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Background Chronic strictures following Roux-en-Y Gastric Bypass (RYGB) are a troublesome complication that can lead to significant morbidity. The use of stents has been described but the need for X-ray and risk of migration have meant limited use in the management of these strictures. Lumen apposing metal stents (LAMS) have traditionally been used for management of pancreatic pseudocysts. They don’t require X-ray and are easy to deploy with a short learning curve. This paper explores the use of LAMS to treat post RYGB strictures and explores their safety and efficacy. Methods A prospective study over a 4-year period looking at 14 patients with post RYGB strictures. These patients were privately insured patients operated within a tertiary Private facility. The patients were followed up for between 1 and 3 years. We have prospectively collected data on the efficacy and safety of LAMS in these patients. Patients were followed up until stent removal or definitive surgery to correct a stricture. Results 421 patients underwent RYGB in the study period. 14 (3.3%) of these patients developed a stricture that resulted in insertion of LAMS. There was no immediate complications and 12 patients had complete resolution of their stricture. There were no reoperations due to migration related issues although a migration rate of 19% was noted. 2 patients required surgery to correct refractory strictures not relieved by a LAMS stent, both of these were strictures associated with marginal ulceration of the gastro jejunostomy. Conclusion LAMS are a safe and effective method to manage post RYGB strictures. They have a high rate of resolution of strictures and can be safely deployed across strictures with no immediate complication. Migration does still appear to be a problem, however, does not appear to affect patient outcome or increase morbidity. Insertion is straightforward and doesn’t appear to be associated with a long learning curve.

Genomic surveillance can provide early insights into new circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. While conducting genomic surveillance (1,663 cases) from December 2020–April 2021 in Arizona, USA, we detected an emergent E484K-harboring variant, B.1.243.1. This finding demonstrates the importance of real-time SARS-CoV-2 surveillance to better inform public health responses.

HPV infection is an established risk factor for cervical cancer. However, more broadly, the role of the cervicovaginal virome in cervical cancer progression is not well understood. While the link between the cervicovaginal bacterial microbiome, human papillomavirus (HPV) infection, and cervical cancer is recognized (P. Łaniewski, D. Barnes, A. Goulder, H. Cui, et al., Sci. Rep. 8:7593, 2018, http://dx.doi.org/10.1038/s41598-018-25879-7 ; A. Mitra, D. A. MacIntyre, Y. S. Lee, A. Smith, et al., Sci. Rep. 5:16865, 2015, http://dx.doi.org/10.1038/srep16865 ; A. Mitra, D. A. MacIntyre, J. R. Marchesi, Y. S. Lee, et al., Microbiome 4:58, 2016, http://dx.doi.org/10.1186/s40168-016-0203-0 ; J. Norenhag, J. Du, M. Olovsson, H. Verstraelen, et al., BJOG, 127:171–180, 2020, http://dx.doi.org/10.1111/1471-0528.15854 ; E. O. Dareng, B. Ma, A. O. Famooto, S. N. Adebamowo, et al., Epidemiol. Infect. 144:123–137, 2016, http://dx.doi.org/10.1017/S0950268815000965 ; A. Audirac-Chalifour, K. Torres-Poveda, M. Bahena-Roman, J. Tellez-Sosa et al., PLoS One 11:e0153274, 2016, http://dx.doi.org/10.1371/journal.pone.0153274 ; M. Di Paola, C. Sani, A. M. Clemente, A. Iossa, et al., Sci. Rep. 7:10200, 2017, http://dx.doi.org/10.1038/s41598-017-09842-6 ), the role of the cervicovaginal virome remains poorly understood. In this pilot study, we conducted metagenomic next-generation sequencing of cervicovaginal lavage specimens to investigate the relationship between the cervicovaginal DNA virome, bacterial microbiome, genital inflammation, and HPV infection. Specific virome alterations were associated with features of the local microenvironment related to HPV persistence and progression to cervical cancer. Cervicovaginal viromes clustered distinctly by genital inflammation state. Genital inflammation was associated with decreased virome richness and alpha diversity and an increased abundance of Anelloviridae species from the genus Alphatorquevirus . Lactobacillus bacteriophages were closely associated with increased Lactobacillus abundance, consistent with phage-host relationships. Interestingly, bacteria-bacteriophage transkingdom interactions were linked to genital inflammation and showed specific interactions with bacterial vaginosis-associated bacteria, including Gardnerella, Prevotella, and Sneathia . Taken together, our results reveal prominent virome interactions with features of the cervicovaginal microenvironment that are associated with HPV and cervical cancer. These findings expand our understanding of the cervicovaginal host-microbiome interactions in women’s health. IMPORTANCE HPV infection is an established risk factor for cervical cancer. However, more broadly, the role of the cervicovaginal virome in cervical cancer progression is not well understood. Here, we identified cervicovaginal DNA virome alterations associated with local microenvironment factors (vaginal microbiota and genital inflammation) that influence HPV persistence and progression to cervical cancer. These findings indicate that the cervicovaginal virome plays an important role in women’s health.

