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Our understanding of mesenchymal stem cells (MSCs) and their biological properties is steadily increasing, with more studies focusing on their therapeutic effects in the domains of immunology, tissue engineering and regenerative medicine. MSCs may be derived from tissues such as bone marrow, adipose, the umbilical cord, as well as from dental tissues (e.g., tooth germ, dental follicle, pulp tissue of exfoliated deciduous and permanent teeth, apical papilla, periodontal ligament, gingiva, and alveolar bone). Gingival mesenchymal stem cells (GMSCs) are non-hematopoietic adult stem cells isolated from the gingival lamina propria. When compared to MSCs purified from various dental and non-dental tissues, GMSCs are more abundant in source, relatively non-invasive to obtain, and genetically stable. In recent years, many studies have found that GMSCs possess the ability of self-renewal, multi-directional differentiation, and chemotaxis to inflammatory sites for immunity regulation. Their molecular and stem-cell properties make them highly suitable for both preclinical and clinical research. Extracellular vesicles (EVs) secreted by GMSCs are of key interest due to their ability to emulate the biological and therapeutic activity of GMSCs themselves. This paper will therefore review the current consensus on GMSCs, surveying their sources and isolation methods, their biological properties, and their therapeutic applications on inflammatory and immune-related diseases.

Purpose: To evaluate the maximal load to failure, cyclic displacement, stiffness, and modes of failure of onlay subpectoral biceps tenodesis with an intramedullary unicortical metal button (MB) versus an inlay, all-suture Caspari-Weber (CW) technique. Methods: Sixteen matched paired human cadaveric proximal humeri were randomly allocated for subpectoral BT with either CW or MB using a high-strength suture (N = 16; 8 male, 8 female, mean age = 82.5 years, range 62-99 years). Specimens were tested on a servohydraulic mechanical testing apparatus under cyclic load for 1,000 cycles and then loaded to failure. Maximal load to failure, displacement, construct stiffness, and mode of failure were compared. Results: There was no significant difference between groups when comparing construct stiffness, creep displacement, or displacement at ultimate load. The maximal load to failure for the CW technique was greater than the unicortical MB (588.36 ± 149.06 N vs 375.83 ± 131.4 N, P = .014). Conclusions: In this study, the all-suture CW biceps tenodesis technique had a greater maximal load to failure than the onlay unicortical MB technique while having similar construct displacement and stiffness. The CW subpectoral biceps tenodesis may offer a lower cost alternative with a mechanically robust fixation when performing an open subpectoral biceps tenodesis. Clinical Relevance: This cadaveric biomechanical study can help guide surgeons when selecting a fixation technique for biceps tenodesis.

Sjögren’s syndrome (SS) is a common autoimmune disease characterized by lymphocytic infiltration and destruction of exocrine glands. The disease manifests primarily in the salivary and lacrimal glands, but other organs are also involved, leading to dry mouth, dry eyes, and other extra-glandular manifestations. Studying the disease in humans is entailed with many limitations and restrictions; therefore, the need for a proper mouse model is mandatory. SS mouse models are categorized, depending on the disease emergence into spontaneous or experimentally manipulated models. The usefulness of each mouse model varies depending on the SS features exhibited by that model; each SS model has advanced our understanding of the disease pathogenesis. In this review article, we list all the available murine models which have been used to study SS and we comment on the characteristics exhibited by each mouse model to assist scientists to select the appropriate model for their specific studies. We also recommend a murine strain that is the most relevant to the ideal SS model, based on our experience acquired during previous and current investigations.

This study aimed at assessing the livelihoods of rice households in Nghe An province of Vietnam. The study was undertaken through household surveys of 396 households in three districts of this province. In this study, the livelihood vulnerability index (LVI) was used for investigating the level of vulnerability to climate change of rice households in Nghe An province, pairwise correlation matrix and beta regression were used for examining the factors affecting the level of vulnerability climate stresses. Overall, the computed LVI showed that respondents were slightly vulnerable to climate change, indicating that households in the study area still had capacities to cope with the change. The beta regression analysis showed that floods, droughts, cold spells, irrigation, institutional factors, and socio-demographic factors were the major factors significantly affecting rice households’ vulnerability in Nghe An province. The findings suggest the need to strengthen the social network between farmers, agricultural cooperatives, and local governments to enhance farmers’ capacity to cope with climate-induced issues, especially floods and droughts in the coastal area. Findings also imply the need to provide farmers with input subsidies, effective irrigation systems, training, and consultant services to reduce households’ vulnerability. Furthermore, this study also highlights the need to promote official financial services with low interest rates in adopting adaptation strategies for sustainable development of the whole region.

