Aligned Bioelectronic Polypyrrole/Collagen Constructs for Peripheral Nerve Interfacing.

Electrical stimulation has shown promise in clinical studies to treat nerve injuries. This work is aimed to create an aligned bioelectronic construct that can be used to bridge a nerve gap, directly interfacing with the damaged nerve tissue to provide growth support. The conductive three-dimensional bioelectronic scaffolds described herein are composite materials, comprised of conductive polypyrrole (PPy) nanoparticles embedded in an aligned collagen hydrogel. The bioelectronic constructs are seeded with dorsal root ganglion derived primary rat neurons and electrically stimulated in vitro. The PPy loaded constructs support a 1.7-fold increase in neurite length in comparison to control collagen constructs. Furthermore, upon electrical stimulation of the PPy-collagen construct, a 1.8-fold increase in neurite length is shown. This work illustrates the potential of bioelectronic constructs in neural tissue engineering and lays the groundwork for the development of novel bioelectronic materials for neural interfacing applications.

The Grief Debate, the DSM, and Clinical Practice.

There has been an ongoing debate regarding grief, whether it may be at times pathological, and whether it is different from depression. This article addresses those questions by tracking the changing course of the Diagnostic and Statistical Manuals of Mental Disorders (DSMs) since DSM-III and by reviewing the debate concerning grief and depression. At the time when DSM-III was being prepared in the late 1970s (it was published in 1980), there was a concern that normal bereavement (or grief) was being diagnosed as major depression. To address this concern, the editors of DSM-III added a category of "uncomplicated bereavement." The fourth edition of the DSM (DSM-IV), published in 1994, then followed by a minor change. However, the editors of DSM-5 decided to eliminate the bereavement exclusion entirely. Their concern was simply whether the individual did or did not suffer from major depression. Since an individual might not warrant a diagnosis of major depression but might still be experiencing grief, the DSM discussion leads directly into the question of whether grief-later called prolonged grief disorder-and depression are separate conditions. Advocates for prolonged grief disorder maintained that grief is different from depression but that patients may present with a mix of grief and depressive symptoms that are clinically difficult to distinguish. Advocates of separate conditions have in fact developed an inventory of symptoms that identify prolonged grief disorder. However, inasmuch as a typical grief presentation will include depressive symptoms, the clinical challenge is to distinguish prolonged grief disorder and major depression, as well as to distinguish both from normal grief. Given the temporal limits of an average consultation, this article argues that making the required distinctions is an unrealistic expectation. Finally, researchers have developed specific treatment programs for prolonged grief disorder, but a conflict between the 2 primary researchers involved and the generalities in which the programs are phrased have led to the suggestion of a different approach to treatment that replaces generalities with a person-centered approach.

Comparison of adaptation characteristics between visually and memory-guided saccades.

Saccade adaptation plays a crucial role in maintaining saccade accuracy. The behavioral characteristics and neural mechanisms of saccade adaptation for an externally cued movement, such as visually guided saccades (VGS), are well studied in nonhuman primates. In contrast, little is known about the saccade adaptation of an internally driven movement, such as memory-guided saccades (MGS), which are guided by visuospatial working memory. As the oculomotor plant changes because of growth, aging, or skeletomuscular problems, both types of saccades need to be adapted. Do both saccade types engage a common adaptation mechanism? In this study, we compared the characteristics of amplitude decrease adaptation in MGS with VGS in nonhuman primates. We found that the adaptation speed was faster for MGS than for VGS. Saccade duration changed during MGS adaptation, whereas saccade peak velocity changed during VGS adaptation. We also compared the adaptation field, that is, the gain change for saccade amplitudes other than the adapted. The gain change for MGS declines on both smaller and larger sides of adapted amplitude, more rapidly for larger than smaller amplitudes, whereas the decline in VGS was reversed. Thus, the differences between VGS and MGS adaptation characteristics support the previously suggested hypothesis that the adaptation mechanisms of VGS and MGS are distinct. Furthermore, the result suggests that the MGS adaptation site is a brain structure that influences saccade duration, whereas the VGS adaptation site influences saccade peak velocity. These results should be beneficial for future neurophysiological experiments.NEW & NOTEWORTHY Plasticity helps to overcome persistent motor errors. Such motor plasticity or adaptation can be investigated with saccades. Thus far our knowledge is primarily about visually guided saccades, an externally cued movement, which we can make only when the object is visible at the time of saccade. However, as the world is complex, we can make saccades even when the object is not visible. Here, we investigate the adaptation of an internally driven movement: the memory-guided saccade.

