Collaborative denoising autoencoder for high glycated haemoglobin prediction.

A pioneering study is presented demonstrating that the presence of high glycated haemoglobin (HbA1c) levels in a patient’s blood can be reliably predicted from routinely collected clinical data. This paves the way for performing early detection of Type-2 Diabetes Mellitus (T2DM). This will save healthcare providers a major cost associated with the administration and assessment of clinical tests for HbA1c. A novel collaborative denoising autoencoder framework is used to address this challenge. The framework builds an independent denoising autoencoder model for the high and low HbA1c level, which extracts feature representations in the latent space. A baseline model using just three features: patient age together with triglycerides and glucose level achieves 76% F1-score with an SVM classifier. The collaborative denoising autoencoder uses 78 features and can predict HbA1c level with 81% F1-score

Guillain-Barré syndrome: a century of progress

In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts — novel findings that identified the disease we now know as Guillain–Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has, however, shown that primary axonal injury can be the underlying disease. The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes. Now, ongoing clinical trials of the complement inhibitor eculizumab are the first targeted immunotherapy in GBS

What works and why in the identification and referral of adults with comorbid obesity in primary care: a realist review

Primary care practitioners (PCPs) are well placed to identify individuals with obesity and weight‐related comorbidities and to refer them to weight management services (WMS), but this does not often happen in practice. In this realist review, we searched six databases for intervention studies targeted at PCPs to improve the identification and referral of adults with comorbid obesity. Realist analysis was used to identify context‐mechanism‐outcome (CMO) configurations across 30 included papers (reporting on 27 studies). Most studies used multiple intervention strategies, categorised into: (a) training, (b) tools to improve identification, (c) tools to improve ease of referral, (d) audit/feedback, (e) working in networks/quality circles, and (f) other. The realist synthesis identified 12 mechanisms through which interventions work to improve identification and referral, including increasing knowledge about obesity and awareness of and confidence in WMS among practitioners, improved communication and trust between practitioners and WMS, and higher priority given to weight management among primary care teams. The theory of “candidacy” (a person's eligibility for medical attention and intervention) provided a robust explanatory framework but required refinement: (a) to take account of the different services (primary care and weight management) that patients must navigate to access support; and (b) to acknowledge the importance of wider contextual factors

Do community medicine residency trainees learn through journal club? An experience from a developing country

BACKGROUND: Journal clubs are an internationally recognized teaching tool in many postgraduate medical education fields. In developing countries lack of funds for current print materials may have limited journal club use. But with advancing information technology trainees in developing countries increasingly have more access to high quality journals online. However, we are aware of no studies describing journal club existence and effectiveness in postgraduate medical training in Pakistan. Also we have found no published effectiveness studies of this teaching modality in Community Medicine (Public Health) in any country. This study evaluated the effectiveness of Community Medicine (Public Health) Resident Journal Club (CMR-JC) in Aga Khan University, Pakistan using international criteria for successful journal clubs (2 years continuous existence and more than 50% attendance) and examining resident and alumni satisfaction. METHODS: Journal club effectiveness criteria were searched using electronic search databases. Departmental records were reviewed from September1999–September 2005. Ninety percent of residents and alumni of Community Medicine Residency Programme participated voluntarily in a confidential survey. RESULTS: The CMR-JC was regularly conducted. More than 95% of residents attended. (Total residents in the CMR-Programme: 32). Twenty-seven out of 29 current residents/alumni responded to the anonymous questionnaire. Acquisition of critical appraisal skills (23 respondents) and keeping up with current literature (18 respondents) were the two most important objectives achieved. Respondents recommended improved faculty participation and incorporating a structured checklist for article review. CONCLUSION: CMR-JC fulfils criteria for effective journal clubs. Residents and alumni agree CMR-JC meets its objectives. Incorporating suggested recommendations will further improve standards. The journal club learning modality should be included in residency training programs in developing countries. Effective use of online resources to support journal clubs is demonstrated as a successful alternative to excessive expenditure for obtaining print journals. Those trying to start or improve journal clubs can benefit from our experience

Structural insights into the transcriptional and translational roles of Ebp1.

