Parasite escape mechanisms drive morphological diversification in avian lice.

Organisms that have repeatedly evolved similar morphologies owing to the same selective pressures provide excellent cases in which to examine specific morphological changes and their relevance to the ecology and evolution of taxa. Hosts of permanent parasites act as an independent evolutionary experiment, as parasites on these hosts are thought to be undergoing similar selective pressures. Parasitic feather lice have repeatedly diversified into convergent ecomorphs in different microhabitats on their avian hosts. We quantified specific morphological characters to determine (i) which traits are associated with each ecomorph, (ii) the quantitative differences between these ecomorphs, and (iii) if there is evidence of displacement among co-occurring lice as might be expected under louse-louse competition on the host. We used nano-computed tomography scan data of 89 specimens, belonging to four repeatedly evolved ecomorphs, to examine their mandibular muscle volume, limb length and three-dimensional head shape data. Here, we find evidence that lice repeatedly evolve similar morphologies as a mechanism to escape host defences, but also diverge into different ecomorphs related to the way they escape these defences. Lice that co-occur with other genera on a host exhibit greater morphological divergence, indicating a potential role of competition in evolutionary divergence.

Cardiac Protein Kinase D1 ablation alters the myocytes ß-adrenergic response.

ß-adrenergic (ß-AR) signaling is essential for the adaptation of the heart to exercise and stress. Chronic stress leads to the activation of Ca2+/calmodulin-dependent kinase II (CaMKII) and protein kinase D (PKD). Unlike CaMKII, the effects of PKD on excitation-contraction coupling (ECC) remain unclear. To elucidate the mechanisms of PKD-dependent ECC regulation, we used hearts from cardiac-specific PKD1 knockout (PKD1 cKO) mice and wild-type (WT) littermates. We measured calcium transients (CaT), Ca2+ sparks, contraction and L-type Ca2+ current in paced cardiomyocytes under acute ß-AR stimulation with isoproterenol (ISO; 100 nM). Sarcoplasmic reticulum (SR) Ca2+ load was assessed by rapid caffeine (10 mM) induced Ca2+ release. Expression and phosphorylation of ECC proteins phospholambam (PLB), troponin I (TnI), ryanodine receptor (RyR), sarcoendoplasmic reticulum Ca2+ ATPase (SERCA) were evaluated by western blotting. At baseline, CaT amplitude and decay tau, Ca2+ spark frequency, SR Ca2+ load, L-type Ca2+ current, contractility, and expression and phosphorylation of ECC protein were all similar in PKD1 cKO vs. WT. However, PKD1 cKO cardiomyocytes presented a diminished ISO response vs. WT with less increase in CaT amplitude, slower [Ca2+]i decline, lower Ca2+ spark rate and lower RyR phosphorylation, but with similar SR Ca2+ load, L-type Ca2+ current, contraction and phosphorylation of PLB and TnI. We infer that the presence of PKD1 allows full cardiomyocyte ß-adrenergic responsiveness by allowing optimal enhancement in SR Ca2+ uptake and RyR sensitivity, but not altering L-type Ca2+ current, TnI phosphorylation or contractile response. Further studies are necessary to elucidate the specific mechanisms by which PKD1 is regulating RyR sensitivity. We conclude that the presence of basal PKD1 activity in cardiac ventricular myocytes contributes to normal ß-adrenergic responses in Ca2+ handling.

I can still hear my baby crying: The ambiguous loss of American Indian/Alaska Native birthmothers.

This study captures the experiences of American Indian/Alaska Native birthmothers who lost a child to adoption and the impact of said loss on their health and wellbeing. Few studies examine the loss experiences of American Indian/Alaska Native birthmothers despite their increased probability to lose a child to foster care and adoption. American Indian/Alaska Native birthmothers are distinct from birthmothers of other races in their experiences of intergenerational and historical child loss, having disproportionately lost their children to systematic practices of child removal via boarding schools, the adoption era, and child welfare. Interview data from 8 American Indian/Alaska Native birthmothers were analyzed using inductive thematic analysis. Five themes emerged including: (1) the social context of losing a child to adoption for American Indian/Alaska Native birthmothers, (2) the ambiguous loss of a child to adoption, (3) grief reactions to the loss, (4) the impact of the loss on birthmother health and wellbeing, and (5) creating resiliency. Findings suggest that American Indian/Alaska Native birthmothers experience ambiguous loss, as well as elevated mental health problems and substance abuse following the loss of a child to adoption.

