BioMed Central - Latest comments

A bigger study is required to confirm the hypothesis

Suvash Shrestha — 2012-05-16T09:49:47Z

I read the article with great interest and felt it addressed very important and relevant topic. However, I would like to point out few things about the study that I believe have reduced the credibility of the findings.

1. The sample selection poses a huge problem. Not only the sample size is small but it is also biased. The findings or the opinions are of the residents in one center among many in New York, leave aside the other hospitals in other states. Residents in community hospitals in other places may have different opinion about the fellowship.

2. The number of residents in "Interested in fellowship" and "Not interested in fellowship" is highly unequal with 37 out of 45 (82%) in the "Interested in fellowship" group. The fact that these two groups are highly unequal makes the comparison between these two groups highly biased and unrealistic.

3. As the authors have also mentioned, currently the research respondents are residents, they are yet to join fellowships, and whatever answers they gave are just ideas and not necessarily what they are going to do in future. This difference in thought and action also reduces the significance of the findings. In my opinion, a retrospective case control study which would enroll doctors doing fellowships at the moment and doctors not doing fellowships and look into their past examination reports would better answer the hypothesis.

4. As the authors have also mentioned, the association should not mean causal relation. The relation could be both ways - academically sound residents go for sub speciality fellowship, while academically poor residents are left behind or residents with interest for fellowships work harder so they score high in the exams.

Link to a properly formatted provisional PDF

Mikolaj Rybinski — 2012-05-15T17:21:07Z

Under this link:

http://www.mimuw.edu.pl/~trybik/sci/tav4sb-preprint.pdf

you will find a properly formatted provisional PDF (with proper equations, accents, and nicely inlined figures). This PDF was built by authors from the original LaTeX sources. The provisional PDF on the journal's site was created from the editors DOC and contains many font-related bugs.

Best regards,
Miko¿aj

Editor's comment - further coverage of this research

Simon Harold PhD — 2012-05-15T14:44:52Z

Readers may like to be aware of coverage of this research in the scientific press. Please see details on our blog "Digging up the past with ancient DNA":

http://blogs.openaccesscentral.com/blogs/bmcseriesblog/entry/digging_up_the_past_with

Further examples of media coverage can be found here:

http://www.msnbc.msn.com/id/47145013/ns/technology_and_science-science/#.T7JatlKKzcs

http://www.sciencedaily.com/releases/2012/04/120422231826.htm

Simon Harold
Executive Editor
BMC Genetics

From the Editor - Award winning research in BMC Ecology

Simon Harold PhD — 2012-05-15T13:01:04Z

This research was a category winner at the 2011 BioMed Central Research Awards.

For further details, please see our blog "Recognition of ant chemical cues research"

http://blogs.openaccesscentral.com/blogs/bmcseriesblog/entry/recognition_of_ant_chemical_cues

Many congratulations to the authors.

Simon Harold
Executive Editor
BMC Ecology

Metformin-induced effects in oxygen consumption

Heikki Savolainen — 2012-05-14T14:10:55Z

Dear Editor,

The authors of this study have to be congratulated for their elegant experiments and reaching the correct conclusions.

The drug is, in fact, an inhibitor of the complex I in the mitochondrial respiratory chain. This seems to be the main reason for the deleterious effects. Two other circumstances may, however, contribute and aggravate it. D-lactate produced excessively from glucose is slowly metabolized by the D-lactic acid oxidase prolonging the metabolic acidosis, and acidotic excessive protons impair the the terminal cytochrome oxidase which is essentially a proton pump to molecular oxygen.

Thus, metformin interferes with the oxidative phosphorylation at several stages.

Low serum 25(OH)D concentrations may explain the findings regarding IL-6, hyperglycemia and glucose control in septic patients

William B. Grant — 2012-05-14T10:18:16Z

The paper by Nakamura et al. [1] reported correlations between interleukin-6 (IL-6) level, hyperglycemia, and glucose control and outcomes of septic patients. Those with failed glucose control had poorer survival rates than those with successful glucose control. Those with failed glucose control had higher IL-6 levels and much higher rates of septic shock.

