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Journal of Integrative Neuroscience Jun 2024Alcohol abuse, a prevalent global health issue, is associated with the onset of cognitive impairment and neurodegeneration. Actin filaments (F-actin) and microtubules...
BACKGROUND
Alcohol abuse, a prevalent global health issue, is associated with the onset of cognitive impairment and neurodegeneration. Actin filaments (F-actin) and microtubules (MTs) polymerized from monomeric globular actin (G-actin) and tubulin form the structural basis of the neuronal cytoskeleton. Precise regulation of the assembly and disassembly of these cytoskeletal proteins, and their dynamic balance, play a pivotal role in regulating neuronal morphology and function. Nevertheless, the effect of prolonged alcohol exposure on cytoskeleton dynamics is not fully understood. This study investigates the chronic effects of alcohol on cognitive ability, neuronal morphology and cytoskeleton dynamics in the mouse hippocampus.
METHODS
Mice were provided access to 5% (v/v) alcohol in drinking water and were intragastrically administered 30% (v/v, 6.0 g/kg/day) alcohol for six weeks during adulthood. Cognitive functions were then evaluated using the Y maze, novel object recognition and Morris water maze tests. Hippocampal histomorphology was assessed through hematoxylin-eosin (HE) and Nissl staining. The polymerized and depolymerized states of actin cytoskeleton and microtubules were separated using two commercial assay kits and quantified by Western blot analysis.
RESULTS
Mice chronically exposed to alcohol exhibited significant deficits in spatial and recognition memory as evidenced by behavioral tests. Histological analysis revealed notable hippocampal damage and neuronal loss. Decreased ratios of F-actin/G-actin and MT/tubulin, along with reduced levels of polymerized F-actin and MTs, were found in the hippocampus of alcohol-treated mice.
CONCLUSIONS
Our findings suggest that chronic alcohol consumption disrupted the assembly of the actin cytoskeleton and MTs in the hippocampus, potentially contributing to the cognitive deficits and pathological injury induced by chronic alcohol intoxication.
Topics: Animals; Hippocampus; Microtubules; Actin Cytoskeleton; Male; Ethanol; Mice; Mice, Inbred C57BL; Central Nervous System Depressants; Disease Models, Animal; Behavior, Animal
PubMed: 38940085
DOI: 10.31083/j.jin2306118 -
Euro Surveillance : Bulletin Europeen... Jun 2024BackgroundSince its emergence in December 2019, over 700 million people worldwide have been infected with SARS-CoV-2 up to May 2024. While early rollout of mRNA...
A longitudinal study on SARS-CoV-2 seroconversion, reinfection and neutralisation spanning several variant waves and vaccination campaigns, Heinsberg, Germany, April 2020 to November 2022.
BackgroundSince its emergence in December 2019, over 700 million people worldwide have been infected with SARS-CoV-2 up to May 2024. While early rollout of mRNA vaccines against COVID-19 has saved many lives, there was increasing immune escape of new virus variants. Longitudinal monitoring of population-wide SARS-CoV-2 antibody responses from regular sample collection irrespective of symptoms provides representative data on infection and seroconversion/seroreversion rates.AimTo examine adaptive and cellular immune responses of a German SARS-CoV-2 outbreak cohort through several waves of infection with different virus variants.MethodsUtilising a 31-month longitudinal seroepidemiological study (n = 1,446; mean age: 50 years, range: 2-103) initiated during the first SARS-CoV-2 superspreading event (February 2020) in Heinsberg, Germany, we analysed acute infection, seroconversion and virus neutralisation at five follow-up visits between October 2020 and November 2022; cellular and cross-protective immunity against SARS-CoV-2 Omicron variants were also examined.ResultsSARS-CoV-2 spike (S)-specific IgAs decreased shortly after infection, while IgGs remained stable. Both increased significantly after vaccination. We predict an 18-month half-life of S IgGs upon infection. Nucleocapsid (N)-specific responses declined over 12 months post-infection but increased (p < 0.0001) during Omicron. Frequencies of SARS-CoV-2-specific TNF-alpha+/IFN-gamma+ CD4+ T-cells declined over 12 months after infection (p < 0.01). SARS-CoV-2 S antibodies and neutralisation titres were highest in triple-vaccinated participants infected between April 2021 and November 2022 compared with infections between April 2020 and January 2021. Cross neutralisation against Omicron BQ.1.18 and XBB.1.5 was very low in all groups.ConclusionInfection and/or vaccination did not provide the population with cross-protection against Omicron variants.
