Osteology-focused redescription and description of the blood-feeding candirus Paracanthopoma parva and Paravandellia alleynei sp.n. (Trichomycteridae: Vandelliinae).

This study resolves a significant impediment to the taxonomy of the Neotropical endemic hematophagous candirus by providing the first high-resolution, CT-based osteological descriptions of type and nontype specimens of Paracanthopoma parva, type species of the genus. We also describe the distinctive new species Paravandellia alleynei based on specimens that were previously misidentified as Parac. parva in the only taxonomic study of that species since its 1935 description. Paracanthopoma parva is distinguished from all nominal congeners by its parietosupraoccipital and caudal skeleton morphology and by various meristics, including numbers of teeth on median premaxilla, vertebrae, and procurrent and principal caudal-fin rays. Paravandellia alleynei differs from both nominal congeners (Paravandellia oxyptera and Paravandellia phaneronema) by the unique morphology of its maxilla, mesethmoid and opercular apparatus, relative position of the pelvic- and anal-fin origins, orientation of the opercular odontodes, and various meristics, including numbers of vertebrae, median premaxillary teeth, medial teeth on premaxilla, branchiostegal rays, opercular and interopercular odontodes, distal claw-like premaxillary teeth, dorsal-fin rays and dentary teeth. This is the first species of Paravandellia recognized from Guyana and the Essequibo River basin. It is currently known only from two type specimens from the lower Essequibo River basin and 43 nontype specimens from the upper Branco River basin. By providing the first skeletal observations for type specimens of the type species Parac. parva and for topotypic specimens of all three nominal species of Paravandellia, we clarify and confirm the diagnosis of Parac. parva and establish a robust foundation for ongoing taxonomic revisions of these two small-sized and species-poor, yet trans-continentally distributed genera, both of which contain considerable unrecognized diversity.

Mandible Biomechanics and Continuously Erupting Teeth: A New Defect Model for Studying Load-Bearing Biomaterials.

Animals with elodont dentition and unfused mandible symphyses are hypothesized to have symmetric incisor morphology. Since these animals maintain their teeth by gnawing, they may provide physiologic feedback on mechanical function when unilateral mandible defects are created that manifest as ipsilateral changes in tooth structure. This defect model would potentially generate important information on the functional/mechanical properties of implants. Rats' and rabbits' mandibles and teeth are analyzed with µCT at baseline and post-intervention (n = 8 for each). Baseline incisors were compared. In a unilateral mandible pilot study, defects-ranging from critical size defect to complete ramus osteotomies-were created to assess effect on dentition (rats, n = 7; rabbits, n = 6). Within 90% confidence intervals, animals showed no baseline left/right differences in their incisors. There are apparent dental changes associated with unilateral defect type and location. Thus, at baseline, animals exhibit statistically significant incisor symmetry and there is an apparent relationship between mandible defect and incisor growth. The baseline symmetry proven here sets the stage to study the degree to which hemi-mandible destabilizing procedures result in measurable & reproducible disruption of dental asymmetry. In a validated model, an implant designed to function under load that prevents incisor asymmetry would provide supporting evidence that the implant has clinically useful load-bearing function.

Nanoparticles for drug delivery in Parkinson's disease.

Although effective symptomatic treatments for Parkinson's disease (PD) have been available for some time, efficient and well-controlled drug delivery to the brain has proven to be challenging. The emergence of nanotechnology has created new opportunities not only for improving the pharmacokinetics of conventional therapies but also for developing novel treatment approaches and disease modifying therapies. Several exciting strategies including drug carrier nanoparticles targeting specific intracellular pathways and structural reconformation of tangled proteins as well as introducing reprogramming genes have already shown promise and are likely to deliver more tailored approaches to the treatment of PD in the future. This paper reviews the role of nanoparticles in PD including a discussion of both their composition and functional capacity as well as their potential to deliver better therapeutic agents.

Ammoglanis natgeorum, a new miniature pencil catfish (Siluriformes: Trichomycteridae) from the lower Atabapo River, Amazonas, Venezuela.

A new species of the sand-dwelling catfish genus Ammoglanis is described from a marginal habitat of the lower Atabapo River, a left-bank blackwater tributary of the upper Orinoco River in Amazonas, Venezuela, adjacent to the border with Colombia. Ammoglanis natgeorum is distinguished from all congeners by trunk pigmentation pattern consisting of scattered ventral chromatophores concentrated around the anal-fin base and numerous additional meristic and anatomical characteristics. A. natgeorum is the second species of Ammoglanis described from the Orinoco River basin after Ammoglanis pulex, and several shared character states (e.g., eight total dorsal-fin rays, overall coloration pattern and presence of two finger-like papillae posterior to chin) suggest that it is more closely related to Ammoglanis obliquus (from the central Amazon basin) and A. pulex than to other congeners.