The findings are consistent with lower 25-hydroxyvitamin D [25(OH)D] concentrations for those with failed glucose control. Vitamin D shifts cytokine production from T-helper 1 (Th1) to Th2 types, which includes reducing IL-6 levels [2]. Serum 25(OH)D concentrations have been found inversely correlated with glucose concentrations [3]. However, treatment with vitamin D seems to be able to increase insulin secretion but may have little impact on glucose control [4]. Thus, the effects of vitamin D deficiency may act over an extended period to reduce glucose control. More importantly, serum 25(OH)D concentrations have been found inversely associated with sepsis [5] and those with lower serum 25(OH)D concentrations have poorer survival with sepsis and other conditions in intensive care units [6-8]. The mechanism whereby vitamin D reduces risk and severity of sepsis is through induction of cathelicidin (LL-37) by the 1,25-dihydroxyvitmin D metabolite [2]. Cathelicidin is considered an antisepsis molecule [9].

The 25(OH)D concentration required for optimal health is at least 40 ng/ml (100 nmol/l) [10]. Based on the link between low serum 25(OH)D concentration and sepsis, increasing serum 25(OH)D concentrations for those diagnosed with sepsis may be beneficial. According to one paper, ¿Theoretically, pharmacological doses of vitamin D (2,000 IU per kg per day for three days) may produce enough of the naturally occurring antibiotic cathelicidin to cure common viral respiratory infections, such as influenza and the common cold, but such a theory awaits further science.¿ [10]. Vitamin D3 is much more effective than is vitamin D2 [11]. Vitamin D3 can now be prescribed in 50,000 IU doses [12].

While the evidence presented in this comment supports use of vitamin D in treating those with sepsis, such treatment should still be considered experimental and should be done in conjunction with standard medical practice.

References
1. Nakamura M, Oda S, Sadahiro T, Watanabe E, Abe R, Nakada T, Morita Y, Hirasawa H. Correlation between high blood interleukin-6 level, hyperglycemia and glucose control in septic patients. Critical Care 2012, 16:R58 (11 April 2012)
2. Khoo AL, Chai LY, Koenen HJ, Oosting M, Steinmeyer A, Zuegel U, Joosten I, Netea MG, van der Ven AJ. Vitamin D(3) down-regulates proinflammatory cytokine response to Mycobacterium tuberculosis through pattern recognition receptors while inducing protective cathelicidin production. Cytokine. 2011 Aug;55(2):294-300.
3. Hirani V. Relationship between vitamin D and hyperglycemia in older people from a nationally representative population survey. J Am Geriatr Soc. 2011;59:1786-1792.
4. Thomas GN, Scragg R, Jiang CQ, Chan W, Marz W, Pilz S, Kim HC, Tomlinson B, Bosch J, Lam TH, Cheung BM, Cheng KK. Hyperglycaemia and vitamin d: a systematic overview. Curr Diabetes Rev. 2012;8:18-31.
5. Jeng L, Yamshchikov AV, Judd SE, Blumberg HM, Martin GS, Ziegler TR, Tangpricha V. Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. J Transl Med. 2009;7:28.
6. Ginde AA, Camargo CA Jr, Shapiro NI. Vitamin D insufficiency and sepsis severity in emergency department patients with suspected infection. Acad Emerg Med. 2011;18:551-554.
7. Youssef DA, El Abbassi AM, Cutchins DC, Chhabra S, Peiris AN. Vitamin D deficiency: implications for acute care in the elderly and in patients with chronic illness. Geriatr Gerontol Int. 2011;11:395-407.
8. Flynn L, Zimmerman LH, McNorton K, Dolman M, Tyburski J, Baylor A, Wilson R, Dolman H. Effects of vitamin D deficiency in critically ill surgical patients. Am J Surg. 2012;203:379-382; discussion 382.
9. Mookherjee N, Rehaume LM, Hancock RE. Cathelicidins and functional analogues as antisepsis molecules. Expert Opin Ther Targets. 2007;11:993-1004.
10. Cannell JJ, Hollis BW. Use of vitamin D in clinical practice. Altern Med Rev. 2008;13:6-20.
11. Heaney RP, Recker RR, Grote J, Horst RL, Armas LA. Vitamin D3 Is more potent than vitamin D2 in humans. J Clin Endocrinol Metab. 2011;96:E447-E452.
12. Cannell J. Bio-Tech 50,000 IU D3 now available for prescription. 28 Feb. 2012. http://www.vitamindcouncil.org/bio-tech-50000-iu-d3-now-available-for-prescription/

