The Association of Mental Health Disorders with the Effectiveness of Treating Facial Synkinesis with Chemodenervation Using Botulinum Toxin A.

Background: Studies suggest that mood disorders may affect perception of facial synkinesis, though none have analyzed effects on perceived benefit from chemodenervation. Objective: To measure the effect of depression, appearance anxiety, and other variables on chemodenervation benefit among patients with post-paralytic facial synkinesis. Design Type: Prospective cohort. Methods: Patients volunteered and completed: Synkinesis Assessment Questionnaire (SAQ), Facial Clinimetric Evaluation Scale (FaCE), Center for Epidemiological Studies Depression Scale (CES-D), and Fear of Negative Appearance Evaluation Scale (FNAES). Multivariate regression was used to analyze the effect of CES-D, FNAES, and demographics on pre- and post-chemodenervation SAQ and FaCE. Results: In total, 100 patients participated, 90% were female. Mean age was 56.4 (SD 12.3) years. The most common paralysis etiology was idiopathic (47%). Average synkinesis duration was 7.6 (6.2) years and treatment duration 4.9 (4.8) years. Older age and prior treatment (p < 0.05) were associated with reduced SAQ improvement; worse CES-D approached significance (p = 0.09). Reported history of anxiety was associated with greater SAQ improvement (p = 0.05). Factors associated with reduced FaCE improvement included higher baseline CES-D and prior treatment (p < 0.05). Conclusions: Older age, worse depression scores, and prior treatments may be associated with reduced patient-graded improvement following chemodenervation. History of anxiety may be associated with greater improvement.

You Can't Be What You Can't See: The Progression of Women in Otolaryngology-Head and Neck Surgery.

Objective: To examine trends in the gender composition of residents and faculty in Otolaryngology-Head and Neck Surgery residency programs in the United States and to investigate the correlation between women's representation in leadership positions and the proportion of women faculty and residents. Methods: A literature review was first performed to analyze trends in the gender composition of residents and faculty in Otolaryngology-Head and Neck Surgery (OHNS) residency programs. Current residency programs were then identified using the Electronic Residency Application Service 2023 Participating Specialties and Programs website. The following data was collected from each program website: gender of associated medical school dean, gender of department chair, gender of residency program director, and total number and gender of fellowship directors, faculty, and residents. Wilcoxon rank sum test and Fischer's exact test were used to analyze relationships between the number of women in leadership positions and the proportion of women faculty and residents. Results: An increase in the number of women chairs, residency program directors, residents, and faculty over the past decade is documented across published literature. One hundred twenty-three current academic residency programs were identified. Women accounted for 42%, 30%, 27%, and 8% of current residents, residency program directors, faculty, and department chairs, respectively. Department chair gender was significantly correlated with number of women faculty (P = .01). Any women in a leadership position were correlated with a statistically significant increase in median percent of women faculty (P = .006). Conclusion: Further understanding of how the mentorship of women promotes gender equity is necessary to promote gender diversity in OHNS.

SARS-CoV-2 infection perturbs the gastrointestinal tract and induces modest microbial translocation across the intestinal barrier.

