Microbiotic Importance

By Darryl Leja, NHGRI - http://www.genome.gov/dmd/img.cfm?node=Photos/Graphics&id=85320, Public Domain, https://commons.wikimedia.org/w/index.php?curid=29534265

Here is a review once again stressing the importance of the microbiota for human health, concentrating on immune system effects that influence “host response to infection, vaccination and cancer, as well as susceptibility to autoimmune and neurodegenerative disorders."  Abstract:

The study of the intestinal microbiota has begun to shift from cataloging individual members of the commensal community to understanding their contributions to the physiology of the host organism in health and disease. Here, we review the effects of the microbiome on innate and adaptive immunological players from epithelial cells and antigen-presenting cells to innate lymphoid cells and regulatory T cells. We discuss recent studies that have identified diverse microbiota-derived bioactive molecules and their effects on inflammation within the intestine and distally at sites as anatomically remote as the brain. Finally, we highlight new insights into how the microbiome influences the host response to infection, vaccination and cancer, as well as susceptibility to autoimmune and neurodegenerative disorders.

Dairy And Type 2 Diabetes

By Stefan Kühn - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=23754

There has been conflicting data with respect to whether dairy consumption affects risk for type 2 diabetes.  The study linked here suggests that the outcomes of dairy vs. diabetes depends on both the type of dairy consumed and the baseline glycemic status (normal, prediabetes, etc.) people have before changing their diets.  The conclusion:

Associations of dairy with incident prediabetes or diabetes varied both by dairy product and type and by baseline glycemic status in this middle-aged US population. Baseline glycemic status may partially underlie prior equivocal evidence regarding the role of dairy intake in diabetes.

Of course, dairy can have other effects besides diabetes.  It’s helpful (in general) for colon cancer and osteoporosis, but excessive dairy is a problem for prostate cancer.  High fat dairy may be helpful for diabetes, in some contexts, but poses a problem for other disorders. Then there is the problem of lactose intolerance for those who exhibit that.  I would suggest each person talks to their health care professional about that is best in their case and, always, to practice moderation. Too much of anything can be a problem.

Is your mind hacked

I have previously shared one of my favorite YouTube talks: Sugar, the Bitter Truth. It is given by Dr. Robert Lustig, an endocrinologist at UCSF, who works on childhood obesity. Anyone who has a weight problem, or has friends and relatives with such problem, should watch it. The only way we can deal with the obesity epidemic is to educate ourselves and take care of ourselves and our loved ones. No one else would do it – government, educational institutions and media are not interested in helping us with our health problems, and 75% of these problems are due to our dismal, sugar-laden diet.

Since Dr. Lustig is on my radar, I recently found out that he has published a new book, The Hacking of the American Mind: The Science Behind the Corporate Takeover of Our Bodies and Brains. 

I am currently swamped in mind-numbing activities at my job and these spill over my time at home. Therefore, I will not be able to read the book any time soon; however, I was happy to hear the summary of the book made by the author himself. I sincerely recommend the YouTube video of 32 minutes, The Hacking of the American Mind with Dr. Robert Lustig. 

The distinction between happiness and pleasure is clearly made by Lustig. So many of us substitute pleasure for happiness today, without being aware of it! 

The second valuable lesson from the book is the knowledge of the four “Cs” of happiness. According to the book author, direct Connection with people, Contribution to others, Coping, and Cooking are the four pillars of happiness that we have neglected.  None of these are for sale – we cannot buy them, but we can make time for them. In a whorl of rushed mindless activity, Lustig reminds us of what truly matters and how we can stop the vicious cycle in which government, profit, and media have thrown us in.

Non-Invasive Blood Test For Pancreatic Cancer: Early Study

One reason pancreatic cancer is so deadly is that it is usually diagnosed late, giving few or no symptoms in its early stages. Development of a non-invasive test – such as a blood test – for this cancer is therefore imperative.  Some developments are shown in this study.  A sensitivity of 64% is obviously not perfect and can stand improvement, but is certainly better than having no test at all and it is a solid starting point for further improvement.  The 99.5% specificity (demonstrating a very low probability of false positives) is excellent.  Abstract:

The earlier diagnosis of cancer is one of the keys to reducing cancer deaths in the future. Here we describe our efforts to develop a noninvasive blood test for the detection of pancreatic ductal adenocarcinoma. We combined blood tests for KRAS gene mutations with carefully thresholded protein biomarkers to determine whether the combination of these markers was superior to any single marker. The cohort tested included 221 patients with resectable pancreatic ductal adenocarcinomas and 182 control patients without known cancer. KRAS mutations were detected in the plasma of 66 patients (30%), and every mutation found in the plasma was identical to that subsequently found in the patient's primary tumor (100% concordance). The use of KRAS in conjunction with four thresholded protein biomarkers increased the sensitivity to 64%. Only one of the 182 plasma samples from the control cohort was positive for any of the DNA or protein biomarkers (99.5% specificity). This combinatorial approach may prove useful for the earlier detection of many cancer types.

