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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 1,400 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 (14.8-1,400 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 -
Microbial Pathogenesis Jun 2024Campylobacter jejuni is one of the major causes of bacterial gastrointestinal disease in humans worldwide. This foodborne pathogen colonizes the intestinal tracts of...
Campylobacter jejuni is one of the major causes of bacterial gastrointestinal disease in humans worldwide. This foodborne pathogen colonizes the intestinal tracts of chickens, and consumption of chicken and poultry products is identified as a common route of transmission. We analyzed two C. jejuni strains after oral challenge with 10 CFU/ml of C. jejuni per chick; one strain was a robust colonizer (A74/C) and the other a poor colonizer (A74/O). We also found extensive phenotypic differences in growth rate, biofilm production, and in vitro adherence, invasion, intracellular survival, and transcytosis. Strains A74/C and A74/O were genotypically similar with respect to their whole genome alignment, core genome, and ribosomal MLST, MLST, flaA, porA, and PFGE typing. The global proteomes of the two congenic strains were quantitatively analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and 618 and 453 proteins were identified from A74/C and A74/O isolates, respectively. Cluster of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that carbon metabolism and motility proteins were distinctively overexpressed in strain A74/C. The robust colonizer also exhibited a unique proteome profile characterized by significantly increased expression of proteins linked to adhesion, invasion, chemotaxis, energy, protein synthesis, heat shock proteins, iron regulation, two-component regulatory systems, and multidrug efflux pump. Our study underlines phenotypic, genotypic, and proteomic variations of the poor and robust colonizing C. jejuni strains, suggesting that several factors may contribute to mediating the different colonization potentials of the isogenic isolates.
PubMed: 38942248
DOI: 10.1016/j.micpath.2024.106766 -
Journal of Oral Biosciences Jun 2024This study aimed to elucidate whether the administration of parathyroid hormone (PTH) results in remodeling- or modeling-based bone formation in different regions of the...
Regional difference in the distribution of alkaline phosphatase, PHOSPHO1, and calcein labeling in the femoral metaphyseal trabeculae in parathyroid hormone-administered mice.
OBJECTIVES
This study aimed to elucidate whether the administration of parathyroid hormone (PTH) results in remodeling- or modeling-based bone formation in different regions of the murine femora, and whether the PTH-driven bone formation would facilitate osteoblastic differentiation into osteocytes.
METHODS
Six-week-old male C57BL/6J mice were employed to examine the distribution of alkaline phosphatase (ALP), PHOSPHO1, podoplanin, and calcein labeling in two distinct long bone regions: the metaphyseal trabeculae close to the chondro-osseous junction (COJ) and those distant from the COJ in three mouse groups, a control group receiving a vehicle (Sham group) and groups receiving hPTH (1-34) twice a day (PTH BID group) or four times a day (PTH QID group) for two weeks.
RESULTS
The Sham group showed PHOSPHO1-reactive mature osteoblasts localized primarily at the COJ, whereas the PTH BID/QID groups exhibited extended lines of PHOSPHO1-reactive osteoblasts even in regions distant from the COJ. The PTH QID group displayed fragmented calcein labeling in trabeculae close to the COJ, whereas continuous labeling was observed in trabeculae distant from the COJ. Osteoblasts tended to express podoplanin and PHOSPHO1 independently in the close and distant regions of the Sham group, while osteoblasts in the PTH-administered groups showed immunoreactivity of podoplanin and PHOSPHO1 together in the close and distant regions.
CONCLUSIONS
Administration of PTH may accelerate remodeling-based bone formation in regions close to the COJ while predominantly inducing modeling-based bone formation in distant regions. PTH appeared to simultaneously facilitate osteoblastic bone mineralization and differentiation into osteocytes in both remodeling- and modeling-based bone formation.
PubMed: 38942193
DOI: 10.1016/j.job.2024.06.007 -
European Journal of Pharmaceutics and... Jun 2024Alzheimer's disease (ALZ) is a neurological disorder characterized by cognitive decline. Rivastigmine (RV), an acetylcholinesterase inhibitor, is commonly used to treat...
Implantable trilayer microneedle transdermal delivery system to enhance bioavailability and brain delivery of rivastigmine for Alzheimer treatment: A proof-of-concept study.
Alzheimer's disease (ALZ) is a neurological disorder characterized by cognitive decline. Rivastigmine (RV), an acetylcholinesterase inhibitor, is commonly used to treat ALZ. Unfortunately, RV is availablein capsule form, which is associated with low drug bioavailability, and in patch form, which can lead to skin irritation upon repeated use. This study successfully fabricated a trilayer dissolving microneedle (TDMN) containing RV with adequate mechanical strength by using the molding method. In vitro release and ex vivo permeation showed that the release and permeation of RV were significantly sustained compared to control without PCL. The release and permeation percentages were 91.34 ± 11.39 % and 13.76 ± 1.49 μg/cm, respectively. In addition, the concentration of RV in plasma and brain after 168 h was measured to be 0.44 ± 0.09 µg/mL and 1.23 ± 0.26 µg/g, respectively, which reached the minimum concentration to inhibit AcHE and BuChe. Pharmacokinetic testing revealed higher AUC values after administration of TDMN, indicating better bioavailability, and RV concentrations in the brain were found to be twice as high as those achieved with oral administration. This study suggests TDMN may enhance the bioavailability and brain delivery of RV.
PubMed: 38942175
DOI: 10.1016/j.ejpb.2024.114382