How do the virulence factors of shigella work together to cause disease?

Shigella is the major cause of bacillary dysentery world-wide. It is divided into four species, named S. flexneri, S. sonnei, S. dysenteriae, and S. boydii, which are distinct genomically and in their ability to cause disease. Shigellosis, the clinical presentation of Shigella infection, is characterized by watery diarrhea, abdominal cramps, and fever. Shigella's ability to cause disease has been attributed to virulence factors, which are encoded on chromosomal pathogenicity islands and the virulence plasmid. However, information on these virulence factors is not often brought together to create a detailed picture of infection, and how this translates into shigellosis symptoms. Firstly, Shigella secretes virulence factors that induce severe inflammation and mediate enterotoxic effects on the colon, producing the classic watery diarrhea seen early in infection. Secondly, Shigella injects virulence effectors into epithelial cells via its Type III Secretion System to subvert the host cell structure and function. This allows invasion of epithelial cells, establishing a replicative niche, and causes erratic destruction of the colonic epithelium. Thirdly, Shigella produces effectors to down-regulate inflammation and the innate immune response. This promotes infection and limits the adaptive immune response, causing the host to remain partially susceptible to re-infection. Combinations of these virulence factors may contribute to the different symptoms and infection capabilities of the diverse Shigella species, in addition to distinct transmission patterns. Further investigation of the dominant species causing disease, using whole-genome sequencing and genotyping, will allow comparison and identification of crucial virulence factors and may contribute to the production of a pan-Shigella vaccine

A protocol to prospectively assess risk factors for medial tibial stress syndrome in distance runners

Abstract Background Medial tibial stress syndrome (MTSS) is a lower leg injury with a reported incidence rate of up to 35% in active individuals. Although numerous prospective studies have tried to identify risk factors for developing MTSS, managing the syndrome remains difficult. One risk factor yet to be extensively explored in MTSS development is reduced lower leg girth. Further investigation of reduced lower leg girth is required due to the important role lower leg musculature plays in attenuating ground reaction forces during the gait cycle. Therefore, the primary aim of this study is to ascertain whether lower leg muscle morphology and function contribute to the development of MTSS. Our ultimate aim is to identify potential risk factors for MTSS that can be targeted in future studies to better manage the injury or, preferably, prevent individuals developing MTSS. Methods This study will be prospective in design and will recruit asymptomatic distance runners. All participants will be tested at base line and participants will have their training data longitudinally tracked over the following 12 months to assess any individuals who develop MTSS symptoms. At base line, outcome measures will include bilateral measures of lower limb anthropometry; cross sectional area (CSA) and thickness of the tibialis anterior, peroneals, flexor digitorum longus, flexor hallucis longus and thickness of soleus, medial and lateral head of gastrocnemius. Tibial bone speed of sound, ankle dorsiflexion range of motion, strength of the six previously described muscles, foot alignment and ankle plantar flexor endurance will also be assessed. Participants will also complete a treadmill running protocol where three-dimensional kinematics, plantar pressure distribution and electromyography data will be collected. Discussion This study will aim to identify characteristics of individuals who develop MTSS and, in turn, identify modifiable risk factors that can be targeted to prevent individuals developing this injury

Reliability of the Tekscan Matscan® System for the Measurement of Postural Stability in Older People With Rheumatoid Arthritis

Postural stability can be measured in clinical and research settings using portable plantar pressure systems. People with rheumatoid arthritis (RA) have decreased postural stability compared to non-RA populations and impaired postural stability is associated with falls in people with RA. The purpose of this study was therefore to investigate the reliability of the TekScan MatScan® system in assessing postural stability in people with RA

Flexural behaviour of reinforced concrete jacketed columns under reversed cyclic loading

The objective of the present study is the development of an analytical model for predicting the response under reversed cyclic loading of structural members with ‘old-type’ detailing, strengthened with reinforced concrete (RC) jacketing. The analytical model introduces one additional degree of freedom between the existing member (core of the retrofitted member) and its outer RC shell, thus allowing slip to take place at the interface between the existing member and the jacket. Shear resistance mechanisms, such as aggregate interlock, friction, and dowel action, are mobilized to resist slip. Existing constitutive models are further improved to describe the mechanisms that resist sliding under cyclic shear reversals and implemented for the first time in an analytical model for deriving the response of RC jacketed members. A calculation algorithm is developed to estimate the flexural response under cyclic loading taking into account slip at the interfaces. The sensitivity of the proposed analytical model to the shear transfer mechanisms degradation rules, as well as to the crack spacing estimation, was evaluated. The validity of the proposed analytical model is assessed against experimental results

Potassium binding adjacent to cationic transition metal fragments: unusual heterobimetallic adducts of a calix[4]arene-based thione ligand

The synthesis of cationic rhodium and iridium complexes of a bis(imidazol-2-thione) functionalised calix[4]arene ligand and their surprising capacity for potassium binding is described. In both cases uptake of the alkali metal into the calix[4]arene cavity occurs despite adverse electrostatic interactions associated with close proximity to the transition metal fragment (Rh+∙∙∙K+ = 3.715(1) Å, Ir+∙∙∙K+ = 3.690(1) Å). The formation and constituent bonding of these unusual heterobimetallic adducts has been interrogated through extensive solution and solid-state characterisation, examination of the host-guest chemistry of the ligand and its upper-rim unfunctionalised calix[4]arene analogue, and computationally using DFT-based energy decomposition analysis (EDA)

