Class VI Unconventional Myosin is Required for Spermatogenesis in Drosophila

We have identified partial loss of function mutations in class VI unconventional myosin, 95F myosin, which results in male sterility. During spermatogenesis the germ line precursor cells undergo mitosis and meiosis to form a bundle of 64 spermatids. The spermatids remain interconnected by cytoplasmic bridges until individualization. The process of individualization involves the formation of a complex of cytoskeletal proteins and membrane, the individualization complex (IC), around the spermatid nuclei. This complex traverses the length of each spermatid resolving the shared membrane into a single membrane enclosing each spermatid. We have determined that 95F myosin is a component of the IC whose function is essential for individualization. In wild-type testes, 95F myosin localizes to the leading edge of the IC. Two independent mutations in 95F myosin reduce the amount of 95F myosin in only a subset of tissues, including the testes. This reduction of 95F myosin causes male sterility as a result of defects in spermatid individualization. Germ line transformation with the 95F myosin heavy chain cDNA rescues the male sterility phenotype. IC movement is aberrant in these 95F myosin mutants, indicating a critical role for 95F myosin in IC movement. This report is the first identification of a component of the IC other than actin. We propose that 95F myosin is a motor that participates in membrane reorganization during individualization.

Acampamento e assentamento rural como contexto de cuidado e educação compartilhados de crianças

Esta pesquisa se insere no campo da Psicologia Cultural do Desenvolvimento Humano e tem como objetivo investigar o compartilhamento da educação e do cuidado de crianças pequenas (1 a 5 anos) em um assentamento e um acampamento rural. Consideramos como compartilhamento da educação a participação de um grupo de pessoas, adultos ou crianças, nos momentos cotidianos da criança. A hipótese inicial da investigação estava relacionada a uma aparente coletivização da educação no acampamento e uma individualização no assentamento, determinados, sobretudo, pelas práticas culturais de cada contexto. Participaram da investigação 10 crianças (5 moradoras de um acampamento rural e 5 de um assentamento rural). A metodologia consistiu em observação participante com a imersão da pesquisadora por uma média de 6 dias no cotidiano familiar e comunitário de cada criança, com anotação em diário de campo das atividades, parceiros e cenários de compartilhamento do cuidado e da educação da criança. Os resultados apontam para: um intenso compartilhamento no grupo de vizinhança no acampamento e no grupo de família extensa no assentamento; a importância do cuidado e educação exercido entre as crianças, especialmente em situações de brincadeira; o histórico de migração como condição relacionada à maior busca pelo compartilhamento; a mulher como principal cuidadora, aspecto intimamente relacionado ao trabalho doméstico e na agricultura.O trabalho propicia reflexões acerca da diversidade dos modos de vida das crianças nestes contextos, sendo que há potencialidades educacionais ali construídas, fruto de uma riqueza cultural latente. Aponta ainda para considerações acerca das políticas públicas e garantia de direitos às crianças.

Saúde mental e os novos paradigmas de cidadania e inclusão social na sociedade contemporânea

Este estudo tem por objetivo analisar as categorias de cidadania e inclusão social na política de desinstitucionalização nos sujeitos em sofrimento psíquico diante do processo de individualização na teoria social contemporânea. Assume como hipótese que a saída do hospital psiquiátrico por si só não garante a inclusão social e nem o livre exercício da cidadania. Considerado o objetivo desta pesquisa, optou-se por fazer uma pesquisa bibliográfica como procedimento metodológico. O material de estudo foi dividido em três conjuntos: (1) 56 artigos científicos, visando a compreender a visão da academia; (2) um conjunto de legislação, composto de 10 leis que implementaram a política de desinstitucionalização no Brasil e a reforma dos serviços de saúde psiquiátrica, visando a compreender as ações do Estado; (3) quatro Relatórios Finais das quatro Conferências Nacionais de Saúde Mental, para também compreender a participação da sociedade civil. Para a análise do material, utilizou-se uma combinação de duas técnicas complementares: leitura bibliográfica com a análise de conteúdo. Dentre os vários processos que caracterizam a sociedade contemporânea, optou-se por analisar a individualização que impacta nas formas de exercício da cidadania e na inclusão social. Na análise dos resultados da categoria de cidadania foram identificadas associações em relação à interdição civil, liberdade, moradia, saúde, trabalho, educação e participação política. Relacionadas à categoria de inclusão social foram identificadas as referências à família, estigma, laços sociais, autonomia, contratualidade e trabalho. Os resultados obtidos indicam que o campo da saúde mental não está em completa consonância com as transformações da sociedade contemporânea, o que provoca um descolamento da realidade social da própria politica de desinstitucionalização e, portanto, maior dificuldade para a efetiva inclusão social e o exercício da cidadania desses indivíduos.

