De novo induction of intratumoral lymphoid structures and vessel normalization enhances immunotherapy in resistant tumors.

The tumor microenvironment confers profound resistance to anti-cancer immunotherapy. By targeting LIGHT, a member of the TNF superfamily of cytokines, to tumor vessels via a vascular targeting peptide (VTP), we developed a reagent with the dual ability to modulate the angiogenic vasculature and to induce tertiary lymphoid structures (TLSs). LIGHT-VTP triggered the influx of endogenous T cells into autochthonous or syngeneic tumors, which are resistant to immunotherapy. LIGHT-VTP in combination with checkpoint inhibition generated a large number of intratumoral effector and memory T cells with ensuing survival benefits, while the addition of anti-tumor vaccination achieved maximal therapeutic efficacy. Thus, the combination treatments stimulated the trafficking of pre-existing endogenous effector T cells as well as their intratumoral activation and were more successful than current immunotherapies, which fail due to tumor-intrinsic resistance mechanisms.

The impact of cancer metastases on COVID-19 outcomes: A COVID-19 and Cancer Consortium registry-based retrospective cohort study.

BACKGROUND: COVID-19 can have a particularly detrimental effect on patients with cancer, but no studies to date have examined if the presence, or site, of metastatic cancer is related to COVID-19 outcomes. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, the authors identified 10,065 patients with COVID-19 and cancer (2325 with and 7740 without metastasis at the time of COVID-19 diagnosis). The primary ordinal outcome was COVID-19 severity: not hospitalized, hospitalized but did not receive supplemental O2, hospitalized and received supplemental O2, admitted to an intensive care unit, received mechanical ventilation, or died from any cause. The authors used ordinal logistic regression models to compare COVID-19 severity by presence and specific site of metastatic cancer. They used logistic regression models to assess 30-day all-cause mortality. RESULTS: Compared to patients without metastasis, patients with metastases have increased hospitalization rates (59% vs. 49%) and higher 30 day mortality (18% vs. 9%). Patients with metastasis to bone, lung, liver, lymph nodes, and brain have significantly higher COVID-19 severity (adjusted odds ratios [ORs], 1.38, 1.59, 1.38, 1.00, and 2.21) compared to patients without metastases at those sites. Patients with metastasis to the lung have significantly higher odds of 30-day mortality (adjusted OR, 1.53; 95% confidence interval, 1.17-2.00) when adjusting for COVID-19 severity. CONCLUSIONS: Patients with metastatic cancer, especially with metastasis to the brain, are more likely to have severe outcomes after COVID-19 whereas patients with metastasis to the lung, compared to patients with cancer metastasis to other sites, have the highest 30-day mortality after COVID-19.

Chronic stress increases adaptive immune response over six weeks in the house sparrow, Passer domesticus.

The vertebrate stress response enables an organism to shift energy towards activities that promote immediate survival when facing a threat to homeostasis, but it can also have detrimental effects on organismal health. Acute and chronic stressors generally have contrasting effects on immune responses, but the timeline of this transition between acute and chronic stressors and their effects on immune responses remains unclear. In this study, we investigate changes in immune markers in captive house sparrows (Passer domesticus) after exposure to normal laboratory conditions, an acute stressor, and chronic stressors for 42 days. Specifically, we examined changes in baseline and stress-induced corticosterone concentrations, body condition, heterophil/lymphocyte (H:L) ratio, hemolysis-hemagglutination, and wound healing. We found that individuals exposed to a single acute stressor had significantly higher stress-induced corticosterone concentrations 24 h after stressor exposure, however this effect was reversed after 48 h. Chronic stressor exposure resulted in generally stronger adaptive immune responses, demonstrated by higher baseline and stress-induced lysis, higher baseline hemagglutination, and slower wound healing. Within-trait correlations also increased with chronic stressor exposure, suggesting limitations on phenotypic plasticity. Most of the effects of chronic stressor exposure on immune markers strengthened over the 42 days of the experiment and differences between captivity-only and treatment groups were not apparent until approximately 20 days of chronic stressor exposure. These results highlight the importance of stressor duration in understanding the effects of chronic stressor exposure on immune responses.

