Biofilm exopolysaccharides alter sensory-neuron-mediated sickness during lung infection.

Infections of the lung cause observable sickness thought to be secondary to inflammation. Signs of sickness are crucial to alert others via behavioral-immune responses to limit contact with contagious individuals. Gram-negative bacteria produce exopolysaccharide (EPS) that provides microbial protection; however, the impact of EPS on sickness remains uncertain. Using genome-engineered Pseudomonas aeruginosa (P. aeruginosa) strains, we compared EPS-producers versus non-producers and a virulent Escherichia coli (E. coli) lung infection model in male and female mice. EPS-negative P. aeruginosa and virulent E. coli infection caused severe sickness, behavioral alterations, inflammation, and hypothermia mediated by TLR4 detection of the exposed lipopolysaccharide (LPS) in lung TRPV1+ sensory neurons. However, inflammation did not account for sickness. Stimulation of lung nociceptors induced acute stress responses in the paraventricular hypothalamic nuclei by activating corticotropin-releasing hormone neurons responsible for sickness behavior and hypothermia. Thus, EPS-producing biofilm pathogens evade initiating a lung-brain sensory neuronal response that results in sickness.

Whakarongo Mai: Listening to the views of tamariki, whanau and kaimahi within the Aotearoa New Zealand child protection system.

BACKGROUND: The Aotearoa New Zealand child protection system consistently fails Maori (Aotearoa New Zealand's Indigenous peoples), with recent reports calling for fundamental changes. Those longer-term shifts are necessary, but short-term changes are also needed. One such change is a shift in the way child protection decisions are made, and the ways in which tamariki (children) and whanau (families) are involved in those processes. OBJECTIVE: This research sought to explore the views of a small group of Maori people with experience of the child protection system on one overarching question, "how should decisions about the safety and wellbeing of tamariki Maori be made, and what role should whanau and tamariki themselves play in that process?" PARTICIPANTS, METHOD AND SETTING: Eight semi-structured interviews were conducted, seven of which were in person and one of which took place online. All participants were Maori, and all of them had involvement with the child protection system in either a personal or a professional capacity. Two of the participants were young people themselves. FINDINGS AND CONCLUSION: Three overarching themes were identified: that the voices of tamariki, whanau and kaimahi (professionals) all have a place, but the current system doesn't strike the right balance, that the value of tikanga (Maori cultural values and practices) cannot be understated, but care is needed for whanau who may not know that tikanga, and that the challenges experienced by whanau in this context are often intergenerational. The paper concludes with a discussion of implications for law and policy.

Neutrophil swarming: Is a good offense the best defense?

The phenomenon of swarming has long been observed in nature as a strategic event that serves as a good offense toward prey and predators. Imaging studies have uncovered that neutrophils employ this swarm-like tactic within infected and inflamed tissues as part of the innate immune response. Much of our understanding of neutrophil swarming builds from observations during sterile inflammation and various bacterial, fungal, and parasitic infections of the skin. However, the architecture and function of the skin differ significantly from vital organs where highly specialized microenvironments carry out critical functions. Therefore, the detrimental extent this perturbation may have on organ function remains unclear. In this review, we examine organ-specific swarming within the skin, liver, and lungs, with a detailed focus on swarming within microvascular environments. In addition, we examine potential "swarmulants" that initiate both transient and persistent swarms that have been implicated in disease.

Inflammatory platelet death drives sepsis.

Thrombocytopenia is common in severe sepsis and is associated with an increased risk of mortality. A new study shows that platelet pyroptosis initiated during infection promotes a feedforward loop of neutrophil-mediated inflammation that worsens outcomes during sepsis.

Surfactant Protein D Influences Mortality During Abdominal Sepsis by Facilitating Escherichia coli Colonization in the Gut.

