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Purpose: To present the successful outcome of a patient with 2 extra vertebrae having spinal deformity. Participant and methods: A 29-year-old female presented with chronic low back pain. Uniquely, the patient demonstrated 2 extra vertebrae, 13 rib bearing vertebrae and 6 non-rib bearing lumbar vertebrae. Radiography assessment demonstrated an exaggerated thoracolumbar kyphosis. Treatment was given to reduce the deformity using spinal rehabilitation and postural rehabilitation methods. Extension traction for the deformity was given as well as corrective exercises and spinal manipulative therapy. Results: After 31 treatments there was dramatic reduction in pain, disability, quality of life and improved X-ray parameters. Following another 24 treatments, the patient reported to be well demonstrated a 14° reduction in thoracolumbar kyphosis and a 50 mm reduction in posterior thoracic translation. A 5-year follow-up showed only slight regression of both deformity and symptoms. Conclusion: This case has demonstrated that patients with an atypical number of vertebrae can benefit from structural spinal rehabilitation and experience improved spinal alignment and reported outcomes. The improved sagittal spine alignment corresponded with the dramatic reduction in chronic pain, disability and improved quality of life. Routine radiographic screening is necessary to diagnose atypical anatomical variants which can and should alter treatment approaches.

Previous investigations have found a correlation between abnormal curvatures and a variety of patient complaints such as cervical pain and disability. However, no study has shown that loss of the cervical curve is a direct result of exposure to a motor vehicle collision (MVC). This investigation presents a retrospective consecutive case series of patients with both a pre-injury cervical lateral radiograph (CLR) and a post-injury CLR after exposure to an MVC. Computer analysis of digitized vertebral body corners on CLRs was performed to investigate the possible alterations in the geometric alignment of the sagittal cervical curve. Methods: Three spine clinic records were reviewed over a 2-year period, looking for patients where both an initial lateral cervical X-ray and an examination were performed prior to the patient being exposed to a MVC; afterwards, an additional exam and radiographic analysis were obtained. A total of 41 patients met the inclusion criteria. Examination records of pain intensity on numerical pain rating scores (NPRS) and neck disability index (NDI), if available, were analyzed. The CLRs were digitized and modeled in the sagittal plane using curve fitting and the least squares error approach. Radiographic variables included total cervical curve (ARA C2–C7), Chamberlain’s line to horizontal (skull flexion), horizontal translation of C2 relative to C7, segmental translations (retrolisthesis and anterolisthesis), and circular modelling radii. Results: There were 15 males and 26 females with an age range of 8–65 years. Most participants were drivers (28) involved in rear-end impacts (30). The pre-injury NPRS was 2.7 while the post injury was 5.0; p < 0.001. The NDI was available on 24/41 (58.5%) patients and increased after the MVC from 15.7% to 32.8%, p < 0.001. An altered cervical curvature was identified following exposure to MVC, characterized by an increase in the mean radius of curvature (265.5 vs. 555.5, p < 0.001) and an approximate 8° reduction of lordosis from C2–C7; p < 0.001. The mid-cervical spine (C3–C5) showed the greatest curve reduction with an averaged localized mild kyphosis at these levels. Four participants (10%) developed segmental translations that were just below the threshold of instability, segmental translations < 3.5 mm. Conclusions: The post-exposure MVC cervical curvature was characterized by an increase in radius of curvature, an approximate 8° reduction in C2–C7 lordosis, a mild kyphosis of the mid-cervical spine, and a slight increase in anterior translation of C2–C7 sagittal balance. The modelling result indicates that the post-MVC cervical sagittal alignment approximates a second-order buckling alignment, indicating a significant alteration in curve geometry. Future biomechanics experiments and clinical investigations are needed to confirm these findings.

