Materiały źródłowe

• #1 Physiology, Fever – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562334/

  Fever, or pyrexia, is the elevation of an individual’s core body temperature above a 'set-point’ regulated by the body’s thermoregulatory center in the hypothalamus. This increase in the body’s 'set-point’ temperature is often due to a physiological process brought about by infectious causes or non-infectious causes such as inflammation, malignancy, or autoimmune processes. […] These processes involve the release of immunological mediators, which trigger the thermoregulatory center of the hypothalamus, leading to an increase in the body’s core temperature. […] Milton and Wendlandt demonstrated that fever is mediated by the pyrogenic activity of prostaglandins (PGs), specifically PGE2. The synthesis of PGE2 begins with membrane phospholipids being converted to arachidonic acid (AA) by phospholipase A2 (PLA2). AA is then converted to PGH2 via cyclooxygenase (COX), after which PGH2 undergoes isomerization to PGE2 by PGE synthase. PGE2 acts via the EP3 receptor to affect specific neurons within the hypothalamus that aid in thermoregulation. […] The action of PGE2 begins when exogenous pyrogens (e.g., bacteria, viruses) stimulate endogenous pyrogens such as IL-1, IL-6, tumor necrosis factor (TNF), and interferon (IFN) to alter the hypothalamic set point via the organum vasculosum of the lamina terminalis (OVLT) and raise the core body temperature.

• #2 Fever in infants and children: Pathophysiology and management – UpToDate

  http://www.uptodate.com/contents/pathophysiology-and-management-of-fever-in-infants-and-children

  Fever is an abnormal elevation of body temperature that occurs as part of a specific biologic response that is mediated and controlled by the central nervous system. […] The pathophysiology and treatment of fever in infants and children will be reviewed here.

• #3 Peculiarities of the Pathogenesis of Fever in Childhood | ClinicSearch

  https://www.clinicsearchonline.org/article/peculiarities-of-the-pathogenesis-of-fever-in-childhood

  Fever is one of the most common symptoms of childhood illnesses and the most common chief complaint in pediatric outpatient departments, especially in emergency departments. Fever is an increase in the hypothalamic set point temperature caused by various pathogenic factors, resulting in an abnormal increase in body temperature. […] Pediatricians are especially vigilant for high fever in children (axillary temperature up to 103.5 F (39.5 C)) which is more likely to cause serious adverse outcomes such as childhood pneumonia and febrile seizures. […] The development of the febrile response is similar to the normal thermoregulatory processes that follow exposure to cold temperatures. However, in fever, the heat balance point is reset to a higher level such that normal peripheral and central body temperatures are now perceived as cold temperature signals by the thermoregulatory circuitry. […] Therefore, fever is distinct from heat stroke and hyperthermia, in which body temperature increases without a corresponding increase in the heat balance point.

• #4 Physiology, Fever – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562334/

  Fever occurs when either endogenous or exogenous pyrogens cause an elevation in the body’s thermoregulatory set-point. In hyperthermia, the set-point is unaltered, and the body temperature becomes elevated in an uncontrolled fashion due to exogenous heat exposure or endogenous heat production. […] Hyperpyrexia is the term for exceptionally high fever (greater than 41 C), which can occur in patients with severe infections. Hyperpyrexia may also be seen in patients with CNS hemorrhages and is associated with a poor outcome. Elevated brain temperature may lead to increased intracranial pressure, ischemic brain injury, exacerbation of cerebral edema, and death.

• #5 Peculiarities of the Pathogenesis of Fever in Childhood | ClinicSearch

  https://www.clinicsearchonline.org/article/peculiarities-of-the-pathogenesis-of-fever-in-childhood

  Fever is one of the most common symptoms of childhood illnesses and the most common chief complaint in pediatric outpatient departments, especially in emergency departments. Fever is an increase in the hypothalamic set point temperature caused by various pathogenic factors, resulting in an abnormal increase in body temperature. […] Pediatricians are especially vigilant for high fever in children (axillary temperature up to 103.5 F (39.5 C)) which is more likely to cause serious adverse outcomes such as childhood pneumonia and febrile seizures. […] The development of the febrile response is similar to the normal thermoregulatory processes that follow exposure to cold temperatures. However, in fever, the heat balance point is reset to a higher level such that normal peripheral and central body temperatures are now perceived as cold temperature signals by the thermoregulatory circuitry. […] Therefore, fever is distinct from heat stroke and hyperthermia, in which body temperature increases without a corresponding increase in the heat balance point.

• #6 Pathogenesis of Fever

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7122269/

  The generation of fever involves the following steps: numerous substances from outside the body, exogenous pyrogens, initiate the fever cycle. Endotoxin of Gram-negative bacteria, with their pyrogenic component lipopolysaccaride, is the most potent exogenous pyrogen. Fever is also a common finding in children without obvious evidence of infection, for example hypersensitivity reaction, autoimmune diseases and malignancy. […] Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. Endogenous pyrogens are transmitted to the hypothalamic thermoregulatory centre, specifically organum vasculosum of the lamina terminalis (OVLT), where they induce synthesis of prostaglandins, of which PGE2 is the most important. These raise the thermostatic set point to initiate the febrile response.

• #7 Pathogenesis of Fever | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-540-78598-9_3

  Although infection is the most common cause of fever, fever is also a common finding in hypersensitivity reaction, autoimmune diseases, and malignancy. […] Febrile response is mediated by endogenous pyrogens (cytokines) in response to invading exogenous pyrogens, primarily microorganisms or their direct products (toxins). […] These endogenous pyrogens act on thermosensitive neurons in the hypothalamus, which ultimately upgrade the set point via prostaglandins. […] The body reacts by increasing the heat production and decreasing the heat loss until the body temperature reaches this elevated set point. […] Fever, in contrast to hyperthermia, will not climb up relentlessly because of an effective central control of the hypothalamic center. […] Cytokines play a pivotal role in the immune response by activation of the B cells and T lymphocytes. The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favor of the protective role of fever.

• #8 Pathogenesis of Fever

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7122269/

  The generation of fever involves the following steps: numerous substances from outside the body, exogenous pyrogens, initiate the fever cycle. Endotoxin of Gram-negative bacteria, with their pyrogenic component lipopolysaccaride, is the most potent exogenous pyrogen. Fever is also a common finding in children without obvious evidence of infection, for example hypersensitivity reaction, autoimmune diseases and malignancy. […] Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. Endogenous pyrogens are transmitted to the hypothalamic thermoregulatory centre, specifically organum vasculosum of the lamina terminalis (OVLT), where they induce synthesis of prostaglandins, of which PGE2 is the most important. These raise the thermostatic set point to initiate the febrile response.

• #9 Peculiarities of the Pathogenesis of Fever in Childhood | ClinicSearch

  https://www.clinicsearchonline.org/article/peculiarities-of-the-pathogenesis-of-fever-in-childhood

  The mechanisms underlying the specificity of fever patterns to certain diseases are not fully understood. For some infectious diseases, it may be related to the life cycle of the pathogen. […] The released parasites activate pyrogenic cytokines, which then lead to fever cycles every 48-72 h (tertian fever). […] Pyrogens are classified into exogenous (produced outside the host) and endogenous (produced within the host) pyrogens based on their site of production. Exogenous pyrogens are essentially parts or whole microorganisms or microbial products such as toxins. […] Endogenous pyrogens are mainly pyrogenic cytokines including interleukins: IL-6, IL-1, interferon gamma (IFN-Y) and ciliary neurotropic factor (CNTF) and tumor necrosis factor (TNF a) and others. […] Fever signals carried by exogenous and endogenous pyrogens ultimately lead to resetting of the thermoregulatory circuitry via two main pathways, namely humoral and neural. […] Activation of the neural pathway is thought to be another mechanism by which fever is rapidly initiated.

• #10 The pathophysiological basis and consequences of fever | Critical Care | Full Text

  https://ccforum.biomedcentral.com/articles/10.1186/s13054-016-1375-5

  There are numerous causes of a raised core temperature. A fever occurring in sepsis may be associated with a survival benefit. However, this is not the case for non-infective triggers. Where heat generation exceeds heat loss and the core temperature rises above that set by the hypothalamus, a combination of cellular, local, organ-specific, and systemic effects occurs and puts the individual at risk of both short-term and long-term dysfunction which, if severe or sustained, may lead to death. […] Pyrogenic fever is a common response to sepsis in critically ill patients, and the generation of fever occurs through several mechanisms. The interaction of exogenous pyrogens (e.g. micro-organisms) or endogenous pyrogens (e.g. interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-) with the organum vasculosum of the lamina terminalis (OVLT) leads to the production of fever. Exogenous pyrogens may stimulate cytokine production, or may act directly on the OVLT.

