Panostotic Expansile Bone Disease With Massive Jaw Tumor Formation and a Novel Mutation in the Signal Peptide of RANK

Precise regulation of bone resorption is critical for skeletal homeostasis. We report a 32‐year‐old man with a panostotic expansile bone disease and a massive hemorrhagic mandibular tumor. Originally from Mexico, he was deaf at birth and became bow‐legged during childhood. There was no family history of skeletal disease. Puberty occurred normally, but during adolescence he experienced difficulty straightening his limbs, sustained multiple fractures, and developed a bony tumor on his chin. By age 18 years, all limbs were misshapen. The mandibular mass grew and protruded from the oral cavity, extending to the level of the lower ribs. Other bony defects included a similar maxillary mass and serpentine limbs. Upon referral at age 27 years, biochemical studies showed serum alkaline phosphatase of 1760 U/L (Nl: 29‐111) and other elevated bone turnover markers. Radiography of the limbs showed medullary expansion and cortical thinning with severe bowing. Although the jaw tumors were initially deemed inoperable, mandibular mass excision and staged partial maxillectomy were eventually performed. Tumor histopathology showed curvilinear trabeculae of woven bone on a background of hypocellular fibrous tissue. Fibrous dysplasia of bone was suspected, but there was no mutation in codon 201 of GNAS in samples from blood or tumor. His clinical and radiographic findings, elevated serum markers, and disorganized bone morphology suggested amplified receptor activator of NF‐κB (RANK) signaling, even though his disorder differed from conditions with known constitutive activation of RANK signaling (eg, familial expansile osteolysis). We found a unique 12‐base pair duplication in the signal peptide of TNFRSF11A, the gene that encodes RANK. No exon or splice site mutations were found in the genes encoding RANK ligand or osteoprotegerin. Alendronate followed by pamidronate therapies substantially decreased his serum alkaline phosphatase activity. This unique patient expands the phenotypes and genetic basis of the mendelian disorders of RANK signaling activation. © 2014 American Society for Bone and Mineral Research.     

Effects of stent design on new clinical issue of longitudinal stent compression in interventional cardiology

In recent years, interventional cardiologists have discussed over a new clinical issue called longitudinal stent compression (LSC), a failure mode not previously observed in coronary stents. This phenomenon occurs when the physician attempts to cross a deployed stent with a second device, causing the stent to dramatically shorten when two devices are accidentally entangled. While this phenomenon has been observed with a number of stent platforms, it seems more common with the Element stent. In this paper, a computational LSC model using finite element analysis was developed. A systematic investigation was conducted in attempts to quantify individual contribution of the stent design pattern, connector number, design parameter, and connector location on LSC. Computational simulations were performed on two representative coronary stents resembling Element and Endeavor for comparison. Simulation results show that the connector number plays the most significant role in LSC. The LSC could be easily tripled or quadrupled for the same stent design simply by increasing the connector number from two to three. The design pattern and design parameter play a secondary role in LSC, with the LSC improved by up to 30 and 65 %, respectively. It was also found that the LSC could be doubled for the Element stent simply by rearranging its connector location. This small design tweak could help improve the current Element LSC significantly, while still maintaining the majority of its excellent deliverability. These findings could provide great insights into this new clinical issue and help optimize future stent design to reduce the associated risk involved in LSC.     

Gland-preserving robotic surgery for benign submandibular gland tumours: a comparison between robotic and open techniques

Benign tumours of the submandibular gland are usually treated surgically. Gland-preserving techniques, which can be used to completely remove the tumour, preserve the function of the gland and reduce complications, but conventional open operations result in obvious scars on the neck. We aimed to investigate the feasibility and efficacy of gland-preserving robotic surgery using a hairline approach. We compared robotic with open techniques for gland-preserving operations to remove benign tumours of the submandibular gland. Patients were matched for age and sex (4 in each group). All patients in the robotic surgery group had their tumours removed successfully through hairline approaches. No patient had operative complications or postoperative functional nerve deficit, and an aesthetically pleasing outcome was achieved by concealing the scars within the hairline. Robotic operations took longer than open operations. No recurrence was noted during follow-up. Gland-preserving robotic surgery is a feasible alternative to conventional techniques and has potential advantages for safety and aesthetic outcome.     

