Gut microbiota and immune profiling of microbiota-humanised versus wildtype mouse models of hepatointestinal schistosomiasis.

Mounting evidence of the occurrence of direct and indirect interactions between the human blood fluke, Schistosoma mansoni, and the gut microbiota of rodent models raises questions on the potential role(s) of the latter in the pathophysiology of hepatointestinal schistosomiasis. However, substantial differences in both the composition and function between the gut microbiota of laboratory rodents and that of humans hinders an in-depth understanding of the significance of such interactions for human schistosomiasis. Taking advantage of the availability of a human microbiota-associated mouse model (HMA), we have previously highlighted differences in infection-associated changes in gut microbiota composition between HMA and wildtype (WT) mice. To further explore the dynamics of schistosome-microbiota relationships in HMA mice, in this study we (i) characterize qualitative and quantitative changes in gut microbiota composition of a distinct line of HMA mice (D2 HMA) infected with S. mansoni prior to and following the onset of parasite egg production; (ii) profile local and systemic immune responses against the parasite in HMA as well as WT mice and (iii) assess levels of faecal inflammatory markers and occult blood as indirect measures of gut tissue damage. We show that patent S. mansoni infection is associated with reduced bacterial alpha diversity in the gut of D2 HMA mice, alongside expansion of hydrogen sulphide-producing bacteria. Similar systemic humoral responses against S. mansoni in WT and D2 HMA mice, as well as levels of faecal lipocalin and markers of alternatively activated macrophages, suggest that these are independent of baseline gut microbiota composition. Qualitative comparative analyses between faecal microbial profiles of S. mansoni-infected WT and distinct lines of HMA mice reveal that, while infection-induced alterations of the gut microbiota composition are highly dependent on the baseline flora, bile acid composition and metabolism may represent key elements of schistosome-microbiota interactions through the gut-liver axis.

Visual access to an outdoor range early in life, but not environmental complexity, increases meat chicken ranging behavior.

Not all chickens access an outdoor range when the opportunity is provided. This may be related to the abrupt change in environments from the stable rearing conditions to the complexity of the outdoor range. We aimed to prepare chickens to range by increasing the complexity of the indoor environment early in life with the intention to encourage range use. Mixed sex Cobb500 chickens were allocated to 1 of 3 treatment groups: visual access (VA) treatment provided VA to the outdoor range from day old via transparent pop-hole covers; environmental complexity (EC) treatment provided an artificial haybale, fan with streamers and a solid vertical barrier; Control treatment was a representative conventional environment. Chickens were given access to the outdoor range at 21 d of age. Behavior in the home pen was assessed in wk 1, 2 and 5 and individual ranging behavior was monitored through radio frequency identification (RFID) technology. The VA chickens were more active compared to EC (P = 0.006) and Control (P = 0.007) chickens and spent more time foraging than control chickens (P = 0.036) during the first week of life. More VA chickens accessed the range area compared to EC chickens (P = 0.015). VA chickens accessed the range sooner after they were first provided access and spent more time on the range than EC and control chickens (P < 0.001). Mortality was lower in the VA treatment compared to EC (P = 0.024) and control group (P = 0.002). There was evidence that VA chickens weighed less than Control and EC chickens, however results were inconsistent between age and sex. Hence, providing meat chickens with VA to an outdoor range early in life increased activity in early life, decreased latency to first access the range and increased time on the range and lowered mortality. Future work should aim to understand the mechanism behind these changes in behavior to develop recommendations for producers to implement in commercial conditions.

A retrospective cohort study of the characteristics of unsuccessful operative vaginal deliveries.

