Factors associated with HPV-associated sexual risk behaviors among sexually active college students.

High-risk sexual behavior is the primary risk factor for the acquisition and persistence of human papillomavirus (HPV) infection and the development of HPV-associated diseases including cancer. Incidence of HPV infection is high among individuals in their late teens and early 20s. Thus, college students represent a historically high-risk group for HPV infection yet are also a group with the ability to independently access HPV vaccination for HPV prevention. To inform future interventions, we examined factors associated with HPV-associated risky sexual behaviors among sexually active college students. Data (N = 741) were from an anonymous online survey distributed to students at a public Midwestern university in 2021. The outcomes were HPV-associated sexual risk behaviors-number of oral or vaginal sexual partners [high (≥ 5) or low (< 5)] and age of oral or vaginal sexual debut [early (< 18 years) or late (≥ 18 years)]. Multivariable logistic regression models estimated the association between HPV-associated risky sexual behaviors and several predictors including age, gender, relationship status, academic level, country of birth, and rural-urban status. Among sexually active students, approximately 47% and 41% had a high number of lifetime vaginal and oral partners, respectively. Among the same group, 60% and 64% had early vaginal and oral sexual debut. Students who were single and dating (aOR = 1.93; 95% CI = 1.21, 3.08) or single and not dating (2.11; 1.28, 3.48) were more likely to have a high number of vaginal lifetime partners compared with married students. Single (vs. married) students were also about twice as likely to have a high number of oral lifetime partners. Relative to graduate students, freshmen/sophomores were more likely to have an early vaginal (2.44; 1.45, 4.11) and oral (2.14; 1.26, 3.63) sexual debut. Interventions tailored to college freshmen/sophomores and unmarried students should encourage students to receive the HPV vaccine for prevention of future HPV-associated diseases.

The novel circular RNA CircMef2c is positively associated with muscle growth in Nile tilapia.

Muscle growth in teleosts is a complex biological process orchestrated by numerous protein-coding genes and non-coding RNAs. A few recent studies suggest that circRNAs are involved in teleost myogenesis, but the molecular networks involved remain poorly understood. In this study, an integrative omics approach was used to determine myogenic circRNAs in Nile tilapia by quantifying and comparing the expression profile of mRNAs, miRNAs, and circRNAs in fast muscle from full-sib fish with distinct growth rates. There were 1947 mRNAs, 9 miRNAs, and 4 circRNAs differentially expressed between fast- and slow-growing individuals. These miRNAs can regulate myogenic genes and have binding sites for the novel circRNA circMef2c. Our data indicate that circMef2c may interact with three miRNAs and 65 differentially expressed mRNAs to form multiple competing endogenous RNA networks that regulate growth, thus providing novel insights into the role of circRNAs in the regulation of muscle growth in teleosts.

CircPrime: a web-based platform for design of specific circular RNA primers.

BACKGROUND: Circular RNAs (circRNAs) are covalently closed-loop RNAs with critical regulatory roles in cells. Tens of thousands of circRNAs have been unveiled due to the recent advances in high throughput RNA sequencing technologies and bioinformatic tools development. At the same time, polymerase chain reaction (PCR) cross-validation for circRNAs predicted by bioinformatic tools remains an essential part of any circRNA study before publication. RESULTS: Here, we present the CircPrime web-based platform, providing a user-friendly solution for DNA primer design and thermocycling conditions for circRNA identification with routine PCR methods. CONCLUSIONS: User-friendly CircPrime web platform ( http://circprime.elgene.net/ ) works with outputs of the most popular bioinformatic predictors of circRNAs to design specific circular RNA primers. CircPrime works with circRNA coordinates and any reference genome from the National Center for Biotechnology Information database).

Photobiomodulation Reduces the Cytokine Storm Syndrome Associated with COVID-19 in the Zebrafish Model.

