scholarly journals Neurotic disorder, headache, and stress: experience of managing a comorbid patient and the role of magnesium drugs

2021 ◽  
pp. 94-100
Author(s):  
V. A. Golovacheva ◽  
G. R. Tabeeva
Keyword(s):  
Magnesium Deficiency ◽  
Clinical Manifestations ◽  
Cardiac Activity ◽  
The Body ◽  
Reproductive Age ◽  
Primary Headaches ◽  
Neurotic Disorder ◽  
Adequate Treatment ◽  
Neurotic Disorders

In the practice of neurologists and therapists, patients with complaints of headache, increased fatigue, and irritability are common. The most frequent causes of headaches in ambulatory patients are primary headaches (migraine and tension headaches). Lack of sleep, stress, symptoms of anxiety and depression, and abuse of analgesic drugs are the most common factors that contribute to the frequency of headaches. Magnesium deficiency is another factor, the role of which has been discussed in the frequency of primary headaches, in the development of neurotic disorders and depression. Clinical manifestations of magnesium deficiency itself usually include such nonspecific symptoms as fatigue, anxiety, irritability, numbness in the extremities, leg cramps, sleep disorders, etc.Magnesium deficiency is widespread among the population of developed countries, especially among women of reproductive age, often occurs during pregnancy, while taking oral contraceptives. Magnesium is involved in the regulation of the nervous system, neuromuscular transmission, cardiac activity, regulation of vascular tone, blood clotting and bone tissue metabolism. Magnesium deficiency is associated with diseases such as coronary heart disease, hypertension, type 2 diabetes, Alzheimer’s disease, migraine, osteoporosis, depression, neurotic disorders (panic disorder, generalized anxiety, various phobias), and fibromyalgia syndrome. Stress can lead to a decrease in magnesium levels in the body, and magnesium deficiency, in turn, reduces tolerance to stressful situations. Timely diagnosis and adequate treatment of magnesium deficiency and associated conditions represent important clinical challenges.The clinical case of a patient with neurotic disorder, headache and magnesium deficiency is presented, and the effectiveness of an interdisciplinary approach including an educational talk, adequate therapy for headache management, magnesium drug therapy and psychological methods is demonstrated. The role of magnesium deficiency in the development of various neurologic diseases is reviewed. The most effective magnesium compounds for therapy are discussed. Principles of diagnosis and treatment of patients with magnesium deficiency are presented.

scholarly journals Millimeter (MM) wave and microwave frequency radiation produce deeply penetrating effects: the biology and the physics

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Martin L. Pall
Keyword(s):  
Magnetic Fields ◽  
Electric Fields ◽  
Cardiac Activity ◽  
Maximum Level ◽  
Voltage Sensor ◽  
The Body ◽  
Time Varying ◽  
The Brain ◽  
Mm Waves

Abstract Millimeter wave (MM-wave) electromagnetic fields (EMFs) are predicted to not produce penetrating effects in the body. The electric but not magnetic part of MM-EMFs are almost completely absorbed within the outer 1 mm of the body. Rodents are reported to have penetrating MM-wave impacts on the brain, the myocardium, liver, kidney and bone marrow. MM-waves produce electromagnetic sensitivity-like changes in rodent, frog and skate tissues. In humans, MM-waves have penetrating effects including impacts on the brain, producing EEG changes and other neurological/neuropsychiatric changes, increases in apparent electromagnetic hypersensitivity and produce changes on ulcers and cardiac activity. This review focuses on several issues required to understand penetrating effects of MM-waves and microwaves: 1. Electronically generated EMFs are coherent, producing much higher electrical and magnetic forces then do natural incoherent EMFs. 2. The fixed relationship between electrical and magnetic fields found in EMFs in a vacuum or highly permeable medium such as air, predicted by Maxwell’s equations, breaks down in other materials. Specifically, MM-wave electrical fields are almost completely absorbed in the outer 1 mm of the body due to the high dielectric constant of biological aqueous phases. However, the magnetic fields are very highly penetrating. 3. Time-varying magnetic fields have central roles in producing highly penetrating effects. The primary mechanism of EMF action is voltage-gated calcium channel (VGCC) activation with the EMFs acting via their forces on the voltage sensor, rather than by depolarization of the plasma membrane. Two distinct mechanisms, an indirect and a direct mechanism, are consistent with and predicted by the physics, to explain penetrating MM-wave VGCC activation via the voltage sensor. Time-varying coherent magnetic fields, as predicted by the Maxwell–Faraday version of Faraday’s law of induction, can put forces on ions dissolved in aqueous phases deep within the body, regenerating coherent electric fields which activate the VGCC voltage sensor. In addition, time-varying magnetic fields can directly put forces on the 20 charges in the VGCC voltage sensor. There are three very important findings here which are rarely recognized in the EMF scientific literature: coherence of electronically generated EMFs; the key role of time-varying magnetic fields in generating highly penetrating effects; the key role of both modulating and pure EMF pulses in greatly increasing very short term high level time-variation of magnetic and electric fields. It is probable that genuine safety guidelines must keep nanosecond timescale-variation of coherent electric and magnetic fields below some maximum level in order to produce genuine safety. These findings have important implications with regard to 5G radiation.

