New Frontiers: Precise Editing of Allergen Genes Using CRISPR

Genome engineering with clustered regularly interspaced short palindromic repeats (CRISPR) technology offers the unique potential for unequivocally deleting allergen genes at the source. Compared to prior gene editing approaches, CRISPR boasts substantial improvements in editing efficiency, throughput, and precision. CRISPR has demonstrated success in several clinical applications such as sickle cell disease and β-thalassemia, and preliminary knockout studies of allergenic proteins using CRISPR editing show promise. Given the advantages of CRISPR, as well as specific DNA targets in the allergen genes, CRISPR gene editing is a viable approach for tackling allergy, which may lead to significant disease improvement. This review will highlight recent applications of CRISPR editing of allergens, particularly cat allergen Fel d 1, and will discuss the advantages and limitations of this approach compared to existing treatment options.

Cultural, Morphological and Pathogenic Variability in Alternaria cyamopsidis Causing Alternaria Blight of Clusterbean in Rajasthan

Background: Alternaria cyamopsidis (Rang. and Rao) causes Alternaria blight of clusterbean and it is one of the significant disease of clusterbean. Studies were conducted to compare the Cultural, morphological and pathogenic variability among ten isolates of Alternaria cyamopsidis from clusterbean, in five districts of Rajasthan viz., Bikaner, Barmer, Churu, Hanumangarh and Jaipur. Methods: During 2016-17 exhaustive survey was conducted in clusterbean growing areas of Rajasthan and collected diseased samples of clusterbean caused by Alternaria. All the samples were processed for isolation, purification and their pathogenicity was proved in cagehouse and laboratory and standard methods were adopted for cultural and morphological variability study. Result: All the isolates showed variation in their morphological characters, i.e., colony color and shape; conidial number, size, width, length, shape and septation on PDA. Out of ten isolates two isolate, viz., AlcyJp1 and AlcyJp2 showed maximum colony diameter 89.50 and 86.30 mm, respectively. All the isolates varied in their spore length and width and virulent on the tested variety of clusterbean for virulence. AlcyJp1 was the most virulent and produced maximum (65.50%) disease intensity, followed by AlcyJp2 isolate (61.22%).

Effectiveness of bioactive compounds in amending the soil infested with soil-borne Ralstonia solanacearum of potato

Three natural bioactive compounds, viz. cow dung, bee propolis and turmeric powder were applied to amend the Ralstonia solanacearum infested soil of potato. Sun dried cow dung @ 30 t/ha, aqueous extraction of turmeric powder @ 30 kg/ha and propolis @ 5 lit/ha were applied to the inoculated soil by mixing with field soil in SAU (Dhaka) and BARI (Gazipur). Data on pH, organic matter, total cfu/ml and avirulent cfu/ml of the treatment applied soil and per cent disease index (PDI) of bacterial wilt of potato were recorded. Significant difference in soil pH and per cent organic matter (OM) occurred in all the amended soil as compared to control. A decreased total cfu/ml of R. solanacearum occurred in all the treated soil, but propolis (8.2 X 107) and cow dung (1.1 X 108) showed the lowest count. However, in increasing the avirulent count of R. solanacearum, turmeric powder (1.8 X 109) showed the highest count compared to other amended soil. Significant disease reduction over control was also observed in all the treatments, but propolis (45.65%) and turmeric powder (43.48%) showed the best results in wilt disease reduction. J. Biodivers. Conserv. Bioresour. Manag. 2021, 7(1): 43-50

MRI-based nomogram for the prediction of prostate cancer diagnosis: A multi-centre validated patient–physician decision tool

Objective: To update and externally validate a magnetic resonance imaging (MRI)-based nomogram for predicting prostate biopsy outcomes with a multi-centre cohort. Materials and methods: Prospective data from five UK-based centres were analysed. All men were biopsy naïve. Those with missing data, no MRI, or prostate-specific antigen (PSA) > 30 ng/mL were excluded. Logistic regression analysis was used to confirm predictors of prostate cancer outcomes including MRI-PIRADS (Prostate Imaging Reporting and Data System) score, PSA density, and age. Clinically significant disease was defined as International Society of Urological Pathology (ISUP) Grade Group ⩾ 2 (Gleason grade ⩾ 7). Biopsy strategy included transrectal and transperineal approaches. Nomograms were produced using logistic regression analysis results. Results: A total of 506 men were included in the analysis with median age 66 (interquartile range (IQR) = 60–69). Median PSA was 6.6 ng/mL (IQR = 4.72–9.26). PIRADS ⩾ 3 was reported in 387 (76.4%). Grade Group ⩾ 2 detection was 227 (44.9%) and 318 (62.8%) for any cancer. Performance of the MRI-based nomogram was an area under curve (AUC) of 0.84 (95% confidence interval (CI) = 0.81–0.88) for Grade Group ⩾ 2% and 0.85 (95% CI = 0.82–0.88) for any prostate cancer. Conclusion: We present external validation of a novel MRI-based nomogram in a multi-centre UK-based cohort, showing good discrimination in identifying men at high risk of having clinically significant disease. These findings support this risk calculator use in the prostate biopsy decision-making process. Level of evidence: 2c