Accepted versio

Pseudonocardia hispaniensis sp. nov., a novel actinomycete isolated from industrial wastewater activated sludge

A novel actinomycete, designated PA3T, was isolated from an oil refinery wastewater treatment plant, located in Palos de la frontera, Huelva, Spain, and characterized taxonomically by using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences showed that the isolate formed a distinct subclade in the Pseudonocardia tree together with Pseudonocardia asaccharolytica DSM 44247T. The chemotaxonomic properties of the isolate, for example, the presence of MK-8 (H4) as the predominant menaquinone and iso-C16:0 as the major fatty acid are consistent with its classification in the genus Pseudonocardia. DNA:DNA pairing experiments between the isolate and the type strain of P. asaccharolytica DSM 44247T showed that they belonged to separate genomic species. The two strains were readily distinguished using a combination of phenotypic properties. Consequently, it is proposed that isolate PA3T represents a novel species for which the name Pseudonocardia hispaniensis sp. nov. is proposed. The type strain is PA3T (= CCM 8391T = CECT 8030T).Cuesta Amat, G.; Soler Hernández, A.; Alonso Molina, JL.; Ruvira, M.; Lucena, T.; Arahal, D.; Goodfellow, M. (2013). Pseudonocardia hispaniensis sp. nov., a novel actinomycete isolated from industrial wastewater activated sludge. Antonie van Leeuwenhoek. 103(1):135-142. doi:10.1007/s10482-012-9792-1S1351421031Alonso JL, Cuesta G, Ramírez GW, Morenilla JJ, Bernácer I, Lloret RM (2009) Manual de técnicas avanzadas para la identificación y control de bacterias filamentosas. Epsar-Generalitat Valenciana, España, p 21–36Ara I, Tsetseg B, Daram D, Suto M, Ando K (2011) Pseudonocardia mongoliensis sp. nov. and Pseudonocardia khuvsgulensis sp. nov., isolated from soil. Int J Syst Evol Microbiol 61:747–756Arahal DR, Sánchez E, Macián MC, Garay E (2008) Value of recN sequences for species identification and as a phylogenetic marker within the family ‘‘Leuconostocaceae’’. Int Microbiol 11:33–39Auffret M, Labbé D, Thouand G, Greer CW, Fayolle-Guichard F (2009) Degradation of a mixture of hydrocarbons, gasoline, and diesel oil additives by Rhodococcus aetherivorans and Rhodococcus wratislaviensis. Appl Environ Microbiol 75:7774–7782Cashion P, Hodler-Franklin MA, McCully J, Franklin M (1977) A rapid method for base ratio determination of bacterial DNA. Anal Biochem 81:461–466Chen HH, Qin S, Li J, Zhang YQ, Xu LH, Jiang CL, Kim CJ, Li WJ (2009) Pseudonocardia endophytica sp. nov., isolated from pharmaceutical plant Lobelia clavata. Int J Syst Evol Microbiol 59:559–563De Ley J, Cattoir H, Reynaerts A (1970) The quantitative measurement of DNA hybridization from renaturation rates. Eur J Biochem 12:133–142Duangmal K, Thamchaipenet A, Matsumoto A, Takahashi Y (2009) Pseudonocardia acaciae sp. nov., isolated from roots of Acacia auriculiformis A. Cunn. ex Benth. Int J Syst Evol Microbiol 59:1487–1491Gordon RE, Barnett DA, Handerhan JE, Pang CH-N (1974) Nocardia coeliaca, Nocardia autotrophica, and the nocardin strain. Int J Syst Bacteriol 24:54–63Hamid ME, Minnikin DE, Goodfellow M, Ridell M (1993) Thin-layer chromatographic analysis of glycolipids and mycolic acids from Mycobacterium farcinogenes, Mycobacterium senegalense and related taxa. Zbl Bakt 279:354–367Hasegawa T, Takizawa M, Tanida S (1983) A rapid analysis for chemical grouping of aerobic actinomycetes. J Gen Microbiol 29:319–322Henssen A (1957) Beiträge zur Morphologie und Systematik der thermophilen Actinomyceten. Arch Mikrobiol 26:373–414Huang,Y, Goodfellow M (2012) Genus Pseudonocardia Hennsen 1957, 408VP emend. In: Goodfellow M, Kämpfer P, Busse H-J, Trujillo