Urologic Chronic Pelvic Pain Syndrome Flares: A Comprehensive, Systematic Review and Meta-Analysis of the Peer-Reviewed Flare Literature.

PURPOSE: We sought to systematically review and summarize the peer-reviewed literature on urologic chronic pelvic pain syndrome flares, including their terminology, manifestation, perceived triggers, management and prevention strategies, impact on quality of life, and insights into pathophysiologic mechanisms, as a foundation for future empirical research. MATERIALS AND METHODS: We searched 6 medical databases for articles related to any aspect of symptom exacerbations for interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. A total of 1486 abstracts and 398 full-text articles were reviewed, and data were extracted by at least 2 individuals. RESULTS: Overall, we identified 59 articles, including 36 qualitative, cross-sectional, or case-control; 15 cohort-based; and 8 experimental articles. The majority of studies described North American patients with confirmed diagnoses. "Flare" was a commonly used term, but additional terminology (eg, exacerbation) was also used. Most flares involved significant increases in pain intensity, but less data were available on flare frequency and duration. Painful, frequent, long-lasting, and unpredictable flares were highly impactful, even over and above participants' nonflare symptoms. A large number of perceived triggers (eg, diet, stress) and management/prevention strategies (eg, analgesics, thermal therapy, rest) were proposed by participants, but few had empirical support. In addition, few studies explored underlying biologic mechanisms. CONCLUSIONS: Overall, we found that flares are painful and impactful, but otherwise poorly understood in terms of manifestation (frequency and duration), triggers, treatment, prevention, and pathophysiology. These summary findings provide a foundation for future flare-related research and highlight gaps that warrant additional empirical studies.

High-pressure injection hand injury: What lies beneath?

ABSTRACT: High-pressure injection injuries are true emergencies that require prompt treatment to avoid devastating complications. This article describes the presentation and management of these injuries and provides clear and concise recommendations for intervention by the ED clinician.

Elucidating the clinical spectrum and molecular basis of HYAL2 deficiency.

PURPOSE: We previously defined biallelic HYAL2 variants causing a novel disorder in 2 families, involving orofacial clefting, facial dysmorphism, congenital heart disease, and ocular abnormalities, with Hyal2 knockout mice displaying similar phenotypes. In this study, we better define the phenotype and pathologic disease mechanism. METHODS: Clinical and genomic investigations were undertaken alongside molecular studies, including immunoblotting and immunofluorescence analyses of variant/wild-type human HYAL2 expressed in mouse fibroblasts, and in silico modeling of putative pathogenic variants. RESULTS: Ten newly identified individuals with this condition were investigated, and they were associated with 9 novel pathogenic variants. Clinical studies defined genotype-phenotype correlations and confirmed a recognizable craniofacial phenotype in addition to myopia, cleft lip/palate, and congenital cardiac anomalies as the most consistent manifestations of the condition. In silico modeling of missense variants identified likely deleterious effects on protein folding. Consistent with this, functional studies indicated that these variants cause protein instability and a concomitant cell surface absence of HYAL2 protein. CONCLUSION: These studies confirm an association between HYAL2 alterations and syndromic cleft lip/palate, provide experimental evidence for the pathogenicity of missense alleles, enable further insights into the pathomolecular basis of the disease, and delineate the core and variable clinical outcomes of the condition.

Wellbeing Wednesdays: nurse-led clinic for improving physical health care in a general adolescent inpatient unit.

BACKGROUND: Young people with mental illness are at high risk of physical health complications. Physical healthcare on a general adolescent inpatient unit is complex. AIM: To establish a wellbeing clinic to improve efficiency and quality of the physical healthcare offered and increase health promotion. METHODS: Plan, Do, Study, Act (PDSA) cycles were used to drive this quality-improvement project. The authors audited 12 records before establishing the clinic and 12 at three further time points (6, 18 and 30 months post-intervention) to guide changes. RESULTS: Results progressively improved over PDSA cycles. Time taken for initial investigations dropped. Compliance with medication monitoring and management of important physical health domains rose from zero in some cases to 100% in all but one area. CONCLUSIONS: Establishing a dedicated physical health clinic in this setting is feasible and leads to improved performance against local and national standards. Mental health teams need to ensure physical health is prioritised.