Gulf War Illness (GWI) is a chronic multi-symptomatic illness that is associated with fatigue, pain, cognitive deficits, and gastrointestinal disturbances and presents a significant challenge to treat in clinics. Our previous studies show a role of an altered Gut–Brain axis pathology in disease development and symptom persistence in GWI. The present study utilizes a mouse model of GWI to study the role of a labdane diterpenoid andrographolide (AG) to attenuate the Gut–Brain axis-linked pathology. Results showed that AG treatment in mice (100 mg/kg) via oral gavage restored bacteriome alterations, significantly increased probiotic bacteria Akkermansia, Lachnospiraceae, and Bifidobacterium, the genera that are known to aid in preserving gut and immune health. AG also corrected an altered virome with significant decreases in virome families Siphoviridae and Myoviridae known to be associated with gastrointestinal pathology. AG treatment significantly restored tight junction proteins that correlated well with decreased intestinal proinflammatory mediators IL-1β and IL-6 release. AG treatment could restore Claudin-5 levels, crucial for maintaining the BBB integrity. Notably, AG could decrease microglial activation and increase neurotrophic factor BDNF, the key to neurogenesis. Mechanistically, microglial conditioned medium generated from IL-6 stimulation with or without AG in a concentration similar to circulating levels found in the GWI mouse model and co-incubated with neuronal cells in vitro, decreased Tau phosphorylation and neuronal apoptosis. In conclusion, we show that AG treatment mitigated the Gut–Brain-Axis associated pathology in GWI and may be considered as a potential therapeutic avenue for the much-needed bench to bedside strategies in GWI.

The SARS-CoV-2 pandemic resulted in a scale-up of viral genomic surveillance globally. However, the wet lab constraints (economic, infrastructural, and personnel) of translating novel virus variant sequence information to meaningful immunological and structural insights that are valuable for the development of broadly acting countermeasures (especially for emerging and re-emerging viruses) remain a challenge in many resource-limited settings. Here, we describe a workflow that couples wastewater surveillance, high-throughput sequencing, phylogenetics, immuno-informatics, and virus capsid structure modeling for the genotype-to-serotype characterization of uncultivated picornavirus sequences identified in wastewater. Specifically, we analyzed canine picornaviruses (CanPVs), which are uncultivated and yet-to-be-assigned members of the family Picornaviridae that cause systemic infections in canines. We analyzed 118 archived (stored at −20 °C) wastewater (WW) samples representing a population of ~700,000 persons in southwest USA between October 2019 to March 2020 and October 2020 to March 2021. Samples were pooled into 12 two-liter volumes by month, partitioned (into filter-trapped solids [FTSs] and filtrates) using 450 nm membrane filters, and subsequently concentrated to 2 mL (1000×) using 10,000 Da MW cutoff centrifugal filters. The 24 concentrates were subjected to RNA extraction, CanPV complete capsid single-contig RT-PCR, Illumina sequencing, phylogenetics, immuno-informatics, and structure prediction. We detected CanPVs in 58.3% (14/24) of the samples generated 13,824,046 trimmed Illumina reads and 27 CanPV contigs. Phylogenetic and pairwise identity analyses showed eight CanPV genotypes (intragenotype divergence <14%) belonging to four clusters, with intracluster divergence of <20%. Similarity analysis, immuno-informatics, and virus protomer and capsid structure prediction suggested that the four clusters were likely distinct serological types, with predicted cluster-distinguishing B-cell epitopes clustered in the northern and southern rims of the canyon surrounding the 5-fold axis of symmetry. Our approach allows forgenotype-to-serotype characterization of uncultivated picornavirus sequences by coupling phylogenetics, immuno-informatics, and virus capsid structure prediction. This consequently bypasses a major wet lab-associated bottleneck, thereby allowing resource-limited settings to leapfrog from wastewater-sourced genomic data to valuable immunological insights necessary for the development of prophylaxis and other mitigation measures.