M, Suzuki KE, Ludwig W, Whitman WB (eds) Bergey’s manual of systematic bacteriology, 2nd edn, vol 5, part B. Springer, New YorkHuang Y, Wang L, Lu Z, Hong L, Liu Z, Tan GYA, Goodfellow M (2002) Proposal to combine the genera Actinobispora and Pseudonocardia in an emended genus Pseudonocardia, and description of Pseudonocardia zijingensis sp. nov. Int J Syst Evol Microbiol 52:977–982Huss VAR, Festl H, Schleifer KH (1983) Studies on the spectrophotometric determination of DNA hybridization from renaturation rates. Syst Appl Microbiol 4:184–192Kaewkla O, Franco CMM (2010) Pseudonocardia adelaidensis sp. nov., an endophytic actinobacterium isolated from the surface-sterilized stem of a grey box tree (Eucalyptus microcarpa). Int J Syst Evol Microbiol 60:2818–2822Kaewkla O, Franco CMM (2011) Pseudonocardia eucalypti sp. nov., an endophytic actinobacterium with a unique knobby spore surface, isolated from roots of a native Australian eucalyptus tree. Int J Syst Evol Microbiol 61:742–746Kämpfer P, Kohlweyer U, Thiemer B, Andreesen JR (2006) Pseudonocardia tetrahydrofuranoxydans sp. nov. Int J Syst Evol Microbiol 56:1535–1538Labeda DP, Goodfellow M, Chun J, Zhi XY, Li WJ (2011) Reassessment of the systematics of the suborder Pseudonocardineae: transfer of genera within the family Actinosynnemataceae Labeda and Kroppenstedt 2000 emend. Zhi et al. 2009 into an emended family Pseudonocardiaceae Embley et al. 1989 emend. Zhi et al. 2009. Int J Syst Evol Microbiol 61:1259–1264Lane DJ (1991) 16S/23S rRNA sequencing. In: Stackebrandt E, Goodfellow M (eds) Nucleic acid techniques in bacterial systematics. Wiley, Chichester, pp 115–148Lechevalier MP, Lechevalier H (1970) Chemical composition as a criterion in the classification of aerobic actinomycetes. Int J Syst Bacteriol 20:435–443Lechevalier MP, Stern AER, Lechevalier HA (1981) Phospholipids in the taxonomy of actinomycetes. Zbl Bakt Suppl 11:111–116Li J, Zhao GZ, Huang HY, Zhu WY, Lee JC, Kim CJ, Xu LH, Zhang LX, Li WJ (2010) Pseudonocardia rhizophila sp. nov., a novel actinomycete isolated from a rhizosphere soil. Antonie Van Leeuwenhoek 98:77–83Liu ZP, Wu JF, Liu ZH, Liu SJ (2006) Pseudonocardia ammonioxydans sp. nov., isolated from coastal sediment. Int J Syst Evol Microbiol 56:555–558Lucena T, Pascual J, Garay E, Arahal DR, Macián MC, Pujalte MJ (2010) Haliea mediterranea sp. nov., a new marine gammaproteobacterium. Int J Syst Evol Microbiol 60:1844–1848Ludwig W et al (2004) ARB: a software environment for sequence data. Nucleic Acids Res 32:1363–1371Mahendra S, Alvarez-Cohen L (2005) Pseudonocardia dioxanivorans sp. nov., a novel actinomycete that grows on 1,4-dioxane. Int J Syst Evol Microbiol 55:593–598Mesbah M, Premachandran U, Whitman WB (1989) Precise measurement of the G+C content of deoxyribonucleic acid by high-performance liquid chromatography. Int J Syst Bacteriol 39:159–167MIDI (2008) Sherlock microbial identification system operating manual, version 6.1. MIDI Inc., NewarkMinnikin DE, O’Donnell AG, Goodfellow M, Alderson G, Athalye M, Schaal A, Parlett JH (1984) An integrated procedure for the extraction of isoprenoid quinones and polar lipids. J Microbiol Methods 2:233–241Nam S-W, Chun J, Kim S, Kim W, Zakrzewska-Czerwinska J, Goodfellow M (2003) Tsukamurella spumae sp. nov., a novel actinomycete associated with foaming in activated sludge plants. Syst Appl Microbiol 26:367–375Okoh A, Ajisebutu S, Babalola G, Trejo-Hernandez MR (2001) Potential of Burkholderia cepacia RQ1 in the biodegradation of heavy crude oil. Int Microbiol 4:83–87Park SW, Park ST, Lee JE, Kim YM (2008) Pseudonocardia carboxydivorans sp. nov., a carbon monoxide-oxidizing actinomycete, and an emended description of the genus Pseudonocardia. Int