INTRODUCTION: Unsuccessful operative vaginal delivery (OVD) is associated with high rates of materno-fetal morbidity. We aimed to examine institutional rates of unsuccessful OVDs (uOVD) and compare them with successful OVD (sOVD) in order to identify factors to aid patient selection and education. METHODS: A 6-month retrospective cohort study was performed on all unsuccessful and successful OVDs in a tertiary level maternity hospital in the Republic of Ireland. Maternal demographics and obstetric factors were assessed to evaluate potential underlying risk factors for unsuccessful operative vaginal delivery versus successful vaginal delivery. RESULTS: There were 4,191 births during the study period with an OVD rate of 14.2% (n = 595) with 28 (4.7% of OVDs) being unsuccessful. Unsuccessful OVD were predominately nulliparous (25; 89.2%) with a mean maternal age of 30.1 years (range 20-42), with more than half (n = 15, 53.5%) being induced. The most common indication for induction was prolonged rupture of membranes (PROM) (n = 7, 25%) which was significantly different from the successful OVD group. A senior obstetrician was significantly more likely to be the primary operator in uOVD when compared to sOVD. (82.1 % V 54.1% p < 0.01). The majority of unsuccessful OVD were vacuum deliveries (n = 17; 60.7%), with a significantly higher mean birthweight when compared to successful OVD (3.695 kg V 3.483 kg; p < 0.01). Following an unsuccessful OVD, women were more likely to have a postpartum haemorrhage (64.2 % V 31.5% p < 0.01) and their infant was more likely to require admission to the neonatal intensive care unit (NICU) (32.1 % V 5.8% p < 0.01) when compared with successful OVD. CONCLUSION: Risk factors for unsuccessful OVD were higher birth weight and induction of labour. There was a higher incidence of postpartum haemorrhage and NICU admission when compared with successful OVD.

Effects of hindgut acidosis on metabolism, inflammation, and production in dairy cows consuming a standard lactation diet.

Postruminal intestinal barrier dysfunction caused by excessive hindgut fermentation may be a source of peripheral inflammation in dairy cattle. Therefore, the study objectives were to evaluate the effects of isolated hindgut acidosis on metabolism, inflammation, and production in lactating dairy cows. Five rumen-cannulated lactating Holstein cows (32.6 ± 7.2 kg/d of milk yield, 242 ± 108 d in milk; 642 ± 99 kg of body weight; 1.8 ± 1.0 parity) were enrolled in a study with 2 experimental periods (P). During P1 (4 d), cows were fed ad libitum a standard lactating cow diet (26% starch dry matter) and baseline data were collected. During P2 (7 d), all cows were fed the same diet ad libitum and abomasally infused with 4 kg/d of pure corn starch (1 kg of corn starch + 1.25 L of H2O/infusion at 0600, 1200, 1800, and 0000 h). Effects of time (hour relative to the first infusion or day) relative to P1 were evaluated using PROC MIXED in SAS (version 9.4; SAS Institute Inc.). Infusing starch markedly reduced fecal pH (5.84 vs. 6.76) and increased fecal starch (2.2 to 9.6% of dry matter) relative to baseline. During P2, milk yield, milk components, energy-corrected milk yield, and voluntary dry matter intake remained unchanged. At 14 h, plasma insulin and ß-hydroxybutyrate increased (2.4-fold and 53%, respectively), whereas circulating glucose concentrations remained unaltered. Furthermore, blood urea nitrogen increased at 2 h (23%) before promptly decreasing below baseline at 14 h (13%). Nonesterified fatty acids tended to decrease from 2 to 26 h (40%). Circulating white blood cells and neutrophils increased on d 4 (36 and 73%, respectively) and somatic cell count increased on d 5 (4.8-fold). However, circulating serum amyloid A and lipopolysaccharide-binding protein concentrations were unaffected by starch infusions. Despite minor changes in postabsorptive energetics and leukocyte dynamics, abomasal starch infusions and the subsequent hindgut acidosis had little or no meaningful effects on biomarkers of immune activation or production variables.

Multi-institutional and multi-disciplinary care: A successfully managed aortic dissection in the third trimester of pregnancy.

Multi-disciplinary collaborative care for pregnant women with complex and emergent conditions is essential. Logistical planning, clear communication and human factor awareness are all non-clinical skills which need to be utilised in order to maximise outcomes. We describe the case of a proximal aortic dissection in the late third trimester of pregnancy diagnosed in a peripheral hospital that was transferred to a cardiothoracic centre for successful operative management 160 km away. This required the time-sensitive mobilisation and liaison of a receiving cardiothoracic, anaesthesiology and perfusionist team in conjunction with obstetric and midwifery support from an affiliated maternity hospital, as well as the national neonatal transport team. We emphasise the importance of multidisciplinary team management in complex cases and how imperative good inter-disciplinary communication is to ensure safe inter-hospital transfer.

Predicting the unpredictable? A climate-based model of the timing of peak pasture infectivity for Dictyocaulus viviparus.

