Disparities in end-of-life care for minoritized racial and ethnic patients during terminal hospitalizations in New York State.

BACKGROUND: Racial and ethnic minorities often receive care at different hospitals than non-Hispanic white patients, but how hospital characteristics influence the occurrence of disparities at the end of life is unknown. The aim of this study was to determine if disparities in end-of-life care were present among minoritized patients during terminal hospitalizations, and if these disparities varied with hospital characteristics. METHODS: We identified hospitalizations where a patient died in New York State, 2016-2018. Using multilevel logistic regression, we examined whether documented end-of-life care (do-not-resuscitate status (DNR), palliative care (PC) encounter) differed by race and ethnicity, and whether these disparities differed based on receiving care in hospitals with varying characteristics (Black or Hispanic-serving hospital; teaching status; bed size; and availability of specialty palliative care). RESULTS: We identified 143,713 terminal hospitalizations in 188 hospitals. Across all hospitals, only Black patients were less likely to have a PC encounter (adjusted odds ratio (aOR) 0.83 [0.80-0.87]) or DNR status (aOR 0.91 [0.87-0.95]) when compared with non-Hispanic White patients, while Hispanic patients were more likely to have DNR status (aOR 1.07 [1.01-1.13]). In non-teaching hospitals, all minoritized groups had decreased odds of PC (aOR 0.80 [0.76-0.85] for Black, aOR 0.91 [0.85-0.98] for Hispanic, aOR 0.93 [0.88-0.98] for Others), while in teaching hospitals, only Black patients had a decreased likelihood of a PC encounter (aOR 0.88 [0.82-0.93]). Also, Black patients in a Black-serving hospitals were less likely to have DNR status (aOR 0.80 [0.73-0.87]). Disparities did not differ based on whether specialty PC was available (p = 0.27 for PC encounter, p = 0.59 for DNR status). CONCLUSION: During terminal hospitalizations, Black patients were less likely than non-Hispanic White patients to have documented end-of-life care. This disparity appears to be more pronounced in non-teaching hospitals than in teaching hospitals.

Development of a Fully Protective Pandemic Avian Influenza Subunit Vaccine in Insect Pupae.

In this study, we pioneered an alternative technology for manufacturing subunit influenza hemagglutinin (HA)-based vaccines. This innovative method involves harnessing the pupae of the Lepidoptera Trichoplusia ni (T. ni) as natural biofactories in combination with baculovirus vectors (using CrisBio® technology). We engineered recombinant baculoviruses encoding two versions of the HA protein (trimeric or monomeric) derived from a pandemic avian H7N1 virus A strain (A/chicken/Italy/5093/99). These were then used to infect T. ni pupae, resulting in the production of the desired recombinant antigens. The obtained HA proteins were purified using affinity chromatography, consistently yielding approximately 75 mg/L of insect extract. The vaccine antigen effectively immunized poultry, which were subsequently challenged with a virulent H7N1 avian influenza virus. Following infection, all vaccinated animals survived without displaying any clinical symptoms, while none of the mock-vaccinated control animals survived. The CrisBio®-derived antigens induced high titers of HA-specific antibodies in the vaccinated poultry, demonstrating hemagglutination inhibition activity against avian H7N1 and human H7N9 viruses. These results suggest that the CrisBio® technology platform has the potential to address major industry challenges associated with producing recombinant influenza subunit vaccines, such as enhancing production yields, scalability, and the speed of development, facilitating the global deployment of highly effective influenza vaccines.

Enhanced Recombinant Protein Expression in Insect Cells by Natural and Recombinant Components of Lepidoptera Hemolymph.

Prior research has established the anti-apoptotic effects in insect cell cultures of Bombyx mori (B. mori) hemolymph, as well as the heightened production yields of recombinant proteins facilitated by baculovirus vectors in insect cells cultivated in media supplemented with this hemolymph. In this study, we investigated the hemolymph of another Lepidoptera species, Trichoplusia ni (T. ni), and observed similar beneficial effects in insect cells cultivated in media supplemented with this natural substance. We observed enhancements in both production yield (approximately 1.5 times higher) and late-stage cell viabilities post-infection (30-40% higher). Storage-protein 2 from B. mori (SP2Bm) has previously been identified as one of the abundant hemolymph proteins potentially responsible for the beneficial effects observed after the use of B. mori hemolymph-supplemented cell culture media. By employing a dual baculovirus vector that co-expresses the SP2Bm protein alongside the GFP protein, we achieved a threefold increase in reporter protein production compared to a baculovirus vector expressing GFP alone. This study underscores the potential of hemolymph proteins sourced from various Lepidoptera species as biotechnological tools to augment baculovirus vector productivities, whether utilized as natural supplements in cell culture media or as hemolymph-derived recombinant proteins co-expressed by baculovirus vectors.

