Targeting the brain 5-HT7 receptor to prevent hypomyelination in a rodent model of perinatal white matter injuries.

Approximately 15 million babies are born prematurely every year and many will face lifetime motor and/or cognitive deficits. Children born prematurely are at higher risk of developing perinatal brain lesions, especially white matter injuries (WMI). Evidence in humans and rodents demonstrates that systemic inflammation-induced neuroinflammation, including microglial and astrocyte reactivity, is the prominent processes of WMI associated with preterm birth. Thus, a new challenge in the field of perinatal brain injuries is to develop new neuroprotective strategies to target neuroinflammation to prevent WMI. Serotonin (5-HT) and its receptors play an important role in inflammation, and emerging evidence indicates that 5-HT may regulate brain inflammation by the modulation of microglial reactivity and astrocyte functions. The present study is based on a mouse model of WMI induced by intraperitoneal (i.p.) injections of IL-1ß during the first 5 days of life. In this model, certain key lesions of preterm brain injuries can be summarized by (i) systemic inflammation, (ii) pro-inflammatory microglial and astrocyte activation, and (iii) inhibition of oligodendrocyte maturation, leading to hypomyelination. We demonstrate that Htr7 mRNA (coding for the HTR7/5-HT7 receptor) is significantly overexpressed in the anterior cortex of IL-1ß-exposed animals, suggesting it as a potential therapeutic target. LP-211 is a specific high-affinity HTR7 agonist that crosses the blood-brain barrier (BBB). When co-injected with IL-1ß, LP-211 treatment prevented glial reactivity, the down-regulation of myelin-associated proteins, and the apparition of anxiety-like phenotypes. Thus, HTR7 may represent an innovative therapeutic target to protect the developing brain from preterm brain injuries.

Bovicin HC5 and nisin reduce cell viability and the thermal resistance of Alicyclobacillus acidoterrestris endospores in fruit juices.

BACKGROUND: Alicyclobacillus acidoterrestris is an important thermoacidophilic spore-forming bacterium in fruit-juice deterioration, and alternative non-thermal methods have been investigated to control fruit juice spoilage. This work aimed to evaluate the capacity of bovicin HC5 and nisin to inhibit the growth of vegetative cells and reduce the thermal resistance of endospores of A. acidoterrestris inoculated (107 CFU mL-1 ) in different fruit juices. The number of viable cells was determined after 12 h incubation at 43 °C in the presence and absence of nisin or bovicin HC5 (10-100 AU mL-1 ). The exposure time (min) required to kill 90% of the initial population (reduction of one log factor) at 90 ºC (D90ºC ) was used to assess the thermal resistance of A. acidoterrestris endospores exposed (80 AU mL-1 ) or non-exposed to the bacteriocins. Additionally, the effect of bovicin and nisin on the morphology and cell structure of A. acidoterrestris was evaluated by atomic force microscopy (AFM). RESULTS: Bovicin HC5 and nisin were bactericidal against A. acidoterrestris inoculated in fruit juices and reduced the D90°C values up to 30-fold. AFM topographical images revealed substantial structural changes in the cellular framework of vegetative cells upon treatment with bovicin HC5 or nisin. CONCLUSIONS: These results emphasize the potential application of lantibiotics as additional hurdles in food processing to control thermoacidophilic spoilage bacteria in fruit juices. © 2022 Society of Chemical Industry.

The unexpected discovery of Brucella abortus Buck 19 vaccine in goats from Ecuador underlines the importance of biosecurity measures.