Outbreaks of cattle lungworm disease (Dictyocaulus viviparus) are explosive and costly. The unpredictability of the disease often encourages farmers to apply blanket anthelmintic treatments to the herd, which impede the acquisition of immunity, increase the risk of drug resistance, and interfere with efforts to reduce anthelmintic use against ubiquitous gastrointestinal nematodes. Improving our understanding of the factors which lead to a high risk of infection with lungworm, (including climatic pressure), would support a more targeted management. We present GLOWORM-FL-DV, the first mathematical model of the free-living stages of D. viviparus. The ecology of D. viviparus is unique compared with other strongylid nematodes due to its relationship with Pilobilus spp. fungi, which enhance the transmission potential. The role of the fungi was therefore incorporated into the model framework, informed by laboratory observations of Pilobolus spp. development and sporulation. The thermal niche of D. viviparus was characterised based on published and laboratory observations. Mortality of parasitic larvae increased significantly below 0oC, and larval development occurred above 1.4oC, whereas the estimated minimum temperature for migration via Pilobolus spp. was 8.8oC. Model predictions were compared with antibody levels in bulk milk tank samples collected at two-weekly intervals from eight dairy herds across Great Britain over two grazing seasons. The model predicted high levels of larval abundance on pasture 46 days (38-52 days) before a rise in antibody levels and 22-26 days before the onset of clinical signs. The model assesses the impact of climate and weather on lungworm larval availability at pasture and provides a framework for the development of a risk forecasting system. This could help to focus vigilance for clinical signs at high-risk times and facilitate the targeted use of anthelmintics to prevent outbreaks, in support of sustainable parasite control.

An objective analysis of quality and readability of online information on COVID-19.

High quality, readable health information is vital to mitigate the impact of the COVID-19 pandemic. The aim of this study was to assess the quality and readability of online COVID-19 information using 6 validated tools. This is a cross-sectional study. "COVID-19" was searched across the three most popular English language search engines. Quality was evaluated using the DISCERN score, Journal of the American Medical Association benchmark criteria and Health On the Net Foundation Code of Conduct. Readability was assessed using the Flesch Reading Ease Score, Flesch-Kincaid Grade Level and Gunning-Fog Index. 41 websites were suitable for analysis. 9.8% fulfilled all JAMA criteria. Only one website was HONCode certified. Mean DISCERN score was 47.8/80 ("fair"). This was highest in websites published by a professional society/medical journal/healthcare provider. Readability varied from an 8th to 12th grade level. The overall quality of online COVID-19 information was "fair". Much of this information was above the recommended 5th to 6th grade level, impeding access for many.

Medicine, media and the law: The effect on training in obstetrics and gynaecology.

The inextricable link between medicine and the legal profession has flourished in the 21st century, with countless newspaper articles and social media content on medical cases visible at every juncture. This is particularly true in the speciality of obstetrics and gynaecology, with one of the highest rates of litigation of all medical specialities. We aimed to evaluate the influence of media and the legal environment on the career of trainees in obstetrics and gynaecology. Under the auspices of the Irish national training body, we distributed a 26-item questionnaire to doctors-in-training (DIT) working in obstetrics and gynaecology in the Republic of Ireland. Descriptive statistics and Chi-squared analyses were performed on the anonymised data. 151 DIT responded to the questionnaire, with a response rate of 86.2 % (sample size = 175). The majority were female (79.9 %, n = 121), Irish (85.5 %, n = 106) and had no children (67.0 %, n = 83). 86.7 % (n = 131) felt that the media did not have a positive impact on patients receiving care, and, further, unfairly represented the speciality (94.1 %; n = 142). Additionally, DIT felt that medico-legal issues had a negative impact on issues such as retention and recruitment. These two areas were implicated in over three quarters of DIT considering leaving the speciality. This study demonstrates that DIT perceive media scrutiny and litigation to have a negative effect on the speciality of obstetrics and gynaecology. Further support integrated into specialist training, is needed to ensure that trainees are adequately equipped to deal with both mainstream and social media as well as interactions they may have with the legal profession as they progress through their career.

The general populations' understanding of first trimester miscarriage: a cross sectional survey.

