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Background: The tendons within the soleus muscle are commonly utilized to delineate location of injury for soleus muscle strains. Strains within the soleus frequently involve the myotendinous (MTJ) or myofascial (MFJ) junctions, although spatial relationship between these tendinous structures are not well understood. This study aimed to structurally identify the MTJs and MFJs within the soleus as a starting point to understanding the distribution of connective tissue for further anatomical classification. Methods: Forty (n = 40) soleus muscles, representing left and right sides from twenty (n = 20) formalin-embalmed cadavers (average age 78 years old; 10 males, 10 females) were dissected in-situ to analyze the distribution and orientation of the MTJs and MFJs within classified morphological variants. Muscles were cut in cross-section at three measured locations, proximal, middle, and distal, which allowed for analyzation of tendons through the course of the muscle. Additionally, anterior surfaces of morphological variants were visualized and reconstructed in three dimensions using a handheld blue light 3D scanner. Results: The study revealed five morphological variants. Bipennate-Midline (n = 25), Bipennate-Medial Deviation (n = 6), Bipennate-Lateral Deviation (n = 3), Unipennate (n = 3), and Hypopennate (n = 3). Muscles included an anterior aponeurosis that was split into medial and lateral components, with each side made up of interconnections between the MTJ and MJF. The average width of the medial aponeurosis was greatest in the middle location, while the average lateral aponeurotic width decreased from proximal to distal. Regression analysis at the middle location revealed that 65 % of the change in width of the medial aponeuroses is due to the width of the medial MFJ. Conclusions: Proximal-to-distal interconnections between the lateral and medial anterior aponeuroses and their corresponding MTJs and MFJs likely play a role in soleus injury patterns, especially in morphological variants. Awareness of anatomical variations in the location and orientation of these tendinous relationships is crucial for understanding lesions on diagnostic imaging.

Background: To optimize patients' functional external rotation outcomes, reverse total shoulder arthroplasties (rTSAs) including a latissimus dorsi tendon transfer were undertaken with promising early results and no significant increase in complications in comparison to traditional rTSAs. This was especially utilized for patients with a pronounced combined loss of elevation and external rotation. The purpose of this study is to evaluate and synthesize the findings of all relevant publications assessing the outcomes of rTSAs with associated latissimus dorsi transfer. Methods: We thoroughly searched the literature within the PubMed database using a standardized methodology. For our inclusion criteria, we included any study regarding rTSAs that contained functional outcome scores for postoperative range of motion (such as elevation, external rotation, etc.) or postoperative outcomes such as complications (reoperation, infection, etc.) and patient satisfaction. For the extraction of data, we used pilot-tested Google Forms to record extracted data. These data were then converted to spreadsheets (Microsoft Excel [Microsoft, Redmond, WA, USA]). This was done on 2 separate scenarios by 2 authors to ensure accuracy. We used the modified Coleman Methodology Score to assess the methodological quality of the studies in our samples. Meta-analysis mathematics and statistical analysis were performed using Stata software 17 (StataCorp, College Station, TX, USA). Results: Our search returned a total of 12 studies containing data of 213 shoulders receiving RTSAs with a latissimus dorsi transfer. Functional outcomes were available for 160 shoulders. The mean preoperative elevation of the affected shoulder was 73.57 degrees, and the mean postoperative elevation was 141.80 degrees. For external rotation, the mean preoperative average was −6.71 degrees, and the mean postoperative average was 22.73 degrees. The absolute Constant score average was 31.56 preoperatively, while the postoperative value was 68.93. In our sample, 25 patients (11.73%) required a revision of the RTSA implant due to complications. Discussion: Combined loss of elevation and external rotation can be a severely debilitating condition for those with a glenohumeral pathology. Latissimus dorsi transfer for this condition has been proven to be an effective modality. The reoperation and complication rate appears to be sizable, and as such surgeons should consider this when considering this modality for their patients.