THE ROLE OF MAGNESIUM DEFICIENCY IN THE PATHOGENESIS OF THE FORMATION OF ARTERIAL HYPERTENSION IN WORKERS OF LOCOMOTIVE CREWS. CORRECTION METHODS

2021 ◽  
Author(s):  
V.G. Yarkova ◽  
◽  
V.A. Zhmurov ◽  
E.B. Klester ◽  
Keyword(s):  
Lipid Metabolism ◽  
Arterial Hypertension ◽  
Cardiovascular System ◽  
Magnesium Deficiency ◽  
Clinical Manifestations ◽  
Occupational Disability ◽  
Functional Studies ◽  
Complex Preparation ◽  
Male Patients

Abstract: Purpose of the study: To assess the effects of magnesium deficiency on the indices of lipid metabolism in patients with an arterial hypertension locomotive crews. Purpose of the work: To assess the effect of magnesium deficiency on the pathogenesis of the formation of arterial hypertension in workers of locomotive crews. Correction methods. Materials and methods: This work presents an analysis of the results of clinical observation, special biochemical and functional studies of 136 male patients with arterial hypertension, workers of locomotive crews. Results: In workers of locomotive crews patients with hypertension, increased individual cardiovascular risk according to the SCORE scale, remodeling of the cardiovascular system, as well as the risk of developing occupational disability are interrelated with signs of magnesium deficiency. Conclusion: The inclusion of a complex preparation of magnesium and vitamin B6 in the therapy of arterial hypertension in workers of locomotive crews has a significant effect on the clinical manifestations of chronic stress, magnesium deficiency, improves the dynamics of lipid metabolism, the structural and functional state of the cardiovascular system, and professionally important qualities.

scholarly journals Physiology of magnesium metabolism and the use of magnesium in intensive care (literature review with the results of own observations, part 1)

2021 ◽  
Vol 17 (5) ◽  
pp. 56-67
Author(s):  
S.V. Kursov ◽  
V.V. Nikonov ◽  
O.V. Biletskyi ◽  
O.I. Fedets ◽  
V.O. Homenko
Keyword(s):  
Intensive Care ◽  
Human Body ◽  
Clinical Medicine ◽  
Magnesium Deficiency ◽  
Biological Fluids ◽  
The Body ◽  
Large Size ◽  
Water Compartment ◽  
Water Space

The first part of the review presents data on the content of magnesium in organs and tissues of the human body, the role of magnesium in the implementation of multiple functions, and the peculiarities of its intake and excretion from the body. A significant part of the review is devoted to methods for determining the concentration of magnesium in biological fluids of the human body. The advantages, disadvantages and limitations of various methods are presented. The most common methods for studying the concentration of magnesium in biological fluids of the body, which are used in clinical medicine all over the world, are photometric methods with dyes. The role of the fraction of ionized magnesium in the body, the content of which is determined electrochemically, is still uncertain. Cellular magnesium studies are extremely complex and time-consuming. Cells of different organs and tissues normally contain very different amounts of magnesium. It is not possible to judge about the presence of magnesium deficiency in the body by its concentration in plasma or serum. To detect a decrease in the tissue content of magnesium, tests with magnesium load and the subsequent observation of the rate of its excretion from the body are used. The causes for the development of hypomagnesemia are extremely numerous. The main of them are: any severe stress, restriction of magnesium intake into the body, an increase in its losses through the gastrointestinal tract and the kidneys in various pathological conditions. The formation of hypomagnesemia is facilitated by therapy with numerous medications, which are very widely used in clinical practice, and especially in the intensive care. Studies on the distribution of magnesium in the body after its intravenous administration have shown that, despite the large size of hydrated magnesium ions, they can not only paradoxically quickly spread in the extracellular water space, but most likely are also able to quickly penetrate through cell membranes, spreading in the intracellular water compartment.

