A broad wastewater screening and clinical data surveillance for virus-related diseases in the metropolitan Detroit area in Michigan.

BACKGROUND: Periodic bioinformatics-based screening of wastewater for assessing the diversity of potential human viral pathogens circulating in a given community may help to identify novel or potentially emerging infectious diseases. Any identified contigs related to novel or emerging viruses should be confirmed with targeted wastewater and clinical testing. RESULTS: During the COVID-19 pandemic, untreated wastewater samples were collected for a 1-year period from the Great Lakes Water Authority Wastewater Treatment Facility in Detroit, MI, USA, and viral population diversity from both centralized interceptor sites and localized neighborhood sewersheds was investigated. Clinical cases of the diseases caused by human viruses were tabulated and compared with data from viral wastewater monitoring. In addition to Betacoronavirus, comparison using assembled contigs against a custom Swiss-Prot human virus database indicated the potential prevalence of other pathogenic virus genera, including: Orthopoxvirus, Rhadinovirus, Parapoxvirus, Varicellovirus, Hepatovirus, Simplexvirus, Bocaparvovirus, Molluscipoxvirus, Parechovirus, Roseolovirus, Lymphocryptovirus, Alphavirus, Spumavirus, Lentivirus, Deltaretrovirus, Enterovirus, Kobuvirus, Gammaretrovirus, Cardiovirus, Erythroparvovirus, Salivirus, Rubivirus, Orthohepevirus, Cytomegalovirus, Norovirus, and Mamastrovirus. Four nearly complete genomes were recovered from the Astrovirus, Enterovirus, Norovirus and Betapolyomavirus genera and viral species were identified. CONCLUSIONS: The presented findings in wastewater samples are primarily at the genus level and can serve as a preliminary "screening" tool that may serve as indication to initiate further testing for the confirmation of the presence of species that may be associated with human disease. Integrating innovative environmental microbiology technologies like metagenomic sequencing with viral epidemiology offers a significant opportunity to improve the monitoring of, and predictive intelligence for, pathogenic viruses, using wastewater.

Wastewater surveillance beyond COVID-19: a ranking system for communicable disease testing in the tri-county Detroit area, Michigan, USA.

Introduction: Throughout the coronavirus disease 2019 (COVID-19) pandemic, wastewater surveillance has been utilized to monitor the disease in the United States through routine national, statewide, and regional monitoring projects. A significant canon of evidence was produced showing that wastewater surveillance is a credible and effective tool for disease monitoring. Hence, the application of wastewater surveillance can extend beyond monitoring SARS-CoV-2 to encompass a diverse range of emerging diseases. This article proposed a ranking system for prioritizing reportable communicable diseases (CDs) in the Tri-County Detroit Area (TCDA), Michigan, for future wastewater surveillance applications at the Great Lakes Water Authority's Water Reclamation Plant (GLWA's WRP). Methods: The comprehensive CD wastewater surveillance ranking system (CDWSRank) was developed based on 6 binary and 6 quantitative parameters. The final ranking scores of CDs were computed by summing the multiplication products of weighting factors for each parameter, and then were sorted based on decreasing priority. Disease incidence data from 2014 to 2021 were collected for the TCDA. Disease incidence trends in the TCDA were endowed with higher weights, prioritizing the TCDA over the state of Michigan. Results: Disparities in incidences of CDs were identified between the TCDA and state of Michigan, indicating epidemiological differences. Among 96 ranked CDs, some top ranked CDs did not present relatively high incidences but were prioritized, suggesting that such CDs require significant attention by wastewater surveillance practitioners, despite their relatively low incidences in the geographic area of interest. Appropriate wastewater sample concentration methods are summarized for the application of wastewater surveillance as per viral, bacterial, parasitic, and fungal pathogens. Discussion: The CDWSRank system is one of the first of its kind to provide an empirical approach to prioritize CDs for wastewater surveillance, specifically in geographies served by centralized wastewater collection in the area of interest. The CDWSRank system provides a methodological tool and critical information that can help public health officials and policymakers allocate resources. It can be used to prioritize disease surveillance efforts and ensure that public health interventions are targeted at the most potentially urgent threats. The CDWSRank system can be easily adopted to geographical locations beyond the TCDA.

