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.

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.

Validating a heat stress model: The effects of an electric heat blanket and nutritional plane on lactating dairy cows.

The efficacy of an electric heat blanket (EHB) has previously been confirmed as an alternative method to evaluate heat stress (HS). However, a pair-feeding design has not been used with the EHB model. Therefore, study objectives were to determine the contribution of the nutritional plane to altered metabolism and productivity during EHB-induced HS. Multiparous Holstein cows (n = 18; 140 ± 10 d in milk) were subjected to 2 experimental periods (P); during P1 (4 d), cows were in thermoneutral conditions with ad libitum feed intake. During P2 (4 d), cows were assigned to 1 of 2 treatments: (1) thermoneutral conditions and pair-fed (PF; n = 8) or (2) EHB-induced HS with ad libitum feed intake (n = 10). Overall, the EHB increased rectal temperature, vaginal temperature, skin temperature, and respiration rate (1.4°C, 1.3°C, 0.8°C, and 42 breaths/min, respectively) relative to PF cows. The EHB reduced dry matter intake (DMI; 47%) and, by design, PF cows had a similar pattern and extent of decreased DMI. Milk yield decreased in EHB and PF cows by 27.3% (12.1 kg) and 13.4% (5.4 kg), respectively, indicating that reduced DMI accounted for only ∼50% of decreased milk synthesis. Milk fat content tended to increase (19%) in the EHB group, whereas in the PF cows it remained similar relative to P1. During P2, milk protein and lactose contents tended to decrease or decreased (1.3 and 2.2%, respectively) in both EHB and PF groups. Milk urea nitrogen remained unchanged in PF controls but increased (34.2%) in EHB cows relative to P1. The EHB decreased blood partial pressure of CO2, total CO2, HCO3, and base excess levels (17, 16, 17, and 81%, respectively) compared with those in PF cows. During P2, the EHB and PF cows had similar decreases (4%) in plasma glucose content, but no differences in circulating insulin were detected. However, a group by day interaction was detected for plasma nonesterified fatty acids; levels progressively increased in PF controls but remained unaltered in the EHB cows. Blood urea nitrogen increased in the EHB cows (61%) compared with the PF controls. In summary, utilizing the EHB model indicated that reduced nutrient intake explains only about 50% of the decrease in milk yield during HS, and the postabsorptive changes in nutrient partitioning are similar to those obtained in climate-controlled chamber studies. Consequently, the EHB is a reasonable and economically feasible model to study environmental physiology of dairy cows.

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.

Effects of continuous and increasing lipopolysaccharide infusion on basal and stimulated metabolism in lactating Holstein cows.

Experimental objectives of this study were to characterize the systemic and intracellular metabolic response to continuous lipopolysaccharide (LPS) infusion in mid-lactation Holstein cows (169 ± 20 d in milk; 681 ± 16 kg of body weight). Following 3 d of acclimation, cows were enrolled in 2 experimental periods (P). During P1 (3 d), cows were fed ad libitum and baseline data were collected. In P2 (8 d), cows were assigned to 1 of 2 treatments: (1) saline-infused and pair-fed (CON-PF; i.v. sterile saline at 40 mL/h; n = 5) or (2) LPS-infused and fed ad libitum (LPS-AL; Escherichia coli O55:B5 at 0.017, 0.020, 0.026, 0.036, 0.055, 0.088, 0.148, and 0.148 µg/kg of body weight per hour for d 1 through 8, respectively; n = 6). During P2, CON-PF cows were pair-fed to LPS-AL cows to eliminate confounding effects of dissimilar nutrient intake. Blood samples were collected on d 1 and 2 of P1 and d 1, 3, 5, and 7 of P2. Following the P2 d 7 a.m. milking, adipose tissue, skeletal muscle, and liver biopsies were collected for reverse transcription quantitative PCR and Western blot analysis. To assess whole-body nutrient trafficking, an i.v. glucose tolerance test (GTT) was performed following the a.m. milking on P2 d 8; 4 h after the GTT, cows received an epinephrine challenge. During P2, there were no treatment differences in circulating glucose. Relative to P1, CON-PF cows had or tended to have decreased plasma ß-hydroxybutyrate and insulin (29 and 47%, respectively) during P2, whereas neither variable changed in LPS-AL cows, leading to an overall increase in ß-hydroxybutyrate and insulin (41 and 140%, respectively) relative to CON-PF cows. Circulating nonesterified fatty acids were increased from d 1 to 3 and subsequently decreased from d 3 to 7 in cows from both treatments. Blood urea nitrogen gradually decreased in CON-PF cows and increased in LPS-AL cows from d 1 to 5 of P2, resulting in an overall 25% increase in LPS-AL versus CON-PF cows. In response to the GTT, the glucose and insulin area under the curve were increased 33 and 56%, respectively, in LPS-AL compared with CON-PF cows; changes reflective of whole-body insulin resistance. However, protein abundance of insulin signaling markers within muscle, liver, and adipose tissue were similar between treatments. There were no observable treatment differences in the glucose or nonesterified fatty acids response to the epinephrine challenge. No treatment differences were observed in hepatic mRNA abundance of key gluconeogenic or lipid export enzymes. In conclusion, chronic LPS exposure altered multiple parameters of basal and stimulated metabolism, but did not appear to affect the molecular machinery evaluated herein.