A phase II study of neoadjuvant liposomal irinotecan with 5-FU and oxaliplatin (NALIRIFOX) in pancreatic adenocarcinoma.

For patients with localized pancreatic cancer with minimal vascular involvement, optimal survivability requires a multidisciplinary approach of surgical resection and systemic chemotherapy. FOLFIRINOX is a combination chemotherapy regimen that offers promising results in the perioperative and metastatic settings; however, it can cause significant adverse effects. Such toxicity can negatively impact some patients, resulting in chemotherapy discontinuation or surgical unsuitability. In an effort to reduce toxicities and optimize outcomes, this investigation explores the safety and feasibility of substituting liposomal irinotecan (nal-IRI) for nonliposomal irinotecan to improve tumor drug delivery and potentially reduce toxicity. This regimen, NALIRIFOX, has the potential to be both safer and more effective when administered in the preoperative setting.

For patients with pancreatic cancer with little to no cancer near the blood vessels, the best life expectancy usually requires surgery and chemotherapy. FOLFIRINOX is a chemotherapy medicine that offers promising results for both patients getting surgery and for patients with widespread disease. However, it can cause harmful side effects. The side effects can be so bad that the chemotherapy has to be stopped or that surgery is no longer possible. In order to reduce the harmful side effects and improve outcomes, this investigation looks into the safety and practicality of using a different version of one of the medicines. The different version hopes to improve drug delivery and reduce harmful side effects. This regimen, NALIRIFOX, can be safer and more effective in patients awaiting surgery. Clinical Trial Registration: UF-STO-PANC-004 (NCT03483038) (ClinicalTrials.gov).

A Place to Call Home: Hearing the Perspectives of People Living with Homelessness and Mental Illness Through Service Evaluation.

There is an ongoing need to incorporate the perspectives of people in supported community housing to improve the provision of integrated mental health services. This study aimed to explore the satisfaction and experiences of people who have received supported housing and mental health services. We conducted a retrospective, mixed methods study using a data mining approach, analyzing consumer satisfaction survey responses collected on discharge from the service over a 7-year period. Responses from 178 consumers aged between 20 and 62 years were included. Quantitative results indicated that consumers rated the quality of services as relatively high. Analysis of qualitative responses identified seven themes describing people's views on how they had benefitted from the service. Consumers reported benefits in terms of practical and emotional supports, responsiveness of the team to their needs, socialization and community integration, personal growth and recovery, and finding 'my place'. Themes of learning and skills development were also important. These results suggest that practical support, together with emotional expressions of care and compassion are most valued by people who participated in this service. This research has implications for service evaluation and for future research, which may include focusing on the key role of connectedness, 'my place' and hope for recovery.

HEMATOLOGIC AND BIOCHEMICAL VALUES OF THE JUVENILE EASTERN GRAY SQUIRREL (SCIURUS CAROLINENSIS).

Venous blood samples were collected from 64 apparently healthy juvenile Eastern gray squirrels (Sciurus carolinensis) after sedation with midazolam at the Wildlife Center of Texas located in Houston, Texas, during 2012. Blood gas (pH, PCO2, PO2, base excess, bicarbonate, oxygen saturation), electrolyte (sodium, potassium), biochemical (total CO2, ionized calcium, glucose), and hematologic parameters (hematocrit, hemoglobin, complete blood count) were determined using the i-STAT point-of-care analyzer. Sex did not affect any analyte. All squirrels recovered uneventfully and were successfully rehabilitated and released. Most values were as expected based on comparison to other young rodent species. These analyte data for healthy juvenile Eastern gray squirrels may be useful in assessment of Eastern gray squirrel population health and management and treatment of individual squirrels presented in need of medical care.

Venous Blood Analytes and Osmolality of Rehabilitated Juvenile Black-bellied Whistling Ducks (Dendrocygna autumnalis).

