Search Results (38)

Background: Studies have suggested a synergism between lenalidomide (LEN) and ibrutinib (IBR) in multiple myeloma (MM). Both downregulate IRF4, a key target and master transcriptional factor regulating myeloma cell survival. Method: A 3 + 3 phase I trial was conducted to determine the maximum tolerated dose (MTD) of IBR in combination with LEN + dexamethasone (DEX) in patients with relapsed/refractory (RR) MM who had at least one prior line of therapy. Three dose levels (DLs) were planned. The cycle length was 28 days. IBR was administered orally daily in doses of 560 mg on DL1-2 and 840 mg on DL3, LEN was administered orally on days 1–21 in doses of 15 mg on DL1 and 25 mg on DL2-3, and DEX was administered orally on days 1, 8, 15, and 22 in a dose of 40 mg if age < 75 years or in a dose of 20 mg if it was ≥75 years for DL1-3. Patients with a glomerular filtration rate (GFR) <60 but ≥30 mL/min were treated in accordance with the manufacturer’s instructions with LEN 10 mg. Dose-limiting toxicities (DLTs) included the following: grade 4 neutropenia lasting more than 5 days, thrombocytopenia, febrile neutropenia, nausea, vomiting or diarrhea; grade 3 thrombocytopenia with bleeding or platelet transfusion; and grade 3–4 hyperglycemia or a thrombotic/embolic event, and other nonhematologic toxicities. The overall response rate (ORR) was defined as the percentage of patients with a partial response (PR), very good partial response (VGPR), or complete response (CR) according to IMWG criteria on two consecutive evaluations at least 4 weeks apart. The clinical benefit rate (CBR) was defined as the percentage of patients with stable disease (SD) or a better outcome on two consecutive evaluations at weeks apart. Results: Fourteen patients (DL1: six patients; DL2: three patients; DL3: five patients) were registered for the study from March 2019 to May 2023, prior to its closure due to limited accrual. Thirteen patients are included in the summary of toxicities and response as one patient on DL3 halted participation prior to the start of the treatment. Two patients on DL3 were excluded from the determination of MTD: one having discontinued cycle 1 treatment due to COVID-19 infection and the another having mistakenly taken 280 mg/day of IBR instead of the assigned 840 mg/day dose during cycle 1. Only one patient developed a DLT, on DL1 with grade 3 non-viral hepatitis. The median number of cycles administered was 4 (range: 1–56). Severe toxicities reported included grade 4 lymphocytopenia (1), grade 4 thrombocytopenia (1), and grade 5 sepsis in the setting of PD (1). Disease responses included a VGPR on DL1 and CR on DL3. Thus, the ORR was 15.4% (90% CI: 2.8–41.0%). One patient on DL1 maintained SD for 4.6 years before discontinuing the treatment to undergo an alternative therapy. Another five patients maintained SD for ≥ 2 consecutive cycles. Thus, the CBR was 61.5% (90% CI: 35.5–83.4%). Conclusions: The combination of LEN with IBR in RR MM proved feasible, with manageable toxicities and the majority of discontinuations being due to disease progression. Full article

Feline infectious peritonitis (FIP) is caused by mutated feline coronaviruses. Immune-mediated hemolytic anemia (IMHA) arises due to immune-mediated erythrocyte destruction and can be non-associative or associative with diseases such as FIP. Records of cats with FIP were reviewed to find those with associative IMHA based on exclusion of other causes of anemia and a positive saline agglutination test and/or Coombs test. The inclusion criteria were met for 45 cats (26 (58%) cats with effusive and 19 (42%) with non-effusive FIP). Median hematocrit was 18% (interquartile range [IQR] 13–20). Anemia was non-regenerative in 36 (80%) cats and regenerative in 5 (11%) cats; 4 (9%) cats had no reticulocyte count available. Concurrent thrombocytopenia was present in 18 (40%) cats. All 45 cats were treated with nucleoside analogs, and 44 (98%) cats with glucocorticoids; in 5 (11%) cats, glucocorticoids were added after starting antiviral treatment due to persistent anemia. Median follow-up was 72 days (IQR 14–246); at the time of last follow-up 33 (73%) cats had survived while 12 (27%) had died or were euthanized. Of the 33 surviving cats, 17 achieved remission of both FIP and IMHA. In three cats, FIP remission was achieved, but IMHA relapsed; in one of these, IMHA relapsed twice. FIP relapsed without IMHA in two cats, and both FIP and IMHA relapsed in one cat. In 9 cats the antiviral and glucocorticoid treatment is still ongoing at the time of the publication. Although FIP is likely an uncommon cause of associative IMHA, as more cats with FIP are treated with antiviral therapy, it is important to consider IMHA as a possible cause of anemia in cats with FIP. Full article