In this study, we present a novel approach to prepare of a colorimetric chemical sensor for H2O2 and a glucose biosensor basing on the use of peroxidase-like activity of silver nanoparticles decorated on reduced graphene oxide sheets (AgNPs@rGO) nanocomposite. Herein, AgNPs@rGO nanocomposite was synthesized by a one-step hydrothermal reducing method and its physico-chemical properties were characterized by X-ray diffraction (XRD), Transmission Electron Microscopy (TEM), Ultraviolet–visible spectroscopy (UV–Vis), Fourier-Transform Infrared spectroscopy (FT-IR) and Energy Dispersive X-ray spectroscopy (EDX). Obtained evaluation results shown that the synthesized AgNPs/rGO nanocomposite has performed an efficient peroxidase-like activity for the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMBred) by H2O2, leading to the oxidized form (TMBox) which presents a typical blue color (maximum of absorbance at λmax = 655 nm). A colorimetric assay for H2O2 detection was designed and fabricated with a limit of detection of 20 μM. Moreover, we have used of AgNPs/rGO nanocomposite combining with glucose oxidase (GOx) to develop of a colorimetric glucose biosensor with a low limit of detection of 40 μM and a linear dynamic range from 125 μM to 1 mM. This glucose test was applied to the detection of glucose in human serum samples.

Head and neck squamous cell carcinomas (HNSCCs) arise in the mucosal linings of the upper aerodigestive tract and are heterogeneous in nature. Risk factors for HNSCCs are smoking, excessive alcohol consumption, and the human papilloma virus. Conventional treatments are surgery, radiotherapy, chemotherapy, or a combined modality; however, no international standard mode of therapy exists. In contrast to the conventional model of clonal evolution in tumor development, there is a newly proposed theory based on the activity of cancer stem cells (CSCs) as the model for carcinogenesis. This “CSC hypothesis” may explain the high mortality rate, low response to treatments, and tendency to develop multiple tumors for HNSCC patients. We review current knowledge on HNSCC etiology and treatment, with a focus on CSCs, including their origins, identifications, and effects on therapeutic options. Keywords: Head and neck cancer, Carcinoma, Squamous cell, Cancer stem cells, Cancer treatment, Antineoplastic agents

Primary thyroid sarcoma is a very rare entity, accounting for less than 1.5% of all malignant thyroid tumors. Primary thyroid rhabdomyosarcoma is extremely rare: Until now, there had been only two child cases and four adult cases diagnosed worldwide. We report herein the case of a 17-year-old female who presented with a large, rapidly growing neck mass. To the best of our knowledge, this is the first reported case of primary alveolar rhabdomyosarcoma in the thyroid. Moreover, this is the only case that shows an outstanding response of RMS in the thyroid to neoadjuvant chemotherapy. It provides an example of a potential new treatment for patients whose tumors cannot be treated surgically.

Purpose: To report the clinical features organisms and treatment outcomes in patients with endophthalmitis after penetrating keratoplasty (PK) Methods: Retrospective noncomparative case series. Results: Eleven eyes of 11 patients with culture positive endophthalmitis after PK were included. The time to diagnosis of endophthalmitis from last PK was less than 1 week in 3/11 (27%), between 1 and 4 weeks in 3/11 (27%), and greater than one month in 5/11 (46%) (range 2–924 days). The distribution of isolates included gram positive (GP) 9/11 (82%), gram negative (GN) 1/11 (9%), and fungal 1/11 (9%) species, respectively. Of GP bacteria tested, 9/9 (100%) were sensitive to Vancomycin. Of fungal isolates tested, none (0/1) were sensitive to Amphoteracin, Fluconazole, and/or Voriconazole. Among patients with rim culture data available, 1/7 (14%) donor rims were culture positive for Candida glabrata and 6/7 (86%) were culture negative. Patients were treated with primary tap and inject in 10/11 (91%) and primary vitrectomy in 1/11 (9%). VA of ≥5/200 was present in 2/11 (18%) at time of endophthalmitis diagnosis, and was recorded in 6/11 (55%) at last follow-up. Conclusions and Importance: Patients with endophthalmitis after PK presented at variable time points after surgery. Gram positive organisms were the most common isolate. VA outcomes after treatment were generally poor.

