Introduction: The recent spread of coronavirus disease 2019 (COVID-19) has disproportionately impacted racial and ethnic minority groups; however, the impact of healthcare utilization on outcome ...disparities remains unexplored. Our study examines racial and ethnic disparities in hospitalization, medication usage, intensive care unit (ICU) admission and in-hospital mortality for COVID-19 patients. Methods: In this retrospective cohort study, we analyzed data for adult patients within an integrated healthcare system in New York City between February 28–August 28, 2020, who had a lab-confirmed COVID-19 diagnosis. Primary outcome was likelihood of inpatient admission. Secondary outcomes were differences in medication administration, ICU admission, and in-hospital mortality. Results: Of 4717 adult patients evaluated in the emergency department (ED), 3219 (68.2%) were admitted to an inpatient setting. Black patients were the largest group (29.1%), followed by Hispanic/Latinx (29.0%), White (22.9%), Asian (3.86%), and patients who reported “other” race-ethnicity (19.0%). After adjusting for demographic, clinical factors, time, and hospital site, Hispanic/Latinx patients had a significantly lower adjusted rate of admission compared to White patients (odds ratio OR 0.51; 95% confidence interval CI 0.34-0.76). Black (OR 0.60; 95% CI 0.43-0.84) and Asian patients (OR 0.47; 95% CI 0.25 - 0.89) were less likely to be admitted to the ICU. We observed higher rates of ICU admission (OR 2.96; 95% CI 1.43-6.15, and OR 1.83; 95% CI 1.26-2.65) and in-hospital mortality (OR 4.38; 95% CI 2.66-7.24; and OR 2.96; 95% CI 2.12-4.14) at two community-based academic affiliate sites relative to the primary academic site. Conclusion: Non-White patients accounted for a disproportionate share of COVID-19 patients seeking care in the ED but were less likely to be admitted. Hospitals serving the highest proportion of minority patients experienced the worst outcomes, even within an integrated health system with shared resources. Limited capacity during the COVID-19 pandemic likely exacerbated pre-existing health disparities across racial and ethnic minority groups.
Organisms belonging to the genus Rhizobium colonize leguminous plant roots and establish a mutually beneficial symbiosis. Biofilms are structured ecosystems in which microbes are embedded in a matrix ...of extracellular polymeric substances, and their development is a multistep process. The biofilm formation processes of
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CFN42 were analyzed at an early (24-h incubation) and mature stage (72 h), comparing cells in the biofilm with cells remaining in the planktonic stage. A genome-wide microarray analysis identified 498 differentially regulated genes, implying that expression of ~8.3 % of the total
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gene content was altered during biofilm formation. In biofilms-attached cells, genes encoding proteins with diverse functions were overexpressed including genes involved in membrane synthesis, transport and chemotaxis, repression of flagellin synthesis, as well as surface components (particularly exopolysaccharides and lipopolysaccharides), in combination with the presence of activators or stimulators of
N
-acyl-homoserine lactone synthesis This suggests that
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is able to sense surrounding environmental conditions and accordingly regulate the transition from planktonic and biofilm growth. In contrast, planktonic cells differentially expressed genes associated with transport, motility (flagellar and twitching) and inhibition of exopolysaccharide synthesis. To our knowledge, this is the first report of nodulation and nitrogen assimilation-related genes being involved in biofilm formation in
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These results contribute to the understanding of the physiological changes involved in biofilm formation by bacteria.
Summary
Elucidating the mechanisms controlling the synthesis of hydroxyectoine is important to design novel genetic engineering strategies for optimizing the production of this biotechnologically ...relevant compatible solute. The genome of the halophilic bacterium Chromohalobacter salexigens carries two ectoine hydroxylase genes, namely ectD and ectE, whose encoded proteins share the characteristic consensus motif of ectoine hydroxylases but showed only a 51.9% identity between them. In this work, we have shown that ectE encodes a secondary functional ectoine hydroxylase and that the hydroxyectoine synthesis mediated by this enzyme contributes to C.␣salexigens thermoprotection. The evolutionary pattern of EctD and EctE and related proteins suggests that they may have arisen from duplication of an ancestral gene preceding the directional divergence that gave origin to the orders Oceanospirillales and Alteromonadales. Osmoregulated expression of ectD at exponential phase, as well as the thermoregulated expression of ectD at the stationary phase, seemed to be dependent on the general stress factor RpoS. In contrast, expression of ectE was always RpoS‐dependent regardless of the growth phase and osmotic or heat stress conditions tested. The data presented here suggest that the AraC‐GlxA‐like EctZ transcriptional regulator, whose encoding gene lies upstream of ectD, plays a dual function under exponential growth as both a transcriptional activator of osmoregulated ectD expression and a repressor of ectE transcription, privileging the synthesis of the main ectoine hydroxylase EctD. Inactivation of ectZ resulted in a higher amount of the total ectoines pool at the expenses of a higher accumulation of ectoine, with maintenance of the hydroxyectoine levels. In addition to the transcriptional control, our results suggest a strong post‐transcriptional regulation of hydroxyectoine synthesis. Data on the accumulation of ectoine and hydroxyectoine in rpoS and ectZ strains pave the way for using these genetic backgrounds for metabolic engineering for hydroxyectoine production.