The Implementation and Utilization of Wastewater-Based Epidemiology: Experiences From a Local Health Department.

Wastewater-based epidemiology has increasingly demonstrated its importance in addressing public health threats. The COVID-19 pandemic brought forth funding for public health agencies to conduct wastewater-based epidemiology. Using a team with diverse skills, a local health department utilized this funding to regularly monitor SARS-CoV-2 in wastewater on university campuses, a K-12 campus, an inpatient psychiatric facility, and a long-term care facility. Between September 2021 and May 2022, more than 760 wastewater samples were collected of which 102 (13.4%) were above a predetermined threshold. When sites exceeded that threshold, local health department staff provided testing resources. Wastewater-based epidemiology is a useful surveillance program that can be effectively conducted by local health departments when provided with funding and a skilled workforce.

Simple methods for early warnings of COVID-19 surges: Lessons learned from 21 months of wastewater and clinical data collection in Detroit, Michigan, United States.

Wastewater-based epidemiology (WBE) has drawn great attention since the Coronavirus disease 2019 (COVID-19) pandemic, not only due to its capability to circumvent the limitations of traditional clinical surveillance, but also due to its potential to forewarn fluctuations of disease incidences in communities. One critical application of WBE is to provide "early warnings" for upcoming fluctuations of disease incidences in communities which traditional clinical testing is incapable to achieve. While intricate models have been developed to determine early warnings based on wastewater surveillance data, there is an exigent need for straightforward, rapid, broadly applicable methods for health departments and partner agencies to implement. Our purpose in this study is to develop and evaluate such early-warning methods and clinical-case peak-detection methods based on WBE data to mount an informed public health response. Throughout an extended wastewater surveillance period across Detroit, MI metropolitan area (the entire study period is from September 2020 to May 2022) we designed eight early-warning methods (three real-time and five post-factum). Additionally, we designed three peak-detection methods based on clinical epidemiological data. We demonstrated the utility of these methods for providing early warnings for COVID-19 incidences, with their counterpart accuracies evaluated by hit rates. "Hit rates" were defined as the number of early warning dates (using wastewater surveillance data) that captured defined peaks (using clinical epidemiological data) divided by the total number of early warning dates. Hit rates demonstrated that the accuracy of both real-time and post-factum methods could reach 100 %. Furthermore, the results indicate that the accuracy was influenced by approaches to defining peaks of disease incidence. The proposed methods herein can assist health departments capitalizing on WBE data to assess trends and implement quick public health responses to future epidemics. Besides, this study elucidated critical factors affecting early warnings based on WBE amid the COVID-19 pandemic.

Five-week warning of COVID-19 peaks prior to the Omicron surge in Detroit, Michigan using wastewater surveillance.

Wastewater-based epidemiology (WBE) is useful in predicting temporal fluctuations of COVID-19 incidence in communities and providing early warnings of pending outbreaks. To investigate the relationship between SARS-CoV-2 concentrations in wastewater and COVID-19 incidence in communities, a 12-month study between September 1, 2020, and August 31, 2021, prior to the Omicron surge, was conducted. 407 untreated wastewater samples were collected from the Great Lakes Water Authority (GLWA) in southeastern Michigan. N1 and N2 genes of SARS-CoV-2 were quantified using RT-ddPCR. Daily confirmed COVID-19 cases for the City of Detroit, and Wayne, Macomb, Oakland counties between September 1, 2020, and October 4, 2021, were collected from a public data source. The total concentrations of N1 and N2 genes ranged from 714.85 to 7145.98 gc/L and 820.47 to 6219.05 gc/L, respectively, which were strongly correlated with the 7-day moving average of total daily COVID-19 cases in the associated areas, after 5 weeks of the viral measurement. The results indicate a potential 5-week lag time of wastewater surveillance preceding COVID-19 incidence for the Detroit metropolitan area. Four statistical models were established to analyze the relationship between SARS-CoV-2 concentrations in wastewater and COVID-19 incidence in the study areas. Under a 5-week lag time scenario with both N1 and N2 genes, the autoregression model with seasonal patterns and vector autoregression model were more effective in predicting COVID-19 cases during the study period. To investigate the impact of flow parameters on the correlation, the original N1 and N2 gene concentrations were normalized by wastewater flow parameters. The statistical results indicated the optimum models were consistent for both normalized and non-normalized data. In addition, we discussed parameters that explain the observed lag time. Furthermore, we evaluated the impact of the omicron surge that followed, and the impact of different sampling methods on the estimation of lag time.

