Latent gammaherpesvirus infection enhances type I IFN response and reduces virus spread in an influenza A virus co-infection model.

Infections with persistent or latent viruses alter host immune homeostasis and have potential to affect the outcome of concomitant acute viral infections such as influenza A virus (IAV). Gammaherpesviruses establish life-long infections and require an on-going immune response to control reactivation. We have used a murine model of co-infection to investigate the response to IAV infection in mice latently infected with the gammaherpesvirus MHV-68. Over the course of infection, latently infected BALB/c mice showed less weight loss, clinical signs, pulmonary cellular infiltration and expression of inflammatory mediators than naïve mice infected with IAV and had significantly more activated CD8+ T cells in the lungs. Four days after IAV infection, virus spread in the lungs of latently infected animals was significantly lower than in naïve animals. By 7 days after IAV infection latently infected lungs express elevated levels of cytokines and chemokines indicating they are primed to respond to the secondary infection. Investigation at an early time point showed that 24 h after IAV infection co-infected animals had higher expression of IFNß and Ddx58 (RIG-I) and a range of ISGs than mice infected with IAV alone suggesting that the type I IFN response plays a role in the protective effect. This effect was mouse strain dependent and did not occur in 129/Sv/Ev mice. These results offer insight into innate immune mechanisms that could be utilized to protect against IAV infection and highlight on-going and persistent viral infections as a significant factor impacting the severity of acute respiratory infections.

Broadening the state of play - the second national survey of Consultation-Liaison Psychiatry services in New Zealand, 2021.

OBJECTIVE: The original national survey of Consultation-Liaison Psychiatry (CLP) services in New Zealand (NZ) that was undertaken in 2018 (CLPSNZ-1) established a baseline but was limited in scope. The aim of the current study was to conduct a more in-depth national survey. METHOD: A 44-question survey was emailed to clinicians at each of the 16 general hospitals in NZ with specialist adult CLP services in 2021. RESULTS: Responses were obtained from all 16 CLP services. These services were found to be under-resourced (with mean total full-time equivalents of 0.26 psychiatrists and 1.10 clinicians per 100 inpatient beds, respectively), operate with highly variable service models (with major variations in operating hours and coverage of age groups, the Emergency Department and outpatients) and provide a predominantly consultation service. CONCLUSION: While many of the findings from CLPSNZ-1 remain relevant, the current survey has extended our understanding of the circumstances, achievements and challenges of this psychiatric subspecialty in NZ.

A survey of the psychiatric care provided for medically ill older adults in general hospitals in New Zealand.

OBJECTIVE: The aim of this study was to conduct an in-depth survey of the psychiatric care provided for medically ill older adults in general hospitals in New Zealand (NZ). METHOD: As part of a larger survey of Consultation-Liaison Psychiatry (CLP) services for all ages in NZ (CLPSNZ-2), a 44-question survey was emailed to clinicians who were involved in providing psychiatric care for medically ill older adults at each of the 16 general hospitals with designated CLP services. RESULTS: Responses were obtained from 22 services at 16 hospitals - 14 CLP services and eight Psychiatry of Old Age (POA) in-reach services. These services were found to be under-resourced, operate with highly variable service models, and predominantly provide inpatient consultations. Services could be conceptualised as six prototypes with variations of POA in-reach to hospitals, scope of CLP cover and collaboration between services. CONCLUSION: The heterogeneity in the psychiatric care for medically ill older adults in NZ means that there is an urgent need to develop more consistent CLP service models that better serve the specialist needs of older adults, and establish the policies, resources and standards needed to support them.

Radiographic Evaluation of Carpal Mechanics and the Scapholunate Angle in a Clenched Fist with Dynamic Computed Tomography Imaging.