Besides the main ectoine hydroxylase EctD, the halophilic bacterium Chromohalobacter salexigens possess a secondary ectoine hydroxylases, EctE, which contributes to C. salexigens thermoprotection. Expression of ectD and ectE is dependent on the growth phase and the general stress factor RpoS. In addition, the EctZ transcriptional regulator plays a dual function under exponential growth as both an activator of osmorregulated ectD expression and a repressor of ectE transcription, privileging the synthesis of the main ectoine hydroxylase EctD.
Organic acidurias and aminoacidopathies are groups of frequent inborn errors of metabolism (IEMs), which are caused by mutations in specific genes that lead to loss of protein/enzyme or transport ...function with important deleterious effects to cell metabolism. Since a considerable number of such disorders are potentially treatable when diagnosed at an early stage of life, diagnosis is crucial for the patients. In the present report, we describe symptomatic individuals referred to our service that were diagnosed with these disorders from 2006 to 2016. We used blood and urine samples from 21,800 patients suspected of aminoacidopathies or organic acidemias that were processed by the analytical techniques reverse phase high-performance liquid chromatography for amino acid quantification and gas chromatography coupled to mass spectrometry for organic acid detection. Analysis of dried blood spots by liquid chromatography-tandem mass spectrometry was used in some cases. We detected 258 cases of organic acidurias, and 117 patients with aminoacidopathies were diagnosed. Once diagnosis was performed, patients were promptly submitted to the available treatments with clear reduction of mortality and morbidity. The obtained data may help pediatricians and metabolic geneticists to become aware of these diseases and possibly expand newborn screening programs in the future.
β‐Cyclodextrin (β‐CD) is being considered a promising therapy for Niemann‐Pick C (NPC) disease because of its ability to mobilise the entrapped cholesterol from lysosomes, however, a major limitation ...is its inability to cross the blood‐brain barrier (BBB) and address the central nervous system (CNS) manifestations of the disease. Considering this, we aimed to design nanoparticles able to cross the BBB and deliver β‐CD into the CNS lysosomes. The physicochemical characteristics of β‐CD‐loaded nanoparticles were evaluated by dynamic light scattering, small‐angle X‐ray scattering, and cryogenic transmission electron microscopy. The in vitro analyses were performed with NPC dermal fibroblasts and the β‐CD‐loaded nanoparticles were tracked in vivo. The nanoparticles showed a mean diameter around 120 nm with a disordered bicontinuous inner structure. The nanoparticles did not cause decrease in cell viability, impairment in the antioxidant enzymes activity, damage to biomolecules or release of reactive species in NPC dermal fibroblasts; also, they did not induce genotoxicity or alter the mitochondrial function in healthy fibroblasts. The β‐CD‐loaded nanoparticles were taken up by lysosomes reducing the cholesterol accumulated in NPC fibroblasts and reached the CNS of mice more intensely than other organs, demonstrating advantages compared to the free β‐CD. The results demonstrated the potential of the β‐CD‐loaded nanoparticles in reducing the brain impairment of NPC.
Objective. The Victorian Government in Australia has developed Healthy Choices guidelines to ensure that healthy foods and drinks are offered and promoted in places such as hospitals. This brief ...report aims to present complex theoretical attributes related to cocreation through an accessible example of a competition to create a new name for the previously understated hospital “kiosk.” Methods. A mixed-methods approach using an online survey and semistructured interviews were used to obtain detailed insights from hospital staff members to engage in a naming competition for a hospital-based cafe. Results. The level of engagement in this activity was higher than anticipated by the management staff. Conclusions. Active involvement of staff members through a cocreation process can enable the development of innovative healthy eating strategies and increase staff engagement to further changes in the cafe. Implications for public health cocreation in public health promises effective stakeholder engagement and requires significant scientific advancement. This brief report illustrates theoretical constructs of cocreation through a naming competition activity that occurred as part of a larger project to improve Wimmera Base Hospital’s food environment.
