Patient-specific mutation of Dync1h1 in mice causes brain and behavioral deficits.

AIMS: Cytoplasmic dynein heavy chain (DYNC1H1) is a multi-subunit protein complex that provides motor force for movement of cargo on microtubules and traffics them back to the soma. In humans, mutations along the DYNC1H1 gene result in intellectual disabilities, cognitive delays, and neurologic and motor deficits. The aim of the study was to generate a mouse model to a newly identified de novo heterozygous DYNC1H1 mutation, within a functional ATPase domain (c9052C > T(P3018S)), identified in a child with motor deficits, and intellectual disabilities. RESULTS: P3018S heterozygous (HET) knockin mice are viable; homozygotes are lethal. Metabolic and EchoMRI™ testing show that HET mice have a higher metabolic rate, are more active, and have less body fat compared to wildtype mice. Neurobehavioral studies show that HET mice perform worse when traversing elevated balance beams, and on the negative geotaxis test. Immunofluorescent staining shows neuronal migration abnormalities in the dorsal and lateral neocortex with heterotopia in layer I. Neuron-subtype specific transcription factors CUX1 and CTGF identified neurons from layers II/III and VI respectively in cortical layer I, and abnormal pyramidal neurons with MAP2+ dendrites projecting downward from the pial surface. CONCLUSION: The HET mice are a good model for the motor deficits seen in the child, and highlights the importance of cytoplasmic dynein in the maintenance of cortical function and dendritic orientation relative to the pial surface. Our results are discussed in the context of other dynein mutant mice and in relation to clinical presentation in humans with DYNC1H1 mutations.

Concurrent colonization of rodent kidneys with multiple species and serogroups of pathogenic Leptospira.

Rodents are important reservoir hosts of pathogenic leptospires in the US Virgin Islands. Our previous work determined that trapped rodents were colonized with Leptospira borgpetersenii serogroup Ballum (n = 48) and/or Leptospira kirschneri serogroup Icterohaemorrhagiae (n = 3). In addition, nine rodents appeared to be colonized with a mixed population comprising more than one species/serogroup. The aim of this study was to validate this finding by characterizing clonal isolates derived from cultures of mixed species. Cultures of presumptive mixed species (designated LR1, LR5, LR37, LR57, LR60, LR61, LR68, LR70, and LR72) were propagated in different media including Hornsby-Alt-Nally (HAN) media, incubated at both 29℃ and 37℃, and T80/40/LH incubated at 29℃. Polyclonal reference antisera specific for serogroup Ballum and Icterohaemorrhagiae were used to enrich for different serogroups followed by subculture on agar plates. Individual colonies were then selected for genotyping and serotyping. Of the nine cultures of mixed species/serogroups, a single clonal isolate was separated in five of them: L. borgpetersenii serogroup Ballum in LR1, LR5, and LR37, and L. kirschneri serogroup Icterohaemorrhagiae in LR60 and LR72. In four of the cultures with mixed species (LR57, LR61, LR68, and LR70), clonal isolates of both L. borgpetersenii serogroup Ballum and L. kirschneri serogroup Icterohaemorrhagiae were recovered. Our results definitively establish that rodents can be colonized with more than one species/serogroup of Leptospira concurrently. The identification and characterization of multiple species/serogroups of Leptospira from individual reservoir hosts of infection are essential to understand the epidemiology and transmission of disease to both human and domestic animal populations.IMPORTANCEPathogenic Leptospira, the causative agent of human and animal leptospirosis, comprise a diverse genus of species/serogroups which are inherently difficult to isolate from mammalian hosts due to fastidious growth requirements. Molecular evidence has indicated that reservoir hosts of Leptospira may shed multiple species concurrently. However, evidence of this phenomena by culture has been lacking. Culture is definitive and is essential for comprehensive characterization of recovered isolates by high-resolution genome sequencing and serotyping. In this work, a protocol using recently developed novel media formulations, in conjunction with reference antisera, was developed and validated to demonstrate the recovery of multiple species/serogroups of pathogenic Leptospira from the same host. The identification and characterization of multiple species/serogroups of Leptospira from individual reservoir hosts of infection are essential to understand the epidemiology and transmission of disease to both human and domestic animal populations.

