Showing posts with label Hope. Show all posts
Showing posts with label Hope. Show all posts

Wednesday, December 10, 2025

How To Help Someone With Depression 

 

Francesco Ciccolella

Jeff Zuckerman and his wife had been married for 30 years when she started battling bipolar disorder and depression. She had her first monthslong manic episode in the spring of 2015. Immediately after, she was thrust into a severe depression. The health crises rocked the couple’s marriage. “You have to understand that for her, depression is not sadness so much as it is emptiness,” explained Mr. Zuckerman, 68, who is a freelance writer and editor in Minneapolis.….Story continues

By: Catherine Pearson

Source: NY Times

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Critics:

Acute stressful situations where the stress experienced is severe is a cause of change psychologically to the detriment of the well-being of the individual, such that symptomatic derealization and depersonalization, and anxiety and hyperarousal, are experienced. The International Classification of Diseases includes a group of mental and behavioral disorders which have their aetiology in reaction to severe stress and the consequent adaptive response.

Chronic stress, and a lack of coping resources available, or used by an individual, can often lead to the development of psychological issues such as delusions, depression and anxiety (see below for further information). Chronic stress also causes brain atrophy, which is the loss of neurons and the connections between them. It affects the part of the brain that is important for learning, responding to the stressors and cognitive flexibility.

Chronic stressors may not be as intense as acute stressors such as natural disaster or a major accident, but persist over longer periods of time and tend to have a more negative effect on health because they are sustained and thus require the body’s physiological response to occur daily. This depletes the body’s energy more quickly and usually occurs over long periods of time, especially when these microstressors cannot be avoided (i.e. stress of living in a dangerous neighborhood).

See allostatic load for further discussion of the biological process by which chronic stress may affect the body. For example, studies have found that caregivers, particularly those of dementia patients, have higher levels of depression and slightly worse physical health than non-caregivers. When humans are under chronic stress, permanent changes in their physiological, emotional, and behavioral responses may occur.

Chronic stress can include events such as caring for a spouse with dementia, or may result from brief focal events that have long term effects, such as experiencing a sexual assault. Studies have also shown that psychological stress may directly contribute to the disproportionately high rates of coronary heart disease morbidity and mortality and its etiologic risk factors. Specifically, acute and chronic stress have been shown to raise serum lipids and are associated with clinical coronary events.

However, it is possible for individuals to exhibit hardiness—a term referring to the ability to be both chronically stressed and healthy. Even though psychological stress is often connected with illness or disease, most healthy individuals can still remain disease-free after being confronted with chronic stressful events. This suggests that there are individual differences in vulnerability to the potential pathogenic effects of stress; individual differences in vulnerability arise due to both genetic and psychological factors.

In addition, the age at which the stress is experienced can dictate its effect on health. Research suggests chronic stress at a young age can have lifelong effects on the biological, psychological, and behavioral responses to stress later in life. The term “stress” had none of its contemporary connotations before the 1920s. It is a form of the Middle English destresse, derived via Old French from the Latin stringere, “to draw tight”.

The word had long been in use in physics to refer to the internal distribution of a force exerted on a material body, resulting in strain. In the 1920s and ’30s, biological and psychological circles occasionally used the term to refer to a mental strain or to a harmful environmental agent that could cause illness. Walter Cannon used it in 1926 to refer to external factors that disrupted what he called homeostasis.

But “…stress as an explanation of lived experience is absent from both lay and expert life narratives before the 1930s”. Physiological stress represents a wide range of physical responses that occur as a direct effect of a stressor causing an upset in the homeostasis of the body. Upon immediate disruption of either psychological or physical equilibrium the body responds by stimulating the nervous, endocrine, and immune systems.

The reaction of these systems causes a number of physical changes that have both short- and long-term effects on the body. The Holmes and Rahe stress scale was developed as a method of assessing the risk of disease from life changes. The scale lists both positive and negative changes that elicit stress. These include things such as a major holiday or marriage, or death of a spouse and firing from a job.

Homeostasis is a concept central to the idea of stress. In biology, most biochemical processes strive to maintain equilibrium (homeostasis), a steady state that exists more as an ideal and less as an achievable condition. Environmental factors, internal or external stimuli, continually disrupt homeostasis; an organism’s present condition is a state of constant flux moving about a homeostatic point that is that organism’s optimal condition for living.

