As we all know, humans evolve from animals, whose anatomical and structs are related to mammal animals.However, the habits between them are different, especially upright walking and sleeping on your back.Animals appeared earlier than humans, so physiological habits animals ， physiological habits may be more in line with the laws of nature, which may lead to the use of some organs or systems of human beings not in line with the laws of natural evolution.In fact, humans often suffer from some common chronic diseases that rarely occur in animals.Such as varicocele and prolapse of inter-vertebral disc, this phenomenon may be related to the human ' s position of special activities and rest.For example, the standing position increases gravity load of the lumbar disc and increases the distance of blood drainage from the spermatic venous, while sleeping on your back aggravates the compression on the spermatic venous.In addition, a series of clinical medical studies prove that sleeping on your back is more harmful compared to sleeping on your side in a variety of disease states These modern medical evidence well support a point in traditional Chinese medicine: it is better to sleep on your side This paper aims to deepen the understanding of traditional Chinese medicine (TCM) and the etiology of some common chronic diseases from the perspective of comparative anatomy between human beings and mammals.
Objectives: CIMAvax-EGF is a therapeutic vaccine registered as switch maintenance therapy.This vaccine induces antibodies against self EGF that affect EGF-EGFR interaction.The aim of this study was to evaluate safety and efficacy of CIMAvax-EGF in the context of primary care. Methods:A phase IV clinical trial was conducted in 65 Policlinic areas and 16 hospitals in Cuba during 3 years.A total of 1081 advanced NSCLC patients were included without other treatment options due to progressive disease or comorbidities.CIMAvax-EGF was administered by intramuscular injection in four sites of administration (4 subdoses of 0.25 ml), every 2 weeks the first 4 doses and after this induction phase monthly reinmunizations were given.Results: A total of 927 patients (85.7 %) received at least one dose of CIMAvaxEGF.Most frequently adverse events related to vaccine were: injection-site reaction (14.5%), fever (7.0%), headache (5.8%), tremors (4.3%), and nausea (4.3%).Most of them were grade1 -2 according CTCAE v3.There were no deaths related to CIMAvaxEGF.The median overall survival (mOS) time for all vaccinated patients was 7.0 months, and in a subgroup of patient who received at least 4 doses of CIMAvaxEGF mOS was 9.98 months (n=715).Patients treated as switch maintenance therapy (n=97) reached a mOS of 12.1 months.In a subgroup of unfit patients (n=213) mOS was 3.97 months, but in those who completed the induction phase mOS was 7.36 months (n=124).Emotional function was improved at months 6 and 12 compared to baseline. Conclusions:CIMAvaxEGF vaccine is a safe treatment option for advanced NSCLC that can be safely administered at primary level of health care.The median OS of treated patients (unselected population) compares with the results reported for second-line treatments and switch maintenance therapies.Patients who completed the induction phase of the treatment reached a better OS.
The APPIRED II study is a randomized controlled phase II clinical study that was set up to test the anti-inflammatory effects of intervenously-dosed bRESCAP in 53 patients undergoing cardiac surgery.bRESCAP is a specific type of bovine intestinal alkaline phosphatase that is currently under development as a biological response modifier for the treatment of various inflammatory diseases.Patients undergoing cardiac surgery are at increased risk to develop a systemic inflammatory response syndrome (SIRS).This syndrome may lead to death by downstream complications like multi-organ failure.In a previous study among patients undergoing coronary artery bypass grafting, it was demonstrated that bRESCAP diminishes the cytokine storm which appeared to be initiated by a significant TNFa response.The current APPIRED II study was set up to further extend these findings in a population of cardiac surgery patients with a higher chance to die from surgery.In APPIRED II, however no significant TNF alpha response occurred.Various other inflammatory markers in plasma of patients were temporarily increased upon surgery but did not respond to bRESCAP treatment.Safety-wise, APPIRED II was successful.No statistically significant differences were observed between placebo treated and bRESCAP treated patients with respect to inflammatory cytokines, haematology, clinical chemistry, cardiac function, body temperature, hospitalization time and the total number of adverse effects.Perioperative mortality was absent in the bRESCAP group.In the placebo group, the perioperative mortality was 12% (n.s.).From the data of the APPIRED II study it can be concluded that short term intravenous treatment of cardiac surgery patients with bRESCAP is safe.Potential TNF alpha lowering effects of bRESCAP treatment could not be demonstrated in this study as no TNF alpha dependent inflammatory responses were observed in any of the patients.