Although the exact mechanism of the pathogenesis of coronavirus SARS-CoV-2 (COVID-19) is not fully understood, oxidative stress and the release of pro-inflammatory cytokines have been highlighted as playing a vital role in the pathogenesis of the disease. In this sense, alternative treatments are needed to reduce the level of inflammation caused by COVID-19. Therefore, this study aimed to investigate the potential effect of red photobiomodulation (PBM) as an attractive therapy to downregulate the cytokine storm caused by COVID-19 in a zebrafish model. RT-qPCR analyses and protein-protein interaction prediction among SARS-CoV-2 and Danio rerio proteins showed that recombinant Spike protein (rSpike) was responsible for generating systemic inflammatory processes with significantly increased levels of pro-inflammatory (il1b, il6, tnfa, and nfkbiab), oxidative stress (romo1) and energy metabolism (slc2a1a and coa1) mRNA markers, with a pattern similar to those observed in COVID-19 cases in humans. On the other hand, PBM treatment was able to decrease the mRNA levels of these pro-inflammatory and oxidative stress markers compared with rSpike in various tissues, promoting an anti-inflammatory response. Conversely, PBM promotes cellular and tissue repair of injured tissues and significantly increases the survival rate of rSpike-inoculated individuals. Additionally, metabolomics analysis showed that the most-impacted metabolic pathways between PBM and the rSpike treated groups were related to steroid metabolism, immune system, and lipid metabolism. Together, our findings suggest that the inflammatory process is an incisive feature of COVID-19 and red PBM can be used as a novel therapeutic agent for COVID-19 by regulating the inflammatory response. Nevertheless, the need for more clinical trials remains, and there is a significant gap to overcome before clinical trials can commence.

Dietary supplementation of Bacillus velezensis improves Vibrio anguillarum clearance in European sea bass by activating essential innate immune mechanisms.

Bacillus spp. supplementation as probiotics in cultured fish diets has a long history of safe and effective use. Specifically, B. velezensis show great promise in fine-tuning the European sea bass disease resistance against the pathogenicity caused by several members of the Vibrio family. However, the immunomodulatory mechanisms behind this response remain poorly understood. Here, to examine the inherent immune variations in sea bass, two equal groups were fed for 30 days with a steady diet, with one treatment supplemented with B. velezensis. The serum bactericidal capacity against live cells of Vibrio anguillarum strain 507 and the nitric oxide and lysozyme lytic activities were assayed. At the cellular level, the phagocytic response of peripheral blood leukocytes against inactivated Candida albicans was determined. Moreover, head-kidney (HK) total leukocytes were isolated from previously in vivo treated fish with LPS of V. anguillarum strain 507. Mechanistically, the expression of some essential proinflammatory genes (interleukin-1 (il1b), tumor necrosis factor-alpha (tnfa), and cyclooxygenase 2 (cox2) and the sea bass specific antimicrobial peptide (AMP) dicentracin (dic) expressions were assessed. Surprisingly, the probiotic supplementation significantly increased all humoral lytic and cellular activities assayed in the treated sea bass. In addition, time-dependent differences were observed between the control and probiotic treated groups for all the HK genes markers subjected to the sublethal LPS dose. Although the il1b was the fastest responding gene to a significant level at 48 h post-injection (hpi), all the other genes followed 72 h in the probiotic supplemented group. Finally, an in vivo bacteria challenge against live V. anguillarum was conducted. The probiotic fed fish observed a significantly higher survival. Overall, our results provide clear vertical evidence on the beneficial immune effects of B. velezensis and unveil some fundamental immune mechanisms behind its application as a probiotic agent in intensively cultured European sea bass.

Olfactory sensory neurons mediate ultrarapid antiviral immune responses in a TrkA-dependent manner.

The nervous system regulates host immunity in complex ways. Vertebrate olfactory sensory neurons (OSNs) are located in direct contact with pathogens; however, OSNs' ability to detect danger and initiate immune responses is unclear. We report that nasal delivery of rhabdoviruses induces apoptosis in crypt OSNs via the interaction of the OSN TrkA receptor with the viral glycoprotein in teleost fish. This signal results in electrical activation of neurons and very rapid proinflammatory responses in the olfactory organ (OO), but dampened inflammation in the olfactory bulb (OB). CD8α+ cells infiltrate the OO within minutes of nasal viral delivery, and TrkA blocking, but not caspase-3 blocking, abrogates this response. Infiltrating CD8α+ cells were TCRαß T cells with a nonconventional phenotype that originated from the microvasculature surrounding the OB and not the periphery. Nasal delivery of viral glycoprotein (G protein) recapitulated the immune responses observed with the whole virus, and antibody blocking of viral G protein abrogated these responses. Ablation of crypt neurons in zebrafish resulted in increased susceptibility to rhabdoviruses. These results indicate a function for OSNs as a first layer of pathogen detection in vertebrates and as orchestrators of nasal-CNS antiviral immune responses.