A individualização da medida cautelar pessoal no processo penal brasileiro

O sistema de medidas cautelares pessoais no processo penal brasileiro não mais gravita em torno da prisão preventiva, uma vez que o legislador instituiu um rol de medidas cautelares menos gravosas, a ela alternativas. Nesse contexto, como deve orientar-se a escolha judicial da medida a ser aplicada ao caso concreto? A constitucional idade de qualquer intervenção no direito fundamental de liberdade depende, essencialmente, de sua fundamentação constitucional, que é controlada a partir da proporcionalidade. A proporcional idade, portanto, é a pedra angular do sistema de medidas cautelares pessoais. A decisão que impõe uma medida cautelar pessoal jamais pode resultar de uma intuição individual misteriosa, senão de um procedimento cognoscitivo estruturado e comprovável de maneira intersubjetiva. Daí a importância da investigação da existência de um direito fundamental do imputado à individualização da medida cautelar pessoal, para afastar qualquer discricionariedade judicial na sua escolha. O objetivo do presente trabalho, portanto, é propor um método racional, baseado no exame da proporcionalidade, para controle intersubjetivo da justificação da decisão judicial que, no processo penal, imponha uma medida cautelar pessoal.

Fetichismo de la subjetividad: individualización, malestar y consumo

Capitalism, like the universe, expands; it is foreseen as without limit and historically presented as if from the outside while paradoxically, unlike the universe, capitalism is an historical and contingent emergence. Many have suggested that its naturalization now leave it easier to imagine the end of the world than the end of capitalism. In consumer capitalism, subjectivity has become a commodity. Thus it is possible to say that consumer society is characterized by a "fetish of subjectivity", in which individualization (as lifestyle) and malaise (as symptom) are combined. The fetish of subjectivity may be one of the most important historical achievements of the relationship between capitalism and subjectivity, promoting highly individualized and intensive rules and requiring a consciousness in terms of the consumer society, a success-oriented life, competition and almost total autonomy in achieving the only goals and objectives culturally defined as legitimate and valid, experienced as decisions taken by each individual. Today’s individualization is is individualistic by nature, and it tends to weaken traditional forms of social ties and to strain social cohesion. Sociology is constituted as a discipline which has studied the problematic relationship between modernity and capitalism, which in turn has also been problematic for sociology itself. Especially the associated processes of modernization have favored the emergence of society as a distinctive phenomenon, of the individual and social action, and of subjectivity, a recurring dimension although not always explicit in its problematic. The nation-state has been a historic, formal and spatial expression of dimensions that express the historical relationship between modernity and capitalism...