AimsThe mid-term results of kinematic alignment (KA) for total knee arthroplasty (TKA) using image derived instrumentation (IDI) have not been reported in detail, and questions remain regarding ligamentous stability and revisions. This paper aims to address the following: 1) what is the distribution of alignment of KA TKAs using IDI; 2) is a TKA alignment category associated with increased risk of failure or poor patient outcomes; 3) does extending limb alignment lead to changes in soft-tissue laxity; and 4) what is the five-year survivorship and outcomes of KA TKA using IDI?MethodsA prospective, multicentre, trial enrolled 100 patients undergoing KA TKA using IDI, with follow-up to five years. Alignment measures were conducted pre- and postoperatively to assess constitutional alignment and final implant position. Patient-reported outcome measures (PROMs) of pain and function were also included. The Australian Orthopaedic Association National Joint Arthroplasty Registry was used to assess survivorship.ResultsThe postoperative HKA distribution varied from 9° varus to 11° valgus. All PROMs showed statistical improvements at one year (p < 0.001), with further improvements at five years for Knee Osteoarthritis Outcome Score symptoms (p = 0.041) and Forgotten Joint Score (p = 0.011). Correlation analysis showed no difference (p = 0.610) between the hip-knee-ankle and joint line congruence angle at one and five years. Sub-group analysis showed no difference in PROMs for patients placed within 3° of neutral compared to those placed > 3°. There were no revisions for tibial loosening; however, there were reports of a higher incidence of poor patella tracking and patellofemoral stiffness.ConclusionPROMs were not impacted by postoperative alignment category. Ligamentous stability was maintained at five years with joint line obliquity. There were no revisions for tibial loosening despite a significant portion of tibiae placed in varus; however, KA executed with IDI resulted in a higher than anticipated rate of patella complications.Cite this article: Bone Jt Open 2022;3(8):656–665.

BackgroundWhile message-based therapy has been shown to be effective in treating a range of mood disorders, it is critical to ensure that providers are meeting a consistently high standard of care over this medium. One recently developed measure of messaging quality–The Facilitative Interpersonal Skills Task for Text (FIS-T)–provides estimates of therapists’ demonstrated ability to convey psychotherapy's common factors (e.g., hopefulness, warmth, persuasiveness) over text. However, the FIS-T's scoring procedure relies on trained human coders to manually code responses, thereby rendering the FIS-T an unscalable quality control tool for large messaging therapy platforms.ObjectiveIn the present study, researchers developed two algorithms to automatically score therapist performance on the FIS-T task.MethodsThe FIS-T was administered to 978 messaging therapists, whose responses were then manually scored by a trained team of raters. Two machine learning algorithms were then trained on task-taker messages and coder scores: a support vector regressor (SVR) and a transformer-based neural network (DistilBERT).ResultsThe DistilBERT model had superior performance on the prediction task while providing a distribution of ratings that was more closely aligned with those of human raters, versus SVR. Specifically, the DistilBERT model was able to explain 58.8% of the variance (R2 = 0.588) in human-derived ratings and realized a prediction mean absolute error of 0.134 on a 1–5 scale.ConclusionsAlgorithms can be effectively used to ensure that digital providers meet a consistently high standard of interactions in the course of messaging therapy. Natural language processing can be applied to develop new quality assurance systems in message-based digital psychotherapy.

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces inflammatory response, cytokine storm, venous thromboembolism, coagulopathy, and multiple organ damage. Resting endothelial cells prevent coagulation, control blood flow, and inhibit inflammation. However, it remains unknown how SARS-CoV-2 induces strong molecular signals in distant cells for immunopathogenesis. In this study, we examined the consequence of human endothelial cells, microvascular endothelial cells (HMEC-1), and liver endothelial cells (TMNK-1) to exosomes isolated from plasma of mild or severe COVID-19 patients. We observed a significant induction of NLRP3, caspase-1, and interleukin-1β (IL-1β) mRNA expression in endothelial cells following exposure to exosomes from severe COVID-19 patients compared with that from patients with mild disease or healthy donors. Activation of caspase-1 was noted in the endothelial cell culture medium following exposure to the COVID-19 exosomes. Furthermore, COVID-19 exosomes significantly induced mature IL-1β secretion in both HMEC-1 and TMNK-1 endothelial cell culture medium. Thus, our results demonstrated for the first time that exosomes from COVID-19 plasma trigger NLRP3 inflammasome in endothelial cells of distant organs resulting in IL-1β secretion and inflammatory response. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global health problem. Although the vaccine controls infection, understanding the molecular mechanism of pathogenesis will help in developing future therapies. Furthermore, several investigators predicted the involvement of endothelial cell-related inflammation in SARS-CoV-2 infection and using extracellular vesicles as a cargo to carry a drug or vaccine for combating SARS-CoV-2 infection. However, the mechanism by which endothelial cells are inflamed remains unknown. Our present study highlights that exosomes from severe COVID-19 patients can enhance inflammasome activity in distant endothelial cells for augmentation of immunopathogenesis and opens an avenue for developing therapies.