A unit process log reduction database for water reuse practitioners.

Pathogen reduction for the purpose of human health protection is a critical function provided by water reuse systems. Pathogen reduction performance potential is dependent on a wide range of design and operational parameters. Poor understanding of pathogen reduction performance has important consequences-under treatment can jeopardize human health, while over treatment can lead to unnecessary costs and environmental impacts. Documented pathogen reduction potential of the unit processes that make up water reuse treatment trains is based on a highly dispersed and unstructured literature, creating an impediment to practitioners looking to design, model or simply better understand these systems. This review presents a database of compiled log reduction values (LRVs) and log reduction credits (LRCs) for unit processes capable of providing some level of pathogen reduction, with a focus on processes suitable for onsite non-potable water reuse systems. Where reported, we have also compiled all relevant design and operational factors associated with the LRVs and LRCs. Overall, we compiled over 1100 individual LRV data entries for 31 unit processes, and LRCs for 8 unit processes. Results show very inconsistent reporting of influencing parameters, representing a limitation to the use of some of the data. As a standalone resource, the database (included as Supplemental Information) provides water reuse practitioners with easy access to LRV and LRC data. The database is also part of a longer-term effort to optimize the balance between human health protection, potential environmental impacts and cost of water reuse treatment trains.

Pre-Operative Characteristics Helping to Avoid Gastrostomy Tube After Mandibular Distraction in Neonates With Pierre-Robin Sequence: A Institutional Case-Series and Review of the Literature.

OBJECTIVE: to investigate the ability of mandibular distraction osteogenesis (MDO) to avoid gastrostomy tube (G-tube). DATA SOURCES: PubMed, EBSCOhost, Cochrane, and Embase. REVIEW METHODS: We retrospectively reviewed the number of MDO cases performed at our institution for patients with Robin Sequence (RS) over the past 10 years. In our institutional review, patients were excluded if they had a G-tube already placed at the time of surgery. We also performed a systematic review of the literature. Articles were excluded if they did not detail feeding outcomes after MDO, or if MDO was performed on patients that did not have RS. RESULTS: In our systematic review, 12 articles were included that comprised a total of 209 neonates with RS that underwent MDO. A total of 174 (83.3%) patients avoided a G-tube once MDO was performed. A total of 14 patients met the inclusion criteria at our institution. Of the 14 RS patients, 9 (64%) avoided having a G-tube placed and all (14/14) avoided tracheostomy. The average birth weight of patients avoiding a G-tube was 3.11 kg compared to 2.25 kg (P = .045) in the group requiring a G-tube. In the group avoiding a G-tube, the average weight at time of operation was 3.46 kg compared to 2.83 kg (P = .037) in the group requiring a G-tube. CONCLUSION: MDO may be considered as a surgical option to prevent G-tube placement for neonates with non-syndromic RS who have difficulty with PO feeding but whose airway obstruction is not severe enough to require respiratory support. Based on our institutional experience, a minimum weight of 3.00 kg correlated with higher success rates of PO intake and avoiding a G-tube.

Recurrent Peritonsillar Abscess Caused by Vaginal Flora: A Common Problem From a Unique Source.

Peritonsillar abscesses (PTAs) are typically caused by group A Streptococcus or mixed oral flora. Gardnerella vaginalis is a part of the normal vaginal microbiome, and overgrowth can cause bacterial vaginosis. We present a case of recurrent PTA with G. vaginalis superinfection, which occurred after the patient performed oral sex on a female after incision and drainage of her initial PTA. The patient continued to have recurrent PTAs until G. vaginalis was identified, and antibiotic coverage was broadened to cover both group A Streptococcus and G. vaginalis. This case highlights the importance of culturing PTA aspirate for directed antibiosis in persistent or recurrent infections. The rare superinfection also raises the question of advising abstinence from oral-genital contact after oral procedures to minimize risk of superinfection.