Epidemiological analysis of chronic rhinitis in pediatric patients.

BACKGROUND: Nonallergic rhinitis is a poorly understood entity, especially among pediatric patients. OBJECTIVE: The objective of this study was to identify clinical features that may distinguish phenotypes of allergic and nonallergic patients and to evaluate the usefulness of current diagnostic modalities. METHODS: We reviewed medical records for 151 pediatric patients with perennial rhinitis, evaluated in a multidisciplinary allergy and otolaryngology clinic. Results obtained by standard history, validated sinus and Nasal Quality of Life Survey (SN-5), epicutaneous allergy testing, acoustic rhinometry, and sinus CT were compared. RESULTS: Nasal congestion was the most frequent primary presenting complaint (62%). Among subjects having a positive allergy test, associated eye symptoms were more frequent (p = 0.01) and responses to the SN-5 allergic domain were higher (p = 0.02). Sinus CT scores were similar among allergic and nonallergic subjects (median 7 and 8, respectively) and did not correlate with symptom scores (p = 0.6). Among nonallergic subjects, quality of life ratings weakly correlated with sinus CT scores (r = 0.4; p = 0.05). By rhinometry, absolute mean cross-sectional area was similar among allergic (0.32 cm(2)) and nonallergic (0.36 cm(2)) subjects and did not correlate with symptom scores (p = 0.8 for allergic and p = 0.6 for nonallergic subjects). Distinct groups of nonallergic patients including those with prominent conjunctival pruritus (n = 24), frequent cold symptoms (n = 3), and chronic sinus disease (n = 2) were observed. CONCLUSION: It is difficult to distinguish allergic and nonallergic rhinitis in patients with perennial disease, but associated eye symptoms and questionnaire responses are predictive of allergy. Acoustic rhinometry and sinus CT suggest that physical obstruction and sinus disease are not related to nasal symptoms including, surprisingly, the sensation of congestion.

CORE: a phylogenetically-curated 16S rDNA database of the core oral microbiome.

Comparing bacterial 16S rDNA sequences to GenBank and other large public databases via BLAST often provides results of little use for identification and taxonomic assignment of the organisms of interest. The human microbiome, and in particular the oral microbiome, includes many taxa, and accurate identification of sequence data is essential for studies of these communities. For this purpose, a phylogenetically curated 16S rDNA database of the core oral microbiome, CORE, was developed. The goal was to include a comprehensive and minimally redundant representation of the bacteria that regularly reside in the human oral cavity with computationally robust classification at the level of species and genus. Clades of cultivated and uncultivated taxa were formed based on sequence analyses using multiple criteria, including maximum-likelihood-based topology and bootstrap support, genetic distance, and previous naming. A number of classification inconsistencies for previously named species, especially at the level of genus, were resolved. The performance of the CORE database for identifying clinical sequences was compared to that of three publicly available databases, GenBank nr/nt, RDP and HOMD, using a set of sequencing reads that had not been used in creation of the database. CORE offered improved performance compared to other public databases for identification of human oral bacterial 16S sequences by a number of criteria. In addition, the CORE database and phylogenetic tree provide a framework for measures of community divergence, and the focused size of the database offers advantages of efficiency for BLAST searching of large datasets. The CORE database is available as a searchable interface and for download at http://microbiome.osu.edu.

Robotic surgical technique for pediatric laryngotracheal reconstruction.

The attributes of robotic technology-steady, precise movements and untiring action in difficult positions and confined spaces-are well suited to surgical procedures that benefit from these qualities. Ironically, the introduction of robotic technology to the specialty of otolaryngology has been limited by the same anatomic constraints that make the technology so appealing: the anatomic areas that currently are accessed using minimally invasive endoscopic methods can be too small to accommodate the robotic apparatus. This article focuses on the authors' experience using the da Vinci robotic surgical system (Intuitive Surgical, Inc., Sunnyvale, California).

Modeling the cholesteatoma microenvironment: coculture of HaCaT keratinocytes with WS1 fibroblasts induces MMP-2 activation, invasive phenotype, and proteolysis of the extracellular matrix.