The Brazilian population in the United States is growing, and many Brazilian workers are employed in settings that may lack occupational health and safety (OHS) protections. In this study, we examined two domains of OHS (measured by the Occupational Health and Safety Vulnerability Survey), namely, Workplace Hazards (potential dangers that may result in injury or illness) and Workplace Vulnerability (inadequate occupational health and safety resources), and described health and demographic characteristics associated with these conditions. Eligible participants were women aged 18 and over, born in Brazil, currently residing in the United States, and employed. A cross-sectional online survey was conducted between July and August 2020. Recruitment occurred through community partnerships and social media. Multivariable models among n = 191 women revealed that greater exposure to Workplace Hazards was associated with employment in private household settings, including childcare and housecleaning (p < 0.001). The association between Workplace Vulnerability and jobs in private household services approached statistical significance (p = 0.07). Both Workplace Hazards and Workplace Vulnerability were associated with lower incomes and educational attainment, as well as having public insurance. Our findings suggest the need for stronger OHS protections and policies, particularly among those working in private household services, to ensure safer working conditions for Brazilian immigrant women. Full article

Medulloblastoma (MB) groups 3 and 4 lack targeted therapies despite their dismal prognoses. Ion channels and pumps have been implicated in promoting MB metastasis and growth; however, their roles remain poorly understood. In this study, we repurposed FDA-approved channel blockers and modulators to investigate their potential anti-tumor effects in MB cell lines (DAOY and D283) and primary cell cultures derived from a patient with MB. For the first time, we report spontaneous calcium signaling in MB cells. Spontaneous calcium signals were significantly reduced by mibefradil (calcium channel blocker), paxilline (calcium-activated potassium channel blocker), and thioridazine (potassium channel blocker). These drugs induced dose-dependent cytotoxicity in both the DAOY and D283 cell lines, as well as in primary cell cultures of a patient with group 3 or 4 MB. In contrast, digoxin and ouabain, inhibitors of the Na/K pump, reduced the calcium signaling by over 90% in DAOY cells and induced approximately 90% cell death in DAOY cells and 80% cell death in D283 cells. However, these effects were significantly diminished in the cells derived from a patient with MB, highlighting the variability in drug sensitivity among MB models. These findings demonstrate that calcium signaling is critical for MB cell survival and that the targeted inhibition of calcium pathways suppresses tumor cell growth across multiple MB models. Full article

The avian influenza virus is a global pathogen with significant health and economic implications. While primarily a pathogen of wild and domestic birds, recent outbreaks of the H5N1 highly pathogenic avian influenza virus (HPAIV) clade 2.3.4.4b have caused mortality in a wide variety of mammals, including members of the Canidae family, on multiple continents. Despite sporadic mortality events globally, the epidemiology and pathobiology of H5N1 HPAIV in wild canids remains poorly defined. During 2022–2024, 41 wild canid carcasses (diagnostic cases), including 23 red foxes and 18 gray foxes, were tested for the influenza A virus (IAV) via PCR, with five red fox kits testing positive (12%). Infected animals had variably severe encephalitis, pneumonia, and occasionally myocarditis associated with strong immunolabeling for IAV. Serum from 269 wild canids in Pennsylvania was tested for antibodies to IAV, including 133 samples collected prior to 2021 (pre-H5N1 HPAIV 2.3.4.4b introduction) and 136 collected after 2022 (post-H5N1 HPAIV 2.3.4.4b introduction). All samples collected prior to 2021 were seronegative for IAV. Two coyotes from 2024 were seropositive for IAV but were negative for antibodies to the H5 and N1 subtypes. Collectively, these data suggest that while sporadic H5N1 HPAIV infection and mortality can occur in wild canids, particularly juvenile red foxes, infection was limited in these outwardly healthy and opportunistically sampled animals. Future studies should utilize a risk-based approach to target sampling of wild canids at increased risk for H5N1 HPAIV infection, such as those around waterfowl habitats or spatially around wild bird or domestic animal outbreaks. Full article

