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1.
Noncoding RNA Res ; 10: 41-54, 2025 Feb.
Article in English | MEDLINE | ID: mdl-39296638

ABSTRACT

In the search for new biomarkers and therapeutic targets for infectious diseases, several molecules have been investigated. Small RNAs, known as microRNAs (miRs), are important regulators of gene expression, and have emerged as promising candidates for these purposes. MiRs are a class of small, endogenous non-coding RNAs that play critical roles in several human diseases, including host-pathogen interaction mechanisms. Recently, miRs signatures have been reported in different infectious diseases, opening new perspectives for molecular diagnosis and therapy. MiR profiles can discriminate between healthy individuals and patients, as well as distinguish different disease stages. Furthermore, the possibility of assessing miRs in biological fluids, such as serum and whole blood, renders these molecules feasible for the development of new non-invasive diagnostic and prognostic tools. In this manuscript, we will comprehensively describe miRs as biomarkers and therapeutic targets in infectious diseases and explore how they can contribute to the advance of existing and new tools. Additionally, we will discuss different miR analysis platforms to understand the obstacles and advances of this molecular approach and propose their potential clinical applications and contributions to public health.

2.
Biomaterials ; 313: 122761, 2025 Feb.
Article in English | MEDLINE | ID: mdl-39241550

ABSTRACT

Biofilm-associated infections (BAIs) continue to pose a major challenge in the medical field. Nanomedicine, in particular, promises significant advances in combating BAIs through the introduction of a variety of nanomaterials and nano-antimicrobial strategies. However, studies to date have primarily focused on the removal of the bacterial biofilm and neglect the subsequent post-biofilm therapeutic measures for BAIs, rendering pure anti-biofilm strategies insufficient for the holistic recovery of affected patients. Herein, we construct an emerging dual-functional composite nanosheet (SiHx@Ga) that responds to pHs fluctuation in the biofilm microenvironment to enable a sequential therapy of BAIs. In the acidic environment of biofilm, SiHx@Ga employs the self-sensitized photothermal Trojan horse strategy to effectively impair the reactive oxygen species (ROS) defense system while triggering oxidative stress and lipid peroxidation of bacteria, engendering potent antibacterial and anti-biofilm effects. Surprisingly, in the post-treatment phase, SiHx@Ga adsorbs free pathogenic nucleic acids released after biofilm destruction, generates hydrogen with ROS-scavenging and promotes macrophage polarization to the M2 type, effectively mitigating damaging inflammatory burst and promoting tissue healing. This well-orchestrated strategy provides a sequential therapy of BAIs by utilizing microenvironmental variations, offering a conceptual paradigm shift in the field of nanomedicine anti-infectives.


Subject(s)
Anti-Bacterial Agents , Biofilms , Gallium , Reactive Oxygen Species , Biofilms/drug effects , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Reactive Oxygen Species/metabolism , Gallium/chemistry , Gallium/pharmacology , Mice , Drug Carriers/chemistry , RAW 264.7 Cells , Humans , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology
4.
Cent Eur J Public Health ; 32(3): 178-182, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39352093

ABSTRACT

OBJECTIVES: Temperature is the most important environmental variable associated with the varicella frequency across the world. The present study compares the incidence of varicella in the districts of Bulgaria against some climatic factors and tries to find environmental variables which account for the differences in the varicella distribution observed among the Bulgarian districts. METHODS: The 28 Bulgarian districts were used as units of observation and their average 10-year varicella incidence (2009-2018) was tested for correlation with the standard bioclimatic variables of WorldClim, version 2. RESULTS: The WorldClim estimates for the annual mean temperature, the maximal temperature of the warmest month, the minimal temperature of the coldest month, the mean temperature of the coldest quarter, and the solar radiation inversely and not significantly correlated with the average 10-year varicella frequency. The precipitation of the warmest quarter and the wind speed correlated positively and also not significantly. Only the mean temperature of the driest quarter correlates significantly with the incidence at district level (Spearman's rank correlation coefficient of -0.45, p = 0.02). The mean of average 10-year varicella incidence rates among districts with driest quarter during the winter (January, February, March) was 387.6 ± 114.1, while among districts with driest quarter during the summer/autumn (July, August, September or August, September, October) 283.3 ± 102.1 (p = 0.02, ANOVA test). CONCLUSIONS: Dry winter and/or wet summer appear as significant determinants for the fluctuant spread of varicella infection in Bulgaria.


