Leaf Extract Against Colorectal cancer

Here is a study suggesting that Ginkgo biloba L. leaf extract may be beneficial against colorectal cancer by affecting important cell signaling pathways that mediate that disease. The authors state: “The outcomes of the present investigation encourage the use of Ginkgo biloba L. leaf extract as a complementary and alternative therapeutic approach to abate CRC.”  As always consult your own physician; in my opinion, “complementary” may be useful, but “alternative” (as in use this but do not use traditional medical treatments) is a mistake. I have heard of too many horror stories of patients eschewing regular treatment for alternatives and then dying if a curable cancer because they realized, too late, that the alternative was really no alternative at all.  But, again, I am not a medical doctor and I am only giving my own opinion based on scientific background as well as personal experience and anecdote.  I would urge all cancer patients to follow the advice of their oncologists and, of course, ask whether other things can complement treatment.

HIF Repression Cancer Therapy

Hypoxia – lack of oxygen – promotes the expression of  hypoxia-inducible factors that mediate cancer progression, including angiogenesis (blood vessel formation) that helps bring oxygen to the tumors.  Blocking those factors is a new form of therapy, described here.  Abstract:

Purpose The von Hippel-Lindau tumor suppressor is inactivated in the majority of clear cell renal cell carcinomas (ccRCCs), leading to inappropriate stabilization of hypoxia-inducible factor-2α (HIF-2α). PT2385 is a first-in-class HIF-2α antagonist. Objectives of this first-in-human study were to characterize the safety, pharmacokinetics, pharmacodynamics, and efficacy, and to identify the recommended phase II dose (RP2D) of PT2385. Patients and Methods Eligible patients had locally advanced or metastatic ccRCC that had progressed during one or more prior regimens that included a vascular endothelial growth factor inhibitor. PT2385 was administered orally at twice-per-day doses of 100 to 1,800 mg, according to a 3 + 3 dose-escalation design, followed by an expansion phase at the RP2D. Results The dose-escalation and expansion phases enrolled 26 and 25 patients, respectively. Patients were heavily pretreated, with a median of four (range, one to seven) prior therapies. No dose-limiting toxicity was observed at any dose. On the basis of safety, pharmacokinetic, and pharmacodynamic profiling, the RP2D was defined as 800 mg twice per day. PT2385 was well tolerated, with anemia (grade 1 to 2, 35%; grade 3, 10%), peripheral edema (grade 1 to 2, 37%; grade 3, 2%), and fatigue (grade 1 to 2, 37%; no grade 3 or 4) being the most common treatment-emergent adverse events. No patients discontinued treatment because of adverse events. Complete response, partial response, and stable disease as best response were achieved by 2%, 12%, and 52% of patients, respectively. At data cutoff, eight patients remained in the study, with 13 patients in the study for ≥ 1 year. Conclusion PT2385 has a favorable safety profile and is active in patients with heavily pretreated ccRCC, validating direct HIF-2α antagonism for the treatment of patients with ccRCC

Exercise Isn't Helping

By Tibor Végh (Tenerife 2010 124.JPG) [CC BY 3.0 (http://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons

Americans are more obese than ever and exercise does not really help that much.

Some take medications. Or, you can just eat less.

No Evidence For Exercise Benefit For Depression And Cognition?

Contrary to popular conceptions, a study here and another one here did not find any positive effect of exercise (at least aerobic exercise) on depression or cognition. However, this is not the last word, and more studies are necessary.  Even if these two studies are correct, exercise has enormous health benefits for physical fitness and overall physical and psychological well-being.