Background: Global COVID-19 vaccination effort faces the challenges of vaccine hesitancy and resistance, rooted in misinformation and institutional distrust. Addressing these barriers with customized messaging is essential, yet the relationship between vaccine hesitancy and other health-seeking behaviors, like COVID-19 testing, has been underexplored. Method: This study assessed COVID-19 vaccine uptake in Southeastern Louisiana across 10 pharmacies and clinics in areas with historically high rates of COVID-19 infection. Using a longitudinal cohort design from Fall 2022 through Fall 2023, a total of 377 participants from diverse backgrounds were surveyed while seeking routine care at partner organizations. Baseline data was collected on demographics, vaccine knowledge, attitudes, and test-seeking behaviors. Information on COVID-19 testing and vaccination were self-reported and verified, as applicable, in the patient’s medical records. All data was analyzed using descriptive statistics, log-binomial to yield risk ratios, and an ordinal logistic regression for vaccine series completion. Results: Among the 377 participants, 207 were unvaccinated while 170 received the vaccine. Among the unvaccinated individuals, 53 received a half-dose, 97 a full dose, and 14 a booster. Notably, 75% of unvaccinated and 89% of vaccinated participants underwent COVID-19 testing. Individuals who were tested were 1.71 times more likely to be vaccinated (95% CI 1.03, 2.84), while previous vaccine refusal was associated with lower vaccine acceptance (0.77; 95% CI 0.54, 1.09). In the bivariate and multivariate analysis, COVID-19 testing behavior was positively associated with COVID-19 vaccine uptake. Conclusions: Exploring the connection between COVID-19 testing and vaccination provides valuable insights for future public health messaging to mitigate vaccine hesitancy. Full article

Background/Objectives: Puerto Rican households often face elevated rates of food insecurity. Frequently, households experiencing food insecurity turn to federal and emergency nutrition assistance for urgent or prolonged aid. This study analyzes factors influencing food insecurity and food assistance program involvement among Puerto Ricans in Holyoke, Massachusetts, amidst the COVID-19 pandemic. Methods: Using a combination of community-based participatory recruitment, purposive sampling, and web-based tools, we collected 284 survey responses. Our paper employed Pearson’s chi-square, logistic regression, and hierarchical linear models to assess relationships between demographic and household attributes and food access outcomes. Results: Variables such as having children in the household and age significantly influenced food relief participation and food insecurity outcomes. Puerto Rican heritage and low educational attainment were strong predictors of obtaining federal food aid. Low-income participants disproportionately faced food shortages and depended on emergency food initiatives. Our findings indicate that demographic and household factors significantly influence food insecurity and accessibility. Conclusions: Our study demonstrates that the pandemic made it challenging for households to obtain consistent, safe, and affordable nourishment. The impacts were unequally spread; hence, Puerto Rican communities and low-income groups were most affected. Full article

