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Translational Andrology and Urology May 2024Penile prosthesis implantation is an effective treatment for erectile dysfunction (ED) with high patient satisfaction and effectiveness. Unfortunately, infections remain... (Review)
Review
Penile prosthesis implantation is an effective treatment for erectile dysfunction (ED) with high patient satisfaction and effectiveness. Unfortunately, infections remain a dreaded complication, often necessitating device removal and imposing a substantial healthcare cost. Biofilms are communities of microorganisms encased in a self-produced polymeric matrix that can attach to penile prostheses. Biofilms have been demonstrated on the majority of explanted prostheses for both infectious and non-infectious revisions and are prevalent even in asymptomatic patients. Biofilms play a role in microbial persistence and exhibit unique antibiotic resistance strategies that can lead to increased infection rates in revision surgery. Biofilms demonstrate physical barriers through the development of an extracellular polymeric substance (EPS) that hinders antibiotic penetrance and the bacteria within biofilms demonstrate reduced metabolic activity that weakens the efficacy of traditional antibiotics. Despite these challenges, new methods are being developed and investigated to prevent and treat biofilms. These treatments include surface modifications, biosurfactants, tissue plasminogen activator (tPA), and nitric oxide (NO) to prevent bacterial adhesion and biofilm formation. Additionally, novel antibiotic treatments are currently under investigation and include antimicrobial peptides (AMPs), bacteriophages, and refillable antibiotic coatings. This article reviews biofilm formation, the challenges that biofilms present to conventional antibiotics, current treatments, and experimental approaches for biofilm prevention and treatment.
PubMed: 38855589
DOI: 10.21037/tau-23-550 -
MedRxiv : the Preprint Server For... May 2024High multiplicity of infection or MOI, the number of genetically distinct parasite strains co-infecting a single human host, characterizes infectious diseases including...
High multiplicity of infection or MOI, the number of genetically distinct parasite strains co-infecting a single human host, characterizes infectious diseases including falciparum malaria at high transmission. It accompanies high asymptomatic prevalence despite high exposure, creating a large transmission reservoir challenging intervention. High MOI and asymptomatic prevalence are enabled by immune evasion of the parasite achieved via vast antigenic diversity. Force of infection or FOI, the number of new infections acquired by an individual host over a given time interval, is the dynamic sister quantity of MOI, and a key epidemiological parameter for monitoring the impact of antimalarial interventions and assessing vaccine or drug efficacy in clinical trials. FOI remains difficult, expensive, and labor-intensive to accurately measure, especially in high-transmission regions, whether directly via cohort studies or indirectly via the fitting of epidemiological models to repeated cross-sectional surveys. We propose here the application of queuing theory to obtain FOI on the basis of MOI, in the form of either a two-moment approximation method or Little's law. We illustrate these methods with MOI estimates obtained under sparse sampling schemes with the recently proposed " coding" method, based on sequences of the multigene family encoding for the major variant surface antigen of the blood stage of malaria infection. The methods are evaluated with simulation output from a stochastic agent-based model, and are applied to an interrupted time-series study from Bongo District in northern Ghana before and immediately after a three-round transient indoor residual spraying (IRS) intervention. We incorporate into the sampling of the simulation output, limitations representative of those encountered in the collection of field data, including under-sampling of genes, missing data, and usage of antimalarial drug treatment. We address these limitations in MOI estimates with a Bayesian framework and an imputation bootstrap approach. We demonstrate that both proposed methods give good and consistent FOI estimates across various simulated scenarios. Their application to the field surveys shows a pronounced reduction in annual FOI during intervention, of more than 70%. The proposed approach should be applicable to the many geographical locations where cohort or cross-sectional studies with regular and frequent sampling are lacking but single-time-point surveys under sparse sampling schemes are available, and for MOI estimates obtained in different ways. They should also be relevant to other pathogens of humans, wildlife and livestock whose immune evasion strategies are based on large antigenic variation resulting in high multiplicity of infection.
PubMed: 38853963
DOI: 10.1101/2024.02.12.24302148 -
In silico design of peptide inhibitors for Dengue virus to treat Dengue virus-associated infections.Scientific Reports Jun 2024Dengue virus is a single positive-strand RNA virus that is composed of three structural proteins including capsid, envelope, and precursor membrane while seven...
