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1.
Nutrients ; 16(13)2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38999856

ABSTRACT

The collective meals market generates significant revenue for the world economy. Food services are responsible for consuming large amounts of water and energy, as well as generating a substantial volume of waste, which is often improperly disposed of. Given the unchecked expansion of food services, the lack of proper management of environmental resources can undermine sustainability principles, posing a threat to future generations. This scoping review aimed to synthesize the existing scientific literature on carbon and water footprints in food services, describing the main methods and tools used and what strategies have been proposed to mitigate the high values of these footprints. The search for articles was performed on 6 June 2024 in seven electronic databases, using MeSH Terms and adaptations for each database from database inception. The search for local studies was complemented by a manual search in the list of references of the studies selected to compose this review. It included quantitative studies assessing footprints (water or carbon) in food services and excluded reviews, studies that reported footprints for diets, and protocols. A total of 2642 studies were identified, and among these, 29 were selected for this review. According to the findings, it was observed that meats, especially beef, contribute more to water and carbon footprint compared to other proteins. Mitigation strategies for the water footprint include promoting plant-based diets, menu changes, and awareness.


Subject(s)
Carbon Footprint , Food Services , Humans , Conservation of Natural Resources , Water , Environment , Meat , Animals
2.
ASAIO J ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38950201

ABSTRACT

Sublethal damage to red blood cells (RBCs) during extracorporeal life support (ECLS) may lead to RBC loss. Using flow cytometry, phosphatidylserine-positive (PhS+) RBCs and RBC extracellular vesicles were quantified as measures of sublethal RBC injury in 41 pediatric ECLS runs, stored RBC units, and normal adult subjects. We estimated the clearance half-life of PhS+ RBCs and compared the rates of RBC loss during pediatric ECLS due to phlebotomy, intravascular hemolysis, and extravascular clearance of PhS+ RBCs. Extracorporeal life support patients had 0.9% PhS+ RBCs, sixfold higher than normal subjects (p < 0.0001). Phosphatidylserine-positive RBCs were increased in stored RBC units (twofold in whole blood derived units, p = 0.0013; 12-fold in apheresis RBC units, p < 0.0001). Phosphatidylserine-positive RBCs were cleared with an average half-life of 15 hours. During ECLS, PhS+ RBC clearance accounted for 7% of RBC loss (1-60%), phlebotomy 12%, and intravascular hemolysis 12%. Increasing PhS+ RBCs occurred in 40% of patients that died on ECLS. Red blood cell extracellular vesicles, another marker of red cell injury/activation, were elevated fivefold during ECLS. Phosphatidylserine exposure on RBCs is increased during ECLS, marking these cells for extravascular clearance with a half-life of ~15 hours and accounting for ~7% of RBC loss.

3.
PLoS One ; 19(7): e0304952, 2024.
Article in English | MEDLINE | ID: mdl-39024308

ABSTRACT

BACKGROUND: While the existence of a complex variety of casual sexual relationships (CSRs) has been acknowledged, studies rarely describe the prevalence of condom use across these relationships or how their hybrid nature, specifically relationship characteristics, affect condom use. This study aims to describe condom use within committed relationships and various types of casual sexual relationships (CSRs), examining the influence of relationship characteristics on condom use among culturally validated relationship types (committed, friends with benefits, hookups, booty call). METHODS: Emerging adults (N = 728, 18-29 years, M = 22.56; SD = 3.01) completed a survey with four blocks: sociodemographics; brief sexual history; relationships over the previous year; and current relationship, assessing relationship type, ten relationship characteristics (e.g., commitment, emotional and sexual exclusivity, partner acquaintance, sexual involvement) and condom use (vaginal, oral, and anal), operationalized by three measures (use at last encounter, likert-type scale and percentage of use). RESULTS: The results showed patterns in condom use by relationship type and illuminated how relationship characteristics-grouped into three factors: commitment, intimacy, and sexuality-mediate condom use. Condom use was more frequent in vaginal than anal and oral sex, and less frequent in committed relationships. No significant differences were found in condom use in vaginal sex between committed relationships and hookups, with condom in these relationships being significantly lower than in booty call. Intimacy mediated between all contrasts tested and condom use in vaginal sex, while sexuality mediated between committed vs. CSRs and condom use in anal and oral sex. CONCLUSIONS: Findings point to the need of considering the diversity of CSRs for understanding condom use and highlight the role of intimacy as a relevant mechanism associated with condom use in vaginal sex and of sexuality in oral and anal sex, which should be taken into consideration in the tailoring of health promoting efforts.