Potent suppression of both spontaneous and carcinogen-induced colitis-associated colorectal cancer in mice by dietary celastrol supplementation.

Celastrol is an anti-inflammatory natural triterpenoid, isolated from the herb Tripterygium wilfordii or thunder god vine. Here, we define mechanisms mediating anti-inflammatory activity of celastrol and demonstrate efficacy of a dietary celastrol supplement for chemoprevention of inflammation-driven carcinogenesis in mice. Dietary celastrol (31.25 ppm in rodent diet from 8 weeks to 25 weeks of age) is well tolerated and protects against LPS-induced acute inflammation in C57BL/6 mice, potently suppressing LPS-induction of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, Interleukin (IL)-6 and IL-1ß. To test whether dietary celastrol suppresses inflammation-driven colorectal cancer (CRC), we employed a unique model of spontaneous, inflammation-driven CRC in mice harboring a germ line deletion of the p27Kip1 gene and a T cell-specific deletion of Smad4 gene (Smad4co/co;Lck-crep27Kip1-/-or DKO), which develop severe intestinal inflammation and carcinogenesis as early as 3 months of age. Exposure of DKO mice to daily dietary celastrol (12.5 ppm in diet) from 6 weeks of age significantly suppressed development of colitis-associated CRC (CAC). Celastrol chemoprevention of CAC in this new model of intestinal neoplasia was associated with significant suppression of iNOS at 4 months of age, and iNOS, COX-2 and NFκB at 6 months of age, with significant reduction in inflammatory cytokines, IL-6 and IL-1ß. Chemoprevetion of CAC by dietary celastrol was further confirmed in the model of azoxymethane (AOM) plus dextran sodium sulfate (DSS)-induced carcinogenesis in C57BL/6 mice. These data suggest the potential for celastrol as a safe and effective dietary supplement in the chemoprevention of CAC in humans.

25-hydroxyvitamin D serum levels in patients with high risk resected melanoma treated in an adjuvant bevacizumab trial.

BACKGROUND: Studies evaluating a relationship of vitamin D in patients with primary melanoma have consistently identified an inverse correlation with Breslow thickness, but an inconsistent impact on survival. Vitamin D in later stages of melanoma has been less studied. METHODS: Vitamin D was measured in serum from 341 patients with resected stage IIB-IIIC melanoma recruited to the AVAST-M adjuvant melanoma randomised trial, collected prior to randomisation, then at 3 and 12 months. Vitamin D levels were compared with patient demographics, known melanoma prognostic factors, disease-free interval (DFI) and overall survival (OS). RESULTS: A total of 73% patients had stage III melanoma, 32% were enroled (and therefore tested) >1 year after primary melanoma diagnosis. Median pre-randomisation vitamin D level was 56.5 (range 12.6-189.0 nmol/L). Vitamin D levels did not significantly vary over 12 months (p = 0.24). Individual pre-randomisation vitamin D levels did not differ significantly for Breslow thickness, tumour ulceration, or disease stage. Neither did pre-randomisation vitamin D predict for DFI (HR = 0.98 per 10 nmol/L increase; 95% confidence interval (CI) 0.93-1.04, p = 0.59) or OS (HR = 0.96 per 10 nmol/L increase, 95% CI 0.90-1.03, p = 0.31). For stage II patients, DFI improved with higher pre-randomisation vitamin D levels for those on bevacizumab (HR = 0.74 per 10 nmol nmol/L increase; 95% CI 0.56-0.97), but not for the observation arm (HR = 1.07 per 10 nmol/L increase; 95% CI 0.85-1.34). CONCLUSIONS: In this stage II/III melanoma cohort, vitamin D did not correlate with known prognostic markers, nor predict for DFI or OS, but there was some evidence of benefit for patients with stage II disease treated with bevacizumab.