SARS-CoV-2 infects via the respiratory tract, but COVID-19 includes an array of non-respiratory symptoms, among them gastrointestinal (GI) manifestations such as vomiting and diarrhea. Here we investigated the GI pathology of SARS-CoV-2 infections in rhesus macaques and humans. Macaques experienced mild infection with USA-WA1/2020 and shed viral RNA in the respiratory tract and stool, including subgenomic RNA indicative of replication in the GI tract. Intestinal immune cell populations were disturbed, with significantly fewer proliferating (Ki67+) jejunal B cells in SARS-CoV-2-infected macaques than uninfected ones. Modest translocation of bacteria/bacterial antigen was observed across the colonic epithelium, with a corresponding significant increase in plasma soluble CD14 (sCD14) that may be induced by LPS. Human plasma demonstrated significant decreases in interleukin (IL)-6 and sCD14 upon recovery from COVID-19, suggesting resolution of inflammation and response to translocated bacteria. sCD14 significantly positively correlated with zonulin, an indicator of gut barrier integrity, and IL-6. These results demonstrate that GI perturbations such as microbial translocation can occur in even mild SARS-CoV-2 infections and may contribute to the COVID-19 inflammatory state.IMPORTANCEThis study investigates gastrointestinal (GI) barrier disruption in SARS-CoV-2 infections and how it may contribute to disease. We observed bacteria or bacterial products crossing from the colon interior (the lumen) to the lamina propria during SARS-CoV-2 infection in macaques. Bacteria/bacterial products are tolerated in the lumen but may induce immune responses if they translocate to the lamina propria. We also observed a significant increase in soluble CD14, which is associated with an immune response to bacterial products. In addition, we observed that humans recovering from COVID-19 experienced a significant decrease in soluble CD14, as well as the inflammatory marker interleukin (IL)-6. IL-6 and sCD14 correlated significantly across macaque and human samples. These findings suggest that SARS-CoV-2 infection results in GI barrier disruption that permits microbial translocation and a corresponding immune response. These findings could aid in developing interventions to improve COVID-19 patient outcomes.

Translocating bacteria in SIV infection are not stochastic and preferentially express cytosine methyltransferases.

Microbial translocation is a significant contributor to chronic inflammation in people living with HIV (PLWH) and is associated with increased mortality and morbidity in individuals treated for long periods with antiretrovirals. The use of therapeutics to treat microbial translocation has yielded mixed effects, in part, because the species and mechanisms contributing to translocation in HIV remain incompletely characterized. To characterize translocating bacteria, we cultured translocators from chronically SIV-infected rhesus macaques. Proteomic profiling of these bacteria identified cytosine-specific methyltransferases as a common feature and therefore, a potential driver of translocation. Treatment of translocating bacteria with the cytosine methyltransferase inhibitor decitabine significantly impaired growth for several species in vitro. In rhesus macaques, oral treatment with decitabine led to some transient decreases in translocator taxa in the gut microbiome. These data provide mechanistic insight into bacterial translocation in lentiviral infection and explore a novel therapeutic intervention that may improve the prognosis of PLWH.

Immunotoxin-mediated depletion of Gag-specific CD8+ T cells undermines natural control of SIV.

Antibody-mediated depletion studies have demonstrated that CD8+ T cells are required for effective immune control of SIV. However, this approach is potentially confounded by several factors, including reactive CD4+ T cell proliferation, and provides no information on epitope specificity, a likely determinant of CD8+ T cell efficacy. We circumvented these limitations by selectively depleting CD8+ T cells specific for the Gag epitope CTPYDINQM (CM9) via the administration of immunotoxin-conjugated tetrameric complexes of CM9/Mamu-A*01. Immunotoxin administration effectively depleted circulating but not tissue-localized CM9-specific CD8+ T cells, akin to the bulk depletion pattern observed with antibodies directed against CD8. However, we found no evidence to indicate that circulating CM9-specific CD8+ T cells suppressed viral replication in Mamu-A*01+ rhesus macaques during acute or chronic progressive infection with a pathogenic strain of SIV. This observation extended to macaques with established infection during and after continuous antiretroviral therapy. In contrast, natural controller macaques experienced dramatic increases in plasma viremia after immunotoxin administration, highlighting the importance of CD8+ T cell-mediated immunity against CM9. Collectively, these data showed that CM9-specific CD8+ T cells were necessary but not sufficient for robust immune control of SIV in a nonhuman primate model and, more generally, validated an approach that could inform the design of next-generation vaccines against HIV-1.

Untangling the role of the microbiome across the stages of HIV disease.

