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1.
Life Sci ; 354: 122948, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39117140

ABSTRACT

The gut-liver axis plays a pivotal role in maintaining body homeostasis. Disruption of the gut-liver axis is linked to a multitude of diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). Probiotic strains from the Lactobacillaceae family are commonly used to mitigate experimental MASLD. Over the years, numerous studies have demonstrated the efficacy of these probiotics, often focusing on the outcome of liver disease. This review aims to further understand MASLD as a systemic metabolic dysfunction and to highlight the effects of probiotics on multi-organ axis, including organs such as the gastrointestinal tract, pancreas, muscle, adipose tissue, and the immune system. We specifically discuss evidence on how supplementation with Lactobacillaceae strains may alleviate MASLD by not only restoring liver health but also by modulating the physiology of other organ systems.

2.
bioRxiv ; 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39131275

ABSTRACT

The global resurgence of syphilis has created a potent stimulus for vaccine development. To identify potentially protective antibodies (Abs) against Treponema pallidum ( TPA ), we used Pyrococcus furiosus thioredoxin ( Pf Trx) to display extracellular loops (ECLs) from three TPA outer membrane protein families (outer membrane factors for efflux pumps, eight-stranded ß-barrels, and FadLs) to assess their reactivity with immune rabbit serum (IRS). Five ECLs from the FadL orthologs TP0856, TP0858 and TP0865 were immunodominant. Rabbits and mice immunized with these five Pf Trx constructs produced ECL-specific Abs that promoted opsonophagocytosis of TPA by rabbit peritoneal and murine bone marrow-derived macrophages at levels comparable to IRS and mouse syphilitic serum. ECL-specific rabbit and mouse Abs also impaired viability, motility, and cellular attachment of spirochetes during in vitro cultivation. The results support the use of ECL-based vaccines and suggest that ECL-specific Abs promote spirochete clearance via Fc receptor-independent as well as Fc receptor-dependent mechanisms. Author Summary: The resurgence of syphilis emphasizes the critical need for vaccine development against Treponema pallidum ( TPA ). Research utilizing immune rabbit serum (IRS) suggests that an effective syphilis vaccine should induce "functional" antibodies (Abs) capable of enhancing the opsonophagocytosis of treponemes by activated macrophages. Structural models of TPA outer membrane proteins (OMPs), specifically the extracellular loops (ECLs), guided the identification of potential vaccine candidates. Antigenic analysis with IRS of individual ECLs from three TPA OMP families scaffolded onto Pyrococcus furiosus thioredoxin ( Pf Trx) revealed five FadL antigenic ECLs. Immunization with immunodominant ECL antigens elicited robust ECL-specific Abs, demonstrating functional opsonic activity in the opsonophagocytosis assays. Furthermore, these Abs effectively inhibited the growth inhibition of in vitro -cultivated TPA in both rabbit and mouse models. Our findings underscore the value of antigenic analysis in identifying promising TPA OMP ECL vaccine targets and highlight the multifaceted protective capacity of ECL Abs against TPA . This approach also extends to identifying potential OMP vaccinogens in other bacterial pathogens, offering valuable insights for broader vaccine development strategies.

3.
Animals (Basel) ; 14(15)2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39123762

ABSTRACT

Commercial crocodilian farms face significant economic and livestock losses attributed to stress, which may be linked to their adopted husbandry practices. The development of appropriate and modernized husbandry guidelines, particularly those focused on stress mitigation, is impeded by the limited understanding of the crocodilian stress response. Fifteen grower Nile crocodiles were subjected to simulated acute transport stress, with blood samples collected at various intervals post-stress. Plasma levels of corticosterone (CORT), dehydroepiandrosterone (DHEA), adrenaline, and noradrenaline were determined using high-performance liquid chromatography. Glucose and lactate were measured using portable meters and the heterophil-to-lymphocyte ratio (HLR) was determined via differential leucocyte counts. Significant differences were elicited after the stressor, with acute fluctuations observed in the fast-acting catecholamines (adrenaline and noradrenaline) when compared to the baseline. Downstream effects of these catecholamines and CORT appear to be associated with a persistent increase in plasma glucose and HLR. Lactate also showed acute fluctuations over time but returned to the baseline by the final measurement. DHEA, which is used in a ratio with CORT, showed fluctuations over time with an inverted release pattern to the catecholamines. The study highlights the temporal dynamics of physiological markers under acute stress, contributing to our understanding of crocodilian stress and potentially informing improved farming practices for conservation and sustainable management.

