Barriers and facilitators to starting insulin in patients with type 2 diabetes: a systematic review.

AIM: To identify the barriers and facilitators to start insulin in patients with type 2 diabetes. METHOD: This was a systematic review. We conducted a systematic search using PubMed, EMBASE, CINAHL and Web of Science (up to 5 June 2014) for original English articles using the terms 'type 2 diabetes', 'insulin', and free texts: 'barrier' or 'facilitate' and 'initiate'. Two pairs of reviewers independently assessed and extracted the data. Study quality was assessed with Qualsyst. RESULTS: A total of 9740 references were identified: 41 full-text articles were assessed for eligibility. Twenty-five articles (15 qualitative, 10 quantitative) were included in the review. Good inter-rater reliability was observed for the Qualsyst score (weighted kappa 0.7). Three main themes identified were as follows: patient-related, healthcare professional and system factors. The main patient-related barriers were fear of pain and injection (n = 18), concerns about side effects of insulin (n = 12), perception that insulin indicated end stage of diabetes (n = 11), inconvenience (n = 10), difficulty in insulin administration (n = 7), punishment (n = 7) and stigma and discrimination (n = 7). Healthcare professionals' barriers were as follows: poor knowledge and skills (n = 9), physician inertia (n = 5) and language barriers (n = 4). System barriers included lack of time (n = 5). The most common facilitators were understanding the benefits of insulin (n = 7), not being afraid of injections (n = 5), and patient education and information (n = 5). CONCLUSION: Major barriers to insulin initiation persist despite availability of newer and safer insulin. Healthcare professionals should explore and address these barriers. Targeted interventions should be developed to overcome these barriers.

A consensus on men's health status and policy in Asia: a Delphi survey.

OBJECTIVE: There is currently no documentation on the availability and implementation of policies related to men's health in Asia. This Delphi study aimed to achieve an Asian consensus on men's health policy based on the opinions and recommendations from men's health key opinion leaders. STUDY DESIGN: A two-phase Delphi online survey was used to gather information from men's health stakeholders across Asian countries. METHODS: All stakeholders were invited to participate in the survey through men's health conferences, personal contacts, recommendations from international men's health organizations and snowballing method. Stakeholders were asked about their concerns on 17 men's health key issues as well as their opinion on the availability and recommendations on men's health policies and programmes in their countries. RESULTS: There were a total of 128 stakeholders (policy makers, clinicians, researchers and consumers), from 28 Asian countries, who responded in the survey. Up to 85% of stakeholders were concerned about various men's health issues in Asia and in their respective country, particularly in smoking, ischaemic heart disease and high blood pressure. There is a lack of men's health policies and programmes in Asia (availability = 11.6-43.5%) and up to 92.9% of stakeholders recommended that these should be developed. CONCLUSIONS: These findings call for policy change and development, and more importantly a concerted effort to elevate men's health status in Asia.

Post mortem changes in relation to different types of clothing.

Post mortem changes are important in estimating post mortem interval (PMI). This project's aim was to study the effect of burial and type of clothing on rate of decomposition, which can contribute to estimating PMI for victims. 12 rabbits (Oryctolagus cuniculus) carcasses were separated into 3 groups: no clothing, light clothing and heavy clothing. Control subjects were placed on the ground surface while test subjects were buried at 30 cm depth graves. Soil samples prior and after decomposition were collected for soil pH and moisture analysis. Post mortem change was assessed using a Total Body Score system. The head, neck and limb regions were found to decay faster than the body trunk region. Mummifi cation occurred on body parts that were exposed directly to the atmosphere while adipocere formed on some buried subjects. Burial delayed decomposition due to lower insect activity and lower soil temperature. The soil layer also blocked the accessibility of majority of the arthropods, causing further delay in decomposition. Clothing enhanced decay for bodies on ground surface because it provided protection for maggots and retained moisture on tissues. However, clothing delayed decomposition in buried bodies because it physically separated the bodies from soil and arthropods. Higher sun exposure and repetitive exhumation showed acceleration of decomposition. The decomposition process increased soil pH and moisture percentage values. Soil pH initially increased until pH 8.0-8.4 followed by a slight decrease while soil moisture percentage changed inconsistently. Burial was significant in affecting post mortem change, F(1,11)=12.991, p<0.05 while type of clothing was not significant, F(2,9)=0.022, p=0.978 and combination of both type of clothing and burial factors were also not significant, F(2,3)=0.429, p=0.686. For validation, an accuracy of 83.33% was achieved based on soil pH and soil moisture percentage analysis.