The 63.6 million Hispanic individuals living in the United States constitute the largest ethnic or racial minority group in the country. Hispanic/Latino households report a high prevalence of food insecurity, and often, food-insecure individuals cope by turning to emergency and federal food assistance programs for immediate or long-term assistance. This paper focuses on Hialeah, Florida, a predominantly Hispanic/Latino city in Miami-Dade County. It examines which demographic factors influence participation in food assistance programs and the occurrences of periods of disrupted food access. This study examines two questions: (1) What factors are associated with participation in food assistance programs? (2) To what extent did study participants use food assistance programs before and during the COVID-19 pandemic? We conducted a survey and collected 684 responses from April to August 2022. We gathered data on participants’ identities, household attributes, and their usage of federal and emergency food assistance programs. We used Pearson’s chi-square tests to identify significant associations between food assistance usage, food access, and respondents’ demographic characteristics. We also used binary logistic regression models to assess probabilities. The findings of this research are significant, indicating that the COVID-19 pandemic exacerbated food access challenges in Hispanic/Latino households in 2022. The data also revealed that low-income households, respondents below the age of 40, individuals born in the United States, those with low educational attainment, and those living in multifamily households had the highest likelihood of using food assistance programs. Single- and non-single-parent households, employment status, languages spoken at home, and number of children in the household were also statistically significant factors in predicting food assistance usage. This research provides valuable insights into how individuals in a city responded to the pandemic by utilizing food assistance programs. Full article

EGFR-targeted therapies are efficacious, but toxicity is common and can be severe. Urokinase type plasminogen activator receptor (uPAR)-targeted drugs are only emerging, so neither their efficacy nor toxicity is fully established. Recombinant eBAT was created by combining cytokines EGF and uPA on the same single-chain molecule with truncated Pseudomonas toxin. Its purpose was to simultaneously target tumors and their vasculature in the tumor microenvironment. In prior studies on mice and dogs, the drug proved efficacious. Here, we report the safety of eBAT in normal wildtype, uPAR knockout, and immunoreplete and immunodeficient tumor-bearing mice, as well as in dogs with spontaneous sarcoma that more closely mirror human cancer onset. In immunocompetent mice, tumor-bearing mice, uPAR knockout mice, and mice receiving species-optimized eBAT, toxicities were mild and self-limiting. Likewise, in dogs with life-threatening sarcoma given dosages found to be biologically active, eBAT was well tolerated. In mice receiving higher doses, eBAT was associated with dose-dependent evidence of liver injury, including portal biliary hyperplasia, oval cell proliferation, lymphoplasmacytic inflammation, periportal hepatocellular microvesicular change, hemorrhage, necrosis, and apoptosis. The results support continuing the clinical development of eBAT as a therapeutic agent for individuals with sarcoma and other cancers. Full article

Despite the numerous food studies conducted in Detroit, none have assessed changes in the food landscape over a decade. No previous study has systematically analyzed food store closures in the city either. We will address these oversights by examining the distribution of food outlets in the city ten years apart. This paper probes the following questions: (1) How has the distribution of Detroit’s food outlets changed in the decade between 2013 and 2023? (2) Does Detroit fit the definition of a food desert in 2013 or 2023? (3) Does Detroit fit the definition of a food swamp in 2013 or 2023? (4) Has supermarket redlining occurred in Detroit in 2013 or 2023? (5) How is population decline related to food outlet distribution? (6) How do food store closures impact food store distribution? We conducted exhaustive searches to collect information on thousands of food outlets from Data Axle, Google, and Bing. The data were analyzed and mapped in SPSS 28 and ArcGIS 10.8. We compared 3499 food outlets identified in 2013 with 2884 identified in 2023. We expanded our search for food outlets in 2023 and found an additional 611 food outlets in categories not studied in 2013. The study’s findings are significant as they unearth evidence of extensive population decline—driven by Black flight—and a vanishing food infrastructure. Detroit lost more than 600 food outlets between 2013 and 2023, a staggering number that underscores the severity of the issue. Moreover, in 2023, we documented food store closures and found 1305 non-operational or closed food outlets in the city. Regardless of the neighborhood’s racial composition, the household median income, or the educational attainment of residents, food store closures were widespread in 2023; 27.3% of the food outlets identified that year were defunct. Despite the massive food store closures, Detroit did not fit the description of a food desert; each of the city’s 54 neighborhoods had between 7 and 300 food outlets. The food swamp thesis did not accurately describe the city either, as supermarkets/large grocery stores were intermingled with convenience and corner stores in both study periods. The data did not find evidence of supermarket redlining, as supermarkets/large grocery stores were found in formerly redlined neighborhoods alongside dollar stores and variety stores in both study periods. Full article