Technical comparison of Abbott's UroVysion® and Biocare's CytoFISH urine fluorescence in situ hybridization (FISH) assays.

BACKGROUND: This study aims to compare the technical performance of Abbott's UroVysion and Biocare's CytoFISH urine cytology probe panel and position the CytoFISH probe panel as an alternative to UroVysion. The CytoFISH probe panel was developed based on clinically sensitive chromosomes found to be amplified in bladder cancers, as well as a locus-specific probe also seen to be amplified in bladder tumors. After extensive testing comparing CytoFISH to UroVysion, we present here our findings for the two assays. MATERIALS AND METHODS: A total of 216 cases representing a mix of male (ages 36-99) and female (ages 46-91) patients were assayed with both probe sets. The CytoFISH and UroVysion probe panels were tested in accordance with the UroVysion procedure, as outlined in the manufacturer's supplied package insert with the following exception: the probe volume used was 3µL for UroVysion and 5µL for CytoFISH. RESULTS: The scoring used for the CytoFISH and UroVysion assays revealed a 95% concordance, suggesting that Biocare's CytoFISH Test has at least the same clinical sensitivity and specificity as claimed by the Abbott UroVysion Kit. We found that the CytoFISH 5p15.2 locus-specific probe was easier to score than UroVysion's 9p21 deletion. CONCLUSION: The high rate of concordance between the two assays suggests that Biocare's CytoFISH assay is a robust alternative to Abbott's UroVysion in the diagnosis and monitoring of bladder carcinoma.

Opioid-stimulant trends in overdose toxicology by race, ethnicity, & gender: An analysis in Delaware, 2013-2019.

Recent upticks of stimulant presence in overdose deaths suggest the opioid epidemic is morphing, which raises questions about what drugs are involved and who is impacted. We investigate annual and growth rate trends in combined opioid-stimulant overdose toxicology between 2013 and 2019 for White, Black, and Hispanic male and female decedents in Delaware. During these years, toxicology shifted to illegal drugs for all with fentanyl leading the increase and opioid-cocaine combinations rising substantially. While combined opioid-cocaine toxicology grew among Black and Hispanic Delawareans, White males continue to report the highest rates overall. These findings depart from historical patterns and may challenge existing opioid epidemic policies.

Prescription Drug Histories among Drug Overdose Decedents in Delaware.

Background: The US opioid epidemic largely featured deaths from prescribed medications during Wave 1 (1990-2010), but its progression since then has resulted more so from deaths to illegal opioids-such as heroin (Wave 2 - 2010-2013) and fentanyl (Wave 3 - 2013-present). As deaths to illegally manufactured fentanyl have increased, attention to the role of prescribed opioids may be waning. However, the shifting nature of today's opioid epidemic demands we monitor how both legal and illegal drugs are involved in overdose deaths. Objectives: The purpose of our study is to investigate the prescription drug (Rx) records of overdose death decedents to illuminate the continued role of prescribed medications in Wave 3 deaths. Methods: We matched drug overdose death data and prescription drug monitoring data to investigate the prescription drug records (i.e. types of opioids and other medications) of Delaware, USA, decedents who died from a drug overdose death between January 1, 2013, and March 31, 2015 (27 months). Results: Fentanyl decedents differed significantly from other decedents in prescribed medications, including the amount and proximity of opioid and Rx fentanyl prescriptions before death. These relationships held while controlling for demographic characteristics and contributing health conditions. Conclusions: Our findings show a continued presence of Rx opioids in overdose deaths and that those dying from fentanyl had different Rx records than those who died from other drugs. Continued monitoring of Rx drugs, improved toxicology testing and greater data access for more research should follow to inform effective interventions.

Understanding Geographic and Neighborhood Variations in Overdose Death Rates.

The current opioid epidemic continues to challenge us in new and potentially troubling ways. For example, research today finds more overdose deaths occurring in rural, rather than urban, geographic areas. Yet, studies have often ignored heterogeneities within these spaces and the neighborhood variations therein. Using geodemographic classification, we investigate neighborhood differences in overdose death rates by geographical areas to further understand where and among what groups the problem might be most concentrated. For deaths between 2013 and 2016, we find significant variation in rates among neighborhoods, defined by their socio-economic and demographic characteristics. For example, overdose death rates vary up to 13-fold among neighborhoods within geographic areas. Our results overall show that while the rural or urban classification of a geographic area is important in understanding the current overdose problem, a more segmented analysis by neighborhood's socio-economic and demographic makeup is also necessary.

