Enhanced nitric oxide production by macrophages treated with a cell-penetrating peptide conjugate.

The SPRY domain-containing SOCS box protein-2 (SPSB2) plays a critical role in the degradation of inducible nitric oxide synthase (iNOS) in macrophages. In this study, we have conjugated a peptide inhibitor of the iNOS-SPSB2 interaction with a cell-penetrating peptide (CPP) for delivery into macrophages, and confirmed its binding to SPSB2. We have assessed the uptake of a fluorophore-tagged analogue by RAW 264.7 and immortalised bone marrow derived macrophage (iBMDM) cell lines, and shown that the CPP-peptide conjugate enhanced NO production. The findings of this study will be useful in further refinement of CPP-peptide conjugates as leads in the development of new antibiotics that target the host innate immune response.

The Norwich Osteoarthritis of the Ankle MRI Score (NOAMS): a reliability study.

AIM: To define and test the inter- and intra-rater reliability of a grading system for staging osteoarthritis (OA) of the ankle with magnetic resonance imaging (MRI) (Norwich Osteoarthritis of the Ankle MRI Score, NOAMS). MATERIALS AND METHODS: The MRI features to be included in the score were defined by a multidisciplinary expert panel through a Delphi process. An anonymised randomised dataset of 50 MRI studies was created from patients with concurrent plain radiographs to include 10 ankles of each of the Kellgren-Lawrence grades 0 to 4. Two experienced musculoskeletal radiologists and two trainees scored each ankle MRI twice independently and blinded to the plain radiographs. RESULTS: The inter-rater kappa coefficient of agreement for cartilage disease was 0.88 (95% confidence interval [CI]: 0.85, 0.91) for experienced raters and 0.71 (95% CI: 0.67, 0.76) for trainees. Inter-rater agreement for subchondral bone marrow oedema and cysts varied from 0.73 to 0.82 for experienced raters and from 0.63 to 0.75 for trainees with lowest 95% CI of 0.48 and 0.63. When bone marrow lesions were combined into a total joint score the level of agreement increased to between 0.88 and 0.97 with lowest 95% CI of 0.86. Combining cartilage zone scores did not increase the reliability coefficients. CONCLUSION: An expert panel considered that cartilage degradation and subchondral bone marrow lesions were the most important features for staging the severity of ankle OA on MRI. Experienced observers can grade the severity of ankle OA on MRI with a clinically useful high degree of reproducibility.

Assessing the cellular toxicity of peptide inhibitors of intracellular protein-protein interactions by microinjection.

Inhibitors of protein-protein interactions can be developed through a number of technologies to provide leads that include cell-impermeable molecules. Redesign of these impermeable leads to provide cell-permeable derivatives can be challenging and costly. We hypothesised that intracellular toxicity of leads could be assessed by microinjection prior to investing in the redesign process. We demonstrate this approach for our development of inhibitors of the protein-protein interaction between inducible nitric-oxide synthase (iNOS) and SPRY domain-containing SOCS box proteins (SPSBs). We microinjected a lead molecule into AD-293 cells and were able to perform an intracellular toxicity assessment. We also investigated the intracellular distribution and localisation of injected inhibitor using a fluorescently-labelled analogue. Our findings show that a lead peptide inhibitor, CP2, had no toxicity even at intracellular concentrations four orders of magnitude higher than its Kd for binding to SPSB2. This early toxicity assessment justifies further development of this cell-impermeable lead to confer cell permeability. Our investigation highlights the utility of microinjection as a tool for assessing toxicity during development of drugs targeting protein-protein interactions.

[Ability of French General Practitioners to detect common mental disorders identified using the Patient Health Questionnaire: Has this changed with the introduction of gatekeeping and registration with a chosen doctor?] / Détection par le médecin généraliste des troubles psychiatriques courants selon l'auto-questionnaire diagnostique le Patient Health Questionnaire : dix ans après, le dispositif du médecin traitant a-t-il modifié la donne ?