Factors causing an organism’s condition to diverge too far from homeostasis can be experienced as stress. A life-threatening situation such as a major physical trauma or prolonged starvation can greatly disrupt homeostasis. On the other hand, an organism’s attempt at restoring conditions back to or near homeostasis, often consuming energy and natural resources, can also be interpreted as stress. The brain cannot sustain an equilibrium under chronic stress; the accumulation of such an ever-deepening deficit is called chronic stress.

The ambiguity in defining this phenomenon was first recognized by Hans Selye (1907–1982) in 1926. In 1951 a commentator loosely summarized Selye’s view of stress as something that “…in addition to being itself, was also the cause of itself, and the result of itself”. First to use the term in a biological context, Selye continued to define stress as “the non-specific response of the body to any demand placed upon it”.

Neuroscientists such as Bruce McEwen and Jaap Koolhaas believe that stress, based on years of empirical research, “should be restricted to conditions where an environmental demand exceeds the natural regulatory capacity of an organism”. The brain cannot live in an harsh family environment, it needs some sort of stability between another brain. People who have reported being raised in harsh environments such as verbal and physical aggression have showed a more immune dysfunction and more metabolic dysfunction.

Indeed, in 1995 Toates already defined stress as a “chronic state that arises only when defense mechanisms are either being chronically stretched or are actually failing,”while according to Ursin (1988) stress results from an inconsistency between expected events (“set value”) and perceived events (“actual value”) that cannot be resolved satisfactorily, which also puts stress into the broader context of cognitive-consistency theory.

Stress can have many profound effects on the human biological systems.Biology primarily attempts to explain major concepts of stress using a stimulus-response paradigm, broadly comparable to how a psychobiological sensory system operates. The central nervous system (brain and spinal cord) plays a crucial role in the body’s stress-related mechanisms. Whether one should interpret these mechanisms as the body’s response to a stressor or embody the act of stress itself is part of the ambiguity in defining what exactly stress is.

The central nervous system works closely with the body’s endocrine system to regulate these mechanisms. The sympathetic nervous system becomes primarily active during a stress response, regulating many of the body’s physiological functions in ways that ought to make an organism more adaptive to its environment. Below there follows a brief biological background of neuroanatomy and neurochemistry and how they relate to stress.

Stress, either severe, acute stress or chronic low-grade stress may induce abnormalities in three principal regulatory systems in the body: serotonin systems, catecholamine systems, and the hypothalamic-pituitary-adrenocortical axis. Aggressive behavior has also been associated with formalities in these systems.

Wednesday, December 3, 2025

New Cancer Treatment Seeks Out Deadly Tumors And Eliminates Them

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Scientists at UCLA have developed an “off-the-shelf” cell-based immunotherapy that was able to track down and kill pancreatic cancer cells even after they had spread to other organs. In a mouse study, the treatment slowed cancer growth, extended survival and remained effective even within the harsh environment of solid tumors. “Even when the cancer tries to evade one attack pathway by changing its molecular signature, our therapy is hitting it from multiple other angles at the same time……Continue reading….

By: Khloe Quill 

Source: Fox News

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Critics:

The treatment of cancer has undergone evolutionary changes as understanding of the underlying biological processes has increased. Tumor removal surgeries have been documented in ancient Egypt, hormone therapy and radiation therapy were developed in the late 19th century. Chemotherapy, immunotherapy and newer targeted therapies are products of the 20th century.

As new information about the biology of good cancer emerges, treatments will be developed and modified to increase effectiveness, precision, survivability, and quality of life. Malignant tumours can be cured if entirely removed by surgery. But if the cancer has already spread (metastasized) to other sites, complete surgical excision is usually impossible. In the Halstedian model of cancer progression, tumors grow locally, then spread to the lymph nodes, then to the rest of the body.

This has given rise to the popularity of local-only treatments such as surgery for small cancers. Even small localized tumors are increasingly recognized as possessing metastatic potential. Examples of surgical procedures for cancer include mastectomy, and lumpectomy for breast cancer, prostatectomy for prostate cancer, and lung cancer surgery for non-small cell lung cancer. The goal of the surgery can be either the removal of only the tumor, the entire organ, or part of the organ.

A single cancer cell is invisible to the naked eye but can regrow into a new tumor, a process called recurrence. For this reason, the pathologist will examine the surgical specimen to determine if a margin of healthy tissue is present, thus decreasing the chance that microscopic cancer cells are left in the patient. In addition to removal of the primary tumor, surgery is often necessary for staging, e.g. determining the extent of the disease and whether it has metastasized to regional lymph nodes.

