researchfindings - Tumblr blog

[researchfindings]

“when the researchers dosed mice with broad-spectrum antibiotics, killing off their gut bacteria, the distance the rodents were able to run dropped by half. But off the antibiotics, the mice mostly regained their previous performance levels.”

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“The autoAb panel included anti-IFN-α2, and five anti-nuclear autoAbs (ANAs) (Ro/SS- A, La/SS-B, U1-snRNP, Jo-1, and P1)”

I suspect that this will lead to more diagnoses of systemic lupus erythematosus post-Covid.

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A comparison between different Covid 19 monoclonal antibodies for post-exposure prophylaxis, pre-exposure prophylaxis, and treatment of active disease.

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The Inherited Autoinflammatory Syndrome: A Decade of Discovery

Familial Mediterranean fever (FMF)- recurrent attacks of fever with associated serosal inflammation, attacks last 1-3 days and recur between every 10 days and twice per year. Concern is amyloidosis. Use colchicine.

Hyperimmunoglobulinemia D syndrome (HIDS)- rarer, European, attacks last 3-7 days. Headache, abdominal pain, diarrhea, cervical lymphadenopathy, arthritis. High Igg. Anakinra (not colchicine).

TNF Receptor Associated Periodic Fever (TRAPS)- rare, Irish/Scottish, attacks last 1-6 weeks. Sterile peritonitis, pleuritis, arthritis, severe myalgias, migratory lymphedema, conjunctivitis, male hernias, erythematous rashes. Etanercept or Anakinra.

Cryptopyrinopathies (IL1 and IL6):

Familial Cold Autoinflammatory Syndrome (FCAS)- midsouth states, start in childhood and get worse. Pruritic, painful rash from cold exposure. Conjunctivitis, fever, joint symptoms, fatigue and headache. Rarely, hearing loss and amyloidosis. Anakinra.

Muckle-Wells Syndrome (MWS)- Europe, first two decades of life. Attacks triggered by cold, stress, and exercise. Fever, rash, arthralgias, abdominal pain and conjunctivitis. Sometimes deafness, nephropathy, amyloidosis. Anakinra.

Neonatal Onset Multisystem Inflammatory Disease (NOMID)- severe. Fevers, rash, hearing loss, major deforming joint disease, uveitis, chronic meningitis, cerebral atrophy, delayed development, amyloidosis, high death rate. Anakinra, steroids, etanercept, possibly thalidomide, as well as a newly developed humanized anti IL-6 receptor monoclonal antibody.

Pyogenic Arthritis, Pyoderma Gangrenosum Acne (PAPA) Syndrome- Acne starts in puberty. Also includes sterile pyogenic arthritis, pyoderma gangrenosum, and sterile skin abscesses. No treatment is listed in this article.

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Cytokines and systemic lupus erythematosus

SLE is an autoimmune rheumatic disease that principally affects women in the childbearing years.1 The prevalence of SLE varies between ethnic groups, being approximately 1:250 among black women, 1:1000 in Chinese women and 1:4300 in white women. SLE affects the joints, skin and blood in over 80% of patients and the kidneys, central nervous system and cardiopulmonary system in 30%–50% of patients. Between 10% and 30% of patients have anticardiolipin antibodies that are associated with arterial and venous thrombosis. The majority of patients demonstrate systemic manifestations, which may include fatigue, malaise, fever, anorexia, nausea and weight loss.

Many cytokines have been implicated in regulating disease activity and in the involvement of different organs in patients with SLE. This article reviews both the role of individual cytokines and discusses possible mechanisms of cytokine action in individual organs.

[researchfindings]

The overfitted brain: Dreams evolved to assist generalization

Summary of new theory from Medscape:

Strange dreams serve an important purpose, he says, and help our brains understand day-to-day experiences in a way that enables deeper learning. Humans, he suggests in a recent study, actually expand their brain power in much the same way that artificial intelligence (AI) systems are trained to become smarter.

In fact, scientists are using deep-learning neural networks to train AI systems.

But when an AI system becomes too familiar with data, it can oversimplify its analysis, becoming an "overfitted brain" that assumes what it sees is a perfect representation of what it will encounter in future.

To counter that problem, scientists introduce a degree of chaos and randomization into their data to deepen machine learning and improve the accuracy of AI systems.

In much the same way, "our brains are so good at learning that we're always in danger of being overfitted," warns Hoel. That can lead to overly simplistic and too-familiar perceptions of the world around us. As a prompt, just like in AI training, our brains introduce chaos as we sleep, which often takes the form of outlandish dreams.