scholarly journals GÉNERO E ORIENTAÇÃO EDUCACIONAL NA INTERACÇÃO MÃES-FILHOS COM PERTURBAÇÕES NEURÓTICAS NO PERÍODO ETÁRIO 7 – 10 ANOS

2019 ◽  
Vol 26 (1) ◽  
pp. 225
Author(s):  
Fernando Oliveira Pereira
Keyword(s):  
Female Gender ◽  
The Body ◽  
Healthy Children ◽  
Age Group ◽  
Neurotic Disorder ◽  
Research Instrument ◽  
Neurotic Disorders ◽  
Parent Attitude ◽  
Attitude Research ◽  
Educational Orientations

O género é a identificação sociocultural da pessoa, cuja especificidade diferencial é pré-definida pela pertença corporal a determinado sexo.Objectivo da investigação: estabelecer especificidades diferenciais nos estilos e orientações educacionais das mães no processo de interacção com as crianças padecentes de perturbações neuróticas do escalão etário 7 – 10 anos em conformidade com o seu género sexual de pertença. Participantes: 99 mães de crianças que sofrem de perturbações neuróticas (66 do sexo masculino e 33 do sexo feminino) e 60 mães de crianças saudáveis (30 do sexo masculino e 30 do sexo feminino).Instrumentos metodológicos: Questionário PARI (Parent Attitude Research Instrument) e entrevista clínico-psicológica. Conclusões: Existem diferenças específicas nos estilos e orientações educacionais que as mães adoptam com os filhos (as) do escalão etário 7 – 10 anos, padecentes de perturbação neurótica, conforme pertencem ao género masculino ou feminino.As diferenças educacionais são em maior quantidade nas mães das crianças do género feminino do que nas do género masculino, quando comparadas com as mães de crianças saudáveis. Os desvios nos estilos e orientações educacionais implementados pelas mães na interacção com as crianças que sofrem de perturbação neurótica são por excesso no género masculino e por defeito no género feminino.GENDER AND EDUCATIONAL ORIENTATION IN THE INTERACTION OF MOTHER-CHILDREN WITH NEUROTIC DISTURBATIONS IN THE AGE PERIOD 7 - 10 YEARS AbstractGender is a socio-cultural identity of the person whose differential specificity is pre-defined by the body belongs to a particular sex.Research Objective: To establish differential characteristics in styles and educational orientations of mothers in the interaction process with children suffering from neurotic disorders of the age group 7-10 years in accordance with their sexual gender belonging. Participants: 99 mothers of children who suffer from neurotic disorders (66 male and 33 female) and 60 mothers of healthy children (30 male and 30 female). Methodological tools: PARI Questionnaire Parent Attitude Research Instrument and clinical and psychological interview. Conclusions: There are specific differences in styles and educational orientations that mothers adopt with the children of the age group 7 - 10 years, who suffer from neurotic disturbance as belonging to the male or female gender. Educational differences are in greater quantities in mothers of children female gender than in male gender, when compared with mothers of healthy children. Deviations in styles and educational orientations implemented by mothers in interaction with children suffering from neurotic disorder are in excess in males and in females by default.Keywords: gender; age; educational orientation; neurotic disorder.GÉNERO Y ORIENTACIÓN EDUCACIONAL EN LA INTERACCIÓN MADRE-HIJOS CON PERTURBACIONES NEURÓTICAS EN EL PERÍODO ETARIO 7 - 10 AÑOSResumen El género es la identificación sociocultural de la persona, cuya especificidad diferencial es pre-definida por la pertenencia corporal a determinado sexo. Objetivo de la investigación: establecer especificidades diferenciales en los estilos y orientaciones educativas de las madres en el proceso de interacción con los niños que padecen de perturbaciones neuróticas del grupo de edad de 7 a 10 años conforme a su género sexual de pertenencia. Participantes: 99 madres de niños que sufren de trastornos neuróticos (66 varones y 33 mujeres) y 60 madres de niños sanos (30 varones y 30 mujeres). Instrumentos metodológicos: Cuestionario PARI (Parent Attitude Research Instrument) y entrevista clínico-psicológica. Conclusiones: Existen diferencias específicas en los estilos y orientaciones educativas que las madres adoptan con los hijos del grupo de edad de 7 a 10 años, que padecen de perturbación neurótica, según pertenecen al género masculino o femenino. Las diferencias educativas son en mayor cantidad en las madres de los niños del género femenino que en las del género masculino, en comparación con las madres de niños sanos. Las desviaciones en los estilos y orientaciones educativas implementadas por las madres en la interacción con los niños que sufren de perturbación neurótica son por exceso en el género masculino y por defecto en el género femenino. Palabras clave: género; etariedade; orientación educativa; perturbación neurótica.