J Syst Evol Microbiol 58:2475–2478Pruesse E, Quast C, Knittel K, Fuchs B, Ludwig W, Peplies J, Glöckner FO (2007) SILVA: a comprehensive online resource for quality checked and aligned ribosomal RNA sequence data compatible with ARB. Nucleic Acids Res 35:7188–7196Qin S, Su YY, Zhang YQ, Wang HB, Jiang CL, Xu LH, Li WJ (2008) Pseudonocardia ailaonensis sp. nov., isolated from soil in China. Int J Syst Evol Microbiol 58:2086–2089Qin S, Zhu WY, Jiang JH, Klenk HP, Li J, Zhao GZ, Xu LH, Li WJ (2010) Pseudonocardia tropica sp. nov., an endophytic actinomycete isolated from the stem of Maytenus austroyunnanensis. Int J Syst Evol Microbiol 60:2524–2528Qin S, Xing K, Fei SM, Lin Q, Chen XM, Li WJ, Jiang JH (2011) Pseudonocardia sichuanensis sp. nov., a novel endophytic actinomycete isolated from the root of Jatropha curcus L. Antonie Van Leeuwenhoek 99:395–401Rehfuss M, Urban J (2005) Rhodococcus phenolicus sp. nov., a novel bioprocessor isolated actinomycete with the ability to degrade chlorobenzene, dichlorobenzene and phenol as sole carbon sources. Syst Appl Microbiol 28:695–701Reichert K, Lipski A, Pradella S, Stackebrandt E, Altendorf K (1998) Pseudonocardia asaccharolitica sp. nov. and Pseudonocardia sulfidoxidans sp. nov., two new dimethyl disulfide-degrading actinomycetes and emended description of the genus Pseudonocardia. Int J Syst Bacteriol 48:441–449Sakiyama Y, Thao NKN, Vinh HV, Giang NM, Miyadoh S, Hop DV, Ando K (2010) Pseudonocardia babensis sp. nov., isolated from plant litter. Int J Syst Evol Microbiol 60:2336–2340Sasser M (1990) Identification of bacteria by gas chromatography of cellular fatty acids. MIDI Tech Note 101:1–7Schäfer J, Busse HJ, Kämpfer P (2009) Pseudonocardia parietis sp. nov., from the indoor environment. Int J Syst Evol Microbiol 59:2449–2452Seviour RJ, Kragelund C, Kong Y, Eales K, Nielsen JL, Nielsen PH (2008) Ecophysiology of the actinobacteria in activated sludge systems. Antonie Van Leeuwenhoek 94:21–33Shirling EB, Gottlieb D (1966) Methods for characterization of Streptomyces species. Int J Syst Bacteriol 16:313–340Staneck JL, Roberts GD (1974) Simplified approach to identification of aerobic actinomycetes by thin-layer chromatography. Appl Microbiol 28:226–231Warwick S, Bowen T, McVeigh HP, Embley TM (1994) A phylogenetic analysis of the family Pseudonocardiaceae and the genera Actinokineospora and Saccharothrix with 16S rRNA sequences and a proposal to combine the genera Amycolata and Pseudonocardia in an emended genus Pseudonocardia. Int J Syst Bacteriol 44:293–299Wayne LG, Brenner DJ, Colwell RR, Grimont PAD, Kandler O, Krichevsky MI, Moore LH, Moore WEC, Murray RGE, Stackebrandt E, Starr MP, Trüper HG (1987) International committee on systematic bacteriology report on the ad hoc committee on the reconciliation of approaches to bacterial systematics. Int J Syst Bacteriol 37:463–464Yarza P, Ludwig W, Euzeby J, Amann R, Schleifer KH, Glöckner FO, Rossello-Mora R (2010) Update of the all-species living tree project based on 16S and 23S rRNA sequence analyses. Syst Appl Microbiol 33:291–299Zhao GZ, Li J, Zhu WY, Li XP, Tian SZ, Zhao LX, Xu LH, Li WJ (2011a) Pseudonocadia bannaensis sp. nov., a novel actinomycete isolated from the surface-sterilized roots of Artemisiae annua L. Antonie Van Leeuwenhoek 100:35–42Zhao GZ, Li J, Huang HY, Zhu WY, Zhao LX, Tang SK, Xu LH, Li WJ (2011b) Pseudonocardia artemisiae sp. nov., isolated from surface-sterilized Artemisia annua L. Int J Syst Evol Microbiol 61:1061–1065Zhao GZ, Li J, Huang HY, Zhu WY, Park DJ, Kim CJ, Xu LH, Li WJ (2011c) Pseudonocardia kunmingensis sp. nov., an actinobacterium isolated from surface-sterilized roots of Artemisia annua L. Int J Syst Evol Microbiol 61:2292–229

