Role of oxidative stress,angiogenesis and chemo-attractant cytokines in the pathogenesis of ischaemic protection induced by remote ischaemic conditioning: Study of a human model of ischaemia-reperfusion induced vascular injury

Aims

We explored the effect of remote ischaemic conditioning (RIC) on endothelial function and on circulating mediators.

Studies of quantitative parameters of virus excretion and transmission in pigs and cattle experimentally infected with foot-and-mouth disease virus

Foot-and-mouth disease virus (FMDV) can be spread by a variety of mechanisms and the rate of spread, the incubation period and the severity of disease depend on a multitude of parameters, including the strain of virus, the dose received, the route of introduction, the animal species and the husbandry conditions. More knowledge with regard to these parameters is urgently needed to improve resource-efficient disease control. This report describes detailed studies of FMDV load, excretion and transmission in pigs infected with FMDV O UKG 2001, O TAW 1997 and C Noville virus and in cattle infected with the O UKG 2001 virus to facilitate use of a "FMDV load framework" for the assessment of transmission risks. Virus replicated rapidly in pigs and cattle exposed by direct contact. The mean incubation period was around 3-4 days for cattle-to-cattle and 1-3 days for pig-to-pig transmission, depending on the intensity of contact. The results confirmed that a strong relation exists between dose and length of incubation period. Clinical disease was severe in pigs but relatively mild in inoculated cattle; contact infection of cattle appeared to increase the severity of lesions. FMDV RNA was recovered in nasal and mouth swabs from inoculated animals soon after they developed a viraemia and probably reflected the early production and excretion of virus. FMDV RNA in nasal and mouth swabs from contact animals could be detected several days before they showed other signs of infection, indicating the possibility of detecting exposed animals during the incubation period. FMDV RNA could also be detected in swab samples after the viraemic phase. This may have represented background environmental virus that had been trapped in the respiratory tract and mouth. Alternatively, it may have indicated a somewhat slower clearance or half-life of viral RNA or an extended low level of FMDV replication at these sites. The pattern of FMDV RNA concentrations in pigs was closely similar to that in cattle, but the amounts of FMDV RNA were higher.     

Status of Foot‐and‐mouth Disease in India

Foot‐and‐mouth disease (FMD) is endemic in India and causes severe economic loss. Status of FMD in the country for five fiscal years is presented. Outbreaks were more in number in 2007–2008 than 2010–2011. Three serotypes of FMD virus (O, A and Asia1) are prevalent. Serotype O was responsible for 80% of the confirmed outbreaks/cases, whereas Asia1 and A caused 12% and 8%, respectively. Geographical region‐wise assessment indicated varying prevalence rate in different regions viz; 43% in Eastern region, 31.5% in Southern region, 11.6% in North‐eastern region, 5% Central region, 4.4% Western region and 4% in Northern region. Highest number of outbreaks/cases was recorded in the month of September and lowest in June. Emergence and re‐emergence of different genotypes/lineages within the serotypes were evident in real‐time investigation carried out from time to time. Continues antigenic divergence in serotype A resulted in change in the vaccine strain in 2009. As on date, all genetic diversity within the serotypes is well tolerated by the vaccine strains. Unrestricted animal movements in the country play a major role in the spread of FMD.     

Alternate vaccine strain selection in the wake of emerging foot-and-mouth disease virus serotype A antigenic variants in India

‘National foot-and-mouth disease (FMD) control programme’ is being implemented in India and therefore predicting vaccine match is a key surveillance task. Recently, a considerable proportion of field viruses (75.6%) showed antigenic drift from the existing serotype A vaccine strain A IND 40/2000 necessitating search for an alternate strain. Here, antigenic relationship (‘r₁’ value) of 87 field viruses with each of the 8 candidate strains was estimated by virus neutralization test. A IND 27/2011 strain emerged to be the one with the widest spectrum of antigenic coverage showing ‘r₁’ value of more than 0.3 with 81.6% of field strains. It achieved a reasonably high titre of log₁₀ 7.5 TCID₅₀/ml in BHK-21 suspension cell which was accompanied by positive charge gaining substitutions (E₈₂–K and E₁₃₁–K in VP2) thought to have adaptive significance. However, potency trial remains to be conducted before A IND 27/2011 finds a place in the vaccine formulation.     

Efficacy of a high potency O1 Manisa monovalent vaccine against heterologous challenge with a FMDV O Mya98 lineage virus in pigs 4 and 7 days post vaccination

Early protection with a high potency (>6PD₅₀) foot-and-mouth disease (FMD) O₁ Manisa (Middle-East South Asia lineage) vaccine against challenge with O/VIT/2010 (O Mya98 lineage) was tested in pigs. Only two pigs that were vaccinated seven days prior to challenge had any demonstrable antibodies as a result of vaccination at the time of challenge. However, 80% and 60% of pigs that were vaccinated seven and four days prior to coronary band challenge were protected. Vaccination significantly reduced the amount of virus excreted in nasal swabs, saliva and faeces compared to unvaccinated and infected controls. Virus and viral RNA could be detected in some pigs until termination of the experiment 14 days after challenge. Antibodies to the non-structural proteins (NSP) were detected in only one pig that was challenged four days post vaccination (dpv) and transiently in two pigs that were challenged seven dpv at only one time point. For each vaccine and control group, a group of unvaccinated pigs were kept in the same room but with no direct contact with the infected pigs to determine whether vaccination prevented transmission. Despite the presence of live virus and viral RNA in these indirect contact pigs, the groups in contact with the vaccinated and infected pigs did not develop clinical signs nor did they sero-convert. Contact pigs in the same room as unvaccinated challenged controls did show signs of disease and virus infection that resulted in sero-conversion to the NSP. A breach of the wall that separated the two groups at nine days post challenge might have contributed to this finding. This study showed that high potency vaccine can provide protection to pigs soon after vaccination and that aerosol transmission within rooms is a rare event.     