Dengue virus is a single positive-strand RNA virus that is composed of three structural proteins including capsid, envelope, and precursor membrane while seven non-structural proteins (NS1, NS2A, NS2B, NS3A, NS3B, NS4, and NS5). Dengue is a viral infection caused by the dengue virus (DENV). DENV infections are asymptomatic or produce only mild illness. However, DENV can occasionally cause more severe cases and even death. There is no specific treatment for dengue virus infections. Therapeutic peptides have several important advantages over proteins or antibodies: they are small in size, easy to synthesize, and have the ability to penetrate the cell membranes. They also have high activity, specificity, affinity, and less toxicity. Based on the known peptide inhibitor, the current study designs peptide inhibitors for dengue virus envelope protein using an alanine and residue scanning technique. By replacing I21 with Q21, L14 with H14, and V28 with K28, the binding affinity of the peptide inhibitors was increased. The newly designed peptide inhibitors with single residue mutation improved the binding affinity of the peptide inhibitors. The inhibitory capability of the new promising peptide inhibitors was further confirmed by the utilization of MD simulation and free binding energy calculations. The molecular dynamics simulation demonstrated that the newly engineered peptide inhibitors exhibited greater stability compared to the wild-type peptide inhibitors. According to the binding free energies MM(GB)SA of these developed peptides, the first peptide inhibitor was the most effective against the dengue virus envelope protein. All peptide derivatives had higher binding affinities for the envelope protein and have the potential to treat dengue virus-associated infections. In this study, new peptide inhibitors were developed for the dengue virus envelope protein based on the already reported peptide inhibitor.
Topics: Dengue Virus; Peptides; Dengue; Antiviral Agents; Humans; Drug Design; Molecular Dynamics Simulation; Viral Envelope Proteins; Computer Simulation; Protein Binding
PubMed: 38849372
DOI: 10.1038/s41598-024-63064-1 -
Acta Medica Portuguesa Jun 2024Chlamydia trachomatis infection is the most prevalent sexually transmitted bacterial infection in the world. Being associated with a large number of asymptomatic...
Chlamydia trachomatis infection is the most prevalent sexually transmitted bacterial infection in the world. Being associated with a large number of asymptomatic carriers, the diagnosis is frequently challenging and requires appropriate laboratory testing. In Portugal, the incidence of the disease has been consistently increasing in recent years, meaning that special awareness is required for case identification, contact tracing and application of appropriate treatments. These recommendations result from the adaptation of the international consensuses on the diagnosis and treatment of Chlamydia trachomatis infection to the Portuguese healthcare setting, with the aim of standardizing the clinical and laboratory approach to symptomatic and nonsymptomatic carriers of the disease.
Topics: Humans; Chlamydia trachomatis; Portugal; Chlamydia Infections
PubMed: 38848698
DOI: 10.20344/amp.21442 -
Indian Dermatology Online Journal 2024Trichostasis spinulosa is a disorder of hair follicles characterized by the retention of vellus telogen club hair, leading to the formation of comedo-like lesions. It...
Trichostasis spinulosa is a disorder of hair follicles characterized by the retention of vellus telogen club hair, leading to the formation of comedo-like lesions. It usually presents over the face and is frequently asymptomatic. We report a 53-year-old female who presented with multiple itchy, discrete, bluish-black, 2-3 mm comedo-like follicular papules and pustules on her breast and lower abdomen for the past 2 years. dermoscopy showed keratotic plugs with a tuft of hair. Extraction dermoscopy yielded a cystic structure filled with keratin and multiple vellus telogen club hairs. Histology showed a cyst lined by squamous epithelium containing abundant laminated keratinous debris and a vellus hair shaft. Truncal or breast involvement, as seen in the present case, is relatively rare, and can be pruritic, causing significant morbidity due to itching and secondary bacterial infections. Dermoscopy, especially extraction dermoscopy, can show diagnostic features and obviate the need for abiopsy.
PubMed: 38845642
DOI: 10.4103/idoj.idoj_544_23 -
MMWR. Morbidity and Mortality Weekly... Jun 2024Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and...
Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and life-threatening (1). Six serogroups (A, B, C, W, X, and Y) account for most cases (2). N. meningitidis is transmitted person-to-person via respiratory droplets and oropharyngeal secretions. Asymptomatic persons can carry N. meningitidis and transmit the bacteria to others, potentially causing illness among susceptible persons. Outbreaks can occur in conjunction with large gatherings (3,4). Vaccines are available to prevent meningococcal disease. Antibiotic prophylaxis for close contacts of infected persons is critical to preventing secondary cases (2).
Topics: Humans; Meningococcal Infections; United States; France; Saudi Arabia; Young Adult; Adult; Adolescent; Male; Female; Neisseria meningitidis; Child; Child, Preschool; United Kingdom; Middle Aged; Infant; Aged; Travel-Related Illness; Disease Outbreaks; Travel
PubMed: 38843099
DOI: 10.15585/mmwr.mm7322e1 -
Frontiers in Cellular and Infection... 2024Recent studies indicate that human spleen contains over 95% of the total parasite biomass during chronic asymptomatic infections caused by . Previous studies have...
Recent studies indicate that human spleen contains over 95% of the total parasite biomass during chronic asymptomatic infections caused by . Previous studies have demonstrated that extracellular vesicles (EVs) secreted from infected reticulocytes facilitate binding to human spleen fibroblasts (hSFs) and identified parasite genes whose expression was dependent on an intact spleen. Here, we characterize the spleen-dependent hypothetical gene (PVX_114580). Using CRISPR/Cas9, PVX_114580 was integrated into 3D7 genome and expressed during asexual stages. Immunofluorescence analysis demonstrated that the protein, which we named (PvSDP1), was located at the surface of infected red blood cells in the transgenic line and this localization was later confirmed in natural infections. Plasma-derived EVs from -infected individuals (PvEVs) significantly increased cytoadherence of 3D7_PvSDP1 transgenic line to hSFs and this binding was inhibited by anti-PvSDP1 antibodies. Single-cell RNAseq of PvEVs-treated hSFs revealed increased expression of adhesion-related genes. These findings demonstrate the importance of parasite spleen-dependent genes and EVs from natural infections in the formation of intrasplenic niches in , a major challenge for malaria elimination.
Topics: Extracellular Vesicles; Plasmodium vivax; Humans; Spleen; Malaria, Vivax; Protozoan Proteins; Erythrocytes; Fibroblasts; Plasmodium falciparum; Cell Adhesion; Host-Parasite Interactions
PubMed: 38828264
DOI: 10.3389/fcimb.2024.1408451 -
International Journal For Parasitology.... Aug 2024Intestinal protozoa, which can be asymptomatic or cause diarrhea, dysentery and even death, are among the main agents that affect nonhuman primates (NHPs) kept under...
Intestinal protozoa, which can be asymptomatic or cause diarrhea, dysentery and even death, are among the main agents that affect nonhuman primates (NHPs) kept under human care. Nevertheless, information on the molecular and morphometric profiles of parabasilids in the Neotropics is still scarce. In this context, the objective of this study was to isolate the Parabasalia protozoa detected in the feces of NHPs and their keepers in Pavlova and TYSGM9 media and to characterize the isolates by molecular biology and morphometry. Fecal samples from NHPs from five Brazilian institutions were analyzed. Direct examination was performed immediately after obtaining the samples. A total of 511 fecal samples from NHPs were collected, and 10.6% contained parabasilids. Regarding the handlers, of the 74 samples analyzed, three were positive. In vitro-generated parabasilid isolates were successfully obtained from all positive samples, as identified via microscopy. Isolates of the parasite were obtained both from New World NHPs, including the genera , , , , , , and and from the Old World primate . Forty-nine NHP isolates were molecularly identified: (16), (14), (13) and (6). The human isolates were identified as sp. (2) and (1). Visualization and morphometric analysis revealed trophozoites with piriform or rounded shapes that presented variable measurements. The isolates previously characterized as had up to five free flagella, while and sp. had up to four free flagella, and had a maximum of three free flagella. These morphometric characteristics corroborated the molecular identification. In general, a variety of parabasilids were observed to infect NHPs, and was isolated from biological samples from both NHPs and their keepers, a finding that reinforces the susceptibility of these hosts to infections by parabasilids in Brazil.
PubMed: 38827824
DOI: 10.1016/j.ijppaw.2024.100946