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Last Build Date: Thu, 27 Apr 2017 08:34:40 GMT

 



TNFRSF13B/TACI

Thu, 27 Apr 2017 07:37:33 GMT

itself

New page

#redirect[[Tumor necrosis factor ligand superfamily member 13B]]



Atacicept

Wed, 26 Apr 2017 21:05:27 GMT

perhaps going no where

New page

{{PharmacologyBox}}
Atacicept is a recombinant fusion protein in development designed to inhibit B cells by inhibiting [[BAFF]] ([[TACI]]), thereby suppressing autoimmune disease.
[[Category:Unlicensed medicines]]
[[Category:Biologics]]



Tumor necrosis factor ligand superfamily member 13B

Wed, 26 Apr 2017 21:05:20 GMT

importance

← Older revision Revision as of 21:05, 26 April 2017
(One intermediate revision not shown)
Line 1: Line 1:
-
{{BiochemistryBox|||Tumor necrosis factor ligand superfamily member 13B, B-cell activating factor, B-cell-activating factor, B lymphocyte stimulator, dendritic cell-derived TNF-like molecule, TNF- and APOL-related leukocyte expressed ligand 1, BLyS, BAFF, TALL-1, [[CD257]]}}[[category:regulatory proteins]][[category:membrane proteins]][[category:cytokines]][[category:clusters of differentiation]]
+
{{BiochemistryBox|||Tumour necrosis factor ligand superfamily member 13B, B-cell activating factor, B-cell-activating factor, B lymphocyte stimulator, dendritic cell-derived TNF-like molecule, TNF- and APOL-related leukocyte expressed ligand 1, Transmembrane activator and CAML interactor, TACI, BLyS, BAFF, TALL-1, [[CD257]]}}[[category:regulatory proteins]][[category:membrane proteins]][[category:cytokines]][[category:clusters of differentiation]]
-
[[Tumour necrosis factor ligand superfamily member 13B]] (commonly known as BAFF or B-cell activating factor) is a 285 amino acid [[TNF]] analogue coded by the [[TNFSF13B]] gene at 13q32-q34 that regulates lymphocyte function. There are three isoforms. Isoform 1 which has membrane and soluble forms (after cleavage at amino acid 133) binds to:
+
[[Tumour necrosis factor ligand superfamily member 13B]] (more commonly known as TACI, BAFF or B-cell activating factor given its importance in immunity) is a 285 amino acid [[TNF]] analogue coded by the [[TNFSF13B]] gene at 13q32-q34 that regulates lymphocyte function. There are three isoforms. Isoform 1 which has membrane and soluble forms (after cleavage at amino acid 133) binds to:
*[[BAFFR/BR3]] a B-cell specific BAFF-receptor that promotes the survival of mature [[B-cell]]s and the B-cell response
*[[BAFFR/BR3]] a B-cell specific BAFF-receptor that promotes the survival of mature [[B-cell]]s and the B-cell response
*[[TNFRSF13B/TACI]]
*[[TNFRSF13B/TACI]]



Transmembrane activator and CAML interactor

Wed, 26 Apr 2017 21:02:06 GMT

redirect

New page

#redirect[[Tumor necrosis factor ligand superfamily member 13B]]



TACI

Wed, 26 Apr 2017 21:01:01 GMT

redirect

New page

#redirect[[Tumor necrosis factor ligand superfamily member 13B]]