• #11 Pathogenesis of Fever

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7122269/

  The generation of fever involves the following steps: numerous substances from outside the body, exogenous pyrogens, initiate the fever cycle. Endotoxin of Gram-negative bacteria, with their pyrogenic component lipopolysaccaride, is the most potent exogenous pyrogen. Fever is also a common finding in children without obvious evidence of infection, for example hypersensitivity reaction, autoimmune diseases and malignancy. […] Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. Endogenous pyrogens are transmitted to the hypothalamic thermoregulatory centre, specifically organum vasculosum of the lamina terminalis (OVLT), where they induce synthesis of prostaglandins, of which PGE2 is the most important. These raise the thermostatic set point to initiate the febrile response.

• #12 Pathogenesis of Fever | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-540-78598-9_3

  Although infection is the most common cause of fever, fever is also a common finding in hypersensitivity reaction, autoimmune diseases, and malignancy. […] Febrile response is mediated by endogenous pyrogens (cytokines) in response to invading exogenous pyrogens, primarily microorganisms or their direct products (toxins). […] These endogenous pyrogens act on thermosensitive neurons in the hypothalamus, which ultimately upgrade the set point via prostaglandins. […] The body reacts by increasing the heat production and decreasing the heat loss until the body temperature reaches this elevated set point. […] Fever, in contrast to hyperthermia, will not climb up relentlessly because of an effective central control of the hypothalamic center. […] Cytokines play a pivotal role in the immune response by activation of the B cells and T lymphocytes. The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favor of the protective role of fever.

• #13 Pathogenesis of Fever

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7122269/

  The generation of fever involves the following steps: numerous substances from outside the body, exogenous pyrogens, initiate the fever cycle. Endotoxin of Gram-negative bacteria, with their pyrogenic component lipopolysaccaride, is the most potent exogenous pyrogen. Fever is also a common finding in children without obvious evidence of infection, for example hypersensitivity reaction, autoimmune diseases and malignancy. […] Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. Endogenous pyrogens are transmitted to the hypothalamic thermoregulatory centre, specifically organum vasculosum of the lamina terminalis (OVLT), where they induce synthesis of prostaglandins, of which PGE2 is the most important. These raise the thermostatic set point to initiate the febrile response.

• #14 Peculiarities of the Pathogenesis of Fever in Childhood | ClinicSearch

  https://www.clinicsearchonline.org/article/peculiarities-of-the-pathogenesis-of-fever-in-childhood

  The mechanisms underlying the specificity of fever patterns to certain diseases are not fully understood. For some infectious diseases, it may be related to the life cycle of the pathogen. […] The released parasites activate pyrogenic cytokines, which then lead to fever cycles every 48-72 h (tertian fever). […] Pyrogens are classified into exogenous (produced outside the host) and endogenous (produced within the host) pyrogens based on their site of production. Exogenous pyrogens are essentially parts or whole microorganisms or microbial products such as toxins. […] Endogenous pyrogens are mainly pyrogenic cytokines including interleukins: IL-6, IL-1, interferon gamma (IFN-Y) and ciliary neurotropic factor (CNTF) and tumor necrosis factor (TNF a) and others. […] Fever signals carried by exogenous and endogenous pyrogens ultimately lead to resetting of the thermoregulatory circuitry via two main pathways, namely humoral and neural. […] Activation of the neural pathway is thought to be another mechanism by which fever is rapidly initiated.

• #15 The pathophysiological basis and consequences of fever | Critical Care | Full Text

  https://ccforum.biomedcentral.com/articles/10.1186/s13054-016-1375-5

  There are numerous causes of a raised core temperature. A fever occurring in sepsis may be associated with a survival benefit. However, this is not the case for non-infective triggers. Where heat generation exceeds heat loss and the core temperature rises above that set by the hypothalamus, a combination of cellular, local, organ-specific, and systemic effects occurs and puts the individual at risk of both short-term and long-term dysfunction which, if severe or sustained, may lead to death. […] Pyrogenic fever is a common response to sepsis in critically ill patients, and the generation of fever occurs through several mechanisms. The interaction of exogenous pyrogens (e.g. micro-organisms) or endogenous pyrogens (e.g. interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-) with the organum vasculosum of the lamina terminalis (OVLT) leads to the production of fever. Exogenous pyrogens may stimulate cytokine production, or may act directly on the OVLT.

• #16 Peculiarities of the Pathogenesis of Fever in Childhood | ClinicSearch

  https://www.clinicsearchonline.org/article/peculiarities-of-the-pathogenesis-of-fever-in-childhood

  The mechanisms underlying the specificity of fever patterns to certain diseases are not fully understood. For some infectious diseases, it may be related to the life cycle of the pathogen. […] The released parasites activate pyrogenic cytokines, which then lead to fever cycles every 48-72 h (tertian fever). […] Pyrogens are classified into exogenous (produced outside the host) and endogenous (produced within the host) pyrogens based on their site of production. Exogenous pyrogens are essentially parts or whole microorganisms or microbial products such as toxins. […] Endogenous pyrogens are mainly pyrogenic cytokines including interleukins: IL-6, IL-1, interferon gamma (IFN-Y) and ciliary neurotropic factor (CNTF) and tumor necrosis factor (TNF a) and others. […] Fever signals carried by exogenous and endogenous pyrogens ultimately lead to resetting of the thermoregulatory circuitry via two main pathways, namely humoral and neural. […] Activation of the neural pathway is thought to be another mechanism by which fever is rapidly initiated.

• #17 The pathophysiological basis and consequences of fever | Critical Care | Full Text

  https://ccforum.biomedcentral.com/articles/10.1186/s13054-016-1375-5

  There are numerous causes of a raised core temperature. A fever occurring in sepsis may be associated with a survival benefit. However, this is not the case for non-infective triggers. Where heat generation exceeds heat loss and the core temperature rises above that set by the hypothalamus, a combination of cellular, local, organ-specific, and systemic effects occurs and puts the individual at risk of both short-term and long-term dysfunction which, if severe or sustained, may lead to death. […] Pyrogenic fever is a common response to sepsis in critically ill patients, and the generation of fever occurs through several mechanisms. The interaction of exogenous pyrogens (e.g. micro-organisms) or endogenous pyrogens (e.g. interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-) with the organum vasculosum of the lamina terminalis (OVLT) leads to the production of fever. Exogenous pyrogens may stimulate cytokine production, or may act directly on the OVLT.

• #18 Physiology, Fever – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562334/

  Fever, or pyrexia, is the elevation of an individual’s core body temperature above a 'set-point’ regulated by the body’s thermoregulatory center in the hypothalamus. This increase in the body’s 'set-point’ temperature is often due to a physiological process brought about by infectious causes or non-infectious causes such as inflammation, malignancy, or autoimmune processes. […] These processes involve the release of immunological mediators, which trigger the thermoregulatory center of the hypothalamus, leading to an increase in the body’s core temperature. […] Milton and Wendlandt demonstrated that fever is mediated by the pyrogenic activity of prostaglandins (PGs), specifically PGE2. The synthesis of PGE2 begins with membrane phospholipids being converted to arachidonic acid (AA) by phospholipase A2 (PLA2). AA is then converted to PGH2 via cyclooxygenase (COX), after which PGH2 undergoes isomerization to PGE2 by PGE synthase. PGE2 acts via the EP3 receptor to affect specific neurons within the hypothalamus that aid in thermoregulation. […] The action of PGE2 begins when exogenous pyrogens (e.g., bacteria, viruses) stimulate endogenous pyrogens such as IL-1, IL-6, tumor necrosis factor (TNF), and interferon (IFN) to alter the hypothalamic set point via the organum vasculosum of the lamina terminalis (OVLT) and raise the core body temperature.

• #19 Peculiarities of the Pathogenesis of Fever in Childhood | ClinicSearch

  https://www.clinicsearchonline.org/article/peculiarities-of-the-pathogenesis-of-fever-in-childhood

  The mechanisms underlying the specificity of fever patterns to certain diseases are not fully understood. For some infectious diseases, it may be related to the life cycle of the pathogen. […] The released parasites activate pyrogenic cytokines, which then lead to fever cycles every 48-72 h (tertian fever). […] Pyrogens are classified into exogenous (produced outside the host) and endogenous (produced within the host) pyrogens based on their site of production. Exogenous pyrogens are essentially parts or whole microorganisms or microbial products such as toxins. […] Endogenous pyrogens are mainly pyrogenic cytokines including interleukins: IL-6, IL-1, interferon gamma (IFN-Y) and ciliary neurotropic factor (CNTF) and tumor necrosis factor (TNF a) and others. […] Fever signals carried by exogenous and endogenous pyrogens ultimately lead to resetting of the thermoregulatory circuitry via two main pathways, namely humoral and neural. […] Activation of the neural pathway is thought to be another mechanism by which fever is rapidly initiated.