Very few, mostly old, and only preliminary serological studies of brucellosis in goats exist in Ecuador. In order to assess the current epidemiological situation, we performed a cross-sectional serological study in the goat populations of Carchi (n = 160 animals), Pichincha (n = 224 animals), and Loja provinces (n = 2024 animals). Only two positive serological results (RB negative and SAT-EDTA ≥400 IU/ml) were obtained in lactating goats from the same farm in Quito (Pichincha province). Additionally, milk was sampled from 220 animals in Pichincha province. The present study indicates a low apparent prevalence in Pichincha province and absence in Carchi and Loja provinces. A total of 25 positive milk ring tests (MRT) were obtained in Pichincha province yielding a prevalence of MRT of 11.16%. Subsequent culture was performed on the positive MRT samples. All results were negative, apart from a single sample, obtained from a serologically positive goat in Quito, that was positive for Brucella abortus strain 19 (B19). Several hypotheses are forwarded concerning this unexpected result. The most likely hypothesis is the possible accidental use of a needle, previously used for vaccination of cattle with the said vaccine, for the administration of drug treatment to the goat. This hypothesis underlines the necessity of biosecurity measures to prevent this type of accidents.

Seeing things the same way: perspectives and lessons learned from research-design collaborations.

Information visualizations are increasingly being developed by informatics researchers to communicate health information to lay audiences. For high-quality results, it is advisable to collaborate with creative professionals such as graphic designers, illustrators, or user interface/user experience designers. However, such collaborations are often a novel experience for both parties, each of which may be unfamiliar with the needs and processes of the other. We have coalesced our experiences from both the research and design perspectives to offer practical guidance in hopes of promoting the success of future collaborations. We offer suggestions for determining design needs, communicating with design professionals, and carrying out the design process. We assert that successful collaborations are predicated on careful and intentional planning at the outset of a project, a thorough understanding of each party's scope expertise, clear communication, and ample time for the design process to unfold.

Assessment of airline industry using a new double-frontier cross-efficiency method based on prospect theory.

Cross-efficiency method (CEM) is a well-known technique based on data envelopment analysis that provides policymakers with a powerful tool to measure the efficiency of decision-making units. However, there are two main gaps in the traditional CEM. First, it neglects the subjective preferences of decision-makers (DMs), and therefore, cannot reflect the importance of self-evaluation compared to peer-evaluations. Second, it ignores the importance of anti-efficient frontier in the overall evaluation. The present study aims to incorporate the prospect theory into the double-frontier CEM to deal with these drawbacks while considering the preferences of DMs towards gains and losses. To address these drawbacks, this paper utilizes an aggregation method based on the prospect theory and consensus degree (APC) to reflect the subjective preferences of DMs. The second issue is also addressed by incorporating APC into the optimistic and pessimistic CEMs. Finally, the double-frontier CEM aggregated using APC (DAPC) is obtained by aggregating two viewpoints. As a real case study, DAPC is applied to evaluate the performance of 17 Iranian airlines based on three inputs and four outputs. The findings demonstrate that both viewpoints are influenced by DMs' preferences. The ranking results achieved for more than half of the airlines based on the two viewpoints are significantly different. The findings confirm that DAPC deals with these differences and leads to more comprehensive ranking results by considering both subjective viewpoints simultaneously. The results also show that to what extent DAPC efficiency for each airline is influenced by each viewpoint. In this regard, the efficiency of IRA is most influenced by the optimistic point of view (80.92%), and on the other hand, the efficiency of IRZ is most influenced by the pessimistic viewpoint (73.45%). KIS is the most efficient airline, followed by PYA. On the other hand, IRA is the least efficient airline, followed by IRC.

COVID-19 Monoclonal Antibody Administration Linked to Drop in Blood Pressure: A Retrospective Cohort Study.

This study reports on hemodynamic changes observed during monoclonal antibody (mAb) administration for patients with severe acute respiratory distress syndrome-coronavirus-2. Findings from this study may have implications for patient safety. Hemodynamic data from 705 patients who received subcutaneous or intravenous mAb therapy during February 1, 2021-September 30, 2021 in clinics in Arkansas, USA were reviewed. Descriptive statistics and paired t-tests were used to assess blood pressure before and after treatment. Results showed 386 (54.7%) patients experienced a drop in systolic blood pressure (SBP) or diastolic blood pressure (DBP) >5 mmHg. The average drop in SBP was 9.2 mmHg for those patients. Two hundred and eighty-one (39.9%) patients experienced a drop in SBP of >10 mmHg with an average drop in SBP of 12.0 mmHg. The Emergency Use Authorization for mAb does not list hypotension as a contraindication for treatment. Our findings suggest mAb therapy should be administered in an environment where vitals are monitored.

