Ivermectin inhibits replication of the malignant catarrhal fever virus alcelaphine herpesvirus 1.

Malignant catarrhal fever is a lymphoproliferative disease of cattle and other ungulates that is caused by genetically and antigenically related gamma herpesviruses of the genus Macavirus. Infection of the natural host species is efficient and asymptomatic but spread to susceptible hosts is often fatal with clinical signs including fever, depression, nasal and ocular discharge. There is no recognised treatment for MCF but a vaccine for one MCF virus, alcelaphine herpesvirus 1 (AlHV-1), has been described. In this paper we describe the inhibition of AlHV-1 replication and propagation by the anthelminthic drug ivermectin. Concentrations of 10 µM or greater led to significant reductions in both copy number and viable titre of virus tested in culture medium, with little replication detected at over 20 µM ivermectin. In the absence of alternative treatments, further testing of ivermectin as a candidate antiviral treatment for MCF may therefore be justified.

Higher alpha diversity and Lactobacillus blooms are associated with better engraftment after Fecal Microbiota Transplant in Inflammatory Bowel Disease.

Background: Fecal Microbiota Transplant (FMT) has proven effective in treating recurrent Clostridioides difficile infection (rCDI) and has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. However, there is little known regarding predictors of engraftment. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn's disease (CD) and ulcerative colitis (UC). Results: Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. The treatment arm received seven days of antibiotics followed by FMT enema and then capsules weekly for seven weeks. We enrolled four subjects with CD and 11 with UC, ages 14-29 years. Due to weekly stool sampling, we were able to create a time series of alpha diversity, beta diversity and engraftment as they related to clinical response. Subjects exhibited a wide range of microbial diversity and donor engraftment as FMT progressed. Specifically, engraftment ranged from 26% to 90% at week 2 and 3% to 92% at two months. Consistent with the current literature, increases over time of both alpha diversity (p< 0.05) and donor engraftment (p< 0.05) correlated with improved clinical response. Additionally, our weekly time series enabled an investigation into the clinical and microbial correlates of engraftment at various time points. We discovered that the post-antibiotic but pre-FMT time point, often overlooked in FMT trials, was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial with publicly available weekly sequencing data. Conclusions: We found that higher residual alpha diversity and Lactobacillus blooms after antibiotic treatment correlated with improved engraftment and clinical response to FMT. Future studies should closely examine the host microbial communities pre-FMT and the impact of antibiotic preconditioning on engraftment and response.

A Meta-Analysis of Parenting Interventions for Immigrants.

In light of increasing migration rates and the unique experiences of immigrants, this meta-analysis examined the effects of parenting interventions for immigrants. Specifically, we described the characteristics of parenting interventions for immigrants, examined cultural and/or linguistic adaptations made to the interventions, analyzed intervention effects, and examined potential moderating variables. Four electronic databases were searched in February 2021 for peer-reviewed articles published in English. Studies that involved immigrant parents, used an experimental design, and investigated an intervention targeting skills that parents could use directly with their children were included. Sixteen group design and two single-case design studies met inclusion criteria. The risk of publication bias was examined using funnel plots and found to be low. Overall, most parenting interventions for immigrants focused on young children and were delivered in groups. Interventions produced small to moderate effects on parent and child outcomes, which is comparable to those for the general population. All studies made cultural adaptations, with the most common being language. Moderator analyses indicate that the effects of interventions with surface structure adaptations were similar to those with deep structure adaptations. Limitations included the low methodological rigor of included studies and the exclusion of grey literature. More works of research on the relative effects of specific adaptations, such as ethnicity matching, are needed to better serve this population.

Prospective cohort study reveals unexpected aetiologies of livestock abortion in northern Tanzania.

