David M. D. Bailey

The endoplasmic reticulum (ER) forms an interconnected network of tubules stretching throughout the cell. Understanding how ER functionality relies on its structural organization is crucial for elucidating cellular vulnerability to ER perturbations, which have been implicated in several neuronal pathologies. One of the key functions of the ER is enabling Ca 2 + signaling by storing large quantities of this ion and releasing it into the cytoplasm in a spatiotemporally controlled manner. Through a combination of physical modeling and live-cell imaging, we demonstrate that alterations in ER shape significantly impact its ability to support efficient local Ca 2 + releases, due to hindered transport of luminal content within the ER. Our model reveals that rapid Ca 2 + release necessitates mobile luminal buffer proteins with moderate binding strength, moving through a well-connected network of ER tubules. These findings provide insight into the functional advantages of normal ER architecture, emphasizing its importance as a kinetically efficient intracellular Ca 2 + delivery system.

Background: Helicobacter pylori infection remains a major public health threat leading to gastrointestinal illness and increased risk of gastric cancer. Mostly affecting populations in developing countries no vaccines are yet available and the disease is controlled by antimicrobials which, in turn, are driving the emergence of AMR.Materials and Methods: We have engineered spores of Bacillus subtilis to display putative H. pylori protective antigens, urease subunit A (UreA) and subunit B (UreB) on the spore surface. Following oral dosing of mice with these spores, we evaluated immunity and colonization in animals challenged with H. pylori.Results: Oral immunization with spores expressing either UreA or UreB showed antigen‐specific mucosal responses (fecal sIgA) including seroconversion and hyperimmunity. Following challenge, colonization by H. pylori was significantly reduced by up to 1‐log.Conclusions: This study demonstrates the utility of bacterial spores for mucosal vaccination to H. pylori infection. The heat stability and robustness of Bacillus spores coupled with their existing use as probiotics make them an attractive solution for either protection against H. pylori infection or potentially for therapy and control of active infection.

INTRODUCTION: The objective of this study was to investigate the impact of the 2-week wait rule on patient waiting times for the diagnosis and treatment of bladder cancer. PATIENTS AND METHODS: Data reporting the waiting times from diagnosis to treatment for 100 consecutive patients newly diagnosed with bladder cancer immediately before and after the implementation of the 2-week wait rule were compared. The data were collected both prospectively and retrospectively from cancer multidisciplinary team meeting files and patient records. Various steps of the patient pathway were analysed including waiting times from referral to consultation as well as time to investigation and first treatment. Data were also analysed based upon tumour stage/grade and whether referrals were made on an urgent or routine basis. RESULTS: One hundred newly diagnosed patients with bladder cancer in each group covered a period of 4–5 years (1997–2001 and 2001–2006). Following the introduction of the 2-week wait rule, there was a 47.6% reduction in the time from referral to first consultation with a specialist (42 days vs 22 days; P < 0.001). The time between first investigation and treatment has not reduced significantly. We also found that, despite the introduction of the 2-week wait rule, only 42% of the patients were diagnosed with bladder cancer using this pathway. Patients referred as ‘routine’ waited longer to be seen in hospital although there was no significant delay in receiving treatment. CONCLUSIONS: The introduction of the 2-week wait rule has significantly reduced the time patients with bladder cancer wait for their first consultation with a specialist. However, there is no significant change in the time between first consultation and treatment.