Molecular phylogenetics of the avian feather louse Philopterus-complex (Phthiraptera: Philopteridae).

The avian feather louse Philopterus-complex (Phthiraptera: Ischnocera: Philopteridae) currently contains 12 genera that have been grouped together because of shared morphological characteristics. Although previously lumped into a single genus (Philopterus), more recent morphological treatments have separated the group into several different genera. Here we evaluate the status of these genera using DNA sequence data from 118 ingroup specimens belonging to ten genera in the Philopterus-complex: Australophilopterus Mey, 2004, Cinclosomicola Mey 2004, Clayiella Eichler, 1940, Corcorides Mey, 2004, Mayriphilopterus Mey, 2004, Paraphilopterus Mey 2004, Philopteroides Mey 2004, Philopterus Nitzsch, 1818, Tyranniphilopterus Mey, 2004, and Vinceopterus Gustafsson, Lei, Chu, Zou, and Bush, 2019. Our sampling includes 97 new louse-host association records. Our analyses suggest that the genus Debeauxoecus Conci, 1941, parasitic on pittas (Aves: Pittidae), is outside of the Philopterus-complex, and that there is strong support for the monophyly of a group containing the remaining genera from the complex. Some diverse genera, such as Philopterus (sensu stricto) and Mayriphilopterus are supported as monophyletic, whereas the genera Australophilopterus, Philopteroides, and Tyranniphilopterus are not. The present study is the largest phylogenetic reconstruction of avian lice belonging to the Philopterus-complex to date and suggests that further generic revision is needed in the group to integrate molecular and morphological information.

Presenting signs and symptoms of artificial urinary sphincter cuff erosion.

PURPOSE: To characterize the most common presentation and clinical risk factors for artificial urinary sphincter (AUS) cuff erosion to distinguish the relative frequency of symptoms that should trigger further evaluation in these patients. MATERIALS AND METHODS: We retrospectively reviewed our tertiary center database to identify men who presented with AUS cuff erosion between 2007 - 2020. A similar cohort of men who underwent AUS placement without erosion were randomly selected from the same database for symptom comparison. Risk factors for cuff erosion - pelvic radiation, androgen deprivation therapy (ADT), high-grade prostate cancer (Gleason score ≥ 8) - were recorded for each patient. Presenting signs and symptoms of cuff erosion were grouped into three categories: obstructive symptoms, worsening incontinence, and localized scrotal inflammation (SI). RESULTS: Of 893 men who underwent AUS placement during the study interval, 61 (6.8%) sustained cuff erosion. Most erosion patients (40/61, 66%) presented with scrotal inflammatory changes including tenderness, erythema, and swelling. Fewer men reported obstructive symptoms (26/61, 43%) and worsening incontinence (21/61, 34%). Men with SI or obstructive symptoms presented significantly earlier than those with worsening incontinence (SI 14 ± 18 vs. obstructive symptoms 15 ± 16 vs. incontinence 37 ± 48 months after AUS insertion, p<0.01). Relative to the non-erosion control group (n=61), men who suffered erosion had a higher prevalence of pelvic radiation (71 vs. 49%, p=0.02). CONCLUSION: AUS cuff erosion most commonly presents as SI symptoms. Obstructive voiding symptoms and worsening incontinence are also common. Any of these symptoms should prompt further investigation of cuff erosion.

Most men with artificial urinary sphincter cuff erosion have low serum testosterone levels.

AIMS: To evaluate the relationship between serum testosterone (T) levels and artificial urinary sphincter (AUS) cuff erosion in a population of incontinent men who underwent AUS placement. METHODS: A retrospective analysis of our single-surgeon AUS database was performed to identify men with T levels within 24 months of AUS placement. Men were stratified into two groups based on serum testosterone: low serum testosterone (LT) (<280 ng/dl) and normal serum testosterone (NT) (>280 ng/dl). Multivariable analysis was performed to control for risk factors. The outcome of interest was the incidence of and time to spontaneous urethral cuff erosion; other risk factors for cuff erosion were also evaluated. RESULTS: Among 161 AUS patients with serum testosterone levels, 84 (52.2%) had LT (mean: 136.8 ng/dl, SD: 150.4 ng/dl) and 77 (47.8%) had NT (mean: 455.8 ng/dl, SD: 197.3 ng/dl). Cuff erosion was identified in 42 men (26.1%) at a median of 7.1 months postoperatively (interquartile range: 3.6-13.4 months), most of whom (30/42, 71.4%) were testosterone deficient. LT levels were less common (54/119, 45.4%) in the non-erosion cohort (p = 0.004). Men with low T were nearly three times as likely to suffer AUS erosion than men with normal T (odds ratio = 2.519, p = 0.021). LT level was the only factor associated with AUS erosion on multivariable analysis. CONCLUSIONS: LT is an independent risk factor for AUS cuff erosion. Men with LT are more likely to present with cuff erosion, but there is no difference in time to erosion.

