The relationship between nutrition, gut dysbiosis, and pediatric sickle cell pain outcomes: A pilot study.

BACKGROUND: Nutritional deficiencies are prevalent in sickle cell disease (SCD) and may be associated with worse pain outcomes. Gut dysbiosis has been reported in patients with SCD and may contribute to both nutritional deficiencies and pain. OBJECTIVES: We tested the association of nutrition, fat-soluble vitamin (FSV) deficiency, and gut microbiome composition on clinical outcomes in SCD. Second, we measured the association between diet and exocrine pancreatic function on FSV levels. METHODS: Using case control design, we enrolled children with SCD (n = 24) and matched healthy controls (HC; n = 17, age, sex, race/ethnicity). Descriptive statistics summarized demographic and clinical data. Wilcoxson-rank tests compared FSV levels between cohorts. Regression modeling tested the association between FSV levels and SCD status. Welch's t-test with Satterthwaite adjustment evaluated associations between microbiota profiles, SCD status, and pain outcomes. RESULTS: Vitamin A and D levels were significantly decreased in participants with HbSS as compared to HC (vitamin A, p = < .0001, vitamin D, p = .014) independent of nutritional status. FSV correlated with dietary intake in SCD and HC cohorts. Gut microbial diversity was reduced in hemoglobin SS (HbSS) compared to hemoglobin SC (HbSC) and HC, p = .037 and .059, respectively. The phyla Erysipelotrichaceae and Betaproteobacteria were higher in SCD children reporting the highest quality-of-life (QoL) scores (p = .008 and .049, respectively), while Clostridia were higher in those with lower QoL scores (p = .03). CONCLUSION: FSV deficiencies and gut dysbiosis are prevalent in children with SCA. Gut microbial composition is significantly different in children with SCD with low QoL scores.

Comparison of bacterial culture with BioFire® FilmArray® multiplex PCR screening of archived cerebrospinal fluid specimens from children with suspected bacterial meningitis in Nigeria.

BACKGROUND: Diagnosis of bacterial meningitis remains a challenge in most developing countries due to low yield from bacterial culture, widespread use of non-prescription antibiotics, and weak microbiology laboratories. The objective of this study was to compare the yield from standard bacterial culture with the multiplex nested PCR platform, the BioFire® FilmArray® Meningitis/Encephalitis Panel (BioFire ME Panel), for cases with suspected acute bacterial meningitis. METHODS: Following Gram stain and bacterial culture on cerebrospinal fluid (CSF) collected from children aged less than 5 years with a clinical suspicion of acute bacterial meningitis (ABM) as defined by the WHO guidelines, residual CSF specimens were frozen and later tested by BioFire ME Panel. RESULTS: A total of 400 samples were analyzed. Thirty-two [32/400 (8%)] of the specimens were culture positive, consisting of; three Salmonella spp. (2 Typhi and 1 non-typhi), three alpha hemolytic Streptococcus, one Staphylococcus aureus, six Neisseria meningitidis, seven Hemophilus influenzae, 11 Streptococcus pneumoniae and 368 were culture negative. Of the 368 culture-negative specimens, the BioFire ME Panel detected at least one bacterial pathogen in 90 (24.5%) samples, consisting of S. pneumoniae, N. meningitidis and H. influenzae, predominantly. All culture positive specimens for H. influenzae, N. meningitidis and S. pneumoniae also tested positive with the BioFire ME Panel. In addition, 12 specimens had mixed bacterial pathogens identified. For the first time in this setting, we have data on the viral agents associated with meningitis. Single viral agents were detected in 11 (2.8%) samples while co-detections with bacterial agents or other viruses occurred in 23 (5.8%) of the samples. CONCLUSIONS: The BioFire® ME Panel was more sensitive and rapid than culture for detecting bacterial pathogens in CSF. The BioFire® ME Panel also provided for the first time, the diagnosis of viral etiologic agents that are associated with meningoencephalitis in this setting. Institution of PCR diagnostics is recommended as a routine test for suspected cases of ABM to enhance early diagnosis and optimal treatment.