Barriers to implementing a national health screening program for men in Malaysia: An online survey of healthcare providers.

INTRODUCTION: This study aimed to determine the views and practices of healthcare providers and barriers they encountered when implementing the national health screening program for men in a public primary care setting in Malaysia. METHODS: An online survey was conducted among healthcare providers across public health clinics in Malaysia. All family medicine specialists, medical officers, nurses and assistant medical officers involved in the screening program for adult men were invited to answer a 51-item questionnaire via email or WhatsApp. The questionnaire comprised five sections: participants' socio-demographic information, current screening practices, barriers and facilitators to using the screening tool, and views on the content and format of the screening tool. RESULTS: A total of 231 healthcare providers from 129 health clinics participated in this survey. Among them, 37.44% perceived the implementation of the screening program as a "top-down decision." Although 37.44% found the screening tool for adult men "useful," some felt that it was "time consuming" to fill out (38.2%) and "lengthy" (28.3%). In addition, 'adult men refuse to answer' (24.1%) was cited as the most common patient-related barrier. CONCLUSIONS: This study provided useful insights into the challenges encountered by the public healthcare providers when implementing a national screening program for men. The screening tool for adult men should be revised to make it more user-friendly. Further studies should explore the reasons why men were reluctant to participate in health screenings, thus enhancing the implementation of screening programs in primary care.

Evolutionary dynamics and sites of illegitimate recombination revealed in the interspersion and sequence junctions of two nonhomologous satellite DNAs in cactophilic Drosophila species.

Satellite DNA (satDNA) is a major component of genomes but relatively little is known about the fine-scale organization of unrelated satDNAs residing at the same chromosome location, and the sequence structure and dynamics of satDNA junctions. We studied the organization and sequence junctions of two nonhomologous satDNAs, pBuM and DBC-150, in three species from the neotropical Drosophila buzzatii cluster (repleta group). In situ hybridization to microchromosomes, interphase nuclei and extended DNA fibers showed frequent interspersion of the two satellites in D. gouveai, D. antonietae and, to a lesser extent, D. seriema. We isolated by PCR six pBuM x DBC-150 junctions: four are exclusive to D. gouveai and two are exclusive to D. antonietae. The six junction breakpoints occur at different positions within monomers, suggesting independent origin. Four junctions showed abrupt transitions between the two satellites, whereas two junctions showed a distinct 10 bp tandem duplication before the junction. Unlike pBuM, DBC-150 junction repeats are more variable than randomly cloned monomers and showed diagnostic features in common to a 3-monomer higher-order repeat seen in the sister species D. serido. The high levels of interspersion between pBuM and DBC-150 repeats suggest extensive rearrangements between the two satellites, maybe favored by specific features of the microchromosomes. Our interpretation is that the junctions evolved by multiples events of illegitimate recombination between nonhomologous satDNA repeats, with subsequent rounds of unequal crossing-over expanding the copy number of some of the junctions.

Detection of dengue viruses and Wolbachia in Aedes aegypti and Aedes albopictus larvae from four urban localities in Kuala Lumpur, Malaysia.

Dengue fever (DF) is currently one of the most important mosquito-borne diseases that affects humans. Dengue fever (DF) and dengue hemorrhagic fever (DHF) are caused by four serotypes of dengue viruses (DENV-1 to DENV-4). The main vector transmitting dengue is Aedes aegypti while Aedes albopictus acts as a secondary vector. As treatment is unavailable and the first dengue vaccine approved in Mexico, Dengvaxia® has yet to be accepted worldwide, prevention of the disease relies heavily on surveillance and control of mosquito vectors. A transgene driver, Wolbachia was found to limit the transmission of dengue virus in Aedes mosquitoes. Wolbachia alone was able to inhibit viral replication, dissemination and transmission in A. aeygpti mosquitoes in experimental studies. In A. albopictus, Wolbachia did not affect the replication of dengue virus but was able to reduce the viral infection of mosquito salivary glands and limit transmission. Studies on Wolbachia have all been carried out in adult Aedes mosquitoes, hence this study was conducted to determine the presence of dengue virus serotypes and Wolbachia in A. aegypti and A. albopictus larvae collected from ovitraps in four localities in Kuala Lumpur viz. Happy Gardens, IMU Bukit Jalil, Ampang and Taman Yarl. Another objective of this study was to determine the association between dengue virus serotypes and the presence of Wolbachia in A. aegypti and A. albopictus larvae. A total of 300 mosquito larvae was collected; 99 (Happy Gardens), 85 (Bukit Jalil), 73 (Ampang) and 43 (Taman Yarl). Out of 300 larvae collected, 284 were identified as A. albopictus and 16 others were identified as A. aegypti. Of the 284 A. albopictus larvae collected, 211 (74.3%) and 73 (25.7%) were found to be negative and positive for dengue virus respectively. The dengue serotypes detected were 2 DENV-2 (2.7%), 58 DENV-3 (79.5%) and 13 DENV-4 (17.8%). DENV-1 was not detected in any of the A. albopictus larvae. For A. aegypti, out of 16 A. aegypti larvae collected, 12 (75%) were found to be negative and 4 (25%) were positive for DENV-2. For the detection of Wolbachia in A. albopictus, 71 out of 284 (25%) and 213 (75%) larvae were found to be positive and negative for Wolbachia respectively. For A. aegypti, 4 (25%) and 12 (75%) out of 16 larvae were positive and negative for Wolbachia respectively. This is the first report of Wolbachia in A. albopictus and A. aegypti larvae in Malaysia. A chisquare test analysis to determine the association between dengue virus and Wolbachia in A. albopictus and A. aegypti larvae collected from the four localities in Kuala Lumpur showed that there was no association (χ2 = 3.080; df = 1; P > 0.05).