Does adding antibiotics to cement reduce the need for early revision in total knee arthroplasty?

BACKGROUND: There is considerable debate about whether antibiotic-loaded bone cement should be used for fixation of TKAs. While antibiotics offer the theoretical benefit of lowering early revision due to infection, they may weaken the cement and thus increase the likelihood of aseptic loosening, perhaps resulting in a higher revision rate. QUESTIONS/PURPOSES: We (1) compared the frequency of early knee revision arthroplasty in patients treated with antibiotic-loaded or non-antibiotic-loaded cement for initial fixation, (2) determined effects of age, sex, comorbidities, and surgeons' antibiotic-loaded cement usage patterns on revision rate, and (3) compared causes of revision (aseptic or septic) between groups. METHODS: Our study sample was taken from the Canadian Joint Replacement Registry and Canada's Hospital Morbidity Database and included cemented TKAs performed between April 1, 2003, and March 31, 2008, including 20,016 TKAs inserted with non-antibiotic-loaded cement and 16,665 inserted with antibiotic-loaded cement. Chi-square test was used to compare the frequency of early revisions between groups. Cox regression modeling was used to determine whether revision rate would change by age, sex, comorbidities, or use of antibiotic-loaded cement. Similar Cox regression modeling was used to compare cause of revision between groups. RESULTS: Two-year revision rates were similar between the groups treated with non-antibiotic-loaded cement and antibiotic-loaded cement (1.40% versus 1.51%, p = 0.41). When controlling for age, sex, comorbidities, diabetes, and surgeons' antibiotic-loaded cement usage patterns, the revision risk likewise was similar between groups. Revision rates for infection were similar between groups; however, there were more revisions for aseptic loosening in the group treated with non-antibiotic-loaded cement (p = 0.02). CONCLUSIONS: The use of antibiotic-loaded cement in TKAs performed for osteoarthritis has no clinically significant effect on reducing revision within 2 years in patients who received perioperative antibiotics. Longer followup and confirmation of these findings with other national registries are warranted.

Types of genetic determinism in direct-to-consumer genetic testing for health.

Prior research has challenged genetic determinism by highlighting the complex ways lay people engage with genetics. However, most of these critiques took place prior to the availability of direct-to-consumer (DTC) genetic health testing and were based on reactions to genetic testing administered in a clinical context due to either symptoms or family history. Today, many lay people interact with genetic health information outside of medicine, and often without pre-existing symptoms or family history. This suggests the need to revisit genetic determinism in the context of this new mode of public engagement with genetic information about health. In this paper we examine how a sample of 39 people who had previously taken a DTC genetic test for health make sense of their results. We find genetic determinism is prominent, but takes on several distinct forms, including protective determinism, motivating determinism, and absolute determinism. Considering this, we argue that genetic determinism should not be treated as a singular or fixed concept and cannot be dismissed as insignificant, given its continued salience for DTC genetic test-takers. Our analysis also pays particular attention to how test-takers interpret negative results (i.e., no elevated risks detected), as this is a common outcome of DTC genetic tests but has not been a focus of prior research.

Identification of equine mares as reservoir hosts for pathogenic species of Leptospira.

