Host evolution shapes gut microbiome composition in Astyanax mexicanus.

The ecological and genetic changes that underlie the evolution of host-microbe interactions remain elusive, primarily due to challenges in disentangling the variables that alter microbiome composition. To understand the impact of host habitat, host genetics, and evolutionary history on microbial community structure, we examined gut microbiomes of river- and three cave-adapted morphotypes of the Mexican tetra, Astyanax mexicanus, in their natural environments and under controlled laboratory conditions. Field-collected samples were dominated by very few taxa and showed considerable interindividual variation. We found that lab-reared fish exhibited increased microbiome richness and distinct composition compared to their wild counterparts, underscoring the significant influence of habitat. Most notably, however, we found that morphotypes reared on the same diet throughout life developed distinct microbiomes suggesting that genetic loci resulting from cavefish evolution shape microbiome composition. We observed stable differences in Fusobacteriota abundance between morphotypes and demonstrated that this could be used as a trait for quantitative trait loci mapping to uncover the genetic basis of microbial community structure.

Home-Based Pediatric Hospice and Palliative Care Provider Visits: Effects on Healthcare Utilization.

OBJECTIVE: This hypothesis-generating study sought to assess the impact of home-based hospice and palliative care (HBHPC) provider home visits (HV) on healthcare use. STUDY DESIGN: Retrospective review of individuals ages 1 month to 21 years receiving an in-person HBHPC provider (MD/DO or APN) HV through 2 HBHPC programs in the Midwest from January 1, 2013, through December 31, 2018. Descriptive statistics were calculated for healthcare use variables. Paired t test or Wilcoxon signed-rank test compared the changes in healthcare use the year before and year after initial provider HVs. RESULTS: The cohort included 195 individuals (49% female), with diagnoses composed of 49% neurologic, 30% congenital chromosomal, 11% oncologic, 7% cardiac, and 3% other. After implementation of HBHPC services, these patients showed decreases in the median (IQR) number of intensive care unit days (before HV, 12 [IQR, 4-37]; after HV, 0 [IQR, 0-8]; P < .001); inpatient admissions (before HV, 1 [IQR, 1-3]; after HV, 1 [IQR, 0-2]; P = .005); and number of inpatient days (before HV, 5 [IQR, 1-19]; after HV, 2 [IQR, 0-8]; P = .009). There was an increase in clinically relevant phone calls to the HBHPC team (before HV, 1 [IQR, 0-4] vs after HV, 4 [IQR, 1-7]; P < .001) and calls to the HBHPC team before emergency department visits (before HV, 0 [IQR, 0-0] vs after HV, 1 [IQR, 1-2]; P < .001). CONCLUSION: HBHPC provider HVs were associated with fewer inpatient admissions, hospital days, and intensive care unit days, and increased clinically relevant phone calls and phone calls before emergency department visit. These findings indicate that HBHPC HV may contribute to decreased inpatient use and increased use of the HBHPC team.

A Note on Preexposure Prophylaxis Preferences Among Women Who Inject Drugs.

ABSTRACT: We informed women who inject drugs about different preexposure prophylaxis (PrEP) formulations; they then ranked their preferences. Daily oral PrEP was most preferred, followed by injectable PrEP and vaginal rings/gels, especially among women of color. Multiple PrEP options should be discussed with women who inject drugs to increase uptake.

Limited Risk Compensation Among Women Who Inject Drugs: Results From the Project Sexual Health Equity Preexposure Prophylaxis Demonstration Study in Philadelphia.

ABSTRACT: The impact of preexposure prophylaxis uptake on sexual and injection-related behaviors among women who inject drugs is poorly understood. Over 24 weeks, preexposure prophylaxis uptake among women who inject drugs was associated with increased sharing of injection equipment but not syringes and no changes in condomless sex, providing limited evidence of risk compensation in this vulnerable population.

In-depth characterization of a new patient-derived xenograft model for metaplastic breast carcinoma to identify viable biologic targets and patterns of matrix evolution within rare tumor types.

Metaplastic breast carcinoma (MBC) is a rare breast cancer subtype with rapid growth, high rates of metastasis, recurrence and drug resistance, and diverse molecular and histological heterogeneity. Patient-derived xenografts (PDXs) provide a translational tool and physiologically relevant system to evaluate tumor biology of rare subtypes. Here, we provide an in-depth comprehensive characterization of a new PDX model for MBC, TU-BcX-4IC. TU-BcX-4IC is a clinically aggressive tumor exhibiting rapid growth in vivo, spontaneous metastases, and elevated levels of cell-free DNA and circulating tumor cell DNA. Relative chemosensitivity of primary cells derived from TU-BcX-4IC was performed using the National Cancer Institute (NCI) oncology drug set, crystal violet staining, and cytotoxic live/dead immunofluorescence stains in adherent and organoid culture conditions. We employed novel spheroid/organoid incubation methods (Pu·MA system) to demonstrate that TU-BcX-4IC is resistant to paclitaxel. An innovative physiologically relevant system using human adipose tissue was used to evaluate presence of cancer stem cell-like populations ex vivo. Tissue decellularization, cryogenic-scanning electron microscopy imaging and rheometry revealed consistent matrix architecture and stiffness were consistent despite serial transplantation. Matrix-associated gene pathways were essentially unchanged with serial passages, as determined by qPCR and RNA sequencing, suggesting utility of decellularized PDXs for in vitro screens. We determined type V collagen to be present throughout all serial passage of TU-BcX-4IC tumor, suggesting it is required for tumor maintenance and is a potential viable target for MBC. In this study we introduce an innovative and translational model system to study cell-matrix interactions in rare cancer types using higher passage PDX tissue.