Purpose: The long-term consequences of injuries to the scapholunate joint can severely limit hand function, and the potential for posttraumatic deformity makes early recognition of these injuries important. The purpose of this study was to evaluate the motion of the scapholunate joint in normal wrists through the radial and ulnar deviation using novel dynamic computed tomography (CT) imaging. Methods: Fifteen participants consented to have their uninjured wrists scanned. A protocol was designed to ensure adequate time, yet limited exposure, for volunteers. Participants began with the hand in a relaxed fist position and then proceeded to clench the hand in a full fist and relax. Once relaxed again, the wrist was maximally ulnarly deviated and then maximally radially deviated in a fluid motion. Dynamic CT imaging was captured throughout the range of motion. Results: The scapholunate angle was measured on dynamic wrist images. The mean range of the scapholunate angle that the wrists moved through was 37.2°-45.9°, and the mean midpoint angle was 41.2° ± 0.4°. All wrists had small, measurable differences in the scapholunate angle when moving from the maximum ulnar deviation to the maximal radial deviation. The average maximum angle change through the range is 11.7°, whereas the average minimum angle change was 0.9°. Conclusions: In this study, scapholunate angle calculations using dynamic wrist CT scans were within the range of accepted normal for the angle in uninjured wrists. With the increased focus on dynamic imaging for wrist motion, it may be possible to derive a standardized protocol for mapping the carpal motion that is clinically applicable and reproducible. Type of study/level of evidence: Diagnostic IV.

Forensic Application of Stable Isotopes to Distinguish between Wild and Captive Turtles.

Wildlife traffickers often claim that confiscated animals were captive-bred rather than wild-caught to launder wild animals and escape prosecution. We used stable isotopes (δ13C and δ15N) derived from the claw tips of wild wood turtles from Maine and captive wood turtles throughout the eastern U.S. to develop a predictive model used to classify confiscated wood turtles as wild or captive. We found that the claw tips of wild and captive wood turtles (Glyptemys insculpta) were isotopically distinct. Captive turtles had significantly higher δ13C and δ15N values than wild turtles. Our model correctly classified all wild turtles as wild (100%) and nearly all captive turtles as captive (94%). All but two of the 71 turtles tested were successfully predicted as wild or captive (97.2% accuracy), yielding a misclassification rate of 2.8%. In addition to our model being useful to law enforcement in Maine, we aim to develop a multi-species model to assist conservation law enforcement efforts to curb illegal turtle trafficking from locations across the eastern United States and Canada.

An Analysis of the Social Determinants of Health in South Carolina's I-95 Corridor.

BACKGROUND: One in four South Carolinians lives in a county along a nearly 200-mile stretch of Interstate 95 (I-95). Stretching from North Carolina to Georgia, this region is among the most rural, economically depressed, and racially/ethnically diverse in the state. Research is needed to identify social factors contributing to adverse health outcomes along the I-95 corridor, guide interventions, and establish a baseline for measuring progress. This study assessed social determinants of health in counties in South Carolina's I-95 corridor relative to the rest of the state. METHOD: Data for South Carolina's 46 counties were extracted from the Centers for Disease Control and Prevention Minority Health Social Vulnerability Index (SVI), which grouped 34 census variables into six themes: socioeconomic status, household composition and disability, minority status and language, housing type and transportation, health care infrastructure, and medical vulnerability. Each theme was ranked from 0 (least vulnerable) to 1 (most vulnerable). Measures between regions were compared using the Wilcoxon-Mann-Whitney test. RESULTS: Compared with counties outside the I-95 corridor (n = 29), counties in the corridor (n = 17) scored higher on socioeconomic status vulnerability (.67 and .82, respectively) and medical vulnerability (.65 and .79, respectively). No statistically significant differences were found across other themes. CONCLUSION: Identifying social determinants of health in South Carolina's I-95 corridor is a crucial first step toward alleviating health disparities in this region. Interventions and policies should be developed in collaboration with local stakeholders to address distal social factors that create and reinforce health disparities.

The evidence for introducing case-finding for delirium and dementia in older medical inpatients in a New Zealand hospital.