Transfusion of incompatible blood to a patient with alloanti-Sc1.

Sc1 is a high-prevalence blood group antigen that is part of the Scianna blood group system. The clinical significance of Scianna antibodies is not well understood because of their rarity; there are only a handful of cases in the literature. This scarcity of information can make it difficult to decide on the best course of action when transfusing a patient with alloantibodies to Scianna blood group antigens. We describe a case of an 85-year-old woman presenting with melena and a hemoglobin of 66 g/L. Upon request for crossmatched blood, a panreactive antibody was found, later elucidated to be alloanti-Sc1. Because of the urgent nature of the transfusion, the patient was transfused with 2 incompatible, presumed Sc1+, red blood cell units with no evidence of an acute or delayed transfusion reaction. This case has been shared with the International Society of Blood Transfusion Rare Donor Working Party, via their Outcome of Incompatible Transfusion form, and adds to the body of evidence on clinical significance of antibodies to the antigens of the Scianna blood group system.

Memory recall: New behavioral protocols for examining distinct forms of context specific recall in animals.

This study outlines two novel protocols for examining context specific recall in animals prior to embarking on neurobiological studies. The approach is distinct from and contrasts with studies investigating associative familiarity that depend upon procedural variations of the widely used novel object recognition task. It uses an event arena in which animals are trained across numerous sessions to search for, find and dig up reward from sandwells during sample and choice trials - a prominent spatial event for a rodent. The arena could be laid out as either of two highly distinct contexts with which the animals became fully familiar throughout training. In one protocol, the location of the correct sandwell in each context remained stable across days, whereas in the other, the correct digging location varied in a counterbalanced manner across each successive session. Thus, context-specific recall of the spatial location of successful digging during choice trials was either from a stable long-term memory or could reflect context specific spatial recency of the location where reward had been available that session. Both protocols revealed effective memory recall in choice and probe tests which, at the point of test, were procedurally identical in both cases.

Cognition and reproductive success in cowbirds.

Understanding the relationships between cognitive abilities and fitness is integral to an evolutionary study of brain and behavior. However, these relationships are often difficult to measure and detect. Here we draw upon an opportunistic sample of brown-headed cowbird (Molothrus ater) subjects that had two separate research experiences: First, they engaged in a large series of cognitive tests in David Sherry's Lab in the Advanced Facility for Avian Research (AFAR) at Western University, then subsequently moved to the Field Avian Research Megalab (FARM) at Wilfrid Laurier University where they lived in large breeding flocks in aviaries with other wild-caught cowbirds. Thus, we had extensive measures of cognitive abilities, breeding behavior, and reproductive success for these birds. We report here, for the fist time, the surprisingly strong connections we found among these different measures. Female cowbirds' spatial cognitive abilities correlated positively with how intensely they were courted by males, and with their overall egg production. Males' spatial cognition correlated positively with their ability to engage in singing contests ("countersinging") with other males. In addition, a separate non-spatial cognitive ability correlated positively with the attractiveness of the songs they sung. In sum, these results suggest the cognitive skills assessed in the lab were strongly connected to breeding behavior and reproductive success. Moreover, since certain cognitive abilities related to different aspects of breeding success, it suggests that cognitive modules may have specialized adaptive value, but also that these specialized skills may interact and influence fitness in surprising ways.

Early detection and intervention for young children with early developmental disabilities in Western Uganda: a mixed-methods evaluation.