Summary: A recent report on screening in the UK proposed that the responsibility for recommendations on population and targeted screening programmes should be held by one new integrated advisory body. There is no wide international consensus on the definition of targeted screening. Our review identified and compared the defining components of screening terms: targeted, population, selective, and cascade screening, and case finding. Definitions of targeted screening and population screening were clearly demarcated by the eligible population; targeted and selective screening were found to be conceptually interchangeable; cascade screening, whilst conceptually similar to targeted screening across several components, was only used within the context of genetic diseases. There was little consensus between different definitions of case finding. These comparisons contributed to an updated definition of targeted screening. Considerable overlap between definition components across terms implies that a broad range of disease areas may fall into the remit of the new advisory body.

While there have been a very large number of academic studies of proposed machine learning-based health predictive models, it is widely recognized that machine learning-based models in all domains typically degrade in performance over time, post training. This known characteristic of machine learning-based models could present significant risks in the healthcare setting to patient quality of care or safety. Nevertheless, there has been little study of the performance degradation of such models on real-world data. In this article, we empirically measure performance degradation of predictive models that predict at time of admission, emergency patient mortality, drawing upon a large dataset of over 1.83 million patient discharge records. We demonstrate important empirical results including both relatively slow performance degradation over two and a half years, but also significant differences in the rate and extent of performance degradation between different machine learning model types and time period of the training set.

Abstract Background Total hip arthroplasty (THA) is traditionally associated with a low complication rate, with complications such as infection, fracture and dislocation requiring readmission or reoperation. We seek to identify the complication rate among the anterior, direct lateral and posterior surgical approaches. Methods We reviewed all THAs performed at the Epworth Healthcare from 1 July 2014 to 30 June 2016. There were 2437 THAs performed by a variety of approaches. No hips were excluded from this study. We surveyed the hospital database and the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) to identify those patients who had been readmitted and/or reoperated on. Details collected included age, gender, laterality of the surgery (left/right/bilateral), surgical approach utilised, complications which occurred. Results There were 29 peri-prosthetic fractures detected (13 anterior, 9 lateral, 7 posterior) and 10 underwent revision of implant, 19 were fixed. The increased rate of revision in the anterior group was statistically significant. There were 14 dislocations (5 anterior, 1 lateral, 8 posterior) of which 8 prostheses were revised. Three cases operated via the anterior approach and 1 by the lateral had early subsidence without fracture, necessitating revision of the femoral prostheses. Operative site infection occurred in 12 cases (2 anterior, 4 lateral, 6 posterior) with 6 requiring revision of implants. Conclusion The complication rates between the 3 main approaches are similar, but individual surgeons should be vigilant for complications unique to their surgical approaches, such as femoral fractures in the anterior approach and dislocations in the posterior approach.

Chronic hepatitis C virus (HCV) infection often leads to end‐stage liver disease, including hepatocellular carcinoma (HCC). We have previously observed reduced expression of microRNA‐30e (miR‐30e) in the liver tissues and sera of patients with HCV‐associated HCC, although biological functions remain unknown. In this study, we demonstrated that HCV infection of hepatocytes transcriptionally reduces miR‐30e expression by modulating CCAAT/enhancer binding protein β. In silico prediction suggests that autophagy‐related gene 5 (ATG5) is a direct target of miR‐30e. ATG5 is involved in autophagy biogenesis, and HCV infection in hepatocytes induces autophagy. We showed the presence of ATG5 in the miR‐30e–Argonaute 2 RNA‐induced silencing complex. Overexpression of miR‐30e in HCV‐infected hepatocytes inhibits autophagy activation. Subsequent studies suggested that ATG5 knockdown in Huh7.5 cells results in the remarkable inhibition of sterol regulatory element binding protein (SREBP)‐1c and fatty acid synthase (FASN) level. We also showed that overexpression of miR‐30e decreased lipid synthesis‐related protein SREBP‐1c and FASN in hepatocytes. Conclusion: We show new mechanistic insights into the interactions between autophagy and lipid synthesis through inhibition of miR‐30e in HCV‐infected hepatocytes.