Male stress urinary incontinence is often underreported.

INTRODUCTION Patient-reported pads per day use is a widely used metric in grading the severity of stress urinary incontinence and guiding surgical decision-making, particularly in mild-to-moderate cases. We sought to compare patient-reported stress urinary incontinence severity by pads per day with objective findings on standing cough test. We hypothesize that patient-reported pads per day often underestimates stress urinary incontinence severity. MATERIALS AND METHODS: We retrospectively reviewed our male stress urinary incontinence surgical database and identified 299 patients with self-reported mild-to-moderate stress urinary incontinence who were evaluated with standing cough test prior to surgical intervention between 2007 and 2019. Patients were evaluated with the Male Stress Incontinence Grading Scale for urinary leakage during a standing cough test. This test has been shown to reliably and accurately predict surgical success. Binary logistic regression analysis was used to identify parameters associated with stress urinary incontinence upgrading in a multivariable model. RESULTS: Among 299 patients with reported mild-to-moderate stress urinary incontinence, 101 (34%) were upgraded to severe stress urinary incontinence by standing cough test. Prior stress urinary incontinence surgery (OR 4.1, 95% CI 2.0-8.0, p < 0.0001) and radiation (OR 3.2, 95% CI 1.7-5.7, p < 0.0001) were significantly associated with Male Stress Incontinence Grading Scale upgrading in multivariable analysis. CONCLUSIONS: Roughly one-third of men who report mild-to-moderate stress urinary incontinence actually have severe incontinence observed on physical examination. All men being evaluated for stress urinary incontinence should undergo standing cough test to accurately grade incontinence severity and guide surgical management.

Artificial Urinary Sphincter Cuff Erosion Heat Map Shows Similar Anatomical Characteristics for Transcorporal and Standard Approach.

PURPOSE: We describe and compare artificial urinary sphincter cuff erosion sites and associated clinical implications. MATERIALS AND METHODS: We retrospectively reviewed men who presented with artificial urinary sphincter erosion treated by a single surgeon between 2007 and 2019 at a tertiary medical center. Transcorporal indications included complications of prior anti-incontinence procedures and prior urethral reconstruction. Location of artificial urinary sphincter cuff erosion defects was assessed by cystoscopy prior to device explantation, and findings were stratified into patients who had transcorporal vs standard artificial urinary sphincter placement. RESULTS: Out of 723 artificial urinary sphincter cases in 611 patients we identified 54 (7.5%) cuff erosions. Erosion developed in 15 of 82 (18.3%) cases of transcorporal artificial urinary sphincter and 39 of 641 (6.1%) cases of standard artificial urinary sphincter (p <0.05). Artificial urinary sphincter cuff erosions occurred predominantly ventrally in both groups (66.7% for transcorporal and 79.5% for standard artificial urinary sphincter, p=0.4) followed by lateral urethral location (33.3% transcorporal and 20.5% standard, p=0.3). Dorsal erosions were rare in both groups (20% transcorporal and 5.1% standard, p=0.1). History of artificial urinary sphincter and previous erosion were associated with transcorporal artificial urinary sphincter erosion. History of radiotherapy, prior urethroplasty, hypogonadism and urethral cuff size were similar between groups. CONCLUSIONS: Artificial urinary sphincter cuff erosions appear to occur ventrally and laterally in most patients regardless of cuff placement. Dorsal erosions were the least common in both groups. The protective effect of transcorporal artificial urinary sphincter could not be conclusively demonstrated.

Across time and space: Hormonal variation across temporal and spatial scales in relation to nesting success.