Using Atomic Force Microscopy to Predict Tumor Specificity of ICAM1 Antibody-Directed Nanomedicines.

Atomic force microscopy (AFM) is a powerful tool to detect in vitro antibody-antigen interactions. To date, however, AFM-measured antibody-antigen interactions have yet to be exploited to predict in vivo tumor specificity of antibody-directed nanomedicines. In this study, we have utilized AFM to directly measure the biomechanical interaction between live triple negative breast cancer (TNBC) cells and an antibody against ICAM1, a recently identified TNBC target. For the first time, we provide proof-of-principle evidence that in vitro TNBC cell-ICAM1 antibody binding force measured by AFM on live cells more precisely correlates with in vivo tumor accumulation and therapeutic efficacy of ICAM1 antibody-directed liposomes than ICAM1 gene and surface protein overexpression levels. These studies demonstrate that live cell-antibody binding force measurements may be used as a novel in vitro metric for predicting the in vivo tumor recognition of antibody-directed nanomedicines.

Image-guided percutaneous management of duodenal perforation following endoscopic retrograde cholangiopancreatography (ERCP): assessment of efficacy and safety.

AIM: To evaluate the efficacy and safety of image-guided percutaneous drain placement for duodenal perforation following endoscopic retrograde cholangiopancreatography (ERCP). MATERIALS AND METHODS: A retrospective review of 7,249 ERCP examinations over a 10-year period was performed to identify cases of duodenal perforation. Indications for ERCP were documented, along with the clinical, laboratory, and imaging findings following perforation. Technical and clinical success of percutaneous drain placement was reviewed. RESULTS: Duodenal perforation occurred in 35 of 7,249 patients during the study period. Management included primary surgical debridement (n=2), conservative management consisting of bowel rest, nasogastric/nasojejunal tube placement (n=20), and percutaneous catheter drainage (n=13). Twenty-seven percutaneous drainage catheters were placed in 13 patients, with a mean duration of catheter drainage of 30.9 days (range 4-108 days). Ten patients were successfully treated with percutaneous management alone, and three required subsequent surgical intervention. CONCLUSION: Percutaneous management of duodenal perforation related to ERCP is associated with high technical and clinical success, and may obviate the need for surgical intervention.

First International Public Health Film Competition 2016-reflections on the development and use of competition judging criteria.

Background: Film competitions can be a helpful method to understand issues of quality in health films. In this paper, we describe the development and use of explicit quality criteria to identify the 'best' films for the first ever international public health film competition. Methods: A film selection committee encompassing a range of stakeholders was compiled. The committee drew up 10 explicit quality criteria to judge films drawing upon other film festival's selection criteria. These criteria were then applied to a broad range of health-related films entered into a film competition to select the 'best' film to screen. Results: Eighty-four films from 20 different countries were submitted to the public health film competition. The originality of the subject covered by the film, the public health importance of the issue and story-telling approach in the film were found to be the most discriminatory criteria to select films. Conclusion: Selection of health films for festivals can be undertaken using explicit quality criteria. There are a number of advantages to such an approach; however, explicit selection involves a large commitment of resources from film festival organizers and there is further research required to test the validity of the quality criteria applied to health-related films.

Accuracy of 64-section MDCT in the diagnosis of cruciate ligament tears.