Hypoglossal nerve stimulation in a rabbit model of obstructive sleep apnea reduces apneas and improves oxygenation.

Based on a prior anesthetized model, we developed an unanesthetized model to evaluate the effects of hypoglossal nerve stimulation (HNS) during sleep. We prepared three rabbits with injections of hyaluronic acid in the base of tongue to produce upper airway obstruction followed by HNS implant. Two rabbits were saline controls, and one, a passive control. Measures were sleep, airflow, effort, oxygen saturation, and heart rate. HNS with electrodes around the right hypoglossal nerve were adjusted to a level without behaviorally disturbing the animal. During HNS stimulation in the tongue-base injected rabbits, obstructive apneas and hypopneas of intermediate (3 to 7 cycles of respiratory effort) or longer (≥8 cycles) duration were largely eliminated while less clinically relevant shorter events (<3) were unaffected, and oxygen saturation was improved. Control animals exhibited no intermediate or long events. In this model HNS can relieve induced sleep apnea, without disturbing the animal: however, despite being non-canine and of substantial size, the model has its challenges.NEW & NOTEWORTHY This report describes a rabbit model for testing the impact of hypoglossal nerve stimulation (HNS) on obstructive apneas. Obstructive sleep apnea (OSA) is induced by injecting hyaluronic acid (as a filler) into the base of the tongue. HNS reduced the length and rate of obstructions and improved oxygenation during sleep. Our efforts with this model advanced understanding of the complexities of this OSA preclinical model for neurostimulation reversal of sleep-disordered breathing.

Single Dose of Pseudoephedrine Induces Simultaneous Bilateral Acute Angle Closure Crisis.

Simultaneous bilateral acute angle closure crisis (AACC) is a sight-threatening ocular emergency. Many "cold and flu" preparations contain compounds with sympathomimetic or anticholinergic qualities that confer a risk of inducing AACC. We present a review of cold and flu preparation-induced AACC, and present a case of simultaneous bilateral AACC triggered by a single oral dose of pseudoephedrine. The challenges facing the clinician in recognizing simultaneous bilateral AACC in the context of an upper respiratory tract infection are addressed. An awareness of this uncommon clinical entity, its pertinent clinical features, risk factors, and the drug classes that may precipitate an attack is critical for the timely diagnosis and management of this ocular emergency. Notably, clinicians must be aware that even a single dose of an implicated medication may trigger an attack of AACC.

Minor Review: An Overview of a Synthetic Nanophase Bone Substitute.

Material is reviewed that consists of reconstituted collagen fibril gel mineralized in a manner that produces biomimetically sized nanoapatites intimately associated with the fibrils. This gel is formed into usable shapes with a modulus and strength that allow it to be surgically press fitted into bony defects. The design paradigm for the material is that the nanoapatites will dissolve into soluble Ca2+ as the collagen is degraded into RGD-containing peptide fragments due to osteoclastic action. This is intended to signal to the osteoclasts to continue removing the material in a biomimetic fashion similar to bony remodeling. Preliminary experiments in a subcutaneous rat model show that the material is biocompatible with respect to inflammatory and immunogenic responses, and that it supports cellular invasion. Preliminary experiments in a critical-sized mandibular defect in rats show that the material is resorbable and functions well as a bone morphogenetic 2 (BMP-2) carrier. We have produced a range of mechanical and biological responses by varying mechanical and chemical processing of the material.

Hypoglossal nerve stimulation in a pre-clinical anesthetized rabbit model relevant to OSA.

We tested the functional effects of hypoglossal (CNXII) stimulation in the anesthetized rabbit before and after injections of saline into the tongue base to obstruct the airway. Data (n = 6) show little or no effect of CN XII trunk stimulation; however, medial branch stimulation (20-100 Hz; 50-500 µs pulse width, and incremental increases from 10 µA) reduced upper airway resistance. Medial branch stimulation was less effective in reducing resistance than anterior advancement of the hyoid. Endoscopic viewing (n-3) of the retropalate showed this region as the narrowest and dynamically changed by anterior hyoid displacement, with less evident effects than CNXII stimulation. We conclude that under these conditions CNXII medial branch stimulation reduces airway resistance, especially after induced obstruction.

Nanophase bone substitute for craniofacial load bearing application: Pilot study in the rodent.