Cat Personalities

By David Corby Edited by: Arad - Image:Kittyplya03042006.JPG, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=1839754

Pet owners no doubt know the personality traits of their animal friends.  The free online article linked here discusses personality types among domestic cats and what these traits can tell us about the well being of the animals and how the information can be used to manage the cats and their environments. The following is from the discussion of the paper, note that while some traits are thought to indicate environmental influences (but I suspect even these likely have some heritable component), Dominance is thought to be more purely biological in mechanism (although there is also the implication that high Extraversion may be as well, with abnormally low Extraversion possibly being, for example, age-related). I'll note from personal experience that guinea pigs also show marked animal-to-animal personality differences when cared for in exactly the same manner and in the same environment.  Dogs also differ markedly, both on a breed and on an individual basis.  From the paper:

The personality profiles of their cats may not only be interesting to cat owners, but may be used to improve welfare, particularly when an individual cat has unusually high or low scores on a factor. Awareness of results being considered extreme on a scale, compared to a sample of 2000+ pet cats, allows the owner to seek advice and consider changes to the environment or management of their cat. Personality profiling may be particularly useful for managing multi-cat households, ideally before obtaining a new cat. The following information provides specific examples.

Cats that score high on Neuroticism (shy) may be stressed and benefit from an assessment of social stress [8] by observing any interactions between the neurotic cat and others (human or non-human animals). These cats may benefit from additional hiding places around the home or access to quiet areas (like cheetahs with high tense-fearful scores [20]). All cats that are allowed to roam outside are at greater risk of disease transmission [42] or injury (road deaths or fights). Cats with low scores for Neuroticism (i.e., they are bold) may travel further (if not confined), compounding this risk.

Cats with high scores for Extraversion (smart, curious, inventive) may need additional stimulation and more complex environmental enrichment to avoid boredom [9], such as extra room to play, additional sensory items or toys, and social interactions with humans and/or other animals [3]. Low scores for Extraversion (clumsiness, aimlessness) may indicate age-related health issues, such as cognitive dysfunction [68], or other health problems, thus requiring further individual assessment from a veterinarian.

High scores on Impulsiveness (erratic, reckless) may also indicate a stressful environment [8, 69], with negative effects on a cat’s health and welfare [70, 71], and owners may need to seek advice from an animal behaviourist to locate the source of stress. Low scores for Impulsiveness are likely to be indicative of cats that are well adjusted to their environment and enjoy routine.

High scores for Agreeableness (friendly) are likely to represent cats that are well adjusted and ‘happy’, potentially serving as a source of enrichment for other cats (see captive elephants (Loxodonta africana) [72] and tigers (Panthera tigris tigris) [73]). Owners typically desire friendly cats [30] for their therapeutic benefits [69], and as a result friendly cats are more likely to be adopted from shelters [2]. Low scores for Agreeableness (irritable/aggressive towards people) may reflect poor socialisation [30], frustration [71], or underlying pain or illness [74].

Further research is needed to understand how extreme scores for the Feline Five factor of Dominance may be used for improving cat welfare. Most of our knowledge about sociality of domestic cats comes from behavioural observations of free-living (feral) colonies, where related adult females cooperate in raising kittens, while there is competition between adult males [8]. High scores for Dominance reflect a cat that is likely to bully other cats in the household, potentially causing stress, aggression or injury [75], with object (food) and social (inter-cat) dominance behaviours observed in situations with forced grouping of cats [29]. This particular personality factor may have a biological basis as oxytocin (a neuropeptide) has been associated with Roughness (consisting of traits irritable, dominant, forceful & moody) in cats [76].

