5 May 2015
(1) A person in the UK who educates or mentors students–e.g., a senior GP educationalist, who works under the director and supervising other GP educators; professional educator
(2) A person who studies the process of learning
PSYCHIATRY A persistent and painful pattern of feelings, behaviours, and perceptions among two or more people in an important personal relationship, such as a husband and wife, or a parent and one or more of their children. Relational disorder is a departure from the other mental health conditions, in that the disorder is not defined by individuals, but rather by the pathological junction or interaction between them–i.e., by the relationship itself.
Relational disorder was proposed as a condition a sui generis. Some workers believed that it should have been included in the 5th edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders–DSM 5 (2013); it was not accepted.
Relational disorder types
• Marital relational disorder
• Parent–child abuse disorder
CELL BIOLOGY Rho-associated, coiled-coil containing protein kinase 1, EC 22.214.171.124, p160ROCK, Renal carcinoma antigen NY-REN-35,Rho-associated, coiled-coil-containing protein kinase 1, Rho kinase, Rho-associated, coiled-coil-containing protein kinase I A gene on chromosome 18q11.1 that encodes a protein kinase, which is a key regulator of actin cytoskeleton and cell polarity. It regulates smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, PFN1 and PPP1R12A.
It phosphorylates FHOD1 and both promote SRC-dependent non-apoptotic plasma membrane blebbing; phosphorylates JIP3 and regulates JNK to JIP3 recruitment in response to UVB-induced stress; suppresses inflammatory cell migration by regulating PTEN phosphorylation and stability; down-regulates VEGF-induced angiogenic endothelial cell activation; promotes keratinocyte terminal differentiation; and plays a role in terminal erythroid differentiation. ROCK1 is required for centrosome positioning and centrosome-dependent exit from mitosis. It may regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles.
Roy Harold Scherer, Jr. (1925-1985), was an American film and television actor and heart-throb, best known as a lead actor in the 1950s and 1960s, often starring opposite Doris Day. There is no way that a man this good looking could be heterosexual. When Rock Hudson was diagnosed with AIDS, 1 billion women murmured in unison, What a waste.
EVIDENCE-BASED MEDICINE A clinical trial term of art for a potential subject/patient who did not meet one or more criteria at screening which was required for participation in the study.
SUBSTANCE ABUSE Bath salts A family of compounds–e.g., 3,4-methylenedioxy- pyrovalerone–MDPV, 4-methylmethcathinone–mephedrone, and 3,4-methylenedioxy-N-methylcathinone–methylone, all of which are related to naturally occurring cathinones derived from the khat plant—Catha edulis and structurally similar to amphetamines.
Synthetic cathinones have been formally marketed as bath salts, plant food and other innocuous products, allowing them to be sold over the counter and until recently escape the FDA’s ability to regulate what is informally billed as “legal cocaine” or “poor man’s cocaine”.
The term bath salts has been (incorrectly) used interchangeably with synthetic cathinones; (illicit) bath salts include substituted amphetamines and substituted phenethylamines.
Epidemiology Abuse of synthetic cathinones is a growing epidemic, evoking nearly 6000 calls to poison centres in the US in 2011.
Route of ingestion Injection, snorting, by mouth
Desired effects Euphoria, elevated mood, increased alertness, allegedly aphrodisiac
Adverse effects Tachycardia, hypertension, hyperthermia, profuse sweating, seizures, automatisms, mydriasis, paranoia, irritability, anxiety, suicidal ideation, suicide, serotonergic syndrome, and kidney damage due to rhabdomyolysis, ischaemia, hypoperfusion. Over half of users studied had neurologic (91%), cardiovascular (77%), and psychological (49%) involvement
Legal status Synthetic cathinones were among the 31 substances banned in US President Obama’s 2012 antidrug bill. Unfortunately, the kitchen chemists have already begun producing agents that escape detection, including halogenated compounds, which are increasingly popular “bath salts”.
4 May 2015
ENVIRONMENT, GLOBAL VILLAGE A herbicide contaminated with 1-20 ppm of 2,3,7,8-tetrachlorodibenzo-p-dioxin–TCDD, causing chloracne, cancer, altered enzyme levels, porphyrin metabolism, immune dysfunction and birth defects of biblical magnitude, because TCDD stores in adipose tissue, its long-term effects are currently unknown*
Agent Orange is a 50:50 mixture of 2,4-D n-butyl ester or 2,4-dichlorophenoxyacetic and 2,4,5-T n-butyl ester or trichlorophenoxyacetic acids in a diesel oil vehicle; AO was used as a general defoliant for forest, brush, broad-leafed crops in Southeast Asia by the American forces as a tactic of warfare, to destroy the jungles that served Viet Cong guerillas during the Vietnam conflict as camouflage; experiments with defoliant chemicals as herbicides began during World War II and four agents of potential military use were weeded out of the 12,000 chemicals tested; the US defoliation effort in Vietnam began in late 1961 and by the time the aerial defoliation program–Operation Ranch Hand ended in 1968, 6603 square miles–17,300 km2 had been sprayed with defoliant, predominantly AO, mostly from fixed wing aircraft.