Thermal annealing behaviour and gel to crystal transition of a low molecular weight hydrogelator.

The thermal annealing behaviour of an electrolyte-triggered calixarene hydrogelator is found to depend strongly on the specific metal chloride used. While the lithium chloride gel showed typical gel-sol transitions as a function of temperature, the magnesium chloride gel was found to repeatedly strengthen with heat-cool cycles. Structural investigations using small-angle neutron scattering, and scanning probe microscopy, suggest that the annealing behaviour is associated with a change in morphology of the fibrous structures supporting the gel. On prolonged standing at room temperature, the magnesium chloride gel underwent a gel-crystal transition, with the collapsing gel accompanied by the deposition of crystals of a magnesium complex of the proline-functionalised calix[4]arene gelator.

Limitations of using feline coronavirus spike protein gene mutations to diagnose feline infectious peritonitis.

Feline infectious peritonitis (FIP) is a fatal disease of cats, and a sequela of systemic feline coronavirus (FCoV) infection. Mutations in the viral spike (S) gene have been associated with FCoVs found in tissues from cats with FIP, but not FCoVs found in faeces from healthy cats, and are implicated in monocyte/macrophage tropism and systemic spread. This study was designed to determine whether S gene mutation analysis can reliably diagnose FIP. Cats were categorised as with FIP (n = 57) or without FIP (n = 45) based on gross post-mortem and histopathological examination including immunohistochemistry for FCoV antigen. RNA was purified from available tissue, fluid and faeces. Reverse-transcriptase quantitative-PCR (RT-qPCR) was performed on all samples using FCoV-specific primers, followed by sequencing of a section of the S gene on RT-qPCR positive samples. Samples were available from a total of 102 cats. Tissue, fluid, and faecal samples from cats with FIP were more likely to be FCoV RT-qPCR-positive (90.4, 78.4 and 64.6% respectively) than those from cats without FIP (7.8, 2.1 and 20% respectively). Identification of S gene mutated FCoVs as an additional step to the detection of FCoV alone, only moderately increased specificity for tissue samples (from 92.6 to 94.6%) but specificity was unchanged for fluid samples (97.9%) for FIP diagnosis; however, sensitivity was markedly decreased for tissue (from 89.8 to 80.9%) and fluid samples (from 78.4 to 60%) for FIP diagnosis. These findings demonstrate that S gene mutation analysis in FCoVs does not substantially improve the ability to diagnose FIP as compared to detection of FCoV alone.

Impact of Medication Onboarding: A Clinical Pharmacist-Run "Onboarding" Telephone Service for Patients Entering a Primary Care Practice.

Background: Previous studies have demonstrated the role of pharmacists during periods of transition of care. However, there are minimal studies that evaluate the impact that a pharmacist can have when a patient transitions his or her care to a new primary care provider (PCP). Objective: To assess the impact of a pharmacist-run medication "onboarding" service for patients new to a primary care (PC) practice. Methods: This prospective cohort study was approved by an institutional review board. Patients ≥50 years old and new to a PC practice were called by a pharmacist to obtain a medication list and identify any medication issues and recommendations. Recommendations were documented in the electronic medical record (EMR) and provided to the PCP prior to patients' first appointments. After each appointment, the EMR was reviewed to determine the status of recommendations. As a comparison, the medication list and PCP's initial appointment notes were reviewed for a similar cohort of patients not receiving a call. Medication-related actions taken at new patients' first appointments were then compared between the pharmacist-assisted (intervention) and usual care (control) groups. Results: Forty-two percent versus 15% of medication issues were enacted in the intervention and control groups (P = .001), respectively. Seventy-seven percent of PCPs found the service beneficial and time-saving during initial new patient visits; 85% felt the service helped them manage patients' medication therapy. Conclusion: A pharmacist-provided medication "onboarding" service results in significantly more medication issues addressed by the PCP compared with new patient visits not preceded by this service.

Depletion of HPV16 early genes induces autophagy and senescence in a cervical carcinogenesis model, regardless of viral physical state.

