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The present study investigated the best photoperiod for culturing pacu (Piaractus mesopotamicus) in recirculation aquaculture systems (RAS) based on its growth performance and hematological and oxidative stress responses. Juveniles (∼ 5 g) were subjected to five treatments (in triplicate): 24 L (light):0D (dark), 15 L: 09D, 12 L:12D, 9 L:15D, and 0 L:24D for 45 days. A total of 225 pacu individuals were randomly distributed among 15 tanks of 210 L (n = 15 per tank). Zootechnical, hematological (glucose, lactate, hematocrit, and hemoglobin), and antioxidant and oxidative stress parameters (glutathione S-transferase (GST), total antioxidant capacity against peroxyl radicals (ACAP), and lipid peroxidation (LPO) were analyzed. The zootechnical parameters (e.g., weight gain, Fulton's condition factor, and specific growth rate) were better and worse with 9 L:15D and 24 L:0D photoperiods, respectively. The hepatosomatic index was higher and lower in the 0 L:24D and 9 L:15D photoperiods. Blood lactate levels and antioxidant and oxidative stress responses were increased in the longest photoperiods (15 L:9D and 24 L:0D). In contrast, the treatments that showed lower oxidative damage (liver, gills, brain, and muscle) were 9 L:15D and 12 L:12D. In conclusion, manipulating artificial light is one way to improve fish growth and health, where the best photoperiod for pacu farming in RAS is 9 L:15D. [ABSTRACT FROM AUTHOR]

Biofloc technology (BFT) is a widely available system for aquaculture production, reducing water, and artificial diet consumption. This study evaluated the survival, growth performance, and hematological parameters of pacu juveniles subjected to different total suspended solids (TSS) concentrations of the BFT system. Juveniles were exposed to five TSS concentrations: 0, 250, 500, 750, and 1000 mg L−1 (or control, BFT250, BFT500, BFT750, and BFT1000) for 30 days. The experimental design was randomized in five treatments and three replicates (9 fish per tank). Except for TSS and settleable solids, the water quality variables did not differ between treatments. The survival rate was 100%, and the weight gain was higher in the control group, followed by BFT1000. The hepatosomatic index was significantly lower in the control group compared to the BFT1000. Generally, the highest blood glucose and pH levels were found in BFT500 and BFT750, respectively. The treatments with TSS showed hematological changes (hematocrit, hemoglobin, and hematimetric indices), with the highest changes occurring in juveniles exposed to values above 500 mg L−1 TSS. In conclusion, although the treatments with TSS can reduce growth, increase HSI, and cause hematological changes, it is a promising alternative for producing pacu juveniles, mainly BFT1000. [ABSTRACT FROM AUTHOR]

Background: Physical activity and exercise have been suggested as effective interventions for the prevention and management of mild cognitive impairment (MCI) and dementia, but there are no international guidelines. Objectives: To create a set of evidence- and expert consensus-based prevention and management recommendations regarding physical activity (any bodily movement produced by skeletal muscles that results in energy expenditure) and exercise (a subset of physical activity that is planned, structured, repetitive), applicable to a range of individuals from healthy older adults to those with MCI/dementia. Methods: Guideline content was developed with input from several scientific and lay representatives' societies. A systematic search across multidisciplinary databases was carried out until October 2021. Recommendations for prevention and management were developed according to the GRADE and complemented by consensus statements from the expert panels. Recommendations: Physical activity may be considered for the primary prevention of dementia. In people with MCI there is continued uncertainty about the role of physical activity in slowing the conversion to dementia. Mind–body interventions have the greatest supporting evidence. In people with moderate dementia, exercise may be used for maintaining disability and cognition. All these recommendations were based on a very low/low certainty of evidence. Conclusions: Although the scientific evidence on the beneficial role of physical activity and exercise in preserving cognitive functions in subjects with normal cognition, MCI or dementia is inconclusive, this panel, composed of scientific societies and other stakeholders, recommends their implementation based on their beneficial effects on almost all facets of health. [ABSTRACT FROM AUTHOR]