BACKGROUND: Early support for children with developmental disabilities is crucial but frequently unavailable in low-resource settings. We conducted a mixed-methods evaluation to assess the feasibility, acceptability, and impact of a programme of early detection and intervention for young children with developmental disabilities in Western Uganda. METHODS: Early child development training for healthcare workers (HCWs) was implemented in three rural districts, and attendance was tracked. HCW knowledge and confidence were assessed pre-/post-intervention, and referral numbers tracked to evaluate impact. Facilitators were trained and mentored to deliver a participatory, group, early intervention programme (EIP) for young children with developmental disabilities and their families. Facilitators were tracked as they were identified, trained, and delivered the intervention, and attendance of families was tracked. Pre-/post-intervention assessments evaluated changes in family quality of life (PedsQL 2.0, Family Impact Module), and child nutritional outcomes. Focus group discussions with stakeholders also assessed feasibility, acceptability and impact. RESULTS: Overall, 93 HCWs from 45 healthcare facilities received training. In the pre-/post-evaluation, median knowledge and confidence scores increased significantly (from 4.0 to 7.0 and from 2.7 to 4.7, respectively (p < 0.001)). HCWs reported feeling empowered to refer and offer care for families with a young child with disability. Referral rates increased significantly from 148 to 251 per annum (70%; p = 0.03). Eleven EIP facilitators were trained, and all delivered the intervention; 84 families were enrolled, of which 78% attended at least 6 out of 10 modules. Amongst those with paired pre-/post-intervention data (n = 48), total family quality of life scores increased significantly (21%, p < 0.001). Improvements were seen across all domains of quality of life, with the largest impacts on emotional functioning and social functioning (p < 0.001). The programme was acceptable to caregivers and facilitators. Caregivers reported improved knowledge, family relationships, hope, emotional wellbeing, and reduced self-stigma. CONCLUSIONS: A programme of early detection and intervention for children with early developmental disabilities and their families was feasible and acceptable in a rural community-based Ugandan setting. HCW training positively impacted knowledge, confidence, attitudes, and referral rates. Families enrolled to the EIP reported significant improvements in quality of life. Important programmatic barriers identified included geographical spread, poverty, gender inequality, and stigma.

Metal vs fibre posts - which is clinically superior for the restoration of endodontically treated teeth?

Data sources Medline/PubMed, Web of Science, Scopus and Cochrane Library databases. Grey literature searches (OpenGrey, ProQuest databases), hand searches in the reference list of eligible studies and relevant journals.Study selection Randomised controlled trials (RCTs) and prospective clinical trials (PCTs) with direct comparisons between metal posts (MPs) and fibre posts (FPs). Trials contained a minimum of ten patients and endodontically treated permanent teeth that had received either single crowns or fixed partial dentures (bridges) and followed up for a minimum of one year. The primary outcome compared the difference in failure rates between FPs and MPs, with subgroup analysis comparing location (anterior/posterior), type of MP (cast post core/preformed MP) and most frequent modes of failure (debond/root fracture).Data extraction and synthesis Study selection, data collection and risk of bias assessments were completed independently by two reviewers. Disagreements were discussed with a third reviewer to reach a consensus. The risk of bias was evaluated using the Cochrane risk of bias tool (RCTs) or the ROBINS-I tool (PCTs). The quality of responses was assessed using the Grading of Recommendations Assessment, Development And Evaluation (GRADE) approach. The meta-analysis (MA) was performed using the Mantel-Haenszel method. Trial heterogeneity was assessed using random- and fixed-effects models. Inter-examiner agreement during the database search and study selection process was checked using the kappa statistic.Results After duplicates were removed, 1,026 articles were assessed and screened by title and abstract. Of these, 21 articles underwent full-text evaluation, with ten articles meeting the eligibility criteria. Eligible studies included six RCTs and four PCTs. A total of 844 endodontically treated teeth (ETT) were restored with intra-radicular posts in 704 participants. Four hundred and fifty-three ETT were restored with FPs and 391 with MPs. The mean age of participants was 42.7 (33.95-55.45) years, with a mean follow-up period of 50.95 (12-154) months. Most studies reported failures during the follow-up period, but the MA revealed no significant difference between FPs and MPs in terms of failure rates (P = 0.39; RR: 0.82 mm; CI: 0.52-1.29). Sub-analysis showed no difference in failure rates between anterior and posterior regions and no difference when comparing FPs to cast post and core vs prefabricated MPs. Root fractures and post debondings were the most common modes of failure, but within these failures, no difference was observed between FPs and MPs.Conclusions No evidence was identified for a difference in failure rates between FPs and MPs. This was independent of the type of MP and position within the arch. Reporting of RCTs and PCTs was variable and further high-quality studies are needed.