Subject(s)
Condoms , Sexual Behavior , Sexual Partners , Humans , Condoms/statistics & numerical data , Female , Male , Adult , Adolescent , Young Adult , Sexual Partners/psychology , Sexual Behavior/psychology , Safe Sex/statistics & numerical data , Surveys and Questionnaires , Interpersonal Relations
4.
Animals (Basel) ; 14(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38891678

ABSTRACT

Insects have been consumed for time immemorial in many regions of the globe. However, in other parts, they are not traditionally eaten. Because they are a more sustainable source of animal protein and provide valuable nutrients as well as bioactive compounds with beneficial effects on the human body, their consumption is encouraged. Knowledge can serve as a tool for better acceptance of insects as food. In this context, the present work investigated the knowledge about the nutritional value and health effects of edible insects in different countries. Data were collected by employing a questionnaire survey translated into the different languages of all participating countries and were treated using statistical tools. A total of 7222 responses were obtained. The results indicated that for many issues, the participants manifested a neutral opinion (neither agree nor disagree), but the participants who manifested agreement/disagreement were generally well informed. They were also able to identify untrue facts and answer accordingly by disagreeing. Factor analysis showed four groups of questions: nutritive value, negative perception and risks, safety and benefits of insects and contamination and harmful components. Finally, significant differences were observed according to the sociodemographic variables studies (sex, age, education, living environment and country), with age and country being the most influential of the sociodemographic factors on knowledge. Therefore, increasing knowledge is envisaged as an essential factor in augmenting the recognition of edible insects as a nutritional food, presenting health benefits apart from being a more sustainable source of animal protein when compared with beef or pork meats.

5.
Can J Respir Ther ; 60: 68-85, 2024.
Article in English | MEDLINE | ID: mdl-38828206

ABSTRACT

Introduction: Pilates exercise may complement traditional pulmonary rehabilitation in individuals with chronic obstructive pulmonary disease (COPD). The objective was to analyze the effects of adding a six-month Pilates exercise program to a three-month pulmonary rehabilitation for individuals with COPD. Methods: Thirty-five participants with COPD (GOLD B) were assigned to the intervention (n=14) or control (n=21) group. Both groups received an initial three months of a pulmonary rehabilitation program. The intervention group further underwent six months of pilates. Participants were evaluated at baseline and at three, six, and nine months. Lung function and strength of respiratory muscles were defined as primary outcomes. Secondary outcomes included cardiac, physical function, and exacerbation episodes. Results: There were no consistent statistically significant differences between groups for the lung function outcomes (p\<0.05). Maximal inspiratory and expiratory pressure increased significantly at three months in both groups (p\<0.05). It was significantly superior in the intervention group at nine months for maximal inspiratory pressure (p=0.005) and six and nine months for maximal expiratory pressure (p=0.027 and p\<0.001, respectively). Changes in muscle strength (knee extension and handgrip) were comparable between groups (p>0.05), but exercise-induced fatigue and balance were significantly superior in the intervention group at the six- and nine-month follow-ups (p\<0.05). Discussion: Pilates exercise programs may be implemented to augment traditional pulmonary rehabilitation with the goal of improving the strength of respiratory muscles. Conclusion: Adding a Pilates exercise program to pulmonary rehabilitation resulted in superior strength of respiratory muscles, higher resistance to exercise-induced fatigue, and improved balance.