AIM: To evaluate the accuracy of non-arthrographic 64-section multidetector computed tomography (CT) in the assessment of cruciate ligament tears. A secondary goal was to determine its accuracy in the diagnosis of additional soft-tissue injuries around the knee. MATERIALS AND METHODS: Forty consecutive outpatients underwent same-day magnetic resonance imaging (MRI) and 64-slice multidetector CT (MDCT) of the knee in this prospective study. MDCT images were independently evaluated for integrity of the anterior (ACL) and posterior cruciate ligaments (PCL), medial and lateral menisci, and medial and lateral collateral ligaments. Recognised secondary signs of ACL tears were also documented. MRI images were subsequently assessed by two radiologists and a consensus reached. RESULTS: The sensitivity of MDCT for ACL tears was 87.5-100%, with a specificity of 100%. The presence of one or more secondary signs of ACL tears on MDCT had a sensitivity of 50-87.5% with a specificity of 100%. The sensitivity of MDCT for PCL tears was 0-25% with a specificity of 100%. The sensitivity for meniscal tears was 9.1-23.1% with a specificity of 96.3-100%. CONCLUSION: 64-section MDCT has very high sensitivity and specificity for ACL tears and, as on MRI, secondary signs, such as buckling of the PCL, are also useful in their diagnosis. MDCT has a low sensitivity for other soft-tissue injuries at the knee; however, its high specificity indicates that apparent PCL, meniscal, and collateral ligament tears can reliably be treated as true-positive findings.

Development of malignant lymphoma after metal-on-metal hip replacement: a case report and review of the literature.

A number of previous studies have reported a potential risk of malignancy, particularly hematological malignancy, developing in patients receiving a metal-on-metal (MoM) hip replacement. We report a case of malignant lymphoma that arose in a patient who had an MoM hip arthroplasty complicated by development of a pseudotumour. The tumour was a B cell follicular lymphoma that involved lymph nodes and bone. Metal ions are known to have a genotoxic effect on lymphoid cells. Although epidemiological studies have not established that there is an increased risk of lymphoma associated with MoM implants, only a relatively short time period has elapsed since re-introduction of this type of implant and long-term follow-up of patients with MoM implants is indicated.

Menorrhagia Outcomes of Minimally Invasive Treatments (MOMITS): A 2 to 5-year follow-up.

We conducted a retrospective postal questionnaire-based study to assess the effectiveness and patient experience of minimally invasive treatments for menorrhagia by performing a two- to five-year follow up of patient symptoms. Questionnaires were distributed to 111 and 117 women following thermal balloon endometrial ablation (TBEA) and levonorgestrel intrauterine system (LNG-IUS), with response rates of 58.5% and 43.6% respectively. Sanitary pad use during the heaviest day of bleeding reduced by 8.4 and 5.2 pads in the TBEA and LNG-IUS groups respectively (p<0.05). An improvement in patients' quality of life (QOL) score exceeding 10 points was found in 79% and 61% in the TBEA and LNG-IUS groups respectively. Patient satisfaction (PS) improved in all areas, more so regarding participation in social activities in the TBEA group (p<0.05). Women undergoing TBEA would recommend the procedure to other women in 95%, and 93% in the LNG-IUS group. TBEA and LNG-IUS are highly acceptable management options for the treatment of menorrhagia, with improvement in QOL, PS and menstrual blood loss.

Updated analysis: central venous access device infection rates in an expanded cohort of paediatric patients with severe haemophilia receiving prophylactic recombinant tissue plasminogen activator.

INTRODUCTION: Central venous access devices (CVADs) are used in the care of paediatric haemophilic patients with difficult peripheral access, but their use is limited by complications such as infection. We previously published our experience with monthly recombinant tissue plasminogen activator (r-tPA) administration to CVADs of haemophilic patients as an intervention for infection prophylaxis, which suggested a 10-fold decrease in infection rate compared to published rates without r-tPA. AIM: This study was conducted to assess the CVAD infection rate in an expanded haemophilia cohort receiving r-tPA over an extended period. METHODS: A retrospective review was performed on patients with haemophilia who received monthly r-tPA to CVADs, with data collected from January 1, 2008 to December 31, 2012. The data were merged with the previously reported data set (collected from June 1, 1998 to December 31, 2007). RESULTS: Over the entire observation period, there were 46 350 CVAD days among 32 patients [26 severe factor VIII (FVIII) deficiency, six severe FIX deficiency]. Eight patients received immune tolerance therapy for inhibitors and 24 patients received prophylactic factor administration. No patients were HIV positive. Three infections were observed, with an overall infection rate of 0.06 infections per 1000 CVAD days. CONCLUSIONS: A low CVAD infection rate, similar to that observed in our previous study (0.04 per 1000 CVAD days), was observed in this expanded haemophilia cohort treated with prophylactic r-tPA, supporting the use of monthly r-tPA as CVAD infection prophylaxis in haemophilia patients.

Primary synovial chondromatosis: a reassessment of malignant potential in 155 cases.