Burden of non-melanoma skin cancer attributable to occupational sun exposure in Canada.

PURPOSE: Outdoor workers are exposed daily to solar ultraviolet radiation, an important contributor in the development of non-melanoma skin cancer. This study aimed to quantify the health burden of non-melanoma skin cancers among outdoor workers in Canada. METHODS: Solar ultraviolet radiation exposure and estimates of exposure levels were applied to employment information from Canada census data to determine the exposed population in the risk exposure period (1961-2001). Risk estimates were drawn from meta-analyses selected based on quality and relevance to the current study. Population-attributable fractions were calculated using Levin's equation and attributable cases were estimated based on incidence data reported by the Canadian Cancer Society. RESULTS: In 2011, 6.31% (4556 cases) of non-melanoma skin cancer cases were estimated to be attributable to occupational exposure to solar ultraviolet radiation. The majority of these cases occurred in men in the agriculture or construction industries. CONCLUSIONS: These estimates of the burden of non-melanoma skin cancer in Canada identify the need for further prevention efforts, particularly in agriculture and construction. Introducing workplace sun safety measures could be an important area for policy development.

Intrinsic Maturational Neonatal Immune Deficiencies and Susceptibility to Group B Streptococcus Infection.

Although a normal member of the gastrointestinal and vaginal microbiota, group B Streptococcus (GBS) can also occasionally be the cause of highly invasive neonatal disease and is an emerging pathogen in both elderly and immunocompromised adults. Neonatal GBS infections are typically transmitted from mother to baby either in utero or during passage through the birth canal and can lead to pneumonia, sepsis, and meningitis within the first few months of life. Compared to the adult immune system, the neonatal immune system has a number of deficiencies, making neonates more susceptible to infection. Recognition of GBS by the host immune system triggers an inflammatory response to clear the pathogen. However, GBS has developed several mechanisms to evade the host immune response. A comprehensive understanding of this interplay between GBS and the host immune system will aid in the development of new preventative measures and therapeutics.

Small angle X-ray scattering as a high-throughput method to classify antimicrobial modes of action.

Multi-drug resistant bacteria are currently undermining our health care system worldwide. While novel antimicrobial drugs, such as antimicrobial peptides, are urgently needed, identification of new modes of action is money and time consuming, and in addition current approaches are not available in a high throughput manner. Here we explore how small angle X-ray scattering (SAXS) as high throughput method can contribute to classify the mode of action for novel antimicrobials and therefore supports fast decision making in drug development. Using data bases for natural occurring antimicrobial peptides or predicting novel artificial peptides, many candidates can be discovered that will kill a selected target bacterium. However, in order to narrow down the selection it is important to know if these peptides follow all the same mode of action. In addition, the mode of action should be different from conventional antibiotics, in consequence peptide candidates can be developed further into drugs against multi-drug resistant bacteria. Here we used one short antimicrobial peptide with unknown mode of action and compared the ultrastructural changes of Escherichia coli cells after treatment with the peptide to cells treated with classic antibiotics. The key finding is that SAXS as a structure sensitive tool provides a rapid feedback on drug induced ultrastructural alterations in whole E. coli cells. We could demonstrate that ultrastructural changes depend on the used antibiotics and their specific mode of action. This is demonstrated using several well characterized antimicrobial compounds and the analysis of resulting SAXS curves by principal component analysis. To understand the result of the PCA analysis, the data is correlated with TEM images. In contrast to real space imaging techniques, SAXS allows to obtain nanoscale information averaged over approximately one million cells. The measurement takes only seconds, while conventional tests to identify a mode of action require days or weeks per single substance. The antimicrobial peptide showed a different mode of action as all tested antibiotics including polymyxin B and is therefore a good candidate for further drug development. We envision SAXS to become a useful tool within the high-throughput screening pipeline of modern drug discovery. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert.