Abstract Background There is increasing evidence suggesting that open-label placebo (OLP) is an effective treatment for several medical conditions defined by self-report. However, little is known about patients’ experiences with OLP, and no studies have directly compared patients’ experiences in double-blind placebo (DBP) conditions. Methods This study was nested in a large randomized-controlled trial comparing the effects of OLP and DBP treatments in individuals with irritable bowel syndrome (IBS). We randomly selected 33 participants for interviews concerning their experiences in the parent trial. The data were qualitatively analyzed using an iterative immersion/crystallization approach. We then compared the qualitative interview data to the quantitative IBS severity data assessed during the parent trial, using a mixed methods approach. Results Two prominent interview themes were identified: (1) the participants’ feelings about their treatment allocation and (2) their reflections about the treatment. Both OLP and DBP participants mentioned hope and curiosity as major feelings driving them to engage with their treatment. However, while DBP participants tended to be more enthusiastic about their allocation, OLP participants were more ambivalent. Furthermore, OLP participants reflected more on their treatment, often involving noticeable cognitive and emotional processes of self-reflection. They offered a variety of explanations for their symptom improvement and were significantly less likely to attribute it to the treatment itself than DBP participants (Χ 2 [3] = 8.28; p = .041). Similarly, the participants’ retrospective narratives of symptom improvement were significantly correlated with their corresponding quantitative IBS severity scores only in DBP (p’s ≤ .006) but not in OLP (p’s ≥ .637). Conclusion OLP and DBP participants share feelings of hope, uncertainty and curiosity but differ in the extent of conscious reflection. The counter-intuitive OLP prompts more self-examination, ambivalent feelings and active engagement compared to DBP. At the same time, OLP participants are more reluctant to attribute symptom improvement to their treatment. Our findings substantially add to the emerging picture of factors that distinguish OLP and DBP and their potential mechanisms.

The present study examines whether self-reported trust in humans and self-reported trust in [(different) products with built-in] artificial intelligence (AI) are associated with one another and with brain structure. We sampled 90 healthy participants who provided self-reported trust in humans and AI and underwent brain structural magnetic resonance imaging assessment. We found that trust in humans, as measured by the trust facet of the personality inventory NEO-PI-R, and trust in AI products, as measured by items assessing attitudes toward AI and by a composite score based on items assessing trust toward products with in-built AI, were not significantly correlated. We also used a concomitant dimensional neuroimaging approach employing a data-driven source-based morphometry (SBM) analysis of gray-matter-density to investigate neurostructural associations with each trust domain. We found that trust in humans was negatively (and significantly) correlated with an SBM component encompassing striato-thalamic and prefrontal regions. We did not observe significant brain structural association with trust in AI. The present findings provide evidence that trust in humans and trust in AI seem to be dissociable constructs. While the personal disposition to trust in humans might be “hardwired” to the brain’s neurostructural architecture (at least from an individual differences perspective), a corresponding significant link for the disposition to trust AI was not observed. These findings represent an initial step toward elucidating how different forms of trust might be processed on the behavioral and brain level.

Purpose: Legionnaire's disease (LD) is a systemic infection caused predominantly by Legionella pneumophila (Lp). Symptoms include fever, cough, headache, body aches and shortness of breath. Legionella pneumophila serogroup 1 (Lp1) is the main serogroup responsible for outbreaks in the United States. In August 2019, a community-associated outbreak of LD was identified in a New York county including 17 cases of Lp1. During this outbreak investigation, potential environmental sources within a 5-mile radius were tested. By using a combination of culture, molecular methods, and whole-genome sequencing (WGS) the Wadsworth Center laboratory (WC) was able to identify the outbreak source. Methods & Materials: WC utilizes a streamlined testing algorithm that combines molecular screening of primary specimens followed by culture on PCR-positive samples. DNA was extracted from clinical and environmental samples using a manual procedure. Following the extraction, a multiplex real-time PCR was performed to detect Lp, Lp1 and other Legionella species. Samples that were positive for Lp1 were directly plated on BCYE, blood agar (TSA with sheep blood) and simultaneously set up using the IDEXX Legiolert™ method. Colonies typical of Lp1 were confirmed by real-time PCR and subjected to WGS and analysis using the in-house developed Legionella clustering (LegioCluster) pipeline to determine isolate relatedness. Results: In total, 53 specimens were tested between August 2019 and December 2019, including 36 environmental samples (cooling towers, fountains, wastewater) and 17 patient specimens. Lp1 DNA was detected in 8 patient specimens and Lp1 was cultured from 6 of 8 specimens. Lp1 was detected and isolated from 4 environmental samples. The IDEXX method was essential in the isolation of Lp1 from 2 clinical and 2 environmental samples. WGS analysis results demonstrated that 4 of the clinical isolates were closely related to each other and to an environmental sample (2-5 SNP differences). All other environmental isolates were not related. Conclusion: The efficient testing algorithm used by WC was instrumental in the isolation of Lp1 in this investigation. The combined use of molecular methods, various culture techniques including the IDEXX platform, and WGS analysis confirmed the source of the outbreak, helping to prevent any further cases.