Large scale production of H2, a clean fuel, can be realized with just water and solar light energy by employing a viable energy conversion device called artificial leaf. In this tutorial review, we discuss on advances achieved recently and technical challenges remained toward the creation of such a leaf. Development of key components like catalysts for water electrolysis process and light harvester for harvesting solar energy as well as strategies being developed for assembling these components to create a complete artificial leaf will be highlighted.

Summary: Accurately predicting cardioactive effects of new molecular entities for therapeutics remains a daunting challenge. Immense research effort has been focused toward creating new screening platforms that utilize human pluripotent stem cell (hPSC)-derived cardiomyocytes and three-dimensional engineered cardiac tissue constructs to better recapitulate human heart function and drug responses. As these new platforms become increasingly sophisticated and high throughput, the drug screens result in larger multidimensional datasets. Improved automated analysis methods must therefore be developed in parallel to fully comprehend the cellular response across a multidimensional parameter space. Here, we describe the use of machine learning to comprehensively analyze 17 functional parameters derived from force readouts of hPSC-derived ventricular cardiac tissue strips (hvCTS) electrically paced at a range of frequencies and exposed to a library of compounds. A generated metric is effective for then determining the cardioactivity of a given drug. Furthermore, we demonstrate a classification model that can automatically predict the mechanistic action of an unknown cardioactive drug. : Analysis methods must be improved in parallel with advancements in drug screening platforms. Machine learning principles are used here to analyze multidimensional datasets to determine cardioactivity of unknown drugs. Furthermore, this study describes the use of multiclassification algorithms to classify unknown drugs based on their mechanistic action and compare their potency with related drugs. Keywords: human pluripotent stem cell-derived cardiomyocytes, drug-induced cardiotoxicity, machine learning, human engineered cardiac tissue, drug classification library

Epipericardial fat necrosis (EPFN) is a rare cause for acute chest. We describe the case of a previously healthy 25-year-old man who presented with sudden onset of left-sided chest pain. Laboratory values showed only mildly elevated d-dimer and electrocardiogram was normal. However, subsequent CT angiogram of the chest revealed fat necrosis in the epipericardial fat, characteristic for EPFN, for which the patient was treated with nonsteroidal anti-inflammatory drug. This case highlights the importance of radiologists to consider the prospect of EPFN in the differential diagnosis of acute chest pain as correct diagnosis allows for conservative management and avoidance of more aggressive techniques in symptomatic patients. Keywords: Epipericardial fat necrosis, Chest pain, Dyspnea

Purpose: To describe a case of Multi-drug resistant Mycobacterium chelonae scleral buckle infection. Observations: A 56 year-old male with history of retinal detachment repair with scleral buckle 20 years prior presented with 8 months of intermittent pain and redness in the left eye. The patient was diagnosed with scleral buckle infection, the buckle was removed, and cultures revealed multi-drug resistant Mycobacterium chelonae. The postoperative course included orbital cellulitis treated with systemic linezolid, clarithromycin, and imipenem. All systemic antibiotics were discontinued on post-operative day 25, visual acuity improved to 20/25, the retina remained attached, and no recurrence occurred over 3 years of follow-up. Conclusions and importance: NTM infections are typically chronic and often require lengthy treatment. SB infection is rare, but often associated with biofilm and antibiotic resistance. In spite of removing the SB, anchoring sutures, sheath surrounding the buckle and associated biofilm, a prolonged course of systemic antibiotics may be necessary in some patients. Keywords: Non-tuberculous mycobacterium, Scleral buckle, Orbital cellulitis