Early-Onset Invasive Candidiasis in Extremely Low Birth Weight Infants: Perinatal Acquisition Predicts Poor Outcome.

BACKGROUND: Neonatal invasive candidiasis (IC) presenting in the first week of life is less common and less well described than later-onset IC. Risk factors, clinical features, and disease outcomes have not been studied in early-onset disease (EOD, ≤7 days) or compared to late-onset disease (LOD, >7 days). METHODS: All extremely low birth weight (ELBW, <1000 g) cases with IC and controls from a multicenter study of neonatal candidiasis enrolled from 2001 to 2003 were included in this study. Factors associated with occurrence and outcome of EOD in ELBW infants were determined. RESULTS: Forty-five ELBW infants and their 84 matched controls were included. Fourteen (31%) ELBW infants had EOD. Birth weight <750 g, gestation <25 weeks, chorioamnionitis, and vaginal delivery were all strongly associated with EOD. Infection with Candida albicans, disseminated disease, pneumonia, and cardiovascular disease were significantly more common in EOD than in LOD. The EOD case fatality rate (71%) was higher than in LOD (32%) or controls (15%) (P = .0001). The rate of neurodevelopmental impairment and mortality combined was similar in EOD (86%) and LOD (72%), but higher than in controls (32%; P = .007). CONCLUSIONS: ELBW infants with EOD have a very poor prognosis compared to those with LOD. The role of perinatal transmission in EOD is supported by its association with chorioamnionitis, vaginal delivery, and pneumonia. Dissemination and cardiovascular involvement are common, and affected infants often die. Empiric treatment should be considered for ELBW infants delivered vaginally who have pneumonia and whose mothers have chorioamnionitis or an intrauterine foreign body.

A Comparison of Outcomes in Patients with Infrapopliteal Disease Randomised to Vein Bypass or Plain Balloon Angioplasty in the Bypass vs. Angioplasty in Severe Ischaemia of the Leg (BASIL) Trial.

OBJECTIVE: The aim was to compare outcomes in a subgroup of patients with infrapopliteal (IP) disease randomised to infrapopliteal vein bypass (VB) or plain balloon angioplasty (PBA) in the original BASIL trial. METHODS: A comparison of outcomes from patients randomised to VB or PBA undergoing revascularisation for severe limb ischaemia (SLI) because of IP disease with or without femoropopliteal disease. Data were extracted from case report forms from the BASIL trial. The primary outcome was amputation free survival (AFS); secondary outcomes included overall survival (OS), 30 day mortality and morbidity, freedom from arterial re-intervention, immediate technical success, repeat and crossover interventions, length of hospital stay, and quality of revascularisation. RESULTS: A total of 104 patients were identified in the BASIL study with IP disease, 56 randomised to IP VB, and 48 to IP PBA. Groups were similar at baseline except for more chronic kidney disease and non-steroidal anti-inflammatory drug use in the VB group, and more previous surgical arterial intervention and antihypertensive use in the PBA group. There were no statistically significant differences in AFS or OS; however, clinically important trends were apparent in favour of a VB first strategy. Patients allocated to VB demonstrated significantly quicker relief of rest pain when compared with PBA (p = .005), but no significant differences in improved tissue healing. Median length of index hospital admission was significantly greater in the VB than in the PBA group (18 vs. 10 days, p < .0001) but there was no difference between the two groups in median total hospital stay between randomisation and the primary endpoint (VB 43.5 vs. PBA 42 days). CONCLUSIONS: Further randomised trials, like BASIL-2 and BEST-CLI, are required to determine whether patients with severe limb ischaemia who require IP revascularisation and who are suitable for VB should have bypass or endovascular intervention as their primary revascularisation procedure.

Association between genotypic diversity and biofilm production in group B Streptococcus.