Formation of vascular-like structures using a chemotaxis-driven multiphase model.

We propose a continuum model for pattern formation, based on the multiphase model framework, to explore in vitro cell patterning within an extracellular matrix (ECM). We demonstrate that, within this framework, chemotaxis-driven cell migration can lead to the formation of cell clusters and vascular-like structures in 1D and 2D respectively. The influence on pattern formation of additional mechanisms commonly included in multiphase tissue models, including cell-matrix traction, contact inhibition, and cell-cell aggregation, are also investigated. Using sensitivity analysis, the relative impact of each model parameter on the simulation outcomes is assessed to identify the key parameters involved. Chemoattractant-matrix binding is further included, motivated by previous experimental studies, and found to reduce the spatial scale of patterning to within a biologically plausible range for capillary structures. Key findings from the in-depth parameter analysis of the 1D models, both with and without chemoattractant-matrix binding, are demonstrated to translate well to the 2D model, obtaining vascular-like cell patterning for multiple parameter regimes. Overall, we demonstrate a biologically-motivated multiphase model capable of generating long-term pattern formation on a biologically plausible spatial scale both in 1D and 2D, with applications for modelling in vitro vascular network formation.

Sensorineural correlates of failed functional recovery after natural regeneration of vestibular hair cells in adult mice.

Vestibular hair cells (HCs) are mechanoreceptors that sense head motions by modulating the firing rate of vestibular ganglion neurons (VGNs), whose central processes project to vestibular nucleus neurons (VNNs) and cerebellar neurons. We explored vestibular function after HC destruction in adult Pou4f3+/DTR (DTR) mice, in which injections of high-dose (50 ng/g) diphtheria toxin (DT) destroyed most vestibular HCs within 2 weeks. At that time, DTR mice had lost the horizontal vestibulo-ocular reflex (aVORH), and their VNNs failed to upregulate nuclear cFos expression in response to a vestibular stimulus (centrifugation). Five months later, 21 and 14% of HCs were regenerated in utricles and horizontal ampullae, respectively. The vast majority of HCs present were type II. This degree of HC regeneration did not restore the aVORH or centrifugation-evoked cFos expression in VNNs. The failure to regain vestibular pathway function was not due to degeneration of VGNs or VNNs because normal neuron numbers were maintained after HC destruction. Furthermore, sinusoidal galvanic stimulation at the mastoid process evoked cFos protein expression in VNNs, indicating that VGNs were able to regulate VNN activity after HC loss. aVORH and cFos responses in VNNs were robust after low-dose (25 ng/g) DT, which compared to high-dose DT resulted in a similar degree of type II HC death and regeneration but spared more type I HCs in both organs. These findings demonstrate that having more type I HCs is correlated with stronger responses to vestibular stimulation and suggest that regenerating type I HCs may improve vestibular function after HC loss.

AMBERff at Scale: Multimillion-Atom Simulations with AMBER Force Fields in NAMD.

All-atom molecular dynamics (MD) simulations are an essential structural biology technique with increasing application to multimillion-atom systems, including viruses and cellular machinery. Classical MD simulations rely on parameter sets, such as the AMBER family of force fields (AMBERff), to accurately describe molecular motion. Here, we present an implementation of AMBERff for use in NAMD that overcomes previous limitations to enable high-performance, massively parallel simulations encompassing up to two billion atoms. Single-point potential energy comparisons and case studies on model systems demonstrate that the implementation produces results that are as accurate as running AMBERff in its native engine.

Cognition and saccadic eye movement performance are impaired in chronic rhinosinusitis.