The lawsuit brought by the exposed Vietnam veterans resulted in a $180 million settlement. The Vietnamese, who suffered terrible birth defects, got jack…God bless America…
ORTHOPAEDICS Arthroerisis A soft tissue movement-limiting operation, in which an implant is placed to restrict joint motion–e.g., that seen in flatfoot. The goals of arthroerisis in the ankle are to restrict excessive range of motion–ROM in the subtalar joint, allowing up to 5% range of motion, while preserving joint functionality. Indications Above age 3, flexible foot type, asymptomatic foot pathology
Complications System formation, silastic breakdown synovitis, device migration, over- or under correction, lateral foot and ankle soft tissue strain.
Note: Advances in prosthetic devices, and variable success rates with surgery designed to limit movement have made arthrodesis and joint replacement the procedures of choice in many cases of articular instability
EVIDENCE-BASED MEDICINE Refutable hypothesis A hypothesis stated with enough precision that it can be tested by acceptable rules of logic, empirical and statistical evidence, and thereby confirmed or disconfirmed.
All valid scientific hypotheses must be falsifiable.
fixed effect model
EVIDENCE-BASED MEDICINE A statistical model that stipulates that the units being analysed–e.g. people in a trial or studies in a meta-analysis, are the ones of interest, and thus constitute the entire population of units. Only within-study variation is taken to influence the uncertainty of results (as reflected in the confidence interval) of a meta-analysis using a fixed-effect model. Variation between the estimates of effect from each study (heterogeneity) does not affect the confidence interval in a fixed-effect model.
Reference Cochrane definition, in www.nsc.nhs.uk/glossary/glossary_ind.htm
sluggish cognitive tempo
PYCHIATRY A constellation of symptoms* described as daydreamy, mentally foggy, easily confused, with periodic staring episodes. Affected individuals are typically hypoactive, lethargic, slow, and sleepy.
*SCT was proposed as a condition a sui generis to be included in the 5th edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorder (DSM-5). It was not accepted in the final version published in May 2013. Children with SCT have slow mental processing and reaction times and, compared to those with ADHD. They have far lower rates of oppositional defiant disorder and conduct disorder, but a greater risk of anxiety, depression, and social withdrawal. SCT is similar, if not identical to ADHD inattentive subtype, but occurs in individuals who would not be regarded as having ADHD. SCT is a descriptive term for what some authors regard as a large (up to half) homogeneous subgroup of individuals diagnosed as ADHD predominantly inattentive–ADHD-PI, which has been proposed as a separate entity for the upcoming DSM 5. In contrast to those with ADHD-PI, who are hyperactive, extroverted, obtrusive, and risk takers,those with SCT are introspective, daydream, and feel as if they’re in the fog.
3 May 2015
GENETICS A term coined by Takayama et al, who identified a 219-residue murine Bcl-2 protein that attenuates transfected cell response to apoptotic stimuli; the name is from the Greek word athánatos, meaning “against death.”
Takayama S, Sato T, Krajewski S, et al (1995) Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity. Cell 80: 279–284uj
Reference EMBO Rep. 2004 February; 5(2): 148–153
MEDIA & MEDICINE, MEDSPEAKUK CASUAL+Y The world’s longest-running (since 1986) emergency medical drama, which was launched in 1986 in the UK on BBC One, where it remains.
Casualty is broadcast weekly and its story lines revolve around the staff and patients of the A&E (accident and emergency) department at the fictional Holby City Hospital located in the equally fictional county of Wyvern. Scenes outside the hospital scenes are shot in Bristol with local landmarks forming the backdrop. and around Bristol. Holby City, another medical drama, was spun off in 1999 as a separate show, and revolves around Holby City’s “upstairs” departments; occasional crossovers between the shows are billed as Casualty @ Holby City
PSYCHIATRY DSM-V The fifth edition of the venerated Diagnostic and Statistical Manual of Mental Disorders, produced by the American Psychiatric Association, the first edition of which was released in 1952. DSM 5 is slated for publication on 22 May 2013 and is likely to continue serving as a touchstone for health professionals who diagnose and manage mental disorders.