Determine the role of surfactant protein D (SPD) in sepsis. DESIGN: Murine in vivo study. SETTING: Research laboratory at an academic medical center. PATIENTS: SPD knockout (SPD-/-) and wild-type (SPD+/+) mice. INTERVENTIONS: SPD-/- and SPD+/+ mice were subjected to cecal ligation and puncture (CLP). After CLP, Escherichia coli bacteremia was assessed in both groups. Cecal contents from both groups were cultured to assess for colonization by E. coli. To control for parental effects on the microbiome, SPD-/- and SPD+/+ mice were bred from heterozygous parents, and levels of E. coli in their ceca were measured. Gut segments were harvested from mice, and SPD protein expression was measured by Western blot. SPD-/- mice were gavaged with green fluorescent protein, expressing E. coli and recombinant SPD (rSPD). MEASUREMENTS AND MAIN RESULTS: SPD-/- mice had decreased mortality and decreased E. coli bacteremia compared with SPD+/+ mice following CLP. At baseline, SPD-/- mice had decreased E. coli in their cecal flora. When SPD-/- and SPD+/+ mice were bred from heterozygous parents and then separated after weaning, less E. coli was cultured from the ceca of SPD-/- mice. E. coli gut colonization was increased by gavage of rSPD in SPD-/- mice. The source of enteric SPD in SPD+/+ mice was the gallbladder. CONCLUSIONS: Enteral SPD exacerbates mortality after CLP by facilitating colonization of the mouse gut with E. coli.

Peritoneal macrophages are impaired in cathelicidin-deficient mice systemically challenged with Escherichia coli.

Cathelicidins are small, cationic peptides produced by macrophages with protective effects against infection although their involvement in phagocytosis is not fully understood. This study demonstrates that fewer macrophages were recruited in mice genetically deficient in cathelicidin (Camp-/-) during acute Escherichia coli-induced peritonitis and those macrophages had impaired phagocytosis. These defects seem due to endogenous functions of murine cathelicidin (CRAMP) as phagocytosis was not improved by synthetic human cathelicidin (LL-37) in a murine phagocytic cell line. This knowledge contributes to understanding the function of cathelicidins in the recruitment and function of phagocytic cells and differential roles between endogenous and exogenous cathelicidins.

Emotional intelligence predicts academic performance: A meta-analysis.

Schools and universities devote considerable time and resources to developing students' social and emotional skills, such as emotional intelligence (EI). The goals of such programs are partly for personal development but partly to increase academic performance. The current meta-analysis examines the degree to which student EI is associated with academic performance. We found an overall effect of ρ = .20 using robust variance estimation (N = 42,529, k = 1,246 from 158 citations). The association is significantly stronger for ability EI (ρ = .24, k = 50) compared with self-rated (ρ = .12, k = 33) or mixed EI (ρ = .19, k = 90). Ability, self-rated, and mixed EI explained an additional 1.7%, 0.7%, and 2.3% of the variance, respectively, after controlling for intelligence and big five personality. Understanding and management branches of ability EI explained an additional 3.9% and 3.6%, respectively. Relative importance analysis suggests that EI is the third most important predictor for all three streams, after intelligence and conscientiousness. Moderators of the effect differed across the three EI streams. Ability EI was a stronger predictor of performance in humanities than science. Self-rated EI was a stronger predictor of grades than standardized test scores. We propose that three mechanisms underlie the EI/academic performance link: (a) regulating academic emotions, (b) building social relationships at school, and (c) academic content overlap with EI. Different streams of EI may affect performance through different mechanisms. We note some limitations, including the lack of evidence for a causal direction. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Delayed Diagnosis of Tandem Spinal Stenosis: A Retrospective Institutional Review.