Healthcare Access and Experiences of Racial Discrimination as Predictors of General Vaccine Hesitancy.

The literature regarding vaccine hesitancy is limited to specific vaccines rather than general vaccine hesitancy. No studies have examined the relationship of general vaccine hesitancy to healthcare access and experiences of racial discrimination. This study fills gaps by examining: (1) socio-demographic factors; (2) associations between healthcare access; and (3) experiences with racial discrimination and general vaccine hesitancy. Survey data were obtained from 2022 US adults from 7 September to 3 October 2021. Racial and ethnic minority populations were oversampled. Age, gender, race, and education were predictors of vaccine hesitancy. Asian respondents had less than two-thirds the odds of being vaccine hesitant. Healthcare access was associated with vaccine hesitancy. Not having health insurance coverage, not having a primary care provider, and not seeing a provider for a routine check-up in the past two years were associated with higher vaccine hesitancy. For every one-point increase in racial discrimination score (0-45), the odds of being more vaccine hesitant increased by a factor of 1.03. The findings demonstrate that policy, systems, and environmental factors are critical to addressing vaccine hesitancy. Given the associations between vaccine hesitancy and racial discrimination and healthcare access, more attention should be given to inequities in the healthcare systems in order to address vaccine hesitancy.

Chronic stress causes striatal disinhibition mediated by SOM-interneurons in male mice.

Chronic stress (CS) is associated with a number of neuropsychiatric disorders, and it may also contribute to or exacerbate motor function. However, the mechanisms by which stress triggers motor symptoms are not fully understood. Here, we report that CS functionally alters dorsomedial striatum (DMS) circuits in male mice, by affecting GABAergic interneuron populations and somatostatin positive (SOM) interneurons in particular. Specifically, we show that CS impairs communication between SOM interneurons and medium spiny neurons, promoting striatal overactivation/disinhibition and increased motor output. Using probabilistic machine learning to analyze animal behavior, we demonstrate that in vivo chemogenetic manipulation of SOM interneurons in DMS modulates motor phenotypes in stressed mice. Altogether, we propose a causal link between dysfunction of striatal SOM interneurons and motor symptoms in models of chronic stress.

Incidence of SARS-CoV-2 infection among COVID-19 vaccinated and unvaccinated healthcare personnel, first responders, and other essential and frontline workers: Eight US locations, January-September 2021.

BACKGROUND: We sought to evaluate the impact of changes in estimates of COVID-19 vaccine effectiveness on the incidence of laboratory-confirmed infection among frontline workers at high risk for SARS-CoV-2. METHODS: We analyzed data from a prospective frontline worker cohort to estimate the incidence of COVID-19 by month as well as the association of COVID-19 vaccination, occupation, demographics, physical distancing, and mask use with infection risk. Participants completed baseline and quarterly surveys, and each week self-collected mid-turbinate nasal swabs and reported symptoms. RESULTS: Among 1018 unvaccinated and 3531 fully vaccinated workers, the monthly incidence of laboratory-confirmed SARS-CoV-2 infection in January 2021 was 13.9 (95% confidence interval [CI]: 10.4-17.4), declining to 0.5 (95% CI -0.4-1.4) per 1000 person-weeks in June. By September 2021, when the Delta variant predominated, incidence had once again risen to 13.6 (95% CI 7.8-19.4) per 1000 person-weeks. In contrast, there was no reportable incidence among fully vaccinated participants at the end of January 2021, and incidence remained low until September 2021 when it rose modestly to 4.1 (95% CI 1.9-3.8) per 1000. Below average facemask use was associated with a higher risk of infection for unvaccinated participants during exposure to persons who may have COVID-19 and vaccinated participants during hours in the community. CONCLUSIONS: COVID-19 vaccination was significantly associated with a lower risk of SARS-CoV-2 infection despite Delta variant predominance. Our data demonstrate the added protective benefit of facemask use among both unvaccinated and vaccinated frontline workers.

