High-stress jobs may to lead to early grave, reveals study

California, May 13: A fasting-mimicking diet could be more effective at treating some types of cancer when combined with vitamin C, suggests a new study conducted by the scientists from USC and the IFOM Cancer Institute in Milan.

In studies on mice, researchers found that the combination delayed tumour progression in multiple mouse models of colorectal cancer; in some mice, it caused disease regression. The results were published in the journal Nature Communications.

"For the first time, we have demonstrated how a completely non-toxic intervention can effectively treat an aggressive cancer," said Valter Longo, the study senior author and the director of the USC Longevity Institute at the USC Leonard Davis School of Gerontology and professor of biological sciences at the USC Dornsife College of Letters, Arts and Sciences.

"We have taken two treatments that are studied extensively as interventions to delay ageing-- a fasting-mimicking diet and vitamin C -- and combined them as a powerful treatment for cancer," added Longo.

The researchers said that while fasting remains a challenging option for cancer patients, a safer, more feasible option is a low-calorie, plant-based diet that causes cells to respond as if the body were fasting.

Their findings suggest that a low-toxicity treatment of fasting-mimicking diet plus vitamin C has the potential to replace more toxic treatments.

Results of prior research on the cancer-fighting potential of vitamin C have been mixed. Recent studies, though, are beginning to show some efficacy, especially in combination with chemotherapy.

In this new study, the research team wanted to find out whether a fasting-mimicking diet could enhance the high-dose vitamin C tumour-fighting action by creating an environment that would be unsustainable for cancer cells but still safe for normal cells.

"Our first in vitro experiment showed remarkable effects. When used alone, fasting-mimicking diet or vitamin C alone reduced cancer cell growth and caused a minor increase in cancer cell death. But when used together, they had a dramatic effect, killing almost all cancerous cells," said Longo.

Longo and his colleagues detected this strong effect only in cancer cells that had a mutation that is regarded as one of the most challenging targets in cancer research.

These mutations in the KRAS gene signal the body is resisting most cancer-fighting treatments, and they reduce a patient's survival rate. KRAS mutations occur in approximately a quarter of all human cancers and are estimated to occur in up to half of all colorectal cancers.

The study also provided clues about why previous studies of vitamin C as a potential anticancer therapy showed limited efficacy. By itself, a vitamin C treatment appears to trigger the KRAS-mutated cells to protect cancer cells by increasing levels of ferritin, a protein that binds iron.

But by reducing levels of ferritin, the scientists managed to increase vitamin C's toxicity for the cancer cells. Amid this finding, the scientists also discovered that colorectal cancer patients with high levels of the iron-binding protein have a lower chance of survival.

"In this study, we observed how fasting-mimicking diet cycles are able to increase the effect of pharmacological doses of vitamin C against KRAS-mutated cancers," said Maira Di Tano, a study co-author at the IFOM, FIRC Institute of Molecular Oncology in Milan, Italy.

"This occurs through the regulation of the levels of iron and of the molecular mechanisms involved in oxidative stress. The results particularly pointed to a gene that regulates iron levels: heme-oxygenase-1," added Tano.

The research team's prior studies showed that fasting and a fasting-mimicking diet slow cancer's progression and make chemotherapy more effective in tumour cells while protecting normal cells from chemotherapy-associated side effects. The combination enhances the immune system's anti-tumour response in breast cancer and melanoma mouse models.

The scientists believe cancer will eventually be treated with low-toxicity drugs in a manner similar to how antibiotics are used to treat infections that kill particular bacteria, but which can be substituted by other drugs if the first is not effective.

To move toward that goal, they say they needed to first test two hypotheses: that their non-toxic combination interventions would work in mice, and that it would look promising for human clinical trials.

In this new study, they said that they've demonstrated both. At least five clinical trials, including one at USC on breast cancer and prostate cancer patients, are now investigating the effects of the fasting-mimicking diets in combination with different cancer-fighting drugs.

The Lockdown is not a cure but a critical strategy to prevent the geographical spread of COVID-19.

While pandemics at this level involves actual life threatening situations for individual's or significant others in one's immediate circle, it envisages a marked disruption in routine life. Even after the pandemic has been contained and will come to pass; it's aftermath will leave a trailblazer which demands planning and implementation of a post pandemic reconstruction of society with potentially traumatic experiences varying in intensity, multiplicity and duration.

Degree of Trauma

It would do well for each one of us to realise that the pandemic is "potentially traumatic", since not everyone will experience COVID -19 as a traumatic event in their lives. Yet, there will be those who may develop post pandemic stress reactions, depression and related dysfunction and pathological reactions while still other exhibit healthy reactions to the same set of circumstances.

"Psychological reactions to the pandemic can be distilled into four distinct prototypical patterns, namely, Resilience, Recovery, Chronic and Delayed patterns which may vary in intensity, multiplicity, and duration. Resilient individual have an ability to bounce back from adversity and experience modest or little disruption in normal functioning and are able to maintain a relatively stable, healthy levels of psychological functioning even after enduring the pandemic. Recovery pattern is characterised by relatively rapid reduction in symptoms and return to normal functioning whereas chronic pattern is characterised by symptoms and dysfunction of a long duration," says Pune-based military psychologist Lt Col Dr Samir Rawat.