Subject(s)
Chickenpox , Climate , Bulgaria/epidemiology , Humans , Chickenpox/epidemiology , Incidence , Seasons
5.
Elife ; 132024 Oct 02.
Article in English | MEDLINE | ID: mdl-39356739

ABSTRACT

Candida glabrata can thrive inside macrophages and tolerate high levels of azole antifungals. These innate abilities render infections by this human pathogen a clinical challenge. How C. glabrata reacts inside macrophages and what is the molecular basis of its drug tolerance are not well understood. Here, we mapped genome-wide RNA polymerase II (RNAPII) occupancy in C. glabrata to delineate its transcriptional responses during macrophage infection in high temporal resolution. RNAPII profiles revealed dynamic C. glabrata responses to macrophages with genes of specialized pathways activated chronologically at different times of infection. We identified an uncharacterized transcription factor (CgXbp1) important for the chronological macrophage response, survival in macrophages, and virulence. Genome-wide mapping of CgXbp1 direct targets further revealed its multi-faceted functions, regulating not only virulence-related genes but also genes associated with drug resistance. Finally, we showed that CgXbp1 indeed also affects fluconazole resistance. Overall, this work presents a powerful approach for examining host-pathogen interaction and uncovers a novel transcription factor important for C. glabrata's survival in macrophages and drug tolerance.

6.
Vet Microbiol ; 298: 110270, 2024 Sep 28.
Article in English | MEDLINE | ID: mdl-39357096

ABSTRACT

Orthoflaviviruses are single-stranded RNA viruses characterized by highly efficient self-amplification of RNA in host cells, which makes them attractive vehicles for vaccines. Numerous preclinical and clinical studies have demonstrated the efficacy and safety of orthoflavivirus replicon vectors for vaccine development. In this study, we constructed Tembusu virus (TMUV) replicon-based single-round infectious particles (SRIPs) as vaccine development platform. To evaluate the potential of TMUV SRIPs as vaccines, we generated SRIPs that express the heterologous Fowl adenovirus 4 (FAdV-4) fiber2 protein and fiber2 head domain, named TMUVRP-fiber2 and TMUVRP-fiber2H, respectively. To assess the immunogenicity of the TMUV SRIPs, SPF chicks were intramuscularly inoculated twice. Our results showed that the TMUVRP-fiber2 vaccines elicited high levels of neutralizing antibodies. Challenge experiments showed that TMUVRP-fiber2 provided full protection against virulent FAdV-4 and significantly reduced viral shedding. Moreover, the immunogenicity of TMUVRP-fiber2H was significantly lower than that of TMUVRP-fiber2, which was reflected in the neutralizing antibody titer, survival rate, and virus shedding after challenge. Therefore, our results suggested that TMUV SRIPs are a promising novel platform for the development of vaccines for existing and emerging poultry diseases.

8.
Transfusion ; 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39360409

ABSTRACT

BACKGROUND: Hyperhemolysis syndrome (HHS) is a catastrophic anemia characterized by destruction of both donor and patient red blood cells (RBC). HHS occurs after transfusion and can cause significant morbidity and mortality. Given the difficulty in diagnosing and managing this process, we provide a detailed overview of our treatment protocol. STUDY DESIGN AND METHODS: Members of the Transfusion Medicine and Hematology faculty at our institution collaborated in an iterative process to produce a consensus approach to patients with HHS. RESULTS: We present diagnostic criteria for HHS: recent transfusion within past 7 days (up to 21 days), rapid hemoglobin decline to below the pretransfusion level (usually hemoglobin drop >25% from pretransfusion), a significant decrease in HbA% (in patients with sickle cell disease or beta thalassemia), low or decreasing reticulocyte count in a patient with worsening anemia, and laboratory evidence of hemolysis. We also describe an in-depth approach to management focusing on optimizing hematopoiesis while dampening the immune response. CONCLUSION: We provide a comprehensive approach to the diagnosis and management of HHS based on contemporary literature and clinical experience designed to optimize outcomes for patients.