There is a renewed interest in investigating individual variation in hormone levels in relation to fitness metrics, as hormones act as mediators of life-history trade-offs. Hormone concentrations, however, are labile, responding to both internal and external stimuli, so the relationship between hormones and fitness can be non-consistent. One explanation of this inconsistent relationship is that a single hormone sample may not be representative of individual phenotypes in a free-living species. We addressed this issue by repeatedly sampling a free-living population of mountain white-crowned sparrows, Zonotrichia leucophrys oriantha, for baseline and stress-induced corticosterone (cort) and testosterone (T) across different stages of the breeding season. We measured (co)variation using three different methods, taking into account inter- and intra-individual variances, to determine whether hormone levels and the stress response are repeatable. We documented the temporal (over 3 months) and spatial (home-range) variation of individual hormone phenotypes and investigated how these components related to nesting success. At the population level, we found significant repeatability in male stress-induced cort concentrations but no repeatability in male or female baseline cort or male T concentrations. Using a new metric of intra-individual variance focusing on the stress response (profile repeatability), we found a wide range of variance scores, with most individuals showing high variation in their stress response. Similarly, we found a low level of repeatability of the reaction norm intercept and slope for the stress response across different life-history stages. Males with higher concentrations of stress-induced cort had more central home-ranges. Males with higher body condition had larger home-ranges; however, home-range size did not relate to male hormone concentrations or nesting success. We also did not find any significant relationship between variation in hormone levels and nesting success. We recommend that future studies combine both physiological and environmental components to better understand the relationship between hormones and fitness.

Using graphic warning labels to counter effects of social cues and brand imagery in cigarette advertising.

Exposure to cigarette advertising can increase the likelihood of youth smoking initiation and may encourage people who already smoke to continue. Requiring prominent, graphic warning labels could reduce these effects. We test whether graphic versus text-only warning labels in cigarette advertisements influence cognitive and emotional factors associated with youth susceptibility to smoking and adult intentions to quit. We conducted two randomized, between-subjects experiments with middle-school youth (n = 474) and adult smokers (n = 451). Both studies employed a two (graphic or text-only warnings) by two (advertisements with social cues or brand imagery) factorial design with a fifth, offset control group (social cue advertisements with the current US Surgeon General's Warning). Graphic warnings outperformed text-only warnings in reducing visual attention to the advertisement, generating visual attention to the warning and arousing more negative affect. Graphic warnings also reduced the appeal of cigarette brands among youth relative to social cue advertisements with the Surgeon General's warnings. None of the warnings (graphic or textual) influenced health risk beliefs. Graphic warning labels on cigarette advertisements appear to have effects similar to those observed on cigarette packs in previous work, with an added benefit of reducing cigarette brand appeal among youth.

Epidemiology and outcomes of Clostridium difficile infection in allogeneic hematopoietic cell and lung transplant recipients.

BACKGROUND: Clostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described. METHODS: We performed a prospective, multicenter study of CDI within 365 days post-allogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12 weeks post-transplant and while hospitalized and contacted monthly up to 18 months post-transplantation. RESULTS: Six sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1 year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27 days vs 90 days; P = .037). CDI was associated with significantly higher mortality from 31 to 180 days post-index date among the allogeneic HCT recipients (Hazard ratio [HR] = 1.80; P = .007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180 days post-index date (HR = 4.7, P = .09). CONCLUSIONS: The epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate post-transplant period.

Induction Immunosuppression and Clinical Outcomes in Kidney Transplant Recipients Infected With Human Immunodeficiency Virus.

There is an increased risk of acute rejection (AR) in human immunodeficiency virus-positive (HIV+) kidney transplant (KT) recipients. Induction immunosuppression is standard of care for those at high risk of AR; however, use in HIV+ patients is controversial, given fears of increased infection rates. We sought to compare clinical outcomes between HIV+ KT recipients who were treated with (i) anti-thymocyte globulin (ATG), (ii) IL-2 receptor blocker, and (iii) no induction. We studied 830 HIV+ KT recipients between 2000 and 2014, as captured in the Scientific Registry of Transplant Recipients, and compared rates of delayed graft function (DGF), AR, graft loss and death. Infections and hospitalizations were ascertained by International Classification of Diseases, Ninth Revision codes in a subset of 308 patients with Medicare. Compared with no induction, neither induction agent was associated with an increased risk of infection (weighted hazard ratio [wHR] 0.80, 95% confidence interval [CI] 0.55-1.18). HIV+ recipients who received induction spent fewer days in the hospital (weighted relative risk [wRR] 0.70, 95% CI 0.52-0.95), had lower rates of DGF (wRR 0.66, 95% CI 0.51-0.84), less graft loss (wHR 0.47, 95% CI 0.24-0.89) and a trend toward lower mortality (wHR 0.60, 95% CI 0.24-1.28). Those who received induction with ATG had lower rates of AR (wRR 0.59, 95% CI 0.35-0.99). Induction in HIV+ KT recipients was not associated with increased infections; in fact, those receiving ATG, the most potent agent, had the lowest rates. In light of the high risk of AR in this population, induction therapy should be strongly considered.