In cervical carcinomas, high-risk human papillomavirus (HR-HPV) may be integrated into host chromosomes or remain extra-chromosomal (episomal). We used the W12 cervical keratinocyte model to investigate the effects of HPV16 early gene depletion on in vitro cervical carcinogenesis pathways, particularly effects shared by cells with episomal versus integrated HPV16 DNA. Importantly, we were able to study the specific cellular consequences of viral gene depletion by using short interfering RNAs known not to cause phenotypic or transcriptional off-target effects in keratinocytes. We found that while cervical neoplastic progression in vitro was characterized by dynamic changes in HPV16 transcript levels, viral early gene expression was required for cell survival at all stages of carcinogenesis, regardless of viral physical state, levels of early gene expression or histology in organotypic tissue culture. Moreover, HPV16 early gene depletion induced changes in host gene expression that were common to both episome-containing and integrant-containing cells. In particular, we observed up-regulation of autophagy genes, associated with enrichment of senescence and innate immune-response pathways, including the senescence-associated secretory phenotype (SASP). In keeping with these observations, HPV16 early gene depletion induced autophagy in both episome-containing and integrant-containing W12 cells, as evidenced by the appearance of autophagosomes, punctate expression of the autophagy marker LC3, conversion of LC3B-I to LC3B-II, and reduced levels of the autophagy substrate p62. Consistent with the reported association between autophagy and senescence pathways, HPV16 early gene depletion induced expression of the senescence marker beta-galactosidase and increased secretion of the SASP-related protein IGFBP3. Together, these data indicate that depleting HR-HPV early genes would be of potential therapeutic benefit in all cervical carcinogenesis pathways, regardless of viral physical state. In addition, the senescence/SASP response associated with autophagy induction may promote beneficial immune effects in bystander cells.

Measuring stress before and during pregnancy: a review of population-based studies of obstetric outcomes.

Mounting evidence from clinic and convenience samples suggests that stress is an important predictor of adverse obstetric outcomes. Using a proposed theoretical framework, this review identified and synthesized the population-based literature on the measurement of stress prior to and during pregnancy in relation to obstetric outcomes. Population-based, peer-reviewed empirical articles that examined stress prior to or during pregnancy in relation to obstetric outcomes were identified in the PubMed and PsycInfo databases. Articles were evaluated to determine the domain(s) of stress (environmental, psychological, and/or biological), period(s) of stress (preconception and/or pregnancy), and strength of the association between stress and obstetric outcomes. Thirteen studies were evaluated. The identified studies were all conducted in developed countries. The majority of studies examined stress only during pregnancy (n = 10); three examined stress during both the preconception and pregnancy periods (n = 3). Most studies examined the environmental domain (e.g. life events) only (n = 9), two studies examined the psychological domain only, and two studies examined both. No study incorporated a biological measure of stress. Environmental stressors before and during pregnancy were associated with worse obstetric outcomes, although some conflicting findings exist. Few population-based studies have examined stress before or during pregnancy in relation to obstetric outcomes. Although considerable variation exists in the measurement of stress across studies, environmental stress increased the risk for poor obstetric outcomes. Additional work using a lifecourse approach is needed to fill the existing gaps in the literature and to develop a more comprehensive understanding of the mechanisms by which stress impacts obstetric outcomes.

CT imaging of intrauterine devices (IUD): expected findings, unexpected findings, and complications.