Not everyone is tickled by the DSM-5. The British Psychological Society weighed in in mid-2011, saying it had more concerns than plaudits, criticised proposed diagnoses as based largely on social norms, with “symptoms” that rely on subjective judgements… not value-free, but rather reflecting current normative social expectations.
Proposed changes to DSM-IV diagnoses
• Asperger syndrome
• Attention Deficit Hyperactivity Disorder
• Bipolar disorder
• Dissociative identity disorder
• Gender identity disorder
• Hypersexual disorder
• Oppositional Defiant Disorder• Personality disorders
• Posttraumatic stress disorder
• Somatoform disorder
Proposed new diagnoses in DSM-5
• Binge Eating
• Complex post-traumatic stress disorder
• Compulsive hoarding
• Depressive personality disorder
• Negativistic (passive-aggressive) personality disorder
• Olfactory reference syndrome*
• Post-traumatic embitterment disorder
• Relational disorder
• Skin Picking Disorder*
• Sluggish cognitive tempo
*Placed in appendix for further research
Proposed, but dropped
• Attenuated psychosis syndrome
• Mixed anxiety depressive disorder.
CELL BIOLOGY Hepatocyte growth factor-regulated tyrosine kinase substrate, Vps27, HRS, human growth factor-regulated tyrosine kinase substrate, protein Pp110 A gene on chromosome 17q25 that encodes a protein which regulates endosomal sorting and plays a key role in the recycling and degrading membrane receptors. The encoded protein sorts monoubiquitinated membrane proteins into multivesicular bodies, targeting the membrane proteins for lysosome-dependent degradation. HGS is also involved in cytokine- and growth factor-mediated intracellular signal transduction. When HGS associates with STAM, it suppresses DNA signalling when stimulated by IL-2 and GM-CSF. HGS may be a direct effector of PI3-kinase in the multivesicular pathway via early endosomes and may regulate trafficking to early and late endosomes by recruiting clathrin. It is involved in down-regulating receptor tyrosine kinase via multivesicular body–MVB formation when complexed with the STAM —ESCRT-0 complex*. HGS may contribute to the efficient recruitment of SMADs to the activin receptor complex. It is involved in receptor recycling through its association with the CART complex, a multiprotein complex required for efficient transferrin receptor recycling but not for EGFR degradation.
*The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to sequential lysosomal sorting/trafficking processes.
multivesicular body biogenesis
CELL BIOLOGY A process in which ubiquitin tagged proteins enter endosomes by forming vesicles, a process that requires ESCRT* complex activity and allows cells to destroy misfolded and damaged proteins.
*Endosomal Sorting Complexes Required for Transport. Without ESCRT-3, defective proteins accumulate, leading to neurodegenerative changes.
2 May 2015
DERMATOLOGY, PATHOLOGY Cornu cutaneum A popular term for a focal hyperkeratotic column arising in head–where it simulates the horn of grazing mammals–and neck, face and yes, even the penis, in the background of a keratinising proliferation–e.g., solar, seborrhoeic, or inverted follicular keratoses, marsupialised tricholemmal or epidermoid cysts, verruca vulgaris, and squamous cell carcinoma* or sebaceous gland carcinoma.
*Up to 20% of cases have underlying squamous cell carcinoma.
CELL BIOLOGY Endosomal Sorting Complexes Required for Transport complex Any of a number—ESCRT-0, ESCRT-1, ESCRT-2, and ESCRT-3—of cytosolic protein complexes which, with various accessory proteins, enable a unique type of cell membrane remodeling in which the membranes bend/bud away from the cytoplasm. ESCRT machinery plays a key role in such cellular processes as multivesicular body biogenesis, cellular abscission, and viral budding.
MOLECULAR Low Density Lipoprotein Receptor-Related Protein 1, IGFBP3R, A2MR, TGFBR5, Alpha-2-Macroglobulin Receptor, Prolow-Density Lipoprotein Receptor-Related Protein 1, APR, TbetaR-V/LRP-1/IGFBP-3 Receptor, CD91, Type V Tgf-Beta Receptor, LRP, Apolipoprotein E Receptor, EC 126.96.36.199, APOER, EC 188.8.131.52 A gene on chromosome 12q13-q14 that encodes a membrane receptor involved in endocytosis and phagocytosis of apoptotic cells. It is required for early embryonic development, and involved in lipid homeostasis, in plasma clearance of chylomicron remnants and activated alpha 2-macroglobulin–LRPAP1, as well as metabolism of complexes between plasminogen activators and their endogenous inhibitors. LRP1 may modulate APP metabolism, kinase-dependent intracellular signaling, neuronal calcium signaling and neurotransmission.