Citrobacter koseri (formerly classified as Citrobacter diversus) is a gram-negative bacillus (GNB) that occurs as an opportunistic pathogen in neonates and immunocompromised patients. Citrobacter species have been implicated in nosocomial settings leading to infections involving the urinary tract, respiratory tract, liver, biliary tract, meninges, and even in rarer conditions—blood stream infection and infective endocarditis (IE). Gram-negative bacilli are responsible for 3% to 4% of all IE cases and have been traditionally associated with intravenous drug users. Patients with non-HACEK (species other than Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, or Kinglella species) GNB IE have poor clinical outcomes with higher rates of in-hospital mortality and complications. The American Heart Association (AHA) and Infectious Diseases Society of America (IDSA) both recommend the use of combination antibiotic therapy with a beta-lactam (penicillins, cephalosporins, or carbapenems) and either an aminoglycoside or fluoroquinolones for 6 weeks (about 1 and a half months) to treat IE due to non-HACEK GNB. Citrobacter koseri is becoming more recognized due to its inherent resistance to ampicillin and emerging drug resistance to beta lactams and aminoglycosides requiring carbapenem therapy. Our case is of a 75-year-old male with no previously reported history of primary or secondary immunodeficiency disorders who developed C koseri blood stream infection. His infectious work-up revealed mitral valve IE and septic cerebral emboli resulting in ischemic infarcts. This case illustrates the importance of recognizing GNB organisms as rising human pathogens in IE cases even without active injection drug use or nosocomial exposure.

Nocardia species are ubiquitous in the environment and can be found worldwide. Direct inhalation remains the most commonly attributed route of infection with Nocardia asteroides complex, causing 50% of invasive infections. Improved molecular methods have identified a significant proportion of N. asteroides complex isolates to be Nocardia cyriacigeorgica. We report a case of a 58-year-old male working as a contractor in Bagram Air Force Base, Afghanistan, with disseminated N. cyriacigeorgica involving the lung, brain, and dermis. Diagnosis was facilitated by early identification of branched, filamentous bacteria using Fite and gram staining along secA DNA sequencing of clinical isolates. Our patient is the first confirmed case of N. cyriacigeorgica infection in Afghanistan.

By coupling long-range polymerase chain reaction, wastewater-based epidemiology, and pathogen sequencing, we show that adenovirus type 41 hexon-sequence lineages, described in children with hepatitis of unknown origin in the United States in 2021, were already circulating within the country in 2019. We also observed other lineages in the wastewater, whose complete genomes have yet to be documented from clinical samples.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare but important condition to consider when investigating a patient with suspected thoracic malignancy. There is very little known about DIPNECH and it is considered to be a precursor to carcinoid tumour of the lung. This case report aims to increase awareness of this largely unknown and rare condition and to better improve its consideration as a differential diagnosis in patients who remain unresponsive to conventional treatment.

We determine the presence and diversity of rhinoviruses in nasopharyngeal swab samples from 248 individuals who presented with influenza‐like illness (ILI) at a university clinic in the Southwest United States between October 1, 2020 and March 31, 2021. We identify at least 13 rhinovirus genotypes (A11, A22, A23, A25, A67, A101, B6, B79, C1, C17, C36, and C56, as well a new genotype [AZ88**]) and 16 variants that contributed to the burden of ILI in the community. We also describe the complete capsid protein gene of a member (AZ88**) of an unassigned rhinovirus A genotype.