4.
Nurs Outlook ; 72(5): 102230, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39033569

ABSTRACT

BACKGROUND: The recent push to "decolonize nursing" has become a critical movement to address institutional racism, but the term has circulated through nursing circles enough to risk becoming a buzzword. PURPOSE: This article clarifies "decolonizing nursing" by addressing the following questions: (a) How has "decolonizing nursing" been discussed in nursing research? (b) What specific projects have been implemented to decolonize nursing? (c) How has decolonizing nursing been related to health equity? METHODS: We conducted a scoping review and searched CINAHL, PubMed, and PsycINFO databases. A total of N = 56 records were included. DISCUSSION: "Decolonization" has referred to a range of ideas related to resisting Western ideals, legitimizing Indigenous knowledge, and repatriating land and territory especially to Indigenous and dispossessed communities. Few empirical studies have examined the relationship between decolonization or colonialism and specific health outcomes. CONCLUSION: Decolonization differs from other social justice initiatives. To clarify what decolonizing nursing means, researchers can engage with historical, interdisciplinary, and community-based participatory research. In turn, nursing research will understand colonialism's historical context, provide evidence that supports policies that protect Indigenous territory, and design clinical interventions that promote health equity for dispossessed populations.

5.
Sci Adv ; 10(26): eadl0030, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38924398

ABSTRACT

How can short-lived molecules selectively maintain the potentiation of activated synapses to sustain long-term memory? Here, we find kidney and brain expressed adaptor protein (KIBRA), a postsynaptic scaffolding protein genetically linked to human memory performance, complexes with protein kinase Mzeta (PKMζ), anchoring the kinase's potentiating action to maintain late-phase long-term potentiation (late-LTP) at activated synapses. Two structurally distinct antagonists of KIBRA-PKMζ dimerization disrupt established late-LTP and long-term spatial memory, yet neither measurably affects basal synaptic transmission. Neither antagonist affects PKMζ-independent LTP or memory that are maintained by compensating PKCs in ζ-knockout mice; thus, both agents require PKMζ for their effect. KIBRA-PKMζ complexes maintain 1-month-old memory despite PKMζ turnover. Therefore, it is not PKMζ alone, nor KIBRA alone, but the continual interaction between the two that maintains late-LTP and long-term memory.


Subject(s)
Intracellular Signaling Peptides and Proteins , Long-Term Potentiation , Mice, Knockout , Protein Kinase C , Animals , Protein Kinase C/metabolism , Protein Kinase C/genetics , Mice , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Memory/physiology , Memory, Long-Term/physiology , Synapses/metabolism , Synapses/physiology , Protein Binding , Phosphoproteins
6.
EClinicalMedicine ; 72: 102641, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38840669

ABSTRACT

Workplace violence (WPV) against healthcare workers (HCW) is a globally growing problem in healthcare systems. Despite decades of research and interventions violent incidents are rising in their severity and frequency. A structured review of PubMed and Scopus databases and supplementary internet searches, resulted in a synthesis of evidence covering multiple countries and healthcare worker populations. High rates of WPV are increasingly common due to unmet patient expectations, poor communication, long wait times and organizational factors such as resourcing and infrastructure. We highlight links between WPV and poor worker health outcomes, staff turnover, reduced patient safety and medical errors. Few prevention and mitigation activities have shown sustained effects, highlighting the challenges in understanding and addressing the complex interplay of factors that drive violence against HCWs. The rapidly rising incidence of WPV requires special consideration and action from multiple stakeholders including patients and visitors, healthcare providers, law enforcement, media and policy makers.

