Use of a local anaesthetic and antiseptic wound formulation for the treatment of lambs naturally infected with Orf virus.

Contagious ecthyma (CE) is a worldwide highly contagious zoonotic viral skin disease of sheep and goats. Treatment for Orf virus (ORFV) infection usually involves topical and oral antibiotics. An anaesthetic and antiseptic topical gel (Multisolfen® or Tri-Solfen®; MS®, Medical Ethics, Australia) has been documented as an efficacious therapy for lesions from mucosal and epithelial viral infections in ruminants. The present study tested a new treatment protocol of MS® for CE therapy on-farm in 150 lambs naturally infected with ORFV. Lambs were divided into three cohorts of 50 lambs each (C, D and E). Cohort C was treated with MS® 3 times with an interval of 3 days between treatments, cohort D was treated daily with hypochlorous acid, whilst cohort E served as untreated controls. The lambs were examined clinically every two days, weight measured weekly, with whole blood and sterile swabs from ORFV lesions collected for haematological analysis and specific ORFV PCR. Cohort C presented fewer lambs displaying ORFV-associated lesions than other cohorts at different times of the experiment. Further, lesions treated with MS® were milder compared with other cohorts. However, following cessation of therapy, most of the lambs again developed ORFV-associated lesions. No differences between cohorts were observed in weight, haematological and PCR results. These findings suggest that topical treatment with MS® is effective for CE in field conditions, especially in the first stages of the clinical course, although treatment with MS® may need to be extended a minimum of 4 weeks.

Implementing adaptive e-learning for newborn care in Tanzania: an observational study of provider engagement and knowledge gains.

INTRODUCTION: To improve healthcare provider knowledge of Tanzanian newborn care guidelines, we developed adaptive Essential and Sick Newborn Care (aESNC), an adaptive e-learning environment. The objectives of this study were to (1) assess implementation success with use of in-person support and nudging strategy and (2) describe baseline provider knowledge and metacognition. METHODS: 6-month observational study at one zonal hospital and three health centres in Mwanza, Tanzania. To assess implementation success, we used the Reach, Efficacy, Adoption, Implementation and Maintenance framework and to describe baseline provider knowledge and metacognition we used Howell's conscious-competence model. Additionally, we explored provider characteristics associated with initial learning completion or persistent activity. RESULTS: aESNC reached 85% (195/231) of providers: 75 medical, 53 nursing and 21 clinical officers; 110 (56%) were at the zonal hospital and 85 (44%) at health centres. Median clinical experience was 4 years (IQR 1-9) and 45 (23%) had previous in-service training for both newborn essential and sick newborn care. Efficacy was 42% (SD ±17%). Providers averaged 78% (SD ±31%) completion of initial learning and 7% (SD ±11%) of refresher assignments. 130 (67%) providers had ≥1 episode of inactivity >30 day, no episodes were due to lack of internet access. Baseline conscious-competence was 53% (IQR: 38%-63%), unconscious-incompetence 32% (IQR: 23%-42%), conscious-incompetence 7% (IQR: 2%-15%), and unconscious-competence 2% (IQR: 0%-3%). Higher baseline conscious-competence (OR 31.6 (95% CI 5.8 to 183.5)) and being a nursing officer (aOR: 5.6 (95% CI 1.8 to 18.1)), compared with medical officer, were associated with initial learning completion or persistent activity. CONCLUSION: aESNC reach was high in a population of frontline providers across diverse levels of care in Tanzania. Use of in-person support and nudging increased reach, initial learning and refresher assignment completion, but refresher assignment completion remains low. Providers were often unaware of knowledge gaps, and lower baseline knowledge may decrease initial learning completion or activity. Further study to identify barriers to adaptive e-learning normalisation is needed.

Use of a Local Anaesthetic/Antiseptic Formulation for the Treatment of Lambs Experimentally Infected with Orf Virus.

