Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events.

The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species

The role of epigenetics in renal ageing

An ability to separate natural ageing processes from processes specific to morbidities is required to understand the heterogeneity of age-related organ dysfunction. Mechanistic insight into how epigenetic factors regulate ageing throughout the life course, linked to a decline in renal function with ageing, is already proving to be of value in the analyses of clinical and epidemiological cohorts. Noncoding RNAs provide epigenetic regulatory circuits within the kidney, which reciprocally interact with DNA methylation processes, histone modification and chromatin. These interactions have been demonstrated to reflect the biological age and function of renal allografts. Epigenetic factors control gene expression and activity in response to environmental perturbations. They also have roles in highly conserved signalling pathways that modulate ageing, including the mTOR and insulin/insulin-like growth factor signalling pathways, and regulation of sirtuin activity. Nutrition, the gut microbiota, inflammation and environmental factors, including psychosocial and lifestyle stresses, provide potential mechanistic links between the epigenetic landscape of ageing and renal dysfunction. Approaches to modify the renal epigenome via nutritional intervention, targeting the methylome or targeting chromatin seem eminently feasible, although caution is merited owing to the potential for intergenerational and transgenerational effects

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

Anomalous origin of the right coronary artery diagnosed by cardiac computed tomography

Case Presentation A 34 year old female with no significant past medical history presented with intermittent left shoulder and chest pain. The pain was burning in nature over her left chest and radiated to her left arm. There were no alleviating or exacerbating factors. Initial electrocardiogram showed sinus bradycardia. Cardiac computed tomography angiography revealed anomalous origin of the right coronary artery, which arises from the left sinus of Valsalva (Figure 1) and then travels towards the right side between the pulmonary outflow tract and the aortic root, where it shows mild narrowing of about 50%, (Figure 2) for a length of approximately 1 cm. The woman performed 9 mets during her exercise stress nuclear test which demonstrated electrocardiographic evidence of ischemia with normal myocardial perfusion

Congestive Heart Failure and Vitamin D Deficiency

Introduction Congestive heart failure (CHF) is a chronic medical condition whoseincidence is rising. The prevalence of CHF is approximately 1% to3% in Western countries. Despite innovations in medical therapy,CHF is associated with high morbidity and mortality rates. CHF patients commonly experience muscle weakness and fatigueas two major symptoms. An altered intracellular handling ofionized calcium has been suggested to play a vital role in impairedmyocardial contraction. In isolated myocytes from patientswith end stage heart failure, systolic ionized calcium levelswere markedly decreased, while diastolic levels were elevated ascompared to healthy controls. In addition, digitalis and betablockermedical therapy is frequently used in CHF patients andis known to increase myocardial ionized calcium levels

Severe Heart Failure and Large Left Ventricular Thrombus Following Acute Myocardial Infarction

Case Presentation A 58 year-old man who recently underwent a left superficialfemoral artery thrombectomy presented with a three-day historyof worsening exertional dyspnea and bilateral pedal edema. Hispast medical history is significant for coronary artery disease,myocardial infarction, and insulin dependent diabetes mellitus.The patient initially presented to an outside hospital where hedeveloped ventricular tachycardia that warranted cardioversionthree times. Initial electrocardiogram showed inferior lead STsegment elevations and lateral lead ST depression

Left atrial myxoma

Case Presentation A 65 year-old female with a past medical history of hypertension and diabetes presented to her cardiologist’s office with symptoms consistent with progressive heart failure over an eight month period. A transthoracic echocardiogram done in the office demonstrated a normal-appearing mitral valve and normal left ventricular systolic function. Additionaly, it also revealed a large left atrial myxoma (pictured above). The mass obstructed flow through the mitral valve, resulting in a mean valvular gradient of 18 mm Hg, consistent with mitral stenosis-like physiology. As a result of these findings, the patient was admitted to our institution for further evaluation. A transesophageal echocardiogram was performed for further assessment and showed a 6.7 x 4.6 cm homogenous mass which appeared to be attached by a stalk to the interatrial septum at the fossa ovalis. The patient subsequently underwent excision of this myxoma along with a patch repair of the interatrial septum. Postoperatively she was stable and discharged home six days later with surgical and cardiac follow-up

Giant negative T waves

Case Presentation A 62 year old Caucasian man with a past medical history significant for (long standing and controlled) HTN, lymphoma (diagnosed 2 yrs ago and currently in remission), and diffuse esophageal spasm presented to an outside hospital with expressive aphasia and right sided weakness. He was treated with tissue plasminogen activator (t-PA) for left MCA embolic stroke with excellent clinical response with very minimal residual expressive aphasia. Further work up and evaluation there revealed a large left ventricular apical mass consistent with thrombus and he was subsequently transferred to our facility for further evaluation and management of this apical mass