Venous blood samples were collected from 129 apparently healthy, rehabilitated juvenile black-bellied whistling ducks (Dendrocygna autumnalis) immediately before release from rehabilitation. Blood gas, electrolyte, and select biochemical and hematologic values were analyzed by using a point-of-care analyzer, and complete blood cell counts and osmolality were determined. Most biochemical analyte values were distributed parametrically, while most hematologic values were nonparametrically distributed. Calculated osmolality values were in poor agreement with measured osmolality values, and values of packed cell volume had poor agreement with hematocrit values determined with the i-STAT 1. The physiologic values reported provide vital information to assess individual duck health and guide fluid therapy in captivity and may prove useful to assess free-living population health of this duck species.

Homopolymer tract organization in the human malarial parasite Plasmodium falciparum and related Apicomplexan parasites.

BACKGROUND: Homopolymeric tracts, particularly poly dA.dT, are enriched within the intergenic sequences of eukaryotic genomes where they appear to act as intrinsic regulators of nucleosome positioning. A previous study of the incomplete genome of the human malarial parasite Plasmodium falciparum reports a higher than expected enrichment of poly dA.dT tracts, far above that anticipated even in this highly AT rich genome. Here we report an analysis of the relative frequency, length and spatial arrangement of homopolymer tracts for the complete P. falciparum genome, extending this analysis to twelve additional genomes of Apicomplexan parasites important to human and animal health. In addition, using nucleosome-positioning data available for P. falciparum, we explore the correlation of poly dA.dT tracts with nucleosome-positioning data over key expression landmarks within intergenic regions. RESULTS: We describe three apparent lineage-specific patterns of homopolymeric tract organization within the intergenic regions of these Apicomplexan parasites. Moreover, a striking pattern of enrichment of overly long poly dA.dT tracts in the intergenic regions of Plasmodium spp. uniquely extends into protein coding sequences. There is a conserved spatial arrangement of poly dA.dT immediately flanking open reading frames and over predicted core promoter sites. These key landmarks are all relatively depleted in nucleosomes in P. falciparum, as would be expected for poly dA.dT acting as nucleosome exclusion sequences. CONCLUSIONS: Previous comparative studies of homopolymer tract organization emphasize evolutionary diversity; this is the first report of such an analysis within a single phylum. Our data provide insights into the evolution of homopolymeric tracts and the selective pressures at play in their maintenance and expansion.

Camelid heat stress: 15 cases (2003-2011).

This case series describes novel findings associated with heat stress in 15 cases in South American camelids that had no pre-existing illnesses and which had clinical signs of illness after exposure to a warm environment. Novel findings include decreased packed cell volume and albumin concentration and mild spinal axonal degeneration. Heat stress should be considered in weak camelids with a history of hyperthermia.

Stress thermique chez les camélidés : 15 cas (2003­2011). Cette série de cas décrit des constatations nouvelles associées au stress thermique dans 15 cas chez des camélidés d'Amérique du Sud qui n'avaient aucune maladie préexistante et qui ont présenté des signes de maladie après l'exposition à un environnement chaud. Les constatations nouvelles comprennent une valeur d'hématocrite réduite et une concentration d'albumine et une légère dégénération rachidienne axonale. Le stress thermique devrait être considéré chez les camélidés affaiblis ayant des antécédents d'hyperthermie.(Traduit par Isabelle Vallières).

Comparison of two analyzers to determine selected venous blood analytes of Quaker parrots (Myiopsitta monachus).