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of sepsis and meningitis and an important factor in premature and stillbirths. Biofilm production has been suggested to be important for GBS pathogenesis alongside many other elements, including phylogenetic lineage and virulence factors, such as pili and capsule type. A complete understanding of the confluence of these components, however, is lacking. To identify associations between biofilm phenotype, pilus profile and lineage, 293 strains from asymptomatic carriers, invasive disease cases, and bovine mastitis cases, were assessed for biofilm production using an in vitro assay. RESULTS: Multilocus sequence type (ST) profile, pilus island profile, and isolate source were associated with biofilm production. Strains from invasive disease cases and/or belonging to the ST-17 and ST-19 lineages were significantly more likely to form weak biofilms, whereas strains producing strong biofilms were recovered more frequently from individuals with asymptomatic colonization. CONCLUSIONS: These data suggest that biofilm production is a lineage-specific trait in GBS and may promote colonization of strains representing lineages other than STs 17 and 19. The findings herein also demonstrate that biofilms must be considered in the treatment of pregnant women, particularly for women with heavy GBS colonization.

Early-onset neonatal sepsis.

Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS.

Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts.

BACKGROUND: Myelodysplastic syndromes are a diverse and common group of chronic hematologic cancers. The identification of new genetic lesions could facilitate new diagnostic and therapeutic strategies. METHODS: We used massively parallel sequencing technology to identify somatically acquired point mutations across all protein-coding exons in the genome in 9 patients with low-grade myelodysplasia. Targeted resequencing of the gene encoding RNA splicing factor 3B, subunit 1 (SF3B1), was also performed in a cohort of 2087 patients with myeloid or other cancers. RESULTS: We identified 64 point mutations in the 9 patients. Recurrent somatically acquired mutations were identified in SF3B1. Follow-up revealed SF3B1 mutations in 72 of 354 patients (20%) with myelodysplastic syndromes, with particularly high frequency among patients whose disease was characterized by ring sideroblasts (53 of 82 [65%]). The gene was also mutated in 1 to 5% of patients with a variety of other tumor types. The observed mutations were less deleterious than was expected on the basis of chance, suggesting that the mutated protein retains structural integrity with altered function. SF3B1 mutations were associated with down-regulation of key gene networks, including core mitochondrial pathways. Clinically, patients with SF3B1 mutations had fewer cytopenias and longer event-free survival than patients without SF3B1 mutations. CONCLUSIONS: Mutations in SF3B1 implicate abnormalities of messenger RNA splicing in the pathogenesis of myelodysplastic syndromes. (Funded by the Wellcome Trust and others.).

Pilus distribution among lineages of group b streptococcus: an evolutionary and clinical perspective.

BACKGROUND: Group B Streptococcus (GBS) is an opportunistic pathogen in both humans and bovines. Epidemiological and phylogenetic analyses have found strains belonging to certain phylogenetic lineages to be more frequently associated with invasive newborn disease, asymptomatic maternal colonization, and subclinical bovine mastitis. Pilus structures in GBS facilitate colonization and invasion of host tissues and play a role in biofilm formation, though few large-scale studies have estimated the frequency and diversity of the three pilus islands (PIs) across diverse genotypes. Here, we examined the distribution of pilus islands (PI) 1, 2a and 2b among 295 GBS strains representing 73 multilocus sequence types (STs) belonging to eight clonal complexes. PCR-based RFLP was also used to evaluate variation in the genes encoding pilus backbone proteins of PI-2a and PI-2b. RESULTS: All 295 strains harbored one of the PI-2 variants and most human-derived strains contained PI-1. Bovine-derived strains lacked PI-1 and possessed a unique PI-2b backbone protein allele. Neonatal strains more frequently had PI-1 and a PI-2 variant than maternal colonizing strains, and most CC-17 strains had PI-1 and PI-2b with a distinct backbone protein allele. Furthermore, we present evidence for the frequent gain and loss of genes encoding certain pilus types. CONCLUSIONS: These data suggest that pilus combinations impact host specificity and disease presentation and that diversification often involves the loss or acquisition of PIs. Such findings have implications for the development of GBS vaccines that target the three pilus islands.

Intrapartum antibiotic prophylaxis selects for mutators in group B streptococci among persistently colonized patients.