6.
J Exp Biol ; 227(14)2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38873751

ABSTRACT

The influence of light spectral properties on circadian rhythms is of substantial interest to laboratory-based investigation of the circadian system and to field-based understanding of the effects of artificial light at night. The trade-offs between intensity and spectrum regarding masking behaviors are largely unknown, even for well-studied organisms. We used a custom LED illumination system to document the response of wild-type house mice (Mus musculus) to 1-h nocturnal exposure of all combinations of four intensity levels (0.01, 0.5, 5 and 50 lx) and three correlated color temperatures (CCT; 1750, 1950 and 3000 K). Higher intensities of light (50 lx) suppressed cage activity substantially, and consistently more for the higher CCT light (91% for 3000 K, 53% for 1750 K). At the lowest intensity (0.01 lx), mean activity was increased, with the greatest increases for the lowest CCT (12.3% increase at 1750 K, 3% increase at 3000 K). Multiple linear regression confirmed the influence of both CCT and intensity on changes in activity, with the scaled effect size of intensity 3.6 times greater than that of CCT. Activity suppression was significantly lower for male than for female mice. Assessment of light-evoked cFos expression in the suprachiasmatic nucleus at 50 lx showed no significant difference between high and low CCT exposure. The significant differences by spectral composition illustrate a need to account for light spectrum in circadian studies of behavior, and confirm that spectral controls can mitigate some, but certainly not all, of the effects of light pollution on species in the wild.


Subject(s)
Circadian Rhythm , Light , Lighting , Animals , Mice/physiology , Male , Circadian Rhythm/physiology , Circadian Rhythm/radiation effects , Female , Behavior, Animal/radiation effects , Behavior, Animal/physiology , Motor Activity/radiation effects , Temperature
7.
J Proteomics ; 304: 105229, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-38880355

ABSTRACT

Mass-tolerant open search methods allow the high-throughput analysis of modified peptides by mass spectrometry. These techniques have paved the way to unbiased analysis of post-translational modifications in biological contexts, as well as of chemical modifications produced during the manipulation of protein samples. In this work, we have analyzed in-depth a wide variety of samples of different biological origin, including cells, extracellular vesicles, secretomes, centrosomes and tissue preparations, using Comet-ReCom, a recently improved version of the open search engine Comet-PTM. Our results demonstrate that glutamic acid residues undergo intensive methyl esterification when protein digestion is performed using in-gel techniques, but not using gel-free approaches. This effect was highly specific to Glu and was not found for other methylable residues such as Asp.


Subject(s)
Glutamic Acid , Methanol , Methanol/chemistry , Methylation , Humans , Glutamic Acid/metabolism , Protein Processing, Post-Translational , Proteomics/methods , Animals
9.
Disabil Health J ; 17(3): 101625, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38839558

ABSTRACT

NARRATIVE SUMMARY: The formation of a patient-reported outcomes registry to provide information about functional changes and pain among adults with cerebral palsy (CP) was identified as a priority to address the gap in knowledge and practice about aging and CP. The Cerebral Palsy Research Network collaborated with consumers, clinicians, and researchers to create an interactive internet platform, MyCP, to host a Community Registry. MyCP also provides educational programming, access to webinars and community forums, and fitness opportunities. The registry hosts surveys on function and pain for adults with CP, which provide cross-sectional and longitudinal data about these important issues. Surveys include previously validated measures with normative values that have been used with other populations and investigator developed questions. Enrollment in the registry is growing but needs to reflect the population of adults with CP, which limits generalizability. Future initiatives involve strategies to increase consumer engagement and enrollment.