Solid organ transplantation from hepatitis B virus-positive donors: consensus guidelines for recipient management.

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non-liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti-HBc+) donors. Organs from anti-HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non-liver recipients but is not recommended in immune non-liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost-effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.

KIR and HLA interactions are associated with control of primary CMV infection in solid organ transplant recipients.

Cytomegalovirus (CMV) infection remains a major source of morbidity and mortality in solid organ transplant recipients. Killer immunoglobulin-like receptors(KIR) are genetically polymorphic natural killer(NK) cell receptors important in antiviral responses. A retrospective, single-center cohort study was performed to study the interaction of KIR genotype and primary control of CMV infection after transplantation.Time to first CMV viremia was determined for a cohort of 531 CMV serology donor positive/recipient negative solid organ transplant recipients. Of the KIR genes,KIR2DL3 and KIR2DS2 were most strongly associated with time to CMV viremia in random survival forest analysis. As KIR2DL3 and KIR2DS2 both interact with HLA-C1, these interactions were evaluated. Seventy six recipients were found to be positive for both KIR2DL3 and KIR2DS2 and expressed only HLA-C1 antigens in both recipient and donor. These patients had a substantially reduced hazard of CMV viremia in the first year after solid organ transplantation (hazard ratio 0.44, 95% CI 0.27­0.72, p=0.0012). In KIR2DL3+/KIR2DS2+/HLA-C1/1 recipients who received an organ from a non-C1/1 donor, this protective effect was not observed. These results improve our understanding of human NK cell function in primary CMV infection after transplant.

Predictive role of imaging in sentinel lymph node dissection for melanoma.

A retrospective study of 67 patients with metastatic melanoma was performed to evaluate if imaging from lymphoscintigraphy could predict a higher miss rate if only the most radioactive node were removed. Following protocol for sentinel node biopsy, the surgeon resected all lymph nodes containing radioactivity > 10% of the most radioactive node. A correlation was performed between the radioactive counts of the lymph nodes and the presence of metastases. The percentage of cases in which the most radioactive node was negative for metastasis on pathology was calculated. Two nuclear medicine physicians read the images from lymphoscintigraphy specifically to determine if the first lymph node visualized became less intense than other nodes on later images. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. In 13 of 67 (19%) patients, the most radioactive lymph node was negative for metastasis while a less radioactive node contained metastatic disease. Consensus reading by the nuclear medicine physicians determined that in 9 cases, the first lymph node visualized became less intense than another lymph node on later images. Of the 9 cases, 4 were true positive and 5 were false positive when correlated with intraoperative count rate and pathology. Of the cases where the most radioactive node was not positive on histopathology (n = 13), the consensus reading by the nuclear medicine physicians reported 4 of them (31%). Imaging by lymphoscintigram had a sensitivity 31%, specificity 91%, positive predictive value 44%, and negative predictive value 85% for predicting whether the most radioactive lymph node at surgery would be negative for metastasis at pathology. We conclude that in patients with melanoma, lymphoscintigraphy has high specificity and negative predictive value but modest sensitivity and positive predictive value for detecting when the sentinel node will not be the most radioactive lymph node during sentinel lymph node dissection. These findings support that dynamic imaging by lymphoscintigraphy has a role in surgical planning but that the imaging protocol could benefit from further optimization.

Technology for transgender healthcare: Access, precarity & community care.

While much of the transgender health literature has focused on poor health outcomes, less research has examined how trans people find reliable information on, and actually go about accessing, gender-affirming healthcare. Through qualitative interviews with creators of trans technologies, that is, technologies designed to address problems that trans people face, we found that digital technologies have become important tools for proliferating access to gender-affirming care and related health information. We found that technologists often employed different processes for creating their technologies, but they coalesced around the goal of enabling and increasing access to gender-affirming care. Creators of trans health technologies also encountered precarious conditions for creating and maintaining their technologies, including regional gaps left by national resources focused on the US east and west coasts. Findings demonstrated that trans tech creators were motivated to create and maintain these technologies as a means of caring for one another and forming trans communities in spite of the precarious conditions trans people face living under systemic oppression.

Glucocorticoids and land cover: a largescale comparative approach to assess a physiological biomarker for avian conservation.

