Gene Therapy For Hearing Loss: Vector Development

One major problem for gene therapy is designing a safe and effector vector for delivering the gene therapy material to the target cells.tissues.  Here is a paper demonstrating high levels of gene delivery in mouse ear cells.  Abstract:

Efforts to develop gene therapies for hearing loss have been hampered by the lack of safe, efficient, and clinically relevant delivery modalities. Here we demonstrate the safety and efficiency of Anc80L65, a rationally designed synthetic vector, for transgene delivery to the mouse cochlea. Ex vivo transduction of mouse organotypic explants identified Anc80L65 from a set of other adeno-associated virus (AAV) vectors as a potent vector for the cochlear cell targets. Round window membrane injection resulted in highly efficient transduction of inner and outer hair cells in mice, a substantial improvement over conventional AAV vectors. Anc80L65 round window injection was well tolerated, as indicated by sensory cell function, hearing and vestibular function, and immunologic parameters. The ability of Anc80L65 to target outer hair cells at high rates, a requirement for restoration of complex auditory function, may enable future gene therapies for hearing and balance disorders.

Continued development of such technologies should eventually have great benefit for human health.

Physiotherapists And Knee Osteoarthritis

How consistent are physiotherapists in the advice they give to knee osteoarthritis patients?  It could be better, it seems.  The important message from the linked paper's abstract: 

Quality indicator compliance less than 50% was found for: education on the importance of weight loss, providing self-management strategies, spreading treatment session over longer periods and regular evaluations of the exercise therapy.

Less than 50% give advice for weight loss!  Shouldn't that be one of the first things one would say, given how many people in Belgium, where this study was conducted, are overweight?

Exercise, DKK1, SFRP1, And Cancer

Here is a study on breast cancer patients suggesting that physical activity/exercise can reduce blood levels of cell signaling factors, one of which is associated with a poor prognosis for patients with various forms of cancer.  Abstract:

Wingless and integration site growth factor (Wnt) signaling is a tumorigenesis-related signaling pathway. Dickkpof-1 (DKK1) and secreted frizzled-related protein-1 (SFRP1) are endogenous negative regulators of Wnt/β-catenin signaling. Accumulating evidence indicates that higher serum levels of DKK1 are correlated with poor prognosis of various types of cancer. Here, we investigated whether exercise training causes changes in the serum levels of DKK1 and SFRP1 in patients with breast cancer.

METHODS:

Twenty-four breast cancer survivors, after chemo- or radiotherapy, participated in this single-blind randomized, controlled pilot study. Subjects were randomized to either an exercise program or a control group for 12 weeks and completed pre- and post-training tests for health-related fitness and body composition as well as blood biomarkers. The serum levels of DKK1 and SFRP1 were measured using enzyme-linked immunosorbent assay as the primary outcome.

RESULTS:

Exercise training for 12 weeks remarkably increased muscle strength, endurance, and flexibility and decreased body fat percentage, waist circumference, and visceral fat area (all p < 0.05). Exercise training lowered serum insulin levels and leptin/adiponectin ratios (all p < 0.05). The levels of DKK1 and SFRP1 were also significantly decreased by exercise training in breast cancer survivors (all p < 0.01).

CONCLUSIONS:

Our results indicate that DKK1 and SFRP1 may be potentially useful biomarkers for evaluating the beneficial effects of long-term exercise on physical fitness and metabolism as well as the prognosis of patients with cancer.

The benefits of exercise are many and the list of positive effects continues to grow.

E-Cigarette And NRT Study

Does use of e-cigarettes and/or nicotine replacement therapy to replace regular cigarettes reduce intake of harmful materials? 

Here is a paper, conclusion from the abstract:

CONCLUSION:

Former smokers with long-term e-cigarette-only or NRT-only use may obtain roughly similar levels of nicotine compared with smokers of combustible cigarettes only, but results varied. Long-term NRT-only and e-cigarette-only use, but not dual use of NRTs or e-cigarettes with combustible cigarettes, is associated with substantially reduced levels of measured carcinogens and toxins relative to smoking only combustible cigarettes.