Subject(s)
Cerebral Palsy , Disabled Persons , Pain , Registries , Humans , Adult , Disabled Persons/statistics & numerical data , Internet , Surveys and Questionnaires , Patient Reported Outcome Measures , Cross-Sectional Studies
10.
bioRxiv ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38766112

ABSTRACT

Sleep disturbances are common features of neurodegenerative disorders including Huntington's disease (HD). The sleep and circadian disruptions are recapitulated in animal models, and these models provide the opportunity to evaluate whether circadian interventions can be effective countermeasures for neurodegenerative disease. Time restricted feeding (TRF) interventions successfully improve activity rhythms, sleep behavior and motor performance in mouse models of HD. Seeking to determine if these benefits of scheduled feeding extend to physiological measures of sleep, electroencephalography (EEG) was used to measure sleep/wake states and polysomnographic patterns in adult mice (six mo-old) under TRF and ad lib feeding (ALF). With each diet, both male and female wild-type (WT) and bacterial artificial chromosome transgenic (BACHD) mice were evaluated. Our findings show that male, but not female, BACHD mice exhibited significant changes in the temporal patterning of wake and nonrapid eye movement (NREM) sleep. The TRF intervention reduced the inappropriate early morning activity by increasing NREM sleep in the male BACHD mice. In addition, the scheduled feeding reduced sleep fragmentation (# bouts) in the male BACHD mice. The phase of the rhythm in rapid-eye movement (REM) sleep was significantly altered by the scheduled feeding. The treatment did impact the power spectral curves during the day in male but not female mice. Sleep homeostasis, as measured by the response to six hours of gentle handling, was not altered by the diet. Thus, TRF improves the temporal patterning and fragmentation of NREM sleep without impacting sleep homeostasis. This work adds critical support to the view that sleep is a modifiable risk factor in neurodegenerative diseases.

11.
Hemasphere ; 8(5): e64, 2024 May.
Article in English | MEDLINE | ID: mdl-38756352

ABSTRACT

Advancements in comprehending myelodysplastic neoplasms (MDS) have unfolded significantly in recent years, elucidating a myriad of cellular and molecular underpinnings integral to disease progression. While molecular inclusions into prognostic models have substantively advanced risk stratification, recent revelations have emphasized the pivotal role of immune dysregulation within the bone marrow milieu during MDS evolution. Nonetheless, immunotherapy for MDS has not experienced breakthroughs seen in other malignancies, partly attributable to the absence of an immune classification that could stratify patients toward optimally targeted immunotherapeutic approaches. A pivotal obstacle to establishing "immune classes" among MDS patients is the absence of validated accepted immune panels suitable for routine application in clinical laboratories. In response, we formed International Integrative Innovative Immunology for MDS (i4MDS), a consortium of multidisciplinary experts, and created the following recommendations for standardized methodologies to monitor immune responses in MDS. A central goal of i4MDS is the development of an immune score that could be incorporated into current clinical risk stratification models. This position paper first consolidates current knowledge on MDS immunology. Subsequently, in collaboration with clinical and laboratory specialists, we introduce flow cytometry panels and cytokine assays, meticulously devised for clinical laboratories, aiming to monitor the immune status of MDS patients, evaluating both immune fitness and identifying potential immune "risk factors." By amalgamating this immunological characterization data and molecular data, we aim to enhance patient stratification, identify predictive markers for treatment responsiveness, and accelerate the development of systems immunology tools and innovative immunotherapies.

12.
Public Health Rep ; : 333549241249339, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780024

ABSTRACT

OBJECTIVES: People with childhood-onset disabilities are living into adulthood, and the prevalence of smoking and illicit drug use among adults with disabilities is high. We evaluated the relationship between disability status and age of disability onset, current cigarette smoking status, and heavy alcohol drinking. METHODS: We conducted a secondary data analysis of the National Health Interview Survey (NHIS), a US survey on illness and disability. Among 2020 NHIS participants aged 22-80 years (n = 28 225), we compared self-reported prevalence of current cigarette smoking and heavy alcohol drinking among those with and without disabilities and among those with childhood- versus adult-onset disabilities. We used adjusted logistic regression analysis to calculate the adjusted odds ratios (AORs) of current smoking and heavy alcohol drinking based on disability status and age of disability onset. RESULTS: Compared with adults without disabilities, adults with disabilities were significantly more likely to report current smoking (23.5% vs 11.2%; P < .001) and significantly less likely to report heavy alcohol drinking (5.3% vs 7.4%; P = .001). The prevalence of these behaviors did not vary significantly by age of disability onset. In adjusted logistic regression models, adults with disabilities had significantly higher odds of current smoking (AOR = 1.76; 95% CI, 1.53-2.03) and similar odds of heavy alcohol drinking (AOR = 0.82; 95% CI, 0.65-1.04) compared with adults without disabilities. The odds of these health behaviors did not vary significantly by age of disability onset. CONCLUSIONS: Adults with disabilities overall may be at high risk for these unhealthy behaviors, particularly smoking, regardless of age of disability onset. Routine screening and cessation counseling related to smoking and unhealthy alcohol use are important for all people with disabilities.