Contagious ecthyma is a highly transmissible eruptive viral disease of the skin and mucosa of sheep and goats distributed worldwide. The treatment of orf lesions is usually based on the use of antiseptics and antibiotics for the management of presumptive secondary infections, increasing risks of antimicrobial resistance. The wound dressing formulation Tri-Solfen® (TS) containing two local anaesthetics (lignocaine and bupivacaine), adrenaline and an antiseptic (cetrimide) in a gel formulation has been demonstrated to reduce suffering and enhance recovery in cattle and buffalo with oral and skin lesions due to foot-and-mouth disease virus infection and reduced the orf viral load in lambs. In the present study, experimental infection with the orf virus was conducted in 50 newborn lambs and 25 animals were treated after the presence of the first lesions with TS and repeated three days later. Daily clinical examination, haematological, serological, biomolecular and post-mortem analyses were conducted during 34 days after treatment. Results indicated that treatment had no effect on weight gain and clinical progression of the lesions. It was determined that seroconversion after experimental infection occurs 34 days after infection and suggested that the deep basal epithelial location of the orf lesions may have prevented the therapy from having altered the clinical course.

Development of pediatric acute care education (PACE): An adaptive electronic learning (e-learning) environment for healthcare providers in Tanzania.

Globally, inadequate healthcare provider (HCP) proficiency with evidence-based guidelines contributes to millions of newborn, infant, and child deaths each year. HCP guideline proficiency would improve patient outcomes. Conventional (in person) HCP in-service education is limited in 4 ways: reach, scalability, adaptability, and the ability to contextualize. Adaptive e-learning environments (AEE), a subdomain of e-learning, incorporate artificial intelligence technology to create a unique cognitive model of each HCP to improve education effectiveness. AEEs that use existing internet access and personal mobile devices may overcome limits of conventional education. This paper provides an overview of the development of our AEE HCP in-service education, Pediatric Acute Care Education (PACE). PACE uses an innovative approach to address HCPs' proficiency in evidence-based guidelines for care of newborns, infants, and children. PACE is novel in 2 ways: 1) its patient-centric approach using clinical audit data or frontline provider input to determine content and 2) its ability to incorporate refresher learning over time to solidify knowledge gains. We describe PACE's integration into the Pediatric Association of Tanzania's (PAT) Clinical Learning Network (CLN), a multifaceted intervention to improve facility-based care along a single referral chain. Using principles of co-design, stakeholder meetings modified PACE's characteristics and optimized integration with CLN. We plan to use three-phase, mixed-methods, implementation process. Phase I will examine the feasibility of PACE and refine its components and protocol. Lessons gained from this initial phase will guide the design of Phase II proof of concept studies which will generate insights into the appropriate empirical framework for (Phase III) implementation at scale to examine effectiveness.

Foot abscesses with no accompanying wound: clinical presentation and pathogens.

INTRODUCTION: Acute bacterial infections of the skin and soft tissue are common and often pose serious complications, most commonly caused by Streptococcus species and Staphylococcus aureus. OBJECTIVE: The authors report clinical presentation and pathogens in patients with a foot abscess and no wound. METHODS: The authors retrospectively evaluated the demographics, clinical presentation, and microbiology from 20 patient records. RESULTS: Twenty patients were identified. Fifteen were male (75%), and 10 patients (50%) had DM. Patients presented to the hospital 7.8 ± 4.8 days after onset of symptoms and underwent surgery 2.0 ± 0.9 days from admission. Patients underwent 2.4 ± 1.0 surgeries while admitted. Patients with DM presented with significantly higher erythrocyte sedimentation rate than patients without DM (66.6 ± 46.1 vs 43.3 ± 26.2; P = .02). There were no polymicrobial infections based on deep intraoperative tissue cultures. Seven patients had methicillin-sensitive S aureus (35%), 4 had Streptococcus agalactiae (20%), 3 had methicillin-resistant S aureus (15%), 1 had Streptococcus pyogenes (5%), 1 had Escherichia coli (5%), 1 had Streptococcus dysgalactiae (5%), 1 had an unidentified Streptococcus species (5%), and 2 had no growth (10%). CONCLUSION: Patients with foot abscess and no wounds had single-pathogen infections, predominantly Staphylococcus and Streptococcus.