OBJECTIVES: The general practitioner (GP) is the most frequently consulted health professional by patients with common mental disorders (CMD). Yet approximately half of cases are not detected by the GP. Many factors linked to the patient, the doctor and the health care system influence detection. For example, detection rates are higher when patients are better known to their GP. On the other hand, patients visiting a different GP for reasons of dissatisfaction with previous care are more likely to be detected on the survey-day. In France, a form of gatekeeping was introduced in 2005 to encourage patients to register with a doctor (most often a GP) of their choice (known as the Preferred Doctor), responsible for care coordination and referral if necessary to secondary care. Visiting a different GP, other than for non-avoidable reasons (for e.g. GP unreachable, patient on holiday), is still possible but financially sanctioned with lower reimbursement rates. We aimed to compare GP detection rates before and after the introduction of this gatekeeping scheme. Patient service use behaviour such as doctor-shopping and GP referral to secondary care were also compared. METHODS: Two cross-sectional surveys using the same study methods were carried out 10 years apart. In 2003, 46 GPs and 1151 patients participated (approximately 25 patients per GP), with a 32.7% GP participation rate. In 2013, 38 GPs participated (of which 29 had participated in the previous study, with a 85.3% "recapture" rate) and 1133 patients (approximately 30 patients per GP). Patient participation rates were 89.8% and 67%, respectively. Patients completed self-report questionnaires in the waiting room of which the DSM-IV diagnostic criteria Patient Health Questionnaire (PHQ) and an adapted version of the Client Service Receipt Inventory (CSRI) on contacts with health care services in the previous six months. For each patient, the GP completed a questionnaire giving his rating of psychiatric illness on a five-point scale with his/her diagnosis for cases, and action undertaken. RESULTS: Of the patients, 27% and 25.4% had a CMD according to the PHQ (defined as a diagnosis of minor or major depression, panic attack, anxiety or somatoform disorder) in 2003 and 2013 respectively. Corresponding detection rates were 51% and 52.6%. Rates were highest for threshold disorders: panic disorder (69.4% and 79.9% in 2003 and 2013, respectively), major depression (75% and 63.3% in 2003 and 2013, respectively) and other anxiety disorders (69.1% and 78.8% in 2003 and 2013, respectively). In 2003, the GPs declared seeing 15.5% for the first time on the survey-day, compared to 9.6% in 2013 (P=0.006). Doctor-shopping declined between the two studies, from 18.4% to 12.1% for practical and mostly unavoidable reasons, and from 9.8% to 4.2% for dissatisfaction reasons (P<0.0001). Referral to specialist doctors increased from 9.7% in 2003 to 14.7% in 2013 (P=0.014). In 2013, on the survey-day, 94.8% of patients had registered with a Preferred Doctor and 81.2% were seeing this Preferred Doctor. In 2003, 93.5% of patients declared having a usual GP and 79.9% were visiting this GP on the survey-day. CONCLUSIONS: This is one of the first studies to report data from two repeated surveys carried out before and after a change in the health service organisation, with data collected from both the patient and the GP. We report relatively high GP detection rates for the two periods, with about 50% of CMDs, including subsyndromic conditions, detected by the GP. Rates are considerably higher for the threshold disorders. The overall detection rate did not increase as expected between the two studies. Detection is a complex topic, involving issues such as the suitability of applying categorical DSM-IV criteria diagnoses to primary care, the relevance of detecting subthreshold conditions and the ability of cross-sectional studies to correctly assess the ability of GPs to recognise cases. The introduction of gatekeeping with the choice of a Preferred Doctor has led to a decline in the frequency of doctor-shopping, whatever its reason, with patients no doubt being better known to the GP. Yet it appears most patients had already chosen a GP they were loyal to before the scheme, with a similar proportion of patients consulting their chosen GP or Preferred Doctor on both survey-days in 2003 and 2013, suggesting the scheme may to some extent only have officialised what already existed with respect to having a usual GP. The French reform still allows for doctor-shopping which can be considered as a positive aspect of the scheme: patients either dissatisfied with previous care or needing to change GP are thus able to "test" and choose the doctor that best suits their needs.

Untangling the relationship between diet and visceral fat mass through blood metabolomics and gut microbiome profiling.