13.
J Phys Chem Lett ; 15(19): 5231-5238, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38718187

ABSTRACT

A sterically encumbered trans-A2B-corrole possessing a perylenediimide (PDI) scaffold in close proximity to the macrocycle has been synthesized via a straightforward route. Electronic communication as probed via steady-state absorption or cyclic voltammetry is weak in the ground state, in spite of the corrole ring and PDI being bridged by an o-phenylene unit. The TDDFT excited-state geometry optimization suggests after excitation the interchromophoric distance is markedly reduced, thus enhancing the through-space electronic coupling between the corrole and the PDI. This is corroborated by the strong deviation of the emission spectrum originating from both PDI and corrole in the dyad. Selective excitation of both donor and acceptor units triggers efficient sub-picosecond electron transfer and hole transfer, respectively, followed by fast charge recombination. In comparison to previously studied corrole-PDI dyads, both charge separation and charge recombination occur faster, because of the structural relaxation in the excited state.

14.
Anim Reprod Sci ; : 107476, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38664134

ABSTRACT

Despite decades of research and handling of semen for use in artificial insemination (AI) and other assisted reproductive technologies, 5-10% of selected boar sires are still considered sub-fertile, escaping current assessment methods for sperm quality and resilience to preservation. As end-product, the ejaculate (emitted spermatozoa sequentially exposed to the composite seminal plasma, the SP) ought to define the homeostasis of the testes, the epididymis, and the accessory sexual glands. Yet, linking findings in the ejaculate to sperm production biology and fertility is suboptimal. The present essay critically reviews how the ejaculate of a fertile boar can help us to diagnose both reproductive health and resilience to semen handling, focusing on methods -available and under development- to identify suitable biomarkers for cryotolerance and fertility. Bulk SP, semen proteins and microRNAs (miRNAs) have, albeit linked to sperm function and fertility after AI, failed to enhance reproductive outcomes at commercial level, perhaps for just being components of a complex functional pathway. Hence, focus is now on the interaction sperm-SP, comparing in vivo with ex vivo, and regarding nano-sized lipid bilayer seminal extracellular vesicles (sEVs) as priority. sEVs transport fragile molecules (lipids, proteins, nucleic acids) which, shielded from degradation, mediate cell-to-cell communication with spermatozoa and the female internal genital tract. Such interaction modulates essential reproductive processes, from sperm homeostasis to immunological female tolerance. sEVs can be harvested, characterized, stored, and manipulated, e.g. can be used for andrological diagnosis, selection of breeders, and alternatively be used as additives to improve cryosurvival and fertility.