OBJECTIVE: The aim of this project was to make the case to the managers of a large urban teaching hospital in New Zealand for the introduction of systematic case-finding for pre-existing cognitive impairment/dementia in older hospital inpatients that screen positive for delirium. METHOD: Two hundred consecutive acute admissions aged 75+ in four medical wards were assessed using the 4AT assessment tool for delirium and the Alzheimer Questionnaire (AQ) for pre-existing cognitive impairment/dementia. Length of stay and mortality at 1 year were also collected. RESULTS: Over a third of the sample screened positive for delirium and nearly two-thirds of these also screened positive for dementia. The median length of stay was 5 days for delirium without dementia and 7 days for delirium with dementia, compared to 3 days for those who screened negative for both. After adjustment for age, gender and ethnic group, people who screened positive for delirium (with or without dementia) had 50% longer length of stay (p < 0.05) and at least double the risk of death (p < 0.05). CONCLUSION: Older hospital inpatients that screen positive for delirium and dementia using 4AT and AQ have longer lengths of stay and higher mortality. Identification may lead to more timely interventions that help to improve health outcomes and reduce hospital costs.

The Prevalence of Systems Thinking in Supply Chain Management: a Systematic Literature Review.

In light of the maelstrom that global Supply Chains must struggle with, we contend that Systems Thinking in Supply Chain Management can be an enabling factor. Systems Thinking can support problem-solving in the reactive crisis mode that practitioners find themselves in, let alone when seeking ways to improve the end-to-end Supply Chain. This paper determines the prevalence of Systems Thinking methodologies within the literature and confirms if these contributions provide benefits to Supply Chain Management beyond the dyad through empirical research? Given the challenges of realising supply chain-wide progression, are these contributions supporting the discipline in pursuing industry advancement strategies? A systematic literature review methodology was employed, evaluating ninety-seven peer-reviewed papers regarding the breadth; from suppliers' supplier to customers customer, and depth; from literature review to empirical research. Five research outcomes are identified, resulting in an established hypothesis. We argue that a positive correlation between Systems Thinking Maturity and Supply Chain Performance leads to a more significant opportunity to go beyond the dyad. The hypothesis led to a research construct that advocates the need to determine empirically whether a correlation exists between Systems Thinking Maturity and Supply Chain Performance.

Concurrent Infection With the Filarial Helminth Litomosoides sigmodontis Attenuates or Worsens Influenza A Virus Pathogenesis in a Stage-Dependent Manner.

Filarial helminths infect approximately 120 million people worldwide initiating a type 2 immune response in the host. Influenza A viruses stimulate a virulent type 1 pro-inflammatory immune response that in some individuals can cause uncontrolled immunopathology and fatality. Although coinfection with filariasis and influenza is a common occurrence, the impact of filarial infection on respiratory viral infection is unknown. The aim of this study was to determine the impact of pre-existing filarial infection on concurrent infection with influenza A virus. A murine model of co-infection was established using the filarial helminth Litomosoides sigmodontis and the H1N1 (A/WSN/33) influenza A virus (IAV). Co-infection was performed at 3 different stages of L. sigmodontis infection (larval, juvenile adult, and patency), and the impact of co-infection was determined by IAV induced weight loss and clinical signs, quantification of viral titres, and helminth counts. Significant alterations of IAV pathogenesis, dependent upon stage of infection, was observed on co-infection with L. sigmodontis. Larval stage L. sigmodontis infection alleviated clinical signs of IAV co-infection, whilst more established juvenile adult infection also significantly delayed weight loss. Viral titres remained unaltered at either infection stage. In contrast, patent L. sigmdodontis infection led to a reversal of age-related resistance to IAV infection, significantly increasing weight loss and clinical signs of infection as well as increasing IAV titre. These data demonstrate that the progression of influenza infection can be ameliorated or worsened by pre-existing filarial infection, with the outcome dependent upon the stage of filarial infection.

The state of play - the first national survey of consultation-liaison psychiatry services in New Zealand.

OBJECTIVE: The aim of this study was to conduct the first national survey of consultation-liaison psychiatry (CLP) services in New Zealand. METHOD: An online survey based on the Multidimensional Matrix for Consultation-Liaison Psychiatry (mMAX-LP) was circulated to a psychiatrist at each of 12 identified CLP services nationally during April-May 2018. Existing data for Middlemore Hospital (where the lead author is based) were added later for completion. RESULTS: Most CLP services in New Zealand are funded and managed by the mental health division, operate within office hours, and have psychologists and other allied health staff external to their service. However, there was significant heterogeneity amongst these services in terms of structure and function and in particular, the coverage of emergency departments and young/older patient groups. CONCLUSION: This first national survey has provided a snapshot of CLP services in New Zealand in 2018 and found striking heterogeneity. The survey has established a baseline for future local and international comparisons.

