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Parasites & Vectors Jun 2024Chicken coccidiosis is a protozoan disease that leads to considerable economic losses in the poultry industry. Live oocyst vaccination is currently the most effective...
Oral vaccination with a recombinant Lactobacillus plantarum expressing the Eimeria tenella rhoptry neck 2 protein elicits protective immunity in broiler chickens infected with Eimeria tenella.
BACKGROUND
Chicken coccidiosis is a protozoan disease that leads to considerable economic losses in the poultry industry. Live oocyst vaccination is currently the most effective measure for the prevention of coccidiosis. However, it provides limited protection with several drawbacks, such as poor immunological protection and potential reversion to virulence. Therefore, the development of effective and safe vaccines against chicken coccidiosis is still urgently needed.
METHODS
In this study, a novel oral vaccine against Eimeria tenella was developed by constructing a recombinant Lactobacillus plantarum (NC8) strain expressing the E. tenella RON2 protein. We administered recombinant L. plantarum orally at 3, 4 and 5 days of age and again at 17, 18 and 19 days of age. Meanwhile, each chick in the commercial vaccine group was immunized with 3 × 10 live oocysts of coccidia. A total of 5 × 10 sporulated oocysts of E. tenella were inoculated in each chicken at 30 days. Then, the immunoprotection effect was evaluated after E. tenella infection.
RESULTS
The results showed that the proportion of CD4 and CD8 T cells, the proliferative ability of spleen lymphocytes, inflammatory cytokine levels and specific antibody titers of chicks immunized with recombinant L. plantarum were significantly increased (P < 0.05). The relative body weight gains were increased and the number of oocysts per gram (OPG) was decreased after E. tenella challenge. Moreover, the lesion scores and histopathological cecum sections showed that recombinant L. plantarum can significantly relieve pathological damage in the cecum. The ACI was 170.89 in the recombinant L. plantarum group, which was higher than the 150.14 in the commercial vaccine group.
CONCLUSIONS
These above results indicate that L. plantarum expressing RON2 improved humoral and cellular immunity and enhanced immunoprotection against E. tenella. The protective efficacy was superior to that of vaccination with the commercial live oocyst vaccine. This study suggests that recombinant L. plantarum expressing the RON2 protein provides a promising strategy for vaccine development against coccidiosis.
Topics: Animals; Eimeria tenella; Chickens; Coccidiosis; Poultry Diseases; Protozoan Vaccines; Lactobacillus plantarum; Administration, Oral; Protozoan Proteins; Vaccination; Antibodies, Protozoan; Vaccines, Synthetic
PubMed: 38943202
DOI: 10.1186/s13071-024-06355-w -
Reproductive Health Jun 2024Access to an on-demand pericoital oral contraceptive pill - used to prevent pregnancy within a defined window around sexual intercourse - could offer women more... (Review)
Review
BACKGROUND
Access to an on-demand pericoital oral contraceptive pill - used to prevent pregnancy within a defined window around sexual intercourse - could offer women more reproductive agency. A contraceptive with this indication is not currently available in any market. This review aims to understand international user appeal for an on-demand pericoital oral contraceptive pill.
METHODS
Systematic scoping review, comprising 30 peer-reviewed papers published between 2014-2023.
RESULTS
Data from 30 papers reporting on research from 16 countries across five World Health Organisation regions suggests widespread user appeal for on-demand oral contraceptive pills that can be used peri- or post-coitally, especially among women who are younger, more educated or who have less frequent sex. Women of varying age, wealth, employment or relationship status, and with different prior experience of using modern contraceptives, were also interested. Women identified clear rationale for use and preference of these types of product: close alignment with women's sexual lives that comprised unplanned, spontaneous or occasional sex; perceived convenience and effectiveness; discreet use of pills to negotiate contextual circumstances that constrained their reproductive agency. Factors inhibiting use included knowledge barriers and attitudes of service providers, a lack of knowledge and misinformation among end-users, women's dislike of menstrual side effects and myths related to the effects of hormone content on future fertility.
CONCLUSIONS
Introduction of an on-demand pericoital oral contraceptive pill could expand contraceptive choice for diverse women experiencing unmet need for modern contraception and constrained sexual and reproductive agency. Priorities for future research include: broadening the geographical scope of evidence to include SE Asia and the Pacific, and international rural and peri-urban settings; documenting the perspectives of adolescents and unmarried young people; identifying opportunities for innovation in the supply channels to enhance appropriate, affordable access to on-demand oral contraceptives; and unpacking how to bring new pericoital contraceptives to the market in a variety of international settings.
