

There is a disparity in sport-related injuries between sexes, with females sustaining non-contact musculoskeletal injuries at a higher rate. Anterior cruciate ligament ruptures are between two and eight times more common than in males, and females also have a higher incidence of ankle sprains, patellofemoral pain, and bone stress injuries. The sequelae of such injuries can be devastating to an athlete, resulting in time out of sport, surgery, and the early onset of osteoarthritis. It is important to identify the causes of this disparity and introduce prevention programmes to reduce the incidence of these injuries. A natural difference reflects the effect of reproductive hormones in females, which have receptors in certain musculoskeletal tissues. Relaxin increases ligamentous laxity. Oestrogen decreases the synthesis of collagen and progesterone does the opposite. Insufficient diet and intensive training can lead to menstrual irregularities, which are common in female athletes and result in injury, whereas oral contraception may have a protective effect against certain injuries. It is important for coaches, physiotherapists, nutritionists, doctors, and athletes to be aware of these issues and to implement preventive measures. This annotation explores the relationship between the menstrual cycle and orthopaedic sports injuries in pre-menopausal females, and proposes recommendations to mitigate the risk of sustaining these injuries.

The Effect of Counterfactual Potency on Behavioral Intentions.

This research examines how counterfactual potency (CP), the multiplicative effect of the likelihoods of the "if" and "then" clauses of counterfactuals, determines the effects of counterfactuals on behavioral intentions. In Study 1, we found that participants who read highly (vs. minimally) mutable vignettes perceived the counterfactuals as more likely and endorsed relevant intentions more. However, CP did not mediate the effect of mutability on intentions. In Studies 2 and 3, we found that CP directly affected intentions and also mediated the effects of mutability on intentions when mutability was specifically manipulated via controllability (Study 2) or norm violation (Study 3). Finally, Study 4 used archival reaction time data to show that more concrete counterfactuals were perceived as more likely and subsequently facilitated intentions. Taken together, the current research provides evidence that more likely counterfactuals facilitate behavioral intentions.

Insecticidal and synergistic activity of dsRNAs targeting buprofezin-specific genes against the small brown planthopper, Laodelphax striatellus.

The small brown planthopper, Laodelphax striatellus, is a dangerous pest in rice fields. Although buprofezin has been used to control L. striatellus for more than a decade, the occurrence of buprofezin-resistant L. striatellus has been recently reported. To develop an alternative pest control strategy, comparative transcriptome analysis of buprofezin-treated and nontreated L. striatellus was performed to screen the buprofezin-specific target genes for RNA interference (RNAi) application. Among six genes downregulated in the buprofezin-treated L. striatellus, RNAi-based silencing of the lipophorin precursor, endocuticle structure glycoprotein, and chitin synthase significantly induced the lethality of L. striatellus in a concentration-dependent manner. In addition, a cocktail of double-stranded RNAs against these three genes showed synergistic effects with buprofezin. These results provide RNAi-based effective approaches to control L. striatellus as well as an efficient method to identify novel target genes for RNAi application.

Development of a Bacillus thuringiensis based dsRNA production platform to control sacbrood virus in Apis cerana.

BACKGROUND: Sacbrood virus (SBV) is a fatal viruses that infects the Asian honey bee, Apis cerana in Korea. Recently, RNA interference (RNAi) has been suggested as a promising strategy for the suppression of honey bee viruses. For the efficient control of SBV infection using RNAi, simple and cost-effective methods to produce double-stranded RNA (dsRNA) are needed. RESULTS: To develop a dsRNA production platform using Bacillus thuringiensis (Bt), pBTdsSBV-VP1 vector was constructed in which the SBV vp1 gene was located between two oppositely oriented cyt promoters. Both strands of the vp1 gene were bidirectionally transcribed under the control of the sporulation-dependent cyt promoter in Bt cells transformed with pBTdsSBV-VP1, and the resulting dsRNA was easily extracted from the Bt transformant, Bt 4Q7/pBTdsSBV-VP1, by inducing its autolysis. The replication of SBV was dramatically suppressed in A. cerana workers who ingested the dsRNA produced from the Bt 4Q7/pBTdsSBV-VP1. CONCLUSION: In this study, we successfully silenced SBV in its host, A. cerana, by the application of exogenous dsRNA produced from an entomopathogenic bacteria, Bt. These results suggested that Bt could be a useful dsRNA production platform to control viral pathogens in their host insects. © 2019 Society of Chemical Industry.

Pathogenic Autoreactive T and B Cells Cross-React with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity.