BACKGROUND/OBJECTIVES: Higher visceral fat mass (VFM) is associated with an increased risk for developing cardio-metabolic diseases. The mechanisms by which an unhealthy diet pattern may influence visceral fat (VF) development has yet to be examined through cutting-edge multi-omic methods. Therefore, our objective was to examine the dietary influences on VFM and identify gut microbiome and metabolite profiles that link food intakes to VFM. SUBJECTS/METHODS: In 2218 twins with VFM, food intake and metabolomics data available we identified food intakes most strongly associated with VFM in 50% of the sample, then constructed and tested the 'VFM diet score' in the remainder of the sample. Using linear regression (adjusted for covariates, including body mass index and total fat mass), we investigated associations between the VFM diet score, the blood metabolomics profile and the fecal microbiome (n=889), and confirmed these associations with VFM. We replicated top findings in monozygotic (MZ) twins discordant (⩾1 s.d. apart) for VFM, matched for age, sex and the baseline genetic sequence. RESULTS: Four metabolites were associated with the VFM diet score and VFM: hippurate, alpha-hydroxyisovalerate, bilirubin (Z,Z) and butyrylcarnitine. We replicated associations between VFM and the diet score (beta (s.e.): 0.281 (0.091); P=0.002), butyrylcarnitine (0.199 (0.087); P=0.023) and hippurate (-0.297 (0.095); P=0.002) in VFM-discordant MZ twins. We identified a single species, Eubacterium dolichum to be associated with the VFM diet score (0.042 (0.011), P=8.47 × 10-5), VFM (0.057 (0.019), P=2.73 × 10-3) and hippurate (-0.075 (0.032), P=0.021). Moreover, higher blood hippurate was associated with elevated adipose tissue expression neuroglobin, with roles in cellular oxygen homeostasis (0.016 (0.004), P=9.82x10-6). CONCLUSIONS: We linked a dietary VFM score and VFM to E. dolichum and four metabolites in the blood. In particular, the relationship between hippurate, a metabolite derived from microbial metabolism of dietary polyphenols, and reduced VFM, the microbiome and increased adipose tissue expression of neuroglobin provides potential mechanistic insight into the influence of diet on VFM.

Changes in social isolation and loneliness following total hip and knee arthroplasty: longitudinal analysis of the English Longitudinal Study of Ageing (ELSA) cohort.

OBJECTIVE: To determine the prevalence and change in social isolation and loneliness in people before and after total hip arthroplasty (THA) and total knee arthroplasty (TKA) in England. DESIGN: The English Longitudinal Study of Ageing (ELSA) dataset, a prospective study of community-dwelling older adults, was used to identify people who had undergone primary THA or TKA because of osteoarthritis. Social isolation was assessed using the ELSA Social Isolation Index. Loneliness was evaluated using the Revised University of California, Los Angeles (UCLA) Loneliness Scale. The prevalence of social isolation and loneliness were calculated and multilevel modelling was performed to assess the potential change of these measures before arthroplasty, within a two-year operative-recovery phase and a following two-year follow-up. RESULTS: The sample consisted of 393 people following THA and TKA. The prevalence of social isolation and loneliness changed from 16.9% to 18.8% pre-operative to 21.8% and 18.9% at the final post-operative follow-up respectively. This was not a statistically significant change for either measure (P = 0.15; P = 0.74). There was a significant difference in social isolation at the recovery phase compared to the pre-operative phase (P = 0.01), where people following arthroplasty reported an increase in social isolation (16.9-21.4%). There was no significant difference between the assessment phases in respect to UCLA Loneliness Scale score (P ≥ 0.74). CONCLUSIONS: Given the negative physical and psychological consequences which social isolation and loneliness can have on individuals following THA or TKA, clinicians should be mindful of this health challenge for this population. The reported prevalence of social isolation and loneliness suggests this is an important issue.

The effect of vitamin D supplementation on knee osteoarthritis, the VIDEO study: a randomised controlled trial.

