Speech and Language Outcomes in Adults and Children with Cochlear Implants

Cochlear implants (CIs) represent a significant engineering and medical milestone in the treatment of hearing loss for both adults and children. In this review, we provide a brief overview of CI technology, describe the benefits that CIs can provide to adults and children who receive them, and discuss the specific limitations and issues faced by CI users. We emphasize the relevance of CIs to the linguistics community by demonstrating how CIs successfully provide access to spoken language. Furthermore, CI research can inform our basic understanding of spoken word recognition in adults and spoken language development in children. Linguistics research can also help us address the major clinical issue of outcome variability and motivate the development of new clinical tools to assess the unique challenges of adults and children with CIs, as well as novel interventions for individuals with poor outcomes.

Effect of Enamel Pretreatment with Pastes Presenting Different Relative Dentin Abrasivity (RDA) Values on Orthodontic Bracket Bonding Efficacy of Microfilled Composite Resin: In Vitro Investigation and Randomized Clinical Trial

Bonding failure is a clinical issue frequently encountered in orthodontic practice. The aim of this study was to evaluate enamel pretreatment both in vitro and clinically using agents with different RDA values before brackets’ bonding, to assess if RDA can affect the Shear Bond Strength (SBS), Adhesive Remnant Index (ARI) and clinical failure rate of orthodontic brackets. For the in vitro study, 220 bovine teeth were pretreated with agents with different RDA values. Subsequently, brackets were bonded. For the clinical study, 20 patients underwent bonding of 20 brackets each with a split-mouth design. Low and high RDA toothpastes were used for enamel pretreatment. SBS, ARI and failures were recorded. Higher SBS values were found for teeth pretreated with lower RDA agents; conversely, lower SBS values were found for teeth pretreated with higher RDA agents (p < 0.05). For high ARI values, RDA increased too (p > 0.05). In the clinical study, a significantly lower failure rate was reported for teeth pretreated with low RDA toothpaste (2.5% in low RDA group, 7.0% in high RDA group; p < 0.05). No significant differences were assessed comparing the two dental arches and anterior and posterior sites. Enamel pretreatment with low RDA toothpastes could increase brackets’ survival rate. Further in vitro and clinical studies would be welcomed to confirm these findings.

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Targeting Mitochondrial Metabolism and RNA Polymerase POLRMT to Overcome Multidrug Resistance in Cancer

Clinically, the prognosis of tumor therapy is fundamentally affected by multidrug resistance (MDR), which is primarily a result of enhanced drug efflux mediated by channels in the membrane that reduce drug accumulation in tumor cells. How to restore the sensitivity of tumor cells to chemotherapy is an ongoing and pressing clinical issue. There is a prevailing view that tumor cells turn to glycolysis for energy supply due to hypoxia. However, studies have shown that mitochondria also play crucial roles, such as providing intermediates for biosynthesis through the tricarboxylic acid (TCA) cycle and a plenty of ATP to fuel cells through the complete breakdown of organic matter by oxidative phosphorylation (OXPHOS). High OXPHOS have been found in some tumors, particularly in cancer stem cells (CSCs), which possess increased mitochondria mass and may be depends on OXPHOS for energy supply. Therefore, they are sensitive to inhibitors of mitochondrial metabolism. In view of this, we should consider mitochondrial metabolism when developing drugs to overcome MDR, where mitochondrial RNA polymerase (POLRMT) would be the focus, as it is responsible for mitochondrial gene expression. Inhibition of POLRMT could disrupt mitochondrial metabolism at its source, causing an energy crisis and ultimately eradicating tumor cells. In addition, it may restore the energy supply of MDR cells to glycolysis and re-sensitize them to conventional chemotherapy. Furthermore, we discuss the rationale and strategies for designing new therapeutic molecules for MDR cancers by targeting POLRMT.