OBJECTIVE: Primary synovial chondromatosis (PSC) is a rare disorder characterised by cartilage formation in synovium-lined joints, tendon sheaths and bursae. It is thought that PSC cartilage arises from the proliferation of mesenchymal cells, which exhibit cartilaginous metaplasia in subintimal connective tissue. There are reports of transformation of PSC to chondrosarcoma, although the precise incidence and nature of this complication is uncertain. In this study we carried out a retrospective review PSC to determine the incidence of sarcomatous change in this condition, in addition to the clinical, radiological and pathological features that characterise this complication MATERIALS AND METHODS: We reviewed 155 cases of PSC and identified 4 cases (3 in the hip joint; 1 in the elbow joint) of aggressive behaviour and chondrosarcoma-like histology. RESULTS: Radiologically, these cases were all reported as showing features consistent with PSC and aggressive extra-articular soft tissue/bone involvement. Histologically, in addition to typical features of PSC, there was morphological evidence of peri-articular soft tissue and, in 2 cases, bone involvement by an infiltrating cartilaginous tumour. These tumours all behaved as locally aggressive neoplasms and did not give rise to metastasis. CONCLUSION: Our findings show that chondrosarcoma arises infrequently in PSC (approximately 2.5 %), and that this complication occurs most commonly in the hip joint (approximately 11 % of cases of hip PSC). These tumours behaved mainly as low-grade, locally aggressive tumours analogous to atypical cartilaginous tumour of bone/grade 1 chondrosarcoma of bone.

12 weeks of simulated barefoot running changes foot-strike patterns in female runners.

To investigate the effect of a transition program of simulated barefoot running (SBR) on running kinematics and foot-strike patterns, female recreational athletes (n=9, age 29 ± 3 yrs) without SBR experience gradually increased running distance in Vibram FiveFingers SBR footwear over 12 weeks. Matched controls (n=10, age 30 ± 4 yrs) continued running in standard footwear. A 3-D motion analysis of treadmill running at 12 km/h(-1) was performed by both groups, barefoot and shod, pre- and post-intervention. Post-intervention data indicated a more-forefoot strike pattern in the SBR group compared to controls; both running barefoot (P>0.05), and shod (P<0.001). When assessed barefoot, there were significant kinematic differences across time in the SBR group for ankle flexion angle at toe-off (P<0.01). When assessed shod, significant kinematic changes occurred across time, for ankle flexion angles at foot-strike (P<0.001) and toe-off (P<0.01), and for range of motion (ROM) in the absorptive phase of stance (P<0.01). A knee effect was recorded in the SBR group for flexion ROM in the absorptive phase of stance (P<0.05). No significant changes occurred in controls. Therefore, a 12-week transition program in SBR could assist athletes seeking a more-forefoot strike pattern and "barefoot" kinematics, regardless of preferred footwear.

Conjoined twins: experience in an Irish tertiary centre.

Conjoined twins are rare, with a reported incidence of 0.19 per 10,000 pregnancies in Europe. We discuss four spontaneous conjoined twin pregnancies presenting to a tertiary referral centre from 2005 to 2011, diagnosed on antenatal dating ultrasound. The cases were monitored closely throughout pregnancy by a multidisciplinary team, with serial surveillance, including ultrasound, fetal echocardiography, magnetic resonance imaging, amniocentesis and further referral to cardiology and paediatric surgery specialists, where indicated. Three female sets were determined antenatally to be not surgically separable; these infants were managed palliatively following a live birth. The male set of conjoined twins was accepted for surgical separation at Great Ormond Street Hospital, London, which was successfully performed electively at 4 months. Of interest, all four parents reside within 20 km of each other, representing a possible cluster of cases. The incidence of conjoined twins in our local population is approximately 0.63 per 10,000 over an 8-year period from 2005 to 2012. This case series highlights a cluster of conjoined twins, managed to viability and delivered in a tertiary referral centre.

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.

Low-temperature-SEM study of dihedral angles in the ice-I/sulfuric acid partially molten system.

The transport and mechanical properties of partially molten materials are influenced by the wetting behaviour of the melt with respect to the crystalline solid. The equilibrium microstructure of an ice + melt system was examined using low-temperature scanning electron microscopy. The samples were prepared by spraying a liquid solution of H(2) O-H(2) SO(4) into liquid nitrogen and packing the frozen particulates into aluminium capsules. Samples were then sintered at -35°C or -55°C (above the eutectic temperature, T(E) =-62°C) for various durations and were quenched in liquid nitrogen to capture the equilibrium microstructure. This paper reports the first quantitative measurements of dihedral angle in this system. The measured median dihedral angle between the solid and vitrified melt is approximately 26 ± 2° at -35°C and increases slightly as temperature decreases and approaches the solidus (32 ± 3° at -55°C).