OBJECTIVES: Miscarriage is a common, yet for many, devastating adverse pregnancy outcome. However, despite this the level of public knowledge on the topic is sub-optimal. We aimed to examine the general public's knowledge of miscarriage as well as their health information seeking behaviours associated with this topic. STUDY DESIGN: We commissioned a national cross-sectional telephone survey of adults in the Republic of Ireland. 967 members of the general public consented to participate to this anonymised telephone survey. Sampling procedures ensured proportionality as per national standards. We examined respondents' definitions of miscarriage, its incidence and clinical findings, as well as the information seeking behaviours of the general population surrounding miscarriage. RESULTS: 699 (72%) of respondents provided an estimate of miscarriage frequency, with 28% of respondents correctly estimating that miscarriage occurs in 21-30% of pregnancies, with 61% under-estimating the incidence. Men were three times more likely than women to under-estimate (aOR3.5; 95% CI 2.4-4.9), as were those without children (aOR 1.7; 95% CI 1.2-2.6), or those living in urban areas (aOR 1.6; 95%CI 1.0-2.4. One third of respondents (33%) believed that the risk of miscarriage was higher following only one miscarriage. While 83% of respondents knew someone who had experienced a miscarriage, just over one third had discussed the topic of miscarriage with a family member/friend. CONCLUSIONS: The general populations' knowledge of miscarriage, its incidence and associated factors is concerning, as are their health information seeking behaviours. Improving the level of knowledge of the general public could be achieved by adopting the topic into existing public health and education strategies. This will allow those experiencing miscarriage to frame their experience and expectations.

The effect of Imatinib Mesylate in diffuse-type Tenosynovial Giant Cell Tumours on MR imaging and PET-CT.

INTRODUCTION: Recurrence rates remain high after surgical treatment of diffuse-type Tenosynovial Giant Cell Tumour (TGCT). Imatinib Mesylate (IM) blocks Colony Stimulating Factor1 Receptor (CSF1R), the driver mechanism in TGCT. The aim of this study was to determine if IM reduces the tumour metabolic activity evaluated by PET-CT and to compare this response with the response seen on MR imaging. MATERIALS AND METHODS: 25 Consecutive patients treated with IM (off label use) for locally advanced (N = 12) or recurrent (N = 13) diffuse-type TGCT were included, 15 male and median age at diagnosis 39 (IQR 31-47) years. The knee was most frequently affected (n = 16; 64%). The effect of IM was assessed pre- and post-IM treatment by comparing MR scans and PET-CT. MR scans were assessed by Tumour Volume Score (TVS), an estimation of the tumour volume as a percentage of the total synovial cavity. PET-CT scans were evaluated based on maximum standardized uptake value (SUV-max). Partial response was defined as more than 50% tumour reduction with TVS and a decrease of at least 30% on SUV-max. RESULTS: Median duration of IM treatment was 7.0 (IQR 4.2-11.5) months. Twenty patients (80%) discontinued IM treatment for poor response or intended surgery. Twenty patients experienced an adverse event grade 1-2, three patients grade 3 (creatinine increment, neutropenic sepsis, liver dysfunction). MR assessment of all joints showed 32% (6/19) partial response and 63% (12/19) stable disease, with a mean difference of 12% (P = 0.467; CI -22.4-46.0) TVS between pre- and post-IM and a significant mean difference of 23% (P = 0.021; CI 4.2-21.6) in all knee lesions. PET-CT, all joints, showed a significantly decreased mean difference of 5.3 (P = 0.004; CI 1.9-8.7) SUV-max between pre- and post-IM treatment (58% (11/19) partial response, 37% (7/19) stable disease). No correlation between MR imaging and PET-CT could be appreciated in 15 patients with complete radiological data. CONCLUSION: This study confirms the moderate radiological response of IM in diffuse-type TGCT. PET-CT is a valuable additional diagnostic tool to quantify response to tyrosine kinase inhibitor treatment. Its value should be assessed further to validate its efficacy in the objective measurement of biological response in targeted systemic treatment of TGCT.

COVID-19 in patients with lung cancer.