Livestock abortion is an important cause of productivity losses worldwide and many infectious causes of abortion are zoonotic pathogens that impact on human health. Little is known about the relative importance of infectious causes of livestock abortion in Africa, including in subsistence farming communities that are critically dependent on livestock for food, income, and wellbeing. We conducted a prospective cohort study of livestock abortion, supported by cross-sectional serosurveillance, to determine aetiologies of livestock abortions in livestock in Tanzania. This approach generated several important findings including detection of a Rift Valley fever virus outbreak in cattle; high prevalence of C. burnetii infection in livestock; and the first report of Neospora caninum, Toxoplasma gondii, and pestiviruses associated with livestock abortion in Tanzania. Our approach provides a model for abortion surveillance in resource-limited settings. Our findings add substantially to current knowledge in sub-Saharan Africa, providing important evidence from which to prioritise disease interventions.

Complications of Morbid Obesity in the Treatment of Acetabular Fractures: Re-evaluating Outcomes a Decade Later.

OBJECTIVES: To determine the rate of perioperative complications between morbidly obese (body mass index greater than 40 kg/m2) and nonmorbidly obese patients undergoing operative treatment of acetabular fractures across 2 periods (2000-2005 and 2012-2019). DESIGN: Retrospective, case-control study. SETTING: Level I academic trauma center. PATIENTS: Four hundred thirty-five consecutive patients from 2000 to 2005 and 216 consecutive patients from 2012 to 2019 with acetabular fractures treated by a single surgeon. INTERVENTION: Operative fixation of acetabular fracture. MAIN OUTCOME MEASUREMENTS: Outcome variables include positioning time, operative time, estimated blood loss, hospital stay, wound complications, and perioperative complications. RESULTS: Twenty-eight morbidly obese and 188 nonmorbidly obese patients from 2012 to 2019, as well as 41 morbidly obese patients and 394 nonmorbidly obese patients from 2000 to 2005 were included in the study. The relative risk (RR) of wound complications between 2012 and 2019 groups was significantly higher for morbidly obese patients (RR = 5.31, P = 0.009) but has decreased significantly for morbidly obese patients between 2000-2005 and 2012-2019 (RR = 0.31, P = 0.017). The rate of total perioperative complications was similar between morbidly obese and nonmorbidly obese groups from 2012 to 2019 (21% vs. 8%, P = 0.230). For morbidly obese patients, the rate of total perioperative complications decreased significantly between 2000-2005 and 2012-2019 (63% vs. 21% P = 0.010). CONCLUSION: Acetabular fracture surgery can be safely performed in morbidly obese patients. Although obesity remains a significant risk factor for wound complications, the risk for morbidly obese patients has decreased significantly since our initial investigation because of adaptations to surgical techniques and surgeon's experience. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Development of a recombinant ELISA for ovine herpesvirus 2, suitable for use in sheep.

The minor capsid protein of ovine herpesvirus 2, identified as a potential antigen for serological testing, was over-expressed and purified to allow its assessment in ELISA. The corresponding gene sequence (OvHV-2 orf65, Ov65) was modified to incorporate epitope tags and internal restriction enzyme sites in an E. coli codon-optimised version of the gene. This codon-optimised gene was then subject to internal deletions to identify regions of the protein that could be removed while maintaining protein solubility and antigenicity. It was found that a derivative with deletion of the conserved 5'-end of the gene (Ov65delB) expressed a polypeptide that was soluble when over-expressed in bacteria and was detected by OvHV-2 specific sera. Proteomic analysis of the affinity purified Ov65delB showed that it contained multiple predicted Ov65 tryptic peptides but also showed contamination by co-purifying E. coli proteins. An indirect ELISA, based on this affinity-purified OV65delB, was optimised for use with sheep and cattle samples and cut-off values were established based on known negative serum samples. Analysis of groups of samples that were either presumed infected (UK sheep) or tested OvHV-2 positive or negative by PCR (cattle MCF diagnostic samples) showed that the assay had 95 % sensitivity and 96 % specificity for sheep serum; and 80 % sensitivity and 95 % specificity for cattle serum. The lower sensitivity with cattle samples appeared to be due to a lack of serological response in some MCF-affected cattle. This recombinant antigen therefore shows promise as the basis of an inexpensive, simple and reliable test that can be used to detect OvHV-2-specific antibody responses in both MCF-affected animals and in OvHV-2 reservoir hosts.