9.
Clin Microbiol Rev ; : e0008023, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39360834

ABSTRACT

SUMMARYThe opportunistic pathogen Mycobacterium abscessus (Mab) causes fatal lung infections that bear similarities-and notable differences-with tuberculosis (TB) pulmonary disease. In contrast to TB, no antibiotic is formally approved to treat Mab disease, there is no reliable cure, and the discovery and development pipeline is incredibly thin. Here, we discuss the factors behind the unsatisfactory cure rates of Mab disease, namely intrinsic resistance and persistence of the pathogen, and the use of underperforming, often parenteral and toxic, repurposed drugs. We propose preclinical strategies to build injectable-free sterilizing and safe regimens: (i) prioritize oral bactericidal antibiotic classes, with an initial focus on approved agents or advanced clinical candidates to provide immediate options for desperate patients, (ii) test drug combinations early, (iii) optimize novel leads specifically for M. abscessus, and (iv) consider pharmacokinetic-pharmacodynamic targets at the site of disease, the lung lesions in which drug tolerant bacterial populations reside. Knowledge and tool gaps in the preclinical drug discovery process are identified, including validated mouse models and computational platforms to enable in vitro mouse-human translation. We briefly discuss recent advances in clinical development, the need for readouts and biomarkers that correlate with cure, and clinical trial concepts adapted to the uniqueness of Mab patient populations for new regimen development. In an era when most pharmaceutical firms have withdrawn from antimicrobial drug discovery, the breakthroughs needed to fill the regimen development pipeline will likely come from partnerships between academia, biotech, pharma, non-profit organizations, and governments, with incentives that reward cooperation.

10.
mSphere ; : e0043024, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39360839

ABSTRACT

The human pathobiont Streptococcus pyogenes forms biofilms and causes infections, such as pharyngotonsillitis and necrotizing fasciitis. Bacterial biofilms are more resilient to antibiotic treatment, and new therapeutic strategies are needed to control biofilm-associated infections, such as recurrent pharyngotonsillitis. Lactiplantibacillus plantarum and Lacticaseibacillus rhamnosus are two bacterial commensals used for their probiotic properties. This study aimed to elucidate the anti-biofilm properties of L. plantarum and L. rhamnosus cell-free supernatants (LPSN and LRSN, respectively) on S. pyogenes biofilms grown in vitro in supplemented minimal medium. When planktonic or biofilm S. pyogenes were exposed to LPSN or LRSN, S. pyogenes survival was reduced significantly in a concentration-dependent manner, and the effect was more pronounced on preformed biofilms. Enzymatic digestion of LPSN and LRSN suggested that glycolipid compounds might cause the antimicrobial effect. In conclusion, this study indicates that L. plantarum and L. rhamnosus produce glycolipid bioactive compounds that reduce the viability of S. pyogenes in planktonic and biofilm cultures.IMPORTANCEStreptococcus pyogenes infections are a significant concern for populations at risk, such as children and the elderly, as non-invasive conditions such as impetigo and strep throat can lead to severe invasive diseases such as necrotizing fasciitis. Despite its susceptibility to current antibiotics, the formation of biofilm by this pathogen decreases the efficacy of antibiotic treatment alone. The ability of commensal lactobacillus to kill S. pyogenes has been documented by previous studies using in vitro settings. The relevance of our study is in using a physiological setup and a more detailed understanding of the nature of the lactobacillus molecule affecting the viability of S. pyogenes. This additional knowledge will help for a better comprehension of the molecules' characteristics and kinetics, which in turn will facilitate new avenues of research for its translation to new therapies.