Equine leptospirosis can result in abortion, stillbirth, neonatal death, placentitis, and uveitis. Horses can also act as subclinical reservoir hosts of infection, which are characterized as asymptomatic carriers that persistently excrete leptospires and transmit disease. In this study, PCR and culture were used to assess urinary shedding of pathogenic Leptospira from 37 asymptomatic mares. Three asymptomatic mares, designated as H2, H8, and H9, were PCR-positive for lipL32, a gene specific for pathogenic species of Leptospira. One asymptomatic mare, H9, was culture-positive, and the recovered isolate was classified as L. kirschneri serogroup Australis serovar Rushan. DNA capture and enrichment of Leptospira genomic DNA from PCR-positive, culture-negative samples determined that asymptomatic mare H8 was also shedding L. kirschneri serogroup Australis, whereas asymptomatic mare H2 was shedding L. interrogans serogroup Icterohaemorrhagiae. Sera from all asymptomatic mares were tested by the microscopic agglutination test (MAT) and 35 of 37 (94.6%) were seropositive with titers ranging from 1:100 to 1:3200. In contrast to asymptomatic mares, mare H44 presented with acute spontaneous abortion and a serum MAT titer of 1:102,400 to L. interrogans serogroup Pomona serovar Pomona. Comparison of L. kirschneri serogroup Australis strain H9 with that of L. interrogans serogroup Pomona strain H44 in the hamster model of leptospirosis corroborated differences in virulence of strains. Since lipopolysaccharide (LPS) is a protective antigen in bacterin vaccines, the LPS of strain H9 (associated with subclinical carriage) was compared with strain H44 (associated with spontaneous abortion). This revealed different LPS profiles and immunoreactivity with reference antisera. It is essential to know what species and serovars of Leptospira are circulating in equine populations to design efficacious vaccines and diagnostic tests. Our results demonstrate that horses in the US can act as reservoir hosts of leptospirosis and shed diverse pathogenic Leptospira species via urine. This report also details the detection of L. kirschneri serogroup Australis serovar Rushan, a species and serotype of Leptospira, not previously reported in the US.

Host population structure and rare dispersal events drive leptospirosis transmission patterns among Rattus norvegicus in Boston, Massachusetts, US.

Leptospirosis (caused by pathogenic bacteria in the genus Leptospira ) is prevalent worldwide but more common in tropical and subtropical regions. Transmission can occur following direct exposure to infected urine from reservoir hosts, such as rats, or a urine-contaminated environment, which then can serve as an infection source for additional rats and other mammals, including humans. The brown rat, Rattus norvegicus , is an important reservoir of leptospirosis in urban settings. We investigated leptospirosis among brown rats in Boston, Massachusetts and hypothesized that rat dispersal in this urban setting influences the movement, persistence, and diversity of Leptospira . We analyzed DNA from 328 rat kidney samples collected from 17 sites in Boston over a seven-year period (2016-2022); 59 rats representing 12 of 17 sites were positive for Leptospira . We used 21 neutral microsatellite loci to genotype 311 rats and utilized the resulting data to investigate genetic connectivity among sampling sites. We generated whole genome sequences for 28 Leptospira isolates obtained from frozen and fresh tissue from some of the 59 Leptospira -positive rat kidneys. When isolates were not obtained, we attempted Leptospira genomic DNA capture and enrichment, which yielded 14 additional Leptospira genomes from rats. We also generated an enriched Leptospira genome from a 2018 human case in Boston. We found evidence of high genetic structure and limited dispersal among rat populations that is likely influenced by major roads and/or other unknown dispersal barriers, resulting in distinct rat population groups within the city; at certain sites these groups persisted for multiple years. We identified multiple distinct phylogenetic clades of L. interrogans among rats, with specific clades tightly linked to distinct rat populations. This pattern suggests L. interrogans persists in local rat populations and movement of leptospirosis in this urban rat community is driven by rat dispersal. Finally, our genomic analyses of the 2018 human leptospirosis case in Boston suggests a link to rats as the source. These findings will be useful for guiding rat control and human leptospirosis mitigation efforts in this and other urban settings.

The role of occipital condyle and atlas anomalies on occipital cervical fusion outcomes in Chiari malformation type I with syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.