15.
Article in English | MEDLINE | ID: mdl-38643455

ABSTRACT

Estrone (E1) constitutes the primary component in oral conjugated equine estrogens (CEEs) and serves as the principal estrogen precursor in the female circulation in the post-menopause. E1 induces endothelium-dependent vasodilation and activate PI3K/NO/cGMP signaling. To assess whether E1 mitigates vascular dysfunction associated with postmenopause and explore the underlying mechanisms, we examined the vascular effects of E1 in ovariectomized (OVX) rats, a postmenopausal experimental model. Blood pressure was measured using tail-cuff plethysmography, and aortic rings were isolated to assess responses to phenylephrine, acetylcholine (ACh), and sodium nitroprusside. Responses to ACh in rings pre-incubated with superoxide dismutase (SOD), catalase (CAT), or apocynin were also evaluated. Protein expression of SOD, CAT, NOX1, NOX2, and NOX4 was determined by Western blotting. E1 treatment resulted in decreased body weight and retroperitoneal fat, increased uterine weight, and prevented elevated blood pressure in the OVX group. Furthermore, E1 improved endothelium-dependent ACh vasodilation, activated compensatory antioxidant mechanisms - i.e. increased SOD and CAT antioxidant enzymes activity, and decreased NOX4 expression. This, in turn, helped prevent oxidative stress and endothelial dysfunction in OVX rats. Additionally, E1 treatment reversed the increased total LDL cholesterol observed in the OVX group. The findings underscore protective effects of E1 on the cardiovascular system, counteracting OVX-related oxidative stress and endothelial dysfunction in Wistar rats. E1 exhibits promising therapeutic benefits for managing cardiovascular health, particularly in postmenopausal conditions.

16.
Theriogenology ; 223: 36-46, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38669840

ABSTRACT

In vitro embryo production (IVP) is of great importance to the porcine industry, as well as for basic research and biomedical applications. Despite the large efforts made in laboratories worldwide to address suboptimal culture conditions, porcine IVP remains inefficient. Nobiletin (Nob, 5,6,7,8,3',4' hexamethoxyflavone) supplementation to in vitro culture (IVC) medium, enhances in vitro embryo development in various species. However, its impact on the quality and developmental capacity of in vitro-produced pig embryos is yet to be established. This study evaluated the effects of different concentrations (2.5 and 5 µM) of Nob during the early culture of in vitro-produced pig embryos on embryo developmental competence, mitochondrial activity, lipid content, intracellular Reactive Oxygen Species (ROS) and Glutathione (GSH) content, Total Cell Number (TCN) per blastocyst, and expression of genes related to embryo development, quality and oxidative stress. Embryos cultured in medium without Nob supplementation and in medium supplemented with 0.01 % dimethyl sulfoxide (DMSO-vehicle for Nob) constituted the Control and DMSO groups, respectively. Embryo development rates were evaluated on Days 2, 6 and 7 of IVC. Additionally, a representative group of embryos was selected to assess mitochondrial activity, lipid, ROS and GSH content (on Days 2 and 6 of IVC), TCN assessment and gene expression analyses (on Day 6 of IVC). No significant differences were observed in any of the parameters evaluated on Day 2 of IVC. In contrast, embryos cultured under the presence of Nob 2.5 showed higher developmental rates on Days 6 and 7 of IVC. In addition, Day 6 embryos showed increased mitochondrial activity, with decreased levels of ROS and GSH in the Nob 2.5 group compared to the other groups. Both Nob 2.5 and Nob 5 embryos showed higher TCN compared to the Control and DMSO groups. Furthermore, Nob 2.5 and Nob 5 upregulated the expression of Superoxide dismutase type 1 (SOD1) and Glucose-6-phosphate dehydrogenase (G6PDH) genes, which could help to counteract oxidative stress during IVC. In conclusion, the addition of Nob during the first 48 h of IVC increased porcine embryo development rates and enhanced their quality, including the upregulation of relevant genes that potentially improved the overall efficiency of the IVP system.