Philosophers of science have argued that epistemic diversity is an asset for the production of scientific knowledge, guarding against the effects of biases, among other advantages. The growing privatization of scientific research, on the contrary, has raised important concerns for philosophers of science, especially with respect to the growing sources of biases in research that it seems to promote. Recently, Holman and Bruner (2017) have shown, using a modified version of Zollman (2010) social network model, that an industrial selection bias can emerge in a scientific community, without corrupting any individual scientist, if the community is epistemically diverse. In this paper, we examine the strength of industrial selection using a reinforcement learning model, which simulates the process of industrial decision-making when allocating funding to scientific projects. Contrary to Holman and Bruner’s model, in which the probability of success of the agents when performing an action is given a priori, in our model the industry learns about the success rate of individual scientists and updates the probability of success on each round. The results of our simulations show that even without previous knowledge of the probability of success of an individual scientist, the industry is still able to disrupt scientific consensus. In fact, the more epistemically diverse the scientific community, the easier it is for the industry to move scientific consensus to the opposite conclusion. Interestingly, our model also shows that having a random funding agent seems to effectively counteract industrial selection bias. Accordingly, we consider the random allocation of funding for research projects as a strategy to counteract industrial selection bias, avoiding commercial exploitation of epistemically diverse communities. [ABSTRACT FROM AUTHOR]

The aim of this work was to verify the effect of temperature on blood parameters, reactive oxygen species, and lipid peroxidation of pacu. After acclimation period, 180 healthy juveniles (29.48 ± 2.73 g) were randomly placed in five RAS (12 fish tank−1; 1.68 g L−1 stocking density) and exposed to five treatments (18, 21, 24 [control], 27, and 30 °C—in triplicate) for 45 days. At the end of the experiment, blood samples (n = 9) were used to measure pH, glucose, lactate, hemoglobin, hematocrit, erythrocytes, MCV, MCH, and MCHC. Tissue (liver and muscle) samples (n = 9) were collected for GST, ACAP, TBARS, P-SH, and NP-SH analysis. Blood glucose, hematocrit, and erythrocytes were higher in pacu maintained at 27 and 30 °C. Blood pH was higher at 18 °C and lactate was higher at 18 and 30 °C compared to other treatments. Hemoglobin was lower at 18 and 21 °C and higher at 27 and 30 °C than at 24 °C. GST in the liver was lower at 18 °C than at 24 °C. P-SH in muscle was lowest at 27 and 30 °C, while NP-SH was higher at 21 °C. Sulfhydryl groups (P-SH and NP-SH) in the liver showed a positive linear relationship with the water temperature (R2 = 0.90). TBARS presented a quadratic relationship with the water temperature in the muscle (R2 = 0.85) and liver (R2 = 0.83). In accordance with the hematological parameters, P. mesopotamicus can be reared in the range between 24 and 27 °C. However, 24.09 °C was the optimum temperature as muscle lipid peroxidation was minimum. [ABSTRACT FROM AUTHOR]

Monocyte-derived macrophages (MDM) are highly permissive to HIV-1 infection potentially due to the downregulation of innate factors during the differentiation process. The environmental milieu and innate anti-viral factors which are modulated during macrophage differentiation, have been associated with their increased permissiveness to HIV-1 infection. Here, we demonstrate that the Army Liposome Formulation containing MPLA, and QS-21 (ALFQ) activated MDM that are normally permissive to HIV-1 infection to generate a proinflammatory environment and upregulated anti-viral factors notably APOBEC3A. Induction of APOBEC3A by ALFQ decreased permissiveness to HIV-1 infection, while knockdown of APOBEC3A with APOBEC3AsiRNA resulted in a significant loss in the restriction of HIV-1 infectivity. The liposome formulation ALF55, with identical lipid composition but lacking QS-21 had no effect. Furthermore, the capacity of ALFQ to modulate MDM permissiveness to HIV-1 infection was predominantly mediated by large ALFQ liposomes. Our findings highlight a relationship between innate immune activation, proinflammatory milieu, and upregulation of anti-HIV proteins. Induction of these responses can switch the HIV-1 permissive MDM into a more refractory phenotype. [ABSTRACT FROM AUTHOR]