Point of care devices can assess electrolyte, blood gas, biochemical, and hematologic values in a critical care setting. Although these devices are commonly used in humans and companion mammals, few studies have assessed their use in avian species. This study compares electrolyte, hemoglobin (Hgb), hematocrit (Hct), acid-base, and venous blood gas parameters between the i-STAT and IRMA TruPoint blood gas analysis systems for 35 Quaker parrots. Agreement between the two analyzers and the effect of gender, time lag between sample analysis, and cartridge expiration were evaluated. Male birds had increased Hgb and Hct compared with females, independent of analyzer method. In expired i-STAT cartridges, only glucose significantly increased. Packed cell volume determined by centrifugation was higher than Hct, as calculated by either analyzer. The analyzers had good agreement for total carbon dioxide, bicarbonate, pH, and Hgb, fair agreement for potassium (K), ionized calcium (iCa), venous partial pressure of carbon dioxide, and base excess, and poor agreement for sodium (Na), venous partial pressure of oxygen (PO2), and oxygen saturation (SO2). Values for Na, iCa, PO2, and SO2 were significantly higher on the IRMA than the i-STAT, while K was significantly lower on the IRMA when compared with the i-STAT. The time lag between sample analyses on the i-STAT and IRMA did not be correlate to any analyte changes. Despite these differences, both the i-STAT and the IRMA appear to be acceptable clinical tools in avian critical care, although reference ranges for each analyzer should be created.

Select Venous Analytes and Fibrinogen Determination Using Two Methods in Brown Pelicans.

The brown pelican (Pelecanus occidentalis) is a species often affected by natural and man-made disasters such as hurricanes and oil spills, as well as general human activities; that subsequently receives medical care and rehabilitation. During rehabilitation, blood may be collected for various tests to help with diagnosis, treatment, and monitoring. Reference intervals for this species are limited, dated, and typically from small sample sizes. Seventy-one presumed healthy brown pelicans were sampled as part of their pre-release examination from rehabilitation at the Wildlife Center of Texas after a large volume stranding from December 2014 to January 2015, and various venous analytes were measured to establish updated reference intervals for brown pelicans. Fibrinogen was measured via heat precipitation and the Abaxis VSPro equine fibrinogen cartridge to determine reference intervals and in an attempt to validate the VSPro for use in avian species. Abaxis VS2 Avian/Reptile Chemistry panel, iSTAT CG4+, and iSTAT Chem8+ results, in addition to body condition score, spun PCV, cloacal temperature, and fibrinogen were measured. Proposed reference intervals for brown pelicans are presented. Fibrinogen results were not comparable between the gold standard method and the VSPro, indicating that the VSPro is not appropriate for use in brown pelicans.

Analysis of the spatial and temporal arrangement of transcripts over intergenic regions in the human malarial parasite Plasmodium falciparum.

BACKGROUND: The ability of the human malarial parasite Plasmodium falciparum to invade, colonise and multiply within diverse host environments, as well as to manifest its virulence within the human host, are activities tightly linked to the temporal and spatial control of gene expression. Yet, despite the wealth of high throughput transcriptomic data available for this organism there is very little information regarding the location of key transcriptional landmarks or their associated cis-acting regulatory elements. Here we provide a systematic exploration of the size and organisation of transcripts within intergenic regions to yield surrogate information regarding transcriptional landmarks, and to also explore the spatial and temporal organisation of transcripts over these poorly characterised genomic regions. RESULTS: Utilising the transcript data for a cohort of 105 genes we demonstrate that the untranscribed regions of mRNA are large and apportioned predominantly to the 5' end of the open reading frame. Given the relatively compact size of the P. falciparum genome, we suggest that whilst transcriptional units are likely to spatially overlap, temporal co-transcription of adjacent transcriptional units is actually limited. Critically, the size of intergenic regions is directly dependent on the orientation of the two transcriptional units arrayed over them, an observation we extend to an analysis of the complete sequences of twelve additional organisms that share moderately compact genomes. CONCLUSIONS: Our study provides a theoretical framework that extends our current understanding of the transcriptional landscape across the P. falciparum genome. Demonstration of a consensus gene-spacing rule that is shared between P. falciparum and ten other moderately compact genomes of apicomplexan parasites reveals the potential for our findings to have a wider impact across a phylum that contains many organisms important to human and veterinary health.

Breakthrough SARS-CoV-2 infections among patients with cancer following two and three doses of COVID-19 mRNA vaccines: a retrospective observational study from the COVID-19 and Cancer Consortium.