Given the immense antigenic load present in the microbiome, we hypothesized that microbiota mimotopes can be a persistent trigger in human autoimmunity via cross-reactivity. Using antiphospholipid syndrome (APS) as a model, we demonstrate cross-reactivity between non-orthologous mimotopes expressed by a common human gut commensal, Roseburia intestinalis (R. int), and T and B cell autoepitopes in the APS autoantigen ß2-glycoprotein I (ß2GPI). Autoantigen-reactive CD4+ memory T cell clones and an APS-derived, pathogenic monoclonal antibody cross-reacted with R. int mimotopes. Core-sequence-dependent anti-R. int mimotope IgG titers were significantly elevated in APS patients and correlated with anti-ß2GPI IgG autoantibodies. R. int immunization of mice induced ß2GPI-specific lymphocytes and autoantibodies. Oral gavage of susceptible mice with R. int induced anti-human ß2GPI autoantibodies and autoimmune pathologies. Together, these data support a role for non-orthologous commensal-host cross-reactivity in the development and persistence of autoimmunity in APS, which may apply more broadly to human autoimmune disease.

Evaluation and utilization of preassembled frozen commercial fast real-time qPCR master mixes for detection of cytomegalovirus and BK virus.

Quantitative DNA detection of cytomegalovirus (CMV) and BK virus (BKV) is critical in the management of transplant patients. Quantitative laboratory-developed procedures for CMV and BKV have been described in which much of the processing is automated, resulting in rapid, reproducible, and high-throughput testing of transplant patients. To increase the efficiency of such assays, the performance and stability of four commercial preassembled frozen fast qPCR master mixes (Roche FastStart Universal Probe Master Mix with Rox, Bio-Rad SsoFast Probes Supermix with Rox, Life Technologies TaqMan FastAdvanced Master Mix, and Life Technologies Fast Universal PCR Master Mix), in combination with in-house designed primers and probes, was evaluated using controls and standards from standard CMV and BK assays. A subsequent parallel evaluation using patient samples was performed comparing the performance of freshly prepared assay mixes versus aliquoted frozen master mixes made with two of the fast qPCR mixes (Life Technologies TaqMan FastAdvanced Master Mix, and Bio-Rad SsoFast Probes Supermix with Rox), chosen based on their performance and compatibility with existing PCR cycling conditions. The data demonstrate that the frozen master mixes retain excellent performance over a period of at least 10 weeks. During the parallel testing using clinical specimens, no difference in quantitative results was observed between the preassembled frozen master mixes and freshly prepared master mixes. Preassembled fast real-time qPCR frozen master mixes perform well and represent an additional strategy laboratories can implement to reduce assay preparation times, and to minimize technical errors and effort necessary to perform clinical PCR.

Clinical, laboratory and radiologic characteristics of 2009 pandemic influenza A/H1N1 pneumonia: primary influenza pneumonia versus concomitant/secondary bacterial pneumonia.

BACKGROUND: Although influenza virus usually involves the upper respiratory tract, pneumonia was seen more frequently with the 2009 pandemic influenza A/H1N1 than with seasonal influenza. METHODS: From September 1, 2009, to January 31, 2010, a specialized clinic for patients (aged ≥15 years) with ILI was operated in Korea University Guro Hospital. RT-PCR assay was performed to diagnose 2009 pandemic influenza A/H1N1. A retrospective case-case-control study was performed to determine the predictive factors for influenza pneumonia and to discriminate concomitant/secondary bacterial pneumonia from primary influenza pneumonia during the 2009-2010 pandemic. RESULTS: During the study period, the proportions of fatal cases and pneumonia development were 0·12% and 1·59%, respectively. Patients with pneumonic influenza were less likely to have nasal symptoms and extra-pulmonary symptoms (myalgia, headache, and diarrhea) compared to patients with non-pneumonic influenza. Crackle was audible in just about half of the patients with pneumonic influenza (38·5% of patients with primary influenza pneumonia and 53·3% of patients with concomitant/secondary bacterial pneumonia). Procalcitonin, C-reactive protein (CRP), and lactate dehydrogenase were markedly increased in patients with influenza pneumonia. Furthermore, procalcitonin (cutoff value 0·35 ng/ml, sensitivity 81·8%, and specificity 66·7%) and CRP (cutoff value 86·5 mg/IU, sensitivity 81·8%, and specificity 59·3%) were discriminative between patients with concomitant/secondary bacterial pneumonia and patients with primary influenza pneumonia. CONCLUSIONS: Considering the subtle manifestations of 2009 pandemic influenza A/H1N1 pneumonia in the early stage, high clinical suspicion is required to detect this condition. Both procalcitonin and CRP would be helpful to differentiate primary influenza pneumonia from concomitant/secondary bacterial pneumonia.