Topics: Humans; Female; Contraceptives, Oral; Contraception Behavior; Coitus; Health Knowledge, Attitudes, Practice; Pregnancy; Sexual Behavior; Patient Acceptance of Health Care; Contraception
PubMed: 38943120
DOI: 10.1186/s12978-024-01829-7 -
BMC Geriatrics Jun 2024Malnutrition of older individuals, leads to significant functional decline, reducing their quality of life. Lifestyle interventions; dietary improvements and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Malnutrition of older individuals, leads to significant functional decline, reducing their quality of life. Lifestyle interventions; dietary improvements and supplementation are explored to enhance the physical function of older adults. The current study aimed to assess the impact of oral nutritional supplements (ONS) on the functional and activity levels of Sri Lankan older adults.
METHODS
This randomized controlled trial included; an intervention group (IG) receiving 200 mL of ONS providing 247 kcal per serving, for 12 weeks and a control group (CG) receiving an equivalent volume of water. Changes in handgrip strength, knee extension strength, gait speed, functional and activity levels were assessed.
RESULTS
The IG showed significant improvements in handgrip strength (43.96 ± 18.61 kg vs. 32.81 ± 17.92 kg; p < 0.001) and knee extension strength (23.45 ± 2.29 kg vs. 16.41 ± 2.09 kg; p < 0.001) following 12 weeks compared to the CG. The IG also exhibited significant improvements in gait speed (1.31 ± 0.52 m/s vs. 0.87 ± 0.26 m/s), Barthel index score, (0.30 ± 0.47 vs. -0.18 ± 0.66), PASE score (0.52 ± 17.79 vs. -1.60 ± 21.77) and IPAQ categories.
CONCLUSIONS
ONS was found to be effective in improving the functional and physical activity levels of malnourished older adults.
TRIAL REGISTRATION
Sri Lanka Clinical Trial Registry SLCTR/2022/021. Registered on 06/10/2022.
Topics: Humans; Male; Aged; Female; Dietary Supplements; Malnutrition; Exercise; Hand Strength; Sri Lanka; Walking Speed; Physical Functional Performance; Aged, 80 and over; Middle Aged; Administration, Oral
PubMed: 38943086
DOI: 10.1186/s12877-024-05164-1 -
Surgical and Radiologic Anatomy : SRA Jun 2024Ultrasonography (US) has become an essential tool for guiding botulinum neurotoxin (BoNT) injections in facial muscles, enhancing precision and safety. This narrative... (Review)
Review
INTRODUCTION
Ultrasonography (US) has become an essential tool for guiding botulinum neurotoxin (BoNT) injections in facial muscles, enhancing precision and safety. This narrative review explores the role of US in BoNT administration, particularly in complex anatomical regions, highlighting its impact on treatment customization, real-time visualization, and complication reduction.
MATERIALS AND METHODS
A comprehensive literature search was conducted using PubMed, MEDLINE, Embase, and Cochrane Library for articles published from January 2018 to December 2023. Search terms included "Botulinum neurotoxin," "facial anatomy," "ultrasonography guided injection," and "facial muscle sonoanatomy." Studies focusing on US-guided BoNT injections in facial muscles were included. Data extraction and synthesis were performed independently by two reviewers, focusing on study design, ultrasonography techniques, outcomes, and conclusions.
RESULTS
The review found that US guidance significantly enhances the precision of BoNT injections by providing real-time visualization of facial muscles and blood vessels, thereby reducing the risk of adverse events. US enables tailored injection strategies, ensuring symmetrical facial expressions and minimizing over-treatment. The technique also offers immediate feedback, allowing for on-the-spot adjustments to improve treatment efficacy and safety. However, the review identified limitations, including potential selection bias and variability in US techniques across different studies.
CONCLUSION
US guidance for BoNT injections into facial muscles offers substantial benefits in terms of precision, safety, and treatment customization. Despite the identified limitations, the integration of US into clinical practice is poised to enhance patient outcomes in aesthetic and therapeutic procedures. Further research is needed to standardize US techniques and broaden the inclusivity of studies to validate these findings comprehensively.
PubMed: 38942935
DOI: 10.1007/s00276-024-03429-3 -
Nature Communications Jun 2024In a pivotal trial (EPIC-HR), a 5-day course of oral ritonavir-boosted nirmatrelvir, given early during symptomatic SARS-CoV-2 infection (within three days of symptoms...
In a pivotal trial (EPIC-HR), a 5-day course of oral ritonavir-boosted nirmatrelvir, given early during symptomatic SARS-CoV-2 infection (within three days of symptoms onset), decreased hospitalization and death by 89.1% and nasal viral load by 0.87 log relative to placebo in high-risk individuals. Yet, nirmatrelvir/ritonavir failed as post-exposure prophylaxis in a trial, and frequent viral rebound has been observed in subsequent cohorts. We develop a mathematical model capturing viral-immune dynamics and nirmatrelvir pharmacokinetics that recapitulates viral loads from this and another clinical trial (PLATCOV). Our results suggest that nirmatrelvir's in vivo potency is significantly lower than in vitro assays predict. According to our model, a maximally potent agent would reduce the viral load by approximately 3.5 logs relative to placebo at 5 days. The model identifies that earlier initiation and shorter treatment duration are key predictors of post-treatment rebound. Extension of treatment to 10 days for Omicron variant infection in vaccinated individuals, rather than increasing dose or dosing frequency, is predicted to lower the incidence of viral rebound significantly.