The multi-dimensional matrix for consultation-liaison psychiatry (mMAX-LP).

OBJECTIVE: Consultation-liaison psychiatry (CLP) services are particularly susceptible to heterogeneity, developing haphazardly in response to local interests and perceived need. This hampers the generalisability of comparisons between services in terms of service models, resource requirements and outcome data. The objective of this paper therefore is to chronicle the development of a method to meaningfully describe, map and compare different CLP services. METHOD: A review of the literature was followed by multiple site visits in both New Zealand and England, and an extended process of consultation and feedback. RESULTS: Sixteen dimensions common to CLP services were extracted to create a multi-dimensional matrix (mMAX-LP) which had three broad clusters (structure, coverage and relationship with physical health services). The model was applied and discussed with the previously visited hospitals over the succeeding five years. Additionally, the matrix was tested, and its utility demonstrated during the planned reconfiguration of CLP services at a large teaching hospital in South Auckland, New Zealand by tracking the evolution of CLP services. CONCLUSIONS: mMAX-LP shows promise as a useful model for profiling and comparing CLP services; mapping their evolution over time; and sign-posting future service development.

Nature and consequences of interactions between Salmonella enterica serovar Dublin and host cells in cattle.

Salmonella enterica is a veterinary and zoonotic pathogen of global importance. While murine and cell-based models of infection have provided considerable knowledge about the molecular basis of virulence of Salmonella, relatively little is known about salmonellosis in naturally-affected large animal hosts such as cattle, which are a reservoir of human salmonellosis. As in humans, Salmonella causes bovine disease ranging from self-limiting enteritis to systemic typhoid-like disease and exerts significant economic and welfare costs. Understanding the nature and consequences of Salmonella interactions with bovine cells will inform the design of effective vaccines and interventions to control animal and zoonotic infections. In calves challenged orally with S. Dublin expressing green fluorescent protein (GFP) we observed that the bacteria were predominantly extracellular in the distal ileal mucosa and within gut-associated lymph nodes 48 h post-infection. Intracellular bacteria, identified by flow cytometry using the GFP signal, were predominantly within MHCII+ macrophage-like cells. In contrast to observations from murine models, these S. Dublin-infected cells had elevated levels of MHCII and CD40 compared to both uninfected cells from the same tissue and cells from the cognate tissue of uninfected animals. Moreover, no gross changes of the architecture of infected lymph nodes were observed as was described previously in a mouse model. In order to further investigate Salmonella-macrophage interactions, net replication of S. enterica serovars that differ in virulence in cattle was measured in bovine blood-derived macrophages by enumeration of gentamicin-protected bacteria and fluorescence dilution, but did not correlate with host-specificity.

Regulation of Ov2 by virus encoded microRNAs.

Herpesviruses encode miRNAs that target both virus and host genes; however their role in herpesvirus biology is still poorly understood. We previously identified thirty five miRNAs encoded by OvHV-2; the causative agent of malignant catarrhal fever (MCF) and are investigating the role of these miRNAs in regulating expression of OvHV-2 genes that play important roles in virus biology. Analysis, using RNAHybrid predicted that two OvHV-2 encoded miRNAs, ovhv2-miR-17-10 and ovhv2-miR-61-1, target transcripts coding for the OvHV-2 bZIP protein Ov2. In other herpesvirus bZIP proteins are known to play important roles in lytic virus replication. Here we show by Flow cytometry and western blotting that ovhv2-miR-17-10 and ovhv2-miR-61-1, reduce the expression of Ov2 protein. The predicted target sites for both miRNAs within the Ov2 gene were disrupted whilst retaining the Ov2 coding sequence. Mutation of the ovhv2-miR-61-1 target sequence restored Ov2 protein expression levels to control levels confirming the identity of its target site. However, it was not possible to determine the binding site of ovhv2-miR-17-10 possibly due to potential G:U pairing introduced during the mutation process. The targeting of Ov2 by two virus-encoded miRNAs suggests an important regulatory role for Ov2 in OvHV-2 replication or reactivation.