Group-specific regional white matter abnormality revealed in diffusion tensor imaging of medial temporal lobe epilepsy without hippocampal sclerosis.

PURPOSE: In comparison to temporal lobe epilepsy (TLE) patients with hippocampal sclerosis (TLE-HS), TLE patients without HS (TLE-NH) have a similar clinical course but may result in worse surgical outcome. We investigated whether the clinical features related to the lack of HS in TLE patients (TLE-NH) can be explained by water diffusion abnormalities throughout diffusion tensor imaging (DTI) by voxel-based analysis. METHODS: Nineteen patients with TLE-HS (left/right TLE 12:7), 18 patients with TLE-NH (left/right TLE 10:8), and 20 controls were included in the study. By statistical parametric mapping (SPM2), the diffusion properties specific to disease characteristics (TLE-HS vs. TLE-NH) were analyzed. RESULTS: In TLE-HS, we found the areas of increased mean diffusivity (MD) in their ipsilateral temporal and extratemporal areas including the hippocampus, parahippocampal, and frontoparietal regions. Left TLE-HS showed a characteristic MD increase in the ipsilateral posterior cingulum, isthmus of corpus callosum, and contralateral occipital and temporal regions, which was not observed in right TLE-HS group. In left TLE-NH, two regions of increased MD were observed in the ipsilateral posterior fornix (within fusiform gyrus) and posterior cingulum. Right TLE-NH did not show any increased MD. DISCUSSION: In left TLE-NH, we could find the water diffusion change along the posterior cingulum, which was quite different from the extensive abnormality from TLE-HS. In addition, there was a lesion-side-specific distribution (left predominant) of pathology in mesial TLE. This provides a possibility that TLE-NH is a heterogeneous or entity different from TLE-HS.

Association between CRHR1 polymorphism and improved lung function in response to inhaled corticosteroid in patients with COPD.

BACKGROUND AND OBJECTIVE: Inhaled corticosteroids are used to treat COPD and asthma. An association between sequence variants in the corticotrophin-releasing hormone receptor 1 (CRHR1) gene and improved lung function in asthmatics treated with inhaled corticosteroids was reported recently. This study investigated the association between the change in lung function in response to inhaled corticosteroids and single-nucleotide CRHR1 polymorphisms in patients with COPD. METHODS: COPD patients (n = 87) with a positive smoking history were recruited from the pulmonary clinics of 11 hospitals in Korea. Patients were treated with fluticasone propionate and salmeterol for 12 weeks and lung function was measured at baseline and after the 12-week treatment. Eighty-four of the 87 subjects were successfully genotyped. RESULTS: Seventy-one patients with the wild-type GG genotype and 13 patients with the heterozygous GT genotype in rs242 941 were evaluated. After 12-week treatment, the change in FEV(1) was significantly higher in patients with wild-type GG genotype (6.0 +/- 0.8% of predicted FEV(1)) than in GT heterozygotes (-0.8 +/- 1.8, P = 0.003). CONCLUSIONS: Improved FEV(1) following inhaled corticosteroid and a long-acting beta2-agonist was associated with CRHR1 genetic polymorphism in patients with COPD.

Impact of depression and its treatment on the bones of growing children.

Depression in adults has been linked to reduced bone mineral density (BMD), osteoporosis, and increased incidence of fractures. Physiologic factors, such as hypothalamic-pituitary-adrenal axis dysfunction and increased circulation of inflammatory cytokines, may adversely impact bone metabolism. In addition, behavioral factors, such as reduced physical activity and altered dietary intake (especially of bone-related nutrients such as calcium and vitamin D), may be implicated. Antidepressant medications also may have an impact on BMD. Childhood and adolescence may be times of particular vulnerability to the adverse effects of depression due to the rapid bone mineral accrual that occurs during periods of growth. This article will review potential contributing factors and resulting consequences of depression on BMD in these populations and also explore areas of needed research.

Frequent met oncogene amplification in a Brca1/Trp53 mouse model of mammary tumorigenesis.