Through vaginal colonization, GBS causes severe pregnancy outcomes including neonatal sepsis and meningitis. Although intrapartum antibiotic prophylaxis (IAP) has reduced early-onset disease rates, persistent GBS colonization has been observed in patients following prophylaxis. To determine whether IAP selects for genomic signatures that enhance GBS survival and persistence in the vaginal tract, whole-genome sequencing was performed on 97 isolates from 58 patients before (prenatal) and after (postpartum) IAP/childbirth. Core-gene mutation analysis identified 7,025 mutations between the paired isolates. Three postpartum isolates accounted for 98% of mutations and were classified as "mutators" because of point mutations within DNA repair systems. In vitro assays revealed stronger biofilms in two mutators. These findings suggest that antibiotics select for mutations that promote survival in vivo, which increases the likelihood of transmission to neonates. They also demonstrate how mutators can provide a reservoir of beneficial mutations that enhance fitness and genetic diversity in the GBS population.

Review of the clinical diagnosis of sacroiliac dysfunction in horses - Challenges and limitations.

Sacroiliac dysfunction (SID) is a condition seen in horses associated with poor performance that affects hind limb gait and impulsion. The condition comprises pain and dysfunction but there lacks clarity around the aetiopathogenesis and whether SID encompasses abnormal joint pathology, abnormal joint movement, abnormal regional biomechanical function, joint laxity and pain, or various combinations of these that may vary over time. Clinical assessment remains challenging for equine clinicians due to the deep location of the sacroiliac joint (SIJ) and surrounding structures which limits access for palpation, diagnostic imaging and joint-specific injection. There is no recognised single reference standard diagnostic test for SID. Clinical diagnosis has been based on ruling out other causes of hind limb lameness, along with combinations of ultrasonography, scintigraphy and periarticular anaesthesia of the SIJ. Recent studies have highlighted the lack of specificity of injections targeting the SIJ, with significant dispersal of injectate into surrounding structures including around the lumbosacral joint (LSJ). Advanced imaging modalities such as computed tomography offers promise for assessment of the structure and pathology of the SIJ and surrounding bony structures. However, there is a need to improve the understanding of the significance of anatomic variation of the sacroiliac region structures, with recent studies reporting detailed anatomic variation in groups of horses with and without SID. There are also limitations around functional assessment of the joint which is still largely reliant on a thorough clinical examination. This review aims to present an update on clinical approaches to the diagnosis of horses with SID, and to consider the challenges and limitations.

Recording of suspected adverse drug reaction reporting in veterinary free-text clinical narratives.

OBJECTIVES: To use text mining approaches to identify instances of suspected adverse drug reactions recorded in first opinion veterinary free-text clinical narratives, and to evaluate whether these were also reported to either the Veterinary Medicines Directorate or the relevant Marketing Authorisation holder in order to derive an estimate of the suspected adverse drug reaction (sADR) minimum under-reporting rate. To characterise sADR reports and explore whether particular features are associated with report submission. MATERIALS AND METHODS: Two regular expressions were developed to identify mentions of "adverse drug reactions" and "side effects" in the free-text clinical narratives of electronic health records contained within the Small Animal Veterinary Surveillance Network database. Consultations containing a match for the developed regular expressions were manually reviewed for inclusion and further classified to determine the suspected product, seriousness and expectedness of the event, and an indication of whether the event had been reported. The associations between event characteristics and reporting were explored using Fisher's exact tests. RESULTS: A total of 10,565 records were manually reviewed from which 827 sADRs were identified. Approximately 90% of these sADRs were not recorded as reported. Suspected adverse drug reactions that were not considered "expected" were recorded as reported more frequently than "expected" sADRs. However, clinical severity did not appear to impact on whether there was a record of reporting. CLINICAL SIGNIFICANCE: This is the first estimate of under reporting sADRs based on real world evidence from veterinary clinical records. The under-reporting rate implied by this study highlights that further interventions are required to improve reporting rate within the veterinary profession in order to support pharmacovigilance activities and improve drug safety.