PURPOSE OF REVIEW: The primate microbiome consists of bacteria, eukaryotes, and viruses that dynamically shape and respond to host health and disease. Understanding how the symbiotic relationship between the host and microbiome responds to HIV has implications for therapeutic design. RECENT FINDINGS: Advances in microbiome identification technologies have expanded our ability to identify constituents of the microbiome and to infer their functional capacity. The dual use of these technologies and animal models has allowed interrogation into the role of the microbiome in lentiviral acquisition, vaccine efficacy, and the response to antiretrovirals. Lessons learned from such studies are now being harnessed to design microbiome-based interventions. SUMMARY: Previous studies considering the role of the microbiome in people living with HIV largely described viral acquisition as an intrusion on the host:microbiome interface. Re-framing this view to consider HIV as a novel, albeit unwelcome, component of the microbiome may better inform the research and development of pre and postexposure prophylaxes.

SIV infection and ARV treatment reshape the transcriptional and epigenetic profile of naïve and memory T cells in vivo.

Human and simian immunodeficiency viruses (HIV and SIV) are lentiviruses that reverse transcribe their RNA genome with subsequent integration into the genome of the target cell. How progressive infection and administration of antiretrovirals (ARVs) longitudinally influence the transcriptomic and epigenetic landscape of particular T cell subsets, and how these may influence the genetic location of integration are unclear. Here, we use RNAseq and ATACseq to study the transcriptomics and epigenetic landscape of longitudinally sampled naïve and memory CD4+ and CD8+ T cells in two species of non-human primates prior to SIV infection, during chronic SIV infection, and after administration of ARVs. We find that SIV infection leads to significant alteration to the transcriptomic profile of all T cell subsets that are only partially reversed by administration of ARVs. Epigenetic changes were more apparent in animals with longer periods of untreated SIV infection and correlated well with changes in corresponding gene expression. Known SIV integration sites did not vary due to SIV status but did contain more open chromatin in rhesus macaque memory T cells, and the expression of proteasome-related genes at the pre-SIV timepoint correlated with subsequent viremia.IMPORTANCEChronic inflammation during progressive human and simian immunodeficiency virus (HIV and SIV) infections leads to significant co-morbidities in infected individuals with significant consequences. Antiretroviral (ARV)-treated individuals also manifest increased levels of inflammation which are associated with increased mortalities. These data will help guide rational development of modalities to reduce inflammation observed in people living with HIV and suggest mechanisms underlying lentiviral integration site preferences.

Factors Associated With Mortality During the First Year Post Infarction: Survival Analysis of Patients With Acute Myocardial Infarction in Colombia.

INTRODUCTION: Cardiovascular diseases account for over 80% of global deaths. Risk factors and social determinants influence mortality in patients post acute myocardial infarction (AMI). OBJECTIVE: To evaluate factors associated with post-AMI mortality during the one-year follow-up. MATERIALS AND METHODS: The study is a prospective cohort study of adults aged 18 years and older with type 1 AMI conducted between October 2021 and January 2024. Intrahospital and outpatient information was collected. Statistical analyses included the Kaplan-Meier survival curve and Cox regression analysis. Proportional hazards and model predictive capacity were evaluated. RESULTS: A total of 1873 patients were included, with a 9.4% mortality rate in the first year. At one year, the estimated survival probability was 88.61% (95% CI: 86.82-90.18). Cox analysis identified several factors associated with mortality, highlighting age (HR = 1.04, 95% CI: 1.02-1.06, p = 0.001), diabetes (HR = 1.77, 95% CI: 1.09-2.87, p = 0.020), renal insufficiency (HR = 2.25, 95% CI: 1.32-3.84, p = 0.003), and type of intervention. The model evaluation showed strong predictive capacity. CONCLUSIONS: It is essential to emphasize the importance of comprehensive management in AMI patients with risk factors such as diabetes and chronic kidney disease, as they are significant predictors of mortality during the first year post infarction.

Effect of Underlying Mental Health Disorders on the Correlation Between Patient- and Surgeon-Graded Synkinesis Scores.