Ov2 is a modulator of OvHV-2 RTA mediated gene expression.

Ovine herpesvirus-2 (OvHV-2) is the causative agent of the sheep-associated form of malignant catarrhal fever, a usually fatal lymphoproliferative disease of bison, deer and cattle. Malignant catarrhal fever is a major cause of cattle loss in Africa with approximately 7% affected annually; and in North America has significant impact on bison farming. Research into the mechanisms by which OvHV-2 induces disease in susceptible species has been hampered by a lack of a cell culture system for the virus. Ov2 is a bZIP protein encoded by OvHV-2. Proteins with bZIP domains in other herpesviruses, such as the Kaposi's sarcoma-associated herpesvirus K8 protein and the BZLF1 protein of Epstein-Barr virus are known to play important roles in lytic virus replication. Using a reporter based system, we demonstrate that Ov2 can modulate the activity of the major virus transactivator (Replication and Transcriptional Activator protein, RTA) to 1) drive expression of viral genes predicted to be required for efficient reactivation of the virus, including ORF49; and 2) differentially regulate the expression of the two virus encoded Bcl-2 homologues Ov4.5 and Ov9.

Retrospective application of transposon-directed insertion-site sequencing to investigate niche-specific virulence of Salmonella Typhimurium in cattle.

BACKGROUND: Salmonella enterica subspecies enterica is an animal and zoonotic pathogen of global importance. Cattle are a significant reservoir of human non-typhoidal salmonellosis and can suffer enteric and systemic disease owing to the ability of Salmonella to survive within the bovine lymphatic system and intestines. Contamination of food can occur due to the incorporation of contaminated peripheral lymph nodes or by direct contamination of carcasses with gut contents. It is essential to understand the mechanisms used by Salmonella to enter and persist within the bovine lymphatic system and how they differ from those required for intestinal colonization to minimize zoonotic infections. RESULTS: Transposon-directed insertion site sequencing (TraDIS) was applied to pools of mutants recovered from mesenteric lymph nodes (MLNs) draining the distal ileum of calves after oral inoculation with a library of 8550 random S. Typhimurium mini-Tn5Km2 mutants in pools of 475 mutants per calf. A total of 8315 mutants representing 2852 different genes were detected in MLNs and their in vivo fitness was calculated. Using the same improved algorithm for analysis of transposon-flanking sequences, the identity and phenotype of mutants recovered from the distal ileal mucosa of the same calves was also defined, enabling comparison with previously published data and of mutant phenotypes across the tissues. Phenotypes observed for the majority of mutants were highly significantly correlated in the two tissues. However, 32 genes were identified in which transposon insertions consistently resulted in differential fitness in the ileal wall and MLNs, suggesting niche-specific roles for these genes in pathogenesis. Defined null mutations affecting ptsN and spvC were confirmed to result in tissue-specific phenotypes in calves, thus validating the TraDIS dataset. CONCLUSIONS: This validation of the role of thousands of Salmonella genes and identification of genes with niche-specific roles in a key target species will inform the design of control strategies for bovine salmonellosis and zoonotic infections, for which efficacious and cross-protective vaccines are currently lacking.

Ultrafast diode-pumped Ti:sapphire laser with broad tunability.

We report a broadly wavelength-tunable femtosecond diode-pumped Ti:sapphire laser, passively mode-locked using both semiconductor saturable absorber mirror (SESAM) and Kerr-lens mode-locking (KLM) techniques. Using two pump laser diodes (operating at 450 nm), an average output power as high as 433 mW is generated during mode-locking with the SESAM. A tunability range of 37 nm (788-825 nm) was achieved with the shortest pulse duration of 62 fs at 812 nm. In the KLM regime, an average output power as high as 382 mW, pulses as short as 54 fs, and a tunability of 120 nm (755-875 nm) are demonstrated.

Quantifying the Survival of Multiple Salmonella enterica Serovars In Vivo via Massively Parallel Whole-Genome Sequencing To Predict Zoonotic Risk.