Staging is a major determinant of prognosis and of the need for adjuvant therapy. Occasionally, surgery is necessary to control symptoms, such as spinal cord compression or bowel obstruction. This is referred to as palliative treatmentSurgery may be performed before or after other forms of treatment. Treatment before surgery is often described as neoadjuvant. In breast cancer, the survival rate of patients who receive neoadjuvant chemotherapy are no different from those who are treated following surgery.

Giving chemotherapy earlier allows oncologists to evaluate the effectiveness of the therapy, and may make removal of the tumor easier. However, the survival advantages of neoadjuvant treatment in lung cancer are less clear. Radiation therapy (radiotherapy) is the use of ionizing radiation to kill cancer cells and shrink tumors by damaging their DNA causing cellular death. Radiation therapy can either damage DNA directly or create charged particles (free radicals) within the cells that can in turn damage the DNA.

Radiation therapy can be administered externally via external beam radiotherapy or internally via brachytherapy. The effects of radiation therapy are localised and confined to the region being treated. Although radiation damages both cancer cells and normal cells, most normal cells can recover from the effects of radiation and function properly. The goal of radiation therapy is to damage as many cancer cells as possible, while limiting harm to nearby healthy tissue.

Hence, it is given in many fractions, allowing healthy tissue to recover between fractions. Radiation therapy may be used to treat almost every type of solid tumor, and may also be used to treat leukemia and lymphoma. Radiation dose to each site depends on a number of factors, including the radio sensitivity of each cancer type and whether there are tissues and organs nearby that may be damaged by radiation. Thus, as with every form of treatment, radiation therapy is not without its side effects.

Radiation therapy can lead to dry mouth from exposure of salivary glands to radiation, resulting in decreased saliva secretion. Post therapy, the salivary glands will resume functioning but rarely in the same fashion. Dry mouth caused by radiation can be a permanent problem. Chemotherapy is the treatment of cancer with drugs (“anticancer drugs”) that can destroy cancer cells. Chemotherapy can be given in a variety of ways such as injections into the muscles, skin, artery, or vein, or it could even be taken by mouth in the form of a pill.

In current usage, the term “chemotherapy” usually refers to cytotoxic drugs which affect rapidly dividing cells in general, in contrast with targeted therapy (see below). Chemotherapy drugs interfere with cell division in various possible ways, e.g. with the duplication of DNA or the separation of newly formed chromosomes. Most forms of chemotherapy target all rapidly dividing cells and are not specific to cancer cells, although some degree of specificity may come from the inability of many cancer cells to repair DNA damage, while normal cells generally can.

Hence, chemotherapy has the potential to harm healthy tissue, especially those tissues that have a high replacement rate (e.g. intestinal lining). These cells usually repair themselves after chemotherapy. Because some drugs work better together than alone, two or more drugs are often given at the same time. This is called “combination chemotherapy”; most chemotherapy regimens are given in a combination. Since chemotherapy affects the whole body, it can have a wide range of side effects.

Patients often find that they start losing their hair since the drugs that are combatting the cancer cells also attack the cells in the hair roots. This powerful treatment can also lead to fatigue, loss of appetite, and vomiting depending on the person. The treatment of some leukaemias and lymphomas requires the use of high-dose chemotherapy, and total body irradiation (TBI). This treatment ablates the bone marrow, and hence the body’s ability to recover and repopulate the blood.

For this reason, bone marrow, or peripheral blood stem cell harvesting is carried out before the ablative part of the therapy, to enable “rescue” after the treatment has been given. This is known as autologous stem cell transplantationTargeted therapy, which first became available in the late 1990s, has had a significant impact in the treatment of some types of cancer, and is currently a very active research area. This constitutes the use of agents specific for the deregulated proteins of cancer cells. 

Small molecule drugs are targeted therapy drugs that are generally inhibitors of enzymatic domains on mutated, overexpressed, or otherwise critical proteins within the cancer cell. Prominent examples are the tyrosine kinase inhibitors imatinib (Gleevec/Glivec) and gefitinib (Iressa). Monoclonal antibody therapy is another strategy in which the therapeutic agent is an antibody which specifically binds to a protein on the surface of the cancer cells.

