Antisense RNA (asRNA) technology: the concept and applications in crop improvement and sustainable agriculture.

Antisense RNA (asRNA) technology is a method used to silence genes and inhibit their expression. Gene function relies on expression, which follows the central dogma of molecular biology. The use of asRNA can regulate gene expression by targeting specific mRNAs, which can result in changes in phenotype, disease resistance, and other traits associated with protein expression profiles. This technology uses short, single-stranded oligonucleotide strands that are complementary to the targeted mRNA. Manipulating and regulating protein expression during its translation can either knock out or knock down the expression of a gene of interest. Therefore, functional genomics can benefit from this technology since it allows for the regulation of protein expression. In this review, we discuss the concept, and applications of asRNA technology which include delaying ripening, prolonging shelf life, biofortification, and increasing biotic and abiotic resistance among others in crop improvement and sustainable agriculture.

A need for greater awareness: a mixed methods study of patient and healthcare professional perspectives on the diagnosis journey for haemophagocytic lymphohistiocytosis (HLH).

OBJECTIVES: Our aim was to better understand and raise awareness of the diagnosis journey and quantify any barriers for timely diagnosis of haemophagocytic lymphohistiocytosis (HLH), to support patients' struggle with diagnosis and reduce time to diagnosis. METHODS: Patients diagnosed with, or caregivers for those diagnosed with primary or secondary HLH and physicians involved in the treatment of HLH were recruited. Quantitative interviews were undertaken with patients/caregivers to quantify key elements of the diagnosis journey, followed by qualitative interviews with participants. Interviews took place between March-May 2021. RESULTS: Thirty-three patients/caregivers and nine physicians took part in this mixed methods study. Lack of physician awareness of HLH was a common frustration for patients/caregivers, causing delayed diagnosis. All physicians indicated bone-marrow testing is a key step in the diagnosis process, and some patients/caregivers had frustrations around testing. Emergency care doctors, although not usually involved in the diagnosis process, were among the most-seen specialists by patients/caregivers. Patients/caregivers suggested potential improvements in available information, such as providing information on treatment options and condition management. DISCUSSION: Patients/caregivers and physicians agreed on the need to raise overall awareness of HLH signs/symptoms among priority groups of physicians to recognise how signs/symptoms can progress and develop. Improvements in the testing process and communication would directly impact the speed of diagnosis and support patients/caregivers during the diagnostic journey, respectively. CONCLUSION: Raising awareness of key issues, such as signs/symptoms, tests and diagnostic procedures, and improved communication and support for patients/caregivers, are key to speeding up HLH diagnosis and improving outcomes.

Summary of the consultation on a strategy for services for chronic obstructive pulmonary disease (COPD) in England.

The Consultation on a Strategy for Services for COPD in England is the culmination of five years' work by respiratory specialists from all disciplines, as well as representatives from the voluntary sector, patients, carers and planners. It has been led by the Department of Health in England and the joint National Directors for the programme, Professor Sue Hill and Dr Robert Winter. The Strategy outlines service standards for providers of COPD care and is complementary to the UK National Institute for Health and Clinical Excellence (NICE) guidelines on the management of COPD. Its key elements are: • preventing the development and progression of COPD • diagnosing COPD accurately and at an early stage • developing structured care based on national guidance • promoting self-management education • reducing the number of people admitted to hospital • improving access to end-of-life care • promoting good asthma services. In essence this is an aspirational strategy which aims to change the way that the NHS in England delivers care for people with COPD by identifying them earlier and managing them optimally in order to reduce the likelihood of progression to the more severe stages of the disease. An economic impact assessment shows that implementing the Strategy will save approximately £1billion over 10 years as well as sparing many people from a debilitating illness. This supplement is based on the Strategy Consultation document as well as the NICE guidelines for COPD management. It aims to elucidate practical implementation of the COPD Strategy, and includes verbatim the Strategy recommendations as well as highly relevant clinical information from the NICE guidelines. Implementation of the Strategy recommendations should lead to optimum care for patients with COPD.

T Cells Genetically Modified to Express an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma.

Purpose Therapies with novel mechanisms of action are needed for multiple myeloma (MM). T cells can be genetically modified to express chimeric antigen receptors (CARs), which are artificial proteins that target T cells to antigens. B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells but not normal essential cells. We conducted the first-in-humans clinical trial, to our knowledge, of T cells expressing a CAR targeting BCMA (CAR-BCMA). Patients and Methods Sixteen patients received 9 × 106 CAR-BCMA T cells/kg at the highest dose level of the trial; we are reporting results of these 16 patients. The patients had a median of 9.5 prior lines of MM therapy. Sixty-three percent of patients had MM refractory to the last treatment regimen before protocol enrollment. T cells were transduced with a γ-retroviral vector encoding CAR-BCMA. Patients received CAR-BCMA T cells after a conditioning chemotherapy regimen of cyclophosphamide and fludarabine. Results The overall response rate was 81%, with 63% very good partial response or complete response. Median event-free survival was 31 weeks. Responses included eradication of extensive bone marrow myeloma and resolution of soft-tissue plasmacytomas. All 11 patients who obtained an anti-MM response of partial response or better and had MM evaluable for minimal residual disease obtained bone marrow minimal residual disease-negative status. High peak blood CAR+ cell levels were associated with anti-MM responses. Cytokine-release syndrome toxicities were severe in some cases but were reversible. Blood CAR-BCMA T cells were predominantly highly differentiated CD8+ T cells 6 to 9 days after infusion. BCMA antigen loss from MM was observed. Conclusion CAR-BCMA T cells had substantial activity against heavily treated relapsed/refractory MM. Our results should encourage additional development of CAR T-cell therapies for MM.

Lesions associated with a novel Mycoplasma sp. in California sea lions (Zalophus californianus) undergoing rehabilitation.

From July 1999 to November 2001, Mycoplasma sp. was cultured from lesions in 16 California sea lions (Zalophus californianus) undergoing rehabilitation. The Mycoplasma sp. was the likely cause of death of four animals in which it was associated with either pneumonia or polyarthritis. The most common lesion associated with this bacterium was subdermal abscessation, found in 12 animals. Other lesions included intramuscular abscesses, septic arthritis, and lymphadenopathy. Infection was associated with a leukocytosis and left shift in 12 animals. Animals with abscesses improved clinically after surgical lancing, irrigation, and systemic antibiotic therapy. The mycoplasma isolates had a consistent 16S rRNA sequence dissimilar from other Mycoplasma spp. and represent a novel species, Mycoplasma zalophi proposed sp. nov.

Systemic mycosis caused by Scedosporium apiospermum in a stranded northern elephant seal (Mirounga angustirostris) undergoing rehabilitation.

A recently weaned, stranded, male northern elephant seal (Mirounga angustirostris) pup that had been undergoing rehabilitation was found severely obtunded with hyponatremia, hypokalemia, hypochloremia, and hypophosphatemia after a history of intermittent regurgitation. The animal was euthanatized, and gross postmortem findings included multifocal abscessation affecting brain, spleen, kidney, muscle, and subcutaneous tissue. Scedosporium apiospermum and mixed bacteria were cultured from brain, kidney, and subcutaneous tissue. Histopathologic examination revealed multiple fungal granulomas of variable size in the kidneys, brain, liver, and skeletal muscle. This is the first report of S. apiospermum infection associated with lesions in a marine mammal.