Salmonella enterica is an animal and zoonotic pathogen of worldwide importance. Salmonella serovars that differ in their host and tissue tropisms exist. Cattle are an important reservoir of human nontyphoidal salmonellosis, and contaminated bovine peripheral lymph nodes enter the food chain via ground beef. The relative abilities of different serovars to survive within the bovine lymphatic system are poorly understood and constrain the development of control strategies. This problem was addressed by developing a massively parallel whole-genome sequencing method to study mixed-serovar infections in vivoSalmonella serovars differ genetically by naturally occurring single nucleotide polymorphisms (SNPs) in certain genes. It was hypothesized that these SNPs could be used as markers to simultaneously identify serovars in mixed populations and quantify the abundance of each member in a population. The performance of the method was validated in vitro using simulated pools containing up to 11 serovars in various proportions. It was then applied to study serovar survival in vivo in cattle challenged orally with the same 11 serovars. All the serovars successfully colonized the bovine lymphatic system, including the peripheral lymph nodes, and thus pose similar risks of zoonosis. This method enables the fates of multiple genetically unmodified strains to be evaluated simultaneously in a single animal. It could be useful in reducing the number of animals required to study mixed-strain infections and in testing the cross-protective efficacy of vaccines and treatments. It also has the potential to be applied to diverse bacterial species which possess shared but polymorphic alleles.IMPORTANCE While some Salmonella serovars are more frequently isolated from lymph nodes rather than the feces and environment of cattle, the relative abilities of serovars to survive within the lymphatic system of cattle remain ill defined. A sequencing-based method which used available information from sequenced Salmonella genomes to study the dynamics of mixed-serovar infections in vivo was developed. The main advantages of the method include the simultaneous identification and quantification of multiple strains without any genetic modification and minimal animal use. This approach could be used in vaccination trials or in epidemiological surveys where an understanding of the dynamics of closely related strains of a pathogen in mixed populations could inform the prediction of zoonotic risk and the development of intervention strategies.

Dynamic CT Scan of the Normal Scapholunate Joint in a Clenched Fist and Radial and Ulnar Deviation.

BACKGROUND: Injuries to the scapholunate can have severe long-term effects on the wrist. Early detection of these injuries can help identify pathology. The purpose of this study was to evaluate the motions of the scapholunate joint in normal wrists in a clenched fist and through radial and ulnar deviation using novel dynamic computed tomography (CT) imaging. METHODS: Fifteen participants below 40 years of age consented to have their wrist scanned. Eight participants were randomized to have the right wrist scanned and 7 the left wrist. Volunteers were positioned at the back of the gantry with the wrist placed on the table, palmar side down. Participants began with the hand in a relaxed fist position and then proceeded through an established range of motion protocol. Dynamic CT imaging was captured throughout the range of motion. RESULTS: The movement in the healthy scapholunate joint through a clenched fist and radial and ulnar deviation is minimal. The averages were 1.19, 1.01, and 0.95 mm, representing the middle, dorsal, and volar measurements, respectively. CONCLUSIONS: This novel dynamic CT scan of the wrist is a user-friendly way of measuring of the scapholunate distance, which is minimal in the normal wrist below 40 years of age.

A candidate gene approach to study nematode resistance traits in naturally infected sheep.

Sheep naturally acquire a degree of resistant immunity to parasitic worm infection through repeated exposure. However, the immune response and clinical outcome vary greatly between animals. Genetic polymorphisms in genes integral to differential T helper cell polarization may contribute to variation in host response and disease outcome. A total of twelve single nucleotide polymorphisms (SNPs) were sequenced in IL23R, RORC2 and TBX21 from genomic DNA of Scottish Blackface lambs. Of the twelve SNPs, six were non-synonymous (missense), four were within the 3' UTRs and two were intronic. The association between nine of these SNPs and the traits of body weight, faecal egg count (FEC) and relative T. circumcincta L3-specific IgA antibody levels was assessed in a population of domestic Scottish Blackface ewe lambs and a population of free-living Soay ewe lambs both naturally infected with a mixture of nematodes. There were no significant associations identified between any of the SNPs and phenotypes recorded in either of the populations after adjustment for multiple testing (Bonferroni corrected P value≤0.002). In the Blackface lambs, there was a nominally significant association (P=0.007) between IL23R p.V324M and weight at 20 weeks. This association may be worthy of further investigation in a larger sample of sheep.