Background: Breakthrough SARS-CoV-2 infections following vaccination against COVID-19 are of international concern. Patients with cancer have been observed to have worse outcomes associated with COVID-19 during the pandemic. We sought to evaluate the clinical characteristics and outcomes of patients with cancer who developed breakthrough SARS-CoV-2 infections after 2 or 3 doses of mRNA vaccines. Methods: We evaluated the clinical characteristics of patients with cancer who developed breakthrough infections using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19; NCT04354701). Analysis was restricted to patients with laboratory-confirmed SARS-CoV-2 diagnosed in 2021 or 2022, to allow for a contemporary unvaccinated control population; potential differences were evaluated using a multivariable logistic regression model after inverse probability of treatment weighting to adjust for potential baseline confounding variables. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported. The primary endpoint was 30-day mortality, with key secondary endpoints of hospitalization and ICU and/or mechanical ventilation (ICU/MV). Findings: The analysis included 2486 patients, of which 564 and 385 had received 2 or 3 doses of an mRNA vaccine prior to infection, respectively. Hematologic malignancies and recent receipt of systemic anti-neoplastic therapy were more frequent among vaccinated patients. Vaccination was associated with improved outcomes: in the primary analysis, 2 doses (aOR: 0.62, 95% CI: 0.44-0.88) and 3 doses (aOR: 0.20, 95% CI: 0.11-0.36) were associated with decreased 30-day mortality. There were similar findings for the key secondary endpoints of ICU/MV (aOR: 0.60, 95% CI: 0.45-0.82 and 0.37, 95% CI: 0.24-0.58) and hospitalization (aOR: 0.60, 95% CI: 0.48-0.75 and 0.35, 95% CI: 0.26-0.46) for 2 and 3 doses, respectively. Importantly, Black patients had higher rates of hospitalization (aOR: 1.47, 95% CI: 1.12-1.92), and Hispanic patients presented with higher rates of ICU/MV (aOR: 1.61, 95% CI: 1.06-2.44). Interpretation: Vaccination against COVID-19, especially with additional doses, is a fundamental strategy in the prevention of adverse outcomes including death, among patients with cancer. Funding: This study was partly supported by grants from the National Cancer Institute grant number P30 CA068485 to C-YH, YS, SM, JLW; T32-CA236621 and P30-CA046592 to C.R.F; CTSA 2UL1TR001425-05A1 to TMW-D; ACS/FHI Real-World Data Impact Award, P50 MD017341-01, R21 CA242044-01A1, Susan G. Komen Leadership Grant Hunt to MKA. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH).

Comparison of the absolute and relative efficiencies of electroporation-based transfection protocols for Plasmodium falciparum.

BACKGROUND: Several electroporation protocols exist to transfect exogenous DNA into Plasmodium falciparum. To date, however, only a subjective analysis of their relative efficiencies has been reported. METHODS: A time-course of luciferase reporter expression is used to provide an objective quantitative analysis of the absolute efficiency of three electroporation techniques; direct electroporation of ring stage infected erythrocytes, preloading of erythrocytes and a novel "double-tap" protocol that combines both approaches. RESULTS: Preloading of erythrocytes shows a mean efficiency of 9.59 x 10(-6), some 5-180 fold more efficient than matched experiments utilizing the "double-tap" and direct electroporation of ring stage infected erythrocytes alone, respectively. CONCLUSION: Evidence presented here provides the first quantitative assessment of both the absolute and relative efficiencies of a key molecular tool used to study the biology and pathogenesis of this important human pathogen.

Identifying resistance in wild and ornamental cherry towards bacterial canker caused by Pseudomonas syringae.

