Infection of immunocompetent mice with acid-water-pretreated Cryptosporidium parvum results in weight loss, and intestinal (structural and physiological) alterations

Cryptosporidiosis, caused by Cryptosporidium, causes self-limited diarrhea in normal hosts but may cause life-threatening diarrhea in immunocompromised persons. Cryptosporidium-induced manifestations, including weight-loss and intestinal physiological alterations are not noted in adult immunocompetent mice. So far, studies that have been used to test the therapeutic efficacy of drugs have been performed using various immunocompromised animal models. There is an urgent need of an immunocompetent small animal model that portrays Cryptosporidium-induced manifestations. In the current studies, we have compared two Cryptosporidium parvum pretreatment methods, we have hence used sodium hypochlorite or acidic water to treat Cryptosporidium parvum, followed by infection by oral gavage in adult immunocompetent C57BL6 mice. We demonstrated manifestations such as weight loss, intestinal structural and physiological alterations such as intestinal, villi blunting, and glucose malabsorption (as studied by the Ussing chamber technique) only in response to infection with C. parvum that has been treated with acidic water and not with sodium hypochlorite. These novel studies reveal that acidic water treatment of C. parvum results in manifestations of cryptosporidiosis in otherwise resistant immunocompetent mice. The current studies open up possibilities of using the normal immunocompetent mice model to test therapeutic drugs against cryptosporidiosis.     

Exploring the Potential of Human Milk and Formula Milk on Infants’ Gut and Health

Early-life gut microbiota plays a role in determining the health and risk of developing diseases in later life. Various perinatal factors have been shown to contribute to the development and establishment of infant gut microbiota. One of the important factors influencing the infant gut microbial colonization and composition is the mode of infant feeding. While infant formula milk has been designed to resemble human milk as much as possible, the gut microbiome of infants who receive formula milk differs from that of infants who are fed human milk. A diverse microbial population in human milk and the microbes seed the infant gut microbiome. Human milk contains nutritional components that promote infant growth and bioactive components, such as human milk oligosaccharides, lactoferrin, and immunoglobulins, which contribute to immunological development. In an attempt to encourage the formation of a healthy gut microbiome comparable to that of a breastfed infant, manufacturers often supplement infant formula with prebiotics or probiotics, which are known to have a bifidogenic effect and can modulate the immune system. This review aims to elucidate the roles of human milk and formula milk on infants’ gut and health.     

Chronic lymphocytic leukaemia Australasian consensus practice statement

Chronic lymphocytic leukaemia (CLL) is the most common haematological malignancy in Australia and New Zealand (ANZ). Considerable changes to diagnostic and management algorithms have occurred within the last decade. The availability of next-generation sequencing and measurable residual disease assessment by flow cytometry allow for advanced prognostication and response assessments. Novel therapies, including inhibitors of Bruton's tyrosine kinase (BTKi) and B-cell lymphoma 2 (BCL2) inhibitors, have transformed the treatment landscape for both treatment-naïve and relapsed/refractory disease, particularly for patients with high-risk genetic aberrations. Recommendations regarding appropriate supportive management continue to evolve, and special considerations are required for patients with CLL with respect to the global SARS-CoV-2 pandemic. The unique funding and treatment environments in Australasia highlight the need for specific local guidance with respect to the investigation and management of CLL. This consensus practice statement was developed by a broadly representative group of ANZ experts in CLL with endorsement by peak haematology bodies, with a view to providing this standardised guidance.     

Dilated cardiomyopathy and chronic cardiac inflammation: Pathogenesis,diagnosis and therapy

Dilated cardiomyopathy (DCM) is typically defined by left ventricular dilation and systolic dysfunction in the absence of a clear precipitant. Idiopathic disease is common; up to 50% of patients with DCM have no cause found despite imaging, genetic and biopsy assessments. Treatment remains focused on managing symptoms, reducing the risk of sudden cardiac death and ameliorating the structural and electrical complications of disease progression. In the absence of aetiology-specific treatments, the condition remains associated with a poor prognosis; mortality is approximately 40% at 10 years. The role of immune-mediated inflammatory injury in the development and progression of DCM was first proposed over 30 years ago. Despite the subsequent failures of three large clinical trials of immunosuppressive treatment (ATTACH, RENEWAL and the Myocarditis Treatment Trial), evidence for an abnormal adaptive immune response in DCM remains significant. In this review, we summarise and discuss available evidence supporting immune dysfunction in DCM, with a specific focus on cellular immunity. We also highlight current clinical and experimental treatments. We propose that the success of future immunosuppressive treatment trials in DCM will be dependent on the deep immunophenotyping of patients, to identify those with active inflammation and/or an abnormal immune response who are most likely to respond to therapy.