Topics: Humans; SARS-CoV-2; COVID-19; Seroconversion; Longitudinal Studies; Germany; Antibodies, Viral; Middle Aged; Adult; Male; Antibodies, Neutralizing; Female; COVID-19 Vaccines; Aged; Reinfection; Seroepidemiologic Studies; Adolescent; Young Adult; Child; Child, Preschool; Aged, 80 and over; Vaccination
PubMed: 38940003
DOI: 10.2807/1560-7917.ES.2024.29.26.2300659 -
Journal of Global Health Jun 2024Malaria infection during pregnancy is associated with an increased risk of maternal death, as well as adverse birth outcomes. Intermittent preventive treatment in...
BACKGROUND
Malaria infection during pregnancy is associated with an increased risk of maternal death, as well as adverse birth outcomes. Intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is known to improve pregnancy outcomes. However, the coverage of IPTp-SP in antenatal care (ANC) in sub-Saharan Africa remains well below the target. This study aims to estimate to what extent malaria service readiness affects the uptake of IPTp-SP during ANC visits in sub-Saharan African countries.
METHODS
This study included 3267 pregnant women attending ANC for the first time and 2797 pregnant women who had attended ANC more than a month ago in six sub-Saharan African countries. The readiness of malaria services at each institution includes four indicators: the presence of IPTp-SP guidelines, SP availability, integration of IPTp-SP service into ANC, and provider training on IPTp-SP. The outcome variable indicates whether a pregnant woman received IPTp-SP at her current ANC visit. A modified Poisson regression model estimated the associations between malaria service readiness and IPTp-SP uptake for women eligible for the first and subsequent doses.
RESULTS
For women eligible for their first dose, visiting an institution with available SP was associated with an increased probability of receiving IPTp-SP (risk ratio (RR) = 1.43; 95% confidence interval (CI) = 1.22 to 1.67, P < 0.001). For women who were eligible for their next dose, the availability of SP (RR = 1.17; 95% CI = 1.04 to 1.32, P = 0.008) and integration of IPTp-SP service into ANC (RR = 1.82; 95% CI = 1.21 to 2.74, P = 0.004) in the institution were associated with increased likelihood of IPTp-SP uptake. Counterfactual predictions indicated that enhanced provider training could boost IPTp-SP uptake in high-uptake countries, while better SP availability and IPTp-SP integration into ANC would significantly impact low-uptake countries.
CONCLUSIONS
For better IPTp-SP coverage, strategies should be customised. High uptake countries should focus on provider training, while low uptake ones should ensure IPTp-SP availability and service integration.
Topics: Humans; Female; Pregnancy; Antimalarials; Africa South of the Sahara; Pyrimethamine; Sulfadoxine; Malaria; Pregnancy Complications, Parasitic; Adult; Drug Combinations; Prenatal Care; Young Adult; Adolescent; Patient Acceptance of Health Care
PubMed: 38939971
DOI: 10.7189/jogh.14.04112 -
Frontiers in Bioscience (Elite Edition) Jun 2024(), also called biotech yeast, is a yeast species with many applications in the biotechnology and pharmaceutical industries. This methylotrophic yeast has garnered... (Review)
Review
(), also called biotech yeast, is a yeast species with many applications in the biotechnology and pharmaceutical industries. This methylotrophic yeast has garnered significant interest as a platform for the production of recombinant proteins. Numerous benefits include effective secretory expression that facilitates the easy purification of heterologous proteins, high cell density with rapid growth, post-translational changes, and stable gene expression with integration into the genome. In the last thirty years, has also been refined as an adaptable cell factory that can produce hundreds of biomolecules in a laboratory setting and on an industrial scale. Indeed, over 5000 recombinant proteins have been generated so far using the expression method, which makes up 30% of the total cell protein or 80% of the total released protein. has been used to manufacture more than 70 commercial products in addition to over 300 industrial processes that have been granted licenses. Among these are useful enzymes for industrial biotechnology, including xylanase, mannanase, lipase, and phytase. The others are biopharmaceuticals, which include human serum albumin, insulin, hepatitis B surface antigen, and epidermal growth factor. Compared to other expression systems, this yeast is also considered a special host for synthesizing subunit vaccines, which have recently been supplanted by alternative vaccination types, such as inactivated/killed and live attenuated vaccines. Moreover, efficient production of recombinant proteins is achieved through multi-level optimization methods, such as codon bias, gene dosage, promoters, signal peptides, and environmental factors. Therefore, although expression systems are efficient and simple with clearly established process procedures, it is still necessary to determine the ideal conditions since these vary depending on the target protein to ensure the highest recombinant protein generation. This review addresses the expression system, its importance in industrial and biopharmaceutical protein production, and some bioprocessing and genetic modification strategies for efficient protein production. will eventually continue contributing as a potent expression system in research areas and industrial applications.