Tumor necrosis factor ligand superfamily member 13B

Wed, 26 Apr 2017 20:54:20 GMT

autoimmunity risk and how to get to be very old ← Older revision Revision as of 20:54, 26 April 2017 Line 1: Line 1: {{BiochemistryBox|||Tumor necrosis factor ligand superfamily member 13B, B-cell activating factor, B-cell-activating factor, B lymphocyte stimulator, dendritic cell-derived TNF-like molecule, TNF- and APOL-related leukocyte expressed ligand 1, BLyS, BAFF, TALL-1, [[CD257]]}}[[category:regulatory proteins]][[category:membrane proteins]][[category:cytokines]][[category:clusters of differentiation]] {{BiochemistryBox|||Tumor necrosis factor ligand superfamily member 13B, B-cell activating factor, B-cell-activating factor, B lymphocyte stimulator, dendritic cell-derived TNF-like molecule, TNF- and APOL-related leukocyte expressed ligand 1, BLyS, BAFF, TALL-1, [[CD257]]}}[[category:regulatory proteins]][[category:membrane proteins]][[category:cytokines]][[category:clusters of differentiation]] -[[Tumour necrosis factor ligand superfamily member 13B]] is a 285 amino acid [[TNF]] analogue coded by the [[TNFSF13B]] gene at 13q32-q34 that regulates lymphocyte function. There are three isoforms. Isoform 1 which has membrane and soluble forms (after cleavage at amino acid 133) binds to:+[[Tumour necrosis factor ligand superfamily member 13B]] (commonly known as BAFF or B-cell activating factor) is a 285 amino acid [[TNF]] analogue coded by the [[TNFSF13B]] gene at 13q32-q34 that regulates lymphocyte function. There are three isoforms. Isoform 1 which has membrane and soluble forms (after cleavage at amino acid 133) binds to: *[[BAFFR/BR3]] a B-cell specific BAFF-receptor that promotes the survival of mature [[B-cell]]s and the B-cell response *[[BAFFR/BR3]] a B-cell specific BAFF-receptor that promotes the survival of mature [[B-cell]]s and the B-cell response *[[TNFRSF13B/TACI]] *[[TNFRSF13B/TACI]] Line 13: Line 13: Delta4BAFF (Isoform 3) acts as a transcription factor for its own parent gene, in association with the NF-kappa-B p50 subunit. This is important in autoimmune disease. It is essential for soluble BAFF release by IFNG/IFN-gamma-stimulated monocytes and for B-cell survival. It regulates the differential expression of a large number of genes involved in the innate immune response and the regulation of apoptosis. Delta4BAFF (Isoform 3) acts as a transcription factor for its own parent gene, in association with the NF-kappa-B p50 subunit. This is important in autoimmune disease. It is essential for soluble BAFF release by IFNG/IFN-gamma-stimulated monocytes and for B-cell survival. It regulates the differential expression of a large number of genes involved in the innate immune response and the regulation of apoptosis.  +  +This differential expression and function of BAFF causes issues so that an inhibitor such as [[atacicept]] is active in [[rheumatoid arthritis]] and causes more relapses in [[multiple sclerosis]]  +  +It was discovered in [[2017]] that a [[TNFSF13B]] variant that results in higher than normal BAFF levels in many of those of Sardinian descent was probably selected for because high BAFF levels reduce [[malaria]] infection, with side-effects possibly related to the enhanced [[humoral immunity]], both good and  bad  +#Longevity  +#Increased incidence [[multiple sclerosis]] (and see paradoxical effect [[atacicept]] above)  +#Increased incidence [[SLE]]Steri M et al. Overexpression of the cytokine BAFF and autoimmunity risk. NEJM 376:1615 2017 {{NoPMIDYet}} {{refsec}} {{refsec}}  +[[Category:Cytokines]] [...]



BAFF

Wed, 26 Apr 2017 20:36:07 GMT

redirect

← Older revision Revision as of 20:36, 26 April 2017
Line 1: Line 1:
-
#redirect[[Tumour necrosis factor ligand superfamily member 13B]]
+
#redirect[[Tumor necrosis factor ligand superfamily member 13B]]



RBBP8

Wed, 26 Apr 2017 20:33:11 GMT

subclude

New page

{{GeneticsBox|||CTIP}}
{{:DNA endonuclease RBBP8}}
[[Category:Genes]]



Jawad syndrome

Wed, 26 Apr 2017 20:31:05 GMT

subclude

New page

{{GeneticsBox|||JWDS}}
[[Category:Genetic syndromes]]
{{:DNA endonuclease RBBP8}}



Seckel syndrome 2

Wed, 26 Apr 2017 20:30:40 GMT

subclude

New page

{{GeneticsBox|||SCKL2}}
[[Category:Genetic syndromes]]
{{:DNA endonuclease RBBP8}}



DNA endonuclease RBBP8

Wed, 26 Apr 2017 20:28:59 GMT

typo

New page


{{BiochemistryBox|||CtBP-interacting protein, retinoblastoma-binding protein 8, retinoblastoma-interacting protein and myosin-like, sporulation in the absence of SPO11 protein 2 homolog, CtIP, RBBP-8, RIM, SAE2, EC:3.1.-.-}}
[[Category:enzymes]]
[[Category:endonucleases]]

The [[RBBP8]] gene codes for [[DNA endonuclease RBBP8]]. This endonuclease cooperates with the [[MRN complex]] in [[DNA]]-end resection, the first step of double-strand break repair through the homologous recombination pathway. This pathway is restricted to S and G2 phases of the cell cycle and preferentially repairs double-strand breaks resulting from replication fork collapse. If active it prevents cells using the classical non-homologous end-joining (NHEJ) double-strand break repair.

Mutations of [[RBBP8]] are associated with:
#[[Seckel syndrome 2]] (SCKL2, {{OMIM|606744}})
#*Rare autosomal recessive disorder with proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and mental retardation.
#[[Jawad syndrome]] (JWDS, {{OMIM|251255}})
#*Characterized by congenital microcephaly, moderately severe mental retardation, and symmetrical digital anomalies.
#[[BRCA1]]-associated breast cancer risk and sensitivity to [[tamoxifen]].