It is important to understand real-world BNT162b2 COVID-19 vaccine effectiveness (VE), especially among racial and ethnic minority groups. We performed a test-negative case-control study to measure BNT162b2 COVID-19 VE in the prevention of COVID-19-associated acute respiratory illness (ARI) hospitalizations at two Atlanta hospitals from May 2021–January 2023 and adjusted for potential confounders by multivariate analysis. Among 5139 eligible adults with ARI, 2763 (53.8%) were enrolled, and 1571 (64.5%) were included in the BNT162b2 analysis. The median age was 58 years (IQR, 44–68), 889 (56.6%) were female, 1034 (65.8%) were African American, 359 (22.9%) were White, 56 (3.6%) were Hispanic ethnicity, 645 (41.1%) were SARS-CoV-2-positive, 412 (26.2%) were vaccinated with a primary series, and 273 (17.4%) had received ≥1 booster of BNT162b2. The overall adjusted VE of the BNT162b2 primary series was 58.5% (95% CI 46.0, 68.1), while the adjusted VE of ≥1 booster was 78.9% (95% CI 70.0, 85.1). The adjusted overall VE of primary series for African American/Black individuals was 64.0% (95% CI 49.9, 74.1) and 82.7% (95% CI 71.9, 89.4) in those who received ≥1 booster. When analysis was limited to the period of Omicron predominance, overall VE of the primary series decreased with widened confidence intervals (24.5%, 95% CI −4.5, 45.4%), while VE of ≥1 booster was maintained at 60.9% (95% CI 42.0, 73.6). BNT162b2 primary series and booster vaccination provided protection against COVID-19-associated ARI hospitalization among a predominantly African American population. Full article

Due to the emerging threat conditions in the work environment, firefighters are at a high risk of exposure to not only toxic substances but also biological agents in the dayroom and during emergency runs. The aim of this study is to evaluate firefighter (career and volunteer) knowledge and practice behaviors on infection control. This study surveyed 444 firefighters (210 career, 234 volunteer) in rural Northwestern Kentucky. The self-reported survey focused on individual characteristics, knowledge on exposure incident control, precautionary actions, and personal protections. We evaluated the descriptive characteristics of knowledge and practice scores stratified by firefighter groups (career and volunteers). The associations between infection control training received (yes/no) and firefighter knowledge and practice scores were also examined. Firefighters who were trained on infection control prevention had significantly higher knowledge scores (M = 63.7, SD = 13.4 vs. M = 59.7, SD = 15.9; p = 0.012). Volunteer firefighters exhibited better infection control practice behaviors than career firefighters (M = 70.6, SD = 13.0 vs. M = 67.4, SD = 11.1; p = 0.05). Firefighters who followed infection control guidelines (M = 69.5, SD = 11.9 vs. M = 58.1, SD = 9.9; p = 0.012) and expressed need for a comprehensive training on personal protective equipment (PPE) selection (β = 3.41, SE = 1.54, aOR = 30.22, 95% CI: 1.47–620.87; p = 0.028) had significantly higher practice scores compared to those who did not. The study results have policy implications for infection prevention and control (IPC) in rural fire departments, both career and volunteer. A review of infection control policies is needed, especially as it relates to training and practice behaviors during emergency calls and in the dayroom. Results also suggest the need to develop strategies to improve the culture of PPE use and training on the selection of PPEs appropriate to the emergency response type. Full article