Considering Predictive Factors in the Diagnosis of Clinically Significant Prostate Cancer in Patients with PI-RADS 3 Lesions

The use of multi-parametric magnetic resonance imaging (mpMRI) in conjunction with the Prostate Imaging Reporting and Data System (PI-RADS) is standard practice in the diagnosis, surveillance, and staging of prostate cancer. The risk associated with lesions graded at a PI-RADS score of 3 is ambiguous. Further characterization of the risk associated with PI-RADS 3 lesions would be useful in guiding further work-up and intervention. This study aims to better characterize the utility of PI-RADS 3 and associated risk factors in detecting clinically significant prostate cancer. From a prospectively maintained IRB-approved dataset of all veterans undergoing mpMRI fusion biopsy at the Southeastern Louisiana Veterans Healthcare System, we identified a cohort of 230 PI-RADS 3 lesions from a dataset of 283 consecutive UroNav-guided biopsies in 263 patients from October 2017 to July 2020. Clinically significant prostate cancer (Gleason Grade ≥ 2) was detected in 18 of the biopsied PI-RADS 3 lesions, representing 7.8% of the overall sample. Based on binomial analysis, PSA densities of 0.15 or greater were predictive of clinically significant disease, as was PSA. The location of the lesion within the prostate was not shown to be a statistically significant predictor of prostate cancer overall (p = 0.87), or of clinically significant disease (p = 0.16). The majority of PI-RADS 3 lesions do not represent clinically significant disease; therefore, it is possible to reduce morbidity through biopsy. PSA density is a potential adjunctive factor in deciding which patients with PI-RADS 3 lesions require biopsy. Furthermore, while the risk of prostate cancer for African-American men has been debated in the literature, our findings indicate that race is not predictive of identifying prostate cancer, with comparable Gleason grade distributions on histology between races.

COEVOLUTION WITH SPATIALLY STRUCTURED RICE LANDRACES MAINTAINS MULTIPLE GENERALIST LINEAGES IN THE RICE BLAST PATHOGEN

Traditional agrosystems, where humans, crops and microbes have coevolved over long periods, can serve as models to understand the eco-evolutionary determinants of disease dynamics and help the engineering of durably resistant agrosystems. Here, we investigated the genetic and phenotypic relationship between rice (Oryza sativa) landraces and their rice blast pathogen (Magnaporthe oryzae) in the traditional Yuanyang terraces of flooded rice paddies in China, where rice landraces have been grown and bred over centuries without significant disease outbreaks. Analyses of genetic subdivision revealed that indica rice plants clustered according to landrace names. Three new diverse lineages of rice blast specific to the Yuanyang terraces coexisted with lineages previously detected at the worldwide scale. Population subdivision in the pathogen population did not mirror pattern of population subdivision in the host. Measuring the pathogenicity of rice blast isolates on landraces revealed generalist life histories. Our results suggest that the implementation of disease control strategies based on the emergence or maintenance of a generalist lifestyle in pathogens may sustainably reduce the burden of disease in crops.

Monitored therapy of sporadic mycobacteriosis caused by Mycobacterium genavense in Atlantic canaries (Serinus canaria) and Bengalese finch (Lonchura striata)

Introduction Mycobacteriosis is a significant disease of companion and wild birds which causes emaciation and widely distributed lesions, as well as being a potential zoonosis. Its primary aetiological agents in birds are Mycobacterium avium subsp. avium and the fastidious Mycobacterium genavense. This study monitored the therapy of birds naturally infected with Mycobacterium genavense to gain understanding of its effectiveness and the interrelation of co-infections with the disease course and pharmacotherapy. Material and Methods Five Atlantic canaries (Serinus canaria) and one Bengalese finch (Lonchura striata) with tentative diagnoses of mycobacteriosis resulting from M. genavense infection were treated twice daily with clarithromycin at 40 mg/kg, ethambutol at 30 mg/kg, and moxifloxacin at 10 mg/kg for 6 months. Two canaries were also found to be carriers of Cryptosporidium galli. Mycobacteria in faecal samples of all birds were investigated by bacterioscopy and quantitative PCR. Results Molecular tests yielded positive results for up to four months after treatment initiation for M. genavense and Cryptosporidium, but microscopy failed to detect the latter after four weeks in specimens from one canary. Co-infections with polyomavirus (in all birds) and circovirus and bornavirus (in canaries) were diagnosed. Two birds died during treatment and one was euthanised because of other disease, 1 month after treatment completion. Three canaries were in relatively good health a year after treatment. Conclusion Canary circovirus and polyomavirus co-infection may suppress the immune system and this may facilitate the development of mycobacteriosis. The set of drugs used led to the complete cure of mycobacteriosis in three canaries. In one bird the disease returned. Clarithromycin was the active drug against C. galli. Molecular methods serve well to monitor mycobacteriosis therapy and identify M. genavense and C. galli carriage.