Four Decades of Epidemiologic Science on HIV Infection and Disease, and Its Impact on Public Health Practice and Policy for Sexual and Gender Minority Persons.

Even at the cusp of the second decade of the new millennia, HIV continues to be a significant public health challenge for sexual and gender minorities (SGM). Men who have sex with men and transgender women, in particular, continue to report higher rates of HIV incidence compared to their heterosexual counterparts, while facing significant barriers to comprehensive sexual healthcare. In Delaware, HIV infection impacts a substantial number of individuals with approximately 14.5 incident cases per 100,000. This ranks Delaware as the 14th highest for HIV incidence among U.S. states. However, the largest healthcare provider in Delaware, Christiana Care Health System, has created many health initiatives to support the health needs of SGM and those living with HIV. The current sustained rate of HIV infection indicates the need for enhanced epidemiologic work to identify HIV cases in subgroups of diverse sexuality and gender identity, collaboration within and across research institution and community organizations, as well as engagement in creative solutions that target the multiple levels of factors contributing to HIV incidence. In addition, it is imperative that local agencies and health organizations continue to support these communities of SGM individuals during the current sociopolitical climate of the national U.S. government.

A Dual Role for P2X7 Receptor during Porphyromonas gingivalis Infection.

Emerging evidence suggests a role for purinergic signaling in the activation of multiprotein intracellular complexes called inflammasomes, which control the release of potent inflammatory cytokines, such as interleukin (IL) -1ß and -18. Porphyromonas gingivalis is intimately associated with periodontitis and is currently considered one of the pathogens that can subvert the immune system by limiting the activation of the NLRP3 inflammasome. We recently showed that P. gingivalis can dampen eATP-induced IL-1ß secretion by means of its fimbriae in a purinergic P2X7 receptor-dependent manner. Here, we further explore the role of this purinergic receptor during eATP-induced IL-1ß processing and secretion by P. gingivalis-infected macrophages. We found that NLRP3 was necessary for eATP-induced IL-1ß secretion as well as for caspase 1 activation irrespective of P. gingivalis fimbriae. Additionally, although the secretion of IL-1ß from P. gingivalis-infected macrophages was dependent on NLRP3, its adaptor protein ASC, or caspase 1, the cleavage of intracellular pro-IL-1ß to the mature form was found to occur independently of NLRP3, its adaptor protein ASC, or caspase 1. Our in vitro findings revealed that P2X7 receptor has a dual role, being critical not only for eATP-induced IL-1ß secretion but also for intracellular pro-IL-1ß processing. These results were relevant in vivo since P2X7 receptor expression was upregulated in a P. gingivalis oral infection model, and reduced IFN-γ and IL-17 were detected in draining lymph node cells from P2rx7(-/-) mice. Furthermore, we demonstrated that P2X7 receptor and NLRP3 transcription were modulated in human chronic periodontitis. Overall, we conclude that the P2X7 receptor has a role in periodontal immunopathogenesis and suggest that targeting of the P2X7/NLRP3 pathway should be considered in future therapeutic interventions in periodontitis.

Paraiotonchium muscadomesticae n. sp. (Tylenchida: lotonchiidae) a Parasite of the House Fly (Musca domestica) in Brazil and a Key to Species of the Genus Paraiotonchium.

Paraiotonchium muscadomesticae n. sp., a parasite of the house fly, Musca domestica L., is described and illustrated from material collected in Brazil. The life cycle of P. muscadomesticae is similar to that of P. autumnale (Nickle), consisting of alternating gamogenetic and parthenogenetic generations. Paraiotonchium muscadomesticae n. sp. can be distinguished from P. nicholasi Slobodyanyuk, P. autumnale (Nickle) Slobodyanyuk, and P. crassirostris (Yatham &Rao) Siddiqi by the shorter body length of young heterosexual females, 652 g.m (530-709) for P. muscadomesticae compared to 750 mum or more (801-1,050) for the others. Paraiotonchium muscadomesticae is close to P. nicholosi but differs from it by V ratio and spicule length (V = 80-84; spicule = 16-21 p.m in P. muscadomesticae compared to V = 73-78; spicule = 25-35 mum in P. nicholasi). Paraiotonchium muscadomesticae and P. nicholasi differ from all species of this genus by the absence of a bursa on males of these two species.