11.
Leg Med (Tokyo) ; 71: 102530, 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39361989

ABSTRACT

INTRODUCTION: Autopsies may expose to infectious risks. The objective of this study is to assess the risk of post-mortem transmission of HIV, HBV, HCV, Mycobacterium tuberculosis (MBT), SARS-CoV2 and prion in the workplace and to estimate the duration of their infectiousness. MATERIAL AND METHOD: the PRISMA 2020 guideline was used. Pubmed, Web of Science, Google Scholar and Sciencedirect databases were assessed until February 28, 2023. We searched for articles in any language and any date of publication. Studies involving animals, transmission between two living people or transmission outside the workplace were excluded. Risk of bias was assessed using the appropriate assessment tools for each type of study. A descriptive analysis was performed. RESULTS: A total of 46 studies were included. Cases of post-mortem transmission were certain for HIV (n = 1) and MBT (n = 18). The longest post-mortem interval for positive diagnostic tests was 17 days for HIV, 60 for HBV, 7 for HCV, 36 for MBT and 17 for SARS-CoV2. The longest post-mortem interval for positive cultures was 21 h for HIV, 6 days for HBV, 36 days for MBT, 17 days for SARS-CoV2. The methodology of the studies was heterogeneous, some of them associated with a high risk of bias. CONCLUSION: There is a lack of consistent data in the literature concerning the infectivity of cadavers, except for MBT. Legislation appears to be based on minimizing contact between the biological agent and the professional. In the absence of recent robust scientific data, workers should systematically follow the best practice recommendations.

12.
Stat Med ; 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39362790

ABSTRACT

Many important questions in infectious disease epidemiology involve associations between covariates (e.g., age or vaccination status) and infectiousness or susceptibility. Because disease transmission produces dependent outcomes, these questions are difficult or impossible to address using standard regression models from biostatistics. Pairwise survival analysis handles dependent outcomes by calculating likelihoods in terms of contact interval distributions in ordered pairs of individuals. The contact interval in the ordered pair i j $$ ij $$ is the time from the onset of infectiousness in i $$ i $$ to infectious contact from i $$ i $$ to j $$ j $$ , where an infectious contact is sufficient to infect j $$ j $$ if they are susceptible. Here, we introduce a pairwise accelerated failure time regression model for infectious disease transmission that allows the rate parameter of the contact interval distribution to depend on individual-level infectiousness covariates for i $$ i $$ , individual-level susceptibility covariates for j $$ j $$ , and pair-level covariates (e.g., type of relationship). This model can simultaneously handle internal infections (caused by transmission between individuals under observation) and external infections (caused by environmental or community sources of infection). We show that this model produces consistent and asymptotically normal parameter estimates. In a simulation study, we evaluate bias and confidence interval coverage probabilities, explore the role of epidemiologic study design, and investigate the effects of model misspecification. We use this regression model to analyze household data from Los Angeles County during the 2009 influenza A (H1N1) pandemic, where we find that the ability to account for external sources of infection increases the statistical power to estimate the effect of antiviral prophylaxis.

13.
Innate Immun ; : 17534259241287311, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39363687

ABSTRACT

Innate lymphoid cells (ILCs) are the main resident lymphocytes that mostly reside in tissues owing to the lack of adaptive antigen receptors. These cells are involved in early anti-infective immunity, antitumour immunity, regulation of tissue inflammation, and maintenance of homeostasis in the internal environment of tissues and have been referred to as the "first armies stationed in the human body". ILCs are widely distributed in the lungs, colon, lymph nodes, oral mucosa and even embryonic tissues. Due to the advantage of their distribution location, they are often among the first cells to come into contact with pathogens.Relevant studies have demonstrated that ILCs play an early role in the defence against a variety of pathogenic microorganisms, including bacteria, viruses, fungi and helminths, before they intervene in the adaptive immune system. ILCs can initiate a rapid, nonspecific response against pathogens prior to the initiation of an adaptive immune response and can generate a protective immune response against specific pathogens, secreting different effectors to play a role.There is growing evidence that ILCs play an important role in host control of infectious diseases. In this paper, we summarize and discuss the current known infectious diseases in which ILCs are involved and ILC contribution to the defence against infectious diseases. Further insights into the mechanisms of ILCs action in different infectious diseases will be useful in facilitating the development of therapeutic strategies for early control of infections.