• #20 Pathogenesis of Fever

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7122269/

  The generation of fever involves the following steps: numerous substances from outside the body, exogenous pyrogens, initiate the fever cycle. Endotoxin of Gram-negative bacteria, with their pyrogenic component lipopolysaccaride, is the most potent exogenous pyrogen. Fever is also a common finding in children without obvious evidence of infection, for example hypersensitivity reaction, autoimmune diseases and malignancy. […] Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. Endogenous pyrogens are transmitted to the hypothalamic thermoregulatory centre, specifically organum vasculosum of the lamina terminalis (OVLT), where they induce synthesis of prostaglandins, of which PGE2 is the most important. These raise the thermostatic set point to initiate the febrile response.

• #21 Physiology, Fever – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562334/

  Fever, or pyrexia, is the elevation of an individual’s core body temperature above a 'set-point’ regulated by the body’s thermoregulatory center in the hypothalamus. This increase in the body’s 'set-point’ temperature is often due to a physiological process brought about by infectious causes or non-infectious causes such as inflammation, malignancy, or autoimmune processes. […] These processes involve the release of immunological mediators, which trigger the thermoregulatory center of the hypothalamus, leading to an increase in the body’s core temperature. […] Milton and Wendlandt demonstrated that fever is mediated by the pyrogenic activity of prostaglandins (PGs), specifically PGE2. The synthesis of PGE2 begins with membrane phospholipids being converted to arachidonic acid (AA) by phospholipase A2 (PLA2). AA is then converted to PGH2 via cyclooxygenase (COX), after which PGH2 undergoes isomerization to PGE2 by PGE synthase. PGE2 acts via the EP3 receptor to affect specific neurons within the hypothalamus that aid in thermoregulation. […] The action of PGE2 begins when exogenous pyrogens (e.g., bacteria, viruses) stimulate endogenous pyrogens such as IL-1, IL-6, tumor necrosis factor (TNF), and interferon (IFN) to alter the hypothalamic set point via the organum vasculosum of the lamina terminalis (OVLT) and raise the core body temperature.

• #22 Fever – Wikipedia

  https://en.wikipedia.org/wiki/Fever

  A pyrogen is a substance that induces fever. […] Endogenous pyrogens are cytokines released from monocytes (which are part of the immune system). […] Major endogenous pyrogens are interleukin 1 and interleukin 6 (IL-6). […] These cytokine factors are released into general circulation, where they migrate to the brain’s circumventricular organs where they are more easily absorbed than in areas protected by the blood-brain barrier. […] The cytokines then bind to endothelial receptors on vessel walls to receptors on microglial cells, resulting in activation of the arachidonic acid pathway. […] Of these, IL-1, TNF, and IL-6 are able to raise the temperature setpoint of an organism and cause fever.

• #23 Peculiarities of the Pathogenesis of Fever in Childhood | ClinicSearch

  https://www.clinicsearchonline.org/article/peculiarities-of-the-pathogenesis-of-fever-in-childhood

  The mechanisms underlying the specificity of fever patterns to certain diseases are not fully understood. For some infectious diseases, it may be related to the life cycle of the pathogen. […] The released parasites activate pyrogenic cytokines, which then lead to fever cycles every 48-72 h (tertian fever). […] Pyrogens are classified into exogenous (produced outside the host) and endogenous (produced within the host) pyrogens based on their site of production. Exogenous pyrogens are essentially parts or whole microorganisms or microbial products such as toxins. […] Endogenous pyrogens are mainly pyrogenic cytokines including interleukins: IL-6, IL-1, interferon gamma (IFN-Y) and ciliary neurotropic factor (CNTF) and tumor necrosis factor (TNF a) and others. […] Fever signals carried by exogenous and endogenous pyrogens ultimately lead to resetting of the thermoregulatory circuitry via two main pathways, namely humoral and neural. […] Activation of the neural pathway is thought to be another mechanism by which fever is rapidly initiated.

• #24 Pathogenesis of Fever

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7122269/

  The generation of fever involves the following steps: numerous substances from outside the body, exogenous pyrogens, initiate the fever cycle. Endotoxin of Gram-negative bacteria, with their pyrogenic component lipopolysaccaride, is the most potent exogenous pyrogen. Fever is also a common finding in children without obvious evidence of infection, for example hypersensitivity reaction, autoimmune diseases and malignancy. […] Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. Endogenous pyrogens are transmitted to the hypothalamic thermoregulatory centre, specifically organum vasculosum of the lamina terminalis (OVLT), where they induce synthesis of prostaglandins, of which PGE2 is the most important. These raise the thermostatic set point to initiate the febrile response.

• #25 Physiology, Fever – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562334/

  Fever, or pyrexia, is the elevation of an individual’s core body temperature above a 'set-point’ regulated by the body’s thermoregulatory center in the hypothalamus. This increase in the body’s 'set-point’ temperature is often due to a physiological process brought about by infectious causes or non-infectious causes such as inflammation, malignancy, or autoimmune processes. […] These processes involve the release of immunological mediators, which trigger the thermoregulatory center of the hypothalamus, leading to an increase in the body’s core temperature. […] Milton and Wendlandt demonstrated that fever is mediated by the pyrogenic activity of prostaglandins (PGs), specifically PGE2. The synthesis of PGE2 begins with membrane phospholipids being converted to arachidonic acid (AA) by phospholipase A2 (PLA2). AA is then converted to PGH2 via cyclooxygenase (COX), after which PGH2 undergoes isomerization to PGE2 by PGE synthase. PGE2 acts via the EP3 receptor to affect specific neurons within the hypothalamus that aid in thermoregulation. […] The action of PGE2 begins when exogenous pyrogens (e.g., bacteria, viruses) stimulate endogenous pyrogens such as IL-1, IL-6, tumor necrosis factor (TNF), and interferon (IFN) to alter the hypothalamic set point via the organum vasculosum of the lamina terminalis (OVLT) and raise the core body temperature.

• #26 Physiology, Fever – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562334/

  Fever, or pyrexia, is the elevation of an individual’s core body temperature above a 'set-point’ regulated by the body’s thermoregulatory center in the hypothalamus. This increase in the body’s 'set-point’ temperature is often due to a physiological process brought about by infectious causes or non-infectious causes such as inflammation, malignancy, or autoimmune processes. […] These processes involve the release of immunological mediators, which trigger the thermoregulatory center of the hypothalamus, leading to an increase in the body’s core temperature. […] Milton and Wendlandt demonstrated that fever is mediated by the pyrogenic activity of prostaglandins (PGs), specifically PGE2. The synthesis of PGE2 begins with membrane phospholipids being converted to arachidonic acid (AA) by phospholipase A2 (PLA2). AA is then converted to PGH2 via cyclooxygenase (COX), after which PGH2 undergoes isomerization to PGE2 by PGE synthase. PGE2 acts via the EP3 receptor to affect specific neurons within the hypothalamus that aid in thermoregulation. […] The action of PGE2 begins when exogenous pyrogens (e.g., bacteria, viruses) stimulate endogenous pyrogens such as IL-1, IL-6, tumor necrosis factor (TNF), and interferon (IFN) to alter the hypothalamic set point via the organum vasculosum of the lamina terminalis (OVLT) and raise the core body temperature.

• #27 Physiology, Fever – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562334/

  Fever, or pyrexia, is the elevation of an individual’s core body temperature above a 'set-point’ regulated by the body’s thermoregulatory center in the hypothalamus. This increase in the body’s 'set-point’ temperature is often due to a physiological process brought about by infectious causes or non-infectious causes such as inflammation, malignancy, or autoimmune processes. […] These processes involve the release of immunological mediators, which trigger the thermoregulatory center of the hypothalamus, leading to an increase in the body’s core temperature. […] Milton and Wendlandt demonstrated that fever is mediated by the pyrogenic activity of prostaglandins (PGs), specifically PGE2. The synthesis of PGE2 begins with membrane phospholipids being converted to arachidonic acid (AA) by phospholipase A2 (PLA2). AA is then converted to PGH2 via cyclooxygenase (COX), after which PGH2 undergoes isomerization to PGE2 by PGE synthase. PGE2 acts via the EP3 receptor to affect specific neurons within the hypothalamus that aid in thermoregulation. […] The action of PGE2 begins when exogenous pyrogens (e.g., bacteria, viruses) stimulate endogenous pyrogens such as IL-1, IL-6, tumor necrosis factor (TNF), and interferon (IFN) to alter the hypothalamic set point via the organum vasculosum of the lamina terminalis (OVLT) and raise the core body temperature.