BACKGROUND: Tandem spinal stenosis (TSS) is defined as simultaneous spinal stenosis in the cervical, thoracic, and/or lumbar regions and may present with both upper and lower motor neuron symptoms, neurogenic claudication, and gait disturbance. Current literature has focused mainly on the prevalence of TSS and treatment methods, while the incidence of delayed TSS diagnosis is not well defined. The purpose of this study was to determine the incidence of delayed TSS diagnosis at our institution and describe the clinical characteristics commonly observed in their particular presentation. METHODS: Following institutional review board approval, an institutional billing database review was performed for patients who underwent a spinal decompression procedure between 2006 and 2016. Thirty-three patients who underwent decompression on 2 separate spinal regions within 1 year were included for review. Patients with delayed diagnosis of TSS following the first surgery were differentiated from those with preoperative diagnosis of TSS. RESULTS: TSS requiring surgical decompression occurred in 33 patients, with the incidence being 2.06% in this cohort. Fifteen patients received a delayed diagnosis after the first surgical decompression (45%) and were found to have a longer interval between decompressions (7.6 ± 2.1 months versus 4.01 ± 3 months, P = .0004). Patients undergoing lumbar decompression as the initial procedure were more likely to have a delayed diagnosis of TSS (8 versus 2 patients, P = .0200). The most common presentation of delayed TSS was pain and myelopathic symptoms that persisted after decompressive surgery. CONCLUSION: TSS should remain within the differential diagnosis for patients at initial presentation of spinal stenosis. In addition, suspicion of TSS should be heightened if preoperative symptoms fail to expectedly improve following decompression even if overt myelopathic signs are not present. LEVEL OF EVIDENCE: 4.

Can Liposomal Bupivacaine Be Safely Utilized in Elective Spine Surgery?

STUDY DESIGN: Single-blinded prospective randomized control trial. OBJECTIVES: To compare the incidence of adverse events (AEs) and hospital length of stay between patients who received liposomal bupivacaine (LB) versus a single saline injection, following posterior lumbar decompression and fusion surgery for degenerative spondylosis. METHODS: From 2015 to 2016, 59 patients undergoing posterior lumbar decompression and fusion surgery were prospectively enrolled and randomized to receive either 60 mL injection of 266 mg LB or 60 mL of 0.9% sterile saline, intraoperatively. Outcome measures included the incidence of postoperative AEs and hospital length of stay. RESULTS: The most common AEs in the treatment group were nausea (39.3%), emesis (18.1%), and hypotension (18.1%). Nausea (23%), constipation (19.2%), and urinary retention (15.3%) were most common in the control group. Patients who received LB had an increased risk of developing nausea (relative risk [RR] = 1.7; 95% confidence interval [CI] = 0.75-3.8), emesis (RR = 2.3; 95% CI = 0.51-10.7), and headaches (RR = 2.36; 95% CI = 0.26-21.4). Patients receiving LB had a decreased risk of developing constipation (RR = 0.78; 95% CI = 0.25-2.43), urinary retention (RR = 0.78; 95% CI = 0.21-2.85), and pruritus (RR = 0.78; 95% = 0.21-2.8) postoperatively. Relative risk values mentioned above failed to reach statistical significance. No significant difference in the hospital length of stay between both groups was found (3.9 vs 3.9 days; P = .92). CONCLUSION: Single-dose injections of LB to the surgical site prior to wound closure did not significantly increase or decrease the incidence or risk of developing AEs postoperatively. Furthermore, no significant difference was found in the hospital length of stay between both groups.

Outcomes of multilevel vertebrectomy for spondylodiscitis.