So, using e-cigarettes or NRT alone results in roughly the same nicotine intake but reduced carcinogens and toxins, which is good.  Using both e-cigarettes and NRT does not seem to lead to a reduction.  If you are a smoker, discuss with your physician; these results suggest to me to use either replacement but not both.  Of course, my father quit “cold turkey” which if you can do it, reduces intake of these substances to zero.  Best yet: do not start smoking to begin with, if you have not already done so.

Vitamin D Helps Against Thyroid Autoimmunity

A paper studying the effectiveness of vitamin D replacement therapy for thyroid autoimmunity syndrome can be found here.  Abstract:

BACKGROUND:
Vitamin D was shown to be related to autoimmune thyroid diseases (AITDs) in the previous studies. We aimed to investigate the relationship between Vitamin D and thyroid autoimmunity.
MATERIALS AND METHODS:
Eighty-two patients, diagnosed with AITD by the endocrinology outpatient clinic, were included in this prospective study. All of the patients had both AITD and Vitamin D deficiency, defined as serum values <20 ng/mL. They were randomly assigned into two groups. The first group included 46 patients and the second one included 36 patients. The first group was treated with Vitamin D for 1 month at 1000 IU/day. The second group served as the control group and was not treated with Vitamin D replacement. Serum thyroid-stimulating hormone, free T4 (fT4), thyroid peroxidase antibody (TPO-Ab), thyroglobulin antibody (TgAb), and Vitamin D levels were measured at the initiation of the study and again at 1 month in all patients.
RESULTS:
Two groups were similar with regard to age, sex, and type of thyroid disease. Whereas TPO-Ab (before; 278.3 ± 218.4 IU/ml and after; 267.9 ± 200.7 IU/ml) and TgAb (before; 331.9 ± 268.1 IU/ml and after; 275.4 ± 187.3 IU/ml) levels were significantly decreased by the Vitamin D replacement therapy in group 1 (P = 0.02, P = 0.03, respectively), the evaluated parameters in the control group did not significantly change (P = 0.869, P = 0.530, respectively). In addition, thyroid function tests did not significantly change with Vitamin D replacement in two groups.
CONCLUSION:
Vitamin D deficiency may contribute to the pathogenesis of AITDs. Since supplementation of the Vitamin D decreased thyroid antibody titers in this study in Vitamin D deficient subjects, in the future Vitamin D may become a part of AITDs' treatment, especially in those with Vitamin D insufficiency. Further clinical and experimental studies are required to understand the effect of Vitamin D on AITD.

The vitamin therapy reduced levels of the thyroid antibodies that cause the problem, and this is good. Unfortunately, there was no change in actual thyroid function.  So, this is a promising initial set of findings suggesting a vitamin D link but more study is required to better understand what is going on, so as to possibly devise additional interventions that can have more optimal effects. Ideally, I believe that one would want to both decrease the antibody levels and also improve thyroid function.  

Save Authors Time

This is a good suggestion, abstract:

Scientific journals ask authors to put their manuscripts, at the submission stage, sometimes in a complex style and a specific pagination format that are time consuming while it is unclear yet that the submitted manuscripts will be accepted. In the case of rejections, authors need to submit to another journal most likely with a different style and formatting that require additional work and time. To save authors' time, publishers should allow authors to submit their manuscripts in any format and to comply with the style required by the targeted journal only in revised versions, but not at the submission step when the manuscripts are not yet approved for publication.

What relevance does this have for the typical person who wants to improve their health?  Well, anything that facilitates the spread of biomedical knowledge is a good thin, anything that hampers that spread is bad.  Journal requirements, as discussed here, are one impediment.  Other times, reviewers nitpick on minor points or let personal biases get in the way of a fair review of important material, and so knowledge of potential use to public health remains unpublished - or the publication is delayed.

Some Articles On Third Hand Smoke

We are all aware of the dangers of smoking, and most people have heard about "second hand smoke" - but what about "third hand smoke?"  