• #28 Pathogenesis of Fever

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7122269/

  The generation of fever involves the following steps: numerous substances from outside the body, exogenous pyrogens, initiate the fever cycle. Endotoxin of Gram-negative bacteria, with their pyrogenic component lipopolysaccaride, is the most potent exogenous pyrogen. Fever is also a common finding in children without obvious evidence of infection, for example hypersensitivity reaction, autoimmune diseases and malignancy. […] Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. Endogenous pyrogens are transmitted to the hypothalamic thermoregulatory centre, specifically organum vasculosum of the lamina terminalis (OVLT), where they induce synthesis of prostaglandins, of which PGE2 is the most important. These raise the thermostatic set point to initiate the febrile response.

• #29 Fever – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/biology-of-infectious-disease/fever

  Body temperature is determined by the balance between heat production by tissues, particularly the liver and muscles, and heat loss from the periphery. […] Fever results when something raises the hypothalamic set point, triggering vasoconstriction and shunting of blood from the periphery to decrease heat loss; sometimes shivering, which increases heat production, is induced. […] Pyrogens are substances that cause fever. Exogenous pyrogens are usually microbes or their products. The best studied are the lipopolysaccharides of gram-negative bacteria (commonly called endotoxins) and Staphylococcus aureus toxin, which causes toxic shock syndrome. Fever is the result of exogenous pyrogens that induce release of endogenous pyrogens, such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and IL-6 and other cytokines, which then trigger cytokine receptors, or of exogenous pyrogens that directly trigger Toll-like receptors in the different intestinal epithelial lineages. […] Prostaglandin E2 synthesis appears to play a critical role.

• #30 Fever – Wikipedia

  https://en.wikipedia.org/wiki/Fever

  Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with body temperature exceeding the normal range due to an increase in the body’s temperature set point in the hypothalamus. […] The increase in set point triggers increased muscle contractions and causes a feeling of cold or chills. This results in greater heat production and efforts to conserve heat. […] When the set point temperature returns to normal, a person feels hot, becomes flushed, and may begin to sweat. […] The trigger of a fever, called a pyrogen, results in the release of prostaglandin E2 (PGE2). PGE2 in turn acts on the hypothalamus, which creates a systemic response in the body, causing heat-generating effects to match a new higher temperature set point. […] When the hypothalamic set point moves back to baseline either spontaneously or via medication normal functions such as sweating, and the reverse of the foregoing processes (e.g., vasodilation, end of shivering, and nonshivering heat production) are used to cool the body to the new, lower setting.

• #31 Fever – Wikipedia

  https://en.wikipedia.org/wiki/Fever

  Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with body temperature exceeding the normal range due to an increase in the body’s temperature set point in the hypothalamus. […] The increase in set point triggers increased muscle contractions and causes a feeling of cold or chills. This results in greater heat production and efforts to conserve heat. […] When the set point temperature returns to normal, a person feels hot, becomes flushed, and may begin to sweat. […] The trigger of a fever, called a pyrogen, results in the release of prostaglandin E2 (PGE2). PGE2 in turn acts on the hypothalamus, which creates a systemic response in the body, causing heat-generating effects to match a new higher temperature set point. […] When the hypothalamic set point moves back to baseline either spontaneously or via medication normal functions such as sweating, and the reverse of the foregoing processes (e.g., vasodilation, end of shivering, and nonshivering heat production) are used to cool the body to the new, lower setting.

• #32 Fever: Everything you need to know – USZ

  https://www.usz.ch/en/disease/fever/

  In the event of a fever, for example, the setpoint is increased to 39 C. The body then takes measures to increase the temperature. […] Increased body temperature can inhibit the multiplication of certain pathogens, as fever creates an environment that is unfavorable for many bacteria and viruses. […] Fever can also increase the activity of certain immune cells such as white blood cells, which help to fight pathogens. […] The body releases so-called pyrogens (fever-inducing substances), which signal the hypothalamus to increase the body temperature. […] The body tries to react to these stress situations by increasing its temperature. […] A higher temperature accelerates certain biochemical processes in the body that can contribute to healing, such as tissue repair. […] Fever is an important mechanism used by the body to fight infections. In most cases it is harmless and does not require immediate treatment. […] Nevertheless, you should be careful, especially if you have a high or prolonged fever or corresponding accompanying symptoms.

• #33 Fever – Wikipedia

  https://en.wikipedia.org/wiki/Fever

  Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with body temperature exceeding the normal range due to an increase in the body’s temperature set point in the hypothalamus. […] The increase in set point triggers increased muscle contractions and causes a feeling of cold or chills. This results in greater heat production and efforts to conserve heat. […] When the set point temperature returns to normal, a person feels hot, becomes flushed, and may begin to sweat. […] The trigger of a fever, called a pyrogen, results in the release of prostaglandin E2 (PGE2). PGE2 in turn acts on the hypothalamus, which creates a systemic response in the body, causing heat-generating effects to match a new higher temperature set point. […] When the hypothalamic set point moves back to baseline either spontaneously or via medication normal functions such as sweating, and the reverse of the foregoing processes (e.g., vasodilation, end of shivering, and nonshivering heat production) are used to cool the body to the new, lower setting.

• #34 Fever – Wikipedia

  https://en.wikipedia.org/wiki/Fever

  Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with body temperature exceeding the normal range due to an increase in the body’s temperature set point in the hypothalamus. […] The increase in set point triggers increased muscle contractions and causes a feeling of cold or chills. This results in greater heat production and efforts to conserve heat. […] When the set point temperature returns to normal, a person feels hot, becomes flushed, and may begin to sweat. […] The trigger of a fever, called a pyrogen, results in the release of prostaglandin E2 (PGE2). PGE2 in turn acts on the hypothalamus, which creates a systemic response in the body, causing heat-generating effects to match a new higher temperature set point. […] When the hypothalamic set point moves back to baseline either spontaneously or via medication normal functions such as sweating, and the reverse of the foregoing processes (e.g., vasodilation, end of shivering, and nonshivering heat production) are used to cool the body to the new, lower setting.

• #35 Peculiarities of the Pathogenesis of Fever in Childhood | ClinicSearch

  https://www.clinicsearchonline.org/article/peculiarities-of-the-pathogenesis-of-fever-in-childhood

  Fever is one of the most common symptoms of childhood illnesses and the most common chief complaint in pediatric outpatient departments, especially in emergency departments. Fever is an increase in the hypothalamic set point temperature caused by various pathogenic factors, resulting in an abnormal increase in body temperature. […] Pediatricians are especially vigilant for high fever in children (axillary temperature up to 103.5 F (39.5 C)) which is more likely to cause serious adverse outcomes such as childhood pneumonia and febrile seizures. […] The development of the febrile response is similar to the normal thermoregulatory processes that follow exposure to cold temperatures. However, in fever, the heat balance point is reset to a higher level such that normal peripheral and central body temperatures are now perceived as cold temperature signals by the thermoregulatory circuitry. […] Therefore, fever is distinct from heat stroke and hyperthermia, in which body temperature increases without a corresponding increase in the heat balance point.

• #36 Fever: Pathogenesis and Treatment | Obgyn Key

  https://obgynkey.com/fever-pathogenesis-and-treatment/

  Fever is the thermoregulated increase in body temperature above normal as the result of a coordinated response to a pathologic insult. […] In children, the pathologic insult most likely to result in fever is infection. […] In the classic model of fever pathogenesis, exogenous pyrogens stimulate the release of circulating endogenous pyrogens, which act via prostaglandins to increase the set point of the hypothalamic thermoregulatory center. […] The first endogenous pyrogen was described originally more than 60 years ago and was derived from leukocytes, primarily granulocytes, and now is known as interleukin-1 (IL-1). […] Regardless of the precise pathogenesis, the height of fever seems to be limited. […] Retrospective studies of hyperpyrexia in children have found that it is unusual for the body temperature to rise above 41.1C (106F), and it rarely rises above 41.7C (107F).

• #37 Physiology, Fever – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562334/

  Fever occurs when either endogenous or exogenous pyrogens cause an elevation in the body’s thermoregulatory set-point. In hyperthermia, the set-point is unaltered, and the body temperature becomes elevated in an uncontrolled fashion due to exogenous heat exposure or endogenous heat production. […] Hyperpyrexia is the term for exceptionally high fever (greater than 41 C), which can occur in patients with severe infections. Hyperpyrexia may also be seen in patients with CNS hemorrhages and is associated with a poor outcome. Elevated brain temperature may lead to increased intracranial pressure, ischemic brain injury, exacerbation of cerebral edema, and death.