BACKGROUND CONTEXT: The incidence of pyogenic vertebral osteomyelitis (PVO) continues to increase in the United States, highlighting the need to recognize unique challenges presented by these cases and develop effective methods of surgical management. To date, no prior research has focused on the outcomes of PVO requiring two or more contiguous corpectomies. PURPOSE: To describe our experience in the operative management of PVO in 56 consecutive patients who underwent multilevel corpectomies (≥2 vertebral bodies) via a combined approach. STUDY DESIGN/SETTING: Single institution retrospective cohort review between January 2002 and December 2015. All patients had been treated at an academic tertiary referral center by one of two fellowship-trained orthopedic spine surgeons. PATIENT SAMPLE: Patient records were cross-referenced with International Classification of Diseases osteomyelitis codes and paravertebral abscess code. Inclusion criteria for the study were patients within the cohort who had adequate medical records for review, a minimum patient age of 18 years, active vertebral osteomyelitis as an indication for surgical intervention, a minimum of 1-year radiographic follow-up, and surgical intervention that included at least two complete vertebral corpectomies. Subsequently, 56 patients met the inclusion criteria and were reviewed for this retrospective analysis. OUTCOME MEASURES: Outcomes of interest were readmission and reoperation rates related to treatment of PVO, 30-day and 1-year mortality rates, radiographic outcomes, perioperative complications, infection control, and length of stay. METHODS: After obtaining approval from the Institutional Review Board, retrospective review was performed on records of all adults with PVO refractory to standard nonoperative treatment who underwent complete corpectomy of two or more contiguous vertebrae at a single institution between January 2002 and December 2015. This study was not funded, and no potential conflict of interest-associated biases were present. RESULTS: Fifty-six patients were identified (63% men; mean age 56.8 years; mean radiographic follow-up 2.8 years). Median length of stay was 13 days with nearly half readmitted (47%) after a median of 222.5 days after surgery. Twelve (22%) posterior revisions were required after a median 54 days for infection, painful or failed hardware, proximal junction kyphosis, adjacent level disease, or extension of the fusion. Thirty-day and 1-year mortality rates were 7.14% and 19.6%, respectively, with an infectious etiology as the most common cause of death. CONCLUSIONS: Multilevel vertebral corpectomy for treatment of refractory vertebral osteomyelitis is associated with relatively high rates of complications and mortality compared with historical controls for 1 or 2 level procedures. We found clinical resolution and absence of complications requiring return to the operating room in 75% of patients when complete extirpation of the involved vertebrae is achieved. Our findings suggest multilevel anterior corpectomies with posterior stabilization may be a reasonable surgical option when approaching patients with complicated spondylodiscitis.

Stigma and access to care in first-episode psychosis.

AIM: Mental health-related stigma is considered a significant barrier to help-seeking and accessing care in those experiencing mental illness. Long duration of untreated psychosis is associated with poorer outcomes. The impact of stigma on the duration of untreated psychosis, in first-episode psychosis remains unexplored. To examine the association between mental health-related stigma and access to care in people experiencing first-episode psychosis in Birmingham, UK. METHODS: We collected data on a prospective cohort of first-episode psychosis. The Stigma Scale was used as a measure of mental health-related stigma, and duration of untreated psychosis as a measure of delay in accessing care. We performed logistic and linear regression analyses to explore the relationship between mental health-related stigma and duration of untreated psychosis, adjusting for sex, age, educational level, religion and ethnicity. RESULTS: On the 89 participants included in this study, linear regression analysis revealed that overall stigma and the discrimination sub-factor were significant predictors of longer duration of untreated psychosis, whereas logistic regression identified the disclosure sub-factor to be a significant predictor of longer duration of untreated psychosis. CONCLUSIONS: These findings demonstrate that stigmatizing views of mental illness from the patient's perspectives can result in delayed access to care. This emphasizes the importance of tackling mental health-related stigma to ensure early treatment and improved outcomes for people experiencing first-episode psychosis.

How relevant is higher-order language deficit (HOLD) to children with complex presentations of attention-deficit hyperactivity disorder?

Attention-deficit hyperactivity disorder (ADHD) is frequently associated with language impairment, autism spectrum disorder (ASD) symptoms and higher-order language deficit (HOLD); yet, their complex relationship is poorly understood. HOLD encompasses deficits in using language for reasoning, problem-solving, causal and critical thinking. This study evaluates the roles of HOLD in children with ADHD. We hypothesise that both our subgroups (ADHD-only and ADHD + 'ASD traits') will have HOLD difficulties, though to a differing degree, as children with ADHD are compromised by executive function deficits, and those with additional ASD traits are further impaired by pragmatic language deficits. Data were reviewed from 36 children with ADHD (± 'ASD traits'), who attended the tier 4 statewide specialist clinic for ADHD patients non-responsive to community care. HOLD was assessed by the Test of Problem Solving-3 Elementary (TOPS-3). The age of the sample ranged from 6 to 12 years with a male-to-female ratio of 8:1. The rate of HOLD in our sample was 47.2% (published controls = 16%). Likewise, the rates of Making Inferences (50.0%, p < 0.001), Sequencing (44.4%, p < 0.001), Negative Questions (33.3%, p = 0.278), Problem-Solving (38.9%, p = 0.022), Predicting (27.8%, p = 0.022) and Determining Causes (30.6%, p = 0.022) were all elevated. When stratified, the rates in ADHD-only group and ADHD + 'ASD traits' group were 37.5% and 55.0%, respectively. Children with ADHD + 'ASD traits' had greater 'Sequencing' deficit. Our exploratory study confirms that HOLD is more common in children with ADHD, including deficits in Making Inferences, Sequencing, Problem-Solving, Predicting, Determining Causes and understanding Negative Questions. Our findings provide preliminary support for the potentially important role played by HOLD in neurodevelopmental disorders.