Smoking remnants can constitute a significant health hazard, and may be particularly problematical for infants.

If smokers needed yet another reason to quit, third hand smoke is something to consider.

Additional Studies On Ketogenic Diets And Epilepsy

More information on ketogenic diets, abstract:

PURPOSE OF REVIEW:High-fat, low-carbohydrate ketogenic diets have been used for almost a century for the treatment of epilepsy. Used traditionally for the treatment of refractory pediatric epilepsies, in recent years the use of ketogenic diets has experienced a revival to include the treatment of adulthood epilepsies as well as conditions ranging from autism to chronic pain and cancer. Despite the ability of ketogenic diet therapy to suppress seizures refractory to antiepileptic drugs and reports of lasting seizure freedom, the underlying mechanisms are poorly understood. This review explores new insights into mechanisms mobilized by ketogenic diet therapies.RECENT FINDINGS:Ketogenic diets act through a combination of mechanisms, which are linked to the effects of ketones and glucose restriction, and to interactions with receptors, channels, and metabolic enzymes. Decanoic acid, a component of medium-chain triclycerides, contributes to seizure control through direct α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor inhibition, whereas drugs targeting lactate dehydrogenase reduce seizures through inhibition of a metabolic pathway. Ketogenic diet therapy also affects DNA methylation, a novel epigenetic mechanism of the diet.SUMMARY:Ketogenic diet therapy combines several beneficial mechanisms that provide broad benefits for the treatment of epilepsy with the potential to not only suppress seizures but also to modify the course of the epilepsy.

Epileptic patients may wish to  discuss these findings with their physician to determine whether dietary modifications may be of use in their own case.

Prevent Aging With Stem Cell Rejuvenation?

Discussion of a possible anti-aging approach, abstract:

Characterized by dysfunction of tissues, organs, organ systems and the whole organism, aging results from the reduced function of effective stem cell populations. Recent advances in aging research have demonstrated that old tissue stem cells can be rejuvenated for the purpose of maintaining the old-organ function by youthful re-calibration of the environment where stem cells reside. Biochemical cues regulating tissue stem cell function include molecular signaling pathways that interact between stem cells themselves and their niches. Historically, plasma fractions have been shown to contain factors capable of controlling age phenotypes; subsequently, signaling pathways involved in the aging process have been identified. Consequently, modulation of signaling pathways such as Notch/Delta, Wnt, transforming growth factor-β, JAK/STAT, mammalian target of rapamycin and p38 mitogen-activated protein kinase has demonstrated potential to rejuvenate stem cell function leading to organismic rejuvenation. Several synthetic agents and natural sources, such as phytochemicals and flavonoids, have been proposed to rejuvenate old stem cells by targeting these pathways. However, several concerns still remain to achieve effective organismic rejuvenation in clinical settings, such as possible carcinogenic actions; thus, further research is still required.

Note the point at the end about "possible carcinogenic actions."  Paradox: while the risk of most cancers increases with age, aging itself can be viewed as an anti-cancer mechanism, diminishing cell reproduction and stem cell activity (and elimination of stem cells) to prevent such cells with mutations from multiplying into tumors.  Thus, anti-aging approaches need to be cognizant of the cancer problem and find solutions to this possible problem.

Parvovirus B19 And Pregnancy

Something pregnant women should be aware of discussed here, abstract: 

Several infections in adults warrant special consideration in pregnant women given the potential fetal consequences. Among these is parvovirus B19 deserves special attention since the harmful effects on the pregnant woman and fetus. It can then cause fetal anemia, non-immune fetal hydrops and fetal death. Among cases with fetal demise, B19 is found in significant numbers, especially in the second and third trimesters of pregnancy. There is no specific treatment or prophylaxis available against B19 infection, but counseling of non-immune mothers and active monitoring of confirmed maternal infections with intervention to correct fetal anemia is likely to decrease mortality.

This may be something that pregnant women should discuss with their physician, if they want to monitor teir status in this regard.