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The majority of Human Immunodeficiency Virus (HIV) negative individuals exposed to Mycobacterium tuberculosis ( Mtb ) control the bacillary infection as latent TB infection (LTBI). Co-infection with HIV, however, drastically increases the risk to progression to tuberculosis (TB) disease. TB is therefore the leading cause of death in people living with HIV (PLWH) globally. Combinatorial antiretroviral therapy (cART) is the cornerstone of HIV care in humans and reduces the risk of reactivation of LTBI. However, the immune control of Mtb infection is not fully restored by cART as indicated by higher incidence of TB in PLWH despite cART. In the macaque model of co-infection, skewed pulmonary CD4 + T EM responses persist, and new TB lesions form despite cART treatment. We hypothesized that regimens that concurrently administer anti-TB therapy and cART would significantly reduce TB in co-infected macaques than cART alone, resulting in superior bacterial control, mitigation of persistent inflammation and lasting protective immunity. We studied components of TB immunity that remain impaired after cART in the lung compartment, versus those that are restored by concurrent 3 months of once weekly isoniazid and rifapentine (3HP) and cART in the rhesus macaque (RM) model of LTBI and Simian Immunodeficiency Virus (SIV) co-infection. Concurrent administration of cART + 3HP did improve clinical and microbiological attributes of Mtb /SIV co-infection compared to cART-naïve or -untreated RMs. While RMs in the cART + 3HP group exhibited significantly lower granuloma volumes after treatment, they, however, continued to harbor caseous granulomas with increased FDG uptake. cART only partially restores the constitution of CD4 + T cells to the lung compartment in co-infected macaques. Concurrent therapy did not further enhance the frequency of reconstituted CD4 + T cells in BAL and lung of Mtb /SIV co-infected RMs compared to cART, and treated animals continued to display incomplete reconstitution to the lung. Furthermore, the reconstituted CD4 + T cells in BAL and lung of cART + 3HP treated RMs exhibited an increased frequencies of activated, exhausted and inflamed phenotype compared to LTBI RMs. cART + 3HP failed to restore the effector memory CD4 + T cell population that was significantly reduced in pulmonary compartment post SIV co-infection. Concurrent therapy was associated with the induction of Type I IFN transcriptional signatures and led to increased Mtb -specific T H1 /T H17 responses correlated with protection, but decreased Mtb -specific TNFa responses, which could have a detrimental impact on long term protection. Our results suggest the mechanisms by which Mtb /HIV co-infected individuals remain at risk for progression due to subsequent infections or reactivation due of persisting defects in pulmonary T cell responses. By identifying lung-specific immune components in this model, it is possible to pinpoint the pathways that can be targeted for host-directed adjunctive therapies for TB/HIV co-infection., Competing Interests: Conflicts of Interest Statement The authors have declared that no conflict of interest exists.

Given their genetic and anatomic similarities to humans, nonhuman primates (NHPs) may serve as animal models for urogenital diseases of humans. The purpose of this study was to examine the frequency of spontaneous urogenital lesions occurring over a 30-year period at the Yerkes and Southwest National Primate Research Centers and to compare and contrast lesions occurring in Old World versus New World primates. Lesions occurring in the chimpanzee ( Pan troglodytes ), baboon ( Papio spp.), rhesus macaque ( Macaca mulatta ), cynomolgus macaque ( Macaca fascicularis ), pig-tailed macaque ( Macaca nemestrina ), sooty mangabey ( Cercocebus atys ), common marmoset ( Callithrix jacchus ), cotton-top tamarin ( Sanguinus oedipus ), and squirrel monkey ( Saimiri sciureus ) are discussed. The most common lesions of the kidney were medullary amyloidosis, renal cysts, renal tubular degeneration, glomerulonephritis or glomerulopathy, nephritis, nephrocalcinosis, pyelonephritis, and hydronephrosis. Specific causes of renal tubular disease included pigmentary nephrosis and tubular lipidosis. Renal tumors, including renal adenoma and carcinoma, lymphoma, and nephroblastoma, were infrequent diagnoses in all species. Endometriosis was the most frequently diagnosed lesion of the female genital tract. Of the animals examined in this study, it was most frequent in Old World primates. Leiomyoma was the most common uterine tumor. Granulosa cell tumor was the most frequently observed neoplasm of the ovaries, followed by teratoma. Of animals included in the study, most ovarian tumors occurred in baboons. Neoplasms of the male reproductive tract included interstitial cell tumor, seminoma, penile squamous cell carcinoma, penile papilloma, and histiocytoma. In New World monkeys, renal lesions were reported more frequently than genital lesions.