Tibial Shaft and Pilon Fractures With Associated Syndesmotic Injury: A Matched Cohort Assessment.

OBJECTIVE: To determine the outcomes of pilon and tibial shaft fractures with syndesmotic injuries compared with similar fractures without syndesmotic injury. DESIGN: Retrospective case-control study. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: All patients over a 5-year period (2012-2017) with tibial shaft or pilon fractures with a concomitant syndesmotic injury and a control group without a syndesmotic injury matched for age, OTA/AO fracture classification, and Gustilo-Anderson open fracture classification. INTERVENTION: Preoperative or intraoperative diagnosis of syndesmotic injury with reduction and fixation of both fracture and syndesmosis. MAIN OUTCOME MEASUREMENT: Rates of deep infection, nonunion, unplanned reoperation, and amputation in patients with a combined syndesmotic injury and tibial shaft or pilon fracture versus those without a syndesmotic injury. RESULTS: A total of 30 patients, including 15 tibial shaft and 15 pilon fractures, were found to have associated syndesmotic injuries. The matched control group comprised 60 patients. The incidence of syndesmotic injury in all tibial shaft fractures was 2.3% and in all pilon fractures was 3.4%. The syndesmotic injury group had more neurologic injuries (23.3% vs. 8.3% P = 0.02), more vascular injuries not requiring repair (30% vs. 15%, P = 0.13), and a higher rate compartment syndrome (6.7% vs. 0%, P = 0.063). Segmental fibula fracture was significantly more common in patients with a syndesmotic injury (36.7% vs. 13.3%, P = 0.04). Fifty percent of the syndesmotic injury group underwent an unplanned reoperation with significantly more unplanned reoperations (50% vs. 27.5%, P = 0.04). The syndesmotic group had a significantly higher deep infection rate (26.7% vs. 8.3% P = 0.047) and higher rate of amputation (26.7% vs. 3.3% P = 0.002) while the nonunion rate was similar (17.4% vs. 16.7% P = 0.85). CONCLUSIONS: Although syndesmotic injuries with tibial shaft or pilon fractures are rare, they are a marker of a potentially limb-threatening injury. Limbs with this combined injury are at increased risk of deep infection, unplanned reoperation, and amputation. The presence of a segmental fibula fracture should raise clinical suspicion to evaluate for syndesmotic injury. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The Clamshell Osteotomy for Diaphyseal Malunion in Deformity Correction and Fracture Surgery.

Diaphyseal malunion poses a great challenge for the orthopedic surgeon, and an inundation of morbidity for the patient. Diaphyseal malunion can cause altered gait, adjacent joint osteoarthritis and body dissatisfaction. This problem is fraught with complications without surgical intervention. There is a myriad of options for the management of a diaphyseal malunion. The clamshell osteotomy was engendered to ameliorate the difficulty in managing this issue. This technique is a viable option to correct diaphyseal malunion about the femur and tibia. Recently, the indications of a clamshell osteotomy have been expanded to function as a derotational or shortening osteotomy.

Geriatric Acetabular Fractures and Femoral Head Protrusio: Methods of Fixation and the Option of Total Hip Arthroplasty.

SUMMARY: Currently, the literature is unclear regarding the optimal treatment algorithm for geriatric acetabular fractures. In a recent epidemiological study, 70% of all acetabular fractures in patients older than 65 years were classified as either associated both column or anterior column/posterior hemitransverse. Within the subset of these fractures, variants with significant femoral head protrusio, which is defined as the displacement of the femoral head medial to the ilioischial line, present with unique challenges. Goals of treatment in these cases should include surgical techniques that minimize the physiologic insult for the patient yet restore hip congruity and stability. "Fix and replace" is becoming an increasingly popular approach in the acute setting; however, its indications are not yet well-established. At our institution, we often favor open reduction and internal fixation alone as an effective and efficient way to treat the protrusio variant, even at the expense of protected weight-bearing. In the following article, we present a systematic approach for the management of geriatric acetabular fracture femoral head protrusio along with specific case examples.