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Review: female sex hormones, autoimmune diseases and immune response

“There has been much evidence of the role of sex steroids in immune reactions. The most common factors are listed as follows:

(1) Effects of gonadectomy and hypogonadism

in male and female animals on humoral and cell-mediated immunity;

(2) Effects of estrogen and progesterone on interleukin (IL)-1 production by human monocytes;

(3) Presence of estrogen receptors in lymphoid and thymus cells;

(4) Various effects of the menopause, menarche, pregnancy and menstrual cycle on the severity of symptoms of autoimmune diseases;

(5) Abnormalities of estrogen metabolism during autoimmune diseases.”

“Sex hormones, such as estrogen and progesterone, can interact with multiple target sites, which by themselves can influence immune responses… These hormones affect the function of T cells, natural killer cells, B cells or macrophages”

“estrogens also decrease T-cell and natural killer cell responses. For example, women taking oral contraceptives exhibit a signifi- cantly lower T-cell proliferation than women not taking oral contraceptives”

“Progesterone resulted in only an increased leukocyte and T-cell concentration in the human endometrium. In the main, progesterone seems to suppress the immune system. For example, in vitro, it down-regulates T-cell proliferation in responding to mitogens, whereas in vivo, progesterone administration produced an increase in CD8+ T-cells”

“The predominance of autoimmune diseases among women suggests that estrogen and/or progesterone may modulate immune susceptibility.”

“To date, no explanation for the high prevalence of SLE in women has been formulated. Variations of the disease’s severity have been observed during the menstrual cycle. Female SLE patients have also reported a significant exacerbation of SLE during the luteal phase.”

“In two interesting animal models, it was shown that estradiol reduced the incidence and severity of [rheumatoid arthritis].”

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“Emerging findings link COVID-19 to cognitive deficits, particularly attention, executive function, and memory. Psychiatric symptoms occur at high rates in COVID-19 survivors, including anxiety, depression, fatigue, sleep disruption, and to a lesser extent posttraumatic stress. Symptoms appear to endure, and severity of acute illness is not directly predictive of severity of cognitive or mental health issues.”

“risk factors for psychiatric symptoms include female sex, perceived stigma related to COVID-19, infection of a family member, social isolation, and prior psychiatry history”

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“performance in the MoCA [cognitive] test was impaired in 18 of 26 COVID-19 patients tested. This indicates that besides cranial nerve affection and other neurological symptoms that were reported previously, cognitive deficits are present in many COVID-19 patients requiring inpatient treatment. With an average score of 21.8/30, the MoCA indicates mild to moderate cognitive impairment in our cohort.”

“the orientation and language abilities on the MoCA in COVID-19 patients were in the range of healthy subjects, whereas memory and executive items were most severely affected, which makes general deterioration unlikely. The… battery corroborates the decline in memory and executive functions but not in general attention or processing speed. This specific pattern can hardly be explained by non-specific factors like fatigue”

“4/13 scans showed microembolic subacute infarcts, which is in line with a previous imaging series in COVID-19 patients”

“Together with our pathological sample that indicates innate immune activation, a systemic cytokine release or cytokine-related hyperinflammation may be a valid explanation for cortical dysfunction, leading to cerebral hypometabolism and cognitive impairment”

“physicians treating COVID-19 inpatients should be aware of this phenomenon and include bedside tests evaluating cognitive function (e.g. MoCA) into their routine workup. Patients suffering from cognitive deficits should be presented to neurologists and possibly allocated to cognitive rehabilitation programs”

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Key Driver of Fish Oil's Antidepressant Effects Revealed

Original Study: Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: relevance for major depression and for human hippocampal neurogenesis

“This ability of PUFAs [omega 3 polyunsaturated fatty acids] to protect neurones from the detrimental effects of inflammation is likely to be relevant for their antidepressant action, at least in the sub-group of patients with major depression characterised by immune dysregulation… characterised by an increase in the production of inflammatory cytokines”

“concentrations of EPA and DHA (both 10 µM), used in this study and in our previous in vitro studies… likely cannot be achieved with consumption of food rich in ω-3 PUFAs, but rather require therapeutic PUFAs supplements.”

“treatment with these metabolites prevented cytokines-induced reduction in neurogenesis and apoptosis… some evidence that higher levels of these metabolites were correlated with less severe depressive symptoms”

“treating human hippocampal cells with EPA or DHA before exposing them to cytokines prevented increased cell death and decreased neurogenesis… these effects were mediated by the formation of several key lipid mediators produced by EPA and DHA”

“22 patients with major depression given either EPA (3 g/day) or DHA (1.4 g/day) for 12 weeks. In both groups, EPA or DHA treatment was associated with an increase in their respective metabolites and significant improvement in depressive symptoms. The average reduction in symptom scores was 64% and 71% in the EPA and DHA groups, respectively, and there was some evidence that higher levels of the same metabolites correlated with less severe depressive symptoms.”