BACKGROUND: Patients with lung cancers may have disproportionately severe coronavirus disease 2019 (COVID-19) outcomes. Understanding the patient-specific and cancer-specific features that impact the severity of COVID-19 may inform optimal cancer care during this pandemic. PATIENTS AND METHODS: We examined consecutive patients with lung cancer and confirmed diagnosis of COVID-19 (n = 102) at a single center from 12 March 2020 to 6 May 2020. Thresholds of severity were defined a priori as hospitalization, intensive care unit/intubation/do not intubate ([ICU/intubation/DNI] a composite metric of severe disease), or death. Recovery was defined as >14 days from COVID-19 test and >3 days since symptom resolution. Human leukocyte antigen (HLA) alleles were inferred from MSK-IMPACT (n = 46) and compared with controls with lung cancer and no known non-COVID-19 (n = 5166). RESULTS: COVID-19 was severe in patients with lung cancer (62% hospitalized, 25% died). Although severe, COVID-19 accounted for a minority of overall lung cancer deaths during the pandemic (11% overall). Determinants of COVID-19 severity were largely patient-specific features, including smoking status and chronic obstructive pulmonary disease [odds ratio for severe COVID-19 2.9, 95% confidence interval 1.07-9.44 comparing the median (23.5 pack-years) to never-smoker and 3.87, 95% confidence interval 1.35-9.68, respectively]. Cancer-specific features, including prior thoracic surgery/radiation and recent systemic therapies did not impact severity. Human leukocyte antigen supertypes were generally similar in mild or severe cases of COVID-19 compared with non-COVID-19 controls. Most patients recovered from COVID-19, including 25% patients initially requiring intubation. Among hospitalized patients, hydroxychloroquine did not improve COVID-19 outcomes. CONCLUSION: COVID-19 is associated with high burden of severity in patients with lung cancer. Patient-specific features, rather than cancer-specific features or treatments, are the greatest determinants of severity.

Effects of maintaining eucalcemia following immunoactivation in lactating Holstein dairy cows.

Periparturient hypocalcemia is a common metabolic disorder and it is ostensibly associated with negative health and production outcomes. Acute infection also markedly decreases circulating Ca, but the reasons for and consequences of it on physiological and immunological parameters are unknown. Objectives were to evaluate the effects of maintaining eucalcemia on production, metabolic, and immune variables following an intravenous lipopolysaccharide (LPS) challenge. Twelve multiparous lactating Holstein cows (717 ± 20 kg of body weight; 176 ± 34 d in milk; parity 3 ± 0.2) were enrolled in a study containing 2 experimental periods (P); during P1 (3 d), cows consumed feed ad libitum and baseline values were obtained. At the initiation of P2 (4 d), cows were randomly assigned to 1 of 2 treatments: (1) LPS administered (LPS-Con; 0.5 µg/kg of body weight LPS; n = 6) or (2) LPS administered + eucalcemic clamp (LPS-Ca; 0.5 µg/kg of body weight LPS; Ca infusion; n = 6). Cows were fasted for the first 12 h during P2. After LPS administration, ionized Ca was determined every 15 min for 6 h and every 30 min for an additional 6 h and intravenous Ca infusion was adjusted in LPS-Ca cows to maintain eucalcemia. Blood ionized Ca was decreased 23% for the first 12 h postbolus in LPS-Con cows, and by design, Ca infusion prevented hypocalcemia. To maintain eucalcemia for the 12 h, 13.7 g of Ca was infused. The total Ca deficit (including Ca not secreted into milk) accumulated over the 12 h was 10.4 and 20.2 g for the LPS-Con and LPS-Ca treatments, respectively. Mild hyperthermia (0.8°C) occurred for ∼6 h post-LPS administration relative to P1. From 6 to 7 h postbolus rectal temperature from LPS-Ca cows was increased (0.6°C) relative to LPS-Con cows. On d 1 of P2, milk yield decreased (61%) in both treatments relative to P1. Relative to LPS-Con cows, milk yield decreased (15%) in LPS-Ca cows during P2. Overall, circulating LPS-binding protein continuously increased postbolus, and at 24 h LPS-binding protein levels in LPS-Ca cows were increased (80%) relative to LPS-Con cows. During P2, serum amyloid A increased (4-fold) in both treatments relative to P1. Administering LPS initially decreased circulating neutrophils, then cell counts progressively increased with time. Calcium infusion decreased neutrophil counts (40%) from 9 to 12 h postbolus relative to LPS-Con cows. Neutrophil function, as assessed by oxidative burst and myeloperoxidase production, did not differ due to treatment. In summary, maintaining eucalcemia (via intravenous Ca infusion) during an immune challenge appeared to intensify inflammation and adversely affect lactation performance.