Bases teóricas dos processos de medicalização: um olhar sobre as forças motrizes

Introdução: O tema medicalização emerge como objeto de estudo no campo da sociologia da saúde, a partir da década de 70, nas vozes de Irving Zola, Ivan Illich, Peter Conrad e Michel Foucalt; as quais indicaram a crescente influência da medicina em campos que até então não lhe pertenciam. E, no decorrer dos anos, o termo vem sendo apropriado por vários campos: na saúde, na educação, na psicologia, entre outros. Esta configuração levou alguns estudiosos da primeira década do século XXI, a se preocupar com o uso impreciso e vago do conceito de medicalização na produção científica. Neste sentido, este estudo busca olhar para os processos de medicalização, tomando-o em sua pluralidade a fim de discernir as principais forças motrizes e coteja-las com as mudanças na contemporaneidade. Objetivo: Recuperar as forças motrizes contidas nas principais contribuições dos autores primários sobre os processos de medicalização. Método: Realizou-se um exercício hermenêutico composto pelos seguintes passos: leitura profunda do texto, fichamento dos aspectos centrais que caracterizam as diversas concepções sobre medicalização. Interpretação do conteúdo por meio da abstração dos núcleos de sentido e dos referenciais teóricos que lhe dão suporte. Resultados: A partir deste movimento reflexivo e crítico conseguiu-se desvelar quatro conceitos nucleares que representam as principais forças motrizes: a indústria, as instituições, o Estado e a sociedade. Zola oferece indícios que o Estado e a indústria teriam levado a sociedade à dependência da medicina. Para Illich, a medicina, por si só, detém o poder comparada as outras instituições. Para Michel Foucault, a medicina deixou de ser uma ciência pura e transformou-se numa instituição subordinada a um sistema econômico e de poder, enfim a uma lógica subjacente aos princípios e regras de governo. Em contrapartida, para Conrad a medicalização não constitui um empreendimento exclusivo da medicina, prevalecendo os interesses de outras instituições e organizações sociais. O sentido com que cada um desses conceitos é usado difere entre os autores e a distinção desses aspectos é chave para compreender a contribuição efetiva de cada um. Da mesma forma, ocorre quando os autores discutem as consequências e os efeitos causados pelos processos de medicalização. Alguns autores direcionam seus efeitos para os indivíduos, num processo de exacerbação da individualização; enquanto que outros focam os efeitos da medicalização nas políticas de saúde e na questão econômica associada ao oneroso custo financeiro para a sociedade e o país. Considerações finais: A recuperação e a compreensão dos significados subjacentes às principais forças motrizes presentes nas contribuições de cada autor apresentadas nesta investigação constituem-se em passo importante para subsidiar a reflexão sobre processos concretos de medicalização no início do século XXI, um período marcado por aceleradas transformações, no qual, entre outros aspectos, a medicina e várias instituições têm sido crescentemente, capturadas para satisfazer, de um lado o consumismo, e de outro, a avidez pelo lucro do mercado capitalista; ao mesmo tempo em que forças desagregadoras atravessam os sujeitos impactando sua autonomia e identidade política, social e econômica.

Estudo observacional do uso da hipodermóclise em cuidados paliativos oncológicos

Hipodermóclise (HDC) é uma importante técnica alternativa para a administração de medicamentos e fluidos pela via subcutânea. É usada com frequência para o controle dos sintomas em pacientes em cuidados paliativos com dificuldade de acesso venoso e que são incapazes de tolerar medicação oral. No entanto, raros estudos abordaram o uso da HDC de uma forma global, para reposição hidroeletrolítica e terapia medicamentosa, tanto na forma contínua quanto intermitente, observando detalhes e complicações do seu uso. Os objetivos deste estudo incluíram caracterizar o uso da HDC para administração de medicamentos, soluções e eletrólitos e avaliar as possíveis complicações locais, identificando também outros fatores que influenciam sua ocorrência. Estudo observacional prospectivo com coleta de dados em prontuário e acompanhamento diário de pacientes internados com câncer avançado, da equipe de Cuidados Paliativos do Instituto do Câncer do Estado de São Paulo (ICESP) em uso de HDC, verificando local de punção, medicamentos administrados e possíveis complicações, acompanhando os detalhes de seu uso. A análise estatística não-paramétrica e método de regressão logística foram realizados. Foram acompanhados 99 pacientes com 243 punções, das quais 166 (68,3%) em coxa e 46 (18,9%) em abdome. Os medicamentos mais utilizados foram morfina em 122 (50,2%) punções, seguido de dipirona em 118 (48,6%) e dexametasona em 86 (35,4%). A solução mais prescrita foi a glicofisiológica em 38 (15,6%) punções, pelo seu aporte calórico. 13,6% das punções (33 de 243) tiveram complicações, sendo apenas seis casos maiores (edema). Complicações ocorreram mais frequentemente até o segundo dia da punção e foram associadas com o número (p=0,007) e o volume (p=0,042) de medicamentos administrados e também com a solução glicofisiológica (p=0,003) e os eletrólitos cloreto de potássio (p=0,037) e cloreto de sódio (p=0,013). Este estudo permitiu o conhecimento de fatores associados a complicações e propõe algumas recomendações, como: individualização da terapia, especialmente relacionada com o volume de escolha, número de medicamentos administrados e evitar a adição de eletrólitos na solução glicofisiológica

A música e o devir

Process philosophies focus on becoming and often have recourse to the musical metaphor. Becoming is whole and indivisible. Bergson’s notion of durée coincides with the Whiteheadian notion of process. Becoming is duration. Every being is temporal; its very essence is temporality. The unveiling of each being is durational and has its own particular temporality; every creature’s individualization is in accordance with its own particular way of enduring. A melody is also whole and indivisible; its very meaning relates to its whole, undivided temporality. A note of music is nothing at an instant; the wholeness of its being thoroughly defines it.