Received: January 20, 2020; Accepted: February 04, 2020; Published: February 10, 2020 It is not common for papers on plant hormones to find their way into any endocrinological journals. Plants and mammals seem as far apart biologically as one could get. But in a number of respects animal and plant hormones do share some common issues in which knowledge in one can help better understanding of the other.
Background: The aim of this study is to determine the changes in serum levels of malondialdehyde, 8-hydroxy-2’-deoxyguanosine, hsCRP and fibrinogen as indicators of oxidative stress and inflammatory markers, in response to non-surgical periodontal treatment. Case description: The patient, a 51-year-old male diagnosed with periodontitis was taken so as to be studied with a therapeutic objective, which should allow after three months the time of diagnosis and after non-surgical treatment. Topical doxycycline was used as adjunctive medication. Conclusion: A significant reduction in both serum levels of pro-inflammatory markers and oxidative stress indicators is observed after periodontal treatment.
Received: December 02, 2019; Accepted: December 12, 2019; Published: December 16, 2019 Following its initial description in 1990 [1], the non-classical class I HLA molecule HLA-G has been well-characterised on extravillous cytotrophoblast as a molecule intimately involved in protection of the foetus from attack by the maternal immune system [2]. In addition to its expression on trophoblast, HLA-G is also found at lower levels in thymus, cornea, nail matrix, haematopoietic progenitors and pancreas [3], where its function is less clear. Unlike classical class I HLA molecules, HLA-G can be expressed as a variety of cell-bound and soluble isoforms [4], including several soluble forms (sHLA-G).
However, according to current guidelines the gold standard of HS first-line-therapy beside surgery still is long-term treatment with systemic or topical antibiotics [3], which do not always stop the disease activity, lead to well-known side effects and bear the risk of resistance development [4]. A first breakthrough in HS therapy has been achieved with Adalimumab, a monoclonal anti-TNFα antibody.
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by permanent degeneration of both lower and upper motor neurons. The main symptoms of ALS are muscle atrophy, fasciculations, spasticity and loss of muscle strength. Loss of muscle strength in the respiratory system eventually leads to death. Without artificial ventilation, death occurs within 2 to 4 years after the onset of symptoms. Five to ten percent of ALS patients have contracted ALS due to genetic causes, having relatives with ALS [1]. Mutations in SOD1 (superoxide dismutase 1) and several other genes have been identified as genetic causes of ALS. The remaining 90% of patients are classified as sporadic ALS patients [2]. The cause of the disease in these cases remains unclear. At present, since no curable treatment of ALS exists, current treatment methods focus on managing symptoms. Gastrostomy is used to counter dysphagia and artificial ventilation is used to provide respiratory support.
Dysregulation of the glutamatergic system underlies the pathophysiology of depression. Both negative and positive modulation of NMDARs exert rapid and sustained antidepressant effects by reversing the dysregulated glutamatergic system. Research in the past decades has identified key signaling pathways activated by these rapid acting antidepressants. Here, we review the converging signaling mechanisms shared by rapid acting antidepressants and discuss the recent progress on distinct actions of NMDAR antagonists and NMDAR positive modulators to trigger rapid antidepressant actions.
In recent years, tumor immunotherapy has obtained remarkable outcomes in the treatment of hematologic malignancies, tumor immunotherapy has been gradually applied to digestive system malignancies (DSMs) and has achieved some results. Chimeric antigen receptor T cells (CAR-T) is a gene-engineered receptor technology that integrates the antibody fragment of malignancy antigen and T cell activation domain to target and kill malignancy cells. CAR-T has been proved to be a strong killer of malignancies in B-cell leukemia and lymphoma. Therefore, a large number of research centers around the world have begun to focus on the application of CAR-T technology in DSMs, and their research has confirmed that CAR-T technology has a clear effect on the treatment of DSMs. Through reading a large number of literatures, we summarized the progress of CAR-T technology and its application in DSMs.