scholarly journals NEUROPHYSIOLOGICAL FEATURES OF THE NOCICEPTIVE TRIGEMINAL PATHWAY DURING DIFFERENT PHASES OF EPISODIC MIGRAINE

2019 ◽  
Vol 19 (1) ◽  
pp. 31-38
Author(s):  
O. Nikiforova ◽  
M. Delva
Keyword(s):  
High Current Density ◽  
Clinical Manifestations ◽  
Blink Reflex ◽  
Episodic Migraine ◽  
Physiological Data ◽  
Primary Headaches ◽  
High Current ◽  
Prodromal Phase ◽  
Stimulation Of

Migraine is one of the most common primary headaches, caused by functional abnormalities of information processing, which can be investigated by neurophysiological means during the various phases of the migraine cycle. The aim of the work was to study neurophysiological changes by means of nociception-specific blink reflex characteristics of trigeminocervical complex and to compare neuro-physiological data with clinical manifestations during various phases of episodic migraine. Methods. A 24-year old female patient with episodic migraine without aura underwent daily nociceptive stimulation of the trigeminal nerve for 30 days. Clinical data were collected directly from the patient using structured questionnaires. Neurophysiological changes were assessed using electromyography study of trigeminocervical blink reflex that was caused by stimulation of the supraorbital nerve with high current density electrode. Results. Within one month, the patient had two migraine attacks, preceded by the prodromal phase, and at the end of both migraine attacks, postdrome symptoms were present. We observed cyclical changes in the characteristics of component R2 of the nociception-specific blink reflex that coincided with clinical manifestations in different phases of the migraine cycle. Conclusions. 1. Electrophysiological excitability of trigeminocervical complex nociceptors differs significantly during different phases of the migraine cycle. 2. The habituation of component R2 is observed in the period between attacks can be considered as a specific phenomenon that probably is the background for migraine attack occurrence. 3. The highest excitability and facilitation of the trigeminocervical complex (increased amplitude and decreased latency of component R2) were observed during ictal phase that is additional evidence of the key role of the brainstem in migraine pathophysiology.

scholarly journals MORPHOLOGICAL FEATURES OF UTERINE POLYPS IN FEMALES OF REPRODUCTIVE AGE

2019 ◽  
pp. 47-52 ◽  
Author(s):  
N. Ye. Gorban ◽  
T. D. Zadorozhna ◽  
I. B. Vovk ◽  
I. V. Zhulkevych
Keyword(s):  
Inflammatory Process ◽  
Morphological Features ◽  
The Body ◽  
Reproductive Age ◽  
Inflammatory Factor ◽  
Medical Sciences ◽  
Women Of Reproductive Age ◽  
Endometrial Polyps ◽  
Chronic Endometritis