The association between obstructive sleep-disordered breathing (oSDB) and arterial stiffness, an independent predictor of cardiovascular outcomes, is not well established in children. This study compared cardiovascular parameters between healthy and oSDB children and aimed to identify predictors of arterial stiffness indices in children with oSDB. Cross-sectional study realized in a tertiary hospital from June 2018 to January 2020. Forty-eight children (3 to 10 years old) with clinical diagnosis of oSDB and indication for adenotonsillectomy and 24 controls were evaluated. Cardiovascular parameters were measured non-invasively by brachial artery oscillometry with a portable device. The main arterial stiffness indices assessed were augmentation index and pulse wave velocity, both derived from the aortic pulse wave. In the oSDB group, the questionnaires Obstructive Sleep Apnea-18 (OSA-18) and Pediatric Quality of Life Inventory version 4.0 (PedsQL 4.0) were applied. The oSDB group had higher values of reflection coefficient (p = 0.044) and augmentation index (p = 0.003) than the control group. Stepwise multiple regression analysis revealed that age, female sex, reflection coefficient, and systolic volume were independent predictors of augmentation index. Higher pulse wave velocity values were associated with worse quality of life assessed by PedsQL 4.0 questionnaire. There was no association with OSA-18. The vascular and hemodynamic parameters were similar in both groups. Conclusion: Children with oSDB have increased augmentation index, an independent predictor of cardiovascular outcomes. The early identification of subclinical cardiovascular changes reinforces the importance of treating the disease, as well as changing lifestyle habits, to prevent complications in adulthood. What is Known: • The association between oSDB and cardiovascular risk in adults is well described in the literature. • Children with oSDB, regardless of their weight or sex, have higher PWV values when compared to non-snoring children. What is New: • Children with oSDB have augmented arterial stiffness, evidenced by the increase in AIx@75, measured non-invasively by brachial artery oscillometry with a portable device. • Low quality of life and therefore a high disease burden in children with oSDB may be a risk factor for arterial stiffness. [ABSTRACT FROM AUTHOR]

Co-transcriptional histone modifications are a ubiquitous feature of RNA polymerase II (RNAPII) transcription, with profound but incompletely understood effects on gene expression. Unlike the covalent marks found at promoters, which are thought to be instructive for transcriptional activation, these modifications occur in gene bodies as a result of transcription, which has made elucidation of their functions challenging. Here we review recent insights into the regulation and roles of two such modifications: monoubiquitylation of histone H2B at lysine 120 (H2Bub1) and methylation of histone H3 at lysine 36 (H3K36me). Both H2Bub1 and H3K36me are enriched in the coding regions of transcribed genes, with highly overlapping distributions, but they were thought to work largely independently. We highlight our recent demonstration that, as was previously shown for H3K36me, H2Bub1 signals to the histone deacetylase (HDAC) complex Rpd3S/Clr6-CII, and that Rpd3S/Clr6-CII and H2Bub1 function in the same pathway to repress aberrant antisense transcription initiating within gene coding regions. Moreover, both of these histone modification pathways are influenced by protein phosphorylation catalyzed by the cyclin-dependent kinases (CDKs) that regulate RNAPII elongation, chiefly Cdk9. Therefore, H2Bub1 and H3K36me are more tightly linked than previously thought, sharing both upstream regulatory inputs and downstream effectors. Moreover, these newfound connections suggest extensive, bidirectional signaling between RNAPII elongation complexes and chromatin-modifying enzymes, which helps to determine transcriptional outputs and should be a focus for future investigation. [ABSTRACT FROM AUTHOR]

The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly transmissible disease. SARS-CoV-2 is estimated to have infected over 153 million people and to have caused over 3.2 million global deaths since its emergence in December 2019. SARS-CoV-2 is the seventh coronavirus known to infect humans, and like other coronaviruses, SARS-CoV-2 infection is characterized by a variety of symptoms including general flu-like symptoms such as a fever, sore throat, fatigue, and shortness of breath. Severe cases often display signs of pneumonia, lymphopenia, acute kidney injury, cardiac injury, cytokine storms, lung damage, acute respiratory distress syndrome (ARDS), multiple organ failure, sepsis, and death. There is evidence that around 30% of COVID-19 cases have central nervous system (CNS) or peripheral nervous system (PNS) symptoms along with or in the absence of the previously mentioned symptoms. In cases of CNS/PNS impairments, patients display dizziness, ataxia, seizure, nerve pain, and loss of taste and/or smell. This review highlights the neurological implications of SARS-CoV-2 and provides a comprehensive summary of the research done on SARS-CoV-2 pathology, diagnosis, therapeutics, and vaccines up to May 5. [ABSTRACT FROM AUTHOR]