Bacterial canker is a major disease of stone fruits and is a critical limiting factor to sweet cherry (Prunus avium) production worldwide. One important strategy for disease control is the development of resistant varieties. Partial varietal resistance in sweet cherry is discernible using shoot or whole tree inoculations; however, these quantitative differences in resistance are not evident in detached leaf assays. To identify novel sources of resistance to canker, we used a rapid leaf pathogenicity test to screen a range of wild cherry, ornamental Prunus species and sweet cherry × ornamental cherry hybrids with the canker pathogens, Pseudomonas syringae pvs syringae, morsprunorum races 1 and 2, and avii. Several Prunus accessions exhibited limited symptom development following inoculation with each of the pathogens, and this resistance extended to 16 P. syringae strains pathogenic on sweet cherry and plum. Resistance was associated with reduced bacterial multiplication after inoculation, a phenotype similar to that of commercial sweet cherry towards nonhost strains of P. syringae. Progeny resulting from a cross of a resistant ornamental species Prunus incisa with susceptible sweet cherry (P. avium) exhibited resistance indicating it is an inherited trait. Identification of accessions with resistance to the major bacterial canker pathogens is the first step towards characterizing the underlying genetic mechanisms of resistance and introducing these traits into commercial germplasm.

Gene expression of innate Th1-, Th2-, and Th17-type cytokines during early life of neonatal foals in response to Rhodococcus equi.

Focusing on the first 3 weeks of life, this study examined the mRNA transcript development of different Th-type cytokines in foals in response to Rhodococcus equi infection in vitro. Results demonstrated the significant up-regulation in expression of Th1-, Th2-, and Th17-type cytokines (IFN-γ, IL-4, IL-6, IL-8, IL-12p35, IL-12p40, IL-17, IL-23p19, and TNF-α) in R. equi infection of bronchial alveolar lavage (BAL) cells of 10-day-old foals. Consequently, signature cytokines of 3 Th cell types, IFN-γ (Th1), IL-4 (Th2), and IL-17 (Th17), were used to compare temporal response patterns of circulating peripheral blood mononuclear cells (PBMCs) to stimulation with R. equi. Foals responded to R. equi stimulation by producing similar amounts of IFN-γ mRNA transcripts from birth through 3 weeks of age, suggesting an absence of age-related impairment in Th1-type cytokine response to R. equi during the first 3 weeks of life. It remains debatable whether this Th1 response to R. equi in foals≤3 weeks of age is generally immature relative to older foals or adult horses. IL-4 expression by R. equi-stimulated PBMCs was significantly decreased at birth, and IL-17 expression was relatively reduced during the first week of life. Among all cytokines studied, IL-17 mRNA transcripts were induced with the highest magnitude of fold-change both in BAL cells and in PBMCs. Under the conditions studied, in vivo administration of a CpG failed to modulate the Th1-, Th2-, and Th17-type cytokine expression patterns in PBMCs.

Brachial artery thrombosis in a dog causing monoparesis mimicking nerve sheath tumor.

There are few differential diagnoses for non-orthopedic thoracic limb lameness in adult dogs aside from nerve tumors and disk-associated nerve compression; this report introduces another etiology. A 9-year-old male castrated mixed dog presented with an episodic history of nonweight-bearing thoracic limb lameness. Additional clinical signs included an atrophied thoracic limb with cool paw pads and painful axillary region. Magnetic resonance imaging, computed tomography, ultrasound, and exploratory surgery confirmed a chronic thrombus of the right brachial artery. No underlying cause for the thrombus was identified. The dog has been successfully managed on long-term rivaroxaban and clopidogrel. Follow-up ultrasound of the thrombus suggested early remodeling.

Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19.