Topics: Humans; SARS-CoV-2; Ritonavir; COVID-19 Drug Treatment; COVID-19; Viral Load; Antiviral Agents; Indazoles; Models, Theoretical; Post-Exposure Prophylaxis; Lactams; Leucine; Nitriles; Proline
PubMed: 38942778
DOI: 10.1038/s41467-024-49458-9 -
International Journal of Biological... Jun 2024Transdermal drug delivery refers to the administration of drugs through the skin, after which the drugs can directly act on or circulate through the body to the target... (Review)
Review
Transdermal drug delivery refers to the administration of drugs through the skin, after which the drugs can directly act on or circulate through the body to the target organs or cells and avoid the first-pass metabolism in the liver and kidneys experienced by oral drugs, reducing the risk of drug poisoning. From the initial singular approach to transdermal drug delivery, there has been a shift toward combining multiple methods to enhance drug permeation efficiency and address the limitations of individual approaches. Technological advancements have also improved the accuracy of drug delivery. Optimizing insulin itself also enables its long-term release via needle-free injectors. In this review, the diverse transdermal delivery methods employed in insulin therapy and their respective advantages and limitations are discussed. By considering factors such as the principles of transdermal penetration, drug delivery efficiency, research progress, synergistic innovations among different methods, patient compliance, skin damage, and posttreatment skin recovery, a comprehensive evaluation is presented, along with prospects for potential novel combinatorial approaches. Furthermore, as insulin is a macromolecular drug, insights gained from its transdermal delivery may also serve as a valuable reference for the use of other macromolecular drugs for treatment.
PubMed: 38942414
DOI: 10.1016/j.ijbiomac.2024.133452 -
International Journal of Biological... Jun 2024Influenza A virus (IAV) causes annual epidemics and occasional pandemics, resulting in significant economic losses and numerous fatalities. Current vaccines, typically...
Influenza A virus (IAV) causes annual epidemics and occasional pandemics, resulting in significant economic losses and numerous fatalities. Current vaccines, typically administered through injection, provide limited protection due to the frequent antigenic shift and drift of IAV strains. Therefore, the development of alternative broad-spectrum vaccine strategies is imperative. Lactic acid bacteria (LAB) represent promising candidates for vaccine engineering due to their low cost, high safety profile, and suitability for oral administration. In this study, we identified a strain of Lactobacillus plantarum (Lp) that is resistant to acid and bile salts and capable of colonizing the intestines of mice. Subsequently, we employed the RecE/T gene editing system to integrate headless hemagglutinins (mini-HA) into the genome of Lp, generating Lp-mini-HA-SP. Remarkably, immunization with Lp-mini-HA-SP elicited serum IgG antibody responses and conferred immune protection against H9N2 and H1N1 influenza virus challenges. Collectively, our findings offer a novel approach for the development of orally administered IAV vaccines and hold significant potential for future drug development endeavors.
PubMed: 38942402
DOI: 10.1016/j.ijbiomac.2024.133453 -
Annals of Vascular Surgery Jun 2024Heparin-induced thrombocytopenia (HIT) is an uncommon complication of heparin therapy with significant risk for severe morbidity and mortality. We investigated the role...
OBJECTIVES
Heparin-induced thrombocytopenia (HIT) is an uncommon complication of heparin therapy with significant risk for severe morbidity and mortality. We investigated the role and outcome of direct oral anticoagulants (DOACs) for the management of HIT.
METHODS
After IRB approval, a retrospective review was performed identifying all patients with positive HIT serotonin-release assays between 2020 and 2022 at two hospitals. Demographic and clinical variables were collected: initial anticoagulant, dosing and indication, interval before onset of HIT, thrombotic complications, platelet nadir and recovery, direct thrombin inhibitor (DTI) and DOAC usage, and clinical outcomes.