Bioarchaeological analyses reveal long-lasting continuity at the periphery of the Late Antique Roman Empire.

The Basel-Waisenhaus burial community (Switzerland) has been traditionally interpreted as immigrated Alamans because of the location and dating of the burial ground - despite the typical late Roman funeral practices. To evaluate this hypothesis, multi-isotope and aDNA analyses were conducted on the eleven individuals buried there. The results show that the burial ground was occupied around AD 400 by people belonging largely to one family, whereas isotope and genetic records most probably point toward a regionally organized and indigenous, instead of an immigrated, community. This strengthens the recently advanced assumption that the withdrawal of the Upper Germanic-Rhaetian limes after the "Crisis of the Third Century AD" was not necessarily related to a replacement of the local population by immigrated Alamannic peoples, suggesting a long-lasting continuity of occupation at the Roman periphery at the Upper and High Rhine region.

Provision of High-Quality Molasses Blocks to Improve Productivity and Address Greenhouse Gas Emissions from Smallholder Cattle and Buffalo: Studies from Lao PDR.

Large ruminant production in developing countries is inefficient with low growth rates and likely high greenhouse gas emissions per unit of meat or milk produced. Trials conducted in Lao PDR from 2017 to 2020, studied ad libitum supplementation for 12 weeks with 20 kg high-quality molasses nutrient blocks (Four Seasons Pty Ltd., Brisbane, Australia), that were either non-medicated; fenbendazole-medicated (Panacur100®, Coopers Australia, 5 g/kg); triclabendazole-medicated (Fasinex®, Novartis Australia, 5 g/kg or 10 g/kg, respectively); or formulated with urea (8% or 10% urea, respectively). Average daily gains were determined for access to all molasses blocks and compared with access to control blocks, no supplementation, or previously determined free-grazing baseline average daily gains (55−84 g in cattle; 92−106 g in buffalo). Productivity was significantly improved following access to all molasses blocks. Average daily gains following access to 8% urea and control blocks were calculated for three age cohorts of cattle: young calves <8 m (238−298 g), growing cattle (143−214 g) and lactating cows (179−191 g). Modelling using IPCC Inventory software model V 2.69 of published data demonstrated a conservative net abatement of 350 kg CO2e was achievable over a 200-day feeding period. An additional trial of Emissions control blocks (n = 200) distributed to farmers (n = 60) and two educational institutions were conducted. Consumption rates (156 g/day) and farmer and institutional acceptance of these blocks were similar to our published findings with other molasses blocks, confirming all formulations of blocks improved animal productivity and body condition score, with healthier animals that were easier to manage. Modelling of changes in greenhouse gas emissions intensity identified an abatement of 470 kg CO2e per Emissions control blocks consumed, delivering a total project emissions abatement of 94 t CO2e. Provision of high-quality molasses blocks significantly improved smallholder large ruminant productivity and addition of greenhouse gas reducing agents is likely to achieve impressive abatement of greenhouse gas emissions due to improved efficiency of rumen fermentation and productivity.

Draft genome assemblies of four manakins.

Manakins are a family of small suboscine passerine birds characterized by their elaborate courtship displays, non-monogamous mating system, and sexual dimorphism. This family has served as a good model for the study of sexual selection. Here we present genome assemblies of four manakin species, including Cryptopipo holochlora, Dixiphia pipra (also known as Pseudopipra pipra), Machaeropterus deliciosus and Masius chrysopterus, generated by Single-tube Long Fragment Read (stLFR) technology. The assembled genome sizes ranged from 1.10 Gb to 1.19 Gb, with average scaffold N50 of 29 Mb and contig N50 of 169 Kb. On average, 12,055 protein-coding genes were annotated in the genomes, and 9.79% of the genomes were annotated as repetitive elements. We further identified 75 Mb of Z-linked sequences in manakins, containing 585 to 751 genes and an ~600 Kb pseudoautosomal region (PAR). One notable finding from these Z-linked sequences is that a possible Z-to-autosome/PAR reversal could have occurred in M. chrysopterus. These de novo genomes will contribute to a deeper understanding of evolutionary history and sexual selection in manakins.