Crystallisation of RNA-protein complexes. II. The application of protein engineering for crystallisation of the U1A protein-RNA complex.

The hairpin is one of the most commonly found structural motifs of RNA and is often a binding site for proteins. Crystallisation of U1A spliceosomal protein bound to a RNA hairpin, its natural binding site on U1snRNA, is described. RNA oligonucleotides were synthesised either chemically or by in vitro transcription using T7 RNA polymerase and purified to homogeneity by gel electrophoresis. Crystallisation trials with the wild-type protein sequence and RNA hairpins containing various stem sequences and overhanging nucleotides only resulted in a cubic crystal form which diffracted to 7-8 A resolution. A new crystal form was grown by using a protein variant containing mutations of two surface residues. The N-terminal sequence of the protein was also varied to reduce heterogeneity which was detected by protein mass spectrometry. A further crystallisation search using the double mutant protein and varying the RNA hairpins resulted in crystals diffracting to beyond 1.7 A. The methods and strategy described in this paper may be applicable to crystallisation of other RNA-protein complexes.

Detection of dengue viruses and Wolbachia in Aedes aegypti and Aedes albopictus larvae from four urban localities in Kuala Lumpur, Malaysia

Dengue fever (DF) is currently one of the most important mosquito-borne diseases that affects humans. Dengue fever (DF) and dengue hemorrhagic fever (DHF) are caused by four serotypes of dengue viruses (DENV-1 to DENV-4). The main vector transmitting dengue is Aedes aegypti while Aedes albopictus acts as a secondary vector. As treatment is unavailable and the first dengue vaccine approved in Mexico, Dengvaxia® has yet to be accepted worldwide, prevention of the disease relies heavily on surveillance and control of mosquito vectors. A transgene driver, Wolbachia was found to limit the transmission of dengue virus in Aedes mosquitoes. Wolbachia alone was able to inhibit viral replication, dissemination and transmission in A. aeygpti mosquitoes in experimental studies. In A. albopictus, Wolbachia did not affect the replication of dengue virus but was able to reduce the viral infection of mosquito salivary glands and limit transmission. Studies on Wolbachia have all been carried out in adult Aedes mosquitoes, hence this study was conducted to determine the presence of dengue virus serotypes and Wolbachia in A. aegypti and A. albopictus larvae collected from ovitraps in four localities in Kuala Lumpur viz. Happy Gardens, IMU Bukit Jalil, Ampang and Taman Yarl. Another objective of this study was to determine the association between dengue virus serotypes and the presence of Wolbachia in A. aegypti and A. albopictus larvae. A total of 300 mosquito larvae was collected; 99 (Happy Gardens), 85 (Bukit Jalil), 73 (Ampang) and 43 (Taman Yarl). Out of 300 larvae collected, 284 were identified as A. albopictus and 16 others were identified as A. aegypti. Of the 284 A. albopictus larvae collected, 211 (74.3%) and 73 (25.7%) were found to be negative and positive for dengue virus respectively. The dengue serotypes detected were 2 DENV-2 (2.7%), 58 DENV-3 (79.5%) and 13 DENV-4 (17.8%). DENV-1 was not detected in any of the A. albopictus larvae. For A. aegypti, out of 16 A. aegypti larvae collected, 12 (75%) were found to be negative and 4 (25%) were positive for DENV-2. For the detection of Wolbachia in A. albopictus, 71 out of 284 (25%) and 213 (75%) larvae were found to be positive and negative for Wolbachia respectively. For A. aegypti, 4 (25%) and 12 (75%) out of 16 larvae were positive and negative for Wolbachia respectively. This is the first report of Wolbachia in A. albopictus and A. aegypti larvae in Malaysia. A chisquare test analysis to determine the association between dengue virus and Wolbachia in A. albopictus and A. aegypti larvae collected from the four localities in Kuala Lumpur showed that there was no association (χ2 = 3.080; df = 1; P > 0.05).