What is the best size descriptor to use for pharmacokinetic studies in the obese?

The prevalence of obesity in the western world is dramatically rising, with many of these individuals requiring therapeutic intervention for a variety of disease states. Despite the growing prevalence of obesity there is a paucity of information describing how doses should be adjusted, or indeed whether they need to be adjusted, in the clinical setting. This review is aimed at identifying which descriptors of body size provide the most information about the relationship between dose and concentration in the obese. The size descriptors, weight, lean body weight, ideal body weight, body surface area, body mass index, fat-free mass, percent ideal body weight, adjusted body weight and predicted normal body weight were considered as potential size descriptors. We conducted an extensive review of the literature to identify studies that have assessed the quantitative relationship between the parameters clearance (CL) and volume of distribution (V) and these descriptors of body size. Surprisingly few studies have addressed the relationship between obesity and CL or V in a quantitative manner. Despite the lack of studies there were consistent findings: (i) most studies found total body weight to be the best descriptor of V. A further analysis of the studies that have addressed V found that total body weight or another descriptor that incorporated fat mass was the preferred descriptor for drugs that have high lipophilicity; (ii) in contrast, CL was best described by lean body mass and no apparent relationship between lipophilicity or clearance mechanism and preference for body size descriptor was found. In conclusion, no single descriptor described the influence of body size on both CL and V equally well. For drugs that are dosed chronically, and therefore CL is of primary concern, dosing for obese patients should not be based on their total weight. If a weight-based dose individualization is required then we would suggest that chronic drug dosing in the obese subject should be based on lean body weight, at least until a more robust size descriptor becomes available.

Quantitative justification for target concentration intervention - parameter variability and predictive performance using population pharmacokinetic models for aminoglycosides

Aims [1] To quantify the random and predictable components of variability for aminoglycoside clearance and volume of distribution [2] To investigate models for predicting aminoglycoside clearance in patients with low serum creatinine concentrations [3] To evaluate the predictive performance of initial dosing strategies for achieving an aminoglycoside target concentration. Methods Aminoglycoside demographic, dosing and concentration data were collected from 697 adult patients (>=20 years old) as part of standard clinical care using a target concentration intervention approach for dose individualization. It was assumed that aminoglycoside clearance had a renal and a nonrenal component, with the renal component being linearly related to predicted creatinine clearance. Results A two compartment pharmacokinetic model best described the aminoglycoside data. The addition of weight, age, sex and serum creatinine as covariates reduced the random component of between subject variability (BSVR) in clearance (CL) from 94% to 36% of population parameter variability (PPV). The final pharmacokinetic parameter estimates for the model with the best predictive performance were: CL, 4.7 l h(-1) 70 kg(-1); intercompartmental clearance (CLic), 1 l h(-1) 70 kg(-1); volume of central compartment (V-1), 19.5 l 70 kg(-1); volume of peripheral compartment (V-2) 11.2 l 70 kg(-1). Conclusions Using a fixed dose of aminoglycoside will achieve 35% of typical patients within 80-125% of a required dose. Covariate guided predictions increase this up to 61%. However, because we have shown that random within subject variability (WSVR) in clearance is less than safe and effective variability (SEV), target concentration intervention can potentially achieve safe and effective doses in 90% of patients.

CEDIA (R) sirolimus assay compared with HPLC-MS/MS and HPLC-UV in transplant recipient specimens

The role of the therapeutic drug monitoring laboratory in support of immunosuppressant drug therapy is well established, and the introduction of sirolimus (SRL) is a new direction in this field. The lack of an immunoassay for several years has restricted the availability of SRL assay services. The recent availability of a CEDIA (R) SRL assay has the potential to improve this situation. The present communication has compared the CEDIA (R) SRL method with 2 established chromatographic methods, HPLC-UV and HPLC-MS/MS. The CEDIA (R) method, run on a Hitachi 917 analyzer, showed acceptable validation criteria with within-assay precision of 9.1% and 3.3%, and bias of 17.1% and 5.8%, at SRL concentrations of 5.0 mu g/L and 20 mu g/L, respectively. The corresponding between-run precision values were 11.5% and 3.3% and bias of 7.1% and 2.9% at 5.0 mu g/L and 20 mu g/L, respectively, The lower limit of quantification was found to be 3.0 mu g/L. A series of 96 EDTA whole-blood samples predominantly from renal transplant recipients were assayed by the 3 methods for comparison. It was found that the CEDIA (R) method showed a Deming regression line of CEDIA = 1.20 X HPLC-MS/MS - 0.07 (r = 0.934, SEE = 1.47), with a mean bias of 20.4%. Serial blood samples from 8 patients included in this evaluation showed that the CEDIA (R) method reflected the clinical fluctuations in the chromatographic methods, albeit with the variable bias noted. The CEDIA (R) method on the H917 analyzer is therefore a useful adjunct to SRL dosage individualization in renal transplant recipients.