Pain can be defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of that injury. Aerobic exercise has been widely studied in painful conditions subjects and is related for the improvement of the fragility syndrome, increasing the pain threshold/tolerance during and after its practice. For healthy subjects, aerobic exercise has already shown to prevent various diseases and strengthen the immune system, fighting infection diseases. The objective of this review was to report the modalities of aerobic exercises associated with the treatment of adjuvant pain reduction of experimental pain or tolerance) in the skeletal muscle system a systematic review of clinical studies. search the recommendation. were selected, reporting results related to pain modulation through aerobic exercise. A total of 20,790 studies from which we evaluated 110 records and, finally, we included 7 studies in the quantitative analysis, following the eligibility criteria. The results revealed that healthy men and women (about 97 patients) increased the pain threshold /tolerance through aerobic exercise. Protocols with different stimulations were evaluated. With low quality of evidence, it is indicated that aerobic exercise increases threshold / tolerance of peripheral pain in healthy people.
Rice is a staple food of most Asian diets and a major contributor to high carbohydrate load.The objective of our study was to evaluate factors that affect digestibility of rice and corroborate in vitro estimated Glycaemic Index (GI) with clinically evaluated GI.We hypothesised that in vitro digestibility and thus estimation of GI may be impacted by multiple parameters including amylose content, particle size and method of cooking.In this study, a commonly consumed South Indian white rice variety, was evaluated for various factors that affect in vitro digestibility.Our results suggest amylose content and particle size of rice to be inversely related to digestibility and estimated Glycaemic Index (GI).Of the five different commonly followed consumer cooking methods tested, electric cooking method increased in vitro digestibility.GI was evaluated in fifty healthy volunteers with the selected variety cooked by an optimized method, showed a high GI of 70 ± 3 (SEM).This study thus extends the current knowledge on factors affecting in vitro digestibility of selected variety of rice and suggests an important role of consumer processing methods.
Inter-individual variation in plants and particularly in hormone content, figures strongly in evolution and behaviour. Homo sapiens and Arabidopsis exhibit similar and substantial phenotypic and molecular variation. Whereas there is a very substantial degree of hormone variation in mankind, reports of inter-individual variation in plant hormone content are virtually absent but are likely to be as large if not larger than that in mankind. Reasons for this absence are discussed. Using an example of inter-individual variation in ethylene content in ripening, the article shows how biological time is compressed by hormones. It further resolves an old issue of very wide hormone dose response that result directly from negative regulation in hormone (and light) transduction. Negative regulation is used because of inter-individual variability in hormone synthesis, receptors and ancillary proteins, a consequence of substantial genomic and environmental variation. Somatic mosaics have been reported for several plant tissues and these too contribute to tissue variation and wide variation in hormone response. The article concludes by examining what variation exists in gravitropic responses. There are multiple sensing systems of gravity vectors and multiple routes towards curvature. These are an aspect of the need for reliability in both inter-individual variation and unpredictable environments. Plant hormone inter-individuality is a new area for research and is likely to change appreciation of the mechanisms that underpin individual behaviour.
Objective: Most of the patients in intensive care unit (ICU) present nutritional challenges which needs to be compensated using enteral tube feeding (ETF). Maxvida™ is a commercially available balanced nutrition supplement with antioxidants, bone strengthening and hemoglobin forming nutrients. However, its benefits in patients have not yet been established. Therefore, the present study aimed to assess the efficacy and tolerability of Maxvida™ in ICU patients. Design : This was a two-week, prospective, open label, investigator-initiated study conducted between June-2016 to August-2016. Methods: Participants of either sex, aged ≥18 years, hospitalized for minimum two days, requiring enteral feeding were given two feeds of Maxvida™ (30 gm diluted in 100 mL of water) along with four standard kitchen feeds at different timings. Primary endpoint was to monitor continuous GI tolerance. Secondary endpoints were change in leukocyte count, nutrient, renal, hepatic and hematological parameters. Data was analyzed descriptively using paired t-test and p value of <0.05 was considered statistically significant. Results : Fifteen (11 males, 4 females, mean age: 46.3 ± 8.9 years) participants were enrolled. None of them reported gastric intolerance. A significant improvement in hemoglobin (p=0.03), hematocrit (p=0.003), white blood cells (p=0.0001*) levels was reported while RBC, platelet, differential leukocyte count also improved gradually. Conclusion: Maxvida™ administered with hospital kitchen feed were found to be safe and gastro-intestinally well tolerated by all the participants.