Vascular cell adhesion molecule-1 (VCAM-1), flow mediated dilatation (FMD) and carotid intima media thickness (IMT) in children with juvenile idiopathic arthritis: Relation to disease activity,functional status and fatigue

Background

There is risk of premature atherosclerosis in juvenile idiopathic arthritis (JIA) patients which predisposes to cardiovascular disease (CVD) in adulthood. This can be assessed by flow mediated dilatation (FMD) and carotid intima media thickness (IMT) of the arterial wall and by soluble vascular cell adhesion molecule (sVCAM-1).

Fetal phenotypes in otopalatodigital spectrum disorders

Otopalatodigital spectrum disorders (OPDSD) include OPD syndromes types 1 and type 2 (OPD1, OPD2), Melnick–Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). These conditions are clinically characterized by variable skeletal dysplasia associated in males, with extra‐skeletal features including brain malformations, cleft palate, cardiac anomalies, omphalocele and obstructive uropathy. Mutations in the FLNA gene have been reported in most FMD and OPD2 cases and in all instances of typical OPD1 and MNS. Here, we report a series of 10 fetuses and a neonatally deceased newborn displaying a multiple congenital anomalies syndrome suggestive of OPDSD and in whom we performed FLNA analysis. We found a global mutation rate of 44%. This series allows expanding the clinical and FLNA mutational spectrum in OPDSD. However, we emphasize difficulties to correctly discriminate OPDSD based on clinical criteria in fetuses due to the major overlap between these conditions. Molecular analyses may help pathologists to refine clinical diagnosis according to the type and the location of FLNA mutations. Discriminating the type of OPDSD is of importance in order to improve the genetic counseling to provide to families.     

Socio‐economic impact of Foot‐and‐Mouth Disease outbreaks and control measures: An analysis of Mongolian outbreaks in 2017

Mongolia is a large landlocked country in Central Asia and has one of the highest per capita livestock ratios in the world. During 2017, reported foot‐and‐mouth disease (FMD) outbreaks in Mongolia increased considerably, prompting widespread disease control measures. This study estimates the socio‐economic impact of FMD and subsequent control measures on Mongolian herders. The analysis encompassed quantification of the impact on subsistence farmers’ livelihoods and food security and estimation of the national‐level gross losses due to reaction and expenditure during 2017. Data were collected from 112 herders across eight provinces that reported disease. Seventy of these herders had cases of FMD, while 42 did not have FMD in their animals but were within quarantine zones. Overall, 86/112 herders reported not drinking milk for a period of time and 38/112 reduced their meat consumption. Furthermore, 55 herders (49.1%) had to borrow money to buy food, medicines and/or pay bills or bank loans. Among herders with FMD cases, the median attack rate was 31.7%, 3.8% and 0.59% in cattle, sheep and goats, respectively, with important differences across provinces. Herders with clinical cases before the winter had higher odds of reporting a reduction in their meat consumption. National‐level gross losses due to FMD in 2017 were estimated using government data. The estimate of gross economic loss was 18.4 billion Mongolian‐tugriks (US$7.35 million) which equates to approximately 0.65% of the Mongolian GDP. The FMD outbreaks combined with current control measures have negatively impacted herders’ livelihoods (including herders with and without cases of FMD) which are likely to reduce stakeholder advocacy. Possible strategies that could be employed to ameliorate the negative effects of the current control policy were identified. The findings and approach are relevant to other FMD endemic regions aiming to control the disease.     

The UK NCRI study of chlorambucil,mitoxantrone and dexamethasone (CMD) versus fludarabine,mitoxantrone and dexamethasone (FMD) for untreated advanced stage follicular lymphoma: molecular response strongly predicts prolonged overall survival

We present a long-term follow-up of the UK chlorambucil, mitoxantrone and dexamethasone (CMD) versus fludarabine, mitoxantrone and dexamethasone (FMD) for untreated advanced, symptomatic follicular lymphoma (FL). This trial was the first to prospectively assess molecular response and the impact on outcomes for 400 patients. The median progression-free survival (PFS) and overall survival (OS) for CMD were 3·6 and 14·6 years vs. 3·0 and 15·7 years for FMD, respectively. Estimates for Restricted Mean Survival Time (RMST) suggested no difference in PFS or OS. For the whole cohort there was a highly significant difference in survival by POD24, with a median OS from a risk-defining event of 3·9 years compared to 13·7 years for all others (RMST P < 0·001). Molecular remission was achieved in 25/46 patients (54·3%) in the CMD arm and 20/41 (48·8%) in the FMD arm (P = 0·6). Molecular negativity resulted in median PFS of 5·6 years vs. 2·3 years for molecularly positive (log-rank P < 0·001) and median OS not reached versus 12·5 years (log-rank P < 0·01). No cases of progression occurred in minimal residual disease (MRD) negative patients after six years of follow-up. Although there was no difference in outcomes between arms, this is the first prospective study to report MRD negativity resulting in significantly improved OS.