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PLoS Biology May 2024Zebrafish are popular research organisms selected for laboratory use due in part to widespread availability from the pet trade. Many contemporary colonies of laboratory...
Zebrafish are popular research organisms selected for laboratory use due in part to widespread availability from the pet trade. Many contemporary colonies of laboratory zebrafish are maintained in aquaculture facilities that monitor and aim to curb infections that can negatively affect colony health and confound experiments. The impact of laboratory control on the microbial constituents associated with zebrafish in research environments compared to the pet trade are unclear. Diseases of unknown causes are common in both environments. We conducted a metatranscriptomic survey to broadly compare the zebrafish-associated microbes in pet trade and laboratory environments. We detected many microbes in animals from the pet trade that were not found in laboratory animals. Cohousing experiments revealed several transmissible microbes including a newly described non-enveloped, double-stranded RNA virus in the Birnaviridae family we name Rocky Mountain birnavirus (RMBV). Infections were detected in asymptomatic animals from the pet trade, but when transmitted to laboratory animals RMBV was associated with pronounced antiviral responses and hemorrhagic disease. These experiments highlight the pet trade as a distinct source of diverse microbes that associate with zebrafish and establish a paradigm for the discovery of newly described pathogenic viruses and other infectious microbes that can be developed for study in the laboratory.
Topics: Animals; Zebrafish; Fish Diseases; Pets; Animals, Laboratory; Aquaculture
PubMed: 38814944
DOI: 10.1371/journal.pbio.3002606 -
Microbiology Spectrum May 2024is the leading cause of bacterial sexually transmitted infections in the USA and of preventable blindness worldwide. This obligate intracellular pathogen replicates...
is the leading cause of bacterial sexually transmitted infections in the USA and of preventable blindness worldwide. This obligate intracellular pathogen replicates within a membrane-bound inclusion, but how it acquires nutrients from the host while avoiding detection by the innate immune system is incompletely understood. accomplishes this in part through the translocation of a unique set of effectors into the inclusion membrane, the lusion membrane proteins (Incs). Incs are ideally positioned at the host-pathogen interface to reprogram host signaling by redirecting proteins or organelles to the inclusion. Using a combination of co-affinity purification, immunofluorescence confocal imaging, and proteomics, we characterize the interaction between an early-expressed Inc of unknown function, Tri1, and tumor necrosis factor receptor-associated factor 7 (TRAF7). TRAF7 is a multi-domain protein with a RING finger ubiquitin ligase domain and a C-terminal WD40 domain. TRAF7 regulates several innate immune signaling pathways associated with infection and is mutated in a subset of tumors. We demonstrate that Tri1 and TRAF7 specifically interact during infection and that TRAF7 is recruited to the inclusion. We further show that the predicted coiled-coil domain of Tri1 is necessary to interact with the TRAF7 WD40 domain. Finally, we demonstrate that Tri1 displaces the native TRAF7 binding partners, mitogen-activated protein kinase kinase kinase 2 (MEKK2), and MEKK3. Together, our results suggest that by displacing TRAF7 native binding partners, Tri1 has the capacity to alter TRAF7 signaling during infection.IMPORTANCE is the leading cause of bacterial sexually transmitted infections in the USA and preventable blindness worldwide. Although easily treated with antibiotics, the vast majority of infections are asymptomatic and therefore go untreated, leading to infertility and blindness. This obligate intracellular pathogen evades the immune response, which contributes to these outcomes. Here, we characterize the interaction between a -secreted effector, Tri1, and a host protein involved in innate immune signaling, TRAF7. We identified host proteins that bind to TRAF7 and demonstrated that Tri1 can displace these proteins upon binding to TRAF7. Remarkably, the region of TRAF7 to which these host proteins bind is often mutated in a subset of human tumors. Our work suggests a mechanism by which Tri1 may alter TRAF7 signaling and has implications not only in the pathogenesis of infections but also in understanding the role of TRAF7 in cancer.
PubMed: 38814079
DOI: 10.1128/spectrum.00453-24 -
World Journal of Gastrointestinal... May 2024Common bile duct (CBD) stones are a common biliary tract disease. For asymptomatic CBD stones, stone removal by endoscopic retrograde cholangiopancreatography (ERCP) is...
Common bile duct (CBD) stones are a common biliary tract disease. For asymptomatic CBD stones, stone removal by endoscopic retrograde cholangiopancreatography (ERCP) is recommended in available guidelines. Because asymptomatic CBD stones is a benign disease with no noticeable symptoms, the risk benefit strategy should be thoroughly considered before performing ERCP in these patients. Clinical care review, technical aspects of the procedure, and patient preferences should also be considered.