Erythrocyte Membrane-Enveloped Molybdenum Disulfide Nanodots for Biofilm Elimination on Implants Via Toxin Neutralization and Immune Modulation

Backgrounds: Implant-related infections (IRIs) caused by bacterial biofilms remain a prevalent but tricky clinical issue, which are characterized by drug resistance, toxin impairment and immunity suppression. Recently, antimicrobial therapies based on reactive oxygen species (ROS) or hyperthermia have been developed to effectively destroy biofilms. However, all of them have failed to simultaneously focus on the immunosuppressive microenvironment of biofilms and tissue damage caused by bacterial toxins. Results Herein, we proposed a one-arrow-three-hawks strategy to orchestrate hyperthermia/ROS antibiofilm therapy, toxin neutralization and immunomodulatory therapies through engineering a bioinspired erythrocyte membrane-enveloped molybdenum disulfide nanodots (EM@MoS2) nanoplatform. In biofilm microenvironment, pore-forming toxins actively attack the erythrocyte membranes on the nanodots and be detained, thus keeping toxins away from their targets and mitigating tissue damage. Under near-infrared laser irradiation, MoS2 nanodots, with superb photothermal and peroxidase-like properties, exert a powerful synergistic antibiofilm effect. More intriguingly, we initially identified that they possess the ability to reverse the immunosuppressive microenvironment through skewing the macrophages from an anti-inflammatory phenotype to a proinflammatory phenotype, which would promote the elimination of biofilm debris and prevention of infection relapse. Systematic in vitro and in vivo evaluations have demonstrated that EM@MoS2 achieves remarkable antibiofilm effect. Conclusion The current study integrated the functions of hyperthermia/ROS therapy, virulence clearance and immune regulation, which could provide an effective paradigm for IRIs therapy.

Functional Hydrogel Dressings for Treatment of Burn Wounds

The therapy of burns is a challenging clinical issue. Burns are long-term injuries, and numerous patients suffer from chronic pain. Burn treatment includes management, infection control, wound debridement and escharotomy, dressing coverage, skin transplantation, and the use of skin substitutes. The future of advanced care of burn wounds lies in the development of “active dressings”. Hydrogel dressings have been employed universally to accelerate wound healing based on their unique properties to overcome the limitations of existing treatment methods. This review briefly introduces the advantages of hydrogel dressings and discusses the development of new hydrogel dressings for wound healing along with skin regeneration. Further, the treatment strategies for burns, ranging from external to clinical, are reviewed, and the functional classifications of hydrogel dressings along with their clinical value for burns are discussed.

DERMATITIS ULCERATIVA EN RATONES BALB/c Cmedc: REPORTE DE 3 CASOS

Ulcerative dermatitis (UD) is a common and spontaneous condition in mice. The disease is characterized by a pruritic skin lesion, pain and a progressive evolution that often results in ulcerations. Sex, environmental conditions, dietary variation, chronic inflammation, barbering and follicular dystrophy are some predisposing factors for the clinical disease development. The aim of this study was report 3 cases of UD in BALBc/Cmedc mice from Center for Comparative Medicine, gross and histopathological lesions were described, and a review about relevance of UD in laboratory mice was made. These cases were characterized by dermatitis, ulcerative and proliferative, chronic, moderate, with neutrophils, hemorrhage and a serocellular crust. Although initial lesions may be mild, lesions in UD typically are unresponsive to treatment and euthanasia is often warranted in severe cases. This is the reason why UD is an important clinical issue that often affects biomedical research by causing problems in mice health and premature removal of animal from laboratory studies.

Tracheal and Cricotracheal Resection With End-to-End Anastomosis for Locally Advanced Thyroid Cancer: A Systematic Review of the Literature on 656 Patients