Palliative Care Clinicians' Views on Metrics for Successful Specialist Palliative Care Delivery in the ICU.

CONTEXT: A quarter of palliative care (PC) clinicians' consultations are now requested from the intensive care unit (ICU). Despite this high usage, a standardized set of quality metrics for PC delivery in the ICU does not exist. OBJECTIVES: To explore PC clinicians' views on how to best measure quality of care delivery in their role as a consultant in the ICU setting. METHODS: Secondary analysis of a parent dataset consisting of qualitative data from semi-structured interviews exploring ways to optimize PC clinicians' role in the ICU. Nineteen participants were recruited across five academic medical centers in the US. Participants included PC physicians (n = 14), nurse practitioners (n = 2), and social workers (n = 3). Thematic analysis with an inductive approach was used to generate themes. RESULTS: We identified two central themes: difficulties in measuring PC quality in the ICU (theme 1) and tension between the role of PC and metrics (theme 2). Theme 1 had two subthemes related to logistical challenges in measuring outcomes and PC clinicians' preference for metrics that incorporate subjective feedback from patients, family members, and the primary ICU team. Theme 2 described how PC clinicians often felt a disconnect between the goal of meeting a metric and their goals in delivering high-quality clinical care. CONCLUSION: Our findings provide insight into PC clinician perspectives on quality metrics and identify major barriers that need to be addressed to successfully implement quality measurement in the ICU setting.

Using Bar Velocity to Assess Post-match Neuromuscular Fatigue in Young Soccer Players.

This study aimed to investigate the recovery of neuromuscular performance using mechanical parameters collected during jump (vertical and horizontal) and strength-power exercises in youth soccer players after official soccer matches. Twenty-one outfield highly trained youth male soccer athletes (age: 18.23 ± 0.73 years; weight: 72.12 ± 6.99 kg; height: 1.78 ± 0.08 m) from two teams competing in the 1st division of U-19 Portuguese National Championship participated in this study. Players completed a battery of physical tests at -2h, +30 min, +24h, and +48h in relation to the match. Countermovement jump height, horizontal jump distance, and bar velocity during the half-squat, bench press, and hip-thrust exercises, at fixed loads, were recorded. Countermovement jump was impaired until 24h post-match (-1.7% from pre to 24h post, p=0.050; ES=-0.82). Half-squat bar velocity was reduced immediately following the match (-6.8 % from pre- p=0.004; ES=-0.64) but recovered at +24h (+2.9%, p=1.00; ES=0.02). Hip-thrust bar velocity was reduced for up to 48h post-match (-7.4% from pre to 48h post, p<0.001; ES=-0.80). No impairments were found in the horizontal jump and bench press at any moment. Our findings show prolonged decrements in strength of the posterior chain following a soccer match, measured in the hip-thrust exercise, while the other exercises displayed faster recovery dynamics.

Rich oleocanthal and oleacein extra virgin olive oil and inflammatory and antioxidant status in people with obesity and prediabetes. The APRIL study: A randomised, controlled crossover study.