OBJECTIVE: Congenital anomalies of the atlanto-occipital articulation may be present in patients with Chiari malformation type I (CM-I). However, it is unclear how these anomalies affect the biomechanical stability of the craniovertebral junction (CVJ) and whether they are associated with an increased incidence of occipitocervical fusion (OCF) following posterior fossa decompression (PFD). The objective of this study was to determine the prevalence of condylar hypoplasia and atlas anomalies in children with CM-I and syringomyelia. The authors also investigated the predictive contribution of these anomalies to the occurrence of OCF following PFD (PFD+OCF). METHODS: The authors analyzed the prevalence of condylar hypoplasia and atlas arch anomalies for patients in the Park-Reeves Syringomyelia Research Consortium database who underwent PFD+OCF. Condylar hypoplasia was defined by an atlanto-occipital joint axis angle (AOJAA) ≥ 130°. Atlas assimilation and arch anomalies were identified on presurgical radiographic imaging. This PFD+OCF cohort was compared with a control cohort of patients who underwent PFD alone. The control group was matched to the PFD+OCF cohort according to age, sex, and duration of symptoms at a 2:1 ratio. RESULTS: Clinical features and radiographic atlanto-occipital joint parameters were compared between 19 patients in the PFD+OCF cohort and 38 patients in the PFD-only cohort. Demographic data were not significantly different between cohorts (p > 0.05). The mean AOJAA was significantly higher in the PFD+OCF group than in the PFD group (144° ± 12° vs 127° ± 6°, p < 0.0001). In the PFD+OCF group, atlas assimilation and atlas arch anomalies were identified in 10 (53%) and 5 (26%) patients, respectively. These anomalies were absent (n = 0) in the PFD group (p < 0.001). Multivariate regression analysis identified the following 3 CVJ radiographic variables that were predictive of OCF occurrence after PFD: AOJAA ≥ 130° (p = 0.01), clivoaxial angle < 125° (p = 0.02), and occipital condyle-C2 sagittal vertical alignment (C-C2SVA) ≥ 5 mm (p = 0.01). A predictive model based on these 3 factors accurately predicted OCF following PFD (C-statistic 0.95). CONCLUSIONS: The authors' results indicate that the occipital condyle-atlas joint complex might affect the biomechanical integrity of the CVJ in children with CM-I and syringomyelia. They describe the role of the AOJAA metric as an independent predictive factor for occurrence of OCF following PFD. Preoperative identification of these skeletal abnormalities may be used to guide surgical planning and treatment of patients with complex CM-I and coexistent osseous pathology.

Animals Exposed to Leptospira Serogroups Not Included in Bacterins in the United States and Puerto Rico.

Leptospirosis is a worldwide zoonotic disease. Pathogenic leptospires colonize the renal tubules and genital tract of animals and are excreted via urine. Transmission occurs via direct contact or through contaminated water or soil. The microscopic agglutination test (MAT) is the gold standard for the serodiagnosis of leptospirosis. The present study aims to evaluate animal exposure to Leptospira in the U.S. and Puerto Rico during the period 2018-2020. The presence of antibodies against pathogenic Leptospira spp. was assessed with the MAT according to the standards of the World Organisation for Animal Health. A total of 568 sera were submitted for diagnostic, surveillance, or import/export testing from the U.S. and Puerto Rico. Seropositivity (≥1:100) was 51.8% (294/568) with agglutinating antibodies found in 115 (39.1%) cattle, 84 (28.6%) exotic animals, 38 (12.9%) horses, 22 (7.5%) goats, 15 (5.1%) dogs, 11 (3.7%) swine, and 9 (3.1%) sheep. The most detected serogroups were Australis, Grippotyphosa, and Ballum. The results showed that animals were exposed to serogroups/serovars not included in commercial bacterins such as Ballum, Bratislava (only in swine vaccine), and Tarassovi. Our findings suggest that more studies should include culture and concomitant genotyping to reduce animal disease and zoonotic risk through efficacious vaccine and diagnostic strategies.

Feasibility of a Novel COVID-19 Telehealth Care Management Program Among Individuals Receiving Treatment for Opioid Use Disorder: Analysis of a Pilot Program.