NF-kappa B

Wed, 26 Apr 2017 20:10:58 GMT

redirect

New page

#redirect[[Nuclear factor-kappaB]]



Nuclear factor NF-kappa-B p105 subunit

Wed, 26 Apr 2017 20:10:05 GMT

subclude

New page

{{BiochemistryBox|||DNA-binding factor KBF1, nuclear factor of kappa light polypeptide gene enhancer in B-cells 1, EBP-1}}
[[Category:Transcription factors]]
{{:NFKB1}}



NFKB1

Wed, 26 Apr 2017 20:07:01 GMT

gene

New page


{{GeneticsBox}}
[[Category:Genes]]

The [[NFKB1]] gene at 4q24 codes for the 968 amino acid [[nuclear factor NF-kappa-B p105 subunit]]. Both the p105 inhibitor form and shorter cleaved p50 form (433 amino acids) formed by cotranslational processing which is the active acceptable substrate for the [[proteasome]] are components of the [[NF-kappa-B]] [[transcription factor]]. However the unprocessed form acts as an inhibitor (I kappa B-like), being able to form cytosolic complexes with [[NF-kappa B]], trapping it in the cytoplasm.

Common variable immunodeficiency 12 (CVID12, {{OMIM|616576}}) is caused by mutations in this gene.
[[Category:immunology]]



SIRT6

Wed, 26 Apr 2017 19:50:37 GMT

wikify ← Older revision Revision as of 19:50, 26 April 2017 Line 3: Line 3: [[Category:Genes]] [[Category:Genes]] -The [[SIRT6]] gene at 19p13.3 codes for the 354 amino acid [[zinc]] containing [[NAD-dependent protein deacetylase sirtuin-6]]. Two isoforms are produced by alternative splicing. It is a [[:Category:Sirtuins|sirtuin]] that localises to the [[nucleus]]. By analogy and association studies in man it would appear to be a key protein deacetylase acting on histones and involved in genomic stability and ageing pathology. In mice it has neuroprotective functions as knockout results in rapid CNS neurodegeration as there is a failure to regulates Tau protein stability[https://www.ncbi.nlm.nih.gov/sites/entrez?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=28355558  Kaluski S, Portillo M, Besnard A, Stein D, Einav M, Zhong L, Ueberham U, Arendt T, Mostoslavsky R, Sahay A, Toiber D. Neuroprotective Functions for the Histone Deacetylase SIRT6. Cell reports. 2017 Mar; 18(13):3052-3062.](Print) ([http://dx.doi.org/10.1016/j.celrep.2017.03.008 Link to article] – subscription may be required.). Alzheimer's disease is associated with low expression. Certain polymorphism are associated with longevity and healthy aging[https://www.ncbi.nlm.nih.gov/sites/entrez?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=28399814  Hirvonen K, Laivuori H, Lahti J, Strandberg T, Eriksson JG, Hackman P. SIRT6 polymorphism rs117385980 is associated with longevity and healthy aging in Finnish men. BMC medical genetics. 2017 Apr; 18(1):41.](Electronic) ([http://dx.doi.org/10.1186/s12881-017-0401-z Link to article] – subscription may be required.). As a corepressor of transcription factors it for example controls the expression of multiple glycolytic genes to regulate glucose homeostasis and expression of tumour necrosis factor. It has a binary interaction with [[transcription factor p65]] which is a subunit of nuclear factor NF-kappa-B. On DNA damage, promotes DNA end resection via deacetylation of [[DNA endonuclease RBBP8]]. It, like other [[:Category:Sirtuins|sirtuins]] is involved in ageing and neurodegeneration, malignancy and the bodies response to inflammation[https://www.ncbi.nlm.nih.gov/sites/entrez?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=27882448  Jęśko H, Wencel P, Strosznajder RP, Strosznajder JB. Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders. Neurochemical research. 2017 Mar; 42(3):876-890.](Print-Electronic) ([http://dx.doi.org/10.1007/s11064-016-2110-y Link to article] – subscription may be required.).+The [[SIRT6]] gene at 19p13.3 codes for the 354 amino acid [[zinc]] containing [[NAD-dependent protein deacetylase sirtuin-6]]. Two isoforms are produced by alternative splicing. It is a [[:Category:Sirtuins|sirtuin]] that localises to the [[nucleus]]. By analogy and association studies in man it would appear to be a key protein deacetylase acting on histones and involved in genomic stability and ageing pathology. In mice it has neuroprotective functions as knockout results in rapid CNS neurodegeration as there is a failure to regulates Tau protein stability[https://www.ncbi.nlm.nih.gov/sites/entrez?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstra[...]