Background: Blood-cerebrospinal fluid (CSF) barrier transporters affect the influx and efflux of drugs. The antiretrovirals tenofovir and emtricitabine may be substrates of blood-brain barrier (BBB) and blood-CSF barrier transporters, but data are limited regarding the pharmacogenetics and pharmacokinetics of their central nervous system (CNS) penetration. Objectives: We investigated genetic polymorphisms associated with CSF disposition of tenofovir and emtricitabine. Method: We collected paired plasma and CSF samples from 47 HIV-positive black South African adults who were virologically suppressed on efavirenz, tenofovir and emtricitabine. We considered 1846 single-nucleotide polymorphisms from seven relevant transporter genes (ABCC5, ABCG2, ABCB1, SLCO2B1, SCLO1A2, SLCO1B1 and ABCC4) and 782 met a linkage disequilibrium (LD)-pruning threshold. Results: The geometric mean (95% confidence interval [CI]) values for tenofovir and emtricitabine CSF-to-plasma concentration ratios were 0.023 (0.021–0.026) and 0.528 (0.460–0.605), respectively. In linear regression models, the lowest p-value for association with the tenofovir CSF-to-plasma ratio was ABCB1 rs1989830 (p = 1.2 × 10−3) and for emtricitabine, it was ABCC5 rs11921035 (p = 1.4 × 10−3). None withstood correction for multiple testing. Conclusion: No genetic polymorphisms were associated with plasma, CSF concentrations or CSF-to-plasma ratios for either tenofovir or emtricitabine.

As a type of relatively new methodology, the transcriptome-wide association study (TWAS) has gained interest due to capacity for gene-level association testing. However, the development of TWAS has outpaced statistical evaluation of TWAS gene prioritization performance. Current TWAS methods vary in underlying biological assumptions about tissue specificity of transcriptional regulatory mechanisms. In a previous study from our group, this may have affected whether TWAS methods better identified associations in single tissues versus multiple tissues. We therefore designed simulation analyses to examine how the interplay between particular TWAS methods and tissue specificity of gene expression affects power and type I error rates for gene prioritization. We found that cross-tissue identification of expression quantitative trait loci (eQTLs) improved TWAS power. Single-tissue TWAS (i.e., PrediXcan) had robust power to identify genes expressed in single tissues, but, often found significant associations in the wrong tissues as well (therefore had high false positive rates). Cross-tissue TWAS (i.e., UTMOST) had overall equal or greater power and controlled type I error rates for genes expressed in multiple tissues. Based on these simulation results, we applied a tissue specificity-aware TWAS (TSA-TWAS) analytic framework to look for gene-based associations with pre-treatment laboratory values from AIDS Clinical Trial Group (ACTG) studies. We replicated several proof-of-concept transcriptionally regulated gene-trait associations, including UGT1A1 (encoding bilirubin uridine diphosphate glucuronosyltransferase enzyme) and total bilirubin levels (p = 3.59×10-12), and CETP (cholesteryl ester transfer protein) with high-density lipoprotein cholesterol (p = 4.49×10-12). We also identified several novel genes associated with metabolic and virologic traits, as well as pleiotropic genes that linked plasma viral load, absolute basophil count, and/or triglyceride levels. By highlighting the advantages of different TWAS methods, our simulation study promotes a tissue specificity-aware TWAS analytic framework that revealed novel aspects of HIV-related traits.

Recently developed quantitative models of psychopathology (i.e., Hierarchical Taxonomy of Psychopathology) identify an Antagonistic Externalizing spectrum that captures the psychological disposition toward criminal and antisocial behavior. The purpose of the present study was to examine relations between Antagonistic psychopathology (and associated Five-Factor model Antagonism/Agreeableness) and neural functioning related to social-cognitive Theory of Mind using a large sample (N = 973) collected as part of the Human Connectome Project (Van Essen et al., 2013a). No meaningful relations between Antagonism/Antagonistic Externalizing and Theory of Mind-related neural activity or synchrony were observed (p < .005). We conclude by outlining methodological considerations (e.g., validity of social cognition task and low test–retest reliability of functional biomarkers) that may account for these null results, and present recommendations for future research.

Psychopathic individuals are notorious for their callous disregard for others’ emotions. Prior research has linked psychopathy to deficits in affective mechanisms underlying empathy (e.g., affective sharing), yet research relating psychopathy to cognitive mechanisms underlying empathy (e.g., affective perspective-taking and Theory of Mind) requires further clarification. To elucidate the neurobiology of cognitive mechanisms of empathy in psychopathy, we administered an fMRI task and tested for global as well as emotion-specific deficits in affective perspective-taking. Adult male incarcerated offenders (N = 94) viewed images of two people interacting, with one individual's face obscured by a shape. Participants were cued to either identify the emotion of the obscured individual or identify the shape from one of two emotion or shape choices presented on each trial. Target emotions included anger, fear, happiness, sadness, and neutral. Contrary to predictions, psychopathy was unrelated to neural activity in the Affective Perspective-taking > Shape contrast. In line with predictions, psychopathy was negatively related to task accuracy during affective perspective-taking for fear, happiness, and sadness. Psychopathy was related to reduced hemodynamic activity exclusively during fear perspective-taking in several areas: left anterior insula extending into posterior orbitofrontal cortex, right precuneus, left superior parietal lobule, and left superior occipital cortex. Although much prior research has emphasized psychopathy-related abnormalities in affective mechanisms mediating empathy, current results add to growing evidence of psychopathy-related abnormalities in a cognitive mechanism related to empathy. These findings highlight brain regions that are hypoactive in psychopathy when explicitly processing another's fear.