PubMed: 38813578
DOI: 10.4253/wjge.v16.i5.227 -
EClinicalMedicine May 2024Urinary tract infections (UTI) affect approximately 250 million people annually worldwide. Patients often experience a cycle of antimicrobial treatment and recurrent UTI...
BACKGROUND
Urinary tract infections (UTI) affect approximately 250 million people annually worldwide. Patients often experience a cycle of antimicrobial treatment and recurrent UTI (rUTI) that is thought to be facilitated by a gut reservoir of uropathogenic (UPEC).
METHODS
125 patients with UTI caused by an antibiotic-resistant organism (ARO) were enrolled from July 2016 to May 2019 in a longitudinal, multi-center cohort study. Multivariate statistical models were used to assess the relationship between uropathogen colonization and recurrent UTI (rUTI), controlling for clinical characteristics. 644 stool samples and 895 UPEC isolates were interrogated for taxonomic composition, antimicrobial resistance genes, and phenotypic resistance. Cohort UTI gut microbiome profiles were compared against published healthy and UTI reference microbiomes, as well as assessed within-cohort for timepoint- and recurrence-specific differences.
FINDINGS
Risk of rUTI was not independently associated with clinical characteristics. The UTI gut microbiome was distinct from healthy reference microbiomes in both taxonomic composition and antimicrobial resistance gene (ARG) burden, with 11 differentially abundant taxa at the genus level. rUTI and non-rUTI gut microbiomes in the cohort did not generally differ, but gut microbiomes from urinary tract colonized patients were elevated in abundance 7-14 days post-antimicrobial treatment. Corresponding UPEC gut isolates from urinary tract colonizing lineages showed elevated phenotypic resistance against 11 of 23 tested drugs compared to non-colonizing lineages.
INTERPRETATION
The gut microbiome is implicated in UPEC urinary tract colonization during rUTI, serving as an ARG-enriched reservoir for UPEC. UPEC can asymptomatically colonize the gut and urinary tract, and post-antimicrobial blooms of gut among urinary tract colonized patients suggest that cross-habitat migration of UPEC is an important mechanism of rUTI. Thus, treatment duration and UPEC populations in both the urinary and gastrointestinal tract should be considered in treating rUTI and developing novel therapeutics.
FUNDING
This work was supported in part by awards from the U.S. Centers for Disease Control and Prevention Epicenter Prevention Program (grant U54CK000482; principal investigator, V.J.F.); to J.H.K. from the Longer Life Foundation (an RGA/Washington University partnership), the National Center for Advancing Translational Sciences (grants KL2TR002346 and UL1TR002345), and the National Institute of Allergy and Infectious Diseases (NIAID) (grant K23A1137321) of the National Institutes of Health (NIH); and to G.D. from NIAID (grant R01AI123394) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant R01HD092414) of NIH. R.T.'s research was funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation; grant 402733540). REDCap is Supported by Clinical and Translational Science Award (CTSA) Grant UL1 TR002345 and Siteman Comprehensive Cancer Center and NCI Cancer Center Support Grant P30 CA091842. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
PubMed: 38813445
DOI: 10.1016/j.eclinm.2024.102490 -
Heliyon May 2024To determine the accuracy of Tc-99 m sestamibi for the diagnosis of acute cholecystitis during a supply chain disruption of mebrofenin.
PURPOSE
To determine the accuracy of Tc-99 m sestamibi for the diagnosis of acute cholecystitis during a supply chain disruption of mebrofenin.
MATERIAL AND METHODS
During a national shortage of Tc-99 m mebrofenin in 2019, our institution initiated sestamibi imaging for suspected cases of acute cholecystitis using a standard hepatobiliary imaging protocol. Forty-one patients underwent hepatobiliary imaging with sestamibi, 39 to assess for acute cholecystitis. The examinations were initially interpreted by one nuclear medicine physician and subsequently overread by 5 blinded nuclear medicine physicians (8-30 years' experience). SPECT/CT was obtained for 8 of these patients at the discretion of the primary interpreter. An additional 23 asymptomatic patients (6 with prior cholecystectomy) underwent abdominal scintigraphy as a negative control to determine the normal time to sestamibi accumulation in the gallbladder. A composite reference standard was used (chart review by 3 physicians). Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were calculated with and without SPECT/CT (mean ± 95%CI).
RESULTS
Of 39 symptomatic patients, 17/39 had acute cholecystitis and 22 did not. The sensitivity, specificity, PPV and NPV for acute cholecystitis at planar imaging were 97.6 ± 4.6, 62.7 ± 5.2, 67.0 ± 3.6, and 97.3 ± 5.2 % (N = 39). The values changed to 95.7 ± 4.7, 77.9 ± 4.7, 72.1 ± 4.1, and 97.0 ± 3.3 % when control patients were included (N = 62). With SPECT/CT, these mildly improved to 98.8 ± 2.3 %, 69.1 ± 4.4 %, 71.3 ± 3.2 %, and 98.7 ± 2.6 % (N = 39), but not significantly different. On average, sestamibi activity was detected in the gallbladder in negative controls within 1 h.