7.
Nat Rev Neurosci ; 25(6): 428-448, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38714834

ABSTRACT

The representation of distinct spaces by hippocampal place cells has been linked to changes in their place fields (the locations in the environment where the place cells discharge strongly), a phenomenon that has been termed 'remapping'. Remapping has been assumed to be accompanied by the reorganization of subsecond cofiring relationships among the place cells, potentially maximizing hippocampal information coding capacity. However, several observations challenge this standard view. For example, place cells exhibit mixed selectivity, encode non-positional variables, can have multiple place fields and exhibit unreliable discharge in fixed environments. Furthermore, recent evidence suggests that, when measured at subsecond timescales, the moment-to-moment cofiring of a pair of cells in one environment is remarkably similar in another environment, despite remapping. Here, I propose that remapping is a misnomer for the changes in place fields across environments and suggest instead that internally organized manifold representations of hippocampal activity are actively registered to different environments to enable navigation, promote memory and organize knowledge.


Subject(s)
Hippocampus , Space Perception , Hippocampus/physiology , Animals , Humans , Space Perception/physiology , Place Cells/physiology
8.
J Biol Chem ; 300(6): 107340, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705390

ABSTRACT

Triclosan (TCS) is an antimicrobial toxicant found in a myriad of consumer products and has been detected in human tissues, including breastmilk. We have evaluated the impact of lactational TCS on UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and bilirubin metabolism in humanized UGT1 (hUGT1) neonatal mice. In hUGT1 mice, expression of the hepatic UGT1A1 gene is developmentally delayed resulting in elevated total serum bilirubin (TSB) levels. We found that newborn hUGT1 mice breastfed or orally treated with TCS presented lower TSB levels along with induction of hepatic UGT1A1. Lactational and oral treatment by gavage with TCS leads to the activation of hepatic nuclear receptors constitutive androstane receptor (CAR), peroxisome proliferator-activated receptor alpha (PPARα), and stress sensor, activating transcription factor 4 (ATF4). When CAR-deficient hUGT1 mice (hUGT1/Car-/-) were treated with TCS, TSB levels were reduced with a robust induction of hepatic UGT1A1, leaving us to conclude that CAR is not tied to UGT1A1 induction. Alternatively, when PPARα-deficient hUGT1 mice (hUGT1/Pparα-/-) were treated with TCS, hepatic UGT1A1 was not induced. Additionally, we had previously demonstrated that TCS is a potent inducer of ATF4, a transcriptional factor linked to the integrated stress response. When ATF4 was deleted in liver of hUGT1 mice (hUGT1/Atf4ΔHep) and these mice treated with TCS, we observed superinduction of hepatic UGT1A1. Oxidative stress genes in livers of hUGT1/Atf4ΔHep treated with TCS were increased, suggesting that ATF4 protects liver from excessive oxidative stress. The increase oxidative stress may be associated with superinduction of UGT1A1. The expression of ATF4 in neonatal hUGT1 hepatic tissue may play a role in the developmental repression of UGT1A1.


Subject(s)
Activating Transcription Factor 4 , Animals, Newborn , Bilirubin , Glucuronosyltransferase , Liver , PPAR alpha , Triclosan , Animals , Glucuronosyltransferase/metabolism , Glucuronosyltransferase/genetics , PPAR alpha/metabolism , PPAR alpha/genetics , Mice , Activating Transcription Factor 4/metabolism , Activating Transcription Factor 4/genetics , Triclosan/pharmacology , Humans , Bilirubin/pharmacology , Bilirubin/metabolism , Liver/metabolism , Liver/drug effects , Mice, Knockout , Female , Constitutive Androstane Receptor , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Cytoplasmic and Nuclear/genetics
9.
Vaccine ; 42(20): 125983, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-38797628