BACKGROUND: Patients with chronic rhinosinusitis (CRS) can experience cognitive dysfunction. The literature on this topic mostly reflects patient-reported measurements. Our goal was to assess cognitive function in patients with CRS using objective measures, including saccadic eye movements-a behavioral response reflecting cognitive and sensory information integration that is often compromised in conditions with impaired cognition. METHODS: Participants (N = 24 with CRS, N = 23 non-CRS healthy controls) enrolled from rhinology clinic underwent sinonasal evaluation, quality of life assessment (Sino-nasal Outcome Test 22 [SNOT-22]), and cognitive assessment with the Neuro-QOL Cognitive Function-Short Form, the Montreal Cognitive Assessment (MoCA), and recording of eye movements using video-oculography. RESULTS: Participants with CRS were more likely to report cognitive dysfunction (Neuro-QOL; 45.8% vs. 8.7%; p = 0.005) and demonstrate mild or greater cognitive impairment (MoCA; 41.7% vs. 8.7%; p = 0.005) than controls. Additionally, participants with CRS performed worse on the MoCA overall and within the executive functioning and memory domains (all p < 0.05) and on the anti-saccade (p = 0.014) and delay saccade (p = 0.044) eye movement tasks. Poorer performance on the MoCA (r = -0.422; p = 0.003) and the anti-saccade (r = -0.347; p = 0.017) and delay saccade (r = -0.419; p = 0.004) eye movement tasks correlated with worse CRS severity according to SNOT-22 scores. CONCLUSION: This study is the first to utilize objective eye movement assessments in addition to researcher-administered cognitive testing in patients with CRS. These patients demonstrated a high prevalence of cognitive dysfunction, most notably within executive functioning and memory domains, with the degree of dysfunction correlating with the severity of CRS.

Associations between baseline cognitive status and motor outcomes after treadmill training in people with Parkinson's disease: a pilot study.

PURPOSE: To determine the effect of baseline cognition on gait outcomes after a treadmill training program for people with Parkinson's disease (PD). METHODS: This pilot clinical trial involved people with PD who were classified as having no cognitive impairment (PD-NCI) or mild cognitive impairment (PD-MCI). Baseline executive function and memory were assessed. The intervention was a 10-week gait training program (twice-weekly treadmill sessions), with structured speed and distance progression and verbal cues for gait quality. Response to intervention was assessed by gait speed measured after week 2 (short-term) and week 10 (long-term). RESULTS: Participants (n = 19; 12 PD-NCI, 7 PD-MCI) had a mean (standard deviation) age of 66.5 (6.3) years, disease duration of 8.8 (6.3) years, and MDS-UPDRS III score of 21.3 (10.7). Gait speed increased at short-term and long-term assessments. The response did not differ between PD-NCI and PD-MCI groups; however, better baseline memory performance and milder PD motor severity were independently associated with greater improvements in gait speed in unadjusted and adjusted models. CONCLUSIONS: These findings suggest that memory impairments and more severe motor involvement can influence the response to gait rehabilitation in PD and highlight the need for treatments optimized for people with greater cognitive and motor impairment.IMPLICATIONS FOR REHABILITATIONCognitive deficits in Parkinson's disease (PD) could impact motor learning and gait rehabilitation, yet little is known about the effects of cognitive impairments on the response to rehabilitation in people with PD.This study demonstrates that the response to gait rehabilitation did not differ between people with PD who had no cognitive impairment and those with mild cognitive impairment.Across all participants, better baseline memory was associated with greater improvements in gait speed.Rehabilitation professionals should be mindful of PD severity, as those with more substantial memory and motor impairments may require additional dosing or support to maximize gait training benefits.

Advanced Formulation Approaches for Emerging Therapeutic Technologies.

In addition to proteins, discussed in the Chapter "Advances in Vaccine Adjuvants: Nanomaterials and Small Molecules", there are a wide range of alternatives to small molecule active ingredients. Cells, extracellular vesicles, and nucleic acids in particular have attracted increasing research attention in recent years. There are now a number of products on the market based on these emerging technologies, the most famous of which are the mRNA-based vaccines against SARS-COV-2. These advanced therapeutic moieties are challenging to formulate however, and there remain significant challenges for their more widespread use. In this chapter, we consider the potential and bottlenecks for developing further medical products based on these systems. Cells, extracellular vesicles, and nucleic acids will be discussed in terms of their mechanism of action, the key requirements for translation, and how advanced formulation approaches can aid their future development. These points will be presented with selected examples from the literature, and with a focus on the formulations which have made the transition to clinical trials and clinical products.