• #38 Fever: Pathogenesis and Treatment | Obgyn Key

  https://obgynkey.com/fever-pathogenesis-and-treatment/

  Fever is the thermoregulated increase in body temperature above normal as the result of a coordinated response to a pathologic insult. […] In children, the pathologic insult most likely to result in fever is infection. […] In the classic model of fever pathogenesis, exogenous pyrogens stimulate the release of circulating endogenous pyrogens, which act via prostaglandins to increase the set point of the hypothalamic thermoregulatory center. […] The first endogenous pyrogen was described originally more than 60 years ago and was derived from leukocytes, primarily granulocytes, and now is known as interleukin-1 (IL-1). […] Regardless of the precise pathogenesis, the height of fever seems to be limited. […] Retrospective studies of hyperpyrexia in children have found that it is unusual for the body temperature to rise above 41.1C (106F), and it rarely rises above 41.7C (107F).

• #39 Pathogenesis of Fever

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7122269/

  The induction of fever results in inhibition of bacterial growth, increased bactericidal effects of neutrophils, production of acute-phase protein synthesis and other physiological changes such as anorexia and somnolence. These changes suggest that fever has an adaptive role in the hosts survival during infection. […] The protective processes of the immune response are optimal at high temperature (around 39.5 C). […] The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favour of the protective role of fever.

• #40 Pathogenesis of Fever | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-540-78598-9_3

  The protective processes of the immune response are optimal at high temperature (around 39.5C). […] Not all effects resulting from fever generation benefit the host; some are harmful and even lethal. This occurs mainly by overproduction of the cytokines or imbalance between cytokines and their inhibitors, such as severe and fulminate infections and septic shock.

• #41 Pathogenesis of Fever

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7122269/

  The induction of fever results in inhibition of bacterial growth, increased bactericidal effects of neutrophils, production of acute-phase protein synthesis and other physiological changes such as anorexia and somnolence. These changes suggest that fever has an adaptive role in the hosts survival during infection. […] The protective processes of the immune response are optimal at high temperature (around 39.5 C). […] The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favour of the protective role of fever.

• #42 Fever | Definition, Characteristics, & Causes | Britannica

  https://www.britannica.com/science/fever

  Fever is a characteristic of many different diseases. […] The mechanism of fever appears to be a defensive reaction by the body against infectious disease. When bacteria or viruses invade the body and cause tissue injury, one of the immune systems responses is to produce pyrogens. These chemicals are carried by the blood to the brain, where they disturb the functioning of the hypothalamus, the part of the brain that regulates body temperature. The pyrogens inhibit heat-sensing neurons and excite cold-sensing ones, and the altering of these temperature sensors deceives the hypothalamus into thinking the body is cooler than it actually is. In response, the hypothalamus raises the bodys temperature above the normal range, thereby causing a fever. The above-normal temperatures are thought to help defend against microbial invasion because they stimulate the motion, activity, and multiplication of white blood cells and increase the production of antibodies. […] At the same time, elevated heat levels may directly kill or inhibit the growth of some bacteria and viruses that can tolerate only a narrow temperature range.

• #43 Pathogenesis of Fever

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7122269/

  The induction of fever results in inhibition of bacterial growth, increased bactericidal effects of neutrophils, production of acute-phase protein synthesis and other physiological changes such as anorexia and somnolence. These changes suggest that fever has an adaptive role in the hosts survival during infection. […] The protective processes of the immune response are optimal at high temperature (around 39.5 C). […] The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favour of the protective role of fever.

• #44 Pathogenesis of Fever | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-540-78598-9_3

  The protective processes of the immune response are optimal at high temperature (around 39.5C). […] Not all effects resulting from fever generation benefit the host; some are harmful and even lethal. This occurs mainly by overproduction of the cytokines or imbalance between cytokines and their inhibitors, such as severe and fulminate infections and septic shock.

• #45 Pathogenesis of Fever

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7122269/

  The induction of fever results in inhibition of bacterial growth, increased bactericidal effects of neutrophils, production of acute-phase protein synthesis and other physiological changes such as anorexia and somnolence. These changes suggest that fever has an adaptive role in the hosts survival during infection. […] The protective processes of the immune response are optimal at high temperature (around 39.5 C). […] The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favour of the protective role of fever.

• #46 Pathogenesis of Fever

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7122269/

  The induction of fever results in inhibition of bacterial growth, increased bactericidal effects of neutrophils, production of acute-phase protein synthesis and other physiological changes such as anorexia and somnolence. These changes suggest that fever has an adaptive role in the hosts survival during infection. […] The protective processes of the immune response are optimal at high temperature (around 39.5 C). […] The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favour of the protective role of fever.

• #47 Pathogenesis of Fever | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-540-78598-9_3

  Although infection is the most common cause of fever, fever is also a common finding in hypersensitivity reaction, autoimmune diseases, and malignancy. […] Febrile response is mediated by endogenous pyrogens (cytokines) in response to invading exogenous pyrogens, primarily microorganisms or their direct products (toxins). […] These endogenous pyrogens act on thermosensitive neurons in the hypothalamus, which ultimately upgrade the set point via prostaglandins. […] The body reacts by increasing the heat production and decreasing the heat loss until the body temperature reaches this elevated set point. […] Fever, in contrast to hyperthermia, will not climb up relentlessly because of an effective central control of the hypothalamic center. […] Cytokines play a pivotal role in the immune response by activation of the B cells and T lymphocytes. The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favor of the protective role of fever.

• #48 Pathogenesis of Fever | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-540-78598-9_3

  The protective processes of the immune response are optimal at high temperature (around 39.5C). […] Not all effects resulting from fever generation benefit the host; some are harmful and even lethal. This occurs mainly by overproduction of the cytokines or imbalance between cytokines and their inhibitors, such as severe and fulminate infections and septic shock.

• #49 Fever in Infants and Children – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/symptoms-in-infants-and-children/fever-in-infants-and-children

  Fever occurs in response to the release of endogenous pyrogenic mediators called cytokines (in particular interleukin-1 [IL-1]). Cytokines stimulate the production of prostaglandins by the hypothalamus; prostaglandins readjust and elevate the temperature set point. […] Fever plays an integral role in fighting infection and, although it may be uncomfortable, does not necessitate treatment in an otherwise healthy child. Some studies even indicate that lowering the temperature can prolong some illnesses. However, fever increases the metabolic rate and the demands on the cardiopulmonary system. Therefore, fever can be detrimental to children with pulmonary or cardiac compromise or neurologic impairment. It can also be the catalyst for febrile seizures, which although typically benign, are very concerning to parents and must also be distinguished from more serious disorders (eg, meningitis).

• #50 Fever in Infants and Children – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/symptoms-in-infants-and-children/fever-in-infants-and-children

  Fever occurs in response to the release of endogenous pyrogenic mediators called cytokines (in particular interleukin-1 [IL-1]). Cytokines stimulate the production of prostaglandins by the hypothalamus; prostaglandins readjust and elevate the temperature set point. […] Fever plays an integral role in fighting infection and, although it may be uncomfortable, does not necessitate treatment in an otherwise healthy child. Some studies even indicate that lowering the temperature can prolong some illnesses. However, fever increases the metabolic rate and the demands on the cardiopulmonary system. Therefore, fever can be detrimental to children with pulmonary or cardiac compromise or neurologic impairment. It can also be the catalyst for febrile seizures, which although typically benign, are very concerning to parents and must also be distinguished from more serious disorders (eg, meningitis).

• #51 Fever in Infants and Children – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/symptoms-in-infants-and-children/fever-in-infants-and-children

  Fever occurs in response to the release of endogenous pyrogenic mediators called cytokines (in particular interleukin-1 [IL-1]). Cytokines stimulate the production of prostaglandins by the hypothalamus; prostaglandins readjust and elevate the temperature set point. […] Fever plays an integral role in fighting infection and, although it may be uncomfortable, does not necessitate treatment in an otherwise healthy child. Some studies even indicate that lowering the temperature can prolong some illnesses. However, fever increases the metabolic rate and the demands on the cardiopulmonary system. Therefore, fever can be detrimental to children with pulmonary or cardiac compromise or neurologic impairment. It can also be the catalyst for febrile seizures, which although typically benign, are very concerning to parents and must also be distinguished from more serious disorders (eg, meningitis).

• #52 Fever – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/fever/symptoms-causes/syc-20352759

  A fever is a temporary rise in body temperature. It’s one part of an overall response from the body’s immune system. A fever is usually caused by an infection. […] When your immune system responds to disease, the hypothalamus can set your body temperature higher. This prompts complex processes that produce more heat and restrict heat loss. The shivering you might experience is one way the body produces heat. […] Fevers below 104 F (40 C) associated with common viral infections, such as the flu, may help the immune system fight disease and are generally not harmful. […] Fever or elevated body temperature might be caused by: A viral infection, A bacterial infection, Heat exhaustion, Certain inflammatory conditions such as rheumatoid arthritis inflammation of the lining of your joints (synovium), A cancerous (malignant) tumor, Some medications, such as antibiotics and drugs used to treat high blood pressure or seizures, Some immunizations, such as the diphtheria, tetanus and acellular pertussis (DTaP), pneumococcal or COVID vaccine. […] Children between the ages of 6 months and 5 years are at increased risk of a seizure that occurs during a fever (febrile seizure). About a third of the children who have one febrile seizure will have another one, most commonly within the next 12 months.