References http://www.genecards.org/cgi-bin/carddisp.pl?gene=LRP1 http://www.uniprot.org/uniprot/Q07954
EVIDENCE-BASED MEDICINE Data which describe other data, especially containing XML tags characterising attributes of values in clinical data fieldsInformatics Data about data, which facilitates its access and use. In data processing, metadata provides information about or documentation of other data managed within an application or environment.
Metadata may include descriptive information about the context, quality and condition, or characteristics of the data.
INFORMATICS Structured data about data, which facilitates its access and use, and helps describe, identify and locate a document–e.g., a book in print or an electronic file in cyberspace.
Metadata is used to determine content target(s) and where, how, and when it should appear.
• Data elements or attributes–e.g., name, size, data type, etc.
• Records or data structures–e.g., length, fields, columns, etc. and
• Data itself–e.g., where it’s located, how it is associated, who owns the data, etc.
MOLECULAR MEDICINE A proprietary–Oxford Biomedica–gene therapy which provides a controlled release of EPO in response to low oxygen concentration in patients with chronic, treatment-refractory anaemia. Repoxygen is packaged as a viral delivery vector* with the EPO gene under hypoxia-inducible factors–HIF-responsive element–HRE control. HRE senses low oxygen concentrations and switch on the EPO gene.
*Because Repoxgen’s protein is of viral origin, it may evoke a potentially fatal immune response.
Repoxygen has the potential for abuse by endurance athletes, but may be of use for “anoxic” sports, including high mountain climbing and deep free diving.
1 May 2015
Bristol Royal Infirmary Inquiry
MEDSPEAK-UK, PAEDIATRICS Bristol Royal Infirmary scandal, Kennedy Inquiry An inquiry into the clinical management of children undergoing complex cardiac surgery at the Bristol Royal Infirmary (UK) between 1984 and 1995 and other related issues, which concluded that the cardiology services provided were suboptimal, and the mortality rates of infant operated for complex heart surgery far exceeded the national norm.
The public inquiry was conducted between October 1998 and July 2001. Evidence from 577 witnesses, including 238 parents, was received in writing. The Inquiry received 900,000 pages of documents, including the medical records of over 1,800 children. Oral evidence of selected witnesses was taken over 96 days
References www.bristol-inquiry.org.uk/search/index.htm www.bristol-inquiry.org.uk/
CELL BIOLOGY Calcineurin-Like EF-Hand Protein 1, CHP, EF-Hand Calcium-Binding Domain-Containing Protein P22, Calcineurin B Homolog, Sid470p, Calcineurin B Homologous Protein 1, P22, Calcineurin Homologous Protein, P24, SLC9A1 Binding Protein A gene on chromosome 15q13.3 that encodes a ubiquitously expressed calcium-binding phosphoprotein which binds to the Na+/H+ exchanger NHE1, acting as an essential cofactor for the physiologic activity of NHE family members. It is involved in various cellular processes, including vesicular trafficking, plasma membrane Na+/H+ exchanger and gene transcription and exocytic membrane traffic. It mediates the association between microtubules and membrane-bound organelles of the endoplasmic reticulum and Golgi apparatus and is required for the targeting and fusion of transcytotic vesicles with the plasma membrane. CHP1 may play a role in the mitogenic regulation of NHE1. The protein shares similarity with calcineurin B and calmodulin, and is an endogenous inhibitor of calcineurin activity. It is expressed in the fetal eye, lung, liver, muscle, heart, kidney, thymus and spleen.
EVIDENCE-BASED MEDICINE A clinical trial with the primary objective of showing that the response to two or more treatments differs by an amount that is clinically insignificant, which is usually demonstrated by showing that the true treatment difference lies between a lower and an upper equivalence margin of clinically acceptable differences.
female sex tourism
GLOBAL VILLAGE, SEXOLOGY Travel by a woman to a tourist destination with the express purpose of engaging in sexual activity with male residents of the destination, which may have a veneer of romance, but is widely viewed as a permutation of prostitution. (Roll your mouse over the image to see the typical originating countries and destinations.)
An estimated 650,000 women from North America and northern Europe have engaged in sex tourism since the 1980s. Jamaica is a popular destination, with up to 80,000/year visiting for sex. Other popular destinations include Italy, Greece, Croatia, Turkey, Slovenia, Montenegro, Spain), Barbados Dominican Republic, Tunisia, Gambia, Kenya, etc. The frequency of sexually-transmitted infections, including that of HIV-1, has not been examined in depth.
MEDSPEAK–UK An adjustment to the tariff paid to an institution for a particular package of healthcare services in the UK, which is triggered when a patient stays for much more (long-stay addition) or much less (short-stay subtraction) time than the “average” patient.
Reference Medical Laboratory World Ap 2006, p5