Background: Little is known about how depression and appearance anxiety affect patient reporting of synkinesis severity. Learning/Study Objective: Measure prevalence of depression and appearance anxiety in facial synkinesis and correlations between subjective and surgeon-graded synkinesis severity. Design Type: Prospective cohort. Methods: Patients with synkinesis volunteered and completed: Synkinesis Assessment Questionnaire (SAQ), facial clinimetric evaluation (FaCE) scale, Center for Epidemiological Studies Depression Scale (CES-D), and Fear of Negative Appearance Evaluation Scale (FNAES). Standardized videos were scored by facial plastic surgeons using Sunnybrook Scale and eFaCE. Multivariate linear regression was used to compare patient- and surgeon-graded metrics. Results: One hundred patients participated, 91 were female. Mean age was 56.4 (12.3). Eight percent identified as Black and 87% White. The most common nerve injury etiology was idiopathic (47%). Mean synkinesis duration was 7.6 years (6.2). Twenty percent and 15% reported history of an anxiety or depressive disorder, respectively. Patient (SAQ, FaCE) and clinician (Sunnybrook, eFaCE) scores were correlated (Pearson's r 0.223-0.294, p < 0.05). Upon adjusting for CES-D/FNAES, correlations between most patient and clinician metrics became stronger. As CES-D and FNAES worsened, patient-clinician correlations weakened. Conclusions: Depression and appearance anxiety may affect patient reporting of synkinesis severity. Worse mental health scores may decorrelate patient and clinician synkinesis assessments.

A systematic review and meta-analysis of mortality in chronic Chagas cardiomyopathy versus other cardiomyopathies: higher risk or fiction?

INTRODUCTION AND OBJECTIVES: Although multiple studies suggest that chronic Chagas cardiomyopathy (CCC) has higher mortality than other cardiomyopathies, the absence of meta-analyses supporting this perspective limits the possibility of generating robust conclusions. The aim of this study was to systematically evaluate the current evidence on mortality risk in CCC compared with that of other cardiomyopathies. METHODS: PubMed/Medline and EMBASE were searched for studies comparing mortality risk between patients with CCC and those with other cardiomyopathies, including in the latter nonischemic cardiomyopathy (NICM), ischemic cardiomyopathy, and non-Chagas cardiomyopathy (nonCC). A random-effects meta-analysis was performed to combine the effects of the evaluated studies. RESULTS: A total of 37 studies evaluating 17 949 patients were included. Patients with CCC had a significantly higher mortality risk compared with patients with NICM (HR, 2.04; 95%CI, 1.60-2.60; I2, 47%; 8 studies) and non-CC (HR, 2.26; 95%CI, 1.65-3.10; I2, 71%; 11 studies), while no significant association was observed compared with patients with ischemic cardiomyopathy (HR, 1.72; 95%CI, 0.80-3.66; I2, 69%; 4 studies) in the adjusted-measures meta-analysis. CONCLUSIONS: Patients with CCC have an almost 2-fold increased mortality risk compared with individuals with heart failure secondary to other etiologies. This finding highlights the need for effective public policies and targeted research initiatives to optimally address the challenges of CCC.

Early Postoperative Complications in Microtia Reconstruction: An Analysis of the NSQIP-P Database.

OBJECTIVES: Microtia and anotia repair require techniques that consider both aesthetics and function. The outcomes of different reconstructive frameworks such as costal cartilage or a porous polyethylene implant have not been evaluated on a national scale. We aim to understand differences in outcomes/complication rates and operative times between different reconstructive frameworks used in microtia/anotia reconstruction. METHODS: This was a retrospective review of the National Surgical Quality Improvement Program Pediatric database between 2012-2019. Patients with ICD-9/10 codes for microtia/anotia were isolated. Reconstruction methods were identified using CPT codes for rib graft, ear cartilage graft, and alloplastic implants (biocompatible implants, porous polyethylene, etc). Outcomes included operative-time, wound complications, and unplanned re-operations within 30 days of surgery. Multivariable logistic regression was performed to control for confounders. RESULTS: We included 593 patients for analysis. Reconstruction with rib grafts (N = 506, 85%) was the most common. In 58 patients (9.8%), an implant was used for the auricular framework, whereas in 47 (7.9%) ear cartilage grafts were used. The overall wound complication rate was 3.4%. On univariate analysis, alloplastic implants exhibited a higher rate of wound complications (8.6% vs. 2.8%, p = 0.037) and longer operative times (350 min vs. 235 min, p < 0.001). After controlling for demographics and comorbidities, implants conferred an independently increased risk of wound complications (OR 3.52, 1.10-9.54, p = 0.020). CONCLUSION: Although the use of alloplastic implants (e.g., porous polyethylene) may confer an increased risk of early complications, the long-term clinical implications of these findings are unclear relative to aesthetic benefits. Multi-institutional studies are needed to validate these findings using patient-specific and surgeon-specific data. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1214-1219, 2024.