14.
Pediatr Allergy Immunol ; 35(10): e14251, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39365274

ABSTRACT

BACKGROUND: Consumption of raw cow's milk has repeatedly been shown to protect from asthma, allergies, and respiratory infections. As raw milk bears potential health hazards, it cannot be recommended for prevention. Therefore, we performed an intervention study with microbially safe but otherwise minimally processed cow's milk. Here we describe feasibility and safety of the trial. METHODS: The MARTHA trial (DRKS00014781) was set up as a double-blind randomized intervention in a population residing in Bavaria. Infants from 6 to 36 months of age consumed minimally processed cow's milk (intervention arm) or ultra-heat-treated (UHT) semi-skimmed milk (comparator arm). RESULTS: At the age of 6 to 12 months, 260 infants were enrolled, with 72% having a family history of atopy. The extensive screening system for milk consumption and symptoms suggestive of adverse events was well accepted with 22,988 completed weekly surveys and an average completion of 82% surveys sent out. The children consumed the study milk on average on 457 days (61% of intervention days). The intervention proved to be safe without any case of milk allergy or milk intolerance under the intervention in both arms. All 6 cases of serious adverse events were unrelated to milk. The most common reason was unscheduled hospitalization of more than 3 days. CONCLUSIONS: The intervention with minimally processed milk and the study instruments proved feasible. During the age of 6 to 36 months, there was no increased risk of milk allergy in a population with a substantial proportion of family history of atopy.


Subject(s)
Feasibility Studies , Milk Hypersensitivity , Milk , Humans , Infant , Animals , Double-Blind Method , Female , Male , Milk/adverse effects , Milk/immunology , Milk Hypersensitivity/prevention & control , Child, Preschool , Germany/epidemiology , Cattle
15.
Cureus ; 16(8): e68319, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39350879

ABSTRACT

Opportunistic infections most often occur in immunocompromised patients, however, they can also occur in immunocompetent patients. While rare, bacterial infections such as those from Streptococcus constellatus (S. constellatus) can cause severe pyogenic infections and abscess formations. It is important to understand the risk factors, diagnostic workup, and management of patients with this rare but enduring bacterial infection. Although most of the literature reports the prevalence of S. constellatus in adults, occurrences should not be overlooked in the pediatric population. We present a case of an immunocompetent 19-year-old female who initially presented with refractory fevers and was found to have an intrahepatic abscess and bilateral tubo-ovarian abscesses. Management of this patient included percutaneous drainage of the hepatic abscess and antibiotic treatment for 28 days.

16.
Elife ; 132024 Oct 01.
Article in English | MEDLINE | ID: mdl-39352247

ABSTRACT

The Gram-negative bacterium Myxococcus xanthus glides on solid surfaces. Dynamic bacterial focal adhesion complexes (bFACs) convert proton motive force from the inner membrane into mechanical propulsion on the cell surface. It is unclear how the mechanical force transmits across the rigid peptidoglycan (PG) cell wall. Here, we show that AgmT, a highly abundant lytic PG transglycosylase homologous to Escherichia coli MltG, couples bFACs to PG. Coprecipitation assay and single-particle microscopy reveal that the gliding motors fail to connect to PG and thus are unable to assemble into bFACs in the absence of an active AgmT. Heterologous expression of E. coli MltG restores the connection between PG and bFACs and thus rescues gliding motility in the M. xanthus cells that lack AgmT. Our results indicate that bFACs anchor to AgmT-modified PG to transmit mechanical force across the PG cell wall.