Role of Topical Anaesthesia in Pain Management of Farm Animals, a Changing Paradigm.

Field evidence indicates that livestock producers are motivated by access to products that readily deliver pain management during husbandry interventions and, more recently, viral epidermal infectious diseases, including FMD. There has been impressive adoption in Australia of a farmer-applied spray-on topical anaesthetic wound formulation (TAF; Tri-Solfen®, Medical Ethics, Australia), initially for managing pain of the breech modification 'mulesing' procedure that reduces susceptibility of sheep to flystrike. Over 120 million lambs have now received pain relief and cattle producers have commenced using the TAF for a range of husbandry procedures. This product has demonstrated efficacy for surgical castration and tail docking of lambs, surgical castration and dehorning of calves, surgical castration of piglets, debridement of lesions of the hoof for lame cattle and, importantly, treatment of clinical FMD lesions, including decubitus ulcerations occurring from prolonged recumbency. Multimodal use of an NSAID for improved pain management is advocated, particularly meloxicam, available by prescription from veterinarians for injection and as an oral formulation (Ilium Buccalgesic®, Troy Laboratories, Australia), with current work assessing the potential for prolonged delivery in molasses blocks. Increased use of TAF with NSAIDs significantly reduces pain and suffering in livestock, with enhanced healing of FMD lesions, reduced viral loads from Orf infections in lambs and diminished necessity of 'antibiotic cover', assisting antimicrobial-resistance (AMR) stewardship.

Corrigendum: Progress With Livestock Welfare in Extensive Production Systems: Lessons From Australia.

[This corrects the article DOI: 10.3389/fvets.2021.674482.].

Comparison of Multisystem Inflammatory Syndrome in Children-Related Myocarditis, Classic Viral Myocarditis, and COVID-19 Vaccine-Related Myocarditis in Children.

Background Although rare, classic viral myocarditis in the pediatric population is a disease that carries significant morbidity and mortality. Since 2020, myocarditis has been a common component of multisystem inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection. In 2021, myocarditis related to mRNA COVID-19 vaccines was recognized as a rare adverse event. This study aims to compare classic, MIS-C, and COVID-19 vaccine-related myocarditis with regard to clinical presentation, course, and outcomes. Methods and Results In this retrospective cohort study, we compared patients aged <21 years hospitalized at our institution with classic viral myocarditis from 2015 to 2019, MIS-C myocarditis from March 2020 to February 2021, and vaccine-related myocarditis from May 2021 to June 2021. Of 201 total participants, 43 patients had classic myocarditis, 149 had MIS-C myocarditis, and 9 had vaccine-related myocarditis. At presentation, ejection fraction was lowest for those with classic myocarditis, with ejection fraction <55% present in 58% of patients. Nearly all patients with MIS-C myocarditis (n=139, 93%) and all patients with vaccine-related myocarditis (n=9, 100%) had normal left ventricular ejection fraction at the time of discharge compared with 70% (n=30) of the classic myocarditis group (P<0.001). At 3 months after discharge, of the 21 children discharged with depressed ejection fraction, none of the 10 children with MIS-C myocarditis had residual dysfunction compared with 3 of the 11 (27%) patients in the classic myocarditis group. Conclusions Compared with classic myocarditis, those with MIS-C myocarditis had better clinical outcomes, including rapid recovery of cardiac function. Patients with vaccine-related myocarditis had prompt resolution of symptoms and improvement of cardiac function.

Unexpected suicide left ventricle post-surgical aortic valve replacement requiring veno-arterial extracorporeal membrane oxygenation support despite gold-standard therapy: a case report.