Post-Weaning Protein Malnutrition Increases Blood Pressure and Induces Endothelial Dysfunctions in Rats

Malnutrition during critical periods in early life may increase the subsequent risk of hypertension and metabolic diseases in adulthood, but the underlying mechanisms are still unclear. We aimed to evaluate the effects of post-weaning protein malnutrition on blood pressure and vascular reactivity in aortic rings (conductance artery) and isolated-perfused tail arteries (resistance artery) from control (fed with Labina®) and post-weaning protein malnutrition rats (offspring that received a diet with low protein content for three months). Systolic and diastolic blood pressure and heart rate increased in the post-weaning protein malnutrition rats. In the aortic rings, reactivity to phenylephrine (10−10–3.10−4 M) was similar in both groups. Endothelium removal or L-NAME (10−4 M) incubation increased the response to phenylephrine, but the L-NAME effect was greater in the aortic rings from the post-weaning protein malnutrition rats. The protein expression of the endothelial nitric oxide isoform increased in the aortic rings from the post-weaning protein malnutrition rats. Incubation with apocynin (0.3 mM) reduced the response to phenylephrine in both groups, but this effect was higher in the post-weaning protein malnutrition rats, suggesting an increase of superoxide anion release. In the tail artery of the post-weaning protein malnutrition rats, the vascular reactivity to phenylephrine (0.001–300 µg) and the relaxation to acetylcholine (10−10–10−3 M) were increased. Post-weaning protein malnutrition increases blood pressure and induces vascular dysfunction. Although the vascular reactivity in the aortic rings did not change, an increase in superoxide anion and nitric oxide was observed in the post-weaning protein malnutrition rats. However, in the resistance arteries, the increased vascular reactivity may be a potential mechanism underlying the increased blood pressure observed in this model