Subject(s)
Cell Wall , Glycosyltransferases , Myxococcus xanthus , Peptidoglycan , Peptidoglycan/metabolism , Cell Wall/metabolism , Myxococcus xanthus/genetics , Myxococcus xanthus/physiology , Myxococcus xanthus/metabolism , Myxococcus xanthus/enzymology , Glycosyltransferases/metabolism , Glycosyltransferases/genetics , Escherichia coli/genetics , Escherichia coli/metabolism , Focal Adhesions/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Bacterial Adhesion
17.
J Infect Public Health ; 17(11): 102547, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39353398

ABSTRACT

Millions of pilgrims travel annually to Makkah and Madinah, Saudi Arabia, for the Hajj, posing unique challenges for public health management and disease control. The large influx of pilgrims from diverse backgrounds traveling to a confined geographic area, coupled with the close proximity and interactions among them, create significant pressure on the healthcare system and heighten the potential for the spread of communicable diseases. This review examines current trends in communicable diseases and their impact, drawing insights from expert perspectives on the required (i.e., meningococcal meningitis, polio, and yellow fever) and recommended vaccinations (influenza, COVID-19) for Hajj participants. The updated COVID-19 vaccine is mandatory for local pilgrims and is strongly recommended for international visitors, with ongoing discussions on adapting protocols to address emerging variants. The timing and strain coverage of influenza vaccination, along with quadrivalent meningococcal vaccination, are also emphasized as critical preventive measures. Diseases such as cholera and yellow fever are addressed underscoring the need for rigorous surveillance and targeted vaccination strategies to mitigate the risk of transmission during the Hajj. By providing up-to-date information on mandated and recommended vaccinations, this review aims to empower pilgrims and healthcare professionals to make informed decisions regarding public health and disease prevention during this significant event.

18.
Front Vet Sci ; 11: 1460993, 2024.
Article in English | MEDLINE | ID: mdl-39355142

ABSTRACT

Positive emotions can reduce disease susceptibility during infectious challenges in humans, and emerging evidence suggests similar effects in farm animals. Because play behaviour may support a positive emotional state in pigs, this study investigates whether rearing pigs with regular intermittent play opportunities enhances disease resilience when challenged with porcine reproductive and respiratory syndrome virus (PRRSV). Litters were assigned to either play (PLY; n = 5 L) or control (CON; n = 4 L) treatments at birth. In PLY, play was promoted with extra space and enrichment items for three hours daily from five days of age (doa). At weaning (25 ± 2 doa; mean ± SD), 28 pigs (14/treatment) were selected for a disease challenge, based on weight, sex, and sow. The pigs were transported to a disease containment facility and at 43 ± 2 doa (day 0 post-inoculation, DPI) inoculated with PRRSV. Skin lesions, blood, rectal temperature, clinical signs, body weight, and behaviour were collected pre- and post-inoculation. Play opportunities for PLY continued every other day until euthanasia of all pigs at 65 ± 2 doa (22 DPI). PLY pigs exhibited fewer skin lesions following transport and throughout the infection compared to CON. Although the viral load did not differ between treatments, PLY pigs had a lower probability of experiencing moderate and severe respiratory distress, with a shorter duration. PLY also performed better throughout the infection, showing higher ADG and greater feed efficiency. The immune response differed as well. PLY pigs had fewer monocytes on 8 DPI than CON, with levels returning to baseline by 21 DPI, whereas CON levels exceeded baseline. Regardless of day of infection, lymphocyte counts tended to be lower in PLY than in CON, and white blood cells and neutrophils were also lower, but only in slow-growing pigs. PLY pigs continued to play during the infection, demonstrating less sickness behaviour and emphasizing the rewarding properties of play. Results suggest that PLY pigs were less affected by PRRSV and developed increased resilience to PRRSV compared to CON. This study demonstrates that rearing pigs in an environment supporting positive experiences through provision of play opportunities can enhance resilience against common modern production challenges, underscoring the value of positive welfare in intensive pig farming.