BACKGROUND: Suicide left ventricle is a well-documented phenomenon occurring after valve replacement, however, it is most commonly described in the mitral valve replacement (MVR) and transcatheter aortic valve replacement (TAVR) population. Cases within the surgical aortic valve replacement (SAVR) population usually resolve with optimal medical and interventional therapies. We describe a case of left ventricular suicide following SAVR presenting with persistent haemodynamic instability despite currently accepted medical and surgical therapies. CASE SUMMARY: A 62-year-old male with severe aortic stenosis presented for SAVR and a MAZE procedure. There were no significant signs of ventricular hypertrophy on preoperative transthoracic echocardiogram (TTE). Intraoperatively, there was mild chordal systolic anterior motion of the mitral valve (SAM) which only occurred when underfilled. During recovery in the intensive care unit, the patient's pulmonary arterial pressures were noted to rise with worsening cardiac output. Subsequent TTE showed severe dynamic left ventricular outflow tract (LVOT) obstruction secondary to SAM. Due to refractory medical management, an alcohol septal ablation was performed. Despite resolution of obstruction, the patient exhibited biochemical signs of systemic hypoperfusion, and thus veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support was initiated. Following 72 h of VA-ECMO support, the patient was weaned with complete resolution of biochemical insults. He was subsequently discharged from the hospital without complication. DISCUSSION: Compared to the TAVR population, suicide ventricle post-SAVR is comparatively rare. Patients who exhibit persistent impaired cardiac output postoperatively should be investigated rapidly with echocardiography. Furthermore, resolution of a LVOT obstruction state from procedural intervention may not immediately follow with improved cardiac output, and may require further supportive management.

Short-term Outcomes of Corticosteroid Monotherapy in Multisystem Inflammatory Syndrome in Children.

Importance: Optimal agents and duration of primary treatment for multisystem inflammatory syndrome in children (MIS-C) remain unclear. Objective: To compare short-term patient outcomes based on initial treatment with corticosteroids, intravenous immunoglobulin (IVIG), or both. Design, Setting, and Participants: This retrospective cohort study included patients in a tertiary-care pediatric hospital system who had MIS-C per the Centers for Disease Control and Prevention case definition during the period March 2020 to February 2021. Exposures: Immunomodulatory therapy within the first 24 hours (patients in the intensive care unit [ICU]) or 48 hours (non-ICU patients): corticosteroids alone, IVIG alone, and IVIG plus corticosteroids. Main Outcomes and Measures: Primary outcome was failure of initial therapy, defined as therapy escalation due to fever or worsening or lack of improvement of laboratory, cardiac, or noncardiac clinical factors after 24 hours (ICU patients) or 48 hours (non-ICU patients) from time of therapy initiation, per clinician assessment. Secondary outcomes included presence of complications, cardiovascular outcomes, fever duration, length of hospital and ICU stays, corticosteroid use duration, and need for readmission. Results: Among 228 eligible patients, 215 patients were included in the univariate analysis; median age was 8 years, and 135 (62.8%) were boys. There were 69 patients in the corticosteroids group, 31 patients in the IVIG group, and 115 patients in the IVIG plus corticosteroids group. Patients in the corticosteroids group had milder disease at presentation. After propensity score weighting including 179 patients (68 in the corticosteroids group and 111 in the IVIG plus corticosteroids group), rates of initial treatment failure were similar between groups. Among patients whose initial treatment failed, treatment failure in the IVIG plus corticosteroids group was more likely to be based on laboratory parameters (odds ratio [OR], 1.96; 95% CI, 1.07-3.60) and less likely to be based on cardiovascular markers (OR, 0.39; 95% CI, 0.2-0.76), per clinician assessment. Patients in the IVIG plus corticosteroids group had a longer median inpatient stay (6 vs 5 days; P = .001) and longer median corticosteroid course duration (10 vs 5 days; P = .04) compared with the corticosteroids group. Forty-nine patients (71% of 69 in the corticosteroids group) recovered after receiving corticosteroid monotherapy for 10 days or less. Conclusions and Relevance: Corticosteroid monotherapy is a reasonable management option for a subset of patients with MIS-C, particularly those with mild disease.

Incidence and Recovery of Acute Kidney Injury in Diabetic and Nondiabetic Patients with Foot Infections.