Importance: Androgen deprivation therapy (ADT) has been theorized to decrease the severity of SARS-CoV-2 infection in patients with prostate cancer owing to a potential decrease in the tissue-based expression of the SARS-CoV-2 coreceptor transmembrane protease, serine 2 (TMPRSS2). Objective: To examine whether ADT is associated with a decreased rate of 30-day mortality from SARS-CoV-2 infection among patients with prostate cancer. Design, Setting, and Participants: This cohort study analyzed patient data recorded in the COVID-19 and Cancer Consortium registry between March 17, 2020, and February 11, 2021. The consortium maintains a centralized multi-institution registry of patients with a current or past diagnosis of cancer who developed COVID-19. Data were collected and managed using REDCap software hosted at Vanderbilt University Medical Center in Nashville, Tennessee. Initially, 1228 patients aged 18 years or older with prostate cancer listed as their primary malignant neoplasm were included; 122 patients with a second malignant neoplasm, insufficient follow-up, or low-quality data were excluded. Propensity matching was performed using the nearest-neighbor method with a 1:3 ratio of treated units to control units, adjusted for age, body mass index, race and ethnicity, Eastern Cooperative Oncology Group performance status score, smoking status, comorbidities (cardiovascular, pulmonary, kidney disease, and diabetes), cancer status, baseline steroid use, COVID-19 treatment, and presence of metastatic disease. Exposures: Androgen deprivation therapy use was defined as prior bilateral orchiectomy or pharmacologic ADT administered within the prior 3 months of presentation with COVID-19. Main Outcomes and Measures: The primary outcome was the rate of all-cause 30-day mortality after COVID-19 diagnosis for patients receiving ADT compared with patients not receiving ADT after propensity matching. Results: After exclusions, 1106 patients with prostate cancer (before propensity score matching: median age, 73 years [IQR, 65-79 years]; 561 (51%) self-identified as non-Hispanic White) were included for analysis. Of these patients, 477 were included for propensity score matching (169 who received ADT and 308 who did not receive ADT). After propensity matching, there was no significant difference in the primary end point of the rate of all-cause 30-day mortality (OR, 0.77; 95% CI, 0.42-1.42). Conclusions and Relevance: Findings from this cohort study suggest that ADT use was not associated with decreased mortality from SARS-CoV-2 infection. However, large ongoing clinical trials will provide further evidence on the role of ADT or other androgen-targeted therapies in reducing COVID-19 infection severity.

CD4+ T-cell localization to the large intestinal mucosa during Trichuris muris infection is mediated by G alpha i-coupled receptors but is CCR6- and CXCR3-independent.

Infection of mice with the gastrointestinal nematode Trichuris muris represents a valuable tool to investigate and dissect intestinal immune responses. Resistant mouse strains respond to T. muris infection by mounting a T helper type 2 response. Previous results have shown that CD4(+) T cells play a critical role in protective immunity, and that CD4(+) T cells localize to the infected large intestinal mucosa to confer protection. Further, transfer of CD4(+) T cells from immune mice to immunodeficient SCID mice can prevent the development of a chronic infection. In the current study, we characterize the protective CD4(+) T cells, describe their chemokine receptor expression and explore the functional significance of these receptors in recruitment to the large intestinal mucosa post-T. muris infection. We show that the ability to mediate expulsion resides within a subpopulation of CD4(+) T cells marked by down-regulation of CD62L. These cells can be isolated from intestine-draining mesenteric lymph nodes (MLN) from day 14 post-infection, but are rare or absent in MLN before this and in spleen at all times post-infection. Among CD4(+) CD62L(low) MLN cells, the two most abundantly expressed chemokine receptors were CCR6 and CXCR3. We demonstrate for the first time that CD4(+) CD62L(low) T-cell migration to the large intestinal mucosa is dependent on the family of G alpha(i)-coupled receptors, to which chemokine receptors belong. CCR6 and CXCR3 were however dispensable for this process because neutralization of CCR6 and CXCR3 did not prevent CD4(+) CD62L(low) cell migration to the large intestinal mucosa during T. muris infection.

Transvenous heartworm extraction in a ferret with caval syndrome.

A 10-month-old ferret was diagnosed with heartworm disease and caval syndrome. Associated clinical signs included weakness and a green-colored urine, identified as biliverdinuria. Despite the animal's small size, removal of three heartworms via transvenous heartworm extraction was successfully performed. Although at least one female worm remained in the right ventricle, the majority of clinical signs related to the presence of the heartworms resolved. The ferret was subsequently managed medically with corticosteroids and monthly heartworm prevention. This case documents the presence of biliverdinuria associated with caval syndrome and successful transvenous heartworm extraction in a ferret.