Correction:Microbiome-driven breeding strategy potentially improves beef fatty acid profile benefiting human health and reduces methane emissions

BACKGROUND: Healthier ruminant products can be achieved by adequate manipulation of the rumen microbiota to increase the flux of beneficial fatty acids reaching host tissues. Genomic selection to modify the microbiome function provides a permanent and accumulative solution, which may have also favourable consequences in other traits of interest (e.g. methane emissions). Possibly due to a lack of data, this strategy has never been explored. RESULTS: This study provides a comprehensive identification of ruminal microbial mechanisms under host genomic influence that directly or indirectly affect the content of unsaturated fatty acids in beef associated with human dietary health benefits C18:3n-3, C20:5n-3, C22:5n-3, C22:6n-3 or cis-9, trans-11 C18:2 and trans-11 C18:1 in relation to hypercholesterolemic saturated fatty acids C12:0, C14:0 and C16:0, referred to as N3 and CLA indices. We first identified that ~27.6% (1002/3633) of the functional core additive log-ratio transformed microbial gene abundances (alr-MG) in the rumen were at least moderately host-genomically influenced (HGFC). Of these, 372 alr-MG were host-genomically correlated with the N3 index (n=290), CLA index (n=66) or with both (n=16), indicating that the HGFC influence on beef fatty acid composition is much more complex than the direct regulation of microbial lipolysis and biohydrogenation of dietary lipids and that N3 index variation is more strongly subjected to variations in the HGFC than CLA. Of these 372 alr-MG, 110 were correlated with the N3 and/or CLA index in the same direction, suggesting the opportunity for enhancement of both indices simultaneously through a microbiome-driven breeding strategy. These microbial genes were involved in microbial protein synthesis (aroF and serA), carbohydrate metabolism and transport (galT, msmX), lipopolysaccharide biosynthesis (kdsA, lpxD, lpxB), or flagellar synthesis (flgB, fliN) in certain genera within the Proteobacteria phyla (e.g. Serratia, Aeromonas). A microbiome-driven breeding strategy based on these microbial mechanisms as sole information criteria resulted in a positive selection response for both indices (1.36±0.24 and 0.79±0.21 sd of N3 and CLA indices, at 2.06 selection intensity). When evaluating the impact of our microbiome-driven breeding strategy to increase N3 and CLA indices on the environmental trait methane emissions (g/kg of dry matter intake), we obtained a correlated mitigation response of −0.41±0.12 sd. CONCLUSION: This research provides insight on the possibility of using the ruminal functional microbiome as information for host genomic selection, which could simultaneously improve several microbiome-driven traits of interest, in this study exemplified with meat quality traits and methane emissions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40168-022-01352-6

Efficient NiII2LnIII2 electrocyclization catalysts for the synthesis of trans-4,5-diaminocyclopent-2-enones from 2-furaldehyde and primary or secondary amines

A series of heterometallic coordination clusters (CCs) [NiII2LnIII2(L1)4Cl2(CH3CN)2] 2CH3CN [Ln = Y (1Y), Sm (1Sm), Eu (1Eu), Gd (1Gd), or Tb (1Tb)] were synthesized by the reaction of (E)-2-(2-hydroxy-3-methoxybenzylidene-amino)phenol) (H2L1) with NiCl2·6(H2O) and LnCl3·x(H2O) in the presence of Et3N at room temperature. These air-stable CCs can be obtained in very high yields from commercially available materials and are efficient catalysts for the room-temperature domino ring-opening electrocyclization synthesis of trans-4,5-diaminocyclopent-2-enones from 2-furaldehyde and primary or secondary amines under a non-inert atmosphere. Structural modification of the catalyst to achieve immobilization or photosensitivity is possible without deterioration in catalytic activity

Economic evaluation of covered stents for transjugular intrahepatic portosystemic stent shunt in patients with variceal bleeding and refractory ascites secondary to cirrhosis

Objectives: Transjugular intrahepatic portosystemic stent shunt (TIPSS) is clinically effective in variceal bleeding and refractory ascites; however, the cost-effectiveness of TIPSS has yet to be evaluated in the UK. This study aimed to establish the cost-effectiveness of (i) pre-emptive TIPSS versus endoscopic band ligation (EBL) in populations with variceal bleeding and (ii) TIPSS versus large volume paracentesis (LVP) in refractory ascites. Methods: A cost-utility analysis was conducted with the perspective including healthcare costs and quality-adjusted life years (QALYs). A Markov model was constructed with a 2-year time horizon, health states for mortality and survival and probabilities for the development of variceal bleeding, ascites and hepatic encephalopathy. A survival analysis was conducted to extrapolate 12-month to 24-month mortality for the refractory ascites indication. Uncertainty was analysed in deterministic and probabilistic sensitivity analyses. Results: TIPSS was cost-effective (dominant) and cost saving for both indications. For variceal bleeding, pre-emptive TIPSS resulted in 0.209 additional QALYs, and saved £600 per patient compared with EBL. TIPSS had a very high probability of being cost-effective (95%) but was not cost saving in scenario analyses driven by rates of variceal rebleeding. For refractory ascites, TIPSS resulted in 0.526 additional QALYs and saved £17 983 per patient and had a 100% probability of being cost-effective and cost saving when compared with LVP. Conclusions: TIPSS is a cost-effective intervention for variceal bleeding and refractory ascites. TIPSS is highly cost-saving for refractory ascites. Robust randomised trial data are required to confirm whether pre-emptive TIPSS is cost saving for variceal bleeding