19.
Front Vet Sci ; 11: 1428713, 2024.
Article in English | MEDLINE | ID: mdl-39355141

ABSTRACT

Introduction: Strengthening global health security relies on adequate protection against infectious diseases through vaccination and treatment. Toll-like receptor (TLR) agonists exhibit properties that can enhance immune responses, making them potential therapeutic agents or vaccine adjuvants. Methods: We conducted an extensive systematic review to assess the efficacy of TLR agonists as therapeutic agents or vaccine adjuvants for infectious diseases and their safety profile in animals, excluding rodents and cold-blooded animals. We collected qualitative and available quantitative data on the efficacy and safety outcomes of TLR agonists and employed descriptive analysis to summarize the outcomes. Results: Among 653 screened studies, 51 met the inclusion criteria. In this review, 82% (42/51) of the studies used TLR agonists as adjuvants, while 18% (9/51) applied TLR agonist as therapeutic agents. The predominant TLR agonists utilized in animals against infectious diseases was CpG ODN, acting as a TLR9 agonist in mammals, and TLR21 agonists in chickens. In 90% (46/51) of the studies, TLR agonists were found effective in stimulating specific and robust humoral and cellular immune responses, thereby enhancing the efficacy of vaccines or therapeutics against infectious diseases in animals. Safety outcomes were assessed in 8% (4/51) of the studies, with one reporting adverse effects. Discussion: Although TLR agonists are efficacious in enhancing immune responses and the protective efficacy of vaccines or therapeutic agents against infectious diseases in animals, a thorough evaluation of their safety is imperative to in-form future clinical applications in animal studies. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=323122.

20.
Hosp Pharm ; 59(5): 584-587, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39355201

ABSTRACT

Background: Many infectious diseases are diagnosed in emergency departments (ED) and patients are prescribed antimicrobial therapy. Results from cultures typically take a few days to become finalized. Following up on these results is necessary when medication changes are indicated due to results that show bacteria are resistant to the prescribed antibiotics. Involving pharmacists in assessing the culture and sensitivity results, and making interventions when needed, is an innovative way to ensure that patients receive appropriate antimicrobial therapy based on the culture and sensitivity data. This study analyzed the impact of pharmacist involvement in the ED's post-discharge positive culture review process on ED re-visits and hospitalizations. Methods: This single-center, pre- and post-implementation study examined the impact of pharmacist involvement in the post-ED visit culture review process on ED re-visits and hospitalizations. Positive microbiological results included documented growth from urine, skin and soft tissue, throat, blood, or stool cultures. Patients included in the study were of 18 years of age or older and had a positive culture result post ED-discharge. Patients were excluded from the study if they were admitted to the hospital or transferred to another facility. The primary outcomes included ED re-visits within 7 days and hospital readmissions within 30 days for the same condition. The secondary outcomes were percentage of pharmacist interventions accepted and types of pharmacist interventions implemented. Results: A total of 141 patients were included in the study, with 65 in the pre-implementation group and 76 in the post-implementation group. The primary outcome of ED re-visits within 7 days for the same condition occurred in 11 (17%) patients in the pre-implementation group and 5 (7%) patients in the post-implementation group (P = .0454). The primary outcome of hospitalizations within 30 days for the same condition occurred in 5 (8%) patients in the pre-implementation group and 1 (1%) patient in the post-implementation group (P = .0137). Seventeen (94%) out of the 18 pharmacist interventions were accepted and implemented. The intervention types implemented were to recommend to: change antibiotic (35%), not initiate antibiotic (24%), initiate antibiotic (24%), and continue antibiotic (18%). Conclusion: Pharmacist involvement in the ED post-discharge positive culture review process showed a decrease in ED re-visits and hospitalizations for the same condition.

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