Using Non-Homogeneous Models of Nucleotide Substitution to Identify Host Shift Events: Application to the Origin of the 1918 ‘Spanish’ Influenza Pandemic Virus

Nonhomogeneous Markov models of nucleotide substitution have received scant attention. Here we explore the possibility of using nonhomogeneous models to identify host shift nodes along phylogenetic trees of pathogens evolving in different hosts. It has been noticed that influenza viruses show marked differences in nucleotide composition in human and avian hosts. We take advantage of this fact to identify the host shift event that led to the 1918 ‘Spanish’ influenza. This disease killed over 50 million people worldwide, ranking it as the deadliest pandemic in recorded history. Our model suggests that the eight RNA segments which eventually became the 1918 viral genome were introduced into a mammalian host around 1882–1913. The viruses later diverged into the classical swine and human H1N1 influenza lineages around 1913–1915. The last common ancestor of human strains dates from February 1917 to April 1918. Because pigs are more readily infected with avian influenza viruses than humans, it would seem that they were the original recipient of the virus. This would suggest that the virus was introduced into humans sometime between 1913 and 1918

The RNA Polymerase PB2 Subunit of Influenza A/HongKong/156/1997 (H5N1) Restrict the Replication of Reassortant Ribonucleoprotein Complexes

BACKGROUND: Genetic reassortment plays a critical role in the generation of pandemic strains of influenza virus. The influenza virus RNA polymerase, composed of PB1, PB2 and PA subunits, has been suggested to influence the efficiency of genetic reassortment. However, the role of the RNA polymerase in the genetic reassortment is not well understood. METHODOLOGY/PRINCIPAL FINDINGS: Here, we reconstituted reassortant ribonucleoprotein (RNP) complexes, and demonstrated that the PB2 subunit of A/HongKong/156/1997 (H5N1) [HK PB2] dramatically reduced the synthesis of mRNA, cRNA and vRNA when introduced into the polymerase of other influenza strains of H1N1 or H3N2. The HK PB2 had no significant effect on the assembly of the polymerase trimeric complex, or on promoter binding activity or replication initiation activity in vitro. However, the HK PB2 was found to remarkably impair the accumulation of RNP. This impaired accumulation and activity of RNP was fully restored when four amino acids at position 108, 508, 524 and 627 of the HK PB2 were mutated. CONCLUSIONS/SIGNIFICANCE: Overall, we suggest that the PB2 subunit of influenza polymerase might play an important role for the replication of reassortant ribonucleoprotein complexes

Scholarly publishing depends on peer reviewers

The peer-review crisis is posing a risk to the scholarly peer-reviewed journal system. Journals have to ask many potential peer reviewers to obtain a minimum acceptable number of peers accepting reviewing a manuscript. Several solutions have been suggested to overcome this shortage. From reimbursing for the job, to eliminating pre- publication reviews, one cannot predict which is more dangerous for the future of scholarly publishing. And, why not acknowledging their contribution to the final version of the article published? PubMed created two categories of contributors: authors [AU] and collaborators [IR]. Why not a third category for the peer-reviewer

Developing and user testing new pharmacy label formats—A study to inform labelling standards

Background Dispensed prescription medicine labels (prescription labels) are important information sources supporting safe and appropriate medicines use. Objective To develop and user test patient-centred prescription label formats. Methods Five stages: developing 12 labels for four fictitious medicines of varying dosage forms; diagnostic user testing of labels (Round 1) with 40 consumers (each testing three labels); iterative label revision, and development of Round 2 labels (n = 7); user testing of labels (Round 2) with 20 consumers (each testing four labels); labelling recommendations. Evaluated labels stated the active ingredient and brand name, using various design features (eg upper case and bold). Dosing was expressed differently across labels: frequency of doses/day, approximate times of day (eg morning), explicit times (eg 7 to 9 AM), and/or explicit dosing interval. Participants’ ability to find and understand medicines information and plan a dosing schedule were assessed. Results Participants demonstrated satisfactory ability to find and understand the dosage for all label formats. Excluding active ingredient and dosing schedule, 14/19 labels (8/12 in Round 1; 6/7 in Round 2) met industry standard on performance. Participants’ ability to correctly identify the active ingredient varied, with clear medicine name sign-posting enabling all participants evaluating these labels to find and understand the active ingredient. When planning a dosing schedule, doses were correctly spaced if the label stated a dosing interval, or frequency of doses/day. Two-thirds planned appropriate dosing schedules using a dosing table. Conclusions Effective prescription label formatting and sign-posting of active ingredient improved communication of information on labels, potentially supporting safe medicines use. Patient and Public Involvement Consumers actively contributed to the development of dispensed prescription medicine labels. Feedback from consumers following the first round was incorporated in revisions of the labels for the next round. Patient and public involvement in this study was critical to the development of readable and understandable dispensed prescription medicine labels