Transcription factor p65

Wed, 26 Apr 2017 19:48:40 GMT

another name

← Older revision Revision as of 19:48, 26 April 2017
Line 1: Line 1:
-
{{BiochemistryBox|||Nuclear factor NF-kappa-B p65 subunit, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, V-REL avian reticuloendotheliosis viral oncogene homolog A, nuclear factor kappa-B subunit 3, transcription factor NFKB3}}
+
{{BiochemistryBox|||Nuclear factor NF-kappa-B p65 subunit, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, V-REL avian reticuloendotheliosis viral oncogene homolog A, nuclear factor kappa-B subunit 3, transcription factor NFKB3, relA}}
[[Category:Transcription factors]]
[[Category:Transcription factors]]



Nuclear factor-kappaB

Wed, 26 Apr 2017 19:47:47 GMT

categorise

← Older revision Revision as of 19:47, 26 April 2017
Line 46: Line 46:
[[Category:Biochemistry]][[Category:Immunology]]
[[Category:Biochemistry]][[Category:Immunology]]
{{refsec}}
{{refsec}}
 +
[[Category:transcription factors]]



RELA

Wed, 26 Apr 2017 19:46:54 GMT

oncogene

New page

{{GeneticsBox|||NFKB3}}
[[Category:Oncogenes]]
[[Category:Genes]]
{{:Transcription factor p65}}



Transcription factor p65

Wed, 26 Apr 2017 19:44:56 GMT

transcription factor

New page


{{BiochemistryBox|||Nuclear factor NF-kappa-B p65 subunit, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, V-REL avian reticuloendotheliosis viral oncogene homolog A, nuclear factor kappa-B subunit 3, transcription factor NFKB3}}
[[Category:Transcription factors]]

The [[RELA]] gene at 11q13.1 codes for the 551 amino acid [[transcription factor p65]] a common subunit of the [[Nuclear factor-kappaB|NF-kappa-B]] [[transcription factor]]. In the cytoplasm it has been found in an inactive form complexed to an inhibitor (I-kappa-B). There are four isoforms generated by alternative splicing and there is complex post translation modification. Its different dimer combinations act as transcriptional activators or repressors. Indeed the heterodimeric complex form of [[NF-kappa-B]] with the first 433 amino acids of [[nuclear factor NF-kappa-B p105 subunit]] (p50) is most abundant and a transcriptional activator although [[NF-kappa-B]]/[[nuclear factor NF-kappa-B p105 subunit]] and homodimers of [[transcription factor p65]] (involved in activation of [[IL-8]] expression) are also active.

The gene on translocation with [[C11orf95]] forms the C11orf95-RELA fusion protein important in the aetiology of two-thirds of supratentorial [[ependymoma]]s.



Category:Sirtuins

Tue, 25 Apr 2017 20:09:20 GMT

categorise

← Older revision Revision as of 20:09, 25 April 2017
Line 2: Line 2:
The seven sirtuins are [[histone]] deacetylases whose activity depends on cellular [[NAD]]+ levels and thus on the cellular metabolic status. They help regulate energy metabolism and mitochondrial function, the stress response and damage repair. Some modulate the course of aging, neurodegenerative disease and malignancy.
The seven sirtuins are [[histone]] deacetylases whose activity depends on cellular [[NAD]]+ levels and thus on the cellular metabolic status. They help regulate energy metabolism and mitochondrial function, the stress response and damage repair. Some modulate the course of aging, neurodegenerative disease and malignancy.
[[Category:regulatory proteins]]
[[Category:regulatory proteins]]
 +
[[Category:Geriatric Medicine]]
 +
[[Category:Oncology]]
 +
[[Category:Inflammation]]
 +
[[Category:Dementia]]



NAD-dependent protein deacetylase sirtuin-6

Tue, 25 Apr 2017 20:06:17 GMT

← Older revision Revision as of 20:06, 25 April 2017
Line 2: Line 2:
[[Category:Sirtuins]]
[[Category:Sirtuins]]
{{:SIRT6}}
{{:SIRT6}}
-
[[Category:regulatory:proteins]]
+
[[Category:regulatory proteins]]



Category:Sirtuins

Tue, 25 Apr 2017 20:06:06 GMT

← Older revision Revision as of 20:06, 25 April 2017
(One intermediate revision not shown)
Line 1: Line 1:
[[Category:Enzymes]]
[[Category:Enzymes]]
The seven sirtuins are [[histone]] deacetylases whose activity depends on cellular [[NAD]]+ levels and thus on the cellular metabolic status. They help regulate energy metabolism and mitochondrial function, the stress response and damage repair. Some modulate the course of aging, neurodegenerative disease and malignancy.
The seven sirtuins are [[histone]] deacetylases whose activity depends on cellular [[NAD]]+ levels and thus on the cellular metabolic status. They help regulate energy metabolism and mitochondrial function, the stress response and damage repair. Some modulate the course of aging, neurodegenerative disease and malignancy.
 +
[[Category:regulatory proteins]]



NAD-dependent protein deacetylase sirtuin-6

Tue, 25 Apr 2017 20:05:27 GMT

subclude

New page

{{BiochemistryBox|||Regulatory protein SIR2 homolog 6, SIR2-like protein 6, sirtuin 6}}
[[Category:Sirtuins]]
{{:SIRT6}}
[[Category:regulatory:proteins]]



Category:Sirtuins

Tue, 25 Apr 2017 20:02:53 GMT

definition

New page

[[Category:Enzymes]]
The seven sirtuins are [[histone]] deacetylases whose activity depends on cellular [[NAD]]+ levels and thus on the cellular metabolic status. They help regulate energy metabolism and mitochondrial function, the stress response and damage repair. Some modulate the course of aging, neurodegenerative disease and malignancy.