CONCLUSION
Tc-99 m sestamibi has excellent sensitivity and NPV for diagnosing acute cholecystitis and can serve as an alternative when mebrofenin is unavailable for evaluating cystic duct obstruction during shortages of standard agents.
PubMed: 38813191
DOI: 10.1016/j.heliyon.2024.e31257 -
Heliyon May 2024Human Papilloma Virus (HPV) is considered one of the most common sexually transmitted infections and has been shown to play an important role in the pathogenesis of... (Review)
Review
Human Papilloma Virus (HPV) is considered one of the most common sexually transmitted infections and has been shown to play an important role in the pathogenesis of squamous cell carcinomas (SCC) of the cervix and head and neck. Manifestations of HPV infections can be manifold, ranging from asymptomatic infections to benign or potentially malignant lesions to intraepithelial neoplasms and invasive carcinomas. The heterogeneity of clinical manifestations from HPV infection depends on the interactions between the viral agent and the host, a direct consequence of the ability on the part of HPV is to remain silent and to evade and convey the action of the host immune system. The oral mucosa represents one of the tissues for which HPV has a distinct tropism and is frequently affected by infection. While much information is available on the role that HPV infection plays in the development of SCC in the oral cavity, there is less information on asymptomatic infections and benign HPV-induced oral lesions. Therefore, the purpose of this review is to analyze, in light of current knowledge, the early clinical and bio-humoral prognostic features related to the risk of HPV malignant transformation, focusing on subclinical conditions, benign lesions, and the correlation between oral infection and infection in other districts. The data show that the main risk associated with HPV infection is related to malignant transformation of lesions. Although HPV-driven OPSCC is associated with a better prognosis than non-HPV-driven OPSCC, primary prevention and early detection of the infection and affected genotype are essential to reduce the risk of malignant neoplastic complications and improve the prognosis.
PubMed: 38813162
DOI: 10.1016/j.heliyon.2024.e31061 -
SAGE Open Medical Case Reports 2024This case report outlines the management of a 43-year-old male with no past medical history presenting with inferior ST-segment elevation myocardial infarction and a...
This case report outlines the management of a 43-year-old male with no past medical history presenting with inferior ST-segment elevation myocardial infarction and a positive "Dead Man Sign." Prompt administration of antiplatelet therapy and emergent percutaneous coronary intervention led to successful revascularization of the occluded right coronary artery and left anterior descending artery. The patient remained asymptomatic throughout hospitalization and was discharged home with instructions for monthly follow-up for 1 year. Subsequent assessments demonstrated normal echocardiography and Electrocardiography (ECG) findings, indicating favorable cardiac recovery. This case emphasizes the critical importance of rapid recognition and intervention in ST-segment elevation myocardial infarction cases, as well as the significance of the Dead Man Sign as a predictor of the occluded culprit coronary vessels, demonstrating favorable outcomes achievable with timely revascularization strategies.
PubMed: 38812830
DOI: 10.1177/2050313X241258738 -
Frontiers in Microbiology 2024The lack of sustainable strategies for combating () highlights the pressing need for novel practical antibacterial tools. In this study, subsp. strain ATCC 11454 (),...
The lack of sustainable strategies for combating () highlights the pressing need for novel practical antibacterial tools. In this study, subsp. strain ATCC 11454 (), known for its production of nisin A, was tested against subsp. . Preliminary investigations showed that nisin A was involved in a strong antagonistic activity exhibited by against . Thus, the efficacy of nisin A was comprehensively assessed through a combination of and experiments. investigations employing viable-quantitative PCR, spot assay, turbidity reduction assay, fluorescence microscopy, and transmission electron microscopy demonstrated nisin's robust bactericidal effect on at a minimal lethal concentration of 0.6 mg/mL. Moreover, results from fluorescence and transmission electron microscopies indicated that nisin directly and rapidly interacts with the membranes of cells, leading to the destruction of bacterial cells in few minutes. In tests, nisin also demonstrated the ability to tackle infections within plants that remained asymptomatic 74 days post inoculation. Furthermore, RPLC-ESI-MS/MS analyses showed that nisin translocated to all parts of the plants and remains intact for up to 9 days. For the first time, this study underscores the nisin-based strategy as a realistic and eco-friendly approach to be further investigated against infections in the field.