Effect of a community-based primary healthcare programme on adverse pregnancy outcomes in Northern Ghana.

BACKGROUND: Pregnancy complications and adverse birth outcomes are among the major contributors to poor maternal and child health. Mothers in remote communities are at higher risk of adverse birth outcomes due to constraints in access to healthcare services. In Ghana, a community-based primary healthcare programme called the Ghana Essential Health Interventions Programme (GEHIP) was implemented in a rural region to help strengthen primary healthcare delivery and improve maternal and child healthcare services delivery. This study assessed the effect of this programme on adverse pregnancy outcomes. METHODS: Baseline and end-line survey data from reproductive-aged women from the GEHIP project were used in this analysis. Difference-in-differences and logistic regressions were used to examine the impact and equity effect of GEHIP on adverse pregnancy outcomes using household wealth index and maternal educational attainment as equity measures. The analysis involves the comparison of project baseline and end-line outcomes in intervention and non-intervention districts. RESULTS: The intervention had a significant effect in the reduction of adverse pregnancy outcomes (OR = 0.96, 95% CI:0.93-0.99). Although disadvantaged groups experience larger reductions in adverse pregnancy outcomes, controlling for covariates, there was no statistically significant equity effect of GEHIP on adverse pregnancy outcomes using either the household wealth index (OR = 0.99, 95% CI:0.85-1.16) or maternal educational attainment (OR = 0.68, 95% CI: 0.44-1.07) as equity measures. CONCLUSION: GEHIP's community-based healthcare programme reduced adverse pregnancy outcomes but no effect on relative equity was established. Factoring in approaches for targeting disadvantaged populations in the implementation of community-based health programs is crucial to ensuring equity in health outcomes.

Electrospun aligned tacrolimus-loaded polycaprolactone biomaterials for peripheral nerve repair.

Background: Efficacious repair of peripheral nerve injury is an unmet clinical need. The implantation of biomaterials containing neurotrophic drugs at the injury site could promote nerve regeneration and improve outcomes for patients. Materials & methods: Random and aligned electrospun poly-ε-caprolactone scaffolds containing encapsulated tacrolimus were fabricated, and the gene expression profile of Schwann cells (SCs) cultured on the surface was elucidated. On aligned fibers, the morphology of SCs and primary rat neurons was investigated. Results: Both scaffold types exhibited sustained release of drug, and the gene expression of SCs was modulated by both nanofibrous topography and the presence of tacrolimus. Aligned fibers promoted the alignment of SCs and orientated outgrowth from neurons. Conclusion: Electrospun PCL scaffolds with tacrolimus hold promise for the repair of peripheral nerve injury.

This article reports the production and testing of fibrous materials loaded with tacrolimus, a drug known to improve nerve regeneration, for the surgical repair of peripheral nerve injury. Materials were created with either a randomly orientated structure or an aligned structure that mimics the anatomy of native nerve, and both displayed long-term release of the loaded drug. Schwann cells, which are a critical cell type in nerve regeneration, were grown on the materials and their behaviour was positively influenced by the fibrous surfaces and/or the presence of tacrolimus. Neurons grown on the aligned materials demonstrated directional outgrowth, which may be also beneficial for increasing the rate of regeneration. These materials have the potential to improve outcomes of nerve repair for patients.

Pediatric Otolaryngology Short-Term Mission Outcomes at a Surgical Mission Hospital in Guatemala.