Cystic degeneration of ductal adenocarcinoma of the pancreatic tail.

We present a 54-year-old Chinese man with a tumour at the pancreatic tail associated with a presumed cystic splenic lesion. Histological examination showed a pancreatic ductal adenocarcinoma with extensive cystic degeneration and invasion of the spleen, a rare imaging presentation for such a tumour.

Erdheim-Chester disease: a rare cause of interstitial lung disease.

Erdheim-Chester disease is a non-Langerhans cell histiocytosis that is progressive and may lead on to multi-organ involvement. Pulmonary involvement is rare, its presentation is nonspecific, and it carries an adverse outcome. Several radiological features, when considered together, may point to the diagnosis. This condition should be considered in the differential diagnosis of interstitial lung disease. We describe a 39-year-old woman who presented with dry cough, malaise and progressive dyspnoea. She was diagnosed to have late stage interstitial lung disease due to Erdheim-Chester disease.

Crystal structure at 1.92 A resolution of the RNA-binding domain of the U1A spliceosomal protein complexed with an RNA hairpin.

The crystal structure of the RNA-binding domain of the small nuclear ribonucleoprotein U1A bound to a 21-nucleotide RNA hairpin has been determined at 1.92 A resolution. The ten-nucleotide RNA loop binds to the surface of the beta-sheet as an open structure, and the AUUGCAC sequence of the loop interacts extensively with the conserved RNP1 and RNP2 motifs and the C-terminal extension of the RNP domain. These interactions include stacking of RNA bases with aromatic side chains of proteins and many direct and water-mediated hydrogen bonds. The structure reveals the stereochemical basis for sequence-specific RNA recognition by the RNP domain.

The cloning of Ty1-copia-like retrotransposons from 10 varieties of banana (Musa Sp.).

Ty1-copia-like retrotransposons have been identified and investigated in several plant species. Here, the internal region of the reverse transcriptase (RT) gene of Ty1-copia-like retrotransposons was amplified by PCR from total genomic DNA of 10 varieties of banana. Two to four clones from each variety were sequenced. Extreme heterogeneity in the sequences of Ty1-copia-like retrotransposons from all the varieties was revealed following sequence analysis of the reverse transcriptase (RT) fragments. The size of the individual RT gene fragments varied between 213 and 309 bp. Southern blots of genomic DNA digested from Musa acuminata and other banana varieties probed with W8 clone from M. acuminata and A4 clone from Pisang Abu Nipah showed similar strong, multiple restriction fragments together with other faint hybridization band patterns with variable intensities indicating the presence of many copies of the Ty1-copia-like retrotransposons in the genomes. There was no correlation between retroelement sequence and the banana species (with A or B genomes) from which it arose, suggesting that the probes are not useful for tracking genomes through breeding populations.

Identification of molecular contacts between the U1 A small nuclear ribonucleoprotein and U1 RNA.

We recently determined the crystal structure of the RNP domain of the U1 small nuclear ribonucleoprotein A and identified Arg and Lys residues involved in U1 RNA binding. These residues are clustered around the two highly conserved segments, RNP1 and RNP2, located in the central two beta strands. We have now studied the U1 RNA binding of mutants where potentially hydrogen bonding residues on the RNA binding surface were replaced by non-hydrogen bonding residues. In the RNP2 segment, the Thr11----Val and Asn15----Val mutations completely abolished, and the Tyr13----Phe and Asn16----Val mutations substantially reduced the U1 RNA binding, suggesting that these residues form hydrogen bonds with the RNA. In the RNP1 segment Arg52----Gln abolished, but Arg52----Lys only slightly affected U1 RNA binding, suggesting that Arg52 may form a salt bridge with phosphates of U1 RNA. Ethylation protection experiments of U1 RNA show that the backbone phosphates of the 3' two-thirds of loop II and the 5' stem are in contact with the U1 A protein. The U1 A protein-U1 RNA binding constant is substantially reduced by A----G and G----A replacements in loop II, but not by C----U or U----C replacements. Based on these biochemical data we propose a structure for the complex between the U1 A ribonucleoprotein and U1 RNA.