PubMed: 38812684
DOI: 10.3389/fmicb.2024.1406672 -
Turkish Journal of Medical Sciences 2024Management of asymptomatic kidney stones is an ongoing debate with follow-up and treatment guidelines based on low-level evidence. Our aim was to evaluate current...
Urologists' opinion on treating asymptomatic stones: Would we treat ourselves as we treat our patients? Survey from European Association of Urology, Young Academic Urologists, Endourology and Urolithiasis working party.
BACKGROUND/AIM
Management of asymptomatic kidney stones is an ongoing debate with follow-up and treatment guidelines based on low-level evidence. Our aim was to evaluate current management of asymptomatic urinary stones.
MATERIALS AND METHODS
A 70-question survey was designed in collaboration with European Association of Urology, Young Academic Urologists, Section of Uro-Technology and Section of Urolithiasis groups and distributed. Responders filled out hypothetical scenarios from 2 perspectives, either as treating physicians, or as patients themselves.
RESULTS
A total of 212 (40.01%) responses were obtained. Median responder age was 39 years. 75% of responders were interested in "urolithiasis". 82.5% had never experienced a renal colic, 89.6% had never undergone urolithiasis treatment.Overall, as the kidney stone scenarios got more complicated, the invasiveness of the treatment preference increased. As "the physician", responders preferred the conservative option in all situations more than they would choose as "the patient". For ureteral stones, conservative approach was most preferred for small stones and ureteroscopy became more preferred as the stone size increased.For smaller kidney stones, the most preferred follow-up schedule was 4-6 monthly, whereas for larger and complicated stones it was 0-3 monthly from both perspectives respectively. For all ureteral stone scenarios, 0-4 weekly follow-up was mostly preferred.Interestingly, having had a renal colic was an independent predictor of an interventional approach, whereas having had an intervention was an independent predictor of a conservative approach.
CONCLUSION
Current treatment and follow-up patterns of asymptomatic urinary stones are in agreement with international guidelines on symptomatic stones.In most of the urolithiasis situations urologists chose a conservative approach for their patients compared to what they would prefer for themselves. Conversely, urologists, in the scenarios as "the patient", would like to have a more frequent follow-up schedule for their stones compared to how they would follow-up their patients.
Topics: Humans; Adult; Urologists; Surveys and Questionnaires; Male; Female; Urology; Kidney Calculi; Ureteroscopy; Practice Patterns, Physicians'; Urolithiasis; Middle Aged; Europe; Attitude of Health Personnel; Asymptomatic Diseases
PubMed: 38812627
DOI: 10.55730/1300-0144.5779 -
Journal of Cardiothoracic Surgery May 2024Quadricuspid aortic valve (QAV) is a rare congenital anomaly characterized by the presence of four cusps instead of the usual three. It is estimated to occur in less...
BACKGROUND
Quadricuspid aortic valve (QAV) is a rare congenital anomaly characterized by the presence of four cusps instead of the usual three. It is estimated to occur in less than 0.05% of the population, with Type A (four equal-sized leaflets) accounting for roughly 30% of QAV subtypes. Based on limited clinical series, the usual presentation is progressive aortic valve regurgitation (AR) with symptoms occurring in the fourth to sixth decade of life. Severe aortic valve stenosis (AS) and acute AR are very uncommon.
CASE PRESENTATION
We describe two cases of Type A QAV in patients who remained asymptomatic until their seventies with very uncommon presentations: one with severe AS and one with acute, severe AR and flail leaflet. In Case A, a 72-year-old patient with history of moderate AS presents to clinic with progressive exertional dyspnea. During work-up for transcatheter vs. surgical replacement pre-operative computed tomography angiogram (CTA) reveals a quadricuspid aortic valve with severe AS, and the patient undergoes surgical aortic valve replacement. Pre-discharge transthoracic echocardiography (TTE) shows good prosthetic valve function with no gradient or regurgitation. In Case B, a 76-year-old patient is intubated upon arrival to the hospital for acute desaturation, found to have wide open AR on catheterization, and transferred for emergent intervention. Intraoperative TEE reveals QAV with flail leaflet and severe AR. Repair is considered but deferred ultimately due to emergent nature. Post-operative TTE demonstrates good prosthetic valve function with no regurgitation and normal biventricular function.
CONCLUSIONS
QAV can present as progressive severe AS and acute AR, with symptoms first occurring in the seventh decade of life. The optimal treatment for QAV remains uncertain. Although aortic valve repair or transcatheter option may be feasible in some patients, aortic valve replacement remains a tenable option.
Topics: Humans; Aged; Aortic Valve; Male; Aortic Valve Stenosis; Aortic Valve Insufficiency; Echocardiography; Female; Heart Valve Prosthesis Implantation
PubMed: 38812010
DOI: 10.1186/s13019-024-02696-w