BACKGROUND: Oleocanthal and oleacein are olive oil phenolic compounds with well known anti-inflammatory and anti-oxidant properties. The main evidence, however, is provided by experimental studies. Few human studies have examined the health benefits of olive oils rich in these biophenols. Our aim was to assess the health properties of rich oleocanthal and oleacein extra virgin olive oil (EVOO), compared to those of common olive oil (OO), in people with prediabetes and obesity. METHODS: Randomised, double-blind, crossover trial done in people aged 40-65 years with obesity (BMI 30-40 kg/m2) and prediabetes (HbA1c 5.7-6.4%). The intervention consisted in substituting for 1 month the oil used for food, both raw and cooked, by EVOO or OO. No changes in diet or physical activity were recommended. The primary outcome was the inflammatory status. Secondary outcomes were the oxidative status, body weight, glucose handling and lipid profile. An ANCOVA model adjusted for age, sex and treatment administration sequence was used for the statistical analysis. RESULTS: A total of 91 patients were enrolled (33 men and 58 women) and finished the trial. A decrease in interferon-γ was observed after EVOO treatment, reaching inter-treatment differences (P = 0.041). Total antioxidant status increased and lipid and organic peroxides decreased after EVOO treatment, the changes reaching significance compared to OO treatment (P < 0.05). Decreases in weight, BMI and blood glucose (p < 0.05) were found after treatment with EVOO and not with OO. CONCLUSIONS: Treatment with EVOO rich in oleocanthal and oleacein differentially improved oxidative and inflammatory status in people with obesity and prediabetes.

The effects of different small-sided games configurations on heart rate, rating of perceived exertion, and running demands in professional soccer players.

We examined the effects of different small-sided games (SSG) configurations on heart rate (HR), rating of perceived exertion (RPE), and running demands in soccer players. Twelve male soccer players (U18) participated in this randomized cross-over study. Players performed three SSG in different "fixed" and "dynamic" pitch sizes (3v3 in large (SSGL) and small (SSGS) fixed area; or 3v3 in dynamic dimensions [SSGD]), with 4x4 minutes interspersed by 2 minutes of rest. HR measures (maximum [HRmax], average [HRavg], and percentage of maximum [%HRmax]), RPE, and running demands were collected across the SGG sessions. The following running activities were recorded: total distance covered (TD), distance covered (DC) at 6-12 km·h-1, ≥ 12-18 km·h-1, and >18 km·h-1, peak running speed, acceleration (ACC) and deceleration (DEC) at 1-2 m·s-2 and 2-3 m·s-2, player load, and high metabolic load distance (HMLD). SSGL displayed higher HRavg, %HRmax, and RPE values than SSGS (p < 0.05). SSGL resulted in higher TD, DC at 6-12 km·h-1, ≥ 12-18 km·h-1, > 18 km·h-1, and higher peak speed than SSGS and SSGD (p < 0.05). Moreover, SSGD presented higher TD and DC at 6-12 km·h-1 and ≥ 12-18 km·h-1 than SSGS (p < 0.05). In contrast, SSGD and SSGS showed higher number of ACC and DEC at 1-2 m·s-2 than SSGL (p < 0.05). In conclusion, the pitch size and playing area of the SSG can be manipulated to promote desired physiological and physical demands in young soccer players.HighlightsWe examined how fixed (small and large) or variable (dynamic) pitch sizes affected the psychophysiological and running demands of young soccer players during small-sided games.Small-sided games with larger pitch sizes and areas per player elicited greater psychophysiological and running demands than small areas.The pitch size designed in the current study does not appear to affect the number of acceleration and deceleration (> 2 m·s-2).Varying the pitch size during the small-sided games (i.e. dynamic condition) could be an interesting constraint to be considered by soccer coaches in order to enhance task variability.

Chrysalises as natural production units for recombinant subunit vaccines.

The baculovirus vector expression system (BEVS) combines cultured insect cells and genetically modified Autographa californica nuclear polyhedrosis virus (AcMNPV)-derived baculovirus vectors. This expression system has been widely used for the expression of hundred of proteins for more than 30 years, existing commercial products manufactured at large scale by this methodology, mainly subunit vaccines. At an industrial scale, insect cells, as any other cultured cells, require artificial media and a strict control of environmental sterile conditions in the complex and expensive bioreactors. Here we describe an efficient alternative to produce recombinant biologics using the versatile and productive baculovirus vectors. It consists in natural biocapsules (pupae from Trichoplusia ni (Hübner) Lepidoptera), containing millions of insect cells in perfect physiological conditions, ready to be programmed by a genetically modified AcMNPV-derived baculovirus vector to produce large quantities of any recombinant protein. This technology, denominated CrisBio, has been tested to produce dozens of proteins, reaching productivities on the range of milligrams per infected pupa, that can be translated into dozens of vaccine doses, for example. The biologics production by CrisBio was industrialized with the design of both insect rearing and pupae storage single-use plastic devices, compatible with machines specifically designed for the automation of pupae manipulation and inoculation. These devices and machines reduce manual operations, increase batches consistency and facilitate the scaled production of any recombinant protein. As a mode of examples, the productivity in CrisBio technology platform of two virus-like particle (VLP) vaccine antigens is described in this work.