Coronavirus disease 2019 (COVID-19) continues to exert mortality worldwide largely due to a lack of treatment options to prevent or ameliorate advanced respiratory dysfunction. Knowledge of the COVID-19 virus-host interaction is rapidly evolving, and significant evidence indicates that an uncontrolled immune response resulting in a cytokine storm can trigger rapid decline. Secondary to massive efforts to slow the spread of the novel coronavirus responsible for COVID-19, antiviral agents and inflammation suppression minimizing cytokine storm development most likely will be required to improve survival rates in hospitalized COVID-19 patients. Vagus nerve stimulation (VNS) is safe and several lines of evidence suggest it is potent enough to regulate the high levels of pro-inflammatory cytokines seen in hospitalized COVID-19 patients. Based on its success in mitigating both chronic and acute inflammation without triggering harmful immunosuppression, transcutaneous auricular vagus nerve stimulation (taVNS) presents a novel potential treatment for COVID-19. A clinical trial is being designed to determine whether taVNS can significantly improve the mortality rate among hospitalized COVID-19 patients by preventing a fatal immune response. *Correspondence to: Patrick Nemechek, Nemechek Autonomic Medicine, 4252 N Verrado Way Suite 200, Buckeye, AZ 85396 Buckeye, USA, E-mail: dr@ autonomicmed.com Received: May 15, 2020; Accepted: June 05, 2020; Published: June 10, 2020 Introduction Coronavirus disease 2019 (COVID-19) has a high mortality rate among hospitalized patients and presents an unprecedented challenge for healthcare systems. In China, where the virus originated, 4,637 COVID-19 deaths have been reported while deaths in the U.S., Italy, and the U.K. have soared to 64,943, 28,236, and 27,583, respectively, as of May 1, 2020 [1]. Many hospitalized COVID-19 patients develop acute respiratory distress syndrome (ARDS) [2] and have high inflammatory markers suggestive of a cytokine storm (Figure 1). Serum cytokines measured in some of the first Chinese COVID-19 patients to be evaluated were significantly higher in severe compared to moderate cases (Figure 2), specifically the pro-inflammatory cytokines interleukin 2R (IL-2R), IL6, IL-10, and tumor necrosis factor α (TNF-α) [3]. The cytokine storm typically leads to immune failure, organ failure, secondary infection, and ultimately death [3,4]. The factors precipitating cytokine storm in a subset of patients remain unclear. COVID-19 patients receive supportive measures such as fluids, antibiotics for secondary infections, mechanical ventilation, and pressure support, but in the presence of cytokine storm, outcomes are poor despite such measures [5] (Figure 3). Risk factors for severe COVID-19 include chronic conditions associated with excessive inflammation such as respiratory and cardiovascular diseases, cancer, hypertension, diabetes, obesity, smoking, and old age [6] (Figure 4). Regardless of COVID-19 infection, older individuals generally experience inflammaging, which is the presence of chronic, low-grade inflammation [7]. With a higher baseline of pre-existing inflammation compared to younger patients, patients over age 60 are more likely to develop an uncontrolled immune response and the dangerous cytokine storm if they contract the virus. The relationship between COVID-19 severity and chronic inflammatory conditions suggests that a preexisting, heavy inflammatory load is the common thread among those most at risk (Figure 5). Dual therapy aimed at reducing the infectious process and improving cytokine regulation is needed to improve COVID-19 outcomes. In addition to supportive care, antiviral medication should be used to block viral replication in conjunction with anti-inflammatory therapy to improve immune regulation. Steroids, anti-inflammatory and anti-cytokine drugs such as tocilizumab, and anti-cytokine signaling drugs such as janus kinase inhibitors are proposed to help regulate inflammation and viral entry in COVID-19 [8]. These drugs are costly, however, and often result in increased risk of secondary infection due to general suppression of the immune system [9,10]. The poor regulation of immune response observed in cytokine storm COVID-19 patients may result from the inability of the vagus nerve to properly regulate the immune system. The vagus nerve is involved in an inflammation controlling reflex triggered when the afferent vagus nerve senses inflammatory products through peripheral receptors (Figure 6). Vagus nerve activity is relayed through the central nervous