ABSTRACT

INTRODUCTION: Pneumococcal meningitis outbreaks occur sporadically in the African meningitis belt. Outbreak control guidelines and interventions are well established for meningococcal but not pneumococcal meningitis. Mathematical modelling is a useful tool for assessing the potential impact of different pneumococcal control strategies. This work aimed to estimate the impact of reactive vaccination with pneumococcal conjugate vaccine (PCV) had it been implemented in past African meningitis belt outbreaks and assess their efficiency relative to existing routine infant immunisation with PCV. METHODS & RESULTS: Using recent pneumococcal meningitis outbreaks in Burkina Faso, Chad, and Ghana as case studies, we investigated the potential impact of reactive vaccination. We calculated the number needed to vaccinate to avert one case (NNV) in each outbreak setting and over all outbreaks and compared this to the NNV for existing routine infant vaccination. We extended previous analyses of reactive vaccination by considering longer-term protection in vaccinees over five years, incorporating a proxy for indirect effects. We found that implementing reactive vaccination in previous pneumococcal meningitis outbreaks could have averted up to 10-20 % of outbreak cases, with the biggest potential impact in Brong Ahafo, Ghana (2015-2016) and Goundi, Chad (2009). The NNV, and hence the value of reactive vaccination, varied greatly. 'Large' (80 + cumulative modelled cases per 100,000 population) and/or 'prolonged' (exceeding a response threshold of 10 suspected cases per 100,000 per week for four weeks or more) outbreaks had NNV estimates under 10,000. For routine infant vaccination with PCV, the estimated NNV ranged from 3,100-5,600 in Burkina Faso and 1,500-2,600 in Ghana. IMPLICATIONS: This analysis provides evidence to inform the design of pneumococcal meningitis outbreak response guidelines. Countries should consider reactive vaccination in each outbreak event, together with maintaining routine infant vaccination as the primary intervention to reduce pneumococcal disease burden and outbreak risk.


Subject(s)
Disease Outbreaks , Meningitis, Pneumococcal , Pneumococcal Vaccines , Humans , Disease Outbreaks/prevention & control , Meningitis, Pneumococcal/prevention & control , Meningitis, Pneumococcal/epidemiology , Ghana/epidemiology , Burkina Faso/epidemiology , Infant , Pneumococcal Vaccines/administration & dosage , Models, Theoretical , Vaccination , Chad/epidemiology , Vaccines, Conjugate/administration & dosage , Child, Preschool , Child , Female
10.
Pediatr Transplant ; 28(4): e14771, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38702924

ABSTRACT

BACKGROUND: We examined the combined effects of donor age and graft type on pediatric liver transplantation outcomes with an aim to offer insights into the strategic utilization of these donor and graft options. METHODS: A retrospective analysis was conducted using a national database on 0-2-year-old (N = 2714) and 3-17-year-old (N = 2263) pediatric recipients. These recipients were categorized based on donor age (≥40 vs <40 years) and graft type. Survival outcomes were analyzed using the Kaplan-Meier and Cox proportional hazards models, followed by an intention-to-treat (ITT) analysis to examine overall patient survival. RESULTS: Living and younger donors generally resulted in better outcomes compared to deceased and older donors, respectively. This difference was more significant among younger recipients (0-2 years compared to 3-17 years). Despite this finding, ITT survival analysis showed that donor age and graft type did not impact survival with the exception of 0-2-year-old recipients who had an improved survival with a younger living donor graft. CONCLUSIONS: Timely transplantation has the largest impact on survival in pediatric recipients. Improving waitlist mortality requires uniform surgical expertise at many transplant centers to provide technical variant graft (TVG) options and shed the conservative mindset of seeking only the "best" graft for pediatric recipients.


Subject(s)
Graft Survival , Kaplan-Meier Estimate , Liver Transplantation , Tissue Donors , Humans , Child, Preschool , Retrospective Studies , Child , Adolescent , Male , Female , Infant , Age Factors , Infant, Newborn , Proportional Hazards Models , Adult , Treatment Outcome , Living Donors
11.
Sci Total Environ ; 931: 172960, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38710393

ABSTRACT

Aquatic plants (macrophytes) are important for ecosystem structure and function. Macrophyte mass developments are, however, often perceived as a nuisance and are commonly managed by mechanical removal. This is costly and often ineffective due to macrophyte regrowth. There is insufficient understanding about what causes macrophyte mass development, what people who use water bodies consider to be a nuisance, or the potential negative effects of macrophyte removal on the structure and function of ecosystems. To address these gaps, we performed a standardized set of in situ experiments and questionnaires at six sites (lakes, reservoirs, and rivers) on three continents where macrophyte mass developments occur. We then derived monetary values of ecosystem services for different scenarios of macrophyte management ("do nothing", "current practice", "maximum removal"), and developed a decision support system for the management of water courses experiencing macrophyte mass developments. We found that (a) macrophyte mass developments often occur in ecosystems which (unintentionally) became perfect habitats for aquatic plants, that (b) reduced ecosystem disturbance can cause macrophyte mass developments even if nutrient concentrations are low, that (c) macrophyte mass developments are indeed perceived negatively, but visitors tend to regard them as less of a nuisance than residents do, that (d) macrophyte removal lowers the water level of streams and adjacent groundwater, but this may have positive or negative overall societal effects, and that (e) the effects of macrophyte removal on water quality, greenhouse gas emissions, and biodiversity vary, and likely depend on ecosystem characteristics and macrophyte life form. Overall, we found that aquatic plant management often does not greatly affect the overall societal value of the ecosystem, and we suggest that the "do nothing" option should not be easily discarded in the management of perceived nuisance mass developments of aquatic plants.