Analysis of immune responses to attenuated alcelaphine herpesvirus 1 formulated with and without adjuvant.

The experimental vaccine for bovine malignant catarrhal fever consists of viable attenuated alcelaphine herpesvirus 1 (AlHV-1) derived by extensive culture passage, combined with an oil-in-water adjuvant, delivered intramuscularly. This immunisation strategy was over 80% effective in previous experimental and field trials and protection appeared to be associated with induction of virus-neutralising antibodies. Whether the vaccine virus is required to be viable at the point of immunisation and whether adjuvant is required to induce the appropriate immune responses remains unclear. To address these issues two studies were performed, firstly to analyse immune responses in the presence and absence of adjuvant and secondly, to investigate immune responses to vaccines containing adjuvant plus viable or inactivated AlHV-1. The first study showed that viable attenuated AlHV-1 in the absence of adjuvant induced virus-specific antibodies but the titres of virus-neutralising antibodies were significantly lower than those induced by vaccine containing viable virus and adjuvant, suggesting adjuvant was required for optimal responses. In contrast, the second study found that the vaccine containing inactivated (>99.9%) AlHV-1 induced similar levels of virus-neutralising antibody to the equivalent formulation containing viable AlHV-1. Together these studies suggest that the MCF vaccine acts as an antigen depot for induction of immune responses, requiring adjuvant and a suitable antigen source, which need not be viable virus. These observations may help in directing the development of alternative MCF vaccine formulations for distribution in the absence of an extensive cold chain.

Overcoming Language Barriers between Interventionists and Immigrant Parents of Children with Autism Spectrum Disorder.

This study used a video prompting intervention to overcome language barriers between English-speaking trainers and Spanish-speaking immigrant parents of children with autism. Parents were taught instructional skills targeting independent dressing. A multiple baseline design across three families and a replication using an alternating treatments design with a fourth family were used to evaluate the effects of the intervention. All mothers reached mastery criterion and generalization of instructional skills was observed for three mothers, with treatment gains maintaining during follow-up. Improvement in independent dressing skills was observed for four children. Findings suggest that video prompting can be used to teach immigrant parents of children with autism who have limited English proficiency when there is a language mismatch between parents and trainers.

Optimisation of waste clean-up after large-scale disasters.

Disaster waste clean-up after large disasters is one of the core activities at the recovery stage of disaster management, which aims to restoring the normal functioning of the disaster affected area. In this paper we considered a waste clean-up system consists of (i) demolition operation, (ii) collection of waste from customer nodes to temporary disaster waste management sites (TDWMSs), (iii) processing at TDWMSs, and (iv) transportation of the waste to final disposal sites in the recovery of disasters. A multi-objective mixed integer programming model is developed to minimise the total clean-up cost and time. Three different approaches are developed to solve the problem, which are tested with artificial instances and a real case study. Results of artificial instances indicate that the models developed can be used to obtain close to optimal solutions within an acceptable computing time. Results of the case study can facilitate the decision-makers to develop the waste clean-up with minimised total cost and clean-up time by selecting the right location of TDWMSs and setting up the proper waste clean-up schedule.

A Model to Improve the Workflow for Radiation Treatments in the Era of Bundled Payments: A Quality Improvement Project Report.

The Centers for Medicare and Medicaid Services has proposed alternate payment models to improve the efficiency and decrease the redundancy of health care. Bundled payments or episode-based care is one example. Herein, we report on the successful implementation of a quality improvement project in which changing the clinical workflow for postoperative radiation treatment to the hip to prevent heterotopic ossification improved the efficiency of patient care and decreased cost by eliminating redundant imaging through multidisciplinary participation. This project is a model for interdisciplinary collaboration to improve patient care and reduce unnecessary health care spending in the era of bundled payment/episodes of care program implementation.