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.

2-Hydroxypropyl-ß-Cyclodextrin Treatment Induces Modest Immune Activation in Healthy Rhesus Macaques.

Experimental simian immunodeficiency virus (SIV) infection of Asian macaques is an excellent model for HIV disease progression and therapeutic development. Recent coformulations of nucleoside analogs and an integrase inhibitor have been used for parenteral antiretroviral (ARV) administration in SIV-infected macaques, successfully resulting in undetectable plasma SIV RNA. In a cohort of SIVmac239-infected macaques, we recently observed that administration of coformulated ARVs resulted in an unexpected increase in plasma levels of soluble CD14 (sCD14), associated with stimulation of myeloid cells. We hypothesized that the coformulation solubilizing agent Kleptose (2-hydroxypropyl-ß-cyclodextrin [HPßCD]) may induce inflammation with myeloid cell activation and the release of sCD14. Herein, we stimulated peripheral blood mononuclear cells (PBMCs) from healthy macaques with HPßCD from different commercial sources and evaluated inflammatory cytokine production in vitro. Treatment of PBMCs resulted in increased sCD14 release and myeloid cell interleukin-1ß (IL-1ß) production-with stimulation varying significantly by HPßCD source-and destabilized lymphocyte CCR5 surface expression. We further treated healthy macaques with Kleptose alone. In vivo, we observed modestly increased myeloid cell activation in response to Kleptose treatment without significant perturbation of the immunological transcriptome or epigenome. Our results demonstrate a need for vehicle-only controls and highlight immunological perturbations that can occur when using HPßCD in pharmaceutical coformulations. IMPORTANCE SIV infection of nonhuman primates is the principal model system for assessing HIV disease progression and therapeutic development. HPßCD has recently been incorporated as a solubilizing agent in coformulations of ARVs in SIV-infected nonhuman primates. Although HPßCD has historically been considered inert, recent findings suggest that HPßCD may contribute to inflammation. Herein, we investigate the contribution of HPßCD to healthy macaque inflammation in vitro and in vivo. We observe that HPßCD causes an induction of sCD14 and IL-1ß from myeloid cells in vitro and demonstrate that HPßCD stimulatory capacity varies by commercial source. In vivo, we observe modest myeloid cell activation in blood and bronchoalveolar lavage specimens absent systemic immune activation. From our findings, it is unclear whether HPßCD stimulation may improve or diminish immune reconstitution in ARV-treated lentiviral infections. Our results demonstrate a need for vehicle-only controls and highlight immunological perturbations that can occur when using HPßCD in pharmaceutical coformulations.

Correction: Mitigation of endemic GI-tract pathogen-mediated inflammation through development of multimodal treatment regimen and its impact on SIV acquisition in rhesus macaques.

[This corrects the article DOI: 10.1371/journal.ppat.1009565.].

Experimental bacterial dysbiosis with consequent immune alterations increase intrarectal SIV acquisition susceptibility.

