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Objective Hypophosphatasia (HPP) is a rare disease characterized by incomplete or defective bone mineralization due to a mutation in the alkaline phosphatase (ALP) gene causing low levels of ALP. Disease presentation is heterogeneous and can present as a chronic pain syndrome like fibromyalgia (FM). Our objective was to determine if there are any potential patients with HPP in the group of patients who were diagnosed with FM. Antiresorptive therapy use can trigger atypical femur fractures in patients with HPP. Methods We performed a retrospective chart review of all patients 18 years or older at a single academic center who were diagnosed with FM and had either a low or a normal ALP level. The following characteristics were reviewed: biological sex; age; history of fractures; diagnosis of osteoporosis, osteopenia, osteoarthritis, and chondrocalcinosis; genetic testing; vitamin B6 level testing; and medications. Results Six hundred eleven patients with FM were identified. Two hundred had at least one low ALP level, and 57 had at least three consecutively low measurements of ALP, 44% of which had a history of fractures. No patients had vitamin B6 levels checked. None of the patients had previous genetic testing for HPP or underwent testing for zinc or magnesium levels. Conclusion The percentage of patients with FM who were found to have consistently low ALP levels was 9.3%. None had vitamin B6 level or genetic testing, suggesting that the diagnosis was not suspected. It is important to diagnose HPP given the availability of enzyme replacement therapy to prevent complications from HPP such as fractures. Our data support screening for this condition as a part of the initial workup of FM.

Polymyalgia rheumatica (PMR) is an inflammatory rheumatic condition characterized by pain and stiffness around the shoulders and hip girdles, an elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) and a dramatic response to corticosteroids. It is usually seen in adults aged over 50 years; about 30% also have giant cell arteritis. Its etiology is unknown. A 72-year-old male received water vapor therapy, a novel, minimally invasive therapy for benign prostate hypertrophy (BPH). On postoperative day 1, he developed severe shoulder pain and weakness, with difficulty with lifting his arms above his head, and hip pain and weakness, with difficulty getting out of a bed or chair. Laboratory results showed elevated ESR and CRP, but a normal creatine kinase level. The patient received low-dose prednisone and had prompt symptom relief. This case illustrates that a diagnosis of PMR after water vapor therapy can be easily overlooked.

Much environmental enforcement in the United States has historically relied on either self-reported data or physical, resource-intensive, infrequent inspections. Advances in remote sensing and computer vision, however, have the potential to augment compliance monitoring by detecting early warning signs of noncompliance. We demonstrate a process for rapid identification of significant structural expansion using Planet’s 3 m/pixel satellite imagery products and focusing on Concentrated Animal Feeding Operations (CAFOs) in the US as a test case. Unpermitted building expansion has been a particular challenge with CAFOs, which pose significant health and environmental risks. Using new hand-labeled dataset of 145,053 images of 1,513 CAFOs, we combine state-of-the-art building segmentation with a likelihood-based change-point detection model to provide a robust signal of building expansion (AUC = 0.86). A major advantage of this approach is that it can work with higher cadence (daily to weekly), but lower resolution (3 m/pixel), satellite imagery than previously used in similar environmental settings. It is also highly generalizable and thus provides a near real-time monitoring tool to prioritize enforcement resources in other settings where unpermitted construction poses environmental risk, e.g. zoning, habitat modification, or wetland protection.

Introduction Nipple-sparing mastectomy (NSM) can be performed for the treatment of breast cancer and risk reduction, but total mammary glandular excision in NSM can be technically challenging. Minimally invasive robot-assisted NSM (RNSM) has the potential to improve the ergonomic challenges of open NSM. Recent studies in RNSM demonstrate the feasibility and safety of the procedure, but this technique is still novel in the USA.Methods and analysis This is a single-arm prospective pilot study to determine the safety, efficacy and potential risks of RNSM. Up to 12 RNSM will be performed to assess the safety and feasibility of the procedure. Routine follow-up visits and study assessments will occur at 14 days, 30 days, 6 weeks, 6 months and 12 months. The primary outcome is to assess the feasibility of removing the breast gland en bloc using the RNSM technique. To assess safety, postoperative complication information will be collected. Secondary outcomes include defining benefits and challenges of RNSM for both surgeons and patients using surveys, as well as defining the breast and nipple-areolar complex sensation recovery following RNSM. Mainly, descriptive analysis will be used to report the findings.Ethics and dissemination The RNSM protocol was reviewed and approved by the US Food and Drug Administration using the Investigational Device Exemption mechanism (reference number G200096). In addition, the protocol was registered with ClinicalTrials.gov (NCT04537312) and approved by The Ohio State University Institutional Review Board, reference number 2020C0094 (18 August 2020). The results of this study will be distributed through peer-reviewed journals and presented at surgical conferences.Trial registration number NCT04537312.