As humans alter landscapes worldwide, land and wildlife managers need reliable tools to assess and monitor responses of wildlife populations. Glucocorticoid (GC) hormone levels are one common physiological metric used to quantify how populations are coping in the context of their environments. Understanding whether GC levels can reflect broad landscape characteristics, using data that are free and commonplace to diverse stakeholders, is an important step towards physiological biomarkers having practical application in management and conservation. We conducted a phylogenetic comparative analysis using publicly available datasets to test the efficacy of GCs as a biomarker for large spatial-scale avian population monitoring. We used hormone data from HormoneBase (51 species), natural history information and US national land cover data to determine if baseline or stress-induced corticosterone varies with the amount of usable land cover types within each species' home range. We found that stress-induced levels, but not baseline, positively correlated with per cent usable land cover both within and across species. Our results indicate that GC concentrations may be a useful biomarker for characterizing populations across a range of habitat availability, and we advocate for more physiological studies on non-traditional species in less studied populations to build on this framework. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.

Unintentionally intentional: unintended effects of spinal stimulation as a platform for multi-modal neurorehabilitation after spinal cord injury.

Electrical stimulation of spinal neurons has emerged as a valuable tool to enhance rehabilitation after spinal cord injury. In separate parameterizations, it has shown promise for improving voluntary movement, reducing symptoms of autonomic dysreflexia, improving functions mediated by muscles of the pelvic floor (e.g., bowel, bladder, and sexual function), reducing spasms and spasticity, and decreasing neuropathic pain, among others. This diverse set of actions is related both to the density of sensorimotor neural networks in the spinal cord and to the intrinsic ability of electrical stimulation to modulate neural transmission in multiple spinal networks simultaneously. It also suggests that certain spinal stimulation parameterizations may be capable of providing multi-modal therapeutic benefits, which would directly address the complex, multi-faceted rehabilitation goals of people living with spinal cord injury. This review is intended to identify and characterize reports of spinal stimulation-based therapies specifically designed to provide multi-modal benefits and those that report relevant unintended effects of spinal stimulation paradigms parameterized to enhance a single consequence of spinal cord injury.

Rapid Targeted Assembly of the Proteome Reveals Evolutionary Variation of GC Content in Avian Lice.

Nucleotide base composition plays an influential role in the molecular mechanisms involved in gene function, phenotype, and amino acid composition. GC content (proportion of guanine and cytosine in DNA sequences) shows a high level of variation within and among species. Many studies measure GC content in a small number of genes, which may not be representative of genome-wide GC variation. One challenge when assembling extensive genomic data sets for these studies is the significant amount of resources (monetary and computational) associated with data processing, and many bioinformatic tools have not been optimized for resource efficiency. Using a high-performance computing (HPC) cluster, we manipulated resources provided to the targeted gene assembly program, automated target restricted assembly method (aTRAM), to determine an optimum way to run the program to maximize resource use. Using our optimum assembly approach, we assembled and measured GC content of all of the protein-coding genes of a diverse group of parasitic feather lice. Of the 499 426 genes assembled across 57 species, feather lice were GC-poor (mean GC = 42.96%) with a significant amount of variation within and between species (GC range = 19.57%-73.33%). We found a significant correlation between GC content and standard deviation per taxon for overall GC and GC3, which could indicate selection for G and C nucleotides in some species. Phylogenetic signal of GC content was detected in both GC and GC3. This research provides a large-scale investigation of GC content in parasitic lice laying the foundation for understanding the basis of variation in base composition across species.

MODERATE ALCOHOL CONSUMPTION INDUCES LASTING IMPACTS ON PREFRONTAL CORTICAL SIGNALING IN MICE.

Both alcohol use disorder (AUD) and Alzheimer's Disease and Related Dementias (ADRD) appear to include disruption in the balance of excitation and inhibition in the cortex, but their potential interactions are unclear. We examined the effect of moderate voluntary binge alcohol consumption on the aged, pre-disease neuronal environment by measuring intrinsic excitability and spontaneous neurotransmission on prefrontal cortical pyramidal (excitatory, glutamatergic) and non-pyramidal (inhibitory, GABAergic) neurons following a prolonged period of abstinence from alcohol in mice. Results highlight that binge alcohol consumption has lasting impacts on the electrophysiological properties of prefrontal cortical neurons. A profound increase in excitatory events onto layer 2/3 non-pyramidal neurons following alcohol consumption was seen, along with altered intrinsic excitability of pyramidal neurons, which could have a range of effects on Alzheimer's Disease progression in humans. These results indicate that moderate voluntary alcohol influences the pre-disease environment in aging and highlight the need for further mechanistic investigation into this risk factor.