Central nervous system is not spared from the deleterious effects of diabetes, since several studies have described neuropsychological and neurobehavioral changes in diabetic subjects, suggesting ...that diabetic encephalopathy should be recognized as a complication of this complex metabolic disorder. In fact, psychiatric manifestations may accompany this encephalopathy, since the prevalence of depression in diabetic patients is much higher than in the general population. Furthermore, evidences from preclinical and clinical studies suggest that GABA plays a role both in the pathophysiology of the diabetic encephalopathy-related depression. So, this review addresses the GABAergic modulation in diabetic encephalopathy-related depression. Data presented from literature support the association between GABA and depressive- like behaviors in diabetic encephalopathy, being this neurotransmitter a potential target for the treatment of diabetes, depression and related comorbidities.
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•Home compost properties were enhanced by Bacillus thuringiensis (Bt) inoculation.•Quality home compost with added biopesticide properties was obtained from biowaste.•Crystal toxin ...was present in the compost after Bt progress during home composting.•Microbiological analysis revealed highly diverse communities in home compost.
Home and community composting are considered potential tools for the self-management of organic waste. The production of added value products from biowaste is an encouraging step further to valorise this waste stream. To increase the profits of homemade compost, this paper presents a strategy to produce enriched home compost with biopesticide properties through a simple and low-cost process. Bacillus thuringiensis (Bt) was inoculated in a home composter bin through a solid inoculum previously prepared using the same waste as substrate. The process was monitored and compared with a home composting control process without inoculation. Final composts were analysed and compared in terms of physicochemical and microbiological properties, respiration and germination indices, indicating the suitability of both to be used as organic amendments. Also, a standardized toxicity test proved that Bt-enriched compost can be safely applied to the soil. Microbiological analysis revealed highly diverse communities in both cases, with limited differences at phylum taxonomic level, but dissimilar relative abundances of species within phylum. Bacteroidetes and Proteobacteria were dominant, with the presence of species able to transform organic matter from vegetal origin, but not usually related to compost. Bt-cristal toxin was clearly present in Bt-enriched compost, indicating the coexistence of Bt with the different microbial populations till the end of the composting process. Although Bt has been widely investigated due to its biopesticide properties, the incorporation of this microorganism to home composting level has not been previously reported.
Oxidative stress has been proposed as an important pathophysiologic feature of various inborn errors of metabolism, including phenylketonuria (PKU). Considering that there are few studies relating ...oxidative stress and inflammation directly in PKU disease, the aim of this study was to evaluate and correlate oxidative damage to biomolecules, antioxidant defenses, pro-inflammatory cytokines, phenylalanine (Phe) and its metabolites (phenyllactic acid--PLA and phenylacetic acid--PAA) levels in urine and plasma from patients with PKU under dietary treatment. We observed a marked increase of isoprostanes, which is a lipid peroxidation biomarker, in urine from these treated patients. Next, we demonstrated that protein oxidative damage, measured by di-tyrosine formation, was significantly increased in urine from PKU treated patients and that decreased urinary antioxidant capacity was also observed. Our findings concerning to the inflammatory cytokines interleukin-6 and interleukin-1β, both significantly increased in these patients, provide evidence that the pro-inflammatory state occurs. Besides, interleukin-1β was positively correlated with isoprostanes. We observed a negative correlation between interleukin-6 and interleukin-10, an anti-inflammatory cytokine. Di-tyrosine was positively correlated with Phe, which indicates oxidative damage to proteins, as well as with PAA. These findings may suggest that the protein damage may be induced by Phe and its metabolite PAA in PKU. Our results indicate that pro-oxidant and pro-inflammatory states occur and are, in part, correlated and protein oxidation seems to be induced by Phe and PPA in PKU patients.
Maple syrup urine disease (MSUD) is a metabolic disease caused by a deficiency in the branched-chain α-keto acid dehydrogenase complex, leading to the accumulation of branched-chain keto acids and ...their corresponding branched-chain amino acids (BCAA) in patients. Treatment involves protein-restricted diet and the supplementation with a specific formula containing essential amino acids (except BCAA) and micronutrients, in order to avoid the appearance of neurological symptoms. Although the accumulation of toxic metabolites is associated to appearance of symptoms, the mechanisms underlying the brain damage in MSUD remain unclear, and new evidence has emerged indicating that oxidative stress contributes to this damage. In this context, this review addresses some of the recent findings obtained from cells lines, animal studies, and from patients indicating that oxidative stress is an important determinant of the pathophysiology of MSUD. Recent works have shown that the metabolites accumulated in the disease induce morphological alterations in C6 glioma cells through nitrogen reactive species generation. In addition, several works demonstrated that the levels of important antioxidants decrease in animal models and also in MSUD patients (what have been attributed to protein-restricted diets). Also, markers of lipid, protein, and DNA oxidative damage have been reported in MSUD, probably secondary to the high production of free radicals. Considering these findings, it is well-established that oxidative stress contributes to brain damage in MSUD, and this review offers new perspectives for the prevention of the neurological damage in MSUD, which may include the use of appropriate antioxidants as a novel adjuvant therapy for patients.
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