Subject(s)
Conservation of Natural Resources , Ecosystem , Conservation of Natural Resources/methods , Plants , Rivers , Environmental Monitoring
12.
J Ethnopharmacol ; 331: 118294, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38729541

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Sepsis poses one of the biggest public health problems, necessitating the search for new therapeutic alternatives. For centuries, propolis has been widely used in folk medicine to treat various inflammatory and infectious diseases. Given its extensive use, it has excellent potential as an adjuvant treatment for patients with sepsis. OBJECTIVE: This study evaluated prophylactic treatment with standardized propolis extract (EPP-AF®) and followed the prognosis of sepsis induced by ligation and cecal ligation and puncture (CLP). METHODS: Initially, for survival assessment, Swiss mice were separated into five groups: Sham (false operated), control (PBS), ATB (received antibiotic, 8 mg/kg), P10 (received EPP-AF®, 10 mg/kg), and P100 (received EPP-AF®, 100 mg/kg). The animals received PBS, antibiotic, or EPP-AF® by the subcutaneous route 6 h before the CLP procedure. Animal survival was assessed every 12 h for five days when all of them were euthanized. RESULTS: We show that the treatment with EPP-AF® significantly increased the life expectancy of animals with sepsis compared to the control group. Interestingly, prophylactic treatment with EPP-AF® showed no effect on the number of colony-forming units in the peritoneum, blood, or lung. However, there was a decrease in cellular influx in the peritoneum. This alteration was unrelated to the number of bone marrow cells or the differential counting of peripheral blood cells. The coagulogram remained unchanged, including the number of platelets and prothrombin time-activated partial thromboplastin time. However, the inflammatory infiltrate and bleeding in the lung tissue were lower in the animals that received EPP-AF®. CONCLUSION: Thus, it was possible to conclude that prophylactic treatment with EPP-AF® preserved the lung parenchyma, resulting in an increased lifespan of mice with sepsis. It can be a helpful adjuvant in prophylactic treatment with antibiotics in presurgical conditions.


Subject(s)
Propolis , Sepsis , Animals , Propolis/pharmacology , Sepsis/drug therapy , Sepsis/mortality , Mice , Male , Bees , Pneumonia/prevention & control , Pneumonia/drug therapy , Disease Models, Animal , Lung/drug effects , Lung/pathology
13.
Int J Pharm ; 656: 124078, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38569978

ABSTRACT

The role of tumor stroma in solid tumors has been widely recognized in cancer progression, metastasis and chemoresistance. Cancer-associated fibroblasts (CAFs) play a crucial role in matrix remodeling and promoting cancer cell stemness and resistance via reciprocal crosstalk. Residual tumor tissue after surgical removal as well as unresectable tumors face therapeutic challenges to achieve curable outcome. In this study, we propose to develop a dual delivery approach by combining p21-activated kinase 1 (PAK1) inhibitor (FRAX597) to inhibit tumor stroma and chemotherapeutic agent paclitaxel (PTX) to kill cancer cells using electrospun nanofibers. First, the role of the PAK1 pathway was established in CAF differentiation, migration and contraction using relevant in vitro models. Second, polycaprolactone polymer-based nanofibers were fabricated using a uniaxial electrospinning technique to incorporate FRAX597 and/or PTX, which showed a uniform texture and a prolonged release of both drugs for 16 days. To test nanofibers, stroma-rich 3D heterospheroid models were set up which showed high resistance to PTX nanofibers compared to stroma-free homospheroids. Interestingly, nanofibers containing PTX and FRAX597 showed strong anti-tumor effects on heterospheroids by reducing the growth and viability by > 90 % compared to either of single drug-loaded nanofibers. These effects were reflected by reduced intra-spheroidal expression levels of collagen 1 and α-smooth muscle actin (α-SMA). Overall, this study provides a new therapeutic strategy to inhibit the tumor stroma using PAK1 inhibitor and thereby enhance the efficacy of chemotherapy using nanofibers as a local delivery system for unresectable or residual tumor. Use of 3D models to evaluate nanofibers highlights these models as advanced in vitro tools to study the effect of controlled release local drug delivery systems before animal studies.