Saliva is a non-invasive, easily accessible tissue, which is regularly collected in large epidemiological studies to examine genetic questions. Recently, it is becoming more common to use saliva to assess DNA methylation. However, DNA extracted from saliva is a mixture of both bacterial and human DNA derived from epithelial and immune cells in the mouth. Thus, there are unique challenges to using salivary DNA in methylation studies that can influence data quality. This study assesses: (1) quantification of human DNA after extraction; (2) delineation of human and bacterial DNA; (3) bisulfite conversion (BSC); (4) quantification of BSC DNA; (5) PCR amplification of BSC DNA from saliva and; (6) quantitation of DNA methylation with a targeted assay. The framework proposed will allow saliva samples to be more widely used in targeted epigenetic studies.

Abstract Genes of the human leukocyte antigen (HLA) system encode cell-surface proteins involved in regulation of immune responses, and the way drugs interact with the HLA peptide binding groove is important in the immunopathogenesis of T-cell mediated drug hypersensitivity syndromes. Nevirapine (NVP), is an HIV-1 antiretroviral with treatment-limiting hypersensitivity reactions (HSRs) associated with multiple class I and II HLA alleles. Here we utilize a novel analytical approach to explore these multi-allelic associations by systematically examining HLA molecules for similarities in peptide binding specificities and binding pocket structure. We demonstrate that primary predisposition to cutaneous NVP HSR, seen across ancestral groups, can be attributed to a cluster of HLA-C alleles sharing a common binding groove F pocket with HLA-C*04:01. An independent association with a group of class II alleles which share the HLA-DRB1-P4 pocket is also observed. In contrast, NVP HSR protection is afforded by a cluster of HLA-B alleles defined by a characteristic peptide binding groove B pocket. The results suggest drug-specific interactions within the antigen binding cleft can be shared across HLA molecules with similar binding pockets. We thereby provide an explanation for multiple HLA associations with cutaneous NVP HSR and advance insight into its pathogenic mechanisms.

Abstract Background Syndromic surveillance of severe acute respiratory infections (SARI) is important to assess seriousness of disease as recommended by WHO for influenza. In 2015 the Robert Koch Institute (RKI) started to collaborate with a private hospital network to develop a SARI surveillance system using case-based data on ICD-10 codes. This first-time description of the system shows its application to the analysis of five influenza seasons. Methods Since week 40/2015, weekly updated anonymized data on discharged patients overall and on patients with respiratory illness including ICD-10 codes of primary and secondary diagnoses are transferred from the network data center to RKI. Retrospective datasets were also provided. Our descriptive analysis is based on data of 47 sentinel hospitals collected between weeks 1/2012 to 20/2016. We applied three different SARI case definitions (CD) based on ICD-10 codes for discharge diagnoses of respiratory tract infections (J09 - J22): basic CD (BCD), using only primary diagnoses; sensitive CD (SCD), using primary and secondary diagnoses; timely CD (TCD), using only primary diagnoses of patients hospitalized up to one week. We compared the CD with regard to severity, age distribution and timeliness and with results from the national primary care sentinel system. Results The 47 sentinel hospitals covered 3.6% of patients discharged from all German hospitals in 2013. The SCD comprised 2.2 times patients as the BCD, and 3.6 times as many as the TCD. Time course of SARI cases corresponded well to results from primary care surveillance and influenza virus circulation. The patients fulfilling the TCD had been completely reported after 3 weeks, which was fastest among the CD. The proportion of SARI cases among patients was highest in the youngest age group of below 5-year-olds. However, the age group 60 years and above contributed most SARI cases. This was irrespective of the CD used. Conclusions In general, available data and the implemented reporting system are appropriate to provide timely and reliable information on SARI in inpatients in Germany. Our ICD-10-based approach proved to be useful for fulfilling requirements for SARI surveillance. The exploratory approach gave valuable insights in data structure and emphasized the advantages of different CD.