Background: Considering the heavy economic burden of osteoporotic fractures, the limits of healthcare resources, and the recent availability of new anti-osteoporosis drugs, there is continuing interest in economic evaluation studies of osteoporosis management strategies. Objectives: This study aims to (1) systematically review recent economic evaluations of drugs for osteoporosis and (2) to apply an osteoporosis-specific guideline to critically appraise them. Methods: A literature search was undertaken using PubMed, EMBASE, National Health Service Economic Evaluation database, and the Cost-Effectiveness Analysis Registry to identify original articles containing economic evaluations of anti-osteoporosis drugs, published between 1 July, 2013 and 31 December, 2019. A recent European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases-International Osteoporosis Foundation (ESCEO-IOF) guideline for the conduct and reporting of economic evaluations in osteoporosis was used to assess the quality of included articles. Results: The database search retrieved 3860 records, of which 27 studies fulfilled the inclusion criteria. These studies were conducted in 15 countries; 12 active drugs were assessed, including various traditional pharmacological treatments such as bisphosphonates, raloxifene, strontium ranelate, denosumab, and teriparatide, and new agents such as abaloparatide, romosozumab, and gastro-resistant risedronate. Eight out of 12 studies that compared traditional oral bisphosphonates to other active interventions (denosumab, zoledronic acid, gastro-resistant risedronate, and teriparatide) suggested that the other active agents were generally cost-effective or dominant. Additionally, the cost-effectiveness of sequential therapy has recently been assessed and indications are that it can lead to extra health benefits (larger gains in quality-adjusted life-year). The key drivers of cost effectiveness included baseline fracture risk, drug effect on the risk of fractures, drug cost, and medication adherence/persistence. The current average score for quality assessment was 17 out of 25 (range 2–15); room for improvement was observed for most studies, which could potentially be explained by the fact that most studies were published prior to the osteoporosis-specific guideline. Greater adherence to guideline recommendations was expected for future studies. The quality of reporting was also suboptimal, especially with regard to treatment side effects, treatment effect after discontinuation, and medication adherence. Conclusions: This updated review provides an overview of recently published cost-effectiveness analyses. In comparison with a previous review, recent economic evaluations of anti-osteoporosis drugs were conducted in more countries and included more active drugs and sequential therapy as interventions/comparators. The updated economic evidence could help decision makers prioritize health interventions and the unmet/unreported quality issues indicated by the osteoporosis-specific guideline could be useful in improving the transparency, quality, and comparability of future economic evaluations in osteoporosis. [ABSTRACT FROM AUTHOR]

Neurological diseases and disorders are leading causes of death and disability worldwide. Many of these pathologies are associated with high levels of neuroinflammation and irreparable tissue damage. As the global burden of these pathologies continues to rise there is a significant need for the development of novel therapeutics. Due to their multipotent properties, stem cells have broad applications for tissue repair; additionally, stem cells have been shown to possess both immunomodulatory and neuroprotective properties. It is now believed that paracrine factors, such as extracellular vesicles (EVs), play a critical role in the functionality associated with stem cells. The diverse biological cargo contained within EVs are proposed to mediate these effects and, to date, the reparative and regenerative effects of stem cell EVs have been demonstrated in a wide range of cell types. While a high potential for their therapeutic use exists, there is a gap of knowledge surrounding their characterization, mechanisms of action, and how they may regulate cells of the CNS. Here, we report the isolation, characterization, and functional assessment of EVs from two sources of human stem cells, mesenchymal stem cells and induced pluripotent stem cells. We demonstrate the ability of these EVs to enhance the processes of cellular migration and angiogenesis, which are critical for both normal cellular development as well as cellular repair. Furthermore, we investigate their reparative effects on damaged cells, specifically those with relevance to the central nervous system. Collectively, our data highlight the similarities and differences among these EV populations and support the view that stem cells EV can be used to repair or partially reverse cellular damage. [ABSTRACT FROM AUTHOR]