Subject(s)
Nanofibers , Paclitaxel , p21-Activated Kinases , Paclitaxel/administration & dosage , Paclitaxel/pharmacology , Nanofibers/administration & dosage , p21-Activated Kinases/antagonists & inhibitors , p21-Activated Kinases/metabolism , Humans , Cell Line, Tumor , Spheroids, Cellular/drug effects , Polyesters/chemistry , Polyesters/administration & dosage , Cancer-Associated Fibroblasts/drug effects , Cancer-Associated Fibroblasts/metabolism , Drug Delivery Systems/methods , Cell Movement/drug effects , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/pharmacology , Drug Liberation , Cell Differentiation/drug effects
14.
JAMA Oncol ; 10(5): 584-591, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38483412

ABSTRACT

Importance: No prior trial has compared hypofractionated postprostatectomy radiotherapy (HYPORT) to conventionally fractionated postprostatectomy (COPORT) in patients primarily treated with prostatectomy. Objective: To determine if HYPORT is noninferior to COPORT for patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at 2 years. Design, Setting, and Participants: In this phase 3 randomized clinical trial, patients with a detectable prostate-specific antigen (PSA; ≥0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA (<0.1 ng/mL) with either pT3 disease or pT2 disease with a positive surgical margin were recruited from 93 academic, community-based, and tertiary medical sites in the US and Canada. Between June 2017 and July 2018, a total of 296 patients were randomized. Data were analyzed in December 2020, with additional analyses occurring after as needed. Intervention: Patients were randomized to receive 62.5 Gy in 25 fractions (HYPORT) or 66.6 Gy in 37 fractions (COPORT). Main Outcomes and Measures: The coprimary end points were the 2-year change in score from baseline for the bowel and urinary domains of the Expanded Prostate Cancer Composite Index questionnaire. Secondary objectives were to compare between arms freedom from biochemical failure, time to progression, local failure, regional failure, salvage therapy, distant metastasis, prostate cancer-specific survival, overall survival, and adverse events. Results: Of the 296 patients randomized (median [range] age, 65 [44-81] years; 100% male), 144 received HYPORT and 152 received COPORT. At the end of RT, the mean GU change scores among those in the HYPORT and COPORT arms were neither clinically significant nor different in statistical significance and remained so at 6 and 12 months. The mean (SD) GI change scores for HYPORT and COPORT were both clinically significant and different in statistical significance at the end of RT (-15.52 [18.43] and -7.06 [12.78], respectively; P < .001). However, the clinically and statistically significant differences in HYPORT and COPORT mean GI change scores were resolved at 6 and 12 months. The 24-month differences in mean GU and GI change scores for HYPORT were noninferior to COPORT using noninferiority margins of -5 and -6, respectively, rejecting the null hypothesis of inferiority (mean [SD] GU score: HYPORT, -5.01 [15.10] and COPORT, -4.07 [14.67]; P = .005; mean [SD] GI score: HYPORT, -4.17 [10.97] and COPORT, -1.41 [8.32]; P = .02). With a median follow-up for censored patients of 2.1 years, there was no difference between HYPORT vs COPORT for biochemical failure, defined as a PSA of 0.4 ng/mL or higher and rising (2-year rate, 12% vs 8%; P = .28). Conclusions and Relevance: In this randomized clinical trial, HYPORT was associated with greater patient-reported GI toxic effects compared with COPORT at the completion of RT, but both groups recovered to baseline levels within 6 months. At 2 years, HYPORT was noninferior to COPORT in terms of patient-reported GU or GI toxic effects. HYPORT is a new acceptable practice standard for patients receiving postprostatectomy radiotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03274687.