BACKGROUND: Increased keratinocyte proliferation, increased keratinocyte migration, elaboration of proteases resulting in proteolysis of the extracellular matrix (ECM), and destruction of surrounding tissues all typify the course of cholesteatoma growth. The contribution of stromal fibroblasts to these behaviors remains relatively unexplored. OBJECTIVES: Our objective for the current studies was to create a simple model with which to study these cholesteatoma behaviors, specifically, cell migration, invasion, and proteolysis of the extracellular matrix as well as the role of fibroblasts in the activated keratinocyte phenotype of cholesteatoma. DESIGN: The authors conducted an in vitro culture model. METHODS: The resulting model consists of activated keratinocytes (HaCaT cells) cocultured with normal dermal fibroblasts (WS1 cells) within a three-dimensional reconstituted ECM. We used a confocal imaging assay and software analysis to quantify total functional proteolysis of the ECM in monotypic and organotypic cocultures. This was accomplished by growing cells on an artificial ECM comprised of Matrigel and DQ-collagen IV. DQ-collagen is a "quenched" fluorescent peptide whose fluorescence is unmasked by proteolytic cleavage. RESULTS: Organotypic cocultures of keratinocytes and fibroblasts exhibited increased cell migration, increased cell invasion, increased matrix metalloproteinase-2 secretion and activation, and increased proteolysis of type IV collagen in three-dimensional ECM. Exposure to NSC27366, inhibitor of the small GTPase, Rac, resulted in reduction in both cell invasion and ECM proteolysis. CONCLUSIONS: Stromal fibroblasts may stimulate the invasive phenotype of keratinocytes, including ECM proteolysis. Increased cell invasion and proteolysis are dependent on the Rac pathway in this model. This simple culture model may help further our understanding of these destructive behaviors in cholesteatoma keratinocytes.

Robotic endoscopic surgery in a porcine model of the infant neck.

Minimally invasive surgery is rapidly becoming the desired surgical standard, especially for pediatric patients. Infants and children are a particular technical challenge, however, because of the small size of target anatomical structures and the small surgical workspace. Computer-assisted robot-enhanced surgical telemanipulators may overcome these challenges by facilitating surgery in a small workspace. We studied the feasibility of performing robotic endoscopic neck surgery on a porcine model of the human infant neck. The study design was a prospective, feasibility pilot study of a small cohort for proof of concept and for a survival model. Sixteen non-survival piglets weighing 4.5-10 kg were used to develop the surgical approach and operative technique. Eight piglets aged 3-6 weeks old and weighing 4.0-9.1 kg underwent survival thyroidectomy by a cervical endoscopic approach using the Zeus surgical robot, which includes the Aesop endoscope holder and "Microwrist" microdissecting instruments. We succeeded in performing endoscopic robotic neck surgery on a piglet as small as 4 kg, in an operative pocket as small as 2 cm(3). Total incision length for all three ports was ≤23 mm. There were no major complications, no major robotic instrument malfunctions or breakages, and no procedures required conversion to open surgery. These results support the feasibility of robotic endoscopic neck surgery on a neck the size of a human infant's.

Evolutions in the management of congenital intranasal skull base defects.

BACKGROUND: Congenital skull base defects have traditionally been treated via an intracranial approach. Recent advances in endoscopic management have made minimally invasive extracranial approaches feasible, with less morbidity. OBJECTIVE: To determine the success of endoscopic treatment of congenital cerebrospinal fluid leaks and encephaloceles. MAIN OUTCOME MEASURES: Retrospective review of congenital cerebrospinal fluid leaks and encephaloceles treated from January 1, 1992, to December 31, 2003. Data collected include demographic characteristics, presenting signs/symptoms, site of the skull base defect, surgical approach, repair technique, and clinical follow-up. RESULTS: Eight patients were treated via the endoscopic approach for congenital cerebrospinal fluid leaks and encephaloceles. The average age at presentation was 6 years (range, birth to 18 years). Three patients presented with meningitis (average age, 6 years), 4 had cerebrospinal fluid rhinorrhea, and 3 developed a nasal obstruction. Five defects originated at the foramen cecum, and 3 others involved the ethmoid roof/cribriform plate only. Our endoscopic approaches were successful on the first attempt, with a mean follow-up of 19 months. One patient experienced nasal stenosis postoperatively. CONCLUSIONS: Continuing progress in the surgical management of congenital skull base defects demonstrates that endoscopic repair is a successful alternative to traditional craniotomy approaches, with less morbidity. This technique requires meticulous preparation and precise grafting of the defect to avoid collateral damage to surrounding structures. While reduction in the risk of meningitis, intracranial complications, and facial growth abnormalities and alleviation of nasal obstruction necessitate the timely repair of these skull base defects, special considerations are discussed regarding the optimal timing of surgical intervention, operative working space, and exposure in a smaller nasal cavity.