Abstract Background Head and neck squamous cell carcinoma (HNSCC) represents one of the most common malignancies worldwide with a high mortality rate mainly due to lack of early detection markers, frequent association with metastasis and aggressive phenotype. Recently, long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancers. The lncRNA prostate cancer-associated transcript 1 (PCAT-1) showed potential oncogenic roles in different cancers, however its role in HNSCC is not known. In this study, we evaluated the role of the PCAT-1 in HNSCC. Methods The expression of PCAT-1 was measured by quantitative real-time PCR in 23 paired human HNSCC tissues and adjacent non-tumor tissue specimens. Cell proliferation after depleting PCAT-1 was determined. Effect of PCAT-1 depletion in HNSCC cell lines was determined by qRT-PCR and Western blot analyses. Finally, JHU029 HNSCC cells was implanted subcutaneously into athymic nude mice and therapeutic potential of PCAT-1 was investigated. Results Up-regulation of PCAT-1 in TCGA dataset of HNSCC was noted. We also observed increased expression of PCAT-1 in archived HNSCC patient samples as compared to adjacent non-tumor tissues. Knockdown of PCAT-1 significantly reduced cell proliferation in HNSCC cell lines. Mechanistic study revealed significant down regulation of c-Myc and AKT1 gene in both RNA and protein levels upon knockdown of PCAT-1. We observed that c-Myc and AKT1 positively correlate with PCAT-1 expression in HNSCC. Further, we observed activation of p38 MAPK and apoptosis signal-regulating kinase 1 upon knockdown of PCAT-1 which induces Caspase 9 and PARP mediated apoptosis. Targeted inhibition of PCAT-1 regresses tumor growth in nude mice. Conclusion Together our data demonstrated an important role of the PCAT-1 in HNSCC and might serve as a target for HNSCC therapy.

Background: In their landmark report on the “Principles and Practice of Screening for Disease” (1968), Wilson and Jungner noted that the practice of screening is just as important for securing beneficial outcomes and avoiding harms as the formulation of principles. Many jurisdictions have since established various kinds of “screening governance organizations” to provide oversight of screening practice. Yet to date there has been relatively little reflection on the nature and organization of screening governance itself, or on how different governance arrangements affect the way screening is implemented and perceived and the balance of benefits and harms it delivers. Methods: An international expert policy workshop convened by Sturdy, Miller and Hogarth. Results: While effective governance is essential to promote beneficial screening practices and avoid attendant harms, screening governance organizations face enduring challenges. These challenges are social and ethical as much as technical. Evidence-based adjudication of the benefits and harms of population screening must take account of factors that inform the production and interpretation of evidence, including the divergent professional, financial and personal commitments of stakeholders. Similarly, when planning and overseeing organized screening programs, screening governance organizations must persuade or compel multiple stakeholders to work together to a common end. Screening governance organizations in different jurisdictions vary widely in how they are constituted, how they relate to other interested organizations and actors, and what powers and authority they wield. Yet we know little about how these differences affect the way screening is implemented, and with what consequences. Conclusions: Systematic research into how screening governance is organized in different jurisdictions would facilitate policy learning to address enduring challenges. Even without such research, informal exchange and sharing of experiences between screening governance organizations can deliver invaluable insights into the social as well as the technical aspects of governance.

According to the American Psychological Association, 49% of the U.S. population suffers from chronic, daily stress. Chronic stress also has significant long-term behavioral and physical health consequences, including an increased risk of cardiovascular disease, cancer, anxiety and depression. In this work, we examine how smartphones and mobile sensing can help address the short and long-term consequences of stress. First, we define a conceptual framework for thinking about the interaction between real-time pervasive devices and the real-time physiology of stress. Second, using this framework, we propose a set of guidelines or requirements for pervasive just-in-time intervention (JITI) systems. Third, based on these guidelines, we specify a three-layer software/hardware architecture to support just-in-time interventions for stress. Several themes emerge from this discussion, including the need for robust and accurate context-sensitive forecasting of future stress. Fourthly we describe our experiments and results demonstrating the feasibility of forecasting future stress from current measurements and the effectiveness of the intervention management approach. Finally we discuss the broader implications of mobile-based stress interventions. Whilst this work focuses on chronic stress, we believe the ideas presented are generalizable to other types of just-in-time pervasive interventions.