Intrauterine devices (IUDs) are a commonly used form of long-acting reversible contraception, which either contain copper or levonorgestrel to prevent pregnancy. Although symptomatic patients with indwelling IUDs may first undergo ultrasound to assess for device malposition and complications, IUDs are commonly encountered on CT in patients undergoing evaluation for unrelated indications. Frequently, IUD malposition and complications may be asymptomatic or clinically unsuspected. For these reasons, it is important for the radiologist to carefully scrutinize the IUD on any study in which it is encountered. To do so, the radiologist must recognize that normally positioned IUDs are located centrally within the uterine cavity. IUDs are extremely effective in preventing pregnancy, though inadvertent pregnancy risk is higher with malpositioned IUDs. Presence of fibroids or Mullerian abnormalities may preclude proper IUD placement. Radiologists play an important role in identifying complications when they arise and special considerations when planning for an IUD placement. There is a wide range of IUD malposition, affecting IUDs differently depending on the type of IUD and its mechanism of action. IUD malposition is the most common complication, but embedment and/or partial perforation can and can lead to difficulty when removed. Retained IUD fragments can result in continued contraceptive effect. Perforated IUDs do not typically cause intraperitoneal imaging findings.

Socioeconomic disparities in the quality of life in children with cancer or brain tumors: the mediating role of family factors.

OBJECTIVE: This study aimed to determine if and to what extent (i) socioeconomic disparities exist in the health-related quality of life (QOL) of children with cancer or brain tumors and healthy children; and (ii) family functioning and burden mediate the relationship between socioeconomic status and children's QOL. METHODS: In this cross-sectional study, parents of children ages 2-18 with (n = 71) and without (n = 135) cancer or brain tumors completed in-person interviewer-assisted surveys assessing sociodemographics (including income and parental education), child QOL (measure: PedsQL), family functioning (measure: Family Adaptability and Cohesion Evaluation Scale IV) and burden (measure: Impact on the Family Scale). For children with cancer, clinical characteristics were captured through medical record abstraction. Multiple linear regression was used to determine the relationship between income and child QOL; the interaction between group status and income was assessed. Staged multivariate regression models were used to assess the role of family factors in this relationship among children with cancer. RESULTS: In multivariate analyses, the effect of income differed by cancer status; lower income was associated with worse QOL in children with cancer but not among healthy children. Among children with cancer, this relationship was significantly attenuated by family burden. CONCLUSIONS: Significant socioeconomic disparities exist in the QOL of children with cancer. Family factors partially explain the relationship between low income and poor QOL outcomes among these children. Lower-income families may have fewer resources to cope with their child's cancer. Increased support, monitoring, and referrals to reduce burden for these families may lead to improved QOL in children with cancer.

Measuring the health-related quality of life (HRQoL) of young children in resource-limited settings: a review of existing measures.

PURPOSE: This review sought to identify and summarize the instruments adapted or developed for measuring HRQoL among young children (<8 years) living in resource-limited settings. METHODS: A review of the literature was conducted in two phases. Phase one searched the PubMed, PsycInfo, Web of Knowledge (Web of Science), African Index Medicus, and SocINDEX databases and identified widely used child HRQoL instruments. Phase two reviewed the articles using the selected HRQoL instruments and extracted information on their use in resource-limited settings including adaption processes. RESULTS: Seven instruments were identified that measured the HRQoL of young children. Six had been used in resource-limited settings. Of the 452 articles using these instruments, a total of 23 (5 %) studies used one of the identified HRQoL instruments in a resource-limited setting. Among these studies, 39 % employed an adaptation process for the use of that instrument. No instruments had been developed specifically for measuring the HRQoL of young children in resource-limited settings. CONCLUSIONS: If pediatric HRQoL instruments are to be used in resource-limited settings, it is critical that they be developed and adequately adapted to those settings. Only then will interventions lead to larger increases in the overall HRQoL and well-being of children.

Complications of second-trimester medical termination of pregnancy for fetal anomalies compared with intrauterine fetal demise.