Subject(s)
Prostatectomy , Prostatic Neoplasms , Radiation Dose Hypofractionation , Humans , Male , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Middle Aged , Aged , Gastrointestinal Diseases/etiology , Prostate-Specific Antigen/blood , Male Urogenital Diseases/etiology , Radiotherapy, Adjuvant/adverse effects , Patient Reported Outcome Measures
15.
J Am Assoc Lab Anim Sci ; 63(4): 418-421, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38458617

ABSTRACT

This study aimed to compare the minimum anesthetic concentration (MAC) of sevoflurane in green iguanas using elec- trical stimulation and tail clamping as noxious stimuli. Seven adult green iguanas (Iguana iguana) weighing 580 to 1,300 g were enrolled. Each iguana was anesthetized twice after a 1-week washout period, with MAC being determined using a tail clamp (MACt) or electrical stimulation (MACe ) techniques. After sevoflurane mask induction and endotracheal intubation, the fraction of expired sevoflurane (Fe 'Sevo) was maintained at 3.1% for 15 min before noxious stimulation. In a bracketing design, the subsequent Fe'Sevo values were increased or decreased by 10% after positive or negative responses, respectively. Each targeted Fe 'Sevo was kept constant for 15 min before stimulation. In MACt, the noxious stimulus involved closing a Kelly hemostatic curved forceps to the first ratchet at the base of the tail. At the same site, in MACe, 2 30 × 0.8-mm hypodermic needles inserted 1 cm apart were connected to an electrical stimulator set to deliver 30 mA at 50 Hz at a 6.5-ms interval. The hemostat and the needles were repositioned 2 cm distally and on alternate tail sides at each stimulation round. Individual MAC was obtained when 2 consecutive crossover events occurred (a positive response preceding a negative response or vice versa), with the MAC of each group represented by the average of the individual MAC values. Median (interquartile range) values for the sevoflurane MAC did not differ significantly between groups (2.2 [2.2 to 2.8%] in MACe and 2.2 [1.8 to 3.5%] in MACt ; P = 0.812). Time to anesthesia induction, time to MAC measurement, heart rate (HR), end-tidal carbon dioxide (ET'CO2), and cloacal temperature were not different between groups. Both the tail-clamping and the electrical stimulation techniques yielded resembling sevoflurane MAC values in green iguanas, which makes the tail clamp a reliable alternative to electrical stimulation-based MAC research in this species.


Subject(s)
Anesthetics, Inhalation , Electric Stimulation , Iguanas , Sevoflurane , Tail , Sevoflurane/pharmacology , Animals , Anesthetics, Inhalation/analysis , Anesthetics, Inhalation/administration & dosage , Electric Stimulation/methods , Male , Female , Methyl Ethers/analysis
16.
J Cannabis Res ; 6(1): 16, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38532457

ABSTRACT

In 2019 and 2020, we investigated the individual and combined effects of two biofertilizers (manure tea and bioinoculant) and one humic acid (HA) product on cannabis biochemical and physiological parameters and soil CO2 evolution under outdoor conditions. Our hypothesis was that HA would increase the microbial activity in the biofertilizers and synergy of both compounds would promote better plant performance and stimulate soil microbial activity. In 2020, the individual and combined application of biofertilizers and HA increased cannabis height, chlorophyll content, photosynthetic efficiency, aboveground biomass, and bucked biomass by 105, 52, 43, 122, and 117%, respectively. Impacts were greater under suboptimal growing conditions caused by planting delay experienced in 2020. In 2019, planting date occurred in-between the most favorable period and chlorophyll content and photosynthetic efficiency were the only parameters influenced by the application of biostimulants. The discrepancies between the two growing seasons reinforce the evidence of other studies that biostimulants efficacy is maximized under stress conditions. This study could not conclusively confirm that the combined use of biofertilizer + HA is a superior practice since affected plant parameters did not differ from application of the compounds singly. Similarly, only one biofertilizer + HA treatment increased soil microbial activity. More research is needed to define optimum rates and combinations of biofertilizer and stimulants for cannabis.