Improving Access to Kidney Transplantation: Perspectives From Dialysis and Transplant Staff in the Southeastern United States.

RATIONALE & OBJECTIVE: There are many barriers to meeting the goal of increasing kidney transplants in the United States. It is important to understand dialysis and transplant center providers' existing practices and identified barriers to increasing the number of dialysis patients who are evaluated for and get wait-listed for a transplant. STUDY DESIGN: Cross-sectional survey of dialysis unit and transplant center staff in End Stage Renal Disease Network 6 (Georgia, North Carolina, South Carolina). SETTING & PARTICIPANTS: Ninety-one transplant staff from all 9 transplant centers in the region and 421 dialysis staff from 421 facilities responded to the survey. PREDICTORS: N/A. OUTCOME: Provider perceptions of barriers faced by patients in the kidney transplant evaluation process and suggestions for improving care. ANALYTICAL APPROACH: Mixed methods. Descriptive analyses of responses to multiple-choice questions and qualitative analysis of open-ended survey responses. RESULTS: The top 5 barriers to kidney transplantation as reported by transplant staff were transportation (63.7%), low health literacy (50.5%), lack of understanding about the transplant process (37.4%), distance to transplant center (29.7%), and low socioeconomic status (28.6%). When asked how dialysis units can help patients complete the evaluation process, the most common responses from transplant center staff were educating patients about transplant (54%), helping patients through steps in the process (35%), and better communication with transplant centers (15%). When dialysis unit staff were asked what could be done to help the facility improve its transplant wait-list rate, the most common responses were educational materials for patients and staff (55%), better communication with transplant centers (12%), and transportation and financial assistance (9%). LIMITATIONS: Survey responses are from 1 end stage renal disease network. CONCLUSIONS: Dialysis units, transplant centers, and ESRD networks can work together to help patients address key barriers to transplantation to improve the country's transplantation rate.

Sex differences in offspring neurodevelopment, cognitive performance and microglia morphology associated with maternal diabetes: Putative targets for insulin therapy.

Diabetes during pregnancy has been shown to affect the central nervous system (CNS) of the offspring, resulting in short- and long-term adverse effects. Children of diabetic mothers are more likely to develop cognitive impairment, also having increased susceptibility to psychiatric disorders. Microglia, the immune cells of the CNS, work as sensors of environmental changes, namely metabolic challenges, as early as the intrauterine period. During this period, microglia is actively involved in processes of neurogenesis, synaptic pruning and detection of any environmental alteration that may impact brain development. The remarkable sex dimorphism in neurodevelopment, as well as sex differences in the morphology and immune function of microglia during development, led us to clarify if maternal diabetes affects specific behavioral traits and microglia morphology during infancy in a sex-specific manner. Another important goal of this study was to clarify if insulin, the gold standard treatment of diabetes during gestation, could prevent maternal diabetes-induced behavioral changes, as well as microglia morphology, also considering sex specificities. Other molecular and cellular players potentially involved in the link between changes in metabolism and behavior were also analyzed in the hippocampus, a brain region implicated in cognition and other behavioral outcomes. Diabetes during pregnancy globally delayed female and male offspring development and was associated with impairments in recognition memory, but only in female offspring. In line with these results, at early and late infancy, some molecular and cellular markers were altered in offspring hippocampus in a sex-specific manner. The strict control of glycemia by insulin during pregnancy prevented most of the negative effects induced by uncontrolled hyperglycemia. Notably, insulin administration to diabetic dams may also modulate offspring development in a way that differs from what is observed in physiological conditions, since it promoted the expedited acquisition of developmental milestones and of discrimination ability at memory test, also inducing a hyper-ramification of male and female hippocampal microglia. Importantly, this study highlights the importance of analyzing the impact of maternal diabetes and insulin therapy, taking into account sex differences, since male and female present different vulnerabilities to hyperglycemia in this critical period of life.