SIRT6

Tue, 25 Apr 2017 19:59:22 GMT

for subclusion

New page


{{GeneticsBox|||SIR2L6}}
[[Category:Genes]]

The [[SIRT6]] gene at 19p13.3 codes for the 354 amino acid [[zinc]] containing [[NAD-dependent protein deacetylase sirtuin-6]]. Two isoforms are produced by alternative splicing. It is a [[:Category:Sirtuins|sirtuin]] that localises to the [[nucleus]]. By analogy and association studies in man it would appear to be a key protein deacetylase acting on histones and involved in genomic stability and ageing pathology. In mice it has neuroprotective functions as knockout results in rapid CNS neurodegeration as there is a failure to regulates Tau protein stability[https://www.ncbi.nlm.nih.gov/sites/entrez?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=28355558 Kaluski S, Portillo M, Besnard A, Stein D, Einav M, Zhong L, Ueberham U, Arendt T, Mostoslavsky R, Sahay A, Toiber D. Neuroprotective Functions for the Histone Deacetylase SIRT6. Cell reports. 2017 Mar; 18(13):3052-3062.](Print) ([http://dx.doi.org/10.1016/j.celrep.2017.03.008 Link to article] – subscription may be required.). Alzheimer's disease is associated with low expression. Certain polymorphism are associated with longevity and healthy aging[https://www.ncbi.nlm.nih.gov/sites/entrez?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=28399814 Hirvonen K, Laivuori H, Lahti J, Strandberg T, Eriksson JG, Hackman P. SIRT6 polymorphism rs117385980 is associated with longevity and healthy aging in Finnish men. BMC medical genetics. 2017 Apr; 18(1):41.](Electronic) ([http://dx.doi.org/10.1186/s12881-017-0401-z Link to article] – subscription may be required.). As a corepressor of transcription factors it for example controls the expression of multiple glycolytic genes to regulate glucose homeostasis and expression of tumour necrosis factor. It has a binary interaction with [[transcription factor p65]] which is a subunit of nuclear factor NF-kappa-B. On DNA damage, promotes DNA end resection via deacetylation of [[DNA endonuclease RBBP8]]. It, like other [[:Category:Sirtuins|sirtuins]] is involved in ageing and neurodegeneration, malignancy and the bodies response to inflammation[https://www.ncbi.nlm.nih.gov/sites/entrez?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=27882448 Jęśko H, Wencel P, Strosznajder RP, Strosznajder JB. Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders. Neurochemical research. 2017 Mar; 42(3):876-890.](Print-Electronic) ([http://dx.doi.org/10.1007/s11064-016-2110-y Link to article] – subscription may be required.).
{{refsec}}



Talk:Main Page

Mon, 24 Apr 2017 06:58:37 GMT

certainly more stable but far from perfect ← Older revision Revision as of 06:58, 24 April 2017 (One intermediate revision not shown)Line 181: Line 181: :::::::::::::::::::::Continues very sick. Fell over when reached MAXCLIENTS of 7 and loss DataBase connection - used to be 10 so I am increasing more slowly just to see if lasts longer [[User:Mlj|Mlj]] 22:18, 11 April 2017 (BST) :::::::::::::::::::::Continues very sick. Fell over when reached MAXCLIENTS of 7 and loss DataBase connection - used to be 10 so I am increasing more slowly just to see if lasts longer [[User:Mlj|Mlj]] 22:18, 11 April 2017 (BST) :::::::::::::::::::::Now seeing if main memory leak was in skins - reverted to 2009 version with a few tidy ups - successfully to date - have not yet updated file upload php on principle some php in v1.16.5 may be causing leak[[User:Mlj|Mlj]] 21:53, 14 April 2017 (BST) :::::::::::::::::::::Now seeing if main memory leak was in skins - reverted to 2009 version with a few tidy ups - successfully to date - have not yet updated file upload php on principle some php in v1.16.5 may be causing leak[[User:Mlj|Mlj]] 21:53, 14 April 2017 (BST) -::::::::::::::::::::::Been in logs this afternoon as server had gone crazy again. Memory leak seems to have been created by a very badly behaviour from bots from range IP range 46.229.168.65 to 46.229.168.75 as before which were not being blocked from php engine or robots.txt. These bots were giving very complex commands including redirection, hidemyself and chasing down every edit a page had had with no lag time, hidden amongst more benign but uncontrolled harvesting. Effectively we have been under a DoS attack from www.semrush.com. It seems the error_log file from Apache will get very big now but if machine survives tonight I will see if I can rotate. Our bot site load has doubled since Jan 2017 due to this (have pretty graph going back to 2010 that shows bot activity had increased over 50 fold since 2014 but was silent to site and our google monitoring by marketing orientated design. Oh well. They will no doubt try other tricks. [[User:Mlj|Mlj]] 23:47, 23 April 2017 (BST)+::::::::::::::::::::::Been in logs this afternoon as server had gone crazy again. [[Image:SiteActivityIncludingBots.png|thumb|Site activity including silent bots]] Memory leak significance seems to have been created by a very badly behaviour from bots from range IP range 46.229.168.65 to 46.229.168.75 as before which were not being blocked from php engine or robots.txt. These bots were giving very complex commands including redirection, hidemyself and chasing down every edit a page had had with no lag time, hidden amongst more benign but uncontrolled harvesting. Effectively we have been under a DoS attack from www.semrush.com. It seems the error_log file from Apache will get very big now but if machine survives tonight I will see if I can rotate. Our bot site load has doubled since Jan 2017 due to this (have pretty graph going back to 2010 that shows bot activity had increased over 50 fold since 2014 but was silent to site and our google monitoring by marketing orientated design. Oh well. They will no doubt try other tricks. Server has been stable for a few hours now [[User:Mlj|Mlj]] 23:47, 23 April 2017 (BST)  +::::::::::::::::::::::Memory leak could still bring server down within a few days reckon. Monitoring and a[...]