Challenges at the Individual and Community Levels

From a psychological perspective, post pandemic reconstruction would entail catering to the problems, concerns and needs of those adversely impacted by the COVID -19 with stress symptoms typically characterised by individual's experiencing an overwhelming trauma of the pandemic (for example, recurring nightmares/ breaking into a cold sweat, flashback of stressful events, increasing irritability, low frustration tolerance or emotional numbing).

It could also manifest in depressive symptoms which may result in lack of interest or diminished pleasure in activities and things which you earlier liked to do, feelings of worthlessness or even survivor guilt in case of a loss of a loved one due to COVID-19, fleeting thoughts of death and suicidal ideation. Physical symptoms, on the other hand could be a decrease in appetite, weight and sleep problems, inability to focus and lack of concentration.

Undoubtedly, the pandemic will cause a financial loss of varying magnitude to many, especially the marginalised and economically disadvantaged strata of daily wage earners; it will also lead to loss of jobs (already beginning to show), homelessness, occupational difficulties and new challenges in interpersonal relations at work and on the home front, besides physical health problems and psychological barriers with new norms of accepted social behaviour (social distancing, handshakes, an obsession for cleanliness to name a few).

Emotional battles

Many factors may influence whether individuals come out stronger and more resilient or surrender to the pandemic. Emotion Regulation is one such long term critical factor that can play an important role in contributing to varying degrees of adaptation with negative or positive outcomes. While we know that primary emotions are fear, anger, disgust, joy, anticipation, acceptance, sadness and surprise, other basic emotions include wonder, love, desire, joy, hatred, sadness, attachment, disgust, rage and even expectancy .

To be able to regulate these emotions and avoid negativity , especially on social media platforms is likely to increase efforts in emotion regulation which involves initiating, increasing or maintaining an emotional response.

This means by regulating or on the other hand by stopping, decreasing or avoiding an emotional response, that is, by down-regulating, depending on the individual's objectives and goals or his /her ability to regulate emotions in the valued and given direction.

"One of the best ways to regulate emotions is through cognitive restructuring wherein we change the way we think; after all it is not the event but the interpretation of the event which is perceived as stressful and finding meaning promotes resilience and reduces risk and vulnerability to stress," advises Dr Rawat.

Adding, "Clearly, we need to have a psychological plan to prevent, mitigate and minimise negative outcomes by post pandemic reconstruction of society at an individual and community level all over the country; this has to be integrated by all leaders across verticals in diverse domains."

Washington D.C., Jan 25: A new study conducted by a team of researchers reveals why individuals who have a history of early life adversity (ELA) are disproportionately prone to opioid addiction.

The study conducted examined how early adversities interact with factors such as increased access to opioids to directly influence brain development and function, causing a higher potential for opioid addiction.

The study was lead by UCI researchers and was published in Molecular Psychiatry.

Tallie Z. Baram, MD, PhD, the Danette Shepard Chair in Neurological Sciences at the UCI School of Medicine and one of the senior researchers for the study, was on the take that the widely known factor genetics that plays major role in addiction vulnerability, cannot be solely held responsible for the recent rise in opioid abuse.

To further clarify, the researchers simulated ELA in rats by limiting bedding and nesting materials during a short, postnatal period of time.

In female rats, this led to striking opioid addiction-like characteristics including an increased relapse- behaviour, for example.

As observed in addicted humans, the rats were willing to work very hard (pay a very high price) to obtain the drug.

Baram said: "Ultimately, we found that conditions during sensitive developmental periods can lead to vulnerability to the addictive effects of opioid drugs, especially in females, which is consistent with the prevalence of ELA in heroin-addicted women."

These findings can be used to highlight the importance given to sex differences in future ELA-related studies on opioid addiction, and in future prevention or intervention strategies being developed to address the growing opioid crisis.

The study conducted examined how early adversities interact with factors such as increased access to opioids to directly influence brain development and function, causing a higher potential for opioid addiction.

The study was lead by UCI researchers and was published in Molecular Psychiatry.

The study found that unpredictable, fragmented early life environments may lead to abnormal maturation of certain brain circuits, which profoundly impacts brain function and persists into adolescence and adulthood.

Tallie Z. Baram, MD, PhD, the Danette Shepard Chair in Neurological Sciences at the UCI School of Medicine and one of the senior researchers for the study, was on the take that the widely known factor genetics that plays major role in addiction vulnerability, cannot be solely held responsible for the recent rise in opioid abuse.

To further clarify, the researchers implanted ELA in rats by limiting bedding and nesting materials during a short, postnatal period of time.

In female rats, this led to striking opioid addiction-like characteristics including an increased relapse- behaviour, for example.

As observed in addicted humans, the rats were willing to work very hard (pay a very high price) to obtain the drug.

Baram said: "Ultimately, we found that conditions during sensitive developmental periods can lead to vulnerability to the addictive effects of opioid drugs, especially in females, which is consistent with the prevalence of ELA in heroin-addicted women."

These findings can be used to highlight the importance given to sex differences in future ELA-related studies on opioid addiction, and in future prevention or intervention strategies being developed to address the growing opioid crisis.