The Efficacy of Liposomal Bupivacaine in Lumbar Spine Surgery.

BACKGROUND: Postoperative pain management in spine surgery holds unique challenges. The purpose of this study is to determine if the local anesthetic liposomal bupivacaine (LB) reduces the total opioid requirement in the first 3 days following posterior lumbar decompression and fusion (PLDF) surgery for degenerative spondylosis. METHODS: Fifty patients underwent PLDF surgery in a prospective randomized control pilot trial between August 2015 and October 2016 and were equally allocated to either a treatment (LB) or a control (saline) group. Assessments included the 72-hour postoperative opioid requirement normalized to 1 morphine milligram equivalent (MME), visual analog scale (VAS), and hospital length of stay. RESULTS: LB did not significantly alter the 72-hour postoperative opioid requirement compared to saline (11.6 vs. 13.4 MME, P = .40). In a subgroup analysis, there was also no significant difference in opioid consumption among narcotic-naive patients with either LB or saline. Among narcotic tolerant patients, however, opioid consumption was higher with saline than LB (20.6 MME vs. 13.3 MME, P = .048). Additionally, pre- and postoperative VAS scores and hospital length of stay were not significantly different with either LB or saline. CONCLUSIONS: In the setting of PLDF surgery, LB injections did not significantly reduce the consumption of opioids in the first 3 postoperative days, nor did the hospital length of stay or VAS pain scores, compared to saline. However, LB could be beneficial in reducing the consumption of opioids in narcotic-tolerant populations. LEVEL OF EVIDENCE: 2.

Mortality Rates After Posterior C1-2 Fusion for Displaced Type II Odontoid Fractures in Octogenarians.

STUDY DESIGN: Retrospective cohort study OBJECTIVE.: To assess 30-day and 1-year mortality rates as well as the most common complications associated with posterior C1-2 fusion in an octogenarian cohort. SUMMARY OF BACKGROUND DATA: Treatment of unstable type II odontoid fractures in elderly patients can present challenges. Recent evidence indicates in patients older than 80 years, posterior C1-2 fusion results in improved survival as compared to other modes of treatment. METHODS: Retrospective analysis of 43 consecutive patients (25 female and 18 male; mean age 84.3 yr, range 80-89 yr; mean Charlson Comorbidity Index 1.4, (range 1-6); mean body mass index 24.8 ±â€Š4.2 kg/m, who underwent posterior C1-C2 fusion for management of unstable type II odontoid fracture by four fellowship trained spine surgeons at a single institution between January 2006 to June 2016. RESULTS: Mean fracture displacement was 5.1 ±â€Š3.6 mm and mean absolute value of angulation was 19.93°â€Š±â€Š12.93°. The most common complications were altered mental status (41.9%, n = 18), dysphagia (27.9%, n = 12) with 50% of those patients (6/12) requiring a feeding tube, and emergency reintubation (9.3%, n = 4). To the date of review completion, 25 of 43 patients expired (58.1%), median survival of 1.76 years from the date of surgery. Thirty-day and 1-year mortality rates were 2.3% and 18.6%, respectively. Patients who developed dysphagia were 14.5 times more likely to have expired at 1 year; dysphagia was also found to be significantly associated with degree of displacement. Fracture displacement was found to be associated with increased odds for 1-year mortality when accounting for age and requirement of a feeding tube. CONCLUSION: Posterior C1-2 fusion results in acceptably low mortality rates in octogenarians with unstable type II odontoid fractures when compared to nonoperative management mortality rates in current literature. Initial fracture displacement is associated with higher mortality rate in this patient population. LEVEL OF EVIDENCE: 4.