Examples include the anti-HER2/neu antibody trastuzumab (Herceptin) used in breast cancer, and the anti-CD20 antibody rituximab, used in a variety of B-cell malignanciesTargeted therapy can also involve small peptides as “homing devices” which can bind to cell surface receptors or affected extracellular matrix surrounding the tumor. Radionuclides which are attached to these peptides (e.g. RGDs) eventually kill the cancer cell if the nuclide decays in the vicinity of the cell.

Especially oligo- or multimers of these binding motifs are of great interest, since this can lead to enhanced tumor specificity and avidity. Photodynamic therapy (PDT) is a ternary treatment for cancer involving a photosensitizer, tissue oxygen, and light (often using lasers). PDT can be used as treatment for basal cell carcinoma (BCC) or lung cancer; PDT can also be useful in removing traces of malignant tissue after surgical removal of large tumors.

In February 2019, medical scientists announced that iridium attached to albumin, creating a photosensitized molecule, can penetrate cancer cells and, after being irradiated with light, destroy the cancer cells. High-energy therapeutic ultrasound could increase higher-density anti-cancer drug load and nanomedicines to target tumor sites by 20x fold higher than traditional target cancer therapy.

Targeted therapies under pre-clinical development as potential cancer treatments include morpholino splice switching oligonucleotides, which induce ERG exon skipping in prostate cancer models, multitargeted kinase inhibitors that inhibit the PI3K with other pathways including MEK and PIM, and inhibitors of NF-κB in models of chemotherapy resistance. Another approach to targeted therapy involves simultaneously targeting multiple genes implicated in cancer development.

For example, concurrent targeting of Integrin β3 and IGF-1R genes in breast cancer has demonstrated significant downregulation of both genes in vitro, as well as induction of programmed cell death (apoptosis) in cancer cells. A systematic review published in Cochrane database found that targeted therapies significantly improve progression-free survival by 35 to 40% in metastatic or relapsed cancer.

While the research points to promising clinical outcomes, there is still limited evidence on the long-term effects of targeted therapies in terms of overall survival, quality of life, and severe adverse events. Cancer immunotherapy refers to a diverse set of therapeutic strategies designed to induce the patient’s own immune system to fight the tumor. Contemporary methods for generating an immune response against tumors include intravesical BCG immunotherapy for superficial bladder cancer, and use of interferons and other cytokines to induce an immune response in renal cell carcinoma and melanoma patients. 

Cancer vaccines to generate specific immune responses are the subject of intensive research for a number of tumors, notably melanoma and renal cell carcinoma. Sipuleucel-T is a vaccine-like strategy for prostate cancer in which dendritic cells from the patient are loaded with prostatic acid phosphatase peptides to induce a specific immune response against prostate-derived cells. It gained FDA approval in 2010.

Allogeneic hematopoietic stem cell transplantation (usually from the bone marrow) from a genetically non-identical donor can be considered a form of immunotherapy, since the donor’s immune cells will often attack the tumor in a phenomenon known as graft-versus-tumor effect. For this reason, allogeneic HSCT leads to a higher cure rate than autologous transplantation for several cancer types, although the side effects are also more severe.

The cell based immunotherapy in which the patients own natural killer cells (NKs) and cytotoxic T cells are used has been in practice in Japan since 1990. NK cells and TCs primarily kill the cancer cells when they are developed. This treatment is given together with the other modes of treatment such as surgery, radiotherapy or chemotherapy and termed autologous immune enhancement therapy (AIET).

Immune checkpoint therapy focuses on two immune checkpoint proteins, cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Under normal conditions, the immune system utilizes checkpoint proteins as negative feedback mechanisms to return to homeostasis once pathogens have been cleared from the body. In a tumor microenvironment, cancer cells can commandeer this physiological regulatory system to “put a brake” on the anti-cancer immune response and evade immune surveillance.

2018 Nobel Prize in medicine is awarded to Dr. James Allison of University of Texas MD Anderson Cancer Center in U.S. and Dr. Tasuku Honjo Kyoto University in Japan for their contributions in advance of PD-1 and CTLA-4 immune checkpoint therapy. The growth of some cancers can be inhibited by providing or blocking certain hormones. Common examples of hormone-sensitive tumors include certain types of breast and prostate cancers.

Blocking estrogen or testosterone is often an important additional treatment. In certain cancers, administration of hormone agonists, such as progestogens may be therapeutically beneficial. Although the side effects from hormone therapy vary depending on the type, patients can experience symptoms such as hot flashes, nausea, and fatigue.

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