Association between Vitamin D Deficiency and Single Nucleotide Polymorphisms in the Vitamin D Receptor and GC Genes and Analysis of Their Distribution in Mexican Postmenopausal Women.

Genome-wide association studies in people with European ancestry suggest that polymorphisms in genes involved in vitamin D (VD) metabolism have an effect on serum concentrations of 25-hydroxyvitamin D. However, nothing is known about these polymorphisms in populations with Amerindian ancestry. Our aim was to evaluate the association between genetic variants on the vitamin D receptor (VDR) and the vitamin D binding protein (GC) genes, involved in the VD pathway, and VD deficiency in 689 unrelated Mexican postmenopausal women. We also described the frequencies of these variants in 355 postmenopausal women from different ethnic groups. Based on our preliminary results of 400 unrelated Mexican postmenopausal women, three single nucleotide polymorphisms (SNPs) were selected for genotyping. The SNPs rs4516035 in VDR and rs2282679 in GC were associated with VD deficiency. Additionally, women who carried three risk alleles had a 3.67 times higher risk of suffering VD deficiency, compared to women with no risk alleles (p = 0.002). The rs4516035-C allele frequency in the Amerindian population was enriched in the South East region of Mexico. In contrast, the highest frequency of the rs2298850-C allele, a proxy for the tag SNP rs2282679, was observed in the South region. Our results indicate that genetic variants in VDR and GC genes are associated with VD deficiency in Mexican postmenopausal women. Moreover, an association was observed for the variants rs3794060 and rs4944957 of the DHCR7/NADSYN1 gene with osteopenia/osteoporosis.

Brote epidémico de hepatitis aguda A en el área sanitaria del Hospital Universitario Virgen de la Victoria (HUVV): un cambio en la epidemiología / Outbreak of acute hepatitis A in the health area served by the Hospital Universitario Virgen de la Victoria (HUVV): a change in epidemiology

En el año 2016 se detectó en la provincia de Málaga un brote de hepatitis A en pacientes con características epidemiológicas especiales, con un predominio de sujetos del sexo masculino. Presentamos 51 casos de hepatitis A aguda con una media de edad de 35,7 años, el 90% varones, con un 55% de casos que reconocían haber mantenido relaciones sexuales con otros hombres en los últimos dos meses. La mitad de ellos requirieron ingreso hospitalario por coagulopatía significativa en el momento del diagnóstico, sin evolución a fallo fulminante, ni encefalopatía en ningún caso. Cuatro casos presentaban ascitis al diagnóstico. Este brote se suma a otros dos publicados en Reino Unido y Holanda con un número de casos similar y epidemiológicamente muy parecidos, lo cual refuerza la importancia de la vigilancia epidemiológica y la necesidad de vacunación en esta población de riesgo, así como de campañas informativas a la población para prevenir la enfermedad

In 2016, an outbreak of hepatitis A was identified in the Malaga province among patients with specific epidemiological characteristics, which were predominantly males. This is a report of 51 subjects with acute hepatitis A and a mean age of 35.7 years, 90% were male and 55% of cases were men who had had sex with other men within the last two months. Half of them required hospitalization for significant coagulopathy at diagnosis and no cases progressed to fulminant failure or encephalopathy. Four patients had ascites at the time of diagnosis. This outbreak adds to those reported in the United Kingdom and the Netherlands with a similar number of cases and epidemiology. These studies highlight the importance of epidemiological surveillance, the need for vaccination in this particular at risk population and the need for informative campaigns in order to prevent this disease

Outbreak of acute hepatitis A in the health area served by the Hospital Universitario Virgen de la Victoria (HUVV): a change in epidemiology.

In 2016, an outbreak of hepatitis A was identified in the Malaga province among patients with specific epidemiological characteristics, which were predominantly males. This is a report of 51 subjects with acute hepatitis A and a mean age of 35.7 years, 90% were male and 55% of cases were men who had had sex with other men within the last two months. Half of them required hospitalization for significant coagulopathy at diagnosis and no cases progressed to fulminant failure or encephalopathy. Four patients had ascites at the time of diagnosis. This outbreak adds to those reported in the United Kingdom and the Netherlands with a similar number of cases and epidemiology. These studies highlight the importance of epidemiological surveillance, the need for vaccination in this particular at risk population and the need for informative campaigns in order to prevent this disease.

