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

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.

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.

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.

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.

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!

Bacteria And Chemotherapy Resistance

Bacteria associated with tumors can mediate resistance the chemotherapy drugs. Thus controlling bacterial species in cancer can enhance the efficacy of chemotherapy.  

There is a general pattern emerging from recent research of the importance of bacteria to human other than the simple paradigm of "there's a bacteria infection, give antibiotics." Bacteria we normally carry with us - such as the gut microbiota - affect human health for better or worse, as chronicled at this blog in a number of posts; now we see that human cancer can be associated with bacteria that affect resistance to chemotherapy.

Targeting human-cancer-bacteria interactions seems like a fruitful area of future research.

Cancer Cell Drug Addiction

By United States: National Institutes of Health - http://www.nih.gov/about/discovery/chronicdiseases/cancer.htm, Public Domain, https://commons.wikimedia.org/w/index.php?curid=25303787

Interestingly, cancer cells can not only become resistant to chemotherapeutic treatments, they can even become "addicted" to the drugs, actually becoming dependent on the drugs for growth!  In that sense, the drug are actually at that point feeding further tumor growth, and removing the drug can cause cancer cell death.  The mechanisms behind this is not well understand, and identifying these mechanisms would be helpful for designing more optimal therapeutic approaches (including alternating therapy regimens).  New data suggest certain cell signaling pathways may be involved.  Stay tuned for further developments; this is an important story.  Abstract:

Observations from cultured cells, animal models and patients raise the possibility that the dependency of tumours on the therapeutic drugs to which they have acquired resistance represents a vulnerability with potential applications in cancer treatment. However, for this drug addiction trait to become of clinical interest, we must first define the mechanism that underlies it. We performed an unbiased CRISPR-Cas9 knockout screen on melanoma cells that were both resistant and addicted to inhibition of the serine/threonine-protein kinase BRAF, in order to functionally mine their genome for 'addiction genes'. Here we describe a signalling pathway comprising ERK2 kinase and JUNB and FRA1 transcription factors, disruption of which allowed addicted tumour cells to survive on treatment discontinuation. This occurred in both cultured cells and mice and was irrespective of the acquired drug resistance mechanism. In melanoma and lung cancer cells, death induced by drug withdrawal was preceded by a specific ERK2-dependent phenotype switch, alongside transcriptional reprogramming reminiscent of the epithelial-mesenchymal transition. In melanoma cells, this reprogramming caused the shutdown of microphthalmia-associated transcription factor (MITF), a lineage survival oncoprotein; restoring this protein reversed phenotype switching and prevented the lethality associated with drug addiction. In patients with melanoma that had progressed during treatment with a BRAF inhibitor, treatment cessation was followed by increased expression of the receptor tyrosine kinase AXL, which is associated with the phenotype switch. Drug discontinuation synergized with the melanoma chemotherapeutic agent dacarbazine by further suppressing MITF and its prosurvival target, B-cell lymphoma 2 (BCL-2), and by inducing DNA damage in cancer cells. Our results uncover a pathway that underpins drug addiction in cancer cells, which may help to guide the use of alternating therapeutic strategies for enhanced clinical responses in drug-resistant cancers.

Mitochondria And Aging: Fruit Flies...And Perhaps Humans As Well

By André Karwath aka Aka - Own work, CC BY-SA 2.5, https://commons.wikimedia.org/w/index.php?curid=227170

The mitochondria are the “powerhouses” of the cell, and problems with mitochondria and mitochondrial function have been associated with a number of diseases and disorders. Increased levels of dysfunctional mitochondria have been linked to aging, and this study linked here shows that “middle-aged” Drosophila (fruit flies) tend to have more elongated, dysfunctional mitochondria. Upregulation if a gene called Drp-1 promotes fission of those aberrant mitochondria, which in turn enhances mitophagy (in simple terms: cellular “clean-up” of the dysfunctional mitochondria) and enhanced mitochondrial function.  This in turn has anti-aging effects in the flies. Now, the objective here is not to improve the health of aging fruit flies (which may or may not be a worthy goal on its own, depending on your perspective), but to apply these findings to the human case, and to see how further investigation into these findings can inform us about ant-aging strategies in humans. This is the basic science-human health link on full display.  Abstract:

The accumulation of dysfunctional mitochondria has been implicated in aging, but a deeper understanding of mitochondrial dynamics and mitophagy during aging is missing. Here, we show that upregulating Drp1-a Dynamin-related protein that promotes mitochondrial fission-in midlife, prolongs Drosophila lifespan and healthspan. We find that short-term induction of Drp1, in midlife, is sufficient to improve organismal health and prolong lifespan, and observe a midlife shift toward a more elongated mitochondrial morphology, which is linked to the accumulation of dysfunctional mitochondria in aged flight muscle. Promoting Drp1-mediated mitochondrial fission, in midlife, facilitates mitophagy and improves both mitochondrial respiratory function and proteostasis in aged flies. Finally, we show that autophagy is required for the anti-aging effects of midlife Drp1-mediated mitochondrial fission. Our findings indicate that interventions that promote mitochondrial fission could delay the onset of pathology and mortality in mammals when applied in midlife. Mitochondrial fission and fusion are important mechanisms to maintain mitochondrial function. Here, the authors report that middle-aged flies have more elongated, or 'hyper-fused' mitochondria, and show that induction of mitochondrial fission in midlife, but not in early life, extends the health and life of flies.

Insulin Analogs And Breast Cancer Risk

By Bakerstmd - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=39243250

Long-acting insulin analogs are used in the treatment of type 2 diabetes.  Given the possible effects of such drugs on cell signaling pathways, the cancer risk needs to be ascertained.  It has been shown that the drug glargine leads to increased risk of breast cancer for women with type 2 diabetes. Assuming various confounding variables were accounted for, this is a serious issue, and drug side effects always need to be considered when planning treatment.  Abstract:

Purpose The association between long-acting insulin analogs and increased breast cancer risk is uncertain, particularly with the short follow-up in previous studies. We assessed this risk long term in women with type 2 diabetes. Methods A population-based cohort of women 40 years or older, all of whom were treated with long-acting (glargine, detemir) or neutral protamine Hagedorn (NPH) insulin between 2002 and 2012, was formed using the United Kingdom's Clinical Practice Research Datalink. Women were followed until February 2015 or breast cancer diagnosis. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% CIs of incident breast cancer, comparing long-acting insulin analogs with NPH overall, as well as by duration and cumulative dose. Results The cohort included 22,395 women who received insulin treatment, with 321 incident breast cancer events occurring during up to 12 years of follow-up (incidence rate 3.3 per 1,000 person-years). Compared with NPH insulin, insulin glargine was associated with an increased risk of breast cancer (HR, 1.44; 95% CI, 1.11 to 1.85), mainly increasing 5 years after glargine initiation (HR, 2.23; 95% CI, 1.32 to 3.77) and after > 30 prescriptions (HR, 2.29; 95% CI, 1.26 to 4.16). The risk was particularly elevated among prior insulin users (HR, 1.53; 95% CI, 1.10 to 2.12) but not for new users, which included fewer patients and for which one cannot rule out an HR of 1.81. The risk associated with insulin detemir was not significantly elevated (HR, 1.17; 95% CI, 0.77 to 1.77). Conclusion Long-term use of insulin glargine is associated with an increased risk of breast cancer in women with type 2 diabetes. The risk associated with insulin detemir remains uncertain because there are fewer users of this insulin.