Validation and adaptation of the Spanish version of the systemic lupus activity questionnaire (S-SLAQ) in an Argentinean population

Objectives To validate the systemic lupus activity questionnaire (SLAQ) in Spanish language. Methods The SLAQ questionnaire was translated and adapted in Spanish. Consecutive SLE patients from 8 centers in Argentina were included. A rheumatologist completed a Systemic Lupus Activity Measure (SLAM), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K, and a physician’s assessment. Reliability was assessed by internal consistency (Cronbach’s alpha), stability by test–retest reliability (intraclass correlation coefficient), and construct validity by evaluating the correlation with clinically relevant scores. Sensitivity and specificity for clinically significant disease activity (SLEDAI ≥6) of different S-SLAQ cut-off points were evaluated. Results We included 97 patients ((93% female, mean age: 40 years (SD14.7)). Internal consistency was excellent (Cronbach’s alpha = 0.84, p < 0.001), and the intraclass correlation coefficient was 0.95 ( p < 0.001). Mean score of S-SLAQ was 8.2 (SD 7.31). Correlation of S-SLAQ was moderate with Patient NRS (r= 0.63 p< 0.001), weak with SLAM-no lab ( r = 0.42, p <0.001) and SLAM ( r = 0.38, p < 0.0001), and very weak with SLEDAI-2K ( r = 0.15, p =0.1394). Using the S-SLAQ cutoff of five points, the sensitivity was 72.2% and specificity was 37.9%, for clinically significant disease activity. Conclusions The S-SLAQ showed good validity and reliability. A good correlation, similar to the original instrument, was observed with patient´s global disease activity. No correlation was found between S-SLAQ and gold standard disease activity measures like SLEDAI-2K and SLAM. The S-SLAQ cutoff point of 5 showed a good sensitivity to identify the active SLE population and therefore could be an appropriate screening instrument for disease activity in clinical and epidemiological studies.

Diagnostic and periprocedural discomfort in inflammatory bowel disease: a concept analysis using the Rodgers evolutionary method

Background: Inflammatory bowel disease (IBD) is a chronic, autoimmune gastrointestinal illness with a significant disease burden. The concept of discomfort in IBD lacks conceptual clarity. Aims: To analyse the concept of diagnostic and periprocedural discomfort in IBD and provide an understanding of its evolution, use in IBD research and implications for clinical practice through its attributes, antecedents, consequences and related terms. Methods: The Rodgers evolutionary concept analysis method guided this inductive approach. Findings: Seven journal articles, a dictionary, a thesaurus and one book were included in this analysis. The analysis yielded 12 surrogate terms, three attributes, five antecedents and one consequence. Diagnostic and periprocedural discomfort in IBD is an unpleasant, multidimensional and subjective experience, with biological, psychological or technical antecedents, which can occur independently of pain. Conclusion: Further research is required to enhance understanding of discomfort to improve the care of people living with IBD and their relationship with healthcare providers.

Hepatitis in Idiopathic Hypereosinophilic Syndrome: Report of an Unusual Case

World Health Organization defines a rare diagnosis Idiopathic hypereosinophilic syndrome (HES) as a persistent eosinophilia for 6 months and resulting in end-organ dysfunction. Most of the patients present with nonspecific symptoms, while others will present with symptoms of the affected organs, commonly those involving the heart, skin, or nervous system. Gastrointestinal or liver involvement is estimated to affect up to one-third of patients with HES, although patients with clinically significant disease are limited to case reports. This is the first report of a patient presenting with idiopathic HES related hepatitis and achalasia. Hypereosinophilic syndrome has been reported to be associated with hepatic dysfunction; liver histology is mainly characterized by a diffuse eosinophilic inflammatory infiltrate. A 49-yr-old woman, diagnosed as a case of idiopathic hypereosinophilic syndrome with bone marrow and pulmonary eosinophilic infiltrates associated with peripheral eosinophilia,high IgE level developed features of chronic gatrornteritis, hepatitis, with a significant eosinophil component. She responded well to systemic glucocorticoid and Imatinib therapy with normalization of liver function tests within a few weeks.