BACKGROUND: The emergence of COVID-19 exacerbated the existing epidemic of opioid use disorder (OUD) across the United States due to the disruption of in-person treatment and support services. Increased use of technology including telehealth and the development of new partnerships may facilitate coordinated treatment interventions that comprehensively address the health and well-being of individuals with OUD. OBJECTIVE: The analysis of this pilot program aimed to determine the feasibility of delivering a COVID-19 telehealth care management program using SMS text messages for patients receiving OUD treatment. METHODS: Eligible individuals were identified from a statewide opioid treatment program (OTP) network. Those who screened positive for COVID-19 symptoms were invited to connect to care management through a secure SMS text message that was compliant with Health Insurance Portability and Accountability Act standards. Care management monitoring for COVID-19 was provided for a period of up to 14 days. Monitoring services consisted of daily SMS text messages from the care manager inquiring about the participant's physical health in relation to COVID-19 symptoms by confirming their temperature, if the participant was feeling worse since the prior day, and if the participant was experiencing symptoms such as coughing or shortness of breath. If COVID-19 symptoms worsened during this observation period, the care manager was instructed to refer participants to the hospital for acute care services. The feasibility of the telehealth care management intervention was assessed by the rates of adoption in terms of program enrollment, engagement as measured by the number of SMS text message responses per participant, and retention in terms of the number of days participants remained in the program. RESULTS: Between January and April 2021, OTP staff members referred 21 patients with COVID-19 symptoms, and 18 (82%) agreed to be contacted by a care manager. Participants ranged in age from 27 to 65 years and primarily identified as female (n=12, 67%) and White (n=15, 83%). The majority of participants were Medicaid recipients (n=14, 78%). There were no statistically significant differences in the demographic characteristics between those enrolled and not enrolled in the program. A total of 12 (67%) patients were enrolled in the program, with 2 (11%) opting out of SMS text message communication and choosing instead to speak with a care manager verbally by telephone. The remaining 10 participants answered a median of 7 (IQR 4-10) SMS text messages and were enrolled in the program for a median of 9 (IQR 7.5-12) days. No participants were referred for acute care services or hospitalized during program enrollment. CONCLUSIONS: These results demonstrate the feasibility of a novel telehealth intervention to monitor COVID-19 symptoms among OTP patients in treatment for OUD. Further research is needed to determine the applicability of this intervention to monitor patients with comorbid chronic conditions in addition to the acceptability among patients and providers using the SMS text messaging modality.

Isolation of Leptospira kirschneri serovar Grippotyphosa from a red panda (Ailurus fulgens) after antimicrobial therapy: Case report.

A 1-year-old female red panda started showing symptoms of illness, including lethargy, anorexia, abdominal discomfort, and vomiting, shortly after transfer to a new zoo. Serum was tested for leptospirosis using the microscopic agglutination test, and a titer of 1:25,600 to serogroup Grippotyphosa was detected. Antimicrobial treatment with doxycycline was initiated. After completion of treatment and resolution of clinical symptoms, a urine sample was collected to ensure clearance of leptospires and cessation of urinary shedding prior to co-housing with other red pandas. A repeat serum sample taken 13 days later had a lower titer of 1:6,400 to serogroup Grippotyphosa. A sample of the animal's urine was cultured in HAN media and was culture positive for Leptospira. The recovered isolate was completely characterized by whole genome sequencing and serotyping with reference antisera, and the isolate was classified as Leptospira kirschneri serogroup Grippotyphosa serovar Grippotyphosa strain RedPanda1.

Leptospira borgpetersenii serovar Hardjo and Leptospira santarosai serogroup Pyrogenes isolated from bovine dairy herds in Puerto Rico.

Leptospirosis is one of the most common zoonotic diseases in the world and endemic in the Caribbean Islands. Bovine leptospirosis is an important reproductive disease. Globally, cattle are recognized as a reservoir host for L. borgpetersenii serovar Hardjo, which is transmitted via urine, semen, and uterine discharges, and can result in abortion and poor reproductive performance. The dairy industry in Puerto Rico comprises up to 25% of agriculture-related income and is historically the most financially important agricultural commodity on the island. In this study, we report the isolation of two different pathogenic Leptospira species, from two different serogroups, from urine samples collected from dairy cows in Puerto Rico: L. borgpetersenii serogroup Sejroe serovar Hardjo and L. santarosai serogroup Pyrogenes. Recovered isolates were classified using whole-genome sequencing, serotyping with reference antisera and monoclonal antibodies, and immunoblotting. These results demonstrate that dairy herds in Puerto Rico can be concurrently infected with more than one species and serovar of Leptospira, and that bacterin vaccines and serologic diagnostics should account for this when applying intervention and diagnostic strategies.

Assessing rodents as carriers of pathogenic Leptospira species in the U.S. Virgin Islands and their risk to animal and public health.