In summary, our Feline Five factors were: Neuroticism, Extraversion, Dominance, Impulsiveness and Agreeableness. Accurate assessment of pet cat personality may help owners manage their cats in a way that optimises cat welfare. Additionally, a greater understanding of cat personality may help owners notice changes in their cat and seek professional assessment by a veterinarian and/or animal behaviour specialist [8, 17, 77].

More On CRISPR Gene Therapy

By Nielsrca - Own work based on figures in Nature Protocols, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=45011253

CRISPR: why the excitement?

Here’s a reason why – gene therapy for muscular dystrophy (in mice – [possibly showing potential for humans).  Abstract:

Rationale: Duchenne muscular dystrophy (DMD) is a severe inherited form of muscular dystrophy caused by mutations in the reading frame of the dystrophin gene disrupting its protein expression. Dystrophic cardiomyopathy is a leading cause of death in DMD patients and currently no effective treatment exists to halt its progression. Recent advancement in genome editing technologies offers a promising therapeutic approach in restoring dystrophin protein expression. However, the impact of this approach on DMD cardiac function has yet to be evaluated. Therefore, we assessed the therapeutic efficacy of CRISPR (clustered regularly interspaced short palindromic repeats)-mediated genome editing on dystrophin expression and cardiac function in mdx/Utr+/- mice after a single systemic delivery of recombinant adeno-associated virus (AAV). Objective: To examine the efficiency and physiological impact of CRISPR-mediated genome editing on cardiac dystrophin expression and function in dystrophic mice. Methods and Results: Here we packaged SaCas9/gRNA constructs into an AAV vector and systemically delivered them to mdx/Utr+/- neonates. We showed that CRIPSR-mediated genome editing efficiently excised the mutant exon 23 in dystrophic mice and immunofluorescence data supported the restoration of dystrophin protein expression in dystrophic cardiac muscles to a level approaching 40%. Moreover, there was a noted restoration in the architecture of cardiac muscle fibers and a reduction in the extent of fibrosis in dystrophin deficient hearts. The contractility of cardiac papillary muscles was also restored in CRISPR-edited cardiac muscles compared to untreated controls. Furthermore, our targeted deep sequencing results confirmed that our AAV-CRISPR-Cas9 strategy was very efficient in deleting the ~23 kb of intervening genomic sequences. Conclusions: This study provides evidence for using CRISPR-based genome editing as a potential therapeutic approach for restoring dystrophic cardiomyopathy structurally and functionally.

And then there is this:

Here we describe the correction of the heterozygous MYBPC3 mutation in human preimplantation embryos with precise CRISPR-Cas9-based targeting accuracy…

Gut Microbiota And Chemotherapy Resistance

https://www.hgsc.bcm.edu/fusobacterium-nucleatum-atcc10953 

Here, at the link, is another paper discussing the importance of gut microbiota to human disease. In this paper, we learn that the bacterial species Fusobacterium (F.) nucleatum is abundant in colorectal cancer tissue of patients exhibiting disease recurrence post chemotherapy.  It was shown that these bacteria promote resistance to anti-colon cancer chemotherapy by targeting particular signaling pathways.  These findings may lead to novel therapies to prevent and/or reverse resistance to chemotherapy. The findings also stress the importance of having an optimal gut microbiotic profile for better health and, if sickness does occur, optimal disease management.

Just something to get through

As I age, the lack of freedom in my life becomes acutely painful. Many impose themselves on my time, for a reason or without a reason.
 

The worse of all is when grumpy people come to let their dark clouds over me. They spill all their poison and negativity out, and in addition to wasting my time, they make me feel like life is not worth the effort.
 

My coping mechanism is to chisel out little niches of me-time within my days. These are the little sacred temples within time, where I feel in control of my life and being true to myself.
 

Why cannot life be a celebration of our individuality and fulfillment? Does it also depend upon our attitude? Probably....  

Why do we celebrate our life only on our birthdays? These are days that sometimes we designate to ourselves and some reflection on our life, and probably this is why we feel that these days are meaningful and memorable.
 

It is likely that the me-time becomes more valuable when we invest some thought and planning in it. Compare the idle staring at the TV screen to ceremonies that are usually carefully planned, and slowly and thoughtfully executed.
 

Do you have any “me” activity every day, activity that you prepare for, and slowly and carefully proceed with?
 

Here is what provoked this post:
“…the saddest adult lesson of all: that so much of life was just something to get through.” The dogs of Littlefield, Suzanne Berne