OBJECTIVE: To assess complication rates of patients undergoing a second-trimester medical termination for intrauterine fetal demise compared with fetal anomalies. METHODS: We performed a retrospective cohort study comparing patients undergoing medical termination for a fetal anomaly versus medical termination for intrauterine fetal demise (IUFD) before 24 weeks of gestation. Data were collected from two urban academic medical centers from 2009 to 2019. Institutional review board approval was obtained from both institutions and patient consent was not required. We included singleton gestations between 14.0 weeks and 23.6 weeks undergoing induction with mifepristone and misoprostol or misoprostol alone. Groups were matched based on gestational age with a 1:1 ratio. The primary outcome was composite complication rate (retained placenta requiring dilation and curettage, suspected infection, hemorrhage, failed induction requiring dilation and evacuation, intensive care unit admission, and readmission). RESULTS: Ninety-five patients were in each group. The groups differed in patient mean age (fetal anomaly 34 years versus 31 years for IUFD, P = 0.005) and mifepristone pretreatment (fetal anomaly 55% versus IUFD 5%, P < 0.001). Composite complication rate was similar (fetal anomaly 14% versus IUFD 17%), and specific complications did not differ. CONCLUSION: Second-trimester medical termination for IUFDs have similar complication rates as those undergoing induction terminations for fetal anomalies.

Complications of second trimester induction for abortion or fetal demise for patients with and without prior cesarean delivery.

OBJECTIVE: Compare complication rates of second trimester induction for abortion or fetal demise for patients with and without prior cesarean delivery. STUDY DESIGN: Retrospective cohort study examining induction for abortion or fetal demise for pregnancies from 14w0d to 23w6d gestation at 2 urban academic medical centers from 2009 to 2019. Exclusion criteria included preterm labor or cervical insufficiency, neonatal interventions, or if misoprostol was not the primary induction method. Complication rates were compared between those with no prior, 1 prior, and 2 or more (2+) prior cesarean deliveries. Complications analyzed were retained placenta, failed induction, infection, hemorrhage, blood transfusion, uterine rupture, intensive care unit admission, death, and readmission. Secondary analysis included cumulative misoprostol dosages and complete abortion rate within 24 hours. RESULTS: Of 520 patients, 411 patients had no prior cesarean delivery, 77 had 1 prior cesarean delivery, and 32 had 2+ prior cesarean deliveries. Eleven patients had a prior vertical uterine incision. About 26.5% of all patients received mifepristone. The 2+ prior cesarean delivery group was significantly older (35 vs 32 vs 32, p < 0.001) and more likely to be induced for fetal demise (62.5 vs 41.56 vs 39.17%, p = 0.04). Both cesarean groups were more likely to be obese (58.62 vs 49.35 vs 34.26%, p = 0.003). Patients with 2+ prior cesarean deliveries were more likely to experience uterine rupture (6.25 vs 0 vs 0%, p = 0.004), and require ICU admission (6.45 vs 1.3 vs 0.49%, p = 0.02). Secondary analysis outcomes were similar. Logistic regression showed patients with 2+ prior cesarean deliveries were more likely to experience a complication than those with 1 prior (adjusted odds ratio [aOR] 2.71, confidence interval [CI] 1.09-6.86, p = 0.03) or 0 prior cesarean deliveries (aOR 3.00, CI 1.30-7.02, p = 0.01). Patients with 1 prior or no prior cesarean deliveries had a similar risk of experiencing a complication (aOR 1.11, CI 0.64-1.89, p = 0.7). CONCLUSIONS: Most patients with prior cesarean deliveries can safely undergo induction in the second trimester for abortion or fetal demise. Patients with 2+ prior cesarean deliveries had a higher rate of at least 1 complication when compared to those with one or no prior cesarean delivery, despite similar misoprostol dosages and rates of complete abortion. IMPLICATIONS: This large 10-year retrospective study examines the impact of prior cesarean delivery on the safety of second trimester induction. While second trimester labor induction abortion remains an option for all patients, specialized counseling for patients with 2 or more prior cesarean deliveries may be warranted.

Isolation and molecular identification of nematode surface mutants with resistance to bacterial pathogens.