Fetus-In-Fetu

By Nisreen M Khalifa et al - Khalifa NM, Maximous DW, Abd-Elsayed AA. Fetus in fetu: a case report. J Med Case Reports. 2, 2. 2008. doi:10.1186/1752-1947-2-2. PMID 18186928., CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=4260020

Although there is nothing practical to learn, for daily living, from this interesting case of fetus-in-fetu, it is nevertheless interesting to read about.  Perhaps the study of such abnormalities can be useful for studies of cancer and other aberrations of developmental processes.  Abstract:

A case of fetus-in- fetu is reported. It occurred in an 8-week-old Korean boy who had been born by cesarean section due to abdominal distension. The fetus-in- fetu was connected to the superior mesenteric artery and consisted of two masses, apparently representing two portions of an acardiac monster. There was an amniotic membrane covering both masses, and the umbilical cord clearly was identifiable. One mass included the brain, eye, trachea, salivary glands, thyroid, pancreas, spleen, etc., while the other mass contained extremity bones, vertebrae, testis, adrenals, and intestinal loops. This is probably a case of separated fetus-in- fetu that showed unusually well-developed internal organs.

The Decrepit Adult

Contrary to previous belief, it seems that in humans, formation of new neurons in the hippocampus, important for learning and memory, essentially stops in childhood.  Abstract:

New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day, whereas other studies find many fewer putative new neurons. Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal development. We also find that the number of proliferating progenitors and young neurons in the dentate gyrus declines sharply during the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult patients with epilepsy and healthy adults (18-77 years; n = 17 post-mortem samples from controls; n = 12 surgical resection samples from patients with epilepsy), young neurons were not detected in the dentate gyrus. In the monkey (Macaca mulatta) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does not continue, or is extremely rare, in adult humans. The early decline in hippocampal neurogenesis raises questions about how the function of the dentate gyrus differs between humans and other species in which adult hippocampal neurogenesis is preserved.

Contraceptives And Breast Cancer

The use of hormonal contraceptives increases the risk of breast cancer in women, associated with duration of use.  The risk increase was relatively small, but nevertheless real.  Abstract:

BACKGROUND:

Little is known about whether contemporary hormonal contraception is associated with an increased risk of breast cancer.

METHODS:

We assessed associations between the use of hormonal contraception and the risk of invasive breast cancer in a nationwide prospective cohort study involving all women in Denmark between 15 and 49 years of age who had not had cancer or venous thromboembolism and who had not received treatment for infertility. Nationwide registries provided individually updated information about the use of hormonal contraception, breast-cancer diagnoses, and potential confounders.

RESULTS:

Among 1.8 million women who were followed on average for 10.9 years (a total of 19.6 million person-years), 11,517 cases of breast cancer occurred. As compared with women who had never used hormonal contraception, the relative risk of breast cancer among all current and recent users of hormonal contraception was 1.20 (95% confidence interval [CI], 1.14 to 1.26). This risk increased from 1.09 (95% CI, 0.96 to 1.23) with less than 1 year of use to 1.38 (95% CI, 1.26 to 1.51) with more than 10 years of use (P=0.002). After discontinuation of hormonal contraception, the risk of breast cancer was still higher among the women who had used hormonal contraceptives for 5 years or more than among women who had not used hormonal contraceptives. Risk estimates associated with current or recent use of various oral combination (estrogen-progestin) contraceptives varied between 1.0 and 1.6. Women who currently or recently used the progestin-only intrauterine system also had a higher risk of breast cancer than women who had never used hormonal contraceptives (relative risk, 1.21; 95% CI, 1.11 to 1.33). The overall absolute increase in breast cancers diagnosed among current and recent users of any hormonal contraceptive was 13 (95% CI, 10 to 16) per 100,000 person-years, or approximately 1 extra breast cancer for every 7690 women using hormonal contraception for 1 year.

CONCLUSIONS:

The risk of breast cancer was higher among women who currently or recently used contemporary hormonal contraceptives than among women who had never used hormonal contraceptives, and this risk increased with longer durations of use; however, absolute increases in risk were small. (Funded by the Novo Nordisk Foundation.).

Hemophilia Gene Therapy Success

Advances in hemophilia gene therapy; abstract:

BACKGROUND:

The prevention of bleeding with adequately sustained levels of clotting factor, after a single therapeutic intervention and without the need for further medical intervention, represents an important goal in the treatment of hemophilia.