OBJECTIVE: Epidemiological data suggest low serum 25-hydroxyvitamin D3 (25-OH-D3) levels are associated with radiological progression of knee osteoarthritis (OA). This study aimed to assess whether vitamin D supplementation can slow the rate of progression. METHOD: A 3-year, double-blind, randomised, placebo-controlled trial of 474 patients aged over 50 with radiographically evident knee OA comparing 800 IU cholecalciferol daily with placebo. Primary outcome was difference in rate of medial joint space narrowing (JSN). Secondary outcomes included lateral JSN, Kellgren & Lawrence grade, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, function, stiffness and the Get up and Go test. RESULTS: Vitamin D supplementation increased 25-OH-D3 from an average of 20.7 (standard deviation (SD) 8.9) µg/L to 30.4 (SD 7.7) µg/L, compared to 20.7 (SD 8.1) µg/L and 20.3 (SD 8.1) µg/L in the placebo group. There was no significant difference in the rate of JSN over 3 years in the medial compartment of the index knee between the treatment group (average -0.01 mm/year) and placebo group (-0.08 mm/year), average difference 0.08 mm/year (95% confidence interval (CI) [-0.14-0.29], P = 0.49). No significant interaction was found between baseline vitamin D levels and treatment effect. There were no significant differences for any of the secondary outcome measures. CONCLUSION: Vitamin D supplementation did not slow the rate of JSN or lead to reduced pain, stiffness or functional loss over a 3-year period. On the basis of these findings we consider that vitamin D supplementation has no role in the management of knee OA.

Measurements of skeletal muscle mass and power are positively related to a Mediterranean dietary pattern in women.

The age-related loss of skeletal muscle and function are risk factors for osteoporosis and fractures. We found that higher adherence to the Mediterranean diet score was significantly associated with greater fat-free mass and leg explosive power suggesting a role for the Mediterranean Diet in prevention of loss of muscle outcomes. INTRODUCTION: The loss of skeletal muscle mass, strength, and function with age are contributing risk factors for the onset of sarcopenia, frailty, osteoporosis, fractures, and mortality. Nutrition may affect the progression and trajectory of these changes in skeletal muscle but the role of the micronutrient-rich Mediterranean diet (MD) has hardly been investigated in relation to these muscle outcomes. METHODS: We examined associations between the MD score (MDS) and FFM% (fat-free mass / weight × 100), FFMI (fat-free mass/height2), hand grip strength, and leg explosive power (LEP, watts/kg) in a cross-sectional study in 2570 women aged 18-79 years from the TwinsUK study. Measurements of body composition were made using dual-energy X-ray absorptiometry and dietary intake assessed by a food frequency questionnaire. FFM%, FFMI, grip strength, and LEP were compared across quartiles of the MDS after adjustment for covariates, with CRP measured in a subgroup (n = 1658). RESULTS: Higher adherence to the MDS was positively associated with measurements of muscle outcomes, with significant differences of 1.7 % for FFM% and 9.6 % for LEP (P trend <0.001), comparing extreme quartiles of intake, but not with grip strength or CRP concentrations. CONCLUSIONS: For the first time in a northern European population, we have observed significant positive associations between the MDS and FFM% and LEP in healthy women that are potentially clinically relevant, independent of the factors known to influence muscle outcomes. Our findings emphasize the potential role for overall diet quality based on the MD in the prevention of age-related loss of skeletal muscle outcomes.

Young people's exposure to point-of-sale tobacco products and promotions.

OBJECTIVES: Point of sale (POS) displays are one of the most important forms of tobacco marketing still permitted in many countries. Reliable methods for measuring exposure to such displays are needed in order to assess their potential impact, particularly on smoking attitudes and uptake among young people. In this study we use a novel method for evaluating POS exposure based on young people's use of retail outlets and recall of tobacco displays and observational data on the characteristics of displays. STUDY DESIGN: Observational audit of retail outlets (n = 96) and school-based pupil survey (n = 1482) in four Scottish communities reflecting different levels of social deprivation and urbanisation, conducted in 2013 before legislation to remove POS displays was implemented in supermarkets. METHODS: Measures were taken of: visibility and placement of tobacco displays; internal and external advertising; display unit size, branding and design; visibility of pack warnings; proximity of tobacco products to products of potential interest to children and young people; pupils' self-reported frequency of visiting retail outlets; and pupils' recall of tobacco displays. Variation in POS exposure across social and demographic groups was assessed. RESULTS: Displays were highly visible within outlets and, in over half the stores, from the public footway outside. Tobacco products were displayed in close proximity to products of interest to children (e.g. confectionery, in 70% of stores). Eighty percent of pupils recalled seeing tobacco displays, with those from deprived areas more likely to recall displays in small shops. When confectioners, tobacconists and newsagents (CTNs) and grocery/convenience stores (two of the outlet types most often visited by young people) were examined separately, average tobacco display unit sizes were significantly larger in those outlets in more deprived areas. CONCLUSIONS: POS displays remain a key vector in most countries for advertising tobacco products, and it is important to develop robust measures of exposure. The data reported in this paper provide a baseline measure for evaluating the efficacy of legislation prohibiting such displays.