MSH6 and PMS2 mutation positive Australian Lynch syndrome families: novel mutations, cancer risk and age of diagnosis of colorectal cancer

Background: Approximately 10% of Lynch syndrome families have a mutation in MSH6 and fewer families have a mutation in PMS2. It is assumed that the cancer incidence is the same in families with mutations in MSH6 as in families with mutations in MLH1/MSH2 but that the disease tends to occur later in life, little is known about families with PMS2 mutations. This study reports on our findings on mutation type, cancer risk and age of diagnosis in MSH6 and PMS2 families. Methods: A total of 78 participants (from 29 families) with a mutation in MSH6 and 7 participants (from 6 families) with a mutation in PMS2 were included in the current study. A database of de-identified patient information was analysed to extract all relevant information such as mutation type, cancer incidence, age of diagnosis and cancer type in this Lynch syndrome cohort. Cumulative lifetime risk was calculated utilising Kaplan-Meier survival analysis. Results: MSH6 and PMS2 mutations represent 10.3% and 1.9%, respectively, of the pathogenic mutations in our Australian Lynch syndrome families. We identified 26 different MSH6 and 4 different PMS2 mutations in the 35 families studied. We report 15 novel MSH6 and 1 novel PMS2 mutations. The estimated cumulative risk of CRC at age 70 years was 61% (similar in males and females) and 65% for endometrial cancer in MSH6 mutation carriers. The risk of developing CRC is different between males and females at age 50 years, which is 34% for males and 21% for females. Conclusion: Novel MSH6 and PMS2 mutations are being reported and submitted to the current databases for identified Lynch syndrome mutations. Our data provides additional information to add to the genotype-phenotype spectrum for both MSH6 and PMS2 mutations

Integrative Genomic Analyses Identify BRF2 as a Novel Lineage-Specific Oncogene in Lung Squamous Cell Carcinoma

William Lockwood and colleagues show that the focal amplification of a gene, BRF2, on Chromosome 8p12 plays a key role in squamous cell carcinoma of the lung

Hypertension and type 2 diabetes: What family physicians can do to improve control of blood pressure - an observational study

Background: The prevalence of type 2 diabetes is rising, and most of these patients also have hypertension, substantially increasing the risk of cardiovascular morbidity and mortality. The majority of these patients do not reach target blood pressure levels for a wide variety of reasons. When a literature review provided no clear focus for action when patients are not at target, we initiated a study to identify characteristics of patients and providers associated with achieving target BP levels in community-based practice. Methods: We conducted a practice- based, cross-sectional observational and mailed survey study. The setting was the practices of 27 family physicians and nurse practitioners in 3 eastern provinces in Canada. The participants were all patients with type 2 diabetes who could understand English, were able to give consent, and would be available for follow-up for more than one year. Data were collected from each patient’s medical record and from each patient and physician/nurse practitioner by mailed survey. Our main outcome measures were overall blood pressure at target (< 130/80), systolic blood pressure at target, and diastolic blood pressure at target. Analysis included initial descriptive statistics, logistic regression models, and multivariate regression using hierarchical nonlinear modeling (HNLM). Results: Fifty-four percent were at target for both systolic and diastolic pressures. Sixty-two percent were at systolic target, and 79% were at diastolic target. Patients who reported eating food low in salt had higher odds of reaching target blood pressure. Similarly, patients reporting low adherence to their medication regimen had lower odds of reaching target blood pressure. Conclusions: When primary care health professionals are dealing with blood pressures above target in a patient with type 2 diabetes, they should pay particular attention to two factors. They should inquire about dietary salt intake, strongly emphasize the importance of reduction, and refer for detailed counseling if necessary. Similarly, they should inquire about adherence to the medication regimen, and employ a variety of patient-oriented strategies to improve adherence