According to modern views based on evidence-based medicine, the concept of "poly-endometrium" is defined as a benign, exophytic nodophilic formation of the uterine mucus that consists of glands and stroma, predominantly fibrous, containing a "tangle" of thick-walled blood vessels. The aim of the study – to learn the morphological features of tissues of polyps of the body of the uterus and endometrium with the establishment of the role of inflammatory factor in the pathogenesis of hyperproliferative changes in women of reproductive age. Materials and Methods. The article presents the results of a survey of 62 patients of reproductive age with polyps in the body of the uterus. The presence of the glandular component in 79.03 % of cases, fibrotic polyps – 12.9 %, and micro-polyps – 8.06 % were determined, respectively. The combination of polyps with non-atypical endometrial hyperplasia was detected in 80 % of patients with micro-polyposis, in 63.6 % of women – with glandular-cystic polyps of the uterine body, in 44.4 % of the examined – with glandular-fibrous endometrial polyps and in 37.5 % of patients – with fibrous polyps. Immunohistochemically, CD138 expression was detected both in the tissues of the polyps of the uterus and adjacent endometrial tissues in 43.5 % of cases, which became a marker of the chronic endometritis in the part of the surveyed, which formed the basis of the pathogenetic approaches in the treatment of such a pathology. For processing data standard procedures using Microsoft Excel were used. The research was conducted in the Laboratory of Pathomorphology of the Department of O. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the National Academy of Medical Sciences of Ukraine, head of the department – Corresponding Member of the National Academy of Medical Sciences of Ukraine, Professor T. Zadorozhna. Results and Discussion. In clinical analysis of complaints of polyps of the body of the uterus, clinical manifestations in the form of menstrual cord disturbance were 13 (20.97 %) patients, in 11 (17.74 %) patients there were no complaints about the desired pregnancy, at the same time as 38 (61.29 %) women were asked to carry out a preventive examination, which does not contradict the results of other researchers. During the morphological study, we established the following features of the polyps of the body of the uterus in women of reproductive age: the most frequently tested polyps of the body of the uterus, which had the glandular component – in 49 (79.03 %) cases, of which the glandular-cystic structure was found in 22 (35.48 %) of patients, the glandular-fibrous structure was in 27 (43.55 %) patients, approximately the same values ​​were found in fibrous polyps of the body of the uterus – 8 (12.90 %) of women and micropolymers of endometrium – in 5 (8.06 %) cases respectively. We found that in all groups of patients with polyps in the body of the uterus, there were signs of non-atypical hyperplasia of the endometrium. It should be noted that, according to literature, endometrial polyps larger than 15 mm were associated with hyperplasia. The above data is an important indication that the unidirectional determination of the positive expression of the CD138 inflammatory marker, both in the tissue of the polyp of the uterus and in the endometrial tissue, indicates the unity of the inflammatory factor in the pathogenesis of hyperproliferative processes and proves the significant role of the inflammatory process in the development of its pathological conditions and justifies the necessity take into account this fact in approaches to the tactics of patient management. Conclusions. The results of the conducted morphological and immunohistochemical research indicate that the basis of the formation of polyps of the body of the uterus is the inflammatory process, which is confirmed morphologically with the presence of chronic endometritis and a positive reaction to CD138. The study of pathogenetic mechanisms for the formation of endometrial pathology is a key factor in the development of methods for correction of these pathological processes, which thus allows to increase the efficiency of treatment and preserve reproductive health.

scholarly journals The Role of Magnesium in the Development of Cardiovascular Diseases and the Possibility of their Prevention and Correction with Magnesium Preparations (Part 1)

2019 ◽  
Vol 15 (5) ◽  
pp. 725-735 ◽  
Author(s):  
A. S. Safaryan ◽  
V. S. Sargsyan ◽  
T. V. Kamyshova ◽  
N. M. Akhmedzhanov ◽  
D. V. Nebieridze ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Magnesium Deficiency ◽  
Magnesium Level ◽  
The Body ◽  
Level Control ◽  
Good Medicine ◽  
Magnesium Salts ◽  
Natural Way