• #53 The pathophysiological basis and consequences of fever | Critical Care | Full Text

  https://ccforum.biomedcentral.com/articles/10.1186/s13054-016-1375-5

  Heat shock proteins (HSP) are a family of cell-derived proteins that offer protection against a range of insults, including heat. […] Non-pyrogenic hyperthermia increases gut bacterial translocation and the gastrointestinal (GI) tract and BBB appear to be more permeable to toxins than during normothermia. […] Most patients fully recover after a period of hyperthermia, but patients exposed to higher temperatures and for longer periods of time are more at risk of complications, which may lead to multi-organ failure and death in extreme cases. […] A mild elevation in core temperature is of benefit in sepsis. Non-pyrogenic hyperthermia is associated with short-term, medium-term, and long-term effects in a variety of organs. The damage occurs via a number of local and systemic mechanisms.

• #54 The pathophysiological basis and consequences of fever | Critical Care | Full Text

  https://ccforum.biomedcentral.com/articles/10.1186/s13054-016-1375-5

  Fever after acute brain damage, from trauma or a vascular event, is common, and is independently associated with a worse outcome. The mechanism of fever generation is probably multi-factorial; 41 % of deaths after traumatic brain injury (TBI) in one series displayed hypothalamic lesions, suggesting thermal dysregulation in some cases. […] Hyperthermia is directly cytotoxic, affecting membrane stability and transmembrane transport protein function. Consequently, ionic transport is disrupted leading to increased intracellular sodium and calcium with a reduced intracellular potassium concentration. […] The role of cytokines in heat stress is unclear, with an inconsistent response to thermal stress. The levels of a number of pro-inflammatory and anti-inflammatory cytokines are elevated at the time of hyperthermia from heatstroke.

• #55 Mackey Family Practice – Fever and Tylenol Dosing in Children

  https://mackeyfamilypractice.com/fever-and-tylenol-dosing-in-children/

  Fever is a normal body response to infection and a symptom of an illness, not an illness itself. […] Temperatures of 100-103 degrees are usual with childhood infections and help combat disease. […] Temperatures of 104 degrees and above may cause convulsions in infants and chills in older children and adults. […] Sudden changes in temperature can precipitate convulsions in infants (up to 2 years of age). […] Temperatures of 105 degrees and above if prolonged can cause brain damage. […] A fever does not necessarily indicate a dangerous infection. The child’s temperature regulating mechanism is not well developed and a fever is often higher than one would expect with a relatively minor infection.

• #56 Fever Symptoms & Treatment (for Parents) (for Parents) | Nemours KidsHealth

  https://kidshealth.org/en/parents/fever.html

  Fevers in kids are usually caused by an infection. A fever helps the body by stimulating the immune system to fight the infection. Doctors also think the higher temperature makes it harder for the germs to grow. […] A few other reasons kids can have a fever: Overdressing: Infants, especially newborns, may get fevers if they’re overdressed, wrapped in a blanket, or in a hot environment because they don’t regulate their body temperature as well as older kids. But because fevers in newborns can be a sign of a serious infection, even infants who are overdressed must be checked by a doctor if they have a fever. […] Immunizations: Babies and kids sometimes get a mild fever that lasts about a day after getting vaccinated. […] A child who is teething might have a slight rise in body temperature, but it’s probably not the cause if the temperature is higher than 100F (37.8C).

• #57 Fever in Children: What to Do, When to Worry | Juno Medical

  https://juno.care/blog-posts/fever-in-children

  Fever is only one aspect of the bodys defense mechanism against infection. When foreign pathogens like viruses or bacteria are detected, the immune system activates in several ways. One way is by raising your body temperature, since viruses and bacteria can only multiply within a certain temperature range. […] So, fevers in children are a healthy sign of a robust immune system. However, its important to note that fevers in children under 3 months old should always be evaluated by a doctor because their immune systems are still immature and even regular viruses and bacteria can be dangerous. […] In the past, higher fevers (over 104 F) were associated with more serious illnesses like pneumonia. However, due to routine infant vaccinations, the number of bacterial illnesses in children have declined significantly and now there is no clear correlation between height of fever and severity of illness.

• #58 Fever Symptoms & Treatment (for Parents) (for Parents) | Nemours KidsHealth

  https://kidshealth.org/en/parents/fever.html

  Fevers in kids are usually caused by an infection. A fever helps the body by stimulating the immune system to fight the infection. Doctors also think the higher temperature makes it harder for the germs to grow. […] A few other reasons kids can have a fever: Overdressing: Infants, especially newborns, may get fevers if they’re overdressed, wrapped in a blanket, or in a hot environment because they don’t regulate their body temperature as well as older kids. But because fevers in newborns can be a sign of a serious infection, even infants who are overdressed must be checked by a doctor if they have a fever. […] Immunizations: Babies and kids sometimes get a mild fever that lasts about a day after getting vaccinated. […] A child who is teething might have a slight rise in body temperature, but it’s probably not the cause if the temperature is higher than 100F (37.8C).

• #59 Fever in Children: What to Do, When to Worry | Juno Medical

  https://juno.care/blog-posts/fever-in-children

  Fever is only one aspect of the bodys defense mechanism against infection. When foreign pathogens like viruses or bacteria are detected, the immune system activates in several ways. One way is by raising your body temperature, since viruses and bacteria can only multiply within a certain temperature range. […] So, fevers in children are a healthy sign of a robust immune system. However, its important to note that fevers in children under 3 months old should always be evaluated by a doctor because their immune systems are still immature and even regular viruses and bacteria can be dangerous. […] In the past, higher fevers (over 104 F) were associated with more serious illnesses like pneumonia. However, due to routine infant vaccinations, the number of bacterial illnesses in children have declined significantly and now there is no clear correlation between height of fever and severity of illness.

• #60 Fever Symptoms & Treatment (for Parents) (for Parents) | Nemours KidsHealth

  https://kidshealth.org/en/parents/fever.html

  Fevers in kids are usually caused by an infection. A fever helps the body by stimulating the immune system to fight the infection. Doctors also think the higher temperature makes it harder for the germs to grow. […] A few other reasons kids can have a fever: Overdressing: Infants, especially newborns, may get fevers if they’re overdressed, wrapped in a blanket, or in a hot environment because they don’t regulate their body temperature as well as older kids. But because fevers in newborns can be a sign of a serious infection, even infants who are overdressed must be checked by a doctor if they have a fever. […] Immunizations: Babies and kids sometimes get a mild fever that lasts about a day after getting vaccinated. […] A child who is teething might have a slight rise in body temperature, but it’s probably not the cause if the temperature is higher than 100F (37.8C).

• #61 Fever – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/fever/symptoms-causes/syc-20352759

  A fever is a temporary rise in body temperature. It’s one part of an overall response from the body’s immune system. A fever is usually caused by an infection. […] When your immune system responds to disease, the hypothalamus can set your body temperature higher. This prompts complex processes that produce more heat and restrict heat loss. The shivering you might experience is one way the body produces heat. […] Fevers below 104 F (40 C) associated with common viral infections, such as the flu, may help the immune system fight disease and are generally not harmful. […] Fever or elevated body temperature might be caused by: A viral infection, A bacterial infection, Heat exhaustion, Certain inflammatory conditions such as rheumatoid arthritis inflammation of the lining of your joints (synovium), A cancerous (malignant) tumor, Some medications, such as antibiotics and drugs used to treat high blood pressure or seizures, Some immunizations, such as the diphtheria, tetanus and acellular pertussis (DTaP), pneumococcal or COVID vaccine. […] Children between the ages of 6 months and 5 years are at increased risk of a seizure that occurs during a fever (febrile seizure). About a third of the children who have one febrile seizure will have another one, most commonly within the next 12 months.

• #62 Six common fever myths explained – Health & Wellbeing

  https://www.abc.net.au/health/features/stories/2015/03/12/4123222.htm

  The belief teething can cause fever in babies is common. But a seven-month study where researchers monitored babies very closely to check what symptoms were linked to the appearance of new teeth found no evidence to support the idea. […] Most children with fevers suffer only minor discomfort, but one in 30 will have a febrile convulsion or fever fit at one time or another. This usually happens between the ages of six months and six years. […] For children, rather than just relying on fever to gauge the severity of your their illness, ask yourself whether they appear to be distressed or in pain, if they are playing or moving around normally in the bed, whether they are alert and interested in their surroundings and whether they are wetting the usual number of nappies. […] While it might seem like a good idea to put a young child in a cold bath to bring down a fever, it’s actually not recommended. Cold water can increase core body temperature by cooling the skin and causing shivering.