An urgent global quest for effective therapies to prevent and treat coronavirus disease 2019 (COVID-19) is ongoing. We previously described REGN-COV2, a cocktail of two potent neutralizing antibodies (REGN10987 and REGN10933) that targets nonoverlapping epitopes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. In this report, we evaluate the in vivo efficacy of this antibody cocktail in both rhesus macaques, which may model mild disease, and golden hamsters, which may model more severe disease. We demonstrate that REGN-COV-2 can greatly reduce virus load in the lower and upper airways and decrease virus-induced pathological sequelae when administered prophylactically or therapeutically in rhesus macaques. Similarly, administration in hamsters limits weight loss and decreases lung titers and evidence of pneumonia in the lungs. Our results provide evidence of the therapeutic potential of this antibody cocktail., (Copyright © 2020, American Association for the Advancement of Science.)

Background: Salivary gland neoplasms are rare in non-human primates., Methods: Thirty-five years of pathology records were reviewed at the Southwest (SNPRC) and Yerkes (YNPRC) National Primate Research Centers. An in-depth literature search for salivary gland neoplasms in non-human primates was performed., Results: Seventeen salivary gland neoplasms (nine from SNPRC and YNPRC, eight from published literature) were identified. There were seven malignant, nine benign, and one of undetermined behavior identified in eight rhesus macaques, six baboons, a chimpanzee, a bonnet macaque, and a moustached tamarin. Parotid gland was the most frequent origin (n = 7), followed by mandibular (n = 4) or minor salivary glands (n = 2). Two animals with salivary gland adenoma had a history of prior radiation exposure., Conclusions: Parotid glands are the most common origin for salivary gland neoplasms. Salivary gland neoplasms should be considered in the differential diagnoses of head and neck masses in non-human primates., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We present a case of hepatocellular carcinoma (HCC) in the placenta of healthy baboon (Papio spp.). Grossly, the fetal, maternal, and placental tissues were unremarkable. Histologically, the placenta contained an unencapsulated, poorly demarcated, infiltrative, solidly cellular neoplasm composed of cells that resembled hepatocytes. The neoplastic cells were diffusely positive for vimentin and focally positive for Ae1/Ae3, Arginase -1, glutamine synthetase, and CD10, and negative for ER, vascular markers (CD31 and D240), S100, glypican, C-reactive protein, FABP, desmin, and beta-catenin; INI1 positivity was similar to non-neoplastic tissues. The case likely represents a unique subtype of HCC., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Disorders of sexual development are rare in non-human primates. We report a case of true hermaphroditism in a 19-year-old, nulliparous, female baboon (Papio spp.). At necropsy, the animal was obese with adequate muscle mass and hydration. Reproductive organs appeared normal with the exception of 2 firm nodular structures in the myometrium (1-1.5 cm diameter) and a thickened, dark endocervical mucosa. Histologically, both gonads were ovotestes and contained discrete areas of ovarian and testicular tissue. There were follicles in various stages of development surrounded by ovarian stroma. Other areas contained hypoplastic seminiferous tubules lined by Sertoli cells, but lacked germ cells and spermatozoa. The uterine lesions were consistent with adenomyosis and cystic endometrial hyperplasia. Cervical lesions were consistent with atypical glandular hyperplasia and squamous metaplasia with dysplasia. We report the first case of ovotesticular disorder of sexual development (OT-DSD), or true hermaphroditism in a baboon., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Obesity in pregnancy (MO) is a risk factor for maternal and/or fetal cardiovascular system disorders. This study evaluated maternal CVS expression of microRNA-29 family and its target molecules in MO to test the hypotheses: CVS miR-29 concentrations are increased in pregnancy and decreased in MO., Methods: Non-pregnant (n=4), pregnant obese (POb, n=4), and pregnant non-obese (PnOb, n=4) baboons (Papio spp.) were studied. Maternal left ventricle (LV), left atrium (LA), and aortic arch (AA) were collected at the end of gestation. Expression of MiR-29 and elastin (ELN) mRNA were quantified., Results: LA miR-29 (a, c) expression was highest in PnOb. In the LV, miR-29b expression trended lower (P=.059) for PnOb animals. ELN mRNA expression correlated positively with miR-29b expression in AA (r=.76, P=.03)., Conclusion: Maternal obesity diminishes miR-29 adaptation to pregnancy. Pharmacologic, tissue-specific targeting of miRNA-29 may represent a strategy for prevention and treatment of MO complications., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Evolutionary approaches are powerful tools for understanding human disorders. The composition of vaginal microbiome is important for reproductive success and has not yet been characterized in the contexts of social structure and vaginal pathology in non-human primates (NHPs). We investigated vaginal size, vulvovaginal pathology and the presence of the main human subtypes of Lactobacillus spp./ BV-related species in the vaginal microflora of baboons (Papio spp.). We performed morphometric measurements of external and internal genitalia (group I, n = 47), analyzed pathology records of animals from 1999-2015 (group II, n = 64 from a total of 12,776), and evaluated vaginal swabs using polymerase chain reaction (PCR) (group III, n = 14). A total of 68 lesions were identified in 64 baboons. Lactobacillus iners, Gardnerella vaginalis, Atopobium vaginae, Megasphaera I, and Megasphaera II were not detected. L. jensenii, L. crispatus, and L. gasseri were detected in 2/14 (14.2%), 1/14 (7.1%), and 1/14 (7.1%) samples, respectively. BVAB2 was detected in 5/14 (35.7%) samples. The differences in the vaginal milieu between NHP and humans might be the factor associated with human-specific pattern of placental development and should be taken in consideration in NHP models of human pharmacology and microbiology.