File:SiteActivityIncludingBots.png

Sun, 23 Apr 2017 23:33:15 GMT

uploaded "[[File:SiteActivityIncludingBots.png]]" Site Activity including bots




Talk:Main Page

Sun, 23 Apr 2017 22:47:45 GMT

Site may be stable for a while. Been bot killing. Touch wood. ← Older revision Revision as of 22:47, 23 April 2017 Line 181: Line 181: :::::::::::::::::::::Continues very sick. Fell over when reached MAXCLIENTS of 7 and loss DataBase connection - used to be 10 so I am increasing more slowly just to see if lasts longer [[User:Mlj|Mlj]] 22:18, 11 April 2017 (BST) :::::::::::::::::::::Continues very sick. Fell over when reached MAXCLIENTS of 7 and loss DataBase connection - used to be 10 so I am increasing more slowly just to see if lasts longer [[User:Mlj|Mlj]] 22:18, 11 April 2017 (BST) :::::::::::::::::::::Now seeing if main memory leak was in skins - reverted to 2009 version with a few tidy ups - successfully to date - have not yet updated file upload php on principle some php in v1.16.5 may be causing leak[[User:Mlj|Mlj]] 21:53, 14 April 2017 (BST) :::::::::::::::::::::Now seeing if main memory leak was in skins - reverted to 2009 version with a few tidy ups - successfully to date - have not yet updated file upload php on principle some php in v1.16.5 may be causing leak[[User:Mlj|Mlj]] 21:53, 14 April 2017 (BST)  +::::::::::::::::::::::Been in logs this afternoon as server had gone crazy again. Memory leak seems to have been created by a very badly behaviour from bots from range IP range 46.229.168.65 to 46.229.168.75 as before which were not being blocked from php engine or robots.txt. These bots were giving very complex commands including redirection, hidemyself and chasing down every edit a page had had with no lag time, hidden amongst more benign but uncontrolled harvesting. Effectively we have been under a DoS attack from www.semrush.com. It seems the error_log file from Apache will get very big now but if machine survives tonight I will see if I can rotate. Our bot site load has doubled since Jan 2017 due to this (have pretty graph going back to 2010 that shows bot activity had increased over 50 fold since 2014 but was silent to site and our google monitoring by marketing orientated design. Oh well. They will no doubt try other tricks. [[User:Mlj|Mlj]] 23:47, 23 April 2017 (BST) ==pubmed_caption_finder== ==pubmed_caption_finder== This has to be updated given PubMed's shift to https from tomorrow. From today it will generate https references BUT  the module still uses http call in php (as https call not recognised) to get all the info. This will no doubt change and give us message "Unable to contact Pubmed. This may be transient - please try again later. If this error recurs, please contact a ganfyd admin." If in due course I can enable php to do https I have version 20 of the module uploaded and ready to go and replace present version 21 (we were on version 19 before today) Cheers[[User:Mlj|Mlj]] 18:37, 26 September 2016 (BST) This has to be updated given PubMed's shift to https from tomorrow. From today it will generate https references BUT  the module still uses http call in php (as https call not recognised) to get all the info. This will no doubt change and give us message "Unable to contact Pubmed. This may be transient - please try again later. If this error recurs, please contact a ganfyd admin." If in due course I can enable php to do https I have version 20 of the module uploaded and ready to go and replace pres[...]