• #63 Fever – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/fever/symptoms-causes/syc-20352759

  A fever is a temporary rise in body temperature. It’s one part of an overall response from the body’s immune system. A fever is usually caused by an infection. […] When your immune system responds to disease, the hypothalamus can set your body temperature higher. This prompts complex processes that produce more heat and restrict heat loss. The shivering you might experience is one way the body produces heat. […] Fevers below 104 F (40 C) associated with common viral infections, such as the flu, may help the immune system fight disease and are generally not harmful. […] Fever or elevated body temperature might be caused by: A viral infection, A bacterial infection, Heat exhaustion, Certain inflammatory conditions such as rheumatoid arthritis inflammation of the lining of your joints (synovium), A cancerous (malignant) tumor, Some medications, such as antibiotics and drugs used to treat high blood pressure or seizures, Some immunizations, such as the diphtheria, tetanus and acellular pertussis (DTaP), pneumococcal or COVID vaccine. […] Children between the ages of 6 months and 5 years are at increased risk of a seizure that occurs during a fever (febrile seizure). About a third of the children who have one febrile seizure will have another one, most commonly within the next 12 months.

• #64 Fever – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/fever/symptoms-causes/syc-20352759

  A fever is a temporary rise in body temperature. It’s one part of an overall response from the body’s immune system. A fever is usually caused by an infection. […] When your immune system responds to disease, the hypothalamus can set your body temperature higher. This prompts complex processes that produce more heat and restrict heat loss. The shivering you might experience is one way the body produces heat. […] Fevers below 104 F (40 C) associated with common viral infections, such as the flu, may help the immune system fight disease and are generally not harmful. […] Fever or elevated body temperature might be caused by: A viral infection, A bacterial infection, Heat exhaustion, Certain inflammatory conditions such as rheumatoid arthritis inflammation of the lining of your joints (synovium), A cancerous (malignant) tumor, Some medications, such as antibiotics and drugs used to treat high blood pressure or seizures, Some immunizations, such as the diphtheria, tetanus and acellular pertussis (DTaP), pneumococcal or COVID vaccine. […] Children between the ages of 6 months and 5 years are at increased risk of a seizure that occurs during a fever (febrile seizure). About a third of the children who have one febrile seizure will have another one, most commonly within the next 12 months.

• #65 Pediatricians say it’s often better to let a child’s fever run its course – The Washington Post

  https://www.washingtonpost.com/national/health/pediatricians-say-its-often-better-to-let-a-childs-fever-run-its-course/2011/04/11/AF6j0fkE_story.html

  Fever is the body’s normal response to infection — it’s a natural defense mechanism. […] A high temperature triggers the body’s production of infection-fighting white blood cells and inhibits the growth of viruses and bacteria. […] If you lower the fever, you may be affecting the body’s ability to respond to that infection. […] Fever is one of the more obvious signs of illness, so of course it worries parents, it worries doctors and brings the underlying illness to everyone’s attention, but most of the fears [about brain damage and other long-term effects] are unfounded. […] For a normal child . . . a fever is not going to get high enough to cause any kind of significant damage, so that’s not something you need to worry about. […] There’s also no reason to panic about fever-related seizures, which are generally short and not related to how high a temperature is, and almost always resolve on their own.

• #66 Pediatricians say it’s often better to let a child’s fever run its course – The Washington Post

  https://www.washingtonpost.com/national/health/pediatricians-say-its-often-better-to-let-a-childs-fever-run-its-course/2011/04/11/AF6j0fkE_story.html

  The literature suggests that there are no long-term or permanent bad results from febrile seizures. […] It’s important to recognize that this is not going to make any difference as far as treating the root cause of the problem, or help children heal any faster. […] A child can have low-grade fever or no fever at all and look pretty ill, or have high a fever, be really sick and still look pretty good: The severity of the illness is not necessarily directly related to how high your fever is. […] The only reason to take an antipyretic like acetaminophen, aspirin or ibuprofen is for comfort, and everybody’s comfort or discomfort level is a little different. […] The signs of a more serious pediatric problem — a bacterial infection, for example — can include decreased activity or lack of responsiveness, headache with neck pain, acute dehydration, difficulty breathing, pain with urination and a fever with abdominal pain.

• #67 Fever Symptoms & Treatment (for Parents) (for Parents) | Nemours KidsHealth

  https://kidshealth.org/en/parents/fever.html

  Fevers in kids are usually caused by an infection. A fever helps the body by stimulating the immune system to fight the infection. Doctors also think the higher temperature makes it harder for the germs to grow. […] A few other reasons kids can have a fever: Overdressing: Infants, especially newborns, may get fevers if they’re overdressed, wrapped in a blanket, or in a hot environment because they don’t regulate their body temperature as well as older kids. But because fevers in newborns can be a sign of a serious infection, even infants who are overdressed must be checked by a doctor if they have a fever. […] Immunizations: Babies and kids sometimes get a mild fever that lasts about a day after getting vaccinated. […] A child who is teething might have a slight rise in body temperature, but it’s probably not the cause if the temperature is higher than 100F (37.8C).

• #68 Fever – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/fever/symptoms-causes/syc-20352759

  A fever is a temporary rise in body temperature. It’s one part of an overall response from the body’s immune system. A fever is usually caused by an infection. […] When your immune system responds to disease, the hypothalamus can set your body temperature higher. This prompts complex processes that produce more heat and restrict heat loss. The shivering you might experience is one way the body produces heat. […] Fevers below 104 F (40 C) associated with common viral infections, such as the flu, may help the immune system fight disease and are generally not harmful. […] Fever or elevated body temperature might be caused by: A viral infection, A bacterial infection, Heat exhaustion, Certain inflammatory conditions such as rheumatoid arthritis inflammation of the lining of your joints (synovium), A cancerous (malignant) tumor, Some medications, such as antibiotics and drugs used to treat high blood pressure or seizures, Some immunizations, such as the diphtheria, tetanus and acellular pertussis (DTaP), pneumococcal or COVID vaccine. […] Children between the ages of 6 months and 5 years are at increased risk of a seizure that occurs during a fever (febrile seizure). About a third of the children who have one febrile seizure will have another one, most commonly within the next 12 months.

• #69 Peculiarities of the Pathogenesis of Fever in Childhood | ClinicSearch

  https://www.clinicsearchonline.org/article/peculiarities-of-the-pathogenesis-of-fever-in-childhood

  In this article, fever was analyzed as an important clinical symptom reflecting the body’s response to various pathogenic agents and inflammatory processes. […] Understanding its causes and consequences, as well as understanding the pathophysiological mechanisms underlying it, play a key role in the diagnosis and treatment of various diseases associated with hyperthermia.

• #70 Peculiarities of the Pathogenesis of Fever in Childhood | ClinicSearch

  https://clinicsearchonline.org/article/peculiarities-of-the-pathogenesis-of-fever-in-childhood

  The mechanisms underlying the specificity of fever patterns to certain diseases are not fully understood. For some infectious diseases, it may be related to the life cycle of the pathogen. […] The febrile response is characterized by an early rapid phase and a delayed late phase. […] Fever signals carried by exogenous and endogenous pyrogens ultimately lead to resetting of the thermoregulatory circuitry via two main pathways, namely humoral and neural. […] Pyrogens are classified into exogenous (produced outside the host) and endogenous (produced within the host) pyrogens based on their site of production. […] Fever, as a protective mechanism, plays a key role in the immune response, promoting the activation of protective cells and the synthesis of cytokines. However, despite its physiological function, fever can lead to significant discomfort in patients and, in some cases, to serious complications, especially in children, the elderly, and people with weakened immunity. […] Understanding its causes and consequences, as well as understanding the pathophysiological mechanisms underlying it, play a key role in the diagnosis and treatment of various diseases associated with hyperthermia.

• #71 Pathogenesis of Fever | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-540-78598-9_3

  Although infection is the most common cause of fever, fever is also a common finding in hypersensitivity reaction, autoimmune diseases, and malignancy. […] Febrile response is mediated by endogenous pyrogens (cytokines) in response to invading exogenous pyrogens, primarily microorganisms or their direct products (toxins). […] These endogenous pyrogens act on thermosensitive neurons in the hypothalamus, which ultimately upgrade the set point via prostaglandins. […] The body reacts by increasing the heat production and decreasing the heat loss until the body temperature reaches this elevated set point. […] Fever, in contrast to hyperthermia, will not climb up relentlessly because of an effective central control of the hypothalamic center. […] Cytokines play a pivotal role in the immune response by activation of the B cells and T lymphocytes. The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favor of the protective role of fever.