An exploratory pilot study shows that a rodent mandibular defect model is useful in determining the biological response to a nanophase collagen/apatite composite designed as a biomimetic load-bearing bone substitute. Using a critical size defect, eight groups of rats (n = 3) were implanted with four renditions of the nanophase bone substitute (NBS) biomaterial. Each rendition was tested with and without recombinant human bone morphogenetic protein 2 (BMP2). NBS biomaterial renditions were: baseline, hyper-densified, d-ribose crosslinked, and d-ribose crosslinked and hyper-densified. Biological outcomes were assessed surgically, radiologically, and histologically. With the limited power available due to the small N's involved, some interesting hypotheses were generated that will be more fully investigated in future studies. BMP2 loaded NBS, when uncrosslinked, resulted in robust bone formation in the entire defect volume (regardless of porosity). Unloaded NBS were well tolerated but did not cause significant new bone formation in the defect volume. Densification alone had little effect on in vivo performance. Crosslinking thwarted implant uptake of BMP2 and resulted in fibrous encapsulation. It is concluded that the nanophase bone substitute is well tolerated in this bone defect model. When loaded with BMP2, implantation resulted in complete bony healing and defect closure with implant density (porosity) having little effect on bone healing or remodeling. Without BMP2 the biomaterial did not result in defect closure. Crosslinking, necessary to increase mechanical properties in an aqueous environment, disrupts osteointegration and BMP2 uptake. Alternate implant fabrication strategies will be necessary to achieve an improved balance between material strength and osteointegration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 520-532, 2018.

Upper Airway Stimulation for Obstructive Sleep Apnea: Patient-Reported Outcomes after 48 Months of Follow-up.

Objective To assess patient-based outcomes of participants in a large cohort study-the STAR trial (Stimulation Therapy for Apnea Reduction)-48 months after implantation with an upper airway stimulation system for moderate to severe obstructive sleep apnea. Study Design A multicenter prospective cohort study. Setting Industry-supported multicenter academic and clinical setting. Subjects Participants (n = 91) at 48 months from a cohort of 126 implanted participants. Methods A total of 126 participants received an implanted upper airway stimulation system in a prospective phase III trial. Patient-reported outcomes at 48 months, including Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), and snoring level, were compared with preimplantation baseline. Results A total of 91 subjects completed the 48-month visit. Daytime sleepiness as measured by ESS was significantly reduced ( P = .01), and sleep-related quality of life as measured by FOSQ significantly improved ( P = .01) when compared with baseline. Soft to no snoring was reported by 85% of bed partners. Two patients required additional surgery without complication for lead malfunction. Conclusion Upper airway stimulation maintained a sustained benefit on patient-reported outcomes (ESS, FOSQ, snoring) at 48 months in select patients with moderate to severe obstructive sleep apnea.

Fetal Alcohol Spectrum Disorders and Challenges Faced by Caregivers: Clinicians' Perspectives.

BackgroundThere is a notable absence of evidence based early interventions for young children with FASD.  ObjectiveThis study examines clinicians' perspectives regarding the needs of caregivers of children with FASD and how such perspectives informed the development of a family-centered early intervention for young children with prenatal alcohol exposure.  Method19 professionals who work with children with prenatal alcohol exposure and / or in out-of-home care were recruited to participate in focus groups. The facilitator used a semi-structured topic guide to elicit feedback from participants. These data were transcribed, coded, and categorized to reflect themes in a manner informed by a grounded theory approach. A second investigator repeated the process. Codes were chosen and assigned to data by consensus.   ResultsThe coded data yielded five distinct perceived challenges faced by caregivers: (1) seeking and possibly receiving a diagnosis; (2) processing emotions and coming to terms with the child's difficulties; (3) seeking support and belonging within a knowledgeable community; (4) developing a new understanding of the child's behavior; and (5) becoming an educator, advocate, and expert on the child and FASD.   ConclusionProfessionals believe specific capacities are essential insofar as the human service systems that caregivers engage are perceived to be under-equipped to respond to the distinct set of challenges faced by children with FASD and their families. Findings are discussed in terms of how the proposed intervention was designed to address such challenges and to cultivate those key capacities in order for families to meet their children's needs.

Three-Year Outcomes of Cranial Nerve Stimulation for Obstructive Sleep Apnea: The STAR Trial.