High-level biocidal products effectively eradicate pathogenic γ-proteobacteria biofilms from aquaculture facilities.

The use of effective biocides as disinfectants is essential in aquaculture facilities. However, while most biocides act effectively on free-living planktonic pathogens, they are seldom useful against biofilms. In this study, we evaluate the biocidal efficacy and antimicrobial specific contact time of three disinfectants, Virkon™Aquatic (VirA), peracetic acid (PerA) and hydrogen peroxide (HydP), on Vibrio anguillarum, V. harveyi, V. alginolyticus, and Photobacterium damselae subspecies piscicida against their both life phases. By using the minimum inhibitory, bactericidal, and eradication concentrations of disinfectants acting on the free-living planktonic state (MIC; MBC) and biofilms (MBIC; MBEC), we determined the in vitro susceptibility of each bacterial strain against three different individual concentrations of VirA, PerA, and HydP added at 1, 5, and 10 min intervals. PerA and VirA had the highest bactericidal efficacies against the free-living planktonic state and biofilm of all bacteria. Kinetically, PerA gave a positive result more quickly in both cases regardless of the strain in question, while the weakest HydP required longer than 10 min to act effectively. Moreover, we conducted a short in vivo safety trial by pouring the suggested MIC of each disinfectant into tanks containing juvenile Gilthead seabream (Sparus aurata). A significant mortality after 24 h was observed pointing to the potential risk a mishap of these chemicals might cause to fish. Nevertheless, collectively, our results support the inclusion of biocides within biosecurity protocols in aquaculture facilities and highlight PerA as the most effective disinfectant for fighting against biofilms produced by V. anguillarum, V. harveyi, V. alginolyticus or P. damselae subsp. piscicida.

Phage Therapy as a Focused Management Strategy in Aquaculture.

Therapeutic bacteriophages, commonly called as phages, are a promising potential alternative to antibiotics in the management of bacterial infections of a wide range of organisms including cultured fish. Their natural immunogenicity often induces the modulation of a variated collection of immune responses within several types of immunocytes while promoting specific mechanisms of bacterial clearance. However, to achieve standardized treatments at the practical level and avoid possible side effects in cultivated fish, several improvements in the understanding of their biology and the associated genomes are required. Interestingly, a particular feature with therapeutic potential among all phages is the production of lytic enzymes. The use of such enzymes against human and livestock pathogens has already provided in vitro and in vivo promissory results. So far, the best-understood phages utilized to fight against either Gram-negative or Gram-positive bacterial species in fish culture are mainly restricted to the Myoviridae and Podoviridae, and the Siphoviridae, respectively. However, the current functional use of phages against bacterial pathogens of cultured fish is still in its infancy. Based on the available data, in this review, we summarize the current knowledge about phage, identify gaps, and provide insights into the possible bacterial control strategies they might represent for managing aquaculture-related bacterial diseases.

Function of Circular RNAs in Fish and Their Potential Application as Biomarkers.

Circular RNAs (circRNAs) are an emerging class of regulatory RNAs with a covalently closed-loop structure formed during pre-mRNA splicing. Recent advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of novel approaches to their identification and functional characterization. CircRNAs are stable, developmentally regulated, and show tissue- and cell-type-specific expression across different taxonomic groups. They play a crucial role in regulating various biological processes at post-transcriptional and translational levels. However, the involvement of circRNAs in fish immunity has only recently been recognized. There is also broad evidence in mammals that the timely expression of circRNAs in muscle plays an essential role in growth regulation but our understanding of their expression and function in teleosts is still very limited. Here, we discuss the available knowledge about circRNAs and their role in growth and immunity in vertebrates from a comparative perspective, with emphasis on cultured teleost fish. We expect that the interest in teleost circRNAs will increase substantially soon, and we propose that they may be used as biomarkers for selective breeding of farmed fish, thus contributing to the sustainability of the aquaculture sector.