17.
World Neurosurg ; 184: e603-e612, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38336211

ABSTRACT

BACKGROUND: The optimal stenting approach for traumatic pseudoaneurysms (PSA) of the extracranial internal carotid artery (ICA) remains underinvestigated. We present a case of a traumatic pseudoaneurysm of the extracranial ICA managed with stenting and review of prior published similar cases. METHODS: The systematic review followed PRISMA-S guidelines and included studies that investigated traumatic pseudoaneurysms of the extracranial ICA managed by stent placement. Statistical analysis assessed the association between the type of injury and stent type, dual antiplatelet therapy (DAPT) duration, and clinical presentation, and the association between stent type and DAPT duration. RESULTS: Our search yielded 82 publications with 135 patients with extracranial ICA PSA treated with stenting. The odds of neck hematoma presentation was 12.2 times greater for patients with penetrating rather than blunt injuries (P = 0.000002). Covered stents had 2.02 times higher odds of use for penetrating rather than blunt injuries compared to bare metal stents. (P = 0.0029). Shorter duration DAPT was seen with bare metal stents having 1.25 higher odds of DAPT duration less than one month compared to covered (P = 0.001). CONCLUSIONS: In traumatic extracranial ICA pseudoaneurysms, covered stents are used more commonly for penetrating injuries compared to blunt injuries. Penetrating injuries are more strongly associated with the presentation of a hematoma compared to blunt injuries. Stent type may influence the recommended DAPT duration. Surgeons should consider these findings when selecting stent type and DAPT duration with patients presenting with traumatic extracranial ICA pseudoaneurysm.


Subject(s)
Aneurysm, False , Carotid Artery Injuries , Carotid Artery, Internal , Stents , Humans , Carotid Artery Injuries/surgery , Carotid Artery Injuries/etiology , Carotid Artery, Internal/surgery , Aneurysm, False/etiology , Aneurysm, False/surgery , Aneurysm, False/diagnostic imaging , Male , Female , Middle Aged , Adult
18.
Anesthesiology ; 140(3): 610-627, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38349760

ABSTRACT

How general anesthetics work remains a topic of ongoing study. A parallel field of research has sought to identify methods to reverse general anesthesia. Reversal agents could shorten patients' recovery time and potentially reduce the risk of postoperative complications. An incomplete understanding of the mechanisms of general anesthesia has hampered the pursuit for reversal agents. Nevertheless, the search for reversal agents has furthered understanding of the mechanisms underlying general anesthesia. The study of potential reversal agents has highlighted the importance of rigorous criteria to assess recovery from general anesthesia in animal models, and has helped identify key arousal systems (e.g., cholinergic, dopaminergic, and orexinergic systems) relevant to emergence from general anesthesia. Furthermore, the effects of reversal agents have been found to be inconsistent across different general anesthetics, revealing differences in mechanisms among these drugs. The presynapse and glia probably also contribute to general anesthesia recovery alongside postsynaptic receptors. The next stage in the search for reversal agents will have to consider alternate mechanisms encompassing the tripartite synapse.


Subject(s)
Anesthetics, General , Animals , Humans , Anesthesia, General/adverse effects , Caffeine , Arousal , Dopamine
19.
AJP Rep ; 14(1): e62-e65, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38370331

ABSTRACT

Maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can affect placental function, but the possibility of intrauterine transmission has been debated. Several authors have published inclusion criteria for vertical transmission, but few reports exist that are able to meet the suggested requirements. Despite the fact that the majority of fetuses born to infected mothers do well, others become critically ill. We present a case of likely intrauterine transmission of a neonate born to a mother who was recently symptomatic with a positive SARS CoV-2 polymerase chain reaction (PCR). The parturient complained of decreased fetal movement and presented at 31 2/7 weeks' gestation with a biophysical profile score of 2/10 and required an emergency cesarean delivery. The neonate went on to develop severe leukopenia with signs of sepsis with a positive SARS CoV-2 PCR on day 4 of life and an otherwise pan-negative workup. Meeting criteria for transplacental transmission requires timely collection of several diagnostic studies that are not standard of care. Further research is needed to support the notion that intrauterine/transplacental infection is possible. Collection swabs should be obtained soon after delivery to help diagnose neonatal infection because early diagnosis is crucial to help identify opportunities for intervention.

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