Predictors of engagement in first-episode psychosis.

Engagement with psychiatric services is critical for ensuring successful outcomes in patients experiencing a first episode of psychosis (FEP). However, it is not known how sociodemographic factors and patient beliefs about the causes of mental illness affect engagement. This study explored predictors of engagement in a cohort of 103 FEP patients presenting to an early-intervention service. Beliefs that mental illness is caused by social stress or thinking odd thoughts predicted higher engagement scores. Patients with no qualifications were found to have higher engagement scores than those educated to a higher level. Ethnicity, gender, age and socioeconomic factors were not significantly correlated with engagement scores. Duration of untreated illness (DUI) significantly predicted higher engagement scores, but only for values >1220days. Duration of untreated psychosis (DUP) was not a significant predictor of patient engagement scores. Patient beliefs about the causes of mental illness are an important factor to be taken into consideration and may represent a target of interventions to increase engagement in FEP.

Ethnicity and pathways to care during first episode psychosis: the role of cultural illness attributions.

BACKGROUND: Studies demonstrate ethnic variations in pathways to care during first episode psychosis (FEP). There are no extant studies, however, that have statistically examined the influence of culturally mediated illness attributions on these variations. METHODS: We conducted an observational study of 123 (45 White; 35 Black; 43 Asian) patients recruited over a two-year period from an Early Intervention Service (EIS) in Birmingham, UK. Sociodemographic factors (age; sex; education; country of birth; religious practice; marital status; living alone), duration of untreated psychosis (DUP), service contacts (general practitioner; emergency services; faith-based; compulsory detention; criminal justice) and illness attributions ("individual;" "natural;" "social;" "supernatural;" "no attribution") were assessed. RESULTS: Ethnic groups did not differ in DUP (p = 0.86). Asian patients were more likely to report supernatural illness attributions in comparison to White (Odds Ratio: 4.02; 95 % Confidence Intervals: 1.52, 10.62) and Black (OR: 3.48; 95 % CI: 1.25, 9.67) patients. In logistic regressions controlling for confounders and illness attributions, Black (OR: 14.00; 95 % CI: 1.30, 151.11) and Asian (OR: 13.29; 95 % CI: 1.26, 140.47) patients were more likely to consult faith-based institutions than White patients. Black patients were more likely to be compulsorily detained than White patients (OR: 4.56; 95 % CI: 1.40, 14.85). CONCLUSION: Illness attributions and sociodemographic confounders do not fully explain the ethnic tendency to seek out faith-based institutions. While Asian and Black patients are more likely to seek help from faith-based organisations, this does not appear to lead to a delay in contact with mental health services.

Polymersome production on a microfluidic platform using pH sensitive block copolymers.

Development of pH sensitive biocompatible block copolymer polymersomes, which are stable in physiological conditions, is enabling the intracellular delivery of water soluble drugs and proteins. As a result, it is becoming increasingly important to develop robust production methods to enhance the polymersome encapsulation efficiency. One way that this could be achieved is through production in microfluidic devices that potentially offer more favourable conditions for encapsulation. Here a flow focussing microfluidic device is used to induce self-assembly of poly(2-(methacryloyloxy)ethyl phosphorylcholine)-poly(2-(diisopropylamino)ethyl methacrylate) (PMPC-b-PDPA) block copolymer by changing the pH of the flows within the microchannels. The laminar flow conditions within the device result in a pH gradient at either interface of the central flow, where diffusion of hydrogen ions enables the deprotonation of the PDPA block copolymer and results in self-assembly of polymersomes. Dynamic light scattering reveals hydrodynamic diameters in the range of 75-275 nm and double membrane structures visualized using transmission electron microscopy indicate that polymersome nanostructures are being produced. The encapsulation efficiency for Bovine Serum Albumin (BSA) was calculated by measuring the spectroscopic absorbance at 279 nm and indicates that the encapsulation efficiency produced in the microfluidic device is equivalent to the standard in solution production method. Critically, the microfluidic system eliminates the use of organic solvents, which limit biological applications, through the pH induced self-assembly process and offers a continuous production method for intracellular delivery polymersomes.