Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists

A Case of Pyoderma Gangrenosum Misdiagnosed as Necrotizing Infection: A Potential Diagnostic Catastrophe

In this article, we present a case of pyoderma gangrenosum (PG), misdiagnosed initially as a necrotizing infection that significantly worsened due to repeated surgical debridement and aggressive wound care therapy, almost resulting in limb amputation despite antibiotic therapy. The PG lesions improved after pancytopenia were further investigated, and the diagnosis and treatment of an underlying hematologic malignancy was initiated. The diagnosis and management of PG is challenging given the paucity of robust clinical evidence, lack of standard diagnostic criteria, and absence of clinical practice guidelines. It is imperative that clinicians recognize PG as a clinical diagnosis that must be considered in any patient with enlarging, sterile, necrotic lesions that are unresponsive to prolonged and appropriate antibiotics. Early recognition can prevent devastating sequelae such as deep tissue and bone infections associated with a chronic open wound, severe cosmetic morbidity, and potential limb amputation

Kisan Call Centre: 'Advisers' mostly rely on own knowledge to guide farmers: Study

Farmers in Maharashtra still prefer seeking agriculture-related information from fellow farmers but the community is fast switching to mobile phones for such information, according to a recent study submitted to the Union Ministry of Agriculture. Led by researcher Sangeeta Shroff from the Agro-Economic Research Centre at Gokhale Institute of Politics and Economics (GIPE), the study aimed at understanding the structure, design, implementation and performance of the Kisan Knowledge Management System, Farmers’ Portal and M-Kisan portal operating in Maharashtra. Tele-calling to the Farmers’ Tele-Advisors (FTA) at Kisan Call Centre (KCC), Pune, is among the most favoured ways for cultivators seeking all kinds of information. The KCC operates with 69 ‘advisers’, who guide farmers, and two supervisers, receiving over 3,000 calls on an average everyday from across Maharashtra and Goa. The study covered 30 ‘advisers’ and 80 farmers from Pune, Ahmednagar, Solapur and Osmanabad districts. The study found that farmers heavily relied on it and mostly sought advices on what pesticide to be sprayed on crops under a disease attack, current market prices, appropriate insecticide to be sprayed on a crop, storage of farm produce, among others. Farmers who took part in the study said they fully depended on the KCC for credit and insurance decisions; 74 per cent of them sought advice on disease control while 67 per cent were keen to know about storage. Advice on sowing or how to improve quality was, however, barely sought from the KCC, leaving it solely to the farmer. Interestingly, the ‘advisers’ admitted they mostly relied on personal knowledge while guiding farmers than on government-provided booklets or information kits. “The ‘advisers’ combined their own knowledge with information gathered from web portals like KKMS, M-Kisan and others while fielding calls from farmers,” an expert at GIPE said. Surprisingly, no reference or guidance was taken from nodal officers or experts at agriculture colleges or universities, both of whom are integral to running these call centres. While 80 per cent of the ‘advisers’ said they had a degree in agriculture, about 13 per cent have a postgraduate degree in the subject but 22 of the 30 ‘advisers’ who participated in the research said they had no previous work experience. Number of farmers dialling the call centre rose from 2.21 lakh in 2004 to 48.01 lakh in 2014-2015. With 2.22 lakh calls, Ahmednagar district tops the charts (see box). Calls to KCCs peak during the harvest season, the study found. “With a fixed cropping pattern for paddy followed along the west coast, very few farmers called KCCs for advice,” the study noted. So far, only five farmers have called the centre from Palghar, the least from among the 36 districts of the state. Similarly, Sindhudurg (2,503), Mumbai (2,776), Ratnagiri (2,821), Raighad (3,433) and Thane (7,636) are among places which logged less number of calls. Interestingly, mobile phones have become the most preferred medium among the farming community to gather information: 62 of the 80 farmers who took part in the study said they gathered information from mobile phones, either through SMS or other means; 34 farmers extensively used internet on cellphones to avail farming-related information. An equal number of farmers also depended on TV

Streptococcus agalactiae infective endocarditis in Canada: a multicenter retrospective nested case control analysis

Background Infective endocarditis (IE) caused by Streptococcus agalactiae (GBS) is increasingly reported and associated with an aggressive course and high mortality rate. Existing literature on GBS IE is limited to case series; we compared the characteristics of patients with GBS IE to patients with GBS bacteremia without IE to identify risk factors for development of IE. Methods A nested case–control study in a cohort of adult patients with GBS bacteremia over a 18-year period was conducted across seven centres in three Canadian cities. A chart review identified patients with possible or definite IE (per Modified Duke Criteria) and patients with IE were matched to those without endocarditis in a 1:3 fashion. Multivariate analyses were completed using logistic regression. Results Of 520 patients with GBS bacteremia, 28 cases of possible or definite IE were identified (5.4%). 68% (19/28) met criteria for definite IE, surgery was performed in 29% (8/28), and the overall in-hospital mortality rate was 29% (8/28). Multivariate analysis demonstrated that IE was associated with injection drug use (OR = 19.6, 95% CI = 3.39–111.11, p = 0.001), prosthetic valve (OR = 11.5, 95% CI = 1.73–76.92, p = 0.011) and lack of identified source of bacteremia (OR = 3.81, 95% CI = 1.24–11.65, p = 0.019). Conclusions GBS bacteremia, especially amongst people who inject drugs, those with prosthetic valves, and those with no apparent source of infection, should increase clinical suspicion for IE.Medicine, Faculty ofNon UBCInfectious Diseases, Division ofMedicine, Department ofRespiratory Medicine, Division ofReviewedFacult