Comparison of the reintroduced MEIA (R) assay with HPLC-MS/MS for the determination of whole-blood sirolimus from transplant recipients

Therapeutic monitoring with dosage individualization of sirolimus drug therapy is standard clinical practice for organ transplant recipients. For several years sirolimus monitoring has been restricted as a result of lack of an immunoassay. The recent reintroduction of the microparticle enzyme immunoassay (MEIA (R)) for sirolimus on the IMx (R) analyser has the potential to address this situation. This Study, using patient samples, has compared the MEIA (R) sirolimus method with an established HPLC-tandem mass spectrometry method (HPLC-MS/MS). An established HPLC-UV assay was used for independent cross-validation. For quality control materials (5, 11, 22 mu g/L), the MEIA (R) showed acceptable validation criteria based on intra-and inter-run precision (CV) and accuracy (bias) of < 8% and < 13%, respectively. The lower limit of quantitation was found to be approximately 3 mu g/L. The performance of the immunoassay was compared with HPLC-MS/MS using EDTA whole-blood samples obtained from various types of organ transplant recipients (n = 116). The resultant Deming regression line was: MEIA = 1.3 x HPLC-MS/MS+ 1.3 (r = 0.967, s(y/x) = 1) with a mean bias of 49.2% +/- 23.1 % (range, -2.4% to 128%; P < 0.001). The reason for the large and variable bias was not explored in this study, but the sirolimus-metabolite cross-reactivity with the MEIA (R) antibody could be a substantive contributing factor. Whereas the MEIA (R) sirolimus method may be an adjunct to sirolimus dosage individualization in transplant recipients, users must consider the implications of the substantial and variable bias when interpreting results. In selected patients where difficult clinical issues arise, reference to a specific chromatographic method may be required.

Prediction of functional capacity in chronic heart failure patients using myocardial tissue Doppler

Background. Exercise therapy improves functional capacity in CHF, but selection and individualization of training would be helped by a simple non-invasive marker of peak VO2. Peak VO2 in these pts is difficult to predict without direct measurement, and LV ejection fraction is a poor predictor. Myocardial tissue velocities are less load-dependent, and may be predictive of the exercise response in CHF pts. We sought to use tissue velocity as a predictor of peak VO2 in CHF pts. Methods. Resting 2D-echocardiography and tissue Doppler imaging were performed in 182 CHF pts (159 male, age 62±10 years) before and after metabolic exercise testing. The majority of these patients (129, 71%) had an ischemic cardiomyopathy, with resting EF of 35±13% and a peak VO2 of 13.5±4.7 ml/kg/min. Results. Neither resting EF (r=0.15) nor peak EF (r=0.18, both p=NS) were correlated with peak VO2. However, peak VO2 correlated with peak systolic velocity in septal (Vss, r=0.31) and lateral walls (Vsl, r=0.26, both p=0.01). In a general linear model (r2 = 0.25), peak VO2 was calculated from the following equation: 9.6 + 0.68*Vss - 0.09*age + 0.06*maximum HR. This model proved to be a superior predictor of peak VO2 (r=0.51, p=0.01) than the standard prediction equations of Wasserman (r= -0.12, p=0.01). Conclusions. Resting tissue Doppler, age and maximum heart rate may be used to predict functional capacity in CHF patients. This may be of use in selecting and following the response to therapy, including for exercise training.