Introduction: Personal, behavioral, and environmental risk factors are correlated to varying degrees with each other and with the overall likelihood of violent reinjury. When used with fidelity, risk assessment instruments, including the violence reinjury risk assessment instrument (VRRAI), identify domains in which individuals present elevated risk levels to aid in matching services with needs. Less is known about the collinearity among risk factors for violently injured individuals admitted to hospitals. Collinearity between risk factors has ramifications for predictive modeling of violent reinjury risk. The objective of this study was to identify significantly correlated risk factors when the VRRAI was used by hospital-based violence intervention programs (HVIP) for clients. Materials and Methods: Victims of violent injury by modality of firearm, stabbing, and physical assault who were admitted to a level 1 trauma center at a single institution were voluntarily enrolled in a hospital-based violence intervention program (HVIP) between September 2020 and June 2022. Violence intervention specialists (VIS) completed the VRRAI within the first month of participant enrollment. The VRRAI is comprised of 29 binary indicators that may signal elevated risk of violent reinjury. Data from completed assessments were used to apply risk-need-responsivity (RNR) principles along with phi coefficients of key indicators to examine overlap and prevalence in the population. Results: A total of 98 participants were enrolled in the HVIP. The median age was 27 years old and 79 (80.6%) were male, while 66 (67.3%) were non-Hispanic Black or African American, 9 (9.2%) were non-Hispanic White, and 17 (17.3%) identified as Hispanic or Latino. Several statistically significant relationships existed between key risk indicators in the VRRAI. Importantly, a robust relationship was found between the two dynamic risk factors of having heavy connection with gangs and a perception of imminent threat of violence (φc = 0.57, p < 0.01). Conclusion: Data suggest that some variables could be consolidated or removed from the VRRAI to create an even shorter instrument that can be performed more rapidly in the clinical setting. The application of the RNR model illustrates a limited number of dynamic risk factors that could be immediately addressed as part of case management should be prioritized among the questions selected from the VRRAI for inquiry at the intake assessment. Full article

Access to fresh, healthy, affordable foods is a pressing concern in cities worldwide. American cities are no exception. Although many scholars study food access in large cities, small and mid-sized American cities can provide valuable information about inequities in the food system. This paper focuses on two adjoining, racially mixed Mid-Michigan cities—Lansing and East Lansing. It examines the extent to which different food outlets exist in the cities and surrounding townships. It probes the following questions: (1) How are food outlets distributed throughout the cities and suburbs? (2) What is the relationship between neighborhood demographic characteristics and the distribution of food outlet types? We collected data on food outlets from September 2020 to June 2022 using Data Axle as our primary source of information. We used ArcGIS 10.8.1 for the spatial mapping and SPSS 28 for statistical analyses. We conducted regression analyses to identify the difference in the likelihood of finding food retailers in census tracts where 0–20% of the residents were People of Color (VL-POC), 20.01–40% of the inhabitants were People of Color (L-POC), 40.1–60% of the residents were People of Color (H-POC), and more than 60% of residents were People of Color (VH-POC). There were 1647 food outlets in the study area: 579 were in Lansing, 220 were in East Lansing, and the remaining 848 were in the surrounding townships. Restaurants dominated the food landscape, while small groceries and convenience stores were the grocery sector’s most common food outlet types. Supermarkets and large grocery stores comprised only 5.6% of the study area’s food outlets. The study finds a nonlinear relationship between the racial composition of census tracts and the prevalence of food outlets. The VH-POC census tracts had very few food outlets. For instance, the tracts had no supermarkets, mass merchandisers or supercenters, small grocery or convenience stores, pharmacies or drug stores, or farmers’ markets. The findings illustrate the diversity and complexity of the Lansing–East Lansing metropolitan area’s food landscape. Full article

Many adolescent health surveys ask if respondents are male or female. Non-response may be due to fear of de-anonymisation or being a gender-nonconforming youth. The present study investigates the frequency of non-response and its potential reasons. To this end, data from 54,833 adolescents aged 11–18 from six countries, participating in the 2018 Health Behaviour in School-aged Children (HBSC) study, were analysed. Respondents were divided into three groups: (1) “Responders” who answered both questions on age and gender, (2) “Age non-responders” who did not answer the question on age, and (3) “Gender non-responders” who answered the question on age but not the one on gender. These groups were compared regarding their non-response to other questions and regarding their health. Overall, 98.0% were responders, 1.6% were age non-responders and 0.4% were gender non-responders. On average, age non-responders skipped more questions (4.2 out or 64) than gender non-responders (3.2) and responders (2.1). Gender non-responders reported more psychosomatic complaints, more frequent substance use and lower family support than responders. This study shows that age and gender non-responders differ in their response styles, suggesting different reasons for skipping the gender question. The health disparities found between the groups suggest that further research should use a more nuanced approach, informed by LGBT+ youth’s insights, to measure sex assigned at birth and gender identity. Full article