Prostate cancer is one of the most common cancers among men. Currently available therapies improve patient survival against local prostate cancer but have shown severe side effects. Advanced prostate cancer is still incurable. Studies have suggested the involvement of non-coding RNAs, especially micro-RNAs (miRNAs), in the regulation of multiple cellular events in cancer and thus several clinical trials are ongoing using miRNAs mimics or inhibitors. We previously demonstrated that miRNA-29b-3p (miR-29b) was downregulated in prostate cancer and that the overexpression of miR-29b limited prostate cancer metastasis. However, the therapeutic potential of the miR-29b against prostate cancer remains unknown. Here, we evaluated the therapeutic role of miR-29b in in vivo prostate tumors in a mouse model. Intratumoral injection of mimic miR-29b significantly inhibited prostate cancer xenograft tumor growth in nude mice. Subsequent study demonstrated that the overexpression of miR-29b reduced prostate cancer cell PC3 proliferation in a time dependent manner and induced cell death. Mechanistic study using a cancer pathway specific transcriptomic array revealed a significant overexpression of the pro-apoptotic gene BCL2L11 (Bim) in the miR-29b overexpressed PC3 cells, which was further verified in PC3 cells overexpressing miR-29b. We also observed a significant induction of Bim protein in miR-29b treated xenograft tumors. The induction of cytosolic accumulation of cytochrome C and PARP cleavage in miR-29b overexpressed PC3 cells was observed. Thus, our results suggest that miR-29b can be used as a potential molecule for prostate cancer therapy.

Spontaneous aortic dissection in pregnancy is rare and life threatening for both the mother and the fetus. Most commonly, it is associated with connective tissue disorders, cardiac valve variants, or trauma. We present the case of a 23-year-old previously healthy woman, 36 weeks pregnant with a syncopal episode after dyspnea and vomiting. She subsequently developed cardiac arrest and underwent aggressive resuscitation, emergent thoracotomy, and cesarean delivery without recovery. On autopsy, she was found to have an aortic dissection of the ascending aorta. This case is presented to raise awareness and review the literature and the clinical approach to critical care for pregnant patients. [West J Emerg Med. 2011;12(4):571–574.]

Head and neck squamous cell carcinoma (HNSCC) remains difficult to treat, and despite of advances in treatment, the overall survival rate has only modestly improved over the past several years. Thus, there is an urgent need for additional therapeutic modalities. We hypothesized that treatment of HNSCC cells with a dietary product such as bitter melon extract (BME) modulates multiple signaling pathways and regresses HNSCC tumor growth in a preclinical model. We observed a reduced cell proliferation in HNSCC cell lines. The mechanistic studies reveal that treatment of BME in HNSCC cells inhibited c-Met signaling pathway. We also observed that BME treatment in HNSCC reduced phosphoStat3, c-myc and Mcl-1 expression, downstream signaling molecules of c-Met. Furthermore, BME treatment in HNSCC cells modulated the expression of key cell cycle progression molecules leading to halted cell growth. Finally, BME feeding in mice bearing HNSCC xenograft tumor resulted in an inhibition of tumor growth and c-Met expression. Together, our results suggested that BME treatment in HNSCC cells modulates multiple signaling pathways and may have therapeutic potential for treating HNSCC.

Emerging information system architectures will often be comprised of distributed systems and data repositories. As a result, providing efficient and secure query assurance over these emerging future information systems is a concern. This paper details the use of temporary time stamps and variable hash granularity to increase the efficiency of query assurance. This approach is implemented against datasets of varying type and size, including encrypted data to illustrate the potential overhead issues present in distributed systems and data repositories.

MBP-1 acts as a general transcriptional repressor. Overexpression of MBP-1 induces cell death in a number of cancer cells and regresses tumor growth. However, the function of endogenous MBP-1 in normal cell growth regulation remains unknown. To unravel the role of endogenous MBP-1, we knocked down MBP-1 expression in primary human foreskin fibroblasts (HFF) by RNA interference. Knockdown of MBP-1 in HFF (HFF-MBPsi-4) resulted in an induction of premature senescence, displayed flattened cell morphology, and increased senescence-associated beta-galactosidase activity. FACS analysis of HFF-MBPsi-4 revealed accumulation of a high number of cells in the G1-phase. A significant upregulation of cyclin D1 and reduction of cyclin A was detected in HFF-MBPsi-4 as compared to control HFF. Senescent fibroblasts exhibited enhanced expression of phosphorylated and acetylated p53, and cyclin-dependent kinase inhibitor, p21. Further analysis suggested that promyolocytic leukemia protein (PML) bodies are dramatically increased in HFF-MBPsi-4. Together, these results demonstrated that knockdown of endogenous MBP-1 is involved in cellular senescence of HFF through p53-p21 pathway.