Progressive osseous heteroplasia in the face of a child.

We describe a rare case of progressive osseous heteroplasia of the face in a child. Biopsy showed osteoma cutis superficially with ectopic bone formation in the deeper tissues including skeletal muscle. Analysis of DNA from peripheral blood leukocytes showed mutations in the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase (GNAS1), confirming the diagnosis of progressive osseous heteroplasia.

Three-dimensional computed tomography of congenital nasal anomalies.

OBJECTIVE: To determine the utility of performing three-dimensional (3D) computed tomography (CT) of congenital naso-frontal anomalies for preoperative planning and counseling and compare it with standard two-dimensional (2D) imaging and intraoperative findings. STUDY DESIGN: Prospective case evaluation of imaging studies and medical records in cohort of patients with congenital nasal anomalies. METHODS: We performed 3D CT imaging of three different types of congenital nasal lesions. Additional preoperative imaging consisted of standard 2D CT scans and/or magnetic resonance imaging (MRI). Information obtained from the 3D CTs was compared with other standard imaging and intraoperative findings. RESULTS: 3D CT was most useful in the case of a large encephalocele with a significant bony defect of the anterior cranial fossa. It provided moderate utility when used to evaluate a nasal dermoid with nasal bone and septal abnormalities and was of limited benefit in the case of a bifid nose with significant external soft tissue deformity and relatively normal bony anatomy. CONCLUSION: Congenital midline nasal anomalies are rare lesions with the potential for intracranial extension and anterior skull base abnormalities. The safe surgical treatment of these lesions depends upon accurate preoperative imaging to assist in establishing the diagnosis, to help guide surgical planning, and to assist in communicating the diagnosis and surgical approach for optimal counseling of families. 3D CT was instrumental in providing additional useful information in cases with significant bony abnormalities at little additional cost or time. It is also beneficial for preoperative counseling of patients and families with limited medical knowledge.

Cine magnetic resonance imaging for evaluation of focal tracheomalacia: innominate artery compression syndrome.

BACKGROUND: The contribution of an 'aberrant innominate artery' to respiratory distress syndromes has been a matter of debate nearly since the introduction of this concept. Recent advances in dynamic imaging are proving to be of value in assessing tracheal function in patients with respiratory distress. We therefore evaluated patients with innominate artery compression syndrome using the cine magnetic resonance imaging (CMRI) modality. OBJECTIVES: To apply the CMRI modality to evaluate patients with respiratory distress who exhibited tracheal compression at the level of the innominate artery. METHODS: A cohort of three patients in respiratory distress underwent bronchoscopy, followed by CMRI using a Siemens 1.5T Vision system. RESULTS: These three patients exhibited tracheal compression at the level of the innominate artery in agreement with their findings during bronchoscopy. All three exhibited dynamic tracheal compression that varied with the respiratory cycle. The degree of tracheal compromise was readily appreciated using the dynamic, real-time CMRI modality. Due to the severity of symptoms, the two children underwent innominate arteriopexy with complete resolution of their symptoms. CONCLUSIONS: CMRI provides extremely rapid acquisition of images, as well as integrated information regarding relationships of mediastinal structures. By providing functional imaging of tracheal patency during the respiratory cycle, CMRI may provide additional insight into innominate artery compression syndrome as more patients are evaluated.

Tourette syndrome manifest as chronic cough.

Gilles de la Tourette syndrome (TS) is a neurobehavioral disorder characterized by the presence of fluctuating involuntary motor and vocal tics. We report the case of a child in whom TS manifest as an involuntary recurrent complex tic presenting as a chronic cough. The clinical and pathological features and management of TS are reviewed.