Subject(s)
Embryo Culture Techniques , Embryonic Development , Flavones , Animals , Embryonic Development/drug effects , Swine/embryology , Embryo Culture Techniques/veterinary , Flavones/pharmacology , Reactive Oxygen Species/metabolism , Oxidative Stress/drug effects , Fertilization in Vitro/veterinary , Glutathione/metabolism , Mitochondria/drug effects , Gene Expression Regulation, Developmental/drug effects
17.
CNS Neurosci Ther ; 30(4): e14727, 2024 04.
Article in English | MEDLINE | ID: mdl-38644593

ABSTRACT

AIMS: Ventral pathway circuits are constituted by the interconnected brain areas that are distributed throughout the brain. These brain circuits are primarily involved in processing of object related information in brain. However, their role in object recognition memory (ORM) enhancement remains unknown. Here, we have studied on the implication of these circuits in ORM enhancement and in reversal of ORM deficit in aging. METHODS: The brain areas interconnected to ventral pathway circuits in rat brain were activated by an expression of a protein called regulator of G-protein signaling 14 of 414 amino acids (RGS14414). RGS14414 is an ORM enhancer and therefore used here as a gain-in-function tool. ORM test and immunohistochemistry, lesions, neuronal arborization, and knockdown studies were performed to uncover the novel function of ventral pathway circuits. RESULTS: An activation of each of the brain areas interconnected to ventral pathway circuits individually induced enhancement in ORM; however, same treatment in brain areas not interconnected to ventral pathway circuits produced no effect. Further study in perirhinal cortex (PRh), area V2 of visual cortex and frontal cortex (FrC), which are brain areas that have been shown to be involved in ORM and are interconnected to ventral pathway circuits, revealed that ORM enhancement seen after the activation of any one of the three brain areas was unaffected by the lesions in other two brain areas either individually in each area or even concurrently in both areas. This ORM enhancement in all three brain areas was associated to increase in structural plasticity of pyramidal neurons where more than 2-fold higher dendritic spines were observed. Additionally, we found that an activation of either PRh, area V2, or FrC not only was adequate but also was sufficient for the reversal of ORM deficit in aging rats, and the blockade of RGS14414 activity led to loss in increase in dendritic spine density and failure in reversal of ORM deficit. CONCLUSIONS: These results suggest that brain areas interconnected to ventral pathway circuits facilitate ORM enhancement by an increase in synaptic connectivity between the local brain area circuits and the passing by ventral pathway circuits and an upregulation in activity of ventral pathway circuits. In addition, the finding of the reversal of ORM deficit through activation of an interconnected brain area might serve as a platform for developing not only therapy against memory deficits but also strategies for other brain diseases in which neuronal circuits are compromised.


Subject(s)
Brain , Memory Disorders , RGS Proteins , Recognition, Psychology , Animals , Recognition, Psychology/physiology , Male , Rats , RGS Proteins/metabolism , RGS Proteins/genetics , Neural Pathways , Aging/physiology
18.
JCI Insight ; 9(7)2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38587079

ABSTRACT

BACKGROUNDBroadly neutralizing monoclonal antibodies (bNAbs) represent a promising strategy for HIV-1 immunoprophylaxis and treatment. 10E8VLS and VRC07-523LS are bNAbs that target the highly conserved membrane-proximal external region (MPER) and the CD4-binding site of the HIV-1 viral envelope glycoprotein, respectively.METHODSIn this phase 1, open-label trial, we evaluated the safety and pharmacokinetics of 5 mg/kg 10E8VLS administered alone, or concurrently with 5 mg/kg VRC07-523LS, via s.c. injection to healthy non-HIV-infected individuals.RESULTSEight participants received either 10E8VLS alone (n = 6) or 10E8VLS and VRC07-523LS in combination (n = 2). Five (n = 5 of 8, 62.5%) participants who received 10E8VLS experienced moderate local reactogenicity, and 1 participant (n = 1/8, 12.5%) experienced severe local reactogenicity. Further trial enrollment was stopped, and no participant received repeat dosing. All local reactogenicity resolved without sequelae. 10E8VLS retained its neutralizing capacity, and no functional anti-drug antibodies were detected; however, a serum t1/2 of 8.1 days was shorter than expected. Therefore, the trial was voluntarily stopped per sponsor decision (Vaccine Research Center, National Institute of Allergy and Infectious Diseases [NIAID], NIH). Mechanistic studies performed to investigate the underlying reason for the reactogenicity suggest that multiple mechanisms may have contributed, including antibody aggregation and upregulation of local inflammatory markers.CONCLUSION10E8VLS resulted in unexpected reactogenicity and a shorter t1/2 in comparison with previously tested bNAbs. These studies may facilitate identification of nonreactogenic second-generation MPER-targeting bNAbs, which could be an effective strategy for HIV-1 immunoprophylaxis and treatment.TRIAL REGISTRATIONClinicaltrials.gov, accession no. NCT03565315.FUNDINGDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH.