GSTT1 and GSTM1 null variants in Mestizo and Amerindian populations from northwestern Mexico and a literature review

Abstract The GSTT1 and GSTM1 genes are key molecules in cellular detoxification. Null variants in these genes are associated with increase susceptibility to developing different types of cancers. The aim of this study was to determine the prevalence of GSTT1 and GSTM1 null genotypes in Mestizo and Amerindian individuals from the Northwestern region of Mexico, and to compare them with those reported worldwide. GSTT1 and GSTM1 null variants were genotyped by multiplex PCR in 211 Mestizos and 211 Amerindian individuals. Studies reporting on frequency of GSTT1 and GSTM1 null variants worldwide were identified by a PubMed search and their geographic distribution were analyzed. We found no significant differences in the frequency of the null genotype for GSTT1 and GSM1 genes between Mestizo and Amerindian individuals. Worldwide frequencies of the GSTT1 and GSTM1 null genotypes ranges from 0.10 to 0.51, and from 0.11 to 0.67, respectively. Interestingly, in most countries the frequency of the GSTT1 null genotype is common or frequent (76%), whereas the frequency of the GSMT1 null genotype is very frequent or extremely frequent (86%). Thus, ethnic-dependent differences in the prevalence of GSTT1 and GSTM1 null variants may influence the effect of environmental carcinogens in cancer risk.

GSTT1 and GSTM1 null variants in Mestizo and Amerindian populations from northwestern Mexico and a literature review.

The GSTT1 and GSTM1 genes are key molecules in cellular detoxification. Null variants in these genes are associated with increase susceptibility to developing different types of cancers. The aim of this study was to determine the prevalence of GSTT1 and GSTM1 null genotypes in Mestizo and Amerindian individuals from the Northwestern region of Mexico, and to compare them with those reported worldwide. GSTT1 and GSTM1 null variants were genotyped by multiplex PCR in 211 Mestizos and 211 Amerindian individuals. Studies reporting on frequency of GSTT1 and GSTM1 null variants worldwide were identified by a PubMed search and their geographic distribution were analyzed. We found no significant differences in the frequency of the null genotype for GSTT1 and GSM1 genes between Mestizo and Amerindian individuals. Worldwide frequencies of the GSTT1 and GSTM1 null genotypes ranges from 0.10 to 0.51, and from 0.11 to 0.67, respectively. Interestingly, in most countries the frequency of the GSTT1 null genotype is common or frequent (76%), whereas the frequency of the GSMT1 null genotype is very frequent or extremely frequent (86%). Thus, ethnic-dependent differences in the prevalence of GSTT1 and GSTM1 null variants may influence the effect of environmental carcinogens in cancer risk.

Heterogenous Distribution of MTHFR Gene Variants among Mestizos and Diverse Amerindian Groups from Mexico.

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. Folate deficiency has been related to several conditions, including neural tube defects (NTDs) and cardiovascular diseases. Hence, MTHFR genetic variants have been studied worldwide, particularly the C677T and A1298C. We genotyped the C677T and A1298C MTHFR polymorphisms in Mexican Amerindians (MAs), from the largest sample included in a genetic study (n = 2026, from 62 ethnic groups), and in a geographically-matched Mexican Mestizo population (MEZ, n = 638). The 677T allele was most frequent in Mexican individuals, particularly in MAs. The frequency of this allele in both MAs and MEZs was clearly enriched in the South region of the country, followed by the Central East and South East regions. In contrast, the frequency of the 1298C risk allele in Mexicans was one of the lowest in the world. Both in MAs and MEZs the variants 677T and 1298C displayed opposite allele frequency gradients from southern to northern Mexico. Our findings suggest that in Mestizos the 677T allele was derived from Amerindians while the 1298C allele was a European contribution. Some subgroups showed an allele frequency distribution that highlighted their genetic diversity. Notably, the distribution of the frequency of the 677T allele was consistent with that of the high incidence of NTDs reported in MEZ.