OBJECTIVE: To describe the 36-month clinical and polysomnography (PSG) outcomes in an obstructive sleep apnea (OSA) cohort treated with hypoglossal cranial nerve upper airway stimulation (UAS). STUDY DESIGN: A multicenter prospective cohort study. SETTING: Industry-supported multicenter academic and clinical setting. SUBJECTS: Participants (n = 116) at 36 months from a cohort of 126 implanted participants. METHODS: Participants were enrolled in a prospective phase III trial evaluating the efficacy of UAS for moderated to severe OSA. Prospective outcomes included apnea-hypopnea index, oxygen desaturation index, other PSG measures, self-reported measures of sleepiness, sleep-related quality of life, and snoring. RESULTS: Of 126 enrolled participants, 116 (92%) completed 36-month follow-up evaluation per protocol; 98 participants additionally agreed to a voluntary 36-month PSG. Self-report daily device usage was 81%. In the PSG group, 74% met the a priori definition of success with the primary outcomes of apnea-hypopnea index, reduced from the median value of 28.2 events per hour at baseline to 8.7 and 6.2 at 12 and 36 months, respectively. Similarly, self-reported outcomes improved from baseline to 12 months and were maintained at 36 months. Soft or no snoring reported by bed partner increased from 17% at baseline to 80% at 36 months. Serious device-related adverse events were rare, with 1 elective device explantation from 12 to 36 months. CONCLUSION: Long-term 3-year improvements in objective respiratory and subjective quality-of-life outcome measures are maintained. Adverse events are uncommon. UAS is a successful and appropriate long-term treatment for individuals with moderate to severe OSA.

Upper Airway Stimulation for Obstructive Sleep Apnea: Self-Reported Outcomes at 24 Months.

OBJECTIVES: To evaluate the long-term (24-mo) effect of cranial nerve upper airway stimulation (UAS) therapy on patient-centered obstructive sleep apnea (OSA) outcome measures. METHODS: Prospective, multicenter, cohort study of 126 patients with moderate to severe OSA who had difficulty adhering to positive pressure therapy and received the surgically implanted UAS system. Outcomes were measured at baseline and postoperatively at 12 mo and 24 mo, and included self- and bedpartner-report of snoring intensity, Epworth Sleepiness Scale (ESS), and Functional Outcomes of Sleep Questionnaire (FOSQ). Additional analysis included FOSQ subscales, FOSQ-10, and treatment effect size. RESULTS: Significant improvement in mean FOSQ score was observed from baseline (14.3) to 12 mo (17.3), and the effect was maintained at 24 mo (17.2). Similar improvements and maintenance of effect were seen with all FOSQ subscales and FOSQ-10. Subjective daytime sleepiness, as measured by mean ESS, improved significantly from baseline (11.6) to 12 mo (7.0) and 24 mo (7.1). Self-reported snoring severity showed increased percentage of "no" or "soft" snoring from 22% at baseline to 88% at 12 mo and 91% at 24 mo. UAS demonstrated large effect size (> 0.8) at 12 and 24 mo for overall ESS and FOSQ measures, and the effect size compared favorably to previously published effect size with other sleep apnea treatments. CONCLUSIONS: In a selected group of patients with moderate to severe OSA and body mass index ≤ 32 kg/m2, hypoglossal cranial nerve stimulation therapy can provide significant improvement in important sleep related quality-of-life outcome measures and the effect is maintained across a 2-y follow-up period.

Photothermal killing of Staphylococcus aureus using antibody-targeted gold nanoparticles.

PURPOSE: The continued emergence of multidrug resistant bacterial infections and the decline in discovery of new antibiotics are major challenges for health care throughout the world. This situation has heightened the need for novel antimicrobial therapies as alternatives to traditional antibiotics. The combination of metallic nanoparticles and laser exposure has been proposed as a strategy to induce physical damage to bacteria, regardless of antibiotic sensitivity. The purpose of this study was to test the antibacterial effect of antibody-targeted gold nanoparticles combined with pulsed laser irradiation. METHODS: Gold nanoparticles conjugated to antibodies specific to Staphylococcus aureus peptidoglycan were incubated with suspensions of methicillin-resistant and methicillin-sensitive S. aureus (MRSA and MSSA). Bacterial suspensions were then exposed to 8 ns pulsed laser irradiation at a wavelength of 532 nm and fluences ranging from 1 to 5 J/cm(2). Viability of the bacteria following laser exposure was determined using colony forming unit assays. Scanning electron microscopy was used to confirm the binding of nanoparticles to bacteria and the presence of cellular damage. RESULTS: The laser-activated nanoparticle treatment reduced the surviving population to 31% of control in the MSSA population, while the survival in the MRSA population was reduced to 58% of control. Significant decreases in bacterial viability occurred when the laser fluence exceeded 1 J/cm(2), and this effect was linear from 0 to 5 J/cm(2) (r (2)=0.97). Significantly less bactericidal effect was observed for nonfunctionalized nanoparticles or functionalized nanoparticles without laser activation. CONCLUSION: Laser-activated nanoparticles targeted to S. aureus surface antigens significantly reduced the percentage of viable organisms and represents a promising new treatment modality that could be used either alone or as an adjunct to existing, conventional antibiotic therapy.