system to the efferent vagus nerve. This pathway involves the splenic nerve, which when activated releases norepinephrine and results in suppression of proinflammatory cytokine production by macrophages and alleviates inflammation in many pathological settings (e.g., endotoxemia, peritonitis, or acute kidney injury) [11]. Electrical stimulation of the vagus nerve using vagus nerve stimulation (VNS) can improve the body’s natural ability to regulate the inflammatory response and may be potent enough to suppress proinflammatory cytokines and prevent death from COVID-19, especially if used early enough in the course of hospitalization [12-17]. Nemechek P (2020) Transcutaneous auricular vagus nerve stimulation holds potential to suppress COVID-19 cytokine storm Volume 4: 2-6 Int Clin Med, 2020 doi: 10.15761/ICM.1000179 Figure 1. Cytokine storm induced by COVID-19 infection in some patients results in organ damage followed by immune failure, organ failure, secondary infection, and death. Figure 2. Elevated serum cytokines observed in severe COVID-19 cases. From Chen G et al., Clinical and immunologic features in severe and moderate Coronavirus Disease [3]. Figure 3. Typical progression of clinical presentation following COVID-19 infection. Following the onset of cytokine storm, patients often experience ARDS and have a high mortality rate despite supportive care measures. Nemechek P (2020) Transcutaneous auricular vagus nerve stimulation holds potential to suppress COVID-19 cytokine storm Volume 4: 3-6 Int Clin Med, 2020 doi: 10.15761/ICM.1000179 Figure 4. Risk factors for severe reaction to COVID-19 and elevated pro-inflammatory state include conditions that already involve high levels of inflammation. Figure 5. Pre-existing inflammatory conditions are characterized by a baseline elevated inflammatory load made even larger upon COVID-19 infection. Figure 6. The vagus inflammatory reflex [11]. Nemechek P (2020) Transcutaneous auricular vagus nerve stimulation holds potential to suppress COVID-19 cytokine storm Volume 4: 4-6 Int Clin Med, 2020 doi: 10.15761/ICM.1000179 In rat models of sepsis, VNS attenuates the release of proinflammatory cytokines, prevents hypotension, modulates coagulation, and prevents fibrinolysis activation, decreasing organ dysfunction and improving survival [18]. Human studies also demonstrate that VNS suppresses the production of proinflammatory cytokines and improves clinical symptoms in rheumatoid arthritis, intractable epilepsy, atrial fibrillation, and Crohn’s Disease [19-22]. This suggests that VNS may be effective in treating disorders characterized by cytokine dysregulation and that it has the potential to prevent hospitalized patients with COVID-19 from progressing to respiratory failure and death. The vagus nerve can be electrically stimulated with an implantable device placed on the vagus nerve or by stimulating the auricular branch of the vagus nerve with a conductive surface in contact with the concha of the ear (transcutaneous auricular VNS; taVNS). Vagus nerve stimulation via afferent vagus nerve fibers in the ear activates the inflammatory reflex and regulates the immune response [23]. taVNS significantly reduces systemic pro-inflammatory cytokines [15] and improves clinical outcome in a variety of medical conditions involving uncontrolled immune activation in instances of chronic inflammation, such as rheumatoid arthritis, and acute inflammation, such as sepsis [13,24]. Vagus nerve stimulation is safe and effective in regulating inflammatory cytokines without suppressing the immune system [25]. Indeed, an implantable VNS device successfully reduced serum cytokines TNF, IL-1β, and IL-6 in epilepsy patients [19] suggesting that VNS can therapeutically assist the vagus nerve in modulating cytokine production (Figure 7). taVNS is applied on the outer ear using a simple device that requires minimal training and is inexpensive, readily manufactured, and reusable, making it an ideal therapeutic option in a global pandemic affecting many resource-limited countries. Based on its success in modulating immune reactions, taVNS may prevent and even counteract the cytokine storm observed among some hospitalized COVID-19 patients (Figure 8). A dual approach to COVID-19 leveraging the blockage of viral replication along with taVNS may help to prevent ARDS, the deadly cytokine storm and system failure, and significantly improve survival. Indeed, a recent case report described clinical improvement in the form of improved respiratory capacity in two COVID-19 patients treated with non-invasive VNS [26].