Purpose: To describe the first published case of X-linked retinoschisis (XLRS) detachment with retinal vasoproliferative tumor (RVPT) and provide a literature review of the subject. Observations: The authors describe a case of a 17 year old male with X-linked retinoschisis who presented with a retinal detachment and a retinal vasoproliferative tumor. The patient was treated with pars plana vitrectomy, endolaser, subtenon's kenalog and anti-VEGF (vascular endothelial growth factor) intravitreal injections. He regained 20/60 vision with a flat macula and had significant resolution of the associated vasoproliferative leakage seen on fluorescein angiography. Conclusions and importance: This case adds XLRS to the conditions associated with RVPT and gives support for treatment with laser photocoagulation and anti-VEGF therapy with bevacizumab to control the exudative process.

Early disease detection is not only vital to reduce disease severity and prevent complications, but also critical to increase success rate of therapy. Saliva has been studied extensively as a potential diagnostic tool over the last decade due to its ease and non-invasive accessibility along with its abundance of biomarkers, such as genetic material and proteins. This review will update the clinician on recent advances in salivary biomarkers to diagnose autoimmune diseases (Sjogren's syndrome, cystic fibrosis), cardiovascular diseases, diabetes, HIV, oral cancer, caries and periodontal diseases. Considering their accuracy, efficacy, ease of use and cost effectiveness, salivary diagnostic tests will be available in dental offices. It is expected that the advent of sensitive and specific salivary diagnostic tools and the establishment of defined guidelines and results following rigorous testing will allow salivary diagnostics to be used as chair-side tests for several oral and systemic diseases in the near future.

Purpose: To describe the importance of considering vaso-occlusive disease on the differential diagnosis of a patient presenting with amaurosis fugax (AF) and unilateral cotton wool spots (CWS). Observations: A 69-year-old female with history of obesity, hyperlipidemia and recent orthopedic surgery, presented with 3 days of worsening monocular AF and CWS in the right eye. She was diagnosed with antiphosphospholipid syndrome based on positive serologic testing for antiphosphatidylserine IgM, anticardiolipin IgM. The patient was treated with lipid lowering medication, long-term aspirin, and has followed a weightloss and physical therapy program under medical supervision. The CWS resolved and AF symptoms have not recurred. Conclusions and importance: Antiphospholipid syndrome can be considered in the differential diagnosis of patients presenting with AF, assymetric CWS, and/or rapid progression of symptoms.

Glioblastoma harbors a dynamic subpopulation of glioblastoma stem-like cells (GSCs) that can propagate tumors in vivo and is resistant to standard chemoradiation. Identification of the cell-intrinsic mechanisms governing this clinically important cell state may lead to the discovery of therapeutic strategies for this challenging malignancy. Here, we demonstrate that the mitotic E3 ubiquitin ligase CDC20-anaphase-promoting complex (CDC20-APC) drives invasiveness and self-renewal in patient tumor-derived GSCs. Moreover, CDC20 knockdown inhibited and CDC20 overexpression increased the ability of human GSCs to generate brain tumors in an orthotopic xenograft model in vivo. CDC20-APC control of GSC invasion and self-renewal operates through pluripotency-related transcription factor SOX2. Our results identify a CDC20-APC/SOX2 signaling axis that controls key biological properties of GSCs, with implications for CDC20-APC-targeted strategies in the treatment of glioblastoma.

Purpose: To report management of inadvertent needle penetration during subtenons triamcinolone acetonide administration resulting in retinal detachment. Observations: A 71-year-old female with history of diabetes, hypothyroidism, and mild myopia underwent subtenons triamcinolone acetonide (TA) injection in the right eye for nodular scleritis. There was unexpected patient movement concurrent with the injection resulting in needle penetration, subretinal and intravitreal injection of TA, superotemporal retinal break, and macula-involving retinal detachment. The patient underwent partial subretinal TA removal, successful retinal detachment repair, and recovered 20/25 visual acuity. Conclusions and importance: In spite of prominent subretinal TA and retinal detachment, successful repair of retinal detachment and recovery of good visual acuity is possible. Keywords: Needle penetration, Retrobulbar injection, Peribulbar injection