Improving the Quality of Colonoscopy Bowel Preparation Using an Educational Video

Colonoscopy is the preferred modality for colon cancer screening. A successful colonoscopy requires proper bowel preparation. Adequate bowel preparation continues to remain a limiting factor. One hundred thirty-three patients scheduled for an outpatient colonoscopy were prospectively randomized in a single-blinded manner to video or nonvideo group. In addition to written bowel preparation instructions, patients in the video group viewed a brief instructional video. Quality of colon preparation was measured using the Ottawa Bowel Preparation Quality scale, while patient satisfaction with preparation was evaluated using a questionnaire. Statistical analyses were used to evaluate the impact of the instructional colonoscopy video. There were significant differences in the quality of colonoscopy preparation between the video and the nonvideo groups. Participants who watched the video had better preparation scores in the right colon (P = 0.0029), mid-colon (P = 0.0027), rectosigmoid (P = 0.0008), fluid content (P = 0.03) and aggregate score (median score 4 versus 5; P = 0.0002). There was no difference between the two groups with regard to patient satisfaction. Income, education level, sex, age and family history of colon cancer had no impact on quality of colonoscopy preparation or patient satisfaction. The addition of an instructional bowel preparation video significantly improved the quality of colon preparation

Impact of the Combination of Daptomycin and Trimethoprim-Sulfamethoxazole on Clinical Outcomes in Methicillin-Resistant Staphylococcus aureus Infections

Complicated Staphylococcus aureus infections, including bacteremia, are often associated with treatment failures, prolonged hospital stays, and the emergence of resistance to primary and even secondary therapies. Daptomycin is commonly used as salvage therapy after vancomycin failure for the treatment of methicillin-resistant S. aureus (MRSA) infections. Unfortunately, the emergence of daptomycin resistance, especially in deep-seated infections, has been reported, prompting the need for alternative or combination therapy. Numerous antibiotic combinations with daptomycin have been investigated clinically and in vitro. Of interest, the combination of daptomycin and trimethoprim-sulfamethoxazole (TMP-SMX) has proved to be rapidly bactericidal in vitro to strains that are both susceptible and nonsusceptible to daptomycin. However, to date, there is limited clinical evidence supporting the use of this combination. This was a multicenter, retrospective case series of patients treated with the combination of daptomycin and TMP-SMX for at least 72 h. The objective of this study was to describe the safety and effectiveness of this regimen in clinical practice. The most commonly stated reason that TMP-SMX was added to daptomycin was persistent bacteremia and/or progressive signs and symptoms of infection. After the initiation of combination therapy, the median time to clearance of bacteremia was 2.5 days. Microbiological eradication was demonstrated in 24 out of 28 patients, and in vitro synergy was demonstrated in 17 of the 17 recovered isolates. Further research with this combination is necessary to describe the optimal role and its impact on patient outcomes

Monitoring of Dynamic Changes and Clonal Evolution in Circulating Tumor DNA From Patients With IDH-Mutated Cholangiocarcinoma Treated With Isocitrate Dehydrogenase Inhibitors

PURPOSE IDH mutations occur in about 30% of patients with cholangiocarcinoma. Analysis of mutations in circulating tumor DNA (ctDNA) can be performed by droplet digital polymerase chain reaction (ddPCR). The analysis of ctDNA is a feasible approach to detect IDH mutations. METHODS We isolated ctDNA from the blood of patients with IDH-mutated advanced cholangiocarcinoma collected at baseline, on therapy, and at progression to isocitrate dehydrogenase (IDH) inhibitors. RESULTS Of 31 patients with IDH1R132 (n = 26) or IDH2R172 mutations (n = 5) in the tumor, IDH mutations were detected in 84% of ctDNA samples analyzed by ddPCR and in 83% of ctDNA samples analyzed by nextgeneration sequencing (NGS). Patients with a low variant allele frequency of ctDNA detected by NGS at baseline had a longer median time to treatment failure compared to patients with high variant allele frequency of ctDNA (3.6 v 1.5 months; P = .008). Patients with a decrease in IDH-mutated ctDNA on therapy by ddPCR compared with no change/increase had a trend to a longer median survival (P = .07). Most frequent emergent alterations in ctDNA by NGS at progression were ARID1A (n = 3) and TP53 mutations (n = 3). CONCLUSION Detection of IDH mutations in ctDNA in patients with advanced cholangiocarcinoma is feasible, and dynamic changes in ctDNA can correspond with the clinical course and clonal evolution.12 month embargo; published 16 February 2022This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]