Aluminum adjuvant potentiates gilthead seabream immune responses but induces toxicity in splenic melanomacrophage centers.

A key goal of a successful vaccine formulation is the strong induction of persistent protective immune responses without producing side-effects. Adjuvants have been proved to be successful in several species at inducing increased immune responses against poorly immunogenic antigens. Fish are not the exception and promising results of adjuvanted vaccine formulations in many species are needed. In this study, over a period of 300 days, we characterized the apparent damage and immune response in gilthead seabream immunized by intraperitoneal injection with the model antigen keyhole limpet hemocyanin (KLH) alone or formulated with Montanide ISA water-in-oil (761 or 763), or Imject™ aluminum hydroxide (aluminium), as adjuvants. Throughout the trial, external tissue damage was examined visually, but no change was observed. Internally, severe adhesions, increased fat tissue, and hepatomegaly were recorded, but, without impairing animal health. At 120 days post priming (dpp), histopathological evaluations of head-kidney, spleen and liver revealed the presence of altered melanomacrophage centers (MMC) in HK and spleen, but not in liver. Surprisingly, in all aluminium treated fish, classical stains unmasked a toxic effect on splenic-MMC, unequivocally characterized by a strong cell depletion. Furthermore, at 170 dpp transmission electron microscopy confirmed this data. Paradoxically, at the same time powerful immune responses were recorded in most vaccinated groups, including the aluminium treatment. Whatever the case, despite the observed adhesions and MMC depletion, fish physiology was not affected, and most side-effects were resolved after 300 dpp. Therefore, our data support adjuvant inclusion, but strongly suggest that use of aluminium must be further explored in detail before it might benefit the rational design of new vaccination strategies in aquaculture.

TRPV4-Mediated Detection of Hyposmotic Stress by Skin Keratinocytes Activates Developmental Immunity.

As an organism is exposed to pathogens during very early development, specific defense mechanisms must take effect. In this study, we used a germ-free zebrafish embryo model to show that osmotic stress regulates the activation of immunity and host protection in newly hatched embryos. Mechanistically, skin keratinocytes were responsible for both sensing the hyposmolarity of the aquatic environment and mediating immune effector mechanisms. This occurred through a transient potential receptor vanilloid 4/Ca(2+)/TGF-ß-activated kinase 1/NF-κB signaling pathway. Surprisingly, the genes encoding antimicrobial effectors, which do not have the potential to cause tissue damage, are constitutively expressed during development, independently of both commensal microbes and osmotic stress. Our results reveal that osmotic stress is associated with the induction of developmental immunity in the absence of tissue damage and point out to the embryo skin as the first organ with full capacities to mount an innate immune response.

ProFUSO: Business process and ontology-based framework to develop ubiquitous computing support systems for chronic patients' management.

New advances in telemedicine, ubiquitous computing, and artificial intelligence have supported the emergence of more advanced applications and support systems for chronic patients. This trend addresses the important problem of chronic illnesses, highlighted by multiple international organizations as a core issue in future healthcare. Despite the myriad of exciting new developments, each application and system is designed and implemented for specific purposes and lacks the flexibility to support different healthcare concerns. Some of the known problems of such developments are the integration issues between applications and existing healthcare systems, the reusability of technical knowledge in the creation of new and more sophisticated systems and the usage of data gathered from multiple sources in the generation of new knowledge. This paper proposes a framework for the development of chronic disease support systems and applications as an answer to these shortcomings. Through this framework our pursuit is to create a common ground methodology upon which new developments can be created and easily integrated to provide better support to chronic patients, medical staff and other relevant participants. General requirements are inferred for any support system from the primary attention process of chronic patients by the Business Process Management Notation. Numerous technical approaches are proposed to design a general architecture that considers the medical organizational requirements in the treatment of a patient. A framework is presented for any application in support of chronic patients and evaluated by a case study to test the applicability and pertinence of the solution.

Teleosts Genomics: Progress and Prospects in Disease Prevention and Control.