The "psychomicrobiotic": Targeting microbiota in major psychiatric disorders: A systematic review.

The gut microbiota is increasingly considered as a symbiotic partner in the maintenance of good health. Metagenomic approaches could help to discover how the complex gut microbial ecosystem participates in the control of the host's brain development and function, and could be relevant for future therapeutic developments, such as probiotics, prebiotics and nutritional approaches for psychiatric disorders. Previous reviews focused on the effects of microbiota on the central nervous system in in vitro and animal studies. The aim of the present review is to synthetize the current data on the association between microbiota dysbiosis and onset and/or maintenance of major psychiatric disorders, and to explore potential therapeutic opportunities targeting microbiota dysbiosis in psychiatric patients.

[Manipulation in the exercise of psychiatric interviews]. / La manipulation dans la pratique de l'entretien psychiatrique.

INTRODUCTION: The term "manipulation" is defined as "getting someone to behave otherwise than he spontaneously would". Unlike cognitive therapies, it does not involve cognitive functioning and may increase psychotherapies' efficiency. METHOD: In the absence of data in the scientific literature (Medline and Web of Science), we propose a synthesis of theoretical data from social psychology with a reflection on its applications in the daily practice of psychiatry. RESULTS: Firstly we present auto-manipulation: the "chilling effect" is the fact that people tend to keep to a decision and to duplicate it, even if it does not work. The commitment of the patient, i.e., the degree to which he/she identifies with his/her act, will be even stronger if the patient's sense of freedom is high. The rationalization process is the ability for individuals to revisit their beliefs after being forced to issue a behavior (that he/she did not adhere to) to justify it a posteriori. In the second part, we present techniques for hetero-manipulation. Priming is to ask about a low effort to "initiate" the behavior. The lure technique is to hide convenience or invent fictitious benefits of a product, but is not ethical. The labeling technique is to assign an individual to a positive value regardless of his or her behavior, which increases the probability of emission of positive behaviors. The touch technique, whatever the cultural context, encourages a patient to have more confidence in his/her therapist and to make them friendly towards the person involved by creating a positive mood, reduces stress in patients before surgery, and improve the academic performance of students. DISCUSSION AND CONCLUSION: We propose reflections on the application of these concepts in daily practice in the psychiatric interview. These techniques seem fundamental in improving therapeutic alliance and the likelihood of good compliance in our patients, and should be known to all practitioners.

A higher alkaline dietary load is associated with greater indexes of skeletal muscle mass in women.

UNLABELLED: Conservation of muscle mass is important for fall and fracture prevention but further understanding of the causes of age-related muscle loss is required. This study found a more alkaline diet was positively associated with muscle mass in women suggesting a role for dietary acid-base load in muscle loss. INTRODUCTION: Conservation of skeletal muscle is important for preventing falls and fractures but age-related loss of muscle mass occurs even in healthy individuals. However, the mild metabolic acidosis associated with an acidogenic dietary acid-base load could influence loss of muscle mass. METHODS: We investigated the association between fat-free mass (FFM), percentage FFM (FFM%) and fat-free mass index (FFMI, weight/height²), measured using dual-energy X-ray absorptiometry in 2,689 women aged 18-79 years from the TwinsUK Study, and dietary acid-base load. Body composition was calculated according to quartile of potential renal acid load and adjusted for age, physical activity, misreporting and smoking habit (FFM, FFMI also for fat mass) and additionally with percentage protein. RESULTS: Fat-free mass was positively associated with a more alkalinogenic dietary load (comparing quartile 1 vs 4: FFM 0.79 kg P < 0.001, FFM% 1.06 % <0.001, FFMI 0.24 kg/m² P = 0.002), and with the ratio of fruits and vegetables to potential acidogenic foods. CONCLUSIONS: We observed a small but significant positive association between a more alkaline diet and muscle mass indexes in healthy women that was independent of age, physical activity and protein intake equating to a scale of effect between a fifth and one half of the observed relationship with 10 years of age. Although protein is important for maintenance of muscle mass, eating fruits and vegetables that supply adequate amounts of potassium and magnesium are also relevant. The results suggest a potential role for diet in the prevention of muscle loss.