Energetic metabolism, milk production, and inflammatory response of transition dairy cows fed rumen-protected glucose.

Objectives were to evaluate the effects of rumen-protected glucose (RPG) supplementation on milk production, post-absorptive metabolism, and inflammatory biomarkers in transition dairy cows. Fifty-two multiparous cows were blocked by previous 305-d mature-equivalent milk (305ME) yield and randomly assigned to 1 of 2 iso-energetic and iso-nitrogenous treatments: (1) control diet (CON; n = 26) or (2) a diet containing RPG (pre-fresh 5.3% of dry matter and 6.0% of dry matter postpartum; n = 26). Cows received their respective dietary treatments from d -21 to 28 relative to calving, and dry matter intake was calculated daily during the same period. Weekly body weight, milk composition, and fecal pH were recorded until 28 d in milk (DIM), and milk yield was recorded through 105 DIM. Blood samples were collected on d -7, 3, 7, 14, and 28 relative to calving. Data were analyzed using repeated measures in the MIXED procedure (SAS Institute Inc., Cary, NC) with previous 305ME as a covariate. Fecal pH was similar between treatments and decreased (0.6 units) postpartum. Dry matter intake pre- and postpartum were unaffected by treatment, as was milk yield during the first 28 or 105 DIM. Milk fat, protein, and lactose concentration were similar for both treatments. Blood urea nitrogen and plasma glucose concentrations were unaffected by treatment; however, results showed increased concentration of circulating insulin (27%), lower nonesterified fatty acids (28%), and lower postpartum ß-hydroxybutyrate (24%) in RPG-fed cows. Overall, circulating lipopolysaccharide-binding protein and haptoglobin did not differ by treatment, but at 7 DIM, RPG-fed cows had decreased lipopolysaccharide-binding protein and haptoglobin concentrations (31 and 27%, respectively) compared with controls. Supplemental RPG improved some biomarkers of post-absorptive energetics and inflammation during the periparturient period, changes primarily characterized by increased insulin and decreased nonesterified fatty acids concentrations, with a concomitant reduction in acute phase proteins without changing milk production and composition.

Mineral rich algae with pine bark improved pain, physical function and analgesic use in mild-knee joint osteoarthritis, compared to Glucosamine: A randomized controlled pilot trial.

INTRODUCTION: Osteoarthritis (OA) is characterised by synovial joint pain, functional disability and affects ∼13 % of people worldwide, of which ∼16-27 % report Knee-OA (KOA). Glucosamine (Glu) is the most widely used nutraceutical treatment for OA despite a lack of scientific consensus, therefore alternative nutraceutical treatments are required. The aim of this study was to investigate the effect of Lithothamnion species, seawater-derived magnesium and pine bark (Aq+) on pain, symptoms and improve physical function in symptomatic (sKOA), compared to Glu. METHODS: 358 participants were screened. In a double-blinded crossover pilot-trial, sKOA participant (n = 30) were randomly assigned to either the Glu group (2000 mg day-1) or Aq+ (3056 mg day-1) for 12 weeks (clinicaltrials.gov:NCT03106584). The Knee Injury and Osteoarthritis Outcome Score was used to assess subjective pain and symptoms. Timed-up-and-Go (TuG) and Six minute walking distance were used to assess functional change and analgesic use was recorded. RESULTS: Aq+ improved pain, with a large effect (P < 0.01, d' = 0.73, 95 %CI 0.201-1.265) and no change for Glu (d' = 0.38, P = 0.06). Only Aq+ improved pain (P < 0.05) for males (d' = 0.91, 95 %CI 0.162-1.667) and females (d' = 0.55, 95 %CI 0.210-1.299). In females, Aq+ improved TuG by -7.02 % (d' = 0.92, 95 %CI 1.699-0.141) while Glu worsened performance by 4.18 % (P = 0.04). Aq+ reduced analgesia by 71.6 %, compared to Glu (P = 0.02; d' = 0.82, 95 %CI 1.524-0.123). Aq+ was superior to Glu at improving pain, KOOS subscales, physical function and analgesia use in mild-sKOA. Given these data, Aq+ should be considered as a supplementary treatment for early-stage-KOA and may have the potential to reduce use of pain medication, although larger replication studies are required.