Ecological studies of UVB and breast cancer rates for African-Americans

William B. Grant — 2012-05-14T10:15:45Z

Ecological studies have long linked low solar UVB doses to increased risk of breast cancer [1]. It was also shown that solar UVB doses were inversely correlated with breast cancer mortality rates for African-Americans [2,3]. In addition, it was argued that lower 25(OH)D concentrations was an important reason why African-American women had poorer survival rates for breast cancer than white-Americans [4]. A paper in press presents evidence that disparities in survival rates for 11 types of cancer are linked to lower 25(OH)D concentrations for African-Americans; consideration was given for socioeconomic status, stage at diagnosis, and treatment [5]. The differences in survival rates were consistent with differences in mean serum 25(OH)D concentrations [6] and 25(OH)D-cancer incidence relations [7].
References
1. Garland FC, Garland CF, Gorham ED, Young JF. Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prev Med. 1990;19(6):614-22.
2. Grant WB. An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer. 2002;94(6):1867-75.
3. Grant WB. Lower vitamin-D production from solar ultraviolet-B irradiance may explain some differences in cancer survival rates. J Natl Med Assoc. 2006;98(3):357-64.
4. Grant WB. Differences in vitamin D status may explain black-white differences in breast cancer survival rates. J Natl Med Assoc. 2008;100(9):1040.
5. Grant WB, Peiris AN. Differences in vitamin D status may account for unexplained disparities in cancer survival rates between African and White Americans. Dermato-Endocrinology. In press.
6. Ginde AA, Liu MC, Camargo CA Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med. 2009;169(6):626-32.
7. Grant WB. Relation between prediagnostic serum 25-hydroxyvitamin D level and incidence of breast, colorectal, and other cancers. J Photochem Photobiol B. 2010;101:130¿136.

Detailed movie protocol for the T-maze test used in this article

Tsuyoshi Miyakawa — 2012-05-14T10:09:59Z

Here is some additional information on the working memory test we used in this article.

Now, we published a movie article showing the detailed protocol for the test utilizing an automatic T-maze apparatus in Journal of Visualized Experiments.

Shoji, H., Hagihara, H., Takao, K., Hattori, S., Miyakawa, T. T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice. J. Vis. Exp. (60), e3300, DOI: 10.3791/3300 (2012).
http://www.jove.com/video/3300

This movie article would be useful, if you are not familiar with the test and want to do similar experiments.

What is a pathogen? Are there non-infectious pathogens?

Olivier Garraud — 2012-05-14T09:36:08Z

What is a pathogen? Are there non-infectious pathogens?

Olivier Garraud1,2*, Gamal Badr3,4, Sandrine Laradi1,2, Fabrice Cognasse1,2.

1. EA3064 Faculty of Medicine, University of Lyon, 42023 Saint-Etienne cedex 2, France
2. Etablissement Français du Sang Auvergne-Loire, 25 boulevard Pasteur, 42023 Saint-Etienne cedex 2, France
3. Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia
4. Zoology Department, Faculty of Science, Assiut University, Assiut, Egypt

In an elegant Q&A article in this journal, Pirofski and Casadevall recently presented their view of what constitutes a pathogen [1]. It is common sense that the word ¿pathogen¿ refers to a microbe, which induces pathogenicity and leads to clinical or sub-clinical (but pathological) infection in a host. Thus, this germ/microbe has an intrinsic property of virulence; however, virulence and pathogenicity are revealed only in susceptible hosts, those that are vulnerable to this type of infection, within a given context. Thus, pathogenicity can be recapitulated as an intrinsic property of the microbe and host susceptibility [2]. Infection of the host can develop grossly due to one of two situations: the microbe escapes any type of immune defense in any non-previously immunized host of the same species, or the defense capacity of the host is impaired. These situations are not mutually exclusive because certain microbes incapacitate innate and/or adaptive immune cells. General consensus exists on these topics, and previously unanswered questions, such as how the host¿s immune system can distinguish between the ¿good, the bad, and the ugly¿, with special mention of commensal microbes, have been clarified with descriptions and fine understanding of the microbiota and so-called ¿physiological inflammation¿ [3, 4].
One can now wonder whether the concept of ¿pathogen¿ applies only and restrictively to microbes, or if it can be extended to other situations. Evidence exists that inert particles, such as metals or crystals, are detrimental to body parts, tissues, or organs, and natural products of cell metabolism, such as inflammatory factors, can also be ¿toxic¿ when in excess or because they interfere with certain conditions in the patient. These materials do not usually go by the term ¿pathogens ¿, but are named by the type of pathology they are responsible for. In this commentary, we would like to put forward the idea that foreign cells or tissues referred to as donor cells that are injected or grafted in order to treat or assist in medical or surgical treatment of a host, referred to as a recipient, may be pathogenic under circumstances that depend on both the foreign (allogeneic) donor cells and the recipient, if he/she is susceptible or vulnerable to this condition. All properties that have been acknowledged for the microbe/host tandem leading to pathogenicity can be found in, for example, transfusion [5]. A notable exception in this example is the intent to treat or assist the patient in the transfusion case, and while virulent microbes are no longer administered in patients with the intent to cure them from an unrel ated disease (as they used to be, e.g. malariatherapy). Foreign cells exhibit characteristics that may lead to unwanted effects in susceptible hosts, i.e. displaying so-called natural or acquired (post-immunization) antibodies directed at host cell surface antigens. The immune status of the host or recipient is acknowledged to matter (e.g., antigen group association, HLA-haplotype that governs antigen presentation; transfusion-related immuno-modulation [TRIM] in patients transfused on multiple occasions with incompatible blood cells and/or receiving aged blood components) [6, 7]. More complex is a situation seemingly related to the blood component itself, which can be altered during storage and emit microparticles with oxygenated lipids and pro-inflammatory (red cells, platelets) and inflammatory products (platelets, residual leukocytes) [8].
Safety measures for collection, production, and delivery have considerably decreased discomfort, incidents, and accidents linked to cell component transfusion, but despite these sustained efforts, inflammatory conditions still persist under certain circumstances and in certain patients. Whether certain donor cells are prone to activation and secretion of inflammatory products is not known, but certain confounding pathological situations favor the occurrence of severe accidents in certain recipients. Transfusion-associated inflammation that is highly expressed certainly represents an unwanted condition; it is rare, though not exceptional, especially with platelet components [9]. Recent experimental evidence indicates that the transfusion of allogenic cells, even to an ¿as compatible as possible¿ host, induces some degree of sub-clinical inflammation comparable to what is observed in the gut in relation to commensal microbes of the microbiota, and evokes remarkably similar cells, such as monocytes and regulatory T-cells. To recapitulate, in our opinion the case of allogeneic cells strongly parallels the case of microbes displaying general characteristics of pathogenicity. This similarity is why transfusiologists usually consider at least leukocytes as pathogens whose deleterious effects in the recipient hosts are neutralized by novel pathogen inactivation processes that have mainly been made available to prevent transfusion transmitted infections but inactivate leukocytes as well [10]. The issue of the pathogenicity of certain elements present within blood products, particularly while aging, is now being questioned so novel safety measures can be implemented. Based on this argument, we wish to extend the concept of pathogen to elements other than microbes, essentially with the intent to call attention to the implementation of prevention measures.

References :

1. Pirofski LA, Casadevall A: Q and A What is a pathogen? A question that begs the point. BMC Biol 2012, 10:6.
2. Suhir H, Etzioni A: The role of Toll-like receptor signaling in human immunodeficiencies. Clin Rev Allergy Immunol 2010, 38(1):11-19.
3. Chung H, Kasper DL: Microbiota-stimulated immune mechanisms to maintain gut homeostasis. Curr Opin Immunol 2010, 22(4):455-460.
4. Jarchum I, Pamer EG: Regulation of innate and adaptive immunity by the commensal microbiota. Curr Opin Immunol 2011, 23(3):353-360.
5. Stroncek DF, Rebulla P: Platelet transfusions. Lancet 2007, 370(9585):427-438.
6. Seghatchian J, Hervig T, Putter JS: Effect of pathogen inactivation on the storage lesion in red cells and platelet concentrates. Transfus Apher Sci 2011, 45(1):75-84.
7. Shaz BH, Stowell SR, Hillyer CD: Transfusion-related acute lung injury: from bedside to bench and back. Blood 2011, 117(5):1463-1471.
8. Morrell CN: Immunomodulatory mediators in platelet transfusion reactions. Hematology Am Soc Hematol Educ Program 2011, 2011:470-474.
9. Semple JW, Italiano JE, Jr., Freedman J: Platelets and the immune continuum. Nat Rev Immunol 2011, 11(4):264-274.
10. Reesink HW, Panzer S, McQuilten ZK, Wood EM, Marks DC, Wendel S, Trigo F, Biagini S, Olyntho S, Devine DV et al: Pathogen inactivation of platelet concentrates. Vox Sang 2010, 99(1):85-95.

Intra-articular hyaluronan for first MTPJ osteoarthritis trial published

Hylton Menz — 2012-05-12T03:17:49Z

The trial described in this protocol paper has now been published in Annals of the Rheumatic Diseases:

http://ard.bmj.com/content/70/10/1838.abstract