Current intensity‐ and polarity‐specific online and aftereffects of transcranial direct current stimulation: An fMRI study

Transcranial direct current stimulation (tDCS) induces polarity‐ and dose‐dependent neuroplastic aftereffects on cortical excitability and cortical activity, as demonstrated by transcranial magnetic stimulation (TMS) and functional imaging (fMRI) studies. However, lacking systematic comparative studies between stimulation‐induced changes in cortical excitability obtained from TMS, and cortical neurovascular activity obtained from fMRI, prevent the extrapolation of respective physiological and mechanistic bases. We investigated polarity‐ and intensity‐dependent effects of tDCS on cerebral blood flow (CBF) using resting‐state arterial spin labeling (ASL‐MRI), and compared the respective changes to TMS‐induced cortical excitability (amplitudes of motor evoked potentials, MEP) in separate sessions within the same subjects (n = 29). Fifteen minutes of sham, 0.5, 1.0, 1.5, and 2.0‐mA anodal or cathodal tDCS was applied over the left primary motor cortex (M1) in a randomized repeated‐measure design. Time‐course changes were measured before, during and intermittently up to 120‐min after stimulation. ROI analyses indicated linear intensity‐ and polarity‐dependent tDCS after‐effects: all anodal‐M1 intensities increased CBF under the M1 electrode, with 2.0‐mA increasing CBF the greatest (15.3%) compared to sham, while all cathodal‐M1 intensities decreased left M1 CBF from baseline, with 2.0‐mA decreasing the greatest (?9.3%) from sham after 120‐min. The spatial distribution of perfusion changes correlated with the predicted electric field, as simulated with finite element modeling. Moreover, tDCS‐induced excitability changes correlated more strongly with perfusion changes in the left sensorimotor region compared to the targeted hand‐knob region. Our findings reveal lasting tDCS‐induced alterations in cerebral perfusion, which are dose‐dependent with tDCS parameters, but only partially account for excitability changes.     

Online detection of concerned HIV-related messages in web forums

Web forums become the means of online communication and information sharing sources for the learning about health care and related treatment knowledge. By adopting web crawlers and natural language processing techniques, the automatic identification approach of the concerned HIV-related messages is proposed to facilitate the health authorities and social support groups in instant counseling. The proposed supervised GA/k-means for classification approach can help construct an effective identification and classification model with acceptable classification performance accompanied with its full flexibility to develop different fitness functions in accordance with the need of different requirements. Furthermore, with the aid of correspondence analysis, the most frequently used terms in concerned HIV-related messages are identified and focus on risky sexual behavior whereas unconcerned messages are those who of worried well.     

Neutrophil extracellular trap fragments stimulate innate immune responses that prevent lung transplant tolerance

Neutrophil extracellular traps (NETs) have been shown to worsen acute pulmonary injury including after lung transplantation. The breakdown of NETs by DNAse‐1 can help restore lung function, but whether there is an impact on allograft tolerance remains less clear. Using intravital 2‐photon microscopy, we analyzed the effects of DNAse‐1 on NETs in mouse orthotopic lung allografts damaged by ischemia‐reperfusion injury. Although DNAse‐1 treatment rapidly degrades intragraft NETs, the consequential release of NET fragments induces prolonged interactions between infiltrating CD4⁺ T cells and donor‐derived antigen presenting cells. DNAse‐1 generated NET fragments also promote human alveolar macrophage inflammatory cytokine production and prime dendritic cells for alloantigen‐specific CD4⁺ T cell proliferation through activating toll‐like receptor (TLR) — Myeloid Differentiation Primary Response 88 (MyD88) signaling pathways. Furthermore, and in contrast to allograft recipients with a deficiency in NET generation due to a neutrophil‐specific ablation of Protein Arginine Deiminase 4 (PAD4), DNAse‐1 administration to wild‐type recipients promotes the recognition of allo‐ and self‐antigens and prevents immunosuppression‐mediated lung allograft acceptance through a MyD88‐dependent pathway. Taken together, these data show that the rapid catalytic release of NET fragments promotes innate immune responses that prevent lung transplant tolerance.     

Relationships between Dairy and Calcium Intake and Mental Health Measures of Higher Education Students in the United States: Outcomes from Moderation Analyses

Background: The prevalence of mental health concerns among university students in the United States (U.S.) continues to increase, while current treatments, including medication and counseling, present shortcomings. Higher dairy and calcium intakes are associated with protective effects on mental health; however, previous studies have focused on investigating singular relationships between dairy and calcium intakes and mental health measures. A more complex exploration of these relationships is warranted to better examine whether increasing dairy and calcium intakes could serve as an intervention to improve mental health. The present study sought to further characterize the relationships between dairy and calcium intake, perceived stress, and a variety of mental health measures using linear regression and moderation analyses. Methods: The present cross-sectional study involved students studying at three large U.S. universities, and data collection occurred from April to May 2020 when students were learning remotely due to the COVID-19 pandemic. An online survey comprising validated tools was distributed among students to assess dairy and calcium intake, perceived stress, anxiety, negative and positive moods, rumination, and resilience, sleep quality and duration, dietary risk, and physical activity. Results: A total of 1233 students completed the study. Higher dairy and calcium intake was coincident with lower perceived stress and higher positive mood scores, while higher calcium intake was also coincident with lower anxiety, rumination, and higher resilience scores. Additionally, as calcium intake increased, the relationship between perceived stress and anxiety and the relationship between perceived stress and negative mood weakened. Dairy intake did not have this effect. Conclusions: Based on the results, and considering that calcium is a shortfall nutrient, universities should consider initiating programs and public health campaigns to promote dairy and calcium intake among this population.