An instrument-free method for the demonstration of efflux pump activity of bacteria.

UNLABELLED: The aim of the study was to develop a simple, inexpensive, reproducible ethidium bromide (EB)-agar based method that is independent of any specialized instrumentation, for the demonstration of efflux pump activity, which is responsible for antibiotic resistance of bacteria. MATERIALS AND METHODS: A series of agar plates containing varying concentrations of EB were swabbed with strains of Escherichia coli or Staphylococcus aureus, which differed with respect to efflux pump activity. The plates were incubated at different temperatures and time periods and the measurements of fluorescence were used to evaluate the efflux activity of each culture. RESULTS: This simple assay allowed us to identify the efflux of EB in different bacteria following an overnight incubation. The minimal concentration of EB that produced fluorescence was significantly greater at 37 degrees C than at 4 degrees C, suggesting the presence of an energy-dependent pump. The method was shown to simultaneously identify strains of a mixed culture that differed from each other with respect to the activity of their efflux pumps. CONCLUSION: The method, in conjunction with the use of antibiotic-containing disks, provides an additional advantage for the easy identification and selection of colonies that differ with respect to antibiotic susceptibility and degree of efflux pump activity. Because the method is very reproducible it may form the basis for interlaboratory standardization of efflux pump activity of multi-drug resistant (MDR) clinical isolates.

Mobile teleradiology system suitable for m-health services supporting content and semantic based image retrieval on a grid infrastructure.

Teleradiology systems tackle the problem of transferring radiological images between medical image workstations for facilitating different medical activities, e.g., diagnosis, treatment and follow up a patient, medical training, or consulting second opinion. Nowadays, m-Health (aka mobile health) is becoming popular because of high quality of mobile displays, although remains a work in progress. In this paper a mobile teleradiology system is reported, which main contribution is the development of a platform: (1) supported by a Grid infrastructure, (2) using biomedical ontologies for adding semantic annotations on medical images, and (3) supporting semantic and content-based image retrieval. Images are located physically in different repositories like; hospitals and diagnostic imaging centers. All these features make the system ubiquitous, portable, and suitable for m-Health services.

An automatic method for the enrichment of DICOM metadata using biomedical ontologies.

This work is a novel contribution for enriching medical images using semantic annotations with a strategy for unifying different ontologies and instances of DICOM medical files. We present the L-MOM library (Library for Mapping of Ontological Metadata) as a tool for making an automatic mapping between instances of DICOM medical files and different medical ontologies (e.g., FMA, RadLex, MeSH). The main contributions are: i) the domain independent L-MOM library which is able to integrate DICOM metadata with ontologies from different domains; ii) a strategy to automatically annotate DICOM data with universally accepted medical ontologies, and provide values of similarity between ontologies and DICOM metadata; and iii) a framework to traverse ontological concepts that characterized clinical studies of patients registered in the framework catalog.

Mycobacterium sp., Rhodococcus erythropolis, and Pseudomonas putida behavior in the presence of organic solvents.

This work aimed at studying the behavior and tolerance of Mycobacterium sp. NRRL B-3805, Rhodococcus erythropolis DCL14 and Pseudomonas putida S12 cells in the presence of various concentrations of water miscible (ethanol, butanol, and dimethylformamide, up to 50% v/v) and water immiscible solvents (dodecane, bis(2-ethylhexyl) phthalate and toluene, up to 5% v/v). When incubated in the presence of these solvents, the cells were found to have lower tolerance to butanol and toluene than to the remaining solvents. Nevertheless, the concentrations of solvents endured by the tested strains show that they are quite solvent-tolerant, confirming their potential as biocatalysts in nonconventional systems. Microscopic observation of samples showed that the hydrophobic Mycobacterium sp. and R. erythropolis cells were able to aggregate to protect the population under stress conditions. Comparison of the results obtained at the single cell level by fluorescence microscopy and colony development on agar plates indicated that the primary effects of most solvents tested were on the cell membrane and replicating capability of the cells.