Genome wide studies based on conventional molecular tools and upcoming omics technologies are beginning to gain functional applications in the control and prevention of diseases in teleosts fish. Herein, we provide insights into current progress and prospects in the use genomics studies for the control and prevention of fish diseases. Metagenomics has emerged to be an important tool used to identify emerging infectious diseases for the timely design of rational disease control strategies, determining microbial compositions in different aquatic environments used for fish farming and the use of host microbiota to monitor the health status of fish. Expounding the use of antimicrobial peptides (AMPs) as therapeutic agents against different pathogens as well as elucidating their role in tissue regeneration is another vital aspect of genomics studies that had taken precedent in recent years. In vaccine development, prospects made include the identification of highly immunogenic proteins for use in recombinant vaccine designs as well as identifying gene signatures that correlate with protective immunity for use as benchmarks in optimizing vaccine efficacy. Progress in quantitative trait loci (QTL) mapping is beginning to yield considerable success in identifying resistant traits against some of the highly infectious diseases that have previously ravaged the aquaculture industry. Altogether, the synopsis put forth shows that genomics studies are beginning to yield positive contribution in the prevention and control of fish diseases in aquaculture.

Biliary strictures complicating liver transplantation in pediatric patients: Experience in a South American transplant center.

OBJECTIVE: To describe the experience of percutaneous transhepatic cholangiography (PTC) with biliary dilatation and drainage after pediatric liver transplantation and to determine the long-term outcome of this procedure. METHODS: Retrospective study from 2001 to 2013. Follow-up after treatment was also undertaken. A survival analysis was performed in patients in whom the procedure and eventual removal of the catheter were successful. RESULTS: In all, 196 children received liver transplants; 40 of them (20 boys and 20 girls; median age of 4 years) were treated using PTC due to biliary complications. Sixty-one PTC procedures were performed in 40 liver transplant recipients. Technically successful PTC was achieved in 87.5% of the patients. The probability of a patient not developing unfavorable outcomes 1, 5, and 10 years after treatment was 88.9%, 83.0%, and 74.1%.

Regulation of immunity and disease resistance by commensal microbes and chromatin modifications during zebrafish development.

How fish larvae are protected from infection before the maturation of adaptive immunity, a process which may take up to several weeks in most species, has long been a matter of speculation. Using a germ-free model, we show that colonization by commensals in newly hatched zebrafish primes neutrophils and induces several genes encoding proinflammatory and antiviral mediators, increasing the resistance of larvae to viral infection. Commensal microbe recognition was found to be mediated mainly through a TLR/MyD88 signaling pathway, and professional phagocytes were identified as the source of these immune mediators. However, the induction of proinflammatory and antiviral genes, but not of antimicrobial effector genes, also required the covalent modification of histone H3 at gene promoters. Interestingly, chromatin modifications were not altered by commensal microbes or hatching. Taken together, our results demonstrate that gene-specific chromatin modifications are associated with the protection of zebrafish larvae against infectious agents before adaptive immunity has developed and prevent pathologies associated with excessive inflammation during development.

Selling Health to the Distracted: Consumer Responses to Source Credibility and Ad Appeal Type in a Direct-to-Consumer Advertisement.

Since 1997, when the U.S. Food and Drug Administration first allowed prescription drug companies to release ads directly targeting the public, direct-to-consumer (DTC) advertising has become an integral part of the pharmaceutical industry marketing toolkit, reaching over $4 billion in 2005. In an experiment where cognitive load, a task that requires the investment of a subject's memory in an unrelated task; source credibility; and advertising appeal type (affective or cognitive) were manipulated, attitude toward the ad was measured for a print DTC meningitis vaccine ad. Main effect results for source credibility and advertising appeal type on attitude toward the ad were found, and interactions between manipulated variables were apparent when the individual difference variables related to a specific illness (vaccination history, living in a dorm, family members or friends who had suffered the illness) were taken into account.

Age- and gender-related variations in morphometric characteristics of thoracic spine pedicle: A study of 4,800 pedicles.