Numerous mutants of the nematode Caenorhabditis elegans with surface abnormalities have been isolated by utilizing their resistance to a variety of bacterial pathogens (Microbacterium nematophilum, Yersinia pseudotuberculosis, and 2 Leucobacter strains), all of which are able to cause disease or death when worms are grown on bacterial lawns containing these pathogens. Previous work led to the identification of 9 srf or bus genes; here, we report molecular identification and characterization of a further 10 surface-affecting genes. Three of these were found to encode factors implicated in glycosylation (srf-2, bus-5, and bus-22), like several of those previously reported; srf-2 belongs to the GT92 family of putative galactosyltransferases, and bus-5 is homologous to human dTDP-D-glucose 4,6-dehydratase, which is implicated in Catel-Manzke syndrome. Other genes encoded proteins with sequence similarity to phosphatidylinositol phosphatases (bus-6), Patched-related receptors (ptr-15/bus-13), steroid dehydrogenases (dhs-5/bus-21), or glypiation factors (bus-24). Three genes appeared to be nematode-specific (srf-5, bus-10, and bus-28). Many mutants exhibited cuticle fragility as revealed by bleach and detergent sensitivity; this fragility was correlated with increased drug sensitivity, as well as with abnormal skiddy locomotion. Most of the genes examined were found to be expressed in epidermal seam cells, which appear to be important for synthesizing nematode surface coat. The results reveal the genetic and biochemical complexity of this critical surface layer, and provide new tools for its analysis.

Genome sequence for "Candidatus Mycoplasma haemominutum," a low-pathogenicity hemoplasma species.

We present the genome sequence of "Candidatus Mycoplasma haemominutum" strain Birmingham 1, a low-pathogenicity feline hemoplasma strain.

Haemoparasites of free-roaming dogs associated with several remote Aboriginal communities in Australia.

BACKGROUND: Tick-borne haemoparasites Babesia vogeli and Anaplasma platys are common among the free-roaming canine populations associated with Aboriginal communities in Australia, whilst the prevalence of haemoplasmas, which are also suspected to be tick-borne, remained unexplored. The aim of this study was to determine the prevalence of haemoplasma infection in these populations, and to identify any correlation with other haemoparasites. Blood was collected from 39 dogs associated with four Aboriginal communities and screened for infection using PCR and serology. DNA was purified and PCR analyses for piroplasms, Anaplasmataceae family bacteria and haemoplasmas performed. Serum was analysed using a commercial haemoparasite ELISA. Prevalence of infection was compared between communities. RESULTS: Seventeen dogs (44%) were infected (PCR positive) with Mycoplasma haemocanis, eight (21%) with 'Candidatus Mycoplasma haematoparvum', 20 (51%) with A. platys, and 17 (44%) with B. vogeli. Two dogs were infected with a novel haemoplasma as determined by DNA amplification and sequencing. Two dogs (5%) were serologically positive for Dirofilaria immitis antigens, one (3%) was positive for Ehrlichia canis antibodies and nine (24nbsp;%) were positive for A. platys antibodies. Co-infections were frequent. Haemoplasma prevalence was highest (73%, 16/22) in Central Australia and lowest (22%, 2/9) in Western Australia (p = 0.017). In contrast, B. vogeli prevalence was low in Central Australia (18%, 4/22) but higher (78%, 7/9) in Western Australia (p = 0.003). CONCLUSIONS: This is the first time haemoplasma infections, including a novel species, have been molecularly documented in Australian dogs. The wide regional variation in prevalence of some of the haemoparasite infections detected in this study warrants further investigation.

A timeline of freedom of movement in the European Economic Area.

The European Economic Area (EEA) provides a common market for goods, labour, services, and capital. Promoting integration between countries through the free movement of labour, or more generally persons, pre-dates the previous forms of the EEA. However, during the Southern and Eastern Expansions of the European Union, there have been transition agreements on persons, designed to restrict immigration. Opening up labour markets to the new member states with signifcantly lower GDP per capita than existing states, has been contentious. This is why the use of transition agreements have permitted periods which existing members can limit immigration. Not all existing member states impose restrictions, and during the Eastern Enlargements, the restrictions were imposed for varying lengths of time by different existing members up to a maximum of seven years. During the transition agreement, the economies of new members and existing members can converge, which is ultimately designed to limit the pull factor of migration. In this note, we provide a concise resource of the timeline of the expansion of full free movement of persons for countries in the EEA and Switzerland.