Topics: Saccharomycetales; Recombinant Proteins; Biological Products; Biotechnology; Pichia
PubMed: 38939917
DOI: 10.31083/j.fbe1602019 -
Innovation in Aging 2024Exercise may reverse functional decline in hospitalized older adults, but the optimal duration is unclear. This study examined the potential relationship between...
Dose-Response Relationship Between Exercise Duration and Enhanced Function and Cognition in Acutely Hospitalized Older Adults: A Secondary Analysis of a Randomized Clinical Trial.
BACKGROUND AND OBJECTIVES
Exercise may reverse functional decline in hospitalized older adults, but the optimal duration is unclear. This study examined the potential relationship between in-hospital multicomponent exercise program duration and changes in physical function, cognition, and muscle function to maximize exercise-related health benefits in acutely hospitalized older patients.
RESEARCH DESIGN AND METHODS
This secondary analysis of a multicenter randomized controlled trial examined the relationship between the duration of an in-hospital multicomponent exercise program and changes in physical function, cognition, and muscle strength in 570 acutely hospitalized older adults. Participants completed 3, 4, or 5-7 consecutive days of exercise based on the progression of their acute medical illness. The acute clinical condition of the older patients was similar across the study groups (i.e., 3/4/5-7 days) at admission. Outcomes included the Short Physical Performance Battery (SPPB) for functional capacity, Gait Velocity Test for gait speed, handgrip for muscle strength, and cognitive tests.
RESULTS
Of the 570 patients included in the analysis, 298 were women (52.3%), and the mean () age was 87.3 (4.8) years. Exercise groups increased SPPB scores compared with controls, with gains of 1.09 points after three days, 1.97 points after four days, and 2.02 points after 5-7 days ( < .001). The 4-day program showed the most significant benefit for functional capacity. Gait velocity increased by 0.11 m/s after 4 and 5-7 days ( = .032). Similar dose-response relationships were seen for handgrip strength and cognition, with 5-7 days showing more significant gains than three days ( < .05).
DISCUSSION AND IMPLICATIONS
Multicomponent exercise programs enhance physical and cognitive function in hospitalized older adults, regardless of exercise dosage. A 4-day program significantly boosts functional capacity, although 5-7 days improves handgrip strength and cognition, highlighting the importance of exercise dosage in countering functional decline. Implementing evidence-based inpatient exercise prescriptions can help reverse muscle weakness and improve cognitive and physical function.Clinical Trial Registration: NCT04600453.
PubMed: 38939651
DOI: 10.1093/geroni/igae053 -
International Journal of Public Health 2024The adoption of vaccines was a crucial factor in overcoming the COVID-19 pandemic. However, vaccination rates between rural and urban areas varied greatly. In this...
OBJETIVES
The adoption of vaccines was a crucial factor in overcoming the COVID-19 pandemic. However, vaccination rates between rural and urban areas varied greatly. In this paper, our objective is to understand the individual and institutional factors associated with the uptake of vaccines in remote rural areas in Colombia.
METHODS
We interviewed a random sample of 800 households (1,592 individuals) in remote rural areas of Antioquia (Colombia) during February 2022 when vaccinations were available. Then, we use a linear probability model to explain the uptake of the COVID-19 vaccine.
RESULTS
The results indicate that the probability of having at least the first dose of the COVID-19 vaccine is positively associated with access to information, trust in police and army, and the perceived risk of contracting COVID-19. Trust in the church is negatively related to vaccination.
CONCLUSION
Institutions can play a critical role in the management of pandemics. Timely information on the risks associated with the disease and perceived riskiness are key factors that mobilize the population to take the COVID-19 vaccine.