Subject(s)
HIV Infections , HIV Seropositivity , HIV-1 , Humans , HIV Infections/drug therapy , HIV Infections/prevention & control , HIV Antibodies , Broadly Neutralizing Antibodies/pharmacology , Antibodies, Monoclonal/pharmacology
19.
Harmful Algae ; 133: 102599, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38485445

ABSTRACT

Cyanobacterial blooms present substantial challenges to managers and threaten ecological and public health. Although the majority of cyanobacterial bloom research and management focuses on factors that control bloom initiation, duration, toxicity, and geographical extent, relatively little research focuses on the role of loss processes in blooms and how these processes are regulated. Here, we define a loss process in terms of population dynamics as any process that removes cells from a population, thereby decelerating or reducing the development and extent of blooms. We review abiotic (e.g., hydraulic flushing and oxidative stress/UV light) and biotic factors (e.g., allelopathic compounds, infections, grazing, and resting cells/programmed cell death) known to govern bloom loss. We found that the dominant loss processes depend on several system specific factors including cyanobacterial genera-specific traits, in situ physicochemical conditions, and the microbial, phytoplankton, and consumer community composition. We also address loss processes in the context of bloom management and discuss perspectives and challenges in predicting how a changing climate may directly and indirectly affect loss processes on blooms. A deeper understanding of bloom loss processes and their underlying mechanisms may help to mitigate the negative consequences of cyanobacterial blooms and improve current management strategies.


Subject(s)
Cyanobacteria , Harmful Algal Bloom , Cyanobacteria/physiology
20.
Disabil Health J ; 17(3): 101593, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38433033

ABSTRACT

BACKGROUND: Adults with cerebral palsy (CP) have unique healthcare needs and risks, including high risk of functional decline. Understanding functional decline is an area of priority for CP research. OBJECTIVE: Describe factors associated with patient-reported changes in function among adults with CP living in the community. METHODS: Cross-sectional analysis of adult patient-reported outcomes collected by the CP Research Network (CPRN) Community Registry. RESULTS: Participants included 263 respondents (76% female (n = 200); mean age 42 years (SD 14); 95% White (n = 249); 92% non-Hispanic (n = 241)). Many reported functional changes, most commonly a decline in gross motor function since childhood (n = 158, 60%). Prevalence of gross motor decline varied significantly by Gross Motor Function Classification System (GMFCS) level (p < 0.001), but neither hand function decline (p = 0.196) nor communication decline (p = 0.994) differed by GMFCS. All types of decline increased with increasing age, with statistically significant differences between age groups (p < 0.001 gross motor; p = 0.003 hand function; p = 0.004 communication). Those with spastic CP (n = 178) most commonly reported gross motor functional decline (n = 108/178, 60.7%). However, the prevalence of gross motor decline did not significantly differ between those with spastic CP and those without spastic CP (p = 0.789). CONCLUSIONS: Many adults in the CPRN Community Registry reported functional decline, most commonly in gross motor function. Functional decline across domains increased with age. Further research into risk stratification and preventive and rehabilitative measures is needed to address functional decline across the lifespan.


Subject(s)
Cerebral Palsy , Patient Reported Outcome Measures , Registries , Humans , Cerebral Palsy/epidemiology , Cerebral Palsy/physiopathology , Female , Cross-Sectional Studies , Adult , Male , Middle Aged , Activities of Daily Living , Disabled Persons/statistics & numerical data , North America/epidemiology , Young Adult , Severity of Illness Index , Prevalence
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