Here, we describe the embryonic central nervous system expression of 5,000 GAL4 lines made using molecularly defined cis-regulatory DNA inserted into a single attP genomic location. We document and annotate the patterns in early embryos when neurogenesis is at its peak, and in older embryos where there is maximal neuronal diversity and the first neural circuits are established. We note expression in other tissues, such as the lateral body wall (muscle, sensory neurons, and trachea) and viscera. Companion papers report on the adult brain and larval imaginal discs, and the integrated data sets are available online (http://www.janelia.org/gal4-gen1). This collection of embryonically expressed GAL4 lines will be valuable for determining neuronal morphology and function. The 1,862 lines expressed in small subsets of neurons (

Background: Conventional techniques used in oral and maxillofacial reconstruction focus mainly on utilizing autologous tissues that have unquestionably improved function and esthetics for many patients, worldwide. However, the success depends on countless factors such as: donor and recipient sites conditions, patient’s medical history, surgeon’s experience, restricted availability of high-quality autogenous tissues or stem cells, and increased surgical cost and time. Materials and Methods: Lately, teaming researchers, scientists, surgeons, and engineers, to address these limitations, have allowed tremendous progress in recombinant protein therapy, cell-based therapy, and gene therapy. Results: Over the past few years, biomedical engineering has been evolving from the laboratory to clinical applications, for replacement of damaged body tissues due to trauma, cancer, congenital or acquired disorders. Conclusions: This review provides an outlook on the content, benefits, recent advances, limitations, and future expectations of biomedical engineering for salivary glands, oral mucosa, dental structures, and maxillofacial reconstruction.

Prompt evaluation and genetic testing of patients who present with recurrent and recalcitrant warts, before onset of severe infection or myelodysplastic syndrome, leads to improved outcomes in patients with GATA2 deficiency.

Background: This paper describes the development of low-cost, effective, non-invasive machine learning-based prediction models for Down Syndrome in the first two trimesters of pregnancy in Vietnam. These models are adaptable to different situations with limited screening capacities at community-based healthcare facilities. Method: Ultrasound and biochemical testing alone and in combination, from both trimesters were employed to build prediction models based on k-Nearest Neighbor, Support Vector Machine, Random Forest, and Extreme Gradient Boosting algorithms. Results: A total of 7,076 pregnant women from a single site in Northern Vietnam were included, and 1,035 had a fetus with Down Syndrome. Combined ultrasound and biochemical testing were required to achieve the highest accuracy in trimester 2, while models based only on biochemical testing performed as well as models based on combined testing during trimester 1. In trimester 1, Extreme Gradient Boosting produced the best model with 94% accuracy and 88% AUC, while Support Vector Machine produced the best model in trimester 2 with 89% accuracy and 84% AUC. Conclusions: This study explored a range of machine learning models under different testing scenarios. Findings point to the potential feasibility of national screening, especially in settings without enough equipment and specialists, after additional model validation and fine tuning is performed.

Cell shape and motility are determined by the cytoskeleton, an interpenetrating network of actin filaments, microtubules, and intermediate filaments. The biophysical properties of each filament type individually have been studied extensively by cell-free reconstitution. By contrast, the interactions between the three cytoskeletal networks are relatively unexplored. They are coupled via crosslinkers of the plakin family such as plectin. These are challenging proteins for reconstitution because of their giant size and multidomain structure. Here we engineer a recombinant actin-vimentin crosslinker protein called ‘ACTIF’ that provides a minimal model system for plectin, recapitulating its modular design with actin-binding and intermediate filament-binding domains separated by a coiled-coil linker for dimerisation. We show by fluorescence and electron microscopy that ACTIF has a high binding affinity for vimentin and actin and creates mixed actin-vimentin bundles. Rheology measurements show that ACTIF-mediated crosslinking strongly stiffens actin-vimentin composites. Finally, we demonstrate the modularity of this approach by creating an ACTIF variant with the intermediate filament binding domain of Adenomatous Polyposis Coli. Our protein engineering approach provides a new cell-free system for the biophysical characterization of intermediate filament-binding crosslinkers and for understanding the mechanical synergy between actin and vimentin in mesenchymal cells.