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Which patients with systemic lupus erythematosus in remission can withdraw low dose steroids? Results from a single inception cohort study

Lupus Foundation of America Summary

“among the [glucocorticoid] withdrawal group, the rate of flares was significantly higher in serologically active clinically quiescent (SACQ) patients… duration of hydroxychloroquine (HCQ) therapy and ≥5 year remission at withdrawal were protective factors, while a SACQ disease and history of lupus nephritis increased the risk of disease flare.”

Among lupus patients in remission, withdrawal of glucocorticoids (steroids) is possible without flare, especially in patients using hydroxychloroquine/Plaquenil and long-term remission (five years or more), with more risk of flare if serology (bloodwork) is active or with history of lupus nephritis.

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Cervical transcutaneous vagal nerve stimulation (ctVNS) improves human cognitive performance under sleep deprivation stress

Medscape Summary

“Two groups (active or sham stimulation) of twenty participants in each group completed 34 h of sustained wakefulness. The ctVNS group performed significantly better on arousal, multi-tasking, and reported significantly lower fatigue ratings compared to sham”

“The sham provides similar sensations (e.g., vibrations) without providing electrical stimulation of the nerves.”

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“a middle aged man who presented to us with the complaints of documented body temperature fluctuations since two months followed gradually by hoarseness of voice, sexual dysfunction and syncope.”

“alternating periods of excessive heat and cold intolerance and body sweating which was associated with excessive shivering and documented fluctuations in body temperature throughout the day since past two months”

“hormone profile revealed pan-hypopituitarism and elevated titre of anti-TPO antibodies”

“treated with prednisolone along with hormone replacement. Rapid response within 30 days was observed in the form of subsidence of temperature fluctuations, improvement in general well being, sexual function”

“patient was empirically started on hormone therapy in the form of prednisolone (60mg/day), levothyroxine (75 mcg/day) and testosterone. Patient improved symptomatically within 30 d of treatment and his temperature fluctuations subsided and there was an improvement in general well being and sexual function”

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Continuation of Antidepressants vs Sequential Psychological Interventions to Prevent Relapse in Depression: An Individual Participant Data Meta-analysis

Depression relapse in patients in depression remission was equivalent in patients who continued antidepressants as it was in patients who tapered off of antidepressants before or while undergoing preventive cognitive therapy or mindfulness-based cognitive therapy.

“Individual data from 714 participants… that compared preventive cognitive therapy or mindfulness-based cognitive therapy during and/or after antidepressant tapering vs antidepressant monotherapy were available”

“Two-stage random-effects meta-analysis found no significant difference in time to depressive relapse between use of a psychological intervention during tapering of antidepressant medication vs antidepressant therapy alone”

“the sequential delivery of a psychological intervention during and/or after tapering [off of antidepressants] may be an effective relapse prevention strategy instead of long-term use of antidepressants”

Medscape Summary

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No safe level of alcohol consumption for brain health: observational cohort study of 25,378 UK Biobank participants

Medscape Summary

“No safe dose of alcohol for the brain was found. Moderate consumption is associated with more widespread adverse effects on the brain than previously recognised. Individuals who binge drink or with high blood pressure and BMI may be more susceptible.”

“Higher volume of alcohol consumption per week was associated with lower grey matter density almost globally… Widespread negative associations were also found between alcohol consumption and all the white matter integrity measures assessed”

“Additive harmful effects of alcohol volume and frequent binging were observed. In contrast there was no evidence that effects can be differentiated according to alcohol beverage type. Brain functional connectivity, related to cognitive function, was also associated with alcohol intake.”

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“It's clear that diabetes is one of the core factors driving poor outcomes in people who have COVID-19. A person with diabetes is more than twice as likely to be hospitalized. If they're hospitalized, risk of death is about 25%, two- to threefold higher than a person without diabetes, and 20%-40% end up in intensive care.”

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Surprising results- completely counterintuitive.

“Investigators had assumed that IBS symptoms would worsen, fueled by new stresses and pressures related to a nationwide lockdown... Now, the hypothesis has changed... "We think that probably just staying at home in a more relaxed way, and in a more controlled environment, could have improved those symptoms," Stefanolo said in an interview.”

“The proportion of patients with severe IBS dropped from 50% (65 patients) in the prepandemic period to 30% (39 patients) during the lockdown”

“Patients reported improvements in global IBS symptoms, pain, and distention. Stool consistency was also improved... Similar improvements from the prepandemic period were observed in anxiety and somatization scores, as well as in symptoms of fibromyalgia and chronic fatigue.

By contrast, headache and pyrosis and/or regurgitation symptoms increased from the prepandemic period, possibly because of weight gain, according to Dr. Stefanolo who said that about 60% of patients reported weight gain during the lockdown.”

“Diet, exercise, and other lifestyle factors such as spending more time with family could be contributing to the improvement in symptoms”