The myeloproliferative neoplasms (MPNs) are characterized by an expansion of the neoplastic hematopoietic stem/progenitor cells (HSPC) and an increased risk of cardiovascular complications. The acquired kinase mutation JAK2V617F is present in hematopoietic cells in a majority of patients with MPNs. Vascular endothelial cells (ECs) carrying the JAK2V617F mutation can also be detected in patients with MPNs. In this study, we show that a murine model with both JAK2V617F-bearing hematopoietic cells and JAK2V617F-bearing vascular ECs recapitulated all the key features of the human MPN disease, which include disease transformation from essential thrombocythemia to myelofibrosis, extramedullary splenic hematopoiesis, and spontaneous cardiovascular complications. We also found that, during aging and MPN disease progression, there was a loss of both HSPC number and HSPC function in the marrow while the neoplastic hematopoiesis was relatively maintained in the spleen, mimicking the advanced phases of human MPN disease. Different vascular niche of the marrow and spleen could contribute to the different JAK2V617F mutant stem cell functions we have observed in this JAK2V617F-positive murine model. These results indicate that the spleen is functionally important for the JAK2V617F mutant neoplastic hematopoiesis during aging and MPN disease progression. Compared to other MPN murine models reported so far, our studies demonstrate that JAK2V617F-bearing vascular ECs play an important role in both the hematologic and cardiovascular abnormalities of MPN.

Abstract Background Transposable elements (TEs) make up > 50% of the human genome, and the majority of retrotransposon insertions are truncated and many are located in introns. However, the effects of retrotransposition on the host genes remain incompletely known. Results We report here that insertion of a chimeric L1 (cL1), but not IAP solo LTR, into intron 6 of Axin1 using CRIPSR/Cas9 induced the kinky tail phenotype with ~ 80% penetrance in heterozygous Axin cL1 mice. Both penetrant (with kinky tails) and silent (without kinky tails) Axin cL1 mice, regardless of sex, could transmit the phenotype to subsequent generations with similar penetrance (~ 80%). Further analyses revealed that a longer Axin1 transcript isoform containing partial cL1-targeted intron was present in penetrant, but absent in silent and wild type mice, and the production of this unique Axin1 transcript appeared to correlate with altered levels of an activating histone modification, H3K9ac. Conclusions The mechanism for Axin cL1 mice is different from those previously identified in mice with spontaneous retrotransposition of IAP, e.g., Axin Fu and A vy , both of which have been associated with DNA methylation changes. Our data suggest that Axin1 locus is sensitive to genetic and epigenetic alteration by retrotransposons and thus, ideally suited for studying the effects of new retrotransposition events on target gene function in mice.

Abstract Objectives The emergence of a SARS‐CoV‐2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross‐neutralise against the G614 variant. Methods Antibody profiling against the SARS‐CoV‐2 S protein of the D614 variant by flow cytometry and assessment of neutralising antibody titres using pseudotyped lentiviruses expressing the SARS‐CoV‐2 S protein of either the D614 or G614 variant tagged with a luciferase reporter were performed on plasma samples from COVID‐19 patients with known D614G status (n = 44 infected with D614, n = 6 infected with G614, n = 7 containing all other clades: O, S, L, V, G, GH or GR). Results Profiling of the anti‐SARS‐CoV‐2 humoral immunity reveals similar neutralisation profiles against both S protein variants, albeit waning neutralising antibody capacity at the later phase of infection. Of clinical importance, patients infected with either the D614 or G614 clade elicited a similar degree of neutralisation against both pseudoviruses, suggesting that the D614G mutation does not impact the neutralisation capacity of the elicited antibodies. Conclusions Cross‐reactivity occurs at the functional level of the humoral response on both the S protein variants, which suggests that existing serological assays will be able to detect both D614 and G614 clades of SARS‐CoV‐2. More importantly, there should be negligible impact towards the efficacy of antibody‐based therapies and vaccines that are currently being developed.

The possibility of controlling photochemical processes in aqueous hydroxypropyl cellulose (HPC) solution by using a weakly scattering medium as a solvent is examined. The temperature-dependent colloidal formation has successfully controlled optical processes through multiple scattering with a sharp threshold and abrupt emergence of dense scatterers.

Focuses on a study on ultrafast microscopy of shock waves using a shock target array with an optical nanogauge. Dynamics of shock wave propagation; Behavior of shocked nanogauges; Information on how shock waves were generated; Results.

Presents a study that examined photothermal laser ablation. Use of poly-methyl methacrylate films; Information on laser polymer surface ablation; Schematic diagram of photothermal ablation process; Diagram of the apparatus used for ultrafast temperature measurements.

One hundred and ninety seven adolescent boys and girls who attended high school and worked part-time participated in a study of the relationship between ego-identity, self-esteem, and three indicators of psychological stress, namely, interpersonal conflict at work, emotional exhaustion resulting from work, and psychological strain in general. Correlation analyses showed that ego-identity was negatively related to interpersonal conflict, emotional exhaustion, and psychological strain. Ego-identity was also positively related to self-esteem. The latter variable, in turn, was negatively associated with interpersonal conflict, emotional exhaustion, and psychological strain. The results of mediation analyses showed that when self-esteem was controlled, ego-identity had no effect on the respective variables of interpersonal conflict, emotional exhaustion, and psychological strain, suggesting that self-esteem is a single, dominant mediator in these relationships. [ABSTRACT FROM AUTHOR]