Pharmacogenomic studies of the anticancer and immunosuppressive thiopurines mercaptopurine and azathioprine

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • 6-Mercaptopurine (6-MP) and azathioprine (AZA) are both inactive prodrugs that require intracellular activation into the active 6-thioguanine nucleotides (6-TGNs). • This metabolic process undergoes three different competitive pathways that are catalysed by three different enzymes; xanthine oxidase (XO), thiopurine methyltransferase (TPMT) and inosine triphosphatase (ITPA), all of which exhibit genetic polymorphisms. • Although the impact of genetic variation in the TPMT gene on treatment outcome and toxicity has been demonstrated, the role of other polymorphisms remains less well known. WHAT THIS STUDY ADDS • New information on the allelic variation of these three enzymes (XO, TPMT and ITPA) and their influence on 6-MP/AZA metabolism and toxicity. • Confirmation of the association of TPMT polymorphism with haematological toxicity. • Identified potential genetic characteristics that may contribute to higher risk of adverse events (such as ITPA IVS2+21A→C mutation). AIMS - To examine the allelic variation of three enzymes involved in 6-mercaptopurine/azathioprine (6-MP/AZA) metabolism and evaluate the influence of these polymorphisms on toxicity, haematological parameters and metabolite levels in patients with acute lymphoblastic leukaemia (ALL) or inflammatory bowel disease (IBD). METHODS - Clinical data and blood samples were collected from 19 ALL paediatric patients and 35 IBD patients who were receiving 6-MP/AZA therapy. All patients were screened for seven genetic polymorphisms in three enzymes involved in mercaptopurine metabolism [xanthine oxidase, inosine triphosphatase (C94→A and IVS2+21A→C) and thiopurine methyltransferase]. Erythrocyte and plasma metabolite concentrations were also determined. The associations between the various genotypes and myelotoxicity, haematological parameters and metabolite concentrations were determined. RESULTS - Thiopurine methyltransferase variant alleles were associated with a preferential metabolism away from 6-methylmercaptopurine nucleotides (P = 0.008 in ALL patients, P = 0.038 in IBD patients) favouring 6-thioguanine nucleotides (6-TGNs) (P = 0.021 in ALL patients). Interestingly, carriers of inosine triphosphatase IVS2+21A→C variants among ALL and IBD patients had significantly higher concentrations of the active cytotoxic metabolites, 6-TGNs (P = 0.008 in ALL patients, P = 0.047 in IBD patients). The study confirmed the association of thiopurine methyltransferase heterozygosity with leucopenia and neutropenia in ALL patients and reported a significant association between inosine triphosphatase IVS2+21A→C variants with thrombocytopenia (P = 0.012). CONCLUSIONS - Pharmacogenetic polymorphisms in the 6-MP pathway may help identify patients at risk for associated toxicities and may serve as a guide for dose individualization.

Psychophysiological responses to visceral and somatic pain in functional chest pain identify clinically relevant pain clusters

Background: Despite chronic pain being a feature of functional chest pain (FCP) its experience is variable. The factors responsible for this variability remain unresolved. We aimed to address these knowledge gaps, hypothesizing that the psychophysiological profiles of FCP patients will be distinct from healthy subjects. Methods: 20 Rome III defined FCP patients (nine males, mean age 38.7 years, range 28-59 years) and 20 healthy age-, sex-, and ethnicity-matched controls (nine males, mean 38.2 years, range 24-49) had anxiety, depression, and personality traits measured. Subjects had sympathetic and parasympathetic nervous system parameters measured at baseline and continuously thereafter. Subjects received standardized somatic (nail bed pressure) and visceral (esophageal balloon distension) stimuli to pain tolerance. Venous blood was sampled for cortisol at baseline, post somatic pain and post visceral pain. Key Results: Patients had higher neuroticism, state and trait anxiety, and depression scores but lower extroversion scores vs controls (all p < 0.005). Patients tolerated less somatic (p < 0.0001) and visceral stimulus (p = 0.009) and had a higher cortisol at baseline, and following pain (all p < 0.001). At baseline, patients had a higher sympathetic tone (p = 0.04), whereas in response to pain they increased their parasympathetic tone (p ≤ 0.008). The amalgamating the data, we identified two psychophysiologically distinct 'pain clusters'. Patients were overrepresented in the cluster characterized by high neuroticism, trait anxiety, baseline cortisol, pain hypersensitivity, and parasympathetic response to pain (all p < 0.03). Conclusions & Inferences: In future, such delineations in FCP populations may facilitate individualization of treatment based on psychophysiological profiling. © 2013 John Wiley & Sons Ltd.