Topics: Humans; Colombia; COVID-19; COVID-19 Vaccines; Rural Population; Female; Male; Adult; Middle Aged; SARS-CoV-2; Vaccination; Young Adult; Adolescent; Trust
PubMed: 38939517
DOI: 10.3389/ijph.2024.1606689 -
Case Reports in Infectious Diseases 2024Coadministering two different classes of antibiotics as empirical therapy can be critical in treating healthcare-associated infections in hospitals. Herein, we report a...
Coadministering two different classes of antibiotics as empirical therapy can be critical in treating healthcare-associated infections in hospitals. Herein, we report a case of acute kidney injury (AKI) caused by coadministration of vancomycin with high-dose meropenem that manifested as a rapid increase in serum creatinine levels and an associated increase in vancomycin trough concentrations. The patient was diagnosed with meningioma at 50 years and was followed up regularly. The patient underwent surgery and antibiotic treatment between 63 and 66 years for suspected meningitis and pneumonia. Coadministration of vancomycin with high-dose meropenem (6.0 g/day) caused AKI; however, no AKI occurred when vancomycin was administered alone or with a low dose of meropenem (1.5 or 3.0 g/day). To our knowledge, this report is the first to show that administering different dosages of meropenem in combination with vancomycin may contribute to the risk of developing AKI. We suggest that coadministered vancomycin and high-dose meropenem (6.0 g/day) may increase the risk of AKI. Our report adds to the limited literature documenting the coadministration of vancomycin with varying doses of meropenem and its impact on the risk of AKI and highlights the importance of investigating AKI risk in response to varying dosages of meropenem when it is coadministered with vancomycin.
PubMed: 38939108
DOI: 10.1155/2024/7956014 -
Frontiers in Neurology 2024Peripheral nerve injuries (PNI) represent one of the primary neuropathies leading to lifelong disability. Nerve regeneration and targeted muscle atrophy stand as the two... (Review)
Review
Peripheral nerve injuries (PNI) represent one of the primary neuropathies leading to lifelong disability. Nerve regeneration and targeted muscle atrophy stand as the two most crucial factors influencing functional rehabilitation post peripheral nerve injury. Over time, traditional Chinese medicine (TCM) rehabilitation approaches such as acupuncture, Tuina, and microneedles serve as pivot means to activate the regeneration of injured nerve Schwann cells. By promoting axon regeneration, these approaches can accomplish nerve repair, reconstruction, and functional rehabilitation. Although TCM rehabilitation approaches have clinically demonstrated effectiveness in promoting the repair and regeneration of PNI, the related molecular mechanisms remain unclear. This significantly hampers the application and promotion of TCM rehabilitation in PNI recovery. Therefore, deeply delving into the cellular and molecular mechanisms of TCM rehabilitation technologies to foster nerve regeneration stands as the most pressing issue. On the other hand, in recent years, novel biomaterials represented by hydrogels, microfluidic platforms, and new chitosan scaffolds have showed their unique roles in treating various degrees of nerve injury. These methods exhibit immense potential in conducting high-throughput cell and organoid culture and synthesizing diverse tissue engineering scaffolds and drug carriers. We believe that the combination of TCM rehabilitation technology and novel biomaterials can more effectively address precise treatment issues such as identification of treatment target and dosage control. Therefore, this paper not only summarizes the molecular mechanisms of TCM rehabilitation technology and novel biomaterials in treating peripheral nerve injury individually, but also explores the research direction of precise treatment by integrating the two at both macro and micro levels. Such integration may facilitate the exploration of cellular and molecular mechanisms related to neurodegeneration and regeneration, providing a scientific and theoretical foundation for the precise functional rehabilitation of PNI in the future.
PubMed: 38938781
DOI: 10.3389/fneur.2024.1421772 -
PeerJ 2024Whether the relationship of intracerebral bleeding risk with lipid profile may vary by sex remains unclear. This study aims to investigate potential sex differences in... (Observational Study)
Observational Study
Sex difference in the association between triglyceride and intracerebral bleeding risk after intravenous thrombolysis for acute ischemic stroke, a multi-center retrospective study.
BACKGROUND
Whether the relationship of intracerebral bleeding risk with lipid profile may vary by sex remains unclear. This study aims to investigate potential sex differences in the association between lipid profile and the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) who received intravenous thrombolysis using recombinant tissue plasminogen activator (r-tPA).
