Biological function of Extracellular Vesicles (EVs): a review of the field.

Extracellular vesicles (EVs) theranostic potential is under intense investigation. There is a wealth of information highlighting the role that EVs and the secretome play in disease and how these are being utilized for clinical trials and novel therapeutic possibilities. However, understanding of the physiological and pathological roles of EVs remain incomplete. The challenge lies in reaching a consensus concerning standardized quality-controlled isolation, storage, and sample preparation parameters. Interest in circulating EV cargo as diagnostic and prognostic biomarkers is steadily growing. Though promising, various limitations need to be addressed before there can be successful, full-scale therapeutic use of approved EVs. These limitations include obtaining or manufacturing from the appropriate medium (e.g., from bodily fluid or cell culture), loading and isolating EVs, stability, and storage, standardization of processing, and determining potency. This review highlights specific topics, including circulation of abnormal EVs contribute to human disease and the theranostic potential of EVs. Theranostics is defined as a combination of the word's therapeutics and diagnostics and describes how a specific medicine or technique can function as both. Key findings include, (1) EVs and the secretome are future theranostics which will be utilized as both biomarkers for diagnosis and as therapeutics, (2) basic and translational research supports clinical trials utilizing EVs/secretome, and (3) additional investigation is required to fully unmask the theranostic potential of EVs/secretome in specific diseases and injuries.

Identifying Stress-Exacerbated Thermal-Injury Induced MicroRNAs.

Using a model of combat and operational stress reaction (COSR), our lab recently showed that exposure to an unpredictable combat stress (UPCS) procedure prior to a thermal injury increases pain sensitivity in male rats. Additionally, our lab has recently shown that circulating extracellular vesicle-microRNAs (EV-miRNAs), which normally function to suppress inflammation, were downregulated in a male rat model of neuropathic pain. In this current study, male and female rats exposed to UPCS, followed by thermal injury, were evaluated for changes in circulating EV-miRNAs. Adult female and male Sprague Dawley rats were exposed to a UPCS procedure for either 2 or 4 weeks. Groups consisted of the following: nonstress (NS), stress (S), NS + thermal injury (TI), and S + TI. Mechanical sensitivity was measured, and plasma was collected at baseline, throughout the UPCS exposure, and post-thermal injury. EV-miRNA isolation was performed, followed by small RNA sequencing and subsequent data analysis. UPCS exposure alone resulted in mechanical allodynia in both male and female rats at specific time points. Thermal-injury induction occurring at peak UPCS resulted in increased mechanical allodynia in the injured hind paw compared to thermal injury alone. Differential expression of the EV-miRNAs was observed between the NS and S groups as well as between NS + TI and S + TI groups. Consistent differences in EV-miRNAs are detectable in both COSR as well as during the development of mechanical sensitivity and potentially serve as key regulators, biomarkers, and targets in the treatment of COSR and thermal-injury induced mechanical sensitivity. PERSPECTIVE: This article presents the effects of unpredictable combat stress and thermal injury on EV-contained microRNAs in an animal model. These same mechanisms may exist in clinical patients and could be future prognostic and diagnostic biomarkers.

Battlefield pain summit 2022: Expert consensus statements.

BACKGROUND: Battlefield pain occurs in combat casualties who experience multiple severe injuries. The nature of battlefield scenarios requires a distinct approach to battlefield pain research. A battlefield pain summit was thus convened to identify shortcomings in the current understanding of battlefield pain management, review the current state of battlefield pain research, and shape the direction of future research. METHODS: On January 10 to 11, 2022, a hybrid in-person and virtual meeting hosted by the US Army Institute of Surgical Research defined research priorities for the Combat Casualty Care Research Program's Battlefield Pain research portfolio. Summit participants identified the following key focus areas under the umbrella of battlefield pain research: battlefield injury patterns; use of ketamine and nonopioid analgesics; analgesic delivery systems; the impact of analgesia on performance, cognition, and survival; training methods; battlefield regional anesthesia; and research models. Preliminary statements presented during the summit were refined and rank ordered through a Delphi process. RESULTS: Consensus was achieved on 7 statements addressing ideal analgesic properties, delivery systems, operational performance concerns, and pain training. Ketamine was identified as safe and effective for battlefield use, and further research into nonopioid analgesics represented a high priority. CONCLUSION: The 7 consensus statements that emerged from this battlefield pain summit serve as a template to define the near-term research priorities for military-specific battlefield pain research.

Pediatric Considerations for Dental Sleep Medicine.

Pediatric obstructive sleep apnea (OSA) is a serious medical condition with numerous health consequences. Dentists are well suited to recognize and provide medical referrals for pediatric patients at risk for OSA. Timely dental sleep medicine interventions may improve signs and symptoms of OSA in growing children. Orthodontic and dentofacial orthopedic treatment may decrease obstructive respiratory events in some pediatric patients. Palatal expansion may be part of a comprehensive orthodontic treatment plan to correct a malocclusion and treat OSA. Orthognathic surgery, mandibular advancement devices, and oropharyngeal exercises may have a role in the management of OSA in pediatric and adolescent patients.

Facial Nerve Paresis: Case Report of Blunt Facial Nerve Injury.

Facial nerve paresis is an uncommon but concerning condition in the pediatric population. The function and anatomy of the facial nerve is complex, and injuries to this structure may be associated with devastating physiological and psychological implications for the affected child and family. The purpose of this paper was to report a case involving a six-year-old Caucasian female who suffered a blunt traumatic injury to the orofacial region resulting in partial paralysis of the seventh cranial nerve. Following the injury, the child was unable to fully elevate the corner of her mouth. The deficit occurred immediately, and she experienced a prolonged course of recovery.

Recurrent TMJ Dislocation Managed with Botulinum Toxin Type A Injections in a Pediatric Patient.

Chronic recurrent temporomandibular joint (TMJ) dislocation is an uncommon condition that is painful and distressing to patients and uniquely challenging for clinicians. Sustained TMJ dislocation is not amenable to manual reduction alone when the etiology is muscular in nature. The purpose of this report was to describe the case of a child presenting with recurring temporomandibular joint dislocation secondary to muscle hyperactivity of unknown etiology that was managed with injections of botulinum toxin type A into the inferior lateral pterygoid muscles. The use of this peripheral antispasmoic neurotoxin is a reasonable, safe, and conservative, palliative treatment option for pediatric patients suffering from chronic recurring TMJ dislocation.

Submerged and Impacted Primary Molars.

Submerged tooth is the one that is depressed below the occlusal plane. Dental ankylosis is thought to be a major cause of submergence. Submerged deciduous teeth have the potential to cause malocclusion not only by prevention of their exfoliation and subsequent replacement by permanent teeth but also by causing tilting of proximal teeth and extrusion of opposing tooth. The purpose of this report is to present three different cases of submerged deciduous teeth and their clinical effects.