Leptospirosis is a global zoonotic disease caused by pathogenic bacteria of the genus Leptospira. We sought to determine if rodents in U.S. Virgin Islands (USVI) are carriers of Leptospira. In total, 140 rodents were sampled, including 112 Mus musculus and 28 Rattus rattus. A positive carrier status was identified for 64/140 (45.7%); 49 (35.0%) were positive by dark-field microscopy, 60 (42.9%) by culture, 63 (45.0%) by fluorescent antibody testing, and 61 (43.6%) by real-time polymerase chain reaction (rtPCR). Molecular typing indicated that 48 isolates were L. borgpetersenii and 3 were L. kirschneri; the remaining nine comprised mixed species. In the single culture-negative sample that was rtPCR positive, genotyping directly from the kidney identified L. interrogans. Serotyping of L. borgpetersenii isolates identified serogroup Ballum and L. kirschneri isolates as serogroup Icterohaemorrhagiae. These results demonstrate that rodents are significant Leptospira carriers and adds to understanding the ecoepidemiology of leptospirosis in USVI.

Complications and outcomes of posterior fossa decompression with duraplasty versus without duraplasty for pediatric patients with Chiari malformation type I and syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.

OBJECTIVE: The aim of this study was to determine differences in complications and outcomes between posterior fossa decompression with duraplasty (PFDD) and without duraplasty (PFD) for the treatment of pediatric Chiari malformation type I (CM1) and syringomyelia (SM). METHODS: The authors used retrospective and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM1-SM who received PFD or PFDD and had at least 1 year of follow-up data. Preoperative, treatment, and postoperative characteristics were recorded and compared between groups. RESULTS: A total of 692 patients met the inclusion criteria for this database study. PFD was performed in 117 (16.9%) and PFDD in 575 (83.1%) patients. The mean age at surgery was 9.86 years, and the mean follow-up time was 2.73 years. There were no significant differences in presenting signs or symptoms between groups, although the preoperative syrinx size was smaller in the PFD group. The PFD group had a shorter mean operating room time (p < 0.0001), fewer patients with > 50 mL of blood loss (p = 0.04), and shorter hospital stays (p = 0.0001). There were 4 intraoperative complications, all within the PFDD group (0.7%, p > 0.99). Patients undergoing PFDD had a 6-month complication rate of 24.3%, compared with 13.7% in the PFD group (p = 0.01). There were no differences between groups for postoperative complications beyond 6 months (p = 0.33). PFD patients were more likely to require revision surgery (17.9% vs 8.3%, p = 0.002). PFDD was associated with greater improvements in headaches (89.6% vs 80.8%, p = 0.04) and back pain (86.5% vs 59.1%, p = 0.01). There were no differences between groups for improvement in neurological examination findings. PFDD was associated with greater reduction in anteroposterior syrinx size (43.7% vs 26.9%, p = 0.0001) and syrinx length (18.9% vs 5.6%, p = 0.04) compared with PFD. CONCLUSIONS: PFD was associated with reduced operative time and blood loss, shorter hospital stays, and fewer postoperative complications within 6 months. However, PFDD was associated with better symptom improvement and reduction in syrinx size and lower rates of revision decompression. The two surgeries have low intraoperative complication rates and comparable complication rates beyond 6 months.

An Examination of Seasonal Trends in Delaware Drug Overdoses, 2016-2020.

Objective: To examine whether overdose deaths and related metrics-overdose calls for service to police and non-fatal overdose emergency department visits-in Delaware follow within-year (i.e., seasonal) patterns during the most recent years of the opioid epidemic (2016-2020). Methods: We begin by providing descriptive statistics on yearly trends in overdose metrics, followed by Analysis of Variance (ANOVA) to analyze whether seasonal variations have a significant impact on the patterns of Delaware's overdose metrics while controlling for annual variations. Results: We find yearly variations across the three overdose-related metrics, with overdose deaths reporting the only consistent increases per year. Within-year, or seasonal, variations show the spring months have the most consistent increases in overdose deaths and overdose calls for service across years we studied. Finally, we report significant differences for all overdose metrics across years and seasons. Conclusions: As in prior studies, we find significant variation in overdose-related metrics by season in Delaware. Policy Implications: These findings lend support to existing interventions in slowing yearly growth in overdose deaths. However, allocation of resources and interventions to specific times of the year-when overdoses are highest-may further reduce risks and harms.