HIV-1 viral transcription persists in patients despite antiretroviral treatment, potentially due to intermittent HIV-1 LTR activation. While several mathematical models have been explored in the context of LTR-protein interactions, in this work for the first time HIV-1 LTR model featuring repressed, intermediate, and activated LTR states is integrated with generation of long (env) and short (TAR) RNAs and proteins (Tat, Pr55, and p24) in T-cells and macrophages using both cell lines and infected primary cells. This type of extended modeling framework allows us to compare and contrast behavior of these two cell types. We demonstrate that they exhibit unique LTR dynamics, which ultimately results in differences in the magnitude of viral products generated. One of the distinctive features of this work is that it relies on experimental data in reaction rate computations. Two RNA transcription rates from the activated promoter states are fit by comparison of experimental data to model predictions. Fitting to the data also provides estimates for the degradation/exit rates for long and short viral RNA. Our experimentally generated data is in reasonable agreement for the T-cell as well macrophage population and gives strong evidence in support of using the proposed integrated modeling paradigm. Sensitivity analysis performed using Latin hypercube sampling method confirms robustness of the model with respect to small parameter perturbations. Finally, incorporation of a transcription inhibitor (F07#13) into the governing equations demonstrates how the model can be used to assess drug efficacy. Collectively, our model indicates transcriptional differences between latently HIV-1 infected T-cells and macrophages and provides a novel platform to study various transcriptional dynamics leading to latency or activation in numerous cell types and physiological conditions. [ABSTRACT FROM AUTHOR]

The identification of tumor antigens capable of eliciting an immune response in vivo may be an effective method to identify therapeutic cancer targets. We have developed a method to identify such antigens using frozen tumor-draining lymph node samples from breast cancer patients. Immune responses in tumor-draining lymph nodes were identified by immunostaining lymph node sections for B-cell markers (CD20&CD23) and Ki67 which revealed cell proliferation in germinal center zones. Antigen-dependent somatic hypermutation (SH) and clonal expansion (CE) were present in heavy chain variable (VH) domain cDNA clones obtained from these germinal centers, but not from Ki67 negative germinal centers. Recombinant VH single-domain antibodies were used to screen tumor proteins and affinity select potential tumor antigens. Neuroplastin (NPTN) was identified as a candidate breast tumor antigen using proteomic identification of affinity selected tumor proteins with a recombinant VH single chain antibody. NPTN was found to be highly expressed in approximately 20% of invasive breast carcinomas and 50% of breast carcinomas with distal metastasis using a breast cancer tissue array. Additionally, NPTN over-expression in a breast cancer cell line resulted in a significant increase in tumor growth and angiogenesis in vivo which was related to increased VEGF production in the transfected cells. These results validate NPTN as a tumor-associated antigen which could promote breast tumor growth and metastasis if aberrantly expressed. These studies also demonstrate that humoral immune responses in tumor-draining lymph nodes can provide antibody reagents useful in identifying tumor antigens with applications for biomarker screening, diagnostics and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Tuberculosis remains a significant global health challenge, with central nervous system tuberculosis (CNS-TB) posing a substantial threat, accounting for 1–10% of all tuberculosis cases. This article explores the diverse manifestations of CNS-TB in children, with a particular focus on tuberculous meningitis and tuberculomas, as well as their associated complications. Diagnostic imaging, including CT and MRI, plays a crucial role in the early detection of CNS-TB. The article emphasizes the pivotal role of imaging in the diagnosis and management of these manifestations, underscoring the importance of early recognition by healthcare professionals. Ultimately, raising awareness among pediatric radiologists, pediatricians, and pediatric neurologists is crucial for prompt intervention and improved outcomes in cases of CNS-TB. [ABSTRACT FROM AUTHOR]

The dorsal raphe (DR) is a heterogeneous nucleus containing dopamine (DA), serotonin (5HT), γ-aminobutyric acid (GABA) and glutamate neurons. Consequently, investigations of DR circuitry require Cre-driver lines that restrict transgene expression to precisely defined cell populations. Here, we present a systematic evaluation of mouse lines targeting neuromodulatory cells in the DR. We find substantial differences in specificity between lines targeting DA neurons, and in penetrance between lines targeting 5HT neurons. Using these tools to map DR circuits, we show that populations of neurochemically distinct DR neurons are arranged in a stereotyped topographical pattern, send divergent projections to amygdala subnuclei, and differ in their presynaptic inputs. Importantly, targeting DR DA neurons using different mouse lines yielded both structural and functional differences in the neural circuits accessed. These results provide a refined model of DR organization and support a comparative, case-by-case evaluation of the suitability of transgenic tools for any experimental application. In addition to serotonin neurons, the dorsal raphe nucleus (DR) also contains dopamine, glutamate, and GABA neurons. Here, the authors systematically compare the neurochemical identity, cell type specificity, anatomical distribution, and connectivity of DR cells targeted by commonly used Cre lines. [ABSTRACT FROM AUTHOR]