Randomized controlled withdrawal study of upper airway stimulation on OSA: short- and long-term effect.

OBJECTIVE: To assess the efficacy and durability of upper airway stimulation via the hypoglossal nerve on obstructive sleep apnea (OSA) severity including objective and subjective clinical outcome measures. STUDY DESIGN: A randomized controlled therapy withdrawal study. SETTING: Industry-supported multicenter academic and clinical setting. SUBJECTS: A consecutive cohort of 46 responders at 12 months from a prospective phase III trial of 126 implanted participants. METHODS: Participants were randomized to either therapy maintenance ("ON") group or therapy withdrawal ("OFF") group for a minimum of 1 week. Short-term withdrawal effect as well as durability at 18 months of primary (apnea hypopnea index and oxygen desaturation index) and secondary outcomes (arousal index, oxygen desaturation metrics, Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, snoring, and blood pressure) were assessed. RESULTS: Both therapy withdrawal group and maintenance group demonstrated significant improvements in outcomes at 12 months compared to study baseline. In the randomized assessment, therapy withdrawal group returned to baseline, and therapy maintenance group demonstrated no change. At 18 months with therapy on in both groups, all objective respiratory and subjective outcome measures showed sustained improvement similar to those observed at 12 months. CONCLUSION: Withdrawal of therapeutic upper airway stimulation results in worsening of both objective and subjective measures of sleep and breathing, which when resumed results in sustained effect at 18 months. Reduction of obstructive sleep apnea severity and improvement of quality of life were attributed directly to the effects of the electrical stimulation of the hypoglossal nerve.

Sternoclavicular osteoradionecrosis following treatment for head and neck cancer.

Osteoradionecrosis (ORN) is a well described complication of radiation therapy (RT) for head and neck cancer (HNC), with a past reported incidence as high as 10-18% [1,4] mostly involving the mandible. ORN rarely involves the sternoclavicular complex in HNC patients treated with RT. Here, we present a case of HNC treated with combined (cytotoxic) chemotherapy and radiation therapy (CCRT) complicated by ORN and osteomyelitis of the sternoclavicular complex involving large segments of both clavicles, the sternum, and the trachea.

A selected review of the recent advances in craniomaxillofacial bone tissue engineering.

PURPOSE OF REVIEW: Craniofacial surgeons must continually make decisions about how to best reconstruct the craniomaxillofacial skeleton (CFS). A high priority has been placed on the search for bone substitute materials (BSMs) that are both mechanically and biologically optimized for these reconstructions. This review is intended to present the complexity of this undertaking to physicians and scientists by reviewing the technological advances published in the last 2 years. RECENT FINDINGS: Advances in bone tissue engineering took place in the areas of scaffolds, bioactive factors (e.g. growth factors, cytokines, and pharmaceuticals), and cellular components. Recent literature highlighted the complex interplay between these elements. Researchers also made great strides in merging high-resolution imaging with computer-aided tissue engineering. SUMMARY: Developing BSMs that fulfill the many needs in the CFS is difficult and there are multiple barriers to clinical translation. However, based on the progress in the last 2 years in the individual elements of BSM development as well as integration of those elements into implantable constructs, it appears that a product with specific CFS applications is on the horizon.

Nanophase bone substitute in vivo response to subcutaneous implantation.

A collagen-apatite composite designed as a load-bearing bone substitute implant is used to characterize the relationship between implant morphology and in vivo behavior. This nanophase bone substitute (NBS) is studied morphologically using a nondestructive imaging technique and biologically using the rodent subcutaneous model. Porosity and pore interconnectivity are correlated with histological outcomes showing cellular invasion occurs with average pore sizes below 100 µm. Crosslinking with D-ribose is shown to affect cellular infiltration in a dose-response manner. These data suggest that collagen-apatite bone substitutes can support cellular infiltration with pore size significantly smaller than 100 µm, an encouraging result regarding development of the NBS into a platform of biomaterials with enhanced mechanical properties. The data also indicate that increasing crosslinking density decreases cellular infiltration of NBS. Thus, modulating mechanical properties of the material by altering crosslink density is likely to produce decreased biological response within the material.