Doctors support organisations

Sat, 22 Apr 2017 21:08:47 GMT

← Older revision Revision as of 21:08, 22 April 2017 Line 1: Line 1: {{SubjectBox}} {{SubjectBox}} Sources of support for doctors include [[Medical indemnity|medical defence organisations ]] and [[Medical trade unions|medical trade unions]]. Sources of support for doctors include [[Medical indemnity|medical defence organisations ]] and [[Medical trade unions|medical trade unions]].  +  +[https://www.doctorshelp.org.uk/ Help me, I'm a doctor] is a portal, established in [[2017]], to help doctors in difficulties to find the most suitable charity to apply to, from the following five charities: [https://www.bma.org.uk/about-us/who-we-are/bma-charities BMA Charities]; [http://www.cameronfund.org.uk/ the Cameron Fund]; [http://www.rmbf.org/ the Royal Medical Benevelont Fund]; and [http://www.samf.org.uk/ the Society for the Assistance of Medical Families (formerly Widows & Orphans)]. In addition, the following organisations (and there are probably many others) exist to support doctors in need. In addition, the following organisations (and there are probably many others) exist to support doctors in need. *[http://www.doctorssupportgroup.com/ The Doctors Support Group (DSG)]. ''"The Doctors Support Group (DSG) Aims To Provide Support And Assistance To Any Medical Professional Or Dentist Facing Suspension, Exclusion, Investigation Of Complaints And/Or Allegations Of Professional Misconduct."'' *[http://www.doctorssupportgroup.com/ The Doctors Support Group (DSG)]. ''"The Doctors Support Group (DSG) Aims To Provide Support And Assistance To Any Medical Professional Or Dentist Facing Suspension, Exclusion, Investigation Of Complaints And/Or Allegations Of Professional Misconduct."'' -*[http://www.bma.org.uk/doctors_health/index.jsp British Medical Association's Doctors for Doctors service]. ''"Confidential, nationwide, non-stop advice and counselling for doctors and medical students."'' Apparently you don't have to be a BMA member to call them.+*[http://www.bma.org.uk/doctors_health/index.jsp British Medical Association's Doctors for Doctors service]. ''"Confidential, nationwide, non-stop advice and counseling for doctors and medical students."'' Apparently you don't have to be a BMA member to call them. *[http://www.sick-doctors-trust.co.uk/ The Sick Doctors Trust]: ''"a wholly independent and confidential organisation, established in 1996, which offers support and help to doctors and medical students suffering any degree of dependence on drugs or alcohol. Our helpline, 0370 444 5163, is available 24 hours/day throughout the year and we are happy to deal with anonymous enquiries. Alternatively, we can be reached by email on help@sick-doctors-trust.co.uk."'' *[http://www.sick-doctors-trust.co.uk/ The Sick Doctors Trust]: ''"a wholly independent and confidential organisation, established in 1996, which offers support and help to doctors and medical students suffering any degree of dependence on drugs or alcohol. Our helpline, 0370 444 5163, is available 24 hours/day throughout the year and we are happy to deal with anonymous enquiries. Alternatively, we can be reached by email on help@sick-doctors-trust.co.uk."'' *[http://www.dsn.org.uk/ Doctors' Support Network and phone [...]



Trazodone

Thu, 20 Apr 2017 20:22:46 GMT

typo ← Older revision Revision as of 20:22, 20 April 2017 (One intermediate revision not shown)Line 4: Line 4: ==Introduction== ==Introduction== -A potential neuroprotective agent but its known side effect profile mean it is unlikely to be tolerated well in those without symptoms. Indeed its wide use out of license[https://www.ncbi.nlm.nih.gov/sites/entrez?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=28228380  Wong J, Motulsky A, Abrahamowicz M, Eguale T, Buckeridge DL, Tamblyn R. Off-label indications for antidepressants in primary care: descriptive study of prescriptions from an indication based electronic prescribing system. BMJ (Clinical research ed.). 2017 Feb; 356:j603.](Electronic) ([http://dx.doi.org/10.1136/bmj.j603 Link to article] – subscription may be required.) in conditions such as [[frontotemporal dementia]][https://www.ncbi.nlm.nih.gov/sites/entrez?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=15178953  Lebert F, Stekke W, Hasenbroekx C, Pasquier F. Frontotemporal dementia: a randomised, controlled trial with trazodone. Dementia and geriatric cognitive disorders. 2004 ; 17(4):355-359.](Print) ([http://dx.doi.org/10.1159/000077171 Link to article] – subscription may be required.) and [[Alzheimers disease]]24495406 suggest in established disease minimal benefit in terms of disease progression in most but some useful actions. Its useful actions tend to take a few weeks to show benefit while side effects such as sedation and falls (due to alpha-1 receptor blockade) tend to manifest more rapidly.+A potential neuroprotective agent but its known side effect profile mean it is unlikely to be tolerated well in those without symptoms. Indeed its wide use out of license[https://www.ncbi.nlm.nih.gov/sites/entrez?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=28228380  Wong J, Motulsky A, Abrahamowicz M, Eguale T, Buckeridge DL, Tamblyn R. Off-label indications for antidepressants in primary care: descriptive study of prescriptions from an indication based electronic prescribing system. BMJ (Clinical research ed.). 2017 Feb; 356:j603.](Electronic) ([http://dx.doi.org/10.1136/bmj.j603 Link to article] – subscription may be required.) in conditions such as [[frontotemporal dementia]][https://www.ncbi.nlm.nih.gov/sites/entrez?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=15178953  Lebert F, Stekke W, Hasenbroekx C, Pasquier F. Frontotemporal dementia: a randomised, controlled trial with trazodone. Dementia and geriatric cognitive disorders. 2004 ; 17(4):355-359.](Print) ([http://dx.doi.org/10.1159/000077171 Link to article] – subscription may be required.) and [[Alzheimers disease]][https://www.ncbi.nlm.nih.gov/sites/entrez?itool=abstract[...]