Introduction: Maternal obesity (MO) remains a serious obstetric problem with acute and chronic morbidities for both mothers and offspring. The mechanisms underlying these adverse consequences of MO remain unknown. Endocannabinoids (ECB) are neuromodulatory lipids released from adipocytes and other tissues. Metabolic crosstalk between placenta and adipocytes may mediate sequelae of MO. The goal of this study was to elucidate placental and systemic ECB in MO., Material and Methods: Placentas, sera, and subcutaneous fat were collected at Cesarean sections performed near term (0.9 G) in four non-obese (nOB) and four obese (OB) baboons (Papio spp.). Concentrations of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured by liquid chromatography coupled to tandem mass spectrometry. AEA and 2-AG pathways were characterized in placentas by Q-RT-PCR, Western blot and immunohistochemistry., Results: Placental 2-AG levels were lower and maternal fat AEA levels were higher in OB (1254.1 ± 401.3 nmol/kg and 17.3 ± 4 nmol/kg) vs. nOB (3124.2 ± 557.3 nmol/kg and 3.1 ± 0.6 nmol/kg) animals. Concentrations of 2-AG correlated positively between maternal fat and placenta (r = 0.82, p = 0.013), but correlated negatively with maternal leptin concentrations (r = -0.72, p = 0.04 and r = -0.83, p = 0.01, respectively)., Conclusion: This is the first study to demonstrate differential ECB pathway regulation in maternal fat and placenta in MO. Differential regulation and function exist for AEA and 2-AG as the major ECB pathways in placenta., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Abruptio placentae is a serious problem with a high rate of maternal and fetal mortality and documented sexual dimorphism in reoccurrence. Macaca fascicularis is a well-described reproductive model; however, there are no data available regarding sexual dimorphism in abruptio placentae in these species., Methods: A retrospective study of pathology and medical records in a large colony of M. fascicularis was performed. Placental specimens were analyzed., Results: The incidence of placenta abruptio in the colony was 15.7/1000 births. In the abruptio placentae group, male fetuses had lower placental disk length and increased femur length compared with female fetuses. The feto-pacental ratio and fetal weight were lower in the male fetuses in the abruption group compared with those in the stillbirth group without abruption placentae., Conclusion: This is the first documentation of male bias in placental and fetal development in abruptio placentae in non-human primates., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Abruptio placentae, defined as premature separation of a normally implanted placenta, is a life threatening pregnancy complication with unknown pathophysiology. A history of abruptio placentae is the major risk factor for this pregnancy complication in humans. We describe the first case of recurrent abruptio placentae in a Macaca fascicularis., Material and Methods: A pregnant M. fascicularis at term gestation was presented with weakness and hypothermia. Cesarean section revealed retroplacental hemorrhage with partial placental separation from the uterus., Results: The weight of the female fetus was within the lower birth weight range for these species. The maternal side of placenta contained necrotic tissue, occupying approximately 60% of the maternal surface. The placental implantation bed demonstrated neutrophil infiltration. Perivascular collections of lymphocytes were noticed in the uterine smooth muscle., Conclusion: This case report underlines the importance of neutrophil infiltration and uterine venous drainage in the cascade of events leading to abruptio placentae., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Earlier studies at the growing edge of colorectal cancer (CRC) in humans and rats have shown dilated neoplastic glands, some with a thin layer of flattened tumor cells (FTCs), some lacking one or more groups of consecutive lining tumor cells (called glandular pores, GPs)., Materials and Methods: The characteristics of the neoplastic glands at the invading edge of CRCs were investigated in 39 baboons. A total of 190 neoplastic glands were studied in the 38 cases of glandular-forming adenocarcinomas., Results: In the studied neoplastic glands FTCs or GPs were recorded in 44.7% (85 glands). FTCs were found in 9.5% (18 glands) and GPs in 35.3% (67 glands). Only 7.9% or 3 out of the 38 animals showed neoplastic glands with GPs in the bulk of the tumor., Conclusion: In similarity to colorectal adenocarcinomas in humans, flattened tumor cells and glandular pores were found at the invading tumor edge of colorectal adenocarcinomas in baboons. A possible mechanism of host invasion is proposed.