OBJECTIVE: The frequency of humanitarian surgical mission trips has grown over recent decades. Unfortunately, research on patient outcomes from these trips has not increased proportionately. We aim to analyze the safety and efficacy of surgeries in a low- and middle-income country missions-based surgery center in Guatemala City, Guatemala, and identify factors that influence surgical outcomes. STUDY DESIGN: Retrospective cohort study. SETTING: Guatemalan surgery center is called the Moore Center. METHODS: Pediatric patients underwent otolaryngology surgery between 2017 and 2019. All patients required follow up. We analyzed the effect of patient, surgical, and geographic factors on follow up and complications with univariate and multivariate analyses. RESULTS:  A total of 1094 otolaryngologic surgeries were performed between 2017 to 2019, which comprised 37.4% adenotonsillectomies, 26.8% cleft lip (CL)/cleft palate (CP) repairs, 13.6% otologic, and 20% "other" surgeries. Patients traveled on average 88 km to the center (±164 km). Eighty-nine percent attended their first follow up and 55% attended their second. The 11% who missed their first follow up lived farther from the center (p < .001) and had a higher ASA classification (p < .001) than the 89% who did attend. Sixty-nine (6.3%) patients had 1 or more complications. CL/CP surgery was associated with more complications than other procedures (p < .001). Of 416 tonsillectomies, 4 patients (1%) had a bleeding episode with 2 requiring reoperation. CONCLUSION: This surgical center models effective surgical care in low-resource areas. Complications and follow-up length vary by diagnosis. Areas to improve include retaining complex patients for follow up and reducing complications for CL/CP repair.

National Trends of Otolaryngology Involvement in Cleft Surgical Management over 10-Years.

OBJECTIVE: Surgical management of cleft lip/palate and cleft rhinoplasty have historically been performed by plastic surgeons. No study has addressed temporal trends in cleft-associated surgeries. This study assesses trends in cleft surgical management and complications in a national database. METHODS: Cross-sectional analysis of the National Surgical Quality Improvement Program Pediatric database from 2012 to 2021. Patients receiving cleft lip and/or palate repair were isolated using CPT codes. A subset receiving cleft rhinoplasty was also analyzed. The yearly proportion of otolaryngologists compared to general plastic surgeons performing surgeries was noted. Regression analysis was used to identify trends and predictors of management by OHNS. RESULTS: We identified 46,618 cases of cleft repair, of which 15.6% (N = 7,255) underwent repair with otolaryngology. On univariate Pearson correlation analysis, neither cleft rhinoplasties performed by OHNS over time (R = 0.371, 95% CI -0.337 to 0.811, p = 0.2907) nor all cases (R = -0.26, -0.76 to 0.44, p = 0.465) exhibited a significant change. On multivariable regression, the operative year was not associated with being treated by otolaryngology (p = 0.826) for all cleft cases but was associated with such in cleft rhinoplasties (OR 1.04, 1.01-1.08, p = 0.024). On multivariable analysis, the operative year was correlated with a higher rate of complications overall (OR 1.04, 1.01-1.07, p = 0.002). Surgeon specialty was not associated with complication rates. CONCLUSIONS: In the last 10 years, no change in the proportion of cleft lip/palate repair performed by OHNS was observed. Otolaryngologists are performing more cleft rhinoplasty but at a marginal rate. Otolaryngologists also manage more complex patients with multiple comorbidities compared to their colleagues. Complication rates have increased overall regardless of surgeon specialty, warranting further investigation. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:671-677, 2024.

The Impact of Childhood Mortality on Fertility in Rural Tanzania: Evidence From the Ifakara and Rufiji Health and Demographic Surveillance Systems.

This manuscript examines the relationship between child mortality and subsequent fertility using longitudinal data on births and childhood deaths occurring among 15,291 Tanzanian mothers between 2000 and 2015. Generalized hazard regression analyses assess the effect of child loss on the hazard of conception, adjusting for child-level, mother-level, and contextual covariates. Results show that time to conception is most reduced if an index child dies during the subsequent birth interval, representing the combined effect of biological and volitional replacement. Deaths occurring during prior birth intervals were associated with accelerated time to conception during future intervals, consistent with hypothesized insurance effects of anticipating future child loss, but this effect is smaller than replacement effects. The analysis reveals that residence in areas of relatively high child mortality is associated with hastened parity progression, again consistent with the insurance hypothesis. Investigation of high-order interactions suggests that insurance effects tend to be greater in low-mortality communities, replacement effects tend to be stronger in high-mortality community contexts, and wealthier families tend to exhibit a weaker insurance response but a stronger replacement response to childhood mortality relative to poorer families.