The article is devoted to the influence of magnesium on the homeostasis of the body and, in particular, on the cardiovascular system. It describes the importance of the presence and effects of magnesium on various key processes and functions occurring in the body. The reasons for the lack of magnesium and ways to replenish it both in the natural way (eating, certain foods) and magnesium preparations are considered. The article provides examples of large randomized studies that prove the importance of the influence of normal magnesium levels on human health in general and on the state of the cardiovascular system. These studies show how magnesium deficiency increases the risk of cardiovascular diseases and how it can be reduced. It is also shown which trace elements and vitamins are closely related to magnesium metabolism, and how they (in particular, potassium and vitamin B6) improve and facilitate the normalization of magnesium levels. It is noted how comorbidity decreases with the normalization of magnesium level – the higher the magnesium level in the blood plasma (closer to the upper limit and more), the less comorbidity and longer life expectancy. Magnesium is an absolutely essential ion and a good medicine. Magnesium deficiency and hypomagnesemia are quite common, difficult to diagnose (due to underestimation and rare level control) and accompany many diseases of the cardiovascular system and beyond. The widespread use of organic magnesium salts would improve the situation as a whole, due to their universal multiple effect on many processes in the body. This is an integral part of therapeutic and preventive measures in patients with already existing diseases and in people who do not have diseases, but who are at risk due to existing hypomagnesemia.

Magnesium metabolism: a case report and literature review

1991 ◽  
Vol 11 (5) ◽  
pp. 62-67 ◽  
Author(s):  
BA Friday ◽  
RA Reinhart
Keyword(s):  
Critical Care ◽  
Ventricular Tachycardia ◽  
Case Report ◽  
Care Setting ◽  
Clinical Manifestations ◽  
The Body ◽  
Mg Deficiency ◽  
Relationship Of ◽  
The Relationship

Magnesium has been shown to play an important role in the body. In the critical care setting of particular concern is the role of Mg++ in the treatment of malignant tachydysrhythmias such as ventricular tachycardia and ventricular fibrillation. Research is being conducted to determine appropriate methods of assessing Mg++ status, the relationship of altered Mg++ states to clinical manifestations, and the treatment of the abnormalities associated with Mg++ deficiency. Safe and effective forms of parenteral and oral Mg++ supplements are currently available.

scholarly journals The Role of Magnesium in the Development of Cardiovascular Diseases and the Possibility of their Prevention and Correction with Magnesium Preparations (Part 2)

2020 ◽  
Vol 16 (3) ◽  
pp. 457-464
Author(s):  
A. S. Safaryan ◽  
V. S. Sargsyan ◽  
D. V. Nebieridze
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Clinical Picture ◽  
Dosage Regimen ◽  
Magnesium Deficiency ◽  
The Body ◽  
Many Body ◽  
Daily Amount ◽  
Iatrogenic Effect

Data on the effect of magnesium on the homeostasis of the body and on the cardiovascular system, are presented in the article. These data supplement information on studies of the role of magnesium in many body processes. The influence of lifestyle on magnesium metabolism, the pathological processes that cause its deficiency, and the clinical picture of hypomagnesemia are presented in the article. The necessary daily amount of magnesium, ways to restore the magnesium deficiency, both nutritional and with the help of magnesium-containing pharmacological preparations, their form, bioavailability and dosage regimen are discussed. Diseases that occur and/or worsen with hypomagnesemia are considered. Data on the iatrogenic effect of many drugs, including cardiological, removing magnesium from the body and ways to solve this issue, are also presented. Hypomagnesemia exacerbates the course of cardiovascular disease. Elimination of magnesium deficiency can contribute a lot to the prevention of morbidity and the optimization of treatment of patients.

scholarly journals Impaired Mitochondrial Mobility in Charcot-Marie-Tooth Disease

2020 ◽  
Author(s):  
Cara Schiavon ◽  
Uri Manor
Keyword(s):  
Clinical Manifestations ◽  
Underlying Mechanism ◽  
The Body ◽  
Charcot Marie Tooth ◽  
Peripheral Neurons ◽  
Charcot Marie Tooth Disease ◽  
Challenges And Opportunities ◽  
Axonal Cmt ◽  
Trafficking Defects

Charcot-Marie-Tooth (CMT) disease is the most commonly inherited neurological disorder, defined by progressive deterioration of the peripheral nerves. Clinical manifestations of CMT mutations are typically limited to peripheral neurons, the longest cells in the body. Currently, mutations in at least 80 different genes are associated with CMT and new mutations are regularly being discovered. A large portion of the proteins mutated in axonal CMT have documented roles in mitochondrial mobility. This suggests that trafficking defects may be a common underlying mechanism in CMT. This review will focus on the potential role of altered mitochondrial mobility in the pathogenesis of axonal CMT, highlighting the challenges and opportunities to this “impaired mobility” model of the disease.

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