In a screen for gene copy number alterations in mouse mammary tumors initiated by loss of the Brca1 and Trp53 genes, we observed that the majority (11 of 15; 73%) had high-level amplification of wild-type Met, encoding a growth factor receptor implicated in tumor progression. Met amplification was localized to unstable double minute chromosomes and was uniquely found in mouse breast tumors driven by loss of Brca1 and Trp53. Whereas analogous MET amplification was not found in human breast cancers, the identification of a dominant somatic genetic lesion in the Brca1/Trp53 mouse model suggests that recurrent secondary hits may also exist in BRCA1-initiated human breast cancer.

Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752.

The success of molecular targeted therapy in cancer may depend on the selection of appropriate tumor types whose survival depends on the drug target, so-called "oncogene addiction." Preclinical approaches to defining drug-responsive subsets are needed if initial clinical trials are to be directed at the most susceptible patient population. Here, we show that gastric cancer cells with high-level stable chromosomal amplification of the growth factor receptor MET are extraordinarily susceptible to the selective inhibitor PHA-665752. Although MET activation has primarily been linked with tumor cell migration and invasiveness, the amplified wild-type MET in these cells is constitutively activated, and its continued signaling is required for cell survival. Treatment with PHA-665752 triggers massive apoptosis in 5 of 5 gastric cancer cell lines with MET amplification but in 0 of 12 without increased gene copy numbers (P = 0.00016). MET amplification may thus identify a subset of epithelial cancers that are uniquely sensitive to disruption of this pathway and define a patient group that is appropriate for clinical trials of targeted therapy using MET inhibitors.

Dual growth factor delivery and controlled scaffold degradation enhance in vivo bone formation by transplanted bone marrow stromal cells.

Supraphysiological concentrations of exogenous growth factors are typically required to obtain bone regeneration, and it is unclear why lower levels are not effective. We hypothesized that delivery of bone progenitor cells along with appropriate combinations of growth factors and scaffold characteristics would allow physiological doses of proteins to be used for therapeutic bone regeneration. We tested this hypothesis by measuring bone formation by rat bone marrow stromal cells (BMSCs) transplanted ectopically in SCID mice using alginate hydrogels. The alginate was gamma-irradiated to vary the degradation rate and then covalently modified with RGD-containing peptides to control cell behavior. In the same delivery vehicle, we incorporated bone morphogenetic protein-2 (BMP2) and transforming growth factor-beta3 (TGF-beta3), either individually or in combination. Individual delivery of BMP2 or TGF-beta3 resulted in negligible bone tissue formation up to 22 weeks, regardless of the implant degradation rate. In contrast, when growth factors were delivered together from readily degradable hydrogels, there was significant bone formation by the transplanted BMSCs as early as 6 weeks after implantation. Furthermore, bone formation, which appeared to occur by endochondral ossification, was achieved with the dual growth factor condition at protein concentrations that were more than an order of magnitude less than those reported previously to be necessary for bone formation. These data demonstrate that appropriate combinations of soluble and biomaterial-mediated regulatory signals in cell-based tissue engineering systems can result in both more efficient and more effective tissue regeneration.

Role of ATP-binding motifs on DNA-binding activity and biological function of Rhp51, a Rad51 homologue in fission yeast.

Rhp51, a RecA and Rad51 homologue of Schizosaccharomyces pombe, plays a pivotal role in homologous recombination and recombinational repair. It has a set of the well-conserved type A and type B ATP-binding motifs, which are highly conserved in all RecA homologues. In a previous study [Kim, Lee, Park, Park and Park (2001) Nucleic Acids Res. 29, 1724-1732], we reported that a single mutation of the conserved lysine in A motif [Lys(155)-->Ala (K155A)] destroyed the DNA repair ability of Rhp51 and that overexpression of this mutant protein conferred dominant negativity. In the present paper, we investigated DNA-binding properties of recombinant Rhp51 and its mutant proteins. Purified Rhp51 protein showed ATP-dependent double- and single-strand DNA-binding activities. To characterize the role of ATP-binding motifs, we generated Rhp51 K155A and Rhp51 Asp(244)-->Gln (D244Q), which have a single amino acid substitution in A and B motifs respectively. Interestingly, K155A and D244Q mutations impaired ATP-dependent DNA binding in a different manner. K155A lost the DNA binding itself, whereas D244Q maintained the binding ability but lost the ATP dependency. However, despite the difference in DNA-binding ability, both mutations failed to rescue the methylmethane sulphonate and UV sensitivity of the rhp51Delta mutant. Together, these results suggested that not only the DNA binding but also the ATP dependence in DNA binding is required for proper in vivo functioning of Rhp51.