Bovine viral diarrhoea virus loses quasispecies diversity rapidly in culture.

Bovine viral diarrhoea (BVD) is an important disease of cattle, with significant impacts on animal health and welfare. The wide host range of the causative pestiviruses may lead to formation of virus reservoirs in other ruminant or wildlife species, presenting a concern for the long-term success of BVD eradication campaigns. It is likely that the quasispecies nature of these RNA viruses contributes to their interspecies transmission by providing genetic plasticity. Understanding the spectrum of sequence variants present in persistently infected (PI) animals is, therefore, essential for studies of virus transmission. To analyse quasispecies diversity without amplification bias, we extracted viral RNA from the serum of a PI cow, and from cell culture fluid after three passages of the same virus in culture, to produce cDNA without amplification. Sequencing of this material using Illumina 250 bp paired-read technology produced full-length virus consensus sequences from both sources and demonstrated the quasispecies diversity of this pestivirus A genotype 1a field strain within serum and after culture. We report the distribution and diversity of over 800 SNPs and provide evidence for a loss of diversity after only three passages in cell culture, implying that cultured viruses cannot be used to understand quasispecies diversity and may not provide reliable molecular markers for source tracing or transmission studies. Additionally, both serum and cultured viruses could be sequenced as a set of 25 overlapping PCR amplicons that demonstrated the same consensus sequences and the presence of many of the same quasispecies variants. The observation that aspects of the quasispecies structure revealed by massively parallel sequencing are also detected after PCR and Sanger sequencing suggests that this approach may be useful for small or difficult to analyse samples.

Efficacy of Fecal Microbiota Transplantation for Clostridium difficile Infection in Children.

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI. METHODS: We performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMT at 18 pediatric centers, from February 1, 2004, to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT. RESULTS: Of 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39-5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26-4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05-4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04-1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations. CONCLUSIONS: Based on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients-factors associated with success differ from those of adult patients.

A randomised vaccine field trial in Kenya demonstrates protection against wildebeest-associated malignant catarrhal fever in cattle.

Wildebeest-associated malignant catarrhal fever (WA-MCF), a fatal disease of cattle caused by alcelaphine herpesvirus 1 (AlHV-1), is one of the most important seasonal diseases of cattle in wildebeest endemic areas, with annual incidence reaching 10%. Here we report efficacy of over 80% for a vaccine based on the attenuated AlHV-1 C500 strain, in preventing fatal WA-MCF in cattle exposed to natural wildebeest challenge. The study was conducted at Kapiti Plains Ranch Ltd, south-east of Nairobi, Kenya. In 2016, 146 cattle were selected for a randomised placebo-controlled trial. Cattle were stratified according to breed and age and randomly assigned to groups given vaccine or culture medium mixed with Emulsigen®. Cattle received prime and boost inoculations one month apart and few adverse reactions (n = 4) were observed. Indirect ELISA demonstrated that all cattle in the vaccine group developed a serological response to AlHV-1. The study herd was grazed with wildebeest from one month after booster vaccination. Three cattle, two that received vaccine and one control, succumbed to conditions unrelated to WA-MCF before the study ended. Twenty-five cattle succumbed to WA-MCF; four of the remaining 71 cattle in the vaccine group (5.6%) and 21 of the remaining 72 control cattle (29.2%; χ2 = 13.6, df = 1, p < 0.001). All of the WA-MCF affected cattle were confirmed by PCR to be infected with AlHV-1 and in 23 cases exhibited histopathology typical of WA-MCF. Vaccine efficacy was determined to be 80.6% (95% CI 46.5-93.0%). Hence, the AlHV-1 C500 vaccine is a safe and potentially effective novel method for controlling WA-MCF in cattle. The implementation of this vaccine may have significant impacts on marginalised cattle keeping communities.