RESULTS
15 patients were included in the study. 8 underwent a vascular procedure, 3 had cardiac surgery, 1 patient had both and was included in both groups, and 5 patients had either non-cardiac, non-vascular surgery or no surgery. 14 patients received unfractionated heparin (93% with therapeutic dosing) and 1 received prophylactic enoxaparin prior to diagnosis of HIT. The average time to diagnosis of HIT was 10.77 days after initial anticoagulation. In-hospital mortality was 27%, related to Covid-19 infection (3/4) and intracranial hemorrhage (1/4). 40% developed thrombosis (67% venous, 33% arterial) after the diagnosis of HIT. 8/11 survivors were discharged on a DOAC. With DOAC therapy, platelet counts rebounded to an average of 265K (+/- 104.6K) within an average of 2.3 days and 364K (+/- 273.9K) within 30 days after initiation of a DOAC. No recurrent thrombosis occurred after DOAC administration and only one patient had persistent thrombocytopenia within 30 days.
CONCLUSIONS
Mortality and thrombosis (arterial and venous) are common complications in patients diagnosed with HIT. In patients who survive to discharge, DOACs are the most common discharge antithrombotic agent, with low rates of recurrent thrombosis and thrombocytopenia.
PubMed: 38942369
DOI: 10.1016/j.avsg.2024.05.005 -
Environmental Pollution (Barking, Essex... Jun 2024Humans indirectly consume approximately 0.02 mg/kg/day of short-chained chlorinated paraffins (SCCPs) through the environment; however, the thymic senescence/damage...
Humans indirectly consume approximately 0.02 mg/kg/day of short-chained chlorinated paraffins (SCCPs) through the environment; however, the thymic senescence/damage induced by SCCPs has not been assessed. In this study, 16 female mice (4-week-old) per group were orally administered 0, 0.01, 0.1, and 1 mg/kg/day of SCCPs for 21 days, and the phenotypes and levels of superoxide dismutase (SOD), malondialdehyde (MDA), Tβ4, αβ TCR, SA-β-Gal, GRP78, PERK/CHOP, P53/P21, and CASPASE-1 of the thymus were assessed as indicators. Another group comprising 16 mice was killed at 4-week-old and these indicators were assessed. Thereafter, the thymuses cultured in vitro were exposed to 0, 14, 140, and 1400 μg/L SCCPs, respectively, and the above indicators were measured after 7-day. Based on the results, the oral administration of ≥0.01 mg/kg/day SCCPs to mice and ≥14 μg/L of SCCPs in medium caused thymic aging features, such as a decrease in the ratio of cortex to medulla, gradual blurring of the boundary between the cortex and medulla, dose-dependent oxidative stress (decreased SOD and increased MDA), and decreased levels of Tβ4 and αβ TCRs in the thymus. The oral administration of ≥1 mg/kg/day of SCCPs also impeded the growth and development of female mice and their thymuses. Exposure to the low levels of SCCPs activated PERK-CHOP in the mouse thymus, which modulated increases in SA-β-Gal, IL-1β, P53, and CASPASE-1 in vivo and in vitro. Overall, environmental levels and human blood concentrations (14.8-1400 μg/L) of SCCPs may induce mouse thymus senescence by activating PERK-CHOP in vivo and in vitro, respectively.
PubMed: 38942270
DOI: 10.1016/j.envpol.2024.124438 -
European Journal of Pharmacology Jun 2024Pulmonary hypertension (PH) is a malignant pulmonary vascular disease with a poor prognosis. Although the development of targeted drugs for this disease has made some...
Pulmonary hypertension (PH) is a malignant pulmonary vascular disease with a poor prognosis. Although the development of targeted drugs for this disease has made some breakthroughs in recent decades, PH remains incurable. Therefore, innovative clinical treatment methods and drugs for PH are still urgently needed. DYZY01 is a new drug whose main ingredient is high-purity cannabidiol, a non-psychoactive constituent of cannabinoids that was demonstrated to have anti-inflammatory and anti-pyroptosis properties. Several recent studies have found cannabidiol could improve experimental PH, whereas the mechanistic effect of it warrants further investigation. Thus, this study aimed to investigate whether DYZY01 can treat PH by inhibiting inflammation and pyroptosis and to reveal its underlying mechanism. We established hypoxia and monocrotaline (MCT)-induced PH rat models in vivo and treated them with either DYZY01 (10,50 mg/kg/d) or Riociguat (10 mg/kg/d) by oral administration. The mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy index (RVHI), and extent of vascular remodeling were measured. Meanwhile, the effect of DYZY01 on human pulmonary arterial endothelial cells (HPAECs) was assessed in vitro. The results indicated that DYZY01 significantly reduced mPAP and RVHI in PH rats and reversed the extent of pulmonary vascular remodeling. This improvement may have been achieved by reducing endothelial cell pyroptosis via inhibiting the NF-κB/NLRP3/Caspase-1 pathway. Furthermore, DYZY01 could improve endothelial vascular function, possibly by regulating the secretion of vasodilator factors and inhibiting the proliferation and migration of pulmonary endothelial cells.
PubMed: 38942262
DOI: 10.1016/j.ejphar.2024.176785