Phylogeny in Aid of the Present and Novel Microbial Lineages: Diversity in Bacillus

Bacillus represents microbes of high economic, medical and biodefense importance. Bacillus strain identification based on 16S rRNA sequence analyses is invariably limited to species level. Secondly, certain discrepancies exist in the segregation of Bacillus subtilis strains. In the RDP/NCBI databases, out of a total of 2611 individual 16S rDNA sequences belonging to the 175 different species of the genus Bacillus, only 1586 have been identified up to species level. 16S rRNA sequences of Bacillus anthracis (153 strains), B. cereus (211 strains), B. thuringiensis (108 strains), B. subtilis (271 strains), B. licheniformis (131 strains), B. pumilus (83 strains), B. megaterium (47 strains), B. sphaericus (42 strains), B. clausii (39 strains) and B. halodurans (36 strains) were considered for generating species-specific framework and probes as tools for their rapid identification. Phylogenetic segregation of 1121, 16S rDNA sequences of 10 different Bacillus species in to 89 clusters enabled us to develop a phylogenetic frame work of 34 representative sequences. Using this phylogenetic framework, 305 out of 1025, 16S rDNA sequences presently classified as Bacillus sp. could be identified up to species level. This identification was supported by 20 to 30 nucleotides long signature sequences and in silico restriction enzyme analysis specific to the 10 Bacillus species. This integrated approach resulted in identifying around 30% of Bacillus sp. up to species level and revealed that B. subtilis strains can be segregated into two phylogenetically distinct groups, such that one of them may be renamed

Population Recovery of Nicobar Long-Tailed Macaque Macaca fascicularis umbrosus following a Tsunami in the Nicobar Islands, India

Natural disasters pose a threat to isolated populations of species with restricted distributions, especially those inhabiting islands. The Nicobar long tailed macaque.Macaca fascicularis umbrosus, is one such species found in the three southernmost islands (viz. Great Nicobar, Little Nicobar and Katchal) of the Andaman and Nicobar archipelago, India. These islands were hit by a massive tsunami (Indian Ocean tsunami, 26 December 2004) after a 9.2 magnitude earthquake. Earlier studies [Umapathy et al. 2003; Sivakumar, 2004] reported a sharp decline in the population of M. f. umbrosus after thetsunami. We studied the distribution and population status of M. f. umbrosus on thethree Nicobar Islands and compared our results with those of the previous studies. We carried out trail surveys on existing paths and trails on three islands to get encounter rate as measure of abundance. We also checked the degree of inundation due to tsunami by using Normalized Difference Water Index (NDWI) on landsat imageries of the study area before and after tsunami. Theencounter rate of groups per kilometre of M. f. umbrosus in Great Nicobar, Little Nicobar and Katchal was 0.30, 0.35 and 0.48 respectively with the mean group size of 39 in Great Nicobar and 43 in Katchal following the tsunami. This was higher than that reported in the two earlier studies conducted before and after the tsunami. Post tsunami, there was a significant change in the proportion of adult males, adult females and immatures, but mean group size did not differ as compared to pre tsunami. The results show that population has recovered from a drastic decline caused by tsunami, but it cannot be ascertained whether it has reached stability because of the altered group structure. This study demonstrates the effect of natural disasters on island occurring species

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Community-based prevention of hepatitis-B-related liver cancer: Australian insights

PROBLEM: Although most primary hepatocellular cancers (HCCs) are attributable to chronic viral hepatitis and largely preventable, such cancers remain a leading cause of cancer-related mortality wherever chronic hepatitis B is endemic. APPROACH: Many HCCs could be prevented by increasing awareness and knowledge of hepatitis B, optimizing the monitoring of chronic hepatitis B and using antiviral treatments - but there are gaps in the implementation of such strategies. LOCAL SETTING: The 'B Positive' programme, based in Sydney, Australia, is designed to improve hepatitis-B-related health outcomes among immigrants from countries with endemic hepatitis B. The programme offers information about disease screening, vaccination and treatment options, as well as optimized access to care. RELEVANT CHANGES: The B Positive programme has been informed by economic modelling. The programme offers culturally tailored education on chronic hepatitis B to target communities and their health practitioners and regular follow-up through a population-based registry of cases. LESSONS LEARNT: As the costs of screening for chronic hepatitis B and follow-up are relatively low and less than one in every four cases may require antiviral drugs, optimizing access to treatment seems an appropriate and cost-effective management option. The identification and accurate staging of cases and the judicious use of antiviral medications are predicated upon an informed and educated health workforce. As establishing community trust is a lengthy process, delaying the implementation of programmes against chronic hepatitis B until antiviral drugs become cheaper is unwarrante

Using a chronic hepatitis B Registry to support population-level liver cancer prevention in Sydney, Australia

Monica C Robotin,1&ndash;3 Ximena Masgoret,1 Mamta Porwal,4 David Goldsbury,5 Chee Khoo,6,7 Jacob George,2,3 1School of Medicine, The University of Notre Dame Australia, Darlinghurst, 2Faculty of Medicine, University of Sydney, Camperdown, 3Storr Liver Center, Westmead Institute for Medical Research, Westmead Hospital, Westmead, 4Australian School of Graduate Management, University of New South Wales, Kensington, 5Cancer Council NSW, Woolloomooloo, 6Royal Australasian College of General Practitioners, Sydney, 7University of Western Sydney, Macarthur, NSW, Australia Background: Approximately 1% of Australians have chronic hepatitis B (CHB), which disproportionately affects people born in hepatitis B-endemic countries. Currently, approximately half of the people affected remain undiagnosed and antiviral treatment uptake is suboptimal (~5%). This increases the likelihood of developing end-stage disease complications, particularly hepatocellular cancer (HCC), and largely accounts for the significant increases in HCC incidence and mortality in Australia over the last decades. As our previous economic modeling suggested that CHB screening and treatment is cost-effective, we tested the feasibility of a primary care-based model of CHB diagnosis and management to prevent HCC.Materials and methods: From 2009 to 2016, the B Positive program trialed a CHB screening and management program in an area of high disease prevalence in Sydney, Australia. Trained local primary care providers (general practitioners) screened and managed their CHB patients using a purpose-built CHB Registry and a risk stratification algorithm, which allocated patients to ongoing primary care-based management or specialist referral.Results: The program enrolled and followed up &gt;1,500 people (25% of the target population). Their median age was 48 years, with most participants being born in China (50%) or Vietnam (32%). The risk stratification algorithm allocated most Registry participants (n=847 or 79%) to primary care-based management, reducing unnecessary specialist referrals. The level of antiviral treatment uptake in Registry patients was 18%, which was the optimal level in this population group.Conclusion: This pilot program demonstrated that primary care-based hepatitis B diagnosis and management is acceptable to patients and their care providers and significantly increases compliance with treatment guidelines. This would suggest that scaling up access to hepatitis B treatment is achievable and can provide a means to operationalize a population-level approach to CHB management and liver cancer prevention. Keywords: hepatitis B Registry, primary care, cancer prevention, antiviral treatment, risk stratificatio