Airway involvement by advanced thyroid carcinoma (TC) constitutes a negative prognosticator, besides being a critical clinical issue since it represents one of the most frequent causes of death in locally advanced disease. It is generally agreed that, for appropriate laryngo-tracheal patterns of invasion, (crico-)tracheal resection and primary anastomosis [(C)TRA] is the preferred surgical technique in this clinical scenario. However, the results of long-term outcomes of (C)TRA are scarce in the literature, due to the rarity of such cases. The relative paucity of data prompts careful review of the available relevant series in order to critically evaluate this surgical technique from the oncologic and functional points of view. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement on the PubMed, Scopus, and Web of Science databases. English-language surgical series published between January 1985 and August 2021, reporting data on ≥5 patients treated for TC infiltrating the airway by (C)TRA were included. Oncologic outcomes, mortality, complications, and tracheotomy-dependency rates were assessed. Pooled proportion estimates were elaborated for each end-point. Thirty-seven studies were included, encompassing a total of 656 patients. Pooled risk of perioperative mortality was 2.0%. Surgical complications were reported in 27.0% of patients, with uni- or bilateral recurrent laryngeal nerve palsy being the most common. Permanent tracheotomy was required in 4.0% of patients. Oncologic outcomes varied among different series with 5- and 10-year overall survival rates ranging from 61% to 100% and 42.1% to 78.1%, respectively. Five- and 10-year disease specific survival rates ranged from 75.8% to 90% and 54.5% to 62.9%, respectively. Therefore, locally advanced TC with airway invasion treated with (C)TRA provides acceptable oncologic outcomes associated with a low permanent tracheotomy rate. The reported incidence of complications, however, indicates the need for judicious patient selection, meticulous surgical technique, and careful postoperative management.

Blockade of CC Chemokine Receptor Type 3 Diminishes Pain and Enhances Opioid Analgesic Potency in a Model of Neuropathic Pain

Neuropathic pain is a serious clinical issue, and its treatment remains a challenge in contemporary medicine. Thus, dynamic development in the area of animal and clinical studies has been observed. The mechanisms of neuropathic pain are still not fully understood; therefore, studies investigating these mechanisms are extremely important. However, much evidence indicates that changes in the activation and infiltration of immune cells cause the release of pronociceptive cytokines and contribute to neuropathic pain development and maintenance. Moreover, these changes are associated with low efficacy of opioids used to treat neuropathy. To date, the role of CC chemokine receptor type 3 (CCR3) in nociception has not been studied. Similarly, little is known about its endogenous ligands (C-C motif ligand; CCL), namely, CCL5, CCL7, CCL11, CCL24, CCL26, and CCL28. Our research showed that the development of hypersensitivity in rats following chronic constriction injury (CCI) of the sciatic nerve is associated with upregulation of CCL7 and CCL11 in the spinal cord and dorsal root ganglia (DRG). Moreover, our results provide the first evidence that single and repeated intrathecal administration of the CCR3 antagonist SB328437 diminishes mechanical and thermal hypersensitivity. Additionally, repeated administration enhances the analgesic properties of morphine and buprenorphine following nerve injury. Simultaneously, the injection of SB328437 reduces the protein levels of some pronociceptive cytokines, such as IL-6, CCL7, and CCL11, in parallel with a reduction in the activation and influx of GFAP-, CD4- and MPO-positive cells in the spinal cord and/or DRG. Moreover, we have shown for the first time that an inhibitor of myeloperoxidase-4-aminobenzoic hydrazide may relieve pain and simultaneously enhance morphine and buprenorphine efficacy. The obtained results indicate the important role of CCR3 and its modulation in neuropathic pain treatment and suggest that it represents an interesting target for future investigations.

The Combined Regulation of Long Non-coding RNA and RNA-Binding Proteins in Atherosclerosis

Atherosclerosis is a complex disease closely related to the function of endothelial cells (ECs), monocytes/macrophages, and vascular smooth muscle cells (VSMCs). Despite a good understanding of the pathogenesis of atherosclerosis, the underlying molecular mechanisms are still only poorly understood. Therefore, atherosclerosis continues to be an important clinical issue worthy of further research. Recent evidence has shown that long non-coding RNAs (lncRNAs) and RNA-binding proteins (RBPs) can serve as important regulators of cellular function in atherosclerosis. Besides, several studies have shown that lncRNAs are partly dependent on the specific interaction with RBPs to exert their function. This review summarizes the important contributions of lncRNAs and RBPs in atherosclerosis and provides novel and comprehensible interaction models of lncRNAs and RBPs.