[Charisma and leadership: new challenges for psychiatry]. / Charisme et leadership: de nouveaux défis pour la psychiatrie.

INTRODUCTION: New challenges arise in medicine, particularly in psychiatry. In the near future, psychiatrists' role may evolve into management of mental health care teams (GPs, nurses, psychologists…) thus creating the need for charisma and leadership. Charisma is defined as « a quality that allows it's possessor to exercise influence, authority over a group ¼; leadership as « the function, the position of chief, and by extension, a dominant position ¼. AIM OF THE STUDY: To offer some reflections on charisma and leadership and the ways to develop them in three situations common in clinical practice: dual communication (between caregivers or with patients), oral communication (e.g., during a symposium) and managing a mental health care team. METHOD: Medline (1966-hits) and Web of Science (1975-hits) were explored according to the PRISMA criteria. The research paradigm was [(psychiatrist OR physician) AND mental health AND (leadership OR charisma)]. RESULTS: Two hundred and eighty articles were found, but only 34 corresponded to our subject and were included in the qualitative analysis. The leader must first ask himself/herself about his/her vision of the future, so as to share it with passion with his/her mental health team. Charisma and leadership are based on several values, among which we can mention: providing understandable, personalized care for the patient, in continuity and confidentiality; adapting care to the general population's request, maintaining one's own physical and mental health, submitting one's daily practice to peer review, engaging in continuous improvement of one's practices in response to new requirements, and recognizing that research and instruction are part of an M.D's professional obligations. The clinician will work on ways to develop his/her own charisma, through interactions with peers and team members, the care of his/her appearance (especially for first meetings) and workplace, and through positive reinforcement (some cognitive-behavioral techniques like assertiveness have been proposed to enhance the charisma, e.g., visualization and affirmation). Leadership does not depend on hierarchical position and administrative responsibilities: leaders should learn to manage and harmonize the different types of personalities within his/her team, paying special attention to passive-aggressive attitudes. We recall here some techniques to improve charisma during oral communication, such as making relationships with people by calling them by their names, making reference to things and people that the audience can identify with (like sport or cooking), using one's own style without trying to imitate someone else, focusing on one major idea, being brief and using anecdotes, using silences effectively and finally having good non-verbal communication. The conclusion should never be neglected, as an audience especially remembers the beginning and the end of a presentation. Although some features are common to all charismatic leaders (dominance, self-confidence, high energy level), a recent theory of leadership (called contingency theory) seeks to examine how different leadership styles can adapt to circumstances. This theory focuses more on the vision, passion, determination and courage of the leader and depends not only on their intrinsic qualities. No research has indeed shown individual characteristics that differentiate leaders from followers. However, doctors have not been prepared in their training to acquire leadership skills that they can use to adapt to the circumstances of their clinical practice. The most important qualities expected of a leader according to the current leadership theorists are: listening, communication, stress management, development of other's capacities, feedback, introspection and risk taking. Moreover, leadership involves positive reinforcement of the team while maintaining the feeling of individual autonomy, and being able to take an innovative decision alone with shared optimism. There is no need to have great management responsibilities in order to succeed in leadership. We reiterate the importance for a charismatic leader to smile, to be able to mock oneself and to regulate one's emotions. CONCLUSION: Charisma seems to be an essential dimension for effective leadership and team management. Beyond psychiatry, we believe these reflections to be useful for all branches of medicine.

[Blood-injection-injury phobia: Physochophysiological and therapeutical specificities]. / La phobie du sang-injection-accident : spécificités psychophysiologiques et thérapeutiques.

INTRODUCTION: Seventy-five percent of patients with blood-injection-injury phobia (BII-phobia) report a history of fainting in response to phobic stimuli. This specificity may lead to medical conditions remaining undiagnosed and untreated, incurring considerable cost for the individual and society. The psychophysiology of BII-phobia remains poorly understood and the literature on effective treatments has been fairly sparse. Aims of the systematic review: to synthesize the psychophysiology of BII-phobia and to propose a systematic review of the literature on effectiveness of different treatments evaluated in this indication. RESULTS: Firstly, the most distinct feature of the psychophysiology of BII-phobia is its culmination in a vasovagal syncope, which has been described as biphasic. The initial phase involves a sