Tuesday, October 31, 2017

The Real Headless Horseman: Obesity

By John Quidor - aQHCpcwsbaMXQA at Google Cultural Institute maximum zoom level, Public Domain, https://commons.wikimedia.org/w/index.php?curid=22126482

For Halloween, we need to remember that much of the “treats” that children are getting are extremely unhealthy. Most treats are sugar/fat/high fructose corn syrup laden candy.  As a once-a-year event, this might be fine (in moderation), but with childhood obesity and metabolic syndrome on the rise, and colon cancer diagnosed at ever-younger ages (possibly due to weight problems), consuming such junk food should not be a habit.  It’s not “The Headless Horseman” stalking the land, but the obesity epidemic, and fewer and fewer of us are as slim as Ichabod Crane.

Monday, October 30, 2017

Do Bacteria Run The Show?

http://www.hypothesisjournal.com/wp-content/uploads/2016/11/HJ479_Fig1.png

Are humans merely vehicles for accomplishing the objectives of bacteria (and life in general) to spread itself?  Here is a hypothesis paper that suggests that prokaryotes (e.g., bacteria) have followed a two-pronged strategy to shape higher eukaryotes (e.g., humans) to achieve the end of spreading bacteria worldwide and spacewide: via the mitochondria (derived from an ancient prokaryote and symbiosis) and the microbiome. Of course, we are not talking about conscious strategies; there is no anthropomorphizing of bacteria!  But the end result of selection and the general tendency of life to find ways of spreading has led to this conclusion. Abstract:

Beyond considering that humans are not just composed of eukaryotic cells but also of a huge number of microbes playing pivotal roles in the overall organism functioning, in this article it is additionally suggested to look at eukaryotic cells as a kind of evolved community of bacteria-derived individuals. Mitochondria are fundamental organelles for energy production, but also for driving cell fate. Although it is perfectly established that mitochondria are phylogenetically linked to bacteria, with theories suggesting they survived in a symbiotic parasitism within an ancestral eukaryotic cell, we alternatively encourage their consideration as the main orchestrators of eukaryogenesis. Bacteria gradually evolved into mitochondria, while the social interrelationship and architecture of a prokaryotic community transformed into eukaryotic cells. Last but not least, given the role of bacteria on Panspermia, and by converging mitochondrion and microbiome potential to respectively modulate cell and whole organism functioning, we wonder whether superior animals and in particular humans might be so far the most evolved product coming from two main bacterial socio-evolutive strategies engaged in an attempt to endure living matter expansion.

Conclusion:

In conclusion, independently of whether humans are simply a “clothing”, a subject hijacked by the host or the final refined product resulting from the convergence of two different microbial socio-evolutive strategies, it might be worth giving more consideration to the fact that the ultimate “aim” of bio-evolution is not humans but the perpetuation of living matter. Humans could be just a piece of the whole biosphere puzzle and might not be necessarily the most important nor the end result. We may simply be the most sophisticated living matter approach, intentional or not, engaged in an attempt to endure a goal of bioevolution that is panspermia (38-44,113-116).

Load And Resistance Training Results

Take home point: to build muscle only, one can use both heavy or lighter resistance.  To build strength, heavy is required.  Thus, if you want both, tend to train on the heavy side – but caveat emptor about injury risk and of course it is your responsibility to get medical consultation before starting any sort of physical activity program.  
Abstract:

The purpose of this paper was to conduct a systematic review of the current body of literature and a meta-analysis to compare changes in strength and hypertrophy between low- versus high-load resistance training protocols. Searches of PubMed/MEDLINE, Cochrane Library and Scopus were conducted for studies that met the following criteria: 1) an experimental trial involving both low- (≤60% 1 RM) and high- (>60% 1 RM) load training; 2) with all sets in the training protocols being performed to momentary muscular failure; 3) at least one method of estimating changes in muscle mass and/or dynamic, isometric or isokinetic strength was used; 4) the training protocol lasted for a minimum of 6 weeks; 5) the study involved participants with no known medical conditions or injuries impairing training capacity. A total of 21 studies were ultimately included for analysis. Gains in 1RM strength were significantly greater in favor of high- versus low-load training, while no significant differences were found for isometric strength between conditions. Changes in measures of muscle hypertrophy were similar between conditions. The findings indicate that maximal strength benefits are obtained from the use of heavy loads while muscle hypertrophy can be equally achieved across a spectrum of loading ranges.

Saturday, October 28, 2017

Type I Diabetes: The Gut Microbiota Connection

By Mikael Häggström.When using this image in external works, it may be cited as:Häggström, Mikael (2014). "Medical gallery of Mikael Häggström 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.008. ISSN 2002-4436. Public Domain.orBy Mikael Häggström, used with permission. - See above. All used images are in public domain., Public Domain, https://commons.wikimedia.org/w/index.php?curid=6055517

The connection between gut microbiota and type 2 diabetes is known, and makes sense, as the long-term effects of the microbiota on the GI tract, food processing, secretion of factors inflammation, etc. can reasonably be seen as contributing to metabolic syndrome, insulin resistance, and, eventually, full-fledged type 2 diabetes. What is less well known is the link between intestinal bacteria and type 1 diabetes.  A review article has looked into this and concluded that two mechanisms may link the gut microbiota to type 1 diabetes.  First, if the infant has its GI tract colonized by sup-optimal bacteria, this will negatively affect the “education” of the immune system, resulting in a child vulnerable to immune system related diseases (e.g., autoimmune problems), including type 1 diabetes.  Note that type 1 diabetes results from autoimmune destruction if insulin-producing cells of the pancreases; therefore, an immune system not properly “trained” to distinguish “self” from “non-self” is “primed” to possibly result in attack against the targeted pancreatic cells.  Second, thus vulnerability, this predisposition, then develops into actual diabetes through the development of the antibodies that attack the pancreatic cells, and this development is associated with decreased diversity of the bacterial population of the gut, accompanied by an increase of certain bacterial species.  Protection against type 1 diabetes may therefore include modulating the colonization of the young intestinal tract to promote those bacterial species that would assist in normal immune function.  Abstract.


PURPOSE OF REVIEW:
The purpose of this review is to summarize potential modulations of the intestinal microbiome aimed at preventing or delaying progression to overt type 1 diabetes in the light of recently identified perturbations of the gut microbiota associated with the development of type 1 diabetes.
RECENT FINDINGS:
Accumulated data suggest that the gut microbiota is involved at two different steps in the evolution of type 1 diabetes. At the first step, the intestinal tract is colonized by a microbial community unable to provide an adequate education of the immune system. As a consequence, the infant acquires susceptibility to immune-mediated diseases, type 1 diabetes included. At the other step, the young child seroconverts to positivity for diabetes-associated autoantibodies. This is preceded or accompanied by a decrease in the diversity of the intestinal microbiota and an increased abundance of Bacteroides species. These changes will affect the disease process promoting progression toward overt type 1 diabetes. By providing specific probiotics, one can affect the colonization of the intestinal tract in the newborn infant or strengthen the immune education in early life. Human milk oligosaccharides function as nutrients for "healthy" bacteria. Dietary interventions applying modified starches can influence the numbers and activities of both autoreactive and regulatory T cells and provide protection against autoimmune diabetes in non-obese diabetic mice. Modulation of the intestinal microbiome holds the promise of effective protection against human type 1 diabetes.





Evolution Of Resistance Training

Here is an article reviewing the evolution of resistance training over time; therefore, originally, it was all about just strength and muscle development and today it is a more integrated system encompassing many aspects of human health.  Abstract:

The history of resistance training research began with anecdotal ideas and a slow growth of research from the late 1890s through the 1970s. The mid-1970s were a nexus point when resistance training studies evolved from just strength assessments to importance in physiological systems, physical health, and physical performance capabilities for individuals interested in physical fitness through to those seeking elite athletic performances. The pursuit of understanding program design and what mediated successful programs continues today as new findings, replication of old concepts, and new visions with the latest technologies fuel both our understanding and interest in this modality. This brief review highlights some of the important scientific contributions to the evolution of our scientific study of resistance training and provides a literature base analysis for greater quantification of the origins and expanse of such investigations.

Friday, October 27, 2017

Not diagnosed? Search CrowdMed



I have previously written about sourcing of diagnosis, but this recent post came out and I decided that the idea is worth sharing again.

New Breast Cancer Risk Gene Variants

Below we see some new studies in which new genetic variants that increase breast cancer risk have been discovered.  Such findings have multiple long-term benefits.  First, to identify at-risk patients, who can then have additional screenings, earlier screening, etc.  Second, to understand the mechanisms by which these variants, or the genes linked to them (if the variants themselves are just "markers" of risk), affect breast cancer, so as to devise new preventive and therapeutic approaches.  Third, to combine points one and two, to devise individualized screening and prevention (and therapy?) regimens for specific individuals.

Paper one; abstract:

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

Paper two; abstract:

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

Thursday, October 26, 2017

Cancer Stem Cell Switch

By Philippe Hupé - Emmanuel Barillot, Laurence Calzone, Philippe Hupé, Jean-Philippe Vert, Andrei Zinovyev, Computational Systems Biology of Cancer Chapman & Hall/CRC Mathematical & Computational Biology , 2012, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18530796

The cancer stem cell hypothesis postulates that at least some cancers are driven by carcinogenic stem cells, that are resistant to treatment.  Forcing those cancer stem cells to stop proliferating (stopping self-renewal) and differentiate (become a more specialized cell type with decreased or no ability to reproduce) is a possible therapeutic approach.  A small RNA that affects gene expression (micro-RNA) called miR-600 can promote a “switch” between self-renewal and proliferation of these cancer stem cells; an example of basic science discoveries that one day can be used for cancer therapy.  Abstract:

Tumors are organized in a cellular hierarchy with a population of cancer stem cell (CSC) driving cancer progression and resistance to treatment. Recently, we identified miR-600 as a bimodal switcher that balances breast CSC-fate from a self-renewing to a differentiation state, with a direct impact on tumor progression.

Yet More On The Microbiota Colon Cancer Connection

A review paper asserts, from the abstract:

From the abstract:


Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death. Most cases of CRC are detected in Western countries, with its incidence increasing year by year. The probability of suffering from colorectal cancer is about 4%-5% and the risk for developing CRC is associated with personal features or habits such as age, chronic disease history and lifestyle. In this context, the gut microbiota has a relevant role, and dysbiosis situations can induce colonic carcinogenesis through a chronic inflammation mechanism. Some of the bacteria responsible for this multiphase process include Fusobacterium spp, Bacteroides fragilis and enteropathogenic Escherichia coli.


It is becoming increasingly clear that modification of gut microbiota, possibly through diet and/or probiotics, will become an important tool in the prevention and treatment of many diseases, including CRC.

Wednesday, October 25, 2017

HMGB Proteins, Wnt Signaling, And Arthritis

HMGB proteins bind DNS to affect gene expression, and are associated with arthritis.  HMGB1 has been linked to inflammation in rheumatoid arthritis, and HMGB2 is associated with age-related osteoarthritis.  Effects of HMGB2 on bone is related to Wnt signaling, which is also often deregulated in cancer. These findings may lead to novel therapies for arthritis, particularly, with respect to Wnt signaling, for osteoarthritis. Abstract: 

The high-mobility group box (HMGB) family includes four members: HMGB1, 2, 3 and 4. HMGB proteins have two functions. In the nucleus, HMGB proteins bind to DNA in a DNA structure-dependent but nucleotide sequence-independent manner to function in chromatin remodeling. Extracellularly, HMGB proteins function as alarmins, which are endogenous molecules released upon tissue damage to activate the immune system. HMGB1 acts as a late mediator of inflammation and contributes to prolonged and sustained systemic inflammation in subjects with rheumatoid arthritis. By contrast, Hmgb2 -/- mice represent a relevant model of aging-related osteoarthritis (OA), which is associated with the suppression of HMGB2 expression in cartilage. Hmgb2 mutant mice not only develop early-onset OA but also exhibit a specific phenotype in the superficial zone (SZ) of articular cartilage. Given the similar expression and activation patterns of HMGB2 and β-catenin in articular cartilage, the loss of these pathways in the SZ of articular cartilage may lead to altered gene expression, cell death and OA-like pathogenesis. Moreover, HMGB2 regulates chondrocyte hypertrophy by mediating Runt-related transcription factor 2 expression and Wnt signaling. Therefore, one possible mechanism explaining the modulation of lymphoid enhancer binding factor 1 (LEF1)-dependent transactivation by HMGB2 is that a differential interaction between HMGB2 and nuclear factors affects the transcription of genes containing LEF1-responsive elements. The multiple functions of HMGB proteins reveal the complex roles of these proteins as innate and endogenous regulators of inflammation in joints and their cooperative roles in cartilage hypertrophy as well as in the maintenance of joint tissue.

Protein Types And Muscle Building

By Adrem68 at Dutch Wikipedia - Transferred from nl.wikipedia to Commons., Public Domain, https://commons.wikimedia.org/w/index.php?curid=3224328

Aging individuals lose muscle mass for a variety of reasons, one of which is reduced muscle protein being synthesized after ingestion of dietary protein.  A study has shown that animal proteins are more anabolic (muscle building) than plant proteins.  However, as the authors seem to have social and political motivations here (e.g., environmental concerns), they state mechanism whereby plant-based proteins can be more effective for muscle building: ingestion of a greater amount of protein, combining plant proteins to get a better intake of amino acids (“the mixing plant foods for a complete protein profile,” I assume), leucine co-ingestion, and “prior exercise or n-3 fatty acid supplementation” can better sensitize muscle to the protein. Abstract:

The age-related loss of skeletal muscle mass and function is caused, at least in part, by a reduced muscle protein synthetic response to protein ingestion. The magnitude and duration of the postprandial muscle protein synthetic response to ingested protein is dependent on the quantity and quality of the protein consumed. This review characterises the anabolic properties of animal-derived and plant-based dietary protein sources in older adults. While approximately 60 % of dietary protein consumed worldwide is derived from plant sources, plant-based proteins generally exhibit lower digestibility, lower leucine content and deficiencies in certain essential amino acids such as lysine and methionine, which compromise the availability of a complete amino acid profile required for muscle protein synthesis. Based on currently available scientific evidence, animal-derived proteins may be considered more anabolic than plant-based protein sources. However, the production and consumption of animal-derived protein sources is associated with higher greenhouse gas emissions, while plant-based protein sources may be considered more environmentally sustainable. Theoretically, the lower anabolic capacity of plant-based proteins can be compensated for by ingesting a greater dose of protein or by combining various plant-based proteins to provide a more favourable amino acid profile. In addition, leucine co-ingestion can further augment the postprandial muscle protein synthetic response. Finally, prior exercise or n-3 fatty acid supplementation have been shown to sensitise skeletal muscle to the anabolic properties of dietary protein. Applying one or more of these strategies may support the maintenance of muscle mass with ageing when diets rich in plant-based protein are consumed.

An Unusual Case With A Positive Ending

By Ildar Sagdejev (Specious) - Own work, GFDL, https://commons.wikimedia.org/w/index.php?curid=4428926

We all need to be thankful that surgeons and emergency medicine doctors exist and can deal with problems such as that described here.  Abstract:

Background  Transorbital intracranial penetrating injury is rare. Damage caused by a huge metallic foreign body is very critical and life-threatening. Method  We report an extremely rare case of transorbital intracranial penetrating metal strip (a car windshield wiper), which has not previously been reported in the literature. Results  Emergency craniotomy was performed; the object was removed successfully, and the patient's life was saved. Conclusion  With the life-threatening penetrating brain injury caused by a huge foreign body, prompt surgical treatment and comprehensive postoperative treatment are important to save patients' lives.

Tuesday, October 24, 2017

Stress, Dopamine, Wnt signaling, And Myelin Loss

Dopamine is related to major aspects of behavior, and abnormal regulation of the dopamine system is linked to depression and other mental disorders. Mice with knocked out dopamine receptors display increased anxiety and depression when confronted with chronic stress. Loss of myelin occurs with multiple sclerosis, and this study shows that chronic stress causes myelin loss in wild-type mice, while the dopamine receptor mutant mice have lower baseline (starting) levels of myelin, but in these mutant mice, myelin levels are not further decreased by stress.  Wnt signaling, which is abnormally regulated in different forms of cancer, is downregulated in the brains of stressed mice; this effect is reversed by lithium treatment (lithium can upregulate Wnt signaling), which normalizes myelin and behavior in stressed wild-type mice.  However, this effect of lithium did not occur in dopamine receptor-mutant mice.  This links the dopamine system with Wnt signaling affecting myelin levels and behavior in mice; the possibility exists that the same association occurs in humans. Stress has previously been linked to multiple sclerosis – with inflammation being one possible mechanism – but the dopamine pathway is another possibility, one that requires further consideration and study. Abstract:

Dopaminergic systems play a major role in reward-related behavior and dysregulation of dopamine (DA) systems can cause several mental disorders, including depression. We previously reported that dopamine D2 receptor knockout (D2R-/-) mice display increased anxiety and depression-like behaviors upon chronic stress. Here, we observed that chronic stress caused myelin loss in wild-type (WT) mice, while the myelin level in D2R-/- mice, which was already lower than that in WT mice, was not affected upon stress. Fewer mature oligodendrocytes (OLs) were observed in the corpus callosum of stressed WT mice, while in D2R-/- mice, both the control and stressed group displayed a decrease in the number of mature OLs. We observed a decrease in the number of active β-catenin (ABC)-expressing and TCF4-expressing cells among OL lineage cells in the corpus callosum of stressed WT mice, while such regulation was not found in D2R-/- mice. Administration of lithium normalized the behavioral impairments and myelin damage induced by chronic stress in WT mice, and restored the number of ABC-positive and TCF4-positive OLs, while such effect was not found in D2R-/- mice. Together, our findings indicate that chronic stress induces myelin loss through the Wnt/β-catenin signaling pathway in association with DA signaling through D2R.

Sunday, October 22, 2017

August Eclipse Pictures

I took some pictures during the August eclipse in the USA.  I was not in the path of totality, but, still, there was, we were told, to be significant coverage of the sun disc.  Walking outside at the time, the slow change was not extremely noticeable, although one could feel a lessening of the sun intensity and a brief cooling of temperature.  However, when looking at before and after pictures I took, the change is actually noticeable.  The eyes and brain get acclimated to gradual change in the sky, particularly then the sun is still bright enough so that marked darkening does not occur .  But looking at the objective evidence of a picture taken several hours before the eclipse to a set of pictures taken during - the distinction is obvious.  Note that, unfortunately, the sun was too bright for an unfiltered phone camera to show any change in the sun disc - the brightness overwhelms and the partial coverage is not seen.  However, the sky color darkening can definitely be seen.  Note that I did not look at the sun (no eclipse glasses - dangerous for the eyes!), just pointed the phone in the general direction and got lucky with some photos. Also, taking unfiltered sun pictures can in theory damage the phone camera, but in my case it did not happen.
BEFORE ECLIPSE
ECLIPSE 1
ECLIPSE 2
ECLIPSE 3
ECLIPSE 4

Friday, October 20, 2017

Vitamin D And Type 2 Diabetes

By Sbrools - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=2067061

Evidence linked here that vitamin D supplementation may help improve symptoms in type 2 diabetes patients.  Abstract:

BACKGROUND:Type 2 diabetes is a global health concern, with an increased prevalence and high cost of treatment.OBJECTIVE:The aim of this systematic review and meta-analysis was to determine the effect of vitamin D supplementation and improved vitamin D status on glycemia and insulin resistance in type 2 diabetic patients.DATA SOURCE:We searched PUBMED/Medline, Cumulative Index to Nursing and Allied Health, and Cochrane Library (until January 2017).STUDY SELECTION:Prospective clinical trials were selected evaluating the impact of vitamin D supplementation on glycosylated hemoglobin (HbA1c), serum fasting plasma glucose (FPG), and homeostatic model assessment of insulin resistance (HOMA-IR) in diabetic patients.DATA EXTRACTION AND SYNTHESIS:We used a random-effects model to synthesize quantitative data, followed by a leave-one-out method for sensitivity analysis. The systematic review registration was CRD42017059555. From a total of 844 entries identified via literature search, 24 controlled trials (1528 individuals diagnosed with type 2 diabetes) were included. The meta-analysis indicated a significant reduction in HbA1c [mean difference: -0.30%; 95% confidence interval (CI): -0.45 to -0.15, P < 0.001], FPG [mean difference: -4.9 mg/dL (-0.27 mmol/L); 95% CI: -8.1 to -1.6 (-0.45 to -0.09 mmol/L), P = 0.003], and HOMA-IR (mean difference: -0.66; 95% CI: -1.06 to -0.26, P = 0.001) following vitamin D supplementation and significant increase in serum 25-hydroxyvitamin D levels [overall increase of 17 ± 2.4 ng/mL (42 ± 6 nmol/L)].CONCLUSIONS:Vitamin D supplementation, a minimum dose of 100 µg/d (4000 IU/d), may significantly reduce serum FPG, HbA1c, and HOMA-IR index, and helps to control glycemic response and improve insulin sensitivity in type 2 diabetic patients.

Tuesday, October 17, 2017

Neck Exercise And Neck Size

By Olek Remesz (wiki-pl: Orem, commons: Orem) - Own work, based on this picture from Gray's Anatomy., CC BY-SA 2.5-2.0-1.0, https://commons.wikimedia.org/w/index.php?curid=2339732

According to standard bodybuilding, one can get sufficient indirect stimulation from heavy lifting to build the neck without direct neck exercises. Here is a study that says that is false; neck muscles were built up only after direct neck work. There are some caveats (how heavy were they lifting?  maybe more time was needed?  bigger sample sizes), but the data are there.  Many bodybuilders say the same about forearms (indirect work is sufficient) - one wonders if indirect work suffices for some because they are mesomorphic "easy gainers" while the rest of us need direct work.  Abstract:

This study examined hypertrophy after head extension resistance training to assess which muscles of the complicated cervical neuromuscular system were used in this activity. We also determined if conventional resistance exercises, which are likely to evoke isometric action of the neck, induce generalized hypertrophy of the cervical muscle. Twenty-two active college students were studied. [mean (SE) age, weight and height: 21 (1) years, 71 (4) kg and 173 (3) cm, respectively]. Subjects were assigned to one of three groups: RESX (head extension exercise and other resistance exercises), RES (resistance exercises without specific neck exercise), or CON (no training). Groups RESX (n = 8) and RES (n = 6) trained 3 days/week for 12 weeks with large-muscle mass exercises (squat, deadlift, push press, bent row and mid-thigh pull). Group RESX also performed three sets of ten repetitions of a head extension exercise 3 days/week with a load equal to the 3 x 10 repetition maximum (RM). Group CON (n = 8) was a control group. The cross-sectional area (CSA) of nine individual muscles or muscle groups was determined by magnetic resonance imaging (MRI) of the cervical region. The CSA data were averaged over four contiguous transaxial slices in which all muscles of interest were visible. The 3 x 10 RM for the head extension exercise increased for RESX after training [from 17.9 (1.0) to 23.9 (1.4) kg, P < 0.05] but not for RES [from 17.6 (1.4) to 17.7 (1.9) kg] or CON [from 10.1 (2.2) to 10.3 (2.1) kg]. RESX showed an increase in total neck muscle CSA after training [from 19.5 (3.0) to 22.0 (3.6) cm2, P < 0.05], but RES and CON did not [from 19.6 (2.9) to 19.7 (2.9) cm2 and 17.0 (2.5) to 17.0 (2.4) cm2, respectively]. This hypertrophy for RESX was due mainly to increases in CSA of 23.9 (3.2), 24.0 (5.8), and 24.9 (5.3)% for the splenius capitis, and semispinalis capitis and cervicis muscles, respectively. The lack of generalized neck muscle hypertrophy in RES was not due to insufficient training. For example, the CSA of their quadriceps femoris muscle group, as assessed by MRI, increased by 7 (1)% after this short-term training (P < 0.05). The results suggest that: (1) the splenius capitis, and semispinalis capitis and cervicis muscles are mainly responsible for head extension; (2) short-term resistance training does not provide a sufficient stimulus to evoke neck muscle hypertrophy unless specific neck exercises are performed; and (3) the postural role of head extensors provides modest loading in bipeds.

Of course care is necessary when exercising the neck, which is a relatively fragile region; one cannot go heavy there, but concentrate more on proper form with repetitions.  And of course check with your physician before starting any exercise program.

Monday, October 16, 2017

Biomarkers For Metastatic Colon Cancer Treatment

Metastatic colon cancer patients would benefit from having biomarkers analyzed, to judge potential response to certain therapeutic approaches.  This makes sense, as variation in signaling pathways can affect response to treatments, particularly those that target the altered pathways or other pathways that communicate with those altered.  Abstract:

BACKGROUND:
Metastatic colorectal cancer (mCRC) patients with mutant KRAS or NRAS are ineligible for anti-epidermal growth factor receptor (anti-EGFR) therapy, as RAS mutations activate downstream pathways independently of EGFR and induce primary resistance. However, even among RAS wild-type (WT) patients, only a fraction responds to anti-EGFR therapy, suggesting that other mechanisms of resistance exist. We hypothesise that different (epi)genetic alterations can lead to primary anti-EGFR resistance and that the crucial end point is the activation of protein signalling pathways.
METHODS:
We analysed the expression and activation of proteins involved in cell signalling, using reverse phase protein arrays, on a multicentre French cohort of RAS WT mCRC treated with anti-EGFR treatment.
RESULTS:
We identify activated EGFR and HER3 as protein biomarkers predictive for better overall survival. Active EGFR signalling and downstream PI3K, but not MAPK, pathway activation are associated with response to anti-EGFR treatment. Left-sided mCRC displays active ErbB2/3 and Wnt pathways and a better response to anti-EGFR therapy compared to right-sided mCRC.
CONCLUSIONS:
We identify active EGFR and PI3K signalling as a key factor for response to anti-EGFR treatment in mCRC and highlight the importance of developing these biomarkers in clinical practice for the selection of RAS WT mCRC patients that would benefit from anti-EGFR treatment. British Journal of Cancer advance online publication 12 October 2017; doi:10.1038/bjc.2017.353 www.bjcancer.com.

Tuesday, October 10, 2017

Review On Antimicrobial Resistance

Left, a phage.  By Adenosine - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8643737

Here is an interesting review on antimicrobial resistance. Such resistance, particularly resistance to antibiotics, is becoming an increasingly significant health concern. Note the mention of phage therapy, which has long been in use in other countries, including some areas of Eastern Europe. That has promise, as one has the wrong types of phages are avoided.  I believe more study on phage therapy should be conducted in the USA. Abstract:

PURPOSE:

To describe the current standards of care and major recent advances with regard to antimicrobial resistance (AMR) and to give a prospective overview for the next 30 years in this field.
METHODS:
Review of medical literature and expert opinion were used in the development of this review.
RESULTS:
There is undoubtedly a large clinical and public health burden associated with AMR in ICU, but it is challenging to quantify the associated excess morbidity and mortality. In the last decade, antibiotic stewardship and infection prevention and control have been unable to prevent the rapid spread of resistant Gram-negative bacteria (GNB), in particular carbapenem-resistant Pseudomonas aeruginosa (and other non-fermenting GNB), extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae (CRE). The situation appears more optimistic currently for Gram-positive, where Staphylococcus aureus, and particularly methicillin-resistant S. aureus (MRSA), remains a cardinal cause of healthcare-associated infections worldwide. Recent advancements in laboratory techniques allow for a rapid identification of the infecting pathogen and antibiotic susceptibility testing. Their impact can be particularly relevant in settings with prevalence of MDR, since they may guide fine-tuning of empirically selected regimen, facilitate de-escalation of unnecessary antimicrobials, and support infection control decisions. Currently, antibiotics are the primary anti-infective solution for patients with known or suspected MDR bacteria in intensive care. Numerous incentives have been provided to encourage researchers to work on alternative strategies to reverse this trend and to provide a means to treat these pathogens. Although some promising antibiotics currently in phase 2 and 3 of development will soon be licensed and utilized in ICU, the continuous development of an alternative generation of compounds is extremely important. There are currently several promising avenues available to fight antibiotic resistance, such as faecal microbiota, and phage therapy.

Sunday, October 8, 2017

Death, Navy SEALs and millennial revolution






THE LAST FLOWERS OF SUMMER 2017
Here everything is touched by the tinge of ending and death. I am trying to celebrate the vestiges of the summer glory - my last flowers made a great bouquet in the living room today. The days are surprisingly warm; however, the leaves are falling and the bare brunches of the trees are stark against the deep blue of the sky. And I have still not recovered from the last winter’s storm in March…

How true this sounds: “…in autumn in the country, you could practically feel everything dying and became aware of your own mortality.


The sentence is from a silly book called The Dead Dance, by M.C. Beaton. I read silly books when I need to get away from the drama of my job. And I do need a distraction these days. This weekend, despite the work overload spilled into my “free” hours, I decided to stop by the local library and get my type of distraction – a few mysteries. I do not watch TV, and do not go to bars or sports events.

Other than that - I quickly visited the http://www.millennial-revolution.com/ website to salivate over Bouquet, Panama, and its culinary highlights. Panama is where the young revolutionary couple has been spending time recently. I can only dream about it. Living through someone else’s good times is pitiful, but there is no way out of the rat race for me. I do not have the money to declare my financial independence.
 

Finally, a student of mine recommended me to watch a commencement speech, Change the World by Making Your Bed - by Admiral William McRaven. If you have not seen it yet, it is worth the six minutes.

Well, I do feel a bit recharged after I took a few hours for myself. I hope you are also recharged and ready for the week ahead!