BACKGROUND: The aim of this study was to evaluate the incidence and recovery of acute kidney injury (AKI) in patients admitted to the hospital with and without diabetes mellitus (DM) with foot infections. METHODS: We retrospectively reviewed 294 patients with DM and 88 without DM admitted to the hospital with foot infections. The Kidney Disease: Improving Global Outcomes guidelines were used to define AKI. Recovery was divided into three categories: full, partial, and no recovery within 90 days of the index AKI. RESULTS: The AKI incidence was 3.0 times higher in patients with DM (DM 48.5% versus no DM 23.9%; 95% confidence interval [CI], 1.74-5.19; P < .01). Acute kidney injury incidence was similar at each stage in people with and without DM (stage 1, DM 58.1% versus no DM 47.6%; stage 2, DM 23.3% versus no DM 33.3%, and stage 3, DM 18.6% versus no DM 19.1%). Twenty-nine patients with diabetes had a second AKI event and four had a third event. In patients without DM, one patient had a second AKI. Cumulative AKI incidence was 4.7 times higher in people with DM (DM 60.9% versus no DM 25.0%; 95% CI, 2.72-8.03; P < .01). Patients with diabetes progressed to chronic kidney disease or in chronic kidney disease stage 39.4% of the time. Patients without diabetes progressed 16.7% of the time, but this trend was not significant (P = .07). Complete recovery was 3.8 times more likely in patients without diabetes (95% CI, 1.26-11.16; P = .02). CONCLUSIONS: Acute kidney injury incidence is higher in patients with diabetes, and complete recovery after an AKI is less likely compared to patients without diabetes.

The standard of integrity may be useful when assessing arguments over qualitative review methods: The case of the Joanna Briggs Institute's rebuttal of a fundamental critique.

One challenge for those reading methodological debates in low consensus fields is determining the outcome when participants do not share standards. When parties to a debate do not agree on the standards to be used in assessing their arguments (i.e., quality), it may be useful to ask first if parties' contributions meet their own expectations (i.e., integrity). Most protocols for review of qualitative research specify some form of quality assessment. These protocols normally require some test of internal coherence. Coherence is also relevant when describing the match between a rebuttal and the argument it answers. In 2019, Nursing Inquiry published a critique and rebuttal of the methods used by the Joanna Briggs Institute. In this essay, we attempted to use the Joanna Briggs Institute's own quality assessment standards to assess their rebuttal of this fundamental critique. We found it possible to use the Joanna Briggs Institute's own quality assessment standards to assess this rebuttal, and we found that JBI's rebuttal did not meet their own standards.

Knowledge, attitudes and practices of smallholder farmers on foot and mouth disease control in two Cambodian provinces.

Food-and-mouth disease (FMD) is endemic in Cambodia. The control programme for FMD has relied on vaccination, with poor vaccination uptake by smallholder farmers becoming an increasing concern. A study to improve the understanding of farmer knowledge, attitudes and practices of FMD control and vaccination was conducted in two Cambodian provinces (Kampong Cham and Pursat). The aim was to identify opportunities to improve the livestock disease control programmes provided by both the government and private sectors. The survey comprised 300 smallholder farmers using a one-on-one interview technique and was completed between January to February 2014. Results identified that over two-thirds of the respondent farmers had not vaccinated their cattle over 2 years (2011-2013). Of those who did, most cattle were vaccinated either once a year or once every 3 years. A booster had never been administered. It was concluded that the FMD vaccine had only been administered through an unreliable and limited government vaccination programme, and private FMD vaccination services were not accessed in the study areas. FMD outbreaks occurred every year during the study period, with a morbidity rate of over 30%. Isolation of first infected cattle from the household herd was not practiced, with treatment identified as the first preference intervention. Farmers often assisted other farmers to restrain and treat infected cattle both before (57%) and after (43%) their own cattle were infected. This indicated that most farmers did not practice basic biosecurity measures and chose to report FMD outbreaks to the village animal health workers (VAHW), friends, neighbours and relatives in preference to government officials. It was concluded that poor knowledge of disease transmission and biosecurity, with low FMD vaccination coverage and a focus on treatment, contribute to regular FMD outbreaks in these communities. Improvement of FMD control requires the cooperation of villagers, VAHWs and village leaders in disease reporting, with either improved funding of government vaccination services or establishing a private FMD vaccination service. Training programmes for farmers on disease transmission, and the importance of biosecurity and vaccination, including information on the cost-benefits of treatment versus full fee bi-annual FMD vaccination, are required.