Thresholds for adding degraded tropical forest to the conservation estate

Logged and disturbed forests are often viewed as degraded and depauperate environments compared with primary forest. However, they are dynamic ecosystems1 that provide refugia for large amounts of biodiversity2,3, so we cannot afford to underestimate their conservation value4. Here we present empirically defined thresholds for categorizing the conservation value of logged forests, using one of the most comprehensive assessments of taxon responses to habitat degradation in any tropical forest environment. We analysed the impact of logging intensity on the individual occurrence patterns of 1,681 taxa belonging to 86 taxonomic orders and 126 functional groups in Sabah, Malaysia. Our results demonstrate the existence of two conservation-relevant thresholds. First, lightly logged forests (68%) of their biomass removed, and these are likely to require more expensive measures to recover their biodiversity value. Overall, our data confirm that primary forests are irreplaceable5, but they also reinforce the message that logged forests retain considerable conservation value that should not be overlooked

A qualitative study exploring medicines use pattern and practice among general public in Malaysia

Objective: The objective of this study is to explore the pattern and practice of medicine use among the general public; and to explore the key factors influencing medicine use among medicine users. Methods: A qualitative approach using focus group discussions was conducted to get in-depth information about medicines use pattern and practice from the general public. Adult people who reported using medicines at the time of study or in the previous month were approached. Two focus group discussions were audio-recorded and transcribed verbatim. The obtained data were analysed using thematic content analysis. Results: This study found that there are some misunderstanding about the appropriate use of medicines. The majority of the participants reported that they were complying with their medication regimen. However, forgetting to take medicines was stated by 4 participants while 2 participants stopped taking medicines when they felt better. In addition, 10 participants reporting using medicines according to their own knowledge and past experience. Whereas 4 participants took medicines according to other informal resources such as family, friends or the media. Seven participants have experienced side effects with using medicines, 4 of them informed their doctor while 3 participants stopped taking medicines without informing their doctor. Conclusion: There was a misunderstanding about medicines use in terms of medication compliance, self-management of the illness and the resources of information about using medicines. Many efforts are still needed from health care professionals to provide sufficient information about medicines use in order to decrease the risk of inappropriate use of medicines and to achieve better therapeutic outcome

Parent’s knowledge and management of their children’s ailments in Malaysia

Minor ailments like sore throat, fever, cough and diarrhea can be relieved with over-the-counter (OTC) medications such as paracetamol or other traditional remedies, without seeking for consultation from general practitioners. Parents usually take the responsibility to come up with some kind of treatment for their children. Objective: (1) to evaluate the parents’ medical knowledge about OTC medicines which are usually used by the parents to treat their children and (2) to evaluate the parents’ management in dealing with their children’s ailments, and (3) to evaluate the association between medical knowledge and the management of children’s ailments related to medicine use among the parents. Methods: A cross-sectional survey was conducted to measure the parents’ knowledge about their children’s ailments. Subjects were selected and information was obtained in September 2008. Non-probability convenient sampling method was used. Parents were recruited from the general public to answer the questionnaires. Results: 197 parents filled in the questionnaires. From the total respondents, 48.2% of them were male. This study showed that most respondents have medium knowledge (6.11 SD=3.6) and a moderate management (4.39 SD=2.7). The results showed that there is a significant difference between the knowledge and the management level of ailments (P=0.033). Regarding the education level of the parents and the socioeconomic status, the p-value showed there was a significant difference between parents’ knowledge and their education level (P=0.012). Conclusion: This study showed that parents have inadequate knowledge and some misconception about how to go about treating their children when they are unwell. It is hoped that by identifying weak areas in parents’ management to their children’s ailments, better planned educational and behavioral modification efforts can be made to elevate the knowledge level among the parents when they medically treat their children

Assessment of health seeking behaviour and self-medication among general public in the state of Penang, Malaysia

Background: Patients’ behaviour in making decisions regarding health is currently changing from passive recipients to recipients who play an active role in taking action to control their health and taking self-care initiatives. Objectives: This study was conducted to evaluate the health seeking behaviour among general public and its associated factors; and to evaluate the medicine taking behaviour in public and the practice of self-medication. Methods: A cross-sectional study was undertaken among general public in Penang Island, Malaysia. A convenience sampling of 888 participants successfully completed the survey. Self-administered questionnaires were distributed among the residents in the north east of Penang Island. Results: This study showed that most of the participants chose to consult the physician when they experience any health problems (66.7%), followed by self-medication (20.9%). The first action for consulting the physician was significantly predicted by Malay respondents and retired people (OR 3.05, 95% CI 1.04-8.89). The prevalence of self-medication was 54%. The practice of self-medication was significantly associated with Chinese participants, educated people, people with alone living status and people with more self-care orientation. Conclusion: Increasing the awareness of the public about the rational choice of getting medical assistance is a very important issue to control their health. A health education program is needed to increase the awareness about the use of medicines among the general public and to enable them to make the right decisions relating to health problems

Isolated Gastric Tuberculosis: A Case Report and Review of Literature

Isolated gastric tuberculosis is a rare condition, even in those parts of the world where intestinal tuberculosis is common. Herein we describe a case of a thirty year old female patient with isolated gastric tuberculosis who presented with features of gastric outlet obstruction