METHODS
This multicenter retrospective observational study analyzed patients with AIS treated with intravenous r-tPA. sICH was defined as a worsening of 4 or higher points in the National Institutes of Health Stroke Scale (NIHSS) score within 36 hours after intravenous thrombolysis in any hemorrhage subtype. We assessed the odds ratio (OR) with 95% confidence interval (CI) of lipid profile for sICH for each sex using logistic regression models adjusted for potential confounding factors.
RESULTS
Of 957 participants (median age 68 (interquartile range, 59-75), men 628 (65.6%)), 56 sICH events (36 (5.7%) in men and 20 (6.1%) in women) were observed. The risk of sICH in men decreased with increasing serum levels of triglyceride after adjustment for confounding factors ( lowest tertile, medium tertile OR 0.39, 95% CI [0.17-0.91], top tertile OR 0.33, 95% CI [0.13-0.84], overall = 0.021; per point increase, adjusted OR 0.29, 95% CI [0.13-0.63], = 0.002). Neither serum levels of total cholesterol nor low-density lipoprotein (LDL) was associated with sICH in men. In women, there was no association between any of the lipid levels and the risk of sICH.
CONCLUSIONS
This study indicated that the association between serum levels of triglyceride and sICH may vary by sex. In men, increased triglyceride levels decrease the risk of sICH; in women, this association was lost. Further studies on the biological mechanisms for sex differences in stroke risk associated with triglyceride are needed.
Topics: Humans; Male; Female; Retrospective Studies; Aged; Triglycerides; Middle Aged; Ischemic Stroke; Cerebral Hemorrhage; Tissue Plasminogen Activator; Sex Factors; Risk Factors; Thrombolytic Therapy; Fibrinolytic Agents
PubMed: 38938613
DOI: 10.7717/peerj.17558 -
Frontiers in Immunology 2024The primary treatment for acute relapses in multiple sclerosis (MS) is the intravenous administration of high-dose methylprednisolone (IVMP). However, the mechanisms...
BACKGROUND
The primary treatment for acute relapses in multiple sclerosis (MS) is the intravenous administration of high-dose methylprednisolone (IVMP). However, the mechanisms through which corticosteroid treatment impacts acute neuroinflammation in people with MS (pwMS) remain not fully understood. In particular, the changes induced by glucocorticoids (GCs) on cells of the innate immune system and the differences between patients with distinct immunotherapies have received little attention to date.
METHODS
We conducted immunophenotyping using flow cytometry on peripheral blood mononuclear cells of pwMS who received IVMP treatment during a relapse. We compared the impact of an IVMP treatment on a broad variety of immune cell subsets within three groups: twelve patients who were treatment-naïve to disease modifying therapies (wDMT) to ten patients on platform therapies (PT) and eighteen patients on fingolimod therapy (FTY).
RESULTS
We observed pronounced interindividual short- and intermediate-term effects of IVMP on distinct immune cells subsets. In addition to the well-documented decrease in T-helper cells (Th cells), we detected significant alterations after the first IVMP infusion within the innate immune response among neutrophil, eosinophil and basophil granulocytes, monocytes and plasmacytoid dendritic cells (pDCs). When comparing patients wDMT to the PT and FTY cohorts, we found that IVMP had a similar impact on innate immune cells across all treatment groups. However, we did not observe a significant further decline in T lymphocyte counts during IVMP in patients with pre-existing lymphopenia under FTY treatment. Although T cell apoptosis is considered the main mechanism of action of GCs, patients with FTY still reported symptom improvement following IVMP treatment.
CONCLUSION
In addition to T cell suppression, our data suggests that further immunoregulatory mechanisms of GC, particularly on cells of the innate immune response, are of greater significance than previously understood. Due to the regulation of the adaptive immune cells by DMTs, the impact of GC on these cells varies depending on the underlying DMT. Additional studies involving larger cohorts and cerebrospinal fluid samples are necessary to gain a deeper understanding of the immune response to GC in pwMS with different DMTs during relapse to define and explain differences in clinical response profiles.
Topics: Humans; Female; Male; Adult; Middle Aged; Multiple Sclerosis; Fingolimod Hydrochloride; Immunity, Innate; Methylprednisolone; Immunophenotyping; Leukocytes, Mononuclear; Adrenal Cortex Hormones; Immunosuppressive Agents; Glucocorticoids
PubMed: 38938576
DOI: 10.3389/fimmu.2024.1404316