Exposure and Carriage of Pathogenic Leptospira in Livestock in St. Croix, U.S. Virgin Islands.

From 2019-2020, the Virgin Islands Department of Health (VIDOH) investigated potential animal reservoirs of Leptospira spp., the pathogenic bacteria that cause leptospirosis. We examined Leptospira exposure and carriage in livestock on the island of St. Croix, United States Virgin Islands (USVI). We utilized the microscopic agglutination test (MAT) to evaluate the sera, and the fluorescent antibody test (FAT), real time polymerase chain reaction (rt-PCR), and bacterial culture to evaluate urine specimens from livestock (n = 126): 28 cattle, 19 goats, 46 pigs, and 33 sheep. Seropositivity was 37.6% (47/125) with agglutinating antibodies to the following serogroups identified: Australis, Djasiman, Icterohaemorrhagiae, Ballum, Sejroe, Cynopteri, Autumnalis, Hebdomadis, Pomona, Canicola, Grippotyphosa, and Pyrogenes. Urine from 4 animals (4.0%, 4/101) was positive by rt-PCR for lipL32: 2 sheep, 1 goat, and 1 bull. Sequencing of secY amplicons identified L. interrogans in 1 sheep and 1 bull. Livestock in USVI harbor pathogenic Leptospira bacteria and could play a role in the zoonotic cycle of leptospirosis.

A multicenter validation of the condylar-C2 sagittal vertical alignment in Chiari malformation type I: a study using the Park-Reeves Syringomyelia Research Consortium.

OBJECTIVE: The condylar-C2 sagittal vertical alignment (C-C2SVA) describes the relationship between the occipitoatlantal joint and C2 in patients with Chiari malformation type I (CM-I). It has been suggested that a C-C2SVA ≥ 5 mm is predictive of the need for occipitocervical fusion (OCF) or ventral brainstem decompression (VBD). The authors' objective was to validate the predictive utility of the C-C2SVA by using a large, multicenter cohort of patients. METHODS: This validation study used a cohort of patients derived from the Park-Reeves Syringomyelia Research Consortium; patients < 21 years old with CM-I and syringomyelia treated from June 2011 to May 2016 were identified. The primary outcome was the need for OCF and/or VBD. After patients who required OCF and/or VBD were identified, 10 age- and sex-matched controls served as comparisons for each OCF/VBD patient. The C-C2SVA (defined as the position of a plumb line from the midpoint of the O-C1 joint relative to the posterior aspect of the C2-3 disc space), pBC2 (a line perpendicular to a line from the basion to the posteroinferior aspect of the C2 body), and clival-axial angle (CXA) were measured on sagittal MRI. The secondary outcome was the need for ≥ 2 CM-related operations. RESULTS: Of the 206 patients identified, 20 underwent OCF/VBD and 14 underwent repeat posterior fossa decompression. A C-C2SVA ≥ 5 mm was 100% sensitive and 86% specific for requiring OCF/VBD, with a 12.6% misclassification rate, whereas CXA < 125° was 55% sensitive and 99% specific, and pBC2 ≥ 9 was 20% sensitive and 88% specific. Kaplan-Meier analysis demonstrated that there was a significantly shorter time to second decompression in children with C-C2SVA ≥ 5 mm (p = 0.0039). The mean C-C2SVA was greater (6.13 ± 1.28 vs 3.13 ± 1.95 mm, p < 0.0001), CXA was lower (126° ± 15.4° vs 145° ± 10.7°, p < 0.05), and pBC2 was similar (7.65 ± 1.79 vs 7.02 ± 1.26 mm, p = 0.31) among those who underwent OCF/VBD versus decompression only. The intraclass correlation coefficient for the continuous measurement of C-C2SVA was 0.52; the kappa value was 0.47 for the binary categorization of C-C2SVA ≥ 5 mm. CONCLUSIONS: These results validated the C-C2SVA using a large, multicenter, external cohort with 100% sensitivity, 86% specificity, and a 12.6% misclassification rate. A C-C2SVA ≥ 5 mm is highly predictive of the need for OCF/VBD in patients with CM-I. The authors recommend that this measurement be considered among the tools to identify the "high-risk" CM-I phenotype.