Transpedicular spinal fusion is the most commonly used fixation technique for the surgical treatment of vertebral disorders. However, the instrumentation of the thoracic spine using this technique continues to be controversial. The objective of the present study was to determine the morphometric characteristics of the thoracic pedicle and to establish how these characteristics vary with gender and age. Two hundred thoracic spines (4800 thoracic pedicles) from individuals of known gender and age were analyzed (in accordance with the order of vertebrae). The spines were divided into six groups according to age and gender. The horizontal and vertical diameters of the thoracic pedicle were determined for each piece. The mean and standard deviation of each variable were determined, and differences between age groups for each gender were evaluated using parametric correlation tests. The pedicle diameters of men and women differed significantly for most groups (P < 0.05). The horizontal diameters decreased from T1 to T5 and increased up to T12. The vertical diameter followed a cephalocaudal pattern of development from T1-T12. The pedicle diameters decreased with increasing age in women, while the opposite trend was observed in men. In men, the dimensions of the thoracic spine pedicle increase with increasing age; in women, they decrease. These differences should be taken into account when selecting the appropriate pedicle screw.

An In-Depth Study on the Inhibition of Quorum Sensing by Bacillus velezensis D-18: Its Significant Impact on Vibrio Biofilm Formation in Aquaculture.

Amid growing concerns about antibiotic resistance, innovative strategies are imperative in addressing bacterial infections in aquaculture. Quorum quenching (QQ), the enzymatic inhibition of quorum sensing (QS), has emerged as a promising solution. This study delves into the QQ capabilities of the probiotic strain Bacillus velezensis D-18 and its products, particularly in Vibrio anguillarum 507 communication and biofilm formation. Chromobacterium violaceum MK was used as a biomarker in this study, and the results confirmed that B. velezensis D-18 effectively inhibits QS. Further exploration into the QQ mechanism revealed the presence of lactonase activity by B. velezensis D-18 that degraded both long- and short-chain acyl homoserine lactones (AHLs). PCR analysis demonstrated the presence of a homologous lactonase-producing gene, ytnP, in the genome of B. velezensis D-18. The study evaluated the impact of B. velezensis D-18 on V. anguillarum 507 growth and biofilm formation. The probiotic not only controls the biofilm formation of V. anguillarum but also significantly restrains pathogen growth. Therefore, B. velezensis D-18 demonstrates substantial potential for preventing V. anguillarum diseases in aquaculture through its QQ capacity. The ability to disrupt bacterial communication and control biofilm formation positions B. velezensis D-18 as a promising eco-friendly alternative to conventional antibiotics in managing bacterial diseases in aquaculture.

Embryonic temperature has long-term effects on muscle circRNA expression and somatic growth in Nile tilapia.

Embryonic temperature has a lasting impact on muscle phenotype in vertebrates, involving complex molecular mechanisms that encompass both protein-coding and non-coding genes. Circular RNAs (circRNAs) are a class of regulatory RNAs that play important roles in various biological processes, but the effect of variable thermal conditions on the circRNA transcriptome and its long-term impact on muscle growth plasticity remains largely unexplored. To fill this knowledge gap, we performed a transcriptomic analysis of circRNAs in fast muscle of Nile tilapia (Oreochromis niloticus) subjected to different embryonic temperatures (24°C, 28°C and 32°C) and then reared at a common temperature (28°C) for 4 months. Nile tilapia embryos exhibited faster development and subsequently higher long-term growth at 32°C compared to those reared at 28°C and 24°C. Next-generation sequencing data revealed a total of 5,141 unique circRNAs across all temperature groups, of which 1,604, 1,531, and 1,169 circRNAs were exclusively found in the 24°C, 28°C and 32°C groups, respectively. Among them, circNexn exhibited a 1.7-fold (log2) upregulation in the 24°C group and a 1.3-fold (log2) upregulation in the 32°C group when compared to the 28°C group. Conversely, circTTN and circTTN_b were downregulated in the 24°C groups compared to their 28°C and 32°C counterparts. Furthermore, these differentially expressed circRNAs were found to have multiple interactions with myomiRs, highlighting their potential as promising candidates for further investigation in the context of muscle growth plasticity. Taken together, our findings provide new insights into the molecular mechanisms that may underlie muscle growth plasticity in response to thermal variation in fish, with important implications in the context of climate change, fisheries and aquaculture.