Contributions of village animal health workers to foot-and-mouth disease control in Cambodia.

Local animal health services in rural communities in Cambodia are mainly provided by village animal health workers (VAHWs), although the participation and contribution of VAHWs to livestock disease prevention are uncertain. The participation of the VAHWs as identified by their 'dropout rate' was examined in a desktop review in December 2020 of the national data on VAHWs recorded between 2011 and 2020. The contribution and involvement of VAHWs in disease prevention programmes were examined in a survey conducted between February and March 2014, then analyzed in the context of other surveys of VAHW knowledge, attitudes and practices. The survey involved guided group discussion with VAHWs (n = 198) from the two Cambodian provinces of Kampong Cham and Pursat. This study identified that VAHWs generated less than 22% of their annual household incomes from animal health services. Less than one-third had vaccinated livestock against foot-and-mouth disease (FMD), with none having vaccinated cattle every 6 months during the study period, and nearly half of the VAHWs having never vaccinated their own cattle against FMD. As no privately provided FMD vaccination services occurred in these communities, with all vaccines delivered through the government-subsidized programme, the findings confirmed that VAHWs only vaccinated animals against FMD when vaccines were made available by the Government. The desktop review found that the number of VAHWs in 2020 declined by more than 24% since 2017, and the proportion of female VAHWs was consistently low, with a mean of 8.26 (±1.019). These findings confirm findings from previous studies that identified considerable weaknesses in the VAHW system in Cambodia, particularly in contributing to FMD control. Cambodian animal health authorities require more effective policies to strengthen the current VAHW system, improving their services delivery; their retention as 'active'; their development of more sustainable roles with lower 'dropout' rates and the prolonged gender inequity. With the limited availability of government-subsidized FMD vaccination currently, extension programmes that engage VAHWs and farmers in seeking privately funded and delivered FMD vaccination that incorporates appropriate multivalent FMD serotype vaccines of high quality, delivered in small dose vials from a robust cold chain, is suggested. This strategy would assist VAHWs to contribute to the provision of private livestock vaccination services that are likely essential for sustainable FMD prevention and control in Cambodia.

The Relevance of SOCS1 Methylation and Epigenetic Therapy in Diverse Cell Populations of Hepatocellular Carcinoma.

The suppressor of cytokine signaling 1 (SOCS1) is a tumor suppressor gene found to be hypermethylated in cancers. It is involved in the oncogenic transformation of cirrhotic liver tissues. Here, we investigated the clinical relevance of SOCS1 methylation and modulation upon epigenetic therapy in diverse cellular populations of hepatocellular carcinoma (HCC). HCC clinical specimens were evaluated for SOCS1 methylation and mRNA expression. The effect of 5-Azacytidine (5-AZA), a demethylation agent, was assessed in different subtypes of HCC cells. We demonstrated that the presence of SOCS1 methylation was significantly higher in HCC compared to peri-HCC and non-tumoral tissues (52% vs. 13% vs. 14%, respectively, p < 0.001). In vitro treatment with a non-toxic concentration of 5-AZA significantly reduced DNMT1 protein expression for stromal subtype lines (83%, 73%, and 79%, for HLE, HLF, and JHH6, respectively, p < 0.01) compared to cancer stem cell (CSC) lines (17% and 10%, for HepG2 and Huh7, respectively), with the strongest reduction in non-tumoral IHH cells (93%, p < 0.001). 5-AZA modulated the SOCS1 expression in different extents among the cells. It was restored in CSC HCC HepG2 and Huh7 more efficiently than sorafenib. This study indicated the relevance of SOCS1 methylation in HCC and how cellular heterogeneity influences the response to epigenetic therapy.