METHODS:

We infused a single-stranded adeno-associated viral (AAV) vector consisting of a bioengineered capsid, liver-specific promoter and factor IX Padua (factor IX-R338L) transgene at a dose of 5×1011 vector genomes per kilogram of body weight in 10 men with hemophilia B who had factor IX coagulant activity of 2% or less of the normal value. Laboratory values, bleeding frequency, and consumption of factor IX concentrate were prospectively evaluated after vector infusion and were compared with baseline values.

RESULTS:

No serious adverse events occurred during or after vector infusion. Vector-derived factor IX coagulant activity was sustained in all the participants, with a mean (±SD) steady-state factor IX coagulant activity of 33.7±18.5% (range, 14 to 81). On cumulative follow-up of 492 weeks among all the participants (range of follow-up in individual participants, 28 to 78 weeks), the annualized bleeding rate was significantly reduced (mean rate, 11.1 events per year [range, 0 to 48] before vector administration vs. 0.4 events per year [range, 0 to 4] after administration; P=0.02), as was factor use (mean dose, 2908 IU per kilogram [range, 0 to 8090] before vector administration vs. 49.3 IU per kilogram [range, 0 to 376] after administration; P=0.004). A total of 8 of 10 participants did not use factor, and 9 of 10 did not have bleeds after vector administration. An asymptomatic increase in liver-enzyme levels developed in 2 participants and resolved with short-term prednisone treatment. One participant, who had substantial, advanced arthropathy at baseline, administered factor for bleeding but overall used 91% less factor than before vector infusion.

CONCLUSIONS:

We found sustained therapeutic expression of factor IX coagulant activity after gene transfer in 10 participants with hemophilia who received the same vector dose. Transgene-derived factor IX coagulant activity enabled the termination of baseline prophylaxis and the near elimination of bleeding and factor use. (Funded by Spark Therapeutics and Pfizer; ClinicalTrials.gov number, NCT02484092 .).

A modern-life fairy tale

Do you like restoring houses and planting gardens? Or at least are you tempted by the thought of doing these activities? Of course, there will be the constraints of time and finances. You will also need imagination, grit and physical resilience. If you would like to relive your fantasies, then watch Escape to the Chateau.

 [Update: there is always a copyright issue, so the links would not work. You may need to search what is available at this time on YouTube.]

The show follows a British couple buying a chateau in France. The building dates back to the 1860s, when it was raised upon the foundations of a 15th-century fort. There are 45 rooms, a moat, 12 sprawling acres of land, and much more. The building has been empty for 40 years, when the couples buys it.

From reconstruction and rebuilding, to orchards and pigs, to boudoirs and gourmet seven-course dinners, it is all in the roller coaster of experiences. It is unbelievable how this couple makes it work.
 
The show is a mix of a fairy tale with incredible amount of work. And this is the reality – enormous effort has to supplement the flights of our imagination. There is no magic wand that we can wave. Here is the website of the creative couple.

Another version of a modern tale is this of the five from Honey Grove farm:

We are a family cohort of makers, bakers, gardeners and beekeepers. We are eaters, too, emboldened by the concepts of commensality and convivality. Our home and land is the inspiration behind all of our creative endeavours and we'd truly love to share it with you...

There are four young people living on six acres on Vancouver Island, BC, Canada, and you can find out more about them on their website. You may ask, who is the fifth on the farm? Well, it is Gus Sims, the dog who "offers workshops on unconditional love and forgiveness."

And now I am back to binge-watching Escape to the Chateau.  Au Revoir!

More On Macular Degeneration

Macular degeneration is a major cause of blindness, and researchers have discovered a new mechanism whereby retinal pigmented epithelium degenerates, casing disease. These discoveries can lead to new treatments for this disease.  Abstract:

Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β production and gasdermin D-dependent interleukin-18 secretion. Decreased DICER1 levels or Alu-RNA accumulation triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin D, interferon-β, and cGAS levels were elevated in the RPE in human eyes with geographic atrophy. Collectively, these data highlight an unexpected role of cGAS in responding to mobile-element transcripts, reveal cGAS-driven interferon signaling as a conduit for mitochondrial-damage-induced inflammasome activation, expand the immune-sensing repertoire of cGAS and caspase-4 to noninfectious human disease, and identify new potential targets for treatment of a major cause of blindness.