Torsade de Pointes

Thu, 20 Apr 2017 07:42:06 GMT

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Syndrome of inappropriate antidiuretic hormone release

Thu, 20 Apr 2017 07:41:12 GMT

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==Introduction==
==Introduction==
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Syndrome of inappropriate [[anti-diuretic hormone]] release (SIADH) is a common cause of [[hyponatraemia]] and is a final pathway of many pathologies that produce [[hyponatraemia]]. Many patients present with a mixed aetiology so may not meet the following prerequisities. A mistake often made in acute hospital medicine is to label and even manage a patient as SIADH when the most important issue is water intoxication, which would be clear from inspection of a fluid balance chart, recent prostate surgery or even an oral history of recent fluid intake.
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Syndrome of inappropriate [[anti-diuretic hormone]] release (SIADH, syndrome of inappropriate antidiuretic hormone secretion) is a common cause of [[hyponatraemia]] and is a final pathway of many pathologies that produce [[hyponatraemia]]. Many patients present with a mixed aetiology so may not meet the following prerequisities. A mistake often made in acute hospital medicine is to label and even manage a patient as SIADH when the most important issue is water intoxication, which would be clear from inspection of a fluid balance chart, recent prostate surgery or even an oral history of recent fluid intake.
==Prerequisites==
==Prerequisites==



Syndrome of inappropriate antidiuretic hormone secretion

Thu, 20 Apr 2017 07:40:05 GMT

redirect

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#redirect[[Syndrome of inappropriate antidiuretic hormone release]]



Trazodone

Thu, 20 Apr 2017 07:38:37 GMT

better update as in the news - likely flash in the pan ← Older revision Revision as of 07:38, 20 April 2017 Line 4: Line 4: ==Introduction== ==Introduction== - +A potential neuroprotective agent but its known side effect profile mean it is unlikely to be tolerated well in those without symptoms. Indeed its wide use out of license[https://www.ncbi.nlm.nih.gov/sites/entrez?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=28228380  Wong J, Motulsky A, Abrahamowicz M, Eguale T, Buckeridge DL, Tamblyn R. Off-label indications for antidepressants in primary care: descriptive study of prescriptions from an indication based electronic prescribing system. BMJ (Clinical research ed.). 2017 Feb; 356:j603.](Electronic) ([http://dx.doi.org/10.1136/bmj.j603 Link to article] – subscription may be required.) in conditions such as [[frontotemporal dementia]][https://www.ncbi.nlm.nih.gov/sites/entrez?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=15178953  Lebert F, Stekke W, Hasenbroekx C, Pasquier F. Frontotemporal dementia: a randomised, controlled trial with trazodone. Dementia and geriatric cognitive disorders. 2004 ; 17(4):355-359.](Print) ([http://dx.doi.org/10.1159/000077171 Link to article] – subscription may be required.) and [[Alzheimers disease]]24495406 suggest in established disease minimal benefit in terms of disease progression in most but some useful actions. Its useful actions tend to take a few weeks to show benefit while side effects such as sedation and falls (due to alpha-1 receptor blockade) tend to manifest more rapidly. ==Clinical Use== ==Clinical Use== - +Only in adults. ===Indications=== ===Indications=== *Depressive illness. Low doses (eg 50mg )have a predominant sedative action. *Depressive illness. Low doses (eg 50mg )have a predominant sedative action. Line 16: Line 16: ==Clinical Issues== ==Clinical Issues== - +Often used out of license as low anticholinergic burden and in low doses useful sedative properties. Can be poorly tolerated due to orthostatic hypotension and associated with suicidal behaviour and hostility in those less than 18. ===Contra-indications=== ===Contra-indications=== - +*Alcohol intoxication  +*Hypnotic intoxication  +*Acute [[myocardial infarction]]  +*Jaundice  +*[[Priapism]] - discontinue immediately ===Cautions and Interactions=== ===Cautions and Interactions=== - +*QT prolonging  +*Epilepsy  +*Severe hepatic or renal impairment  +*Cardiac disease, including angina, conduction disorders or AV block, recent myocardial infarction  +*[[Hyperthyroidism]]  +*Paranoia (can make worse) ===Side effects=== ===Side effects=== - +*[[Orthostatic hypotension]]  +*[[Sedation]]  +*Sexual arousal  +*[[Syncope]]  +*[[Agranulocytosis]]  +*[[Hyponatraemia]] ([[syndrome of inap[...]