Variations in the composition of the intestinal bacterial microbiome correlate with acquisition of some sexually transmitted pathogens. To experimentally assess the contribution of intestinal dysbiosis to rectal lentiviral acquisition, we induce dysbiosis in rhesus macaques (RMs) with the antibiotic vancomycin prior to repeated low-dose intrarectal challenge with simian immunodeficiency virus (SIV) SIVmac239X. Vancomycin administration reduces T helper 17 (TH17) and TH22 frequencies, increases expression of host bacterial sensors and antibacterial peptides, and increases numbers of transmitted-founder (T/F) variants detected upon SIV acquisition. We observe that SIV acquisition does not correlate with measures of dysbiosis but rather associates with perturbations in the host antimicrobial program. These findings establish a functional association between the intestinal microbiome and susceptibility to lentiviral acquisition across the rectal epithelial barrier.

Extreme alkalaemia with mixed alkalosis due to suspected acute-on-chronic respiratory alkalosis.

Herein we present a case of severe alkalaemia (pH 7.81) due to suspected acute-on-chronic respiratory alkalosis in a patient with chronic anxiety and metabolic alkalosis secondary to emesis. The patient was managed in the intensive care unit with significant improvement and discharged in stable condition. The case report emphasises considering a broad differential of aetiologies that can cause acid-base status derangements and identifying the appropriate therapeutic approach.

State of the Evidence for Facial Skin Cancer Reconstruction.

This review provides a comprehensive presentation of the evidence available in facial reconstruction post-Mohs micrographic surgery. Given the large diversity in post-Mohs reconstruction, there are limited guidelines in the management of defects. The aim of the present work is to provide a review of the best evidence as it pertains to several considerations in facial reconstruction. Data suggests that Mohs micrographic surgery and many reconstructive procedures can be performed as outpatient procedures under local anesthesia, with narcotic pain medication only given in certain patient populations following a minority of reconstructive procedures. Perioperative and topical antibiotics are generally not indicated. Aspirin and warfarin can generally be continued for most reconstructive procedures, but clopidogrel and novel anticoagulants may predispose to increased bleeding complications. Delayed reconstruction appears to be safe, although data are discordant on this topic. No specific wound closure technique or suture choice appears to be consistently superior. Given the lack of robust comparative studies, consistent methodology, and variable defect sizes/locations, no robust evidence-based guidelines can be generated for reconstruction techniques of facial subsites.

Host Genetics and Environment Shape the Composition of the Gastrointestinal Microbiome in Nonhuman Primates.

The bacterial component of the gastrointestinal tract microbiome is comprised of hundreds of species, the majority of which live in symbiosis with the host. The bacterial microbiome is influenced by host diet and disease history, and host genetics may additionally play a role. To understand the degree to which host genetics shapes the gastrointestinal tract microbiome, we studied fecal microbiomes in 4 species of nonhuman primates (NHPs) held in separate facilities but fed the same base diet. These animals include Chlorocebus pygerythrus, Chlorocebus sabaeus, Macaca mulatta, and Macaca nemestrina. We also followed gastrointestinal tract microbiome composition in 20 Macaca mulatta (rhesus macaques [RMs]) as they transitioned from an outdoor to indoor environment and compared 6 Chlorocebus pygerythrus monkeys that made the outdoor to indoor transition to their 9 captive-born offspring. We found that genetics can influence microbiome composition, with animals of different genera (Chlorocebus versus Macaca) having significantly different gastrointestinal (GI) microbiomes despite controlled diets. Animals within the same genera have more similar microbiomes, although still significantly different, and animals within the same species have even more similar compositions that are not significantly different. Significant differences were also not observed between wild-born and captive-born Chlorocebus pygerythrus, while there were significant changes in RMs as they transitioned into captivity. Together, these results suggest that the effects of captivity have a larger impact on the microbiome than other factors we examined within a single NHP species, although host genetics does significantly influence microbiome composition between NHP genera and species. IMPORTANCE Our data point to the degree to which host genetics can influence GI microbiome composition and suggest, within primate species, that individual host genetics is unlikely to significantly alter the microbiome. These data are important for the development of therapeutics aimed at altering the microbiome within populations of genetically disparate members of primate species.