• #72 Pathogenesis of Fever

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7122269/

  The generation of fever involves the following steps: numerous substances from outside the body, exogenous pyrogens, initiate the fever cycle. Endotoxin of Gram-negative bacteria, with their pyrogenic component lipopolysaccaride, is the most potent exogenous pyrogen. Fever is also a common finding in children without obvious evidence of infection, for example hypersensitivity reaction, autoimmune diseases and malignancy. […] Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. Endogenous pyrogens are transmitted to the hypothalamic thermoregulatory centre, specifically organum vasculosum of the lamina terminalis (OVLT), where they induce synthesis of prostaglandins, of which PGE2 is the most important. These raise the thermostatic set point to initiate the febrile response.

• #73 Physiology, Fever – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562334/

  Fever, or pyrexia, is the elevation of an individual’s core body temperature above a 'set-point’ regulated by the body’s thermoregulatory center in the hypothalamus. This increase in the body’s 'set-point’ temperature is often due to a physiological process brought about by infectious causes or non-infectious causes such as inflammation, malignancy, or autoimmune processes. […] These processes involve the release of immunological mediators, which trigger the thermoregulatory center of the hypothalamus, leading to an increase in the body’s core temperature. […] Milton and Wendlandt demonstrated that fever is mediated by the pyrogenic activity of prostaglandins (PGs), specifically PGE2. The synthesis of PGE2 begins with membrane phospholipids being converted to arachidonic acid (AA) by phospholipase A2 (PLA2). AA is then converted to PGH2 via cyclooxygenase (COX), after which PGH2 undergoes isomerization to PGE2 by PGE synthase. PGE2 acts via the EP3 receptor to affect specific neurons within the hypothalamus that aid in thermoregulation. […] The action of PGE2 begins when exogenous pyrogens (e.g., bacteria, viruses) stimulate endogenous pyrogens such as IL-1, IL-6, tumor necrosis factor (TNF), and interferon (IFN) to alter the hypothalamic set point via the organum vasculosum of the lamina terminalis (OVLT) and raise the core body temperature.

• #74 Pathogenesis of Fever | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-540-78598-9_3

  Although infection is the most common cause of fever, fever is also a common finding in hypersensitivity reaction, autoimmune diseases, and malignancy. […] Febrile response is mediated by endogenous pyrogens (cytokines) in response to invading exogenous pyrogens, primarily microorganisms or their direct products (toxins). […] These endogenous pyrogens act on thermosensitive neurons in the hypothalamus, which ultimately upgrade the set point via prostaglandins. […] The body reacts by increasing the heat production and decreasing the heat loss until the body temperature reaches this elevated set point. […] Fever, in contrast to hyperthermia, will not climb up relentlessly because of an effective central control of the hypothalamic center. […] Cytokines play a pivotal role in the immune response by activation of the B cells and T lymphocytes. The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favor of the protective role of fever.

• #75 Fever – Wikipedia

  https://en.wikipedia.org/wiki/Fever

  Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with body temperature exceeding the normal range due to an increase in the body’s temperature set point in the hypothalamus. […] The increase in set point triggers increased muscle contractions and causes a feeling of cold or chills. This results in greater heat production and efforts to conserve heat. […] When the set point temperature returns to normal, a person feels hot, becomes flushed, and may begin to sweat. […] The trigger of a fever, called a pyrogen, results in the release of prostaglandin E2 (PGE2). PGE2 in turn acts on the hypothalamus, which creates a systemic response in the body, causing heat-generating effects to match a new higher temperature set point. […] When the hypothalamic set point moves back to baseline either spontaneously or via medication normal functions such as sweating, and the reverse of the foregoing processes (e.g., vasodilation, end of shivering, and nonshivering heat production) are used to cool the body to the new, lower setting.

• #76 Fever – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/biology-of-infectious-disease/fever

  Body temperature is determined by the balance between heat production by tissues, particularly the liver and muscles, and heat loss from the periphery. […] Fever results when something raises the hypothalamic set point, triggering vasoconstriction and shunting of blood from the periphery to decrease heat loss; sometimes shivering, which increases heat production, is induced. […] Pyrogens are substances that cause fever. Exogenous pyrogens are usually microbes or their products. The best studied are the lipopolysaccharides of gram-negative bacteria (commonly called endotoxins) and Staphylococcus aureus toxin, which causes toxic shock syndrome. Fever is the result of exogenous pyrogens that induce release of endogenous pyrogens, such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and IL-6 and other cytokines, which then trigger cytokine receptors, or of exogenous pyrogens that directly trigger Toll-like receptors in the different intestinal epithelial lineages. […] Prostaglandin E2 synthesis appears to play a critical role.

• #77 Pathogenesis of Fever

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7122269/

  The induction of fever results in inhibition of bacterial growth, increased bactericidal effects of neutrophils, production of acute-phase protein synthesis and other physiological changes such as anorexia and somnolence. These changes suggest that fever has an adaptive role in the hosts survival during infection. […] The protective processes of the immune response are optimal at high temperature (around 39.5 C). […] The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favour of the protective role of fever.

• #78 Fever – All for Kids

  https://www.afkpeds.org/our-services/sick-kids/fever/

  Fever is caused by pyrogens which are substances released into the blood stream by the bodys white blood cells as they attack invading bacteria or viruses. […] Thus, fever is actually a signal to the rest of the bodys white blood cells that there is an infection present and that they should fight harder. […] Therefore fever is the normal response of the body to infection. […] With fever, bacteria and viruses are killed more efficiently. […] Fever alone caused by the normal infections that kids get, usually between 101 to 104 F, is not dangerous. […] Because serious illnesses do cause fever, your following our advice in this section may be crucial to your childs health. […] Fever is part of the defense mechanism of the body and as such is beneficial in fighting off infections. […] Fever is a physiologic signal to the white bloods cells in the body. They fight much harder in response to the presence of fever. […] Febrile seizures (seizures which occur with fever alone as the cause) do occur rarely with fever in young children. […] Although quite frightening when they occur, febrile seizures are harmless and result in no permanent brain damage.

• #79 Information About Fever in Children — Northwestern Children’s Practice

  https://www.nwcppediatrics.com/fever

  Fever in a child is one of the most common symptoms managed by pediatricians and is a frequent cause of parental concern. Fever accounts for one-third of all presenting conditions in children. Fever, however, is not the primary illness, but is a physiological mechanism that has beneficial effects in fighting infection. Fever slows the growth and reproduction of viruses and bacteria, and enhances the body’s immune response. Most fevers are of short duration, are benign and may actually be protective. Fever, in and of itself, is not known to endanger a generally healthy child; in contrast, fever actually may be of benefit. Some studies have shown that fever actually helps the body recover more quickly from viral infections. The degree of fever does not always correlate with the severity of illness. In addition, there is no evidence that fever worsens the course of an illness or that it causes long-term neurological complications.

• #80 Mayo Clinic Q and A: Child with recurrent fever may have periodic fever syndrome – Mayo Clinic News Network

  https://newsnetwork.mayoclinic.org/discussion/mayo-clinic-q-and-a-child-with-recurrent-fever-may-have-periodic-fever-syndrome/

  Some parents worry about the effects having a high fever on a regular basis may have on their child. But this condition doesn’t cause any long-term problems. And, contrary to popular belief, a fever itself is not dangerous. Usually, it’s the infection or other illness that accompanies a fever that causes health concerns. Because there is no underlying infection with periodic fever syndrome, other than making the child feel miserable, the fever is harmless.

• #81 Information About Fever in Children — Northwestern Children’s Practice

  https://www.nwcppediatrics.com/fever

  The primary goal of treating a child with a fever should be to improve the child’s comfort rather than focusing on the normalization of the body temperature. The desire to improve the overall comfort of the febrile child should be balanced against the desire to simply lower the body temperature. […] Many physicians continue to encourage the use of antipyretics, believing that most benefits result from improved comfort and the accompanying improvements in activity and feeding, less irritability, and a more reliable sense of the child’s overall clinical condition. Treating with fever medication does not prevent febrile seizures.

• #82 Peculiarities of the Pathogenesis of Fever in Childhood | ClinicSearch

  https://www.clinicsearchonline.org/article/peculiarities-of-the-pathogenesis-of-fever-in-childhood

  In this article, fever was analyzed as an important clinical symptom reflecting the body’s response to various pathogenic agents and inflammatory processes. […] Understanding its causes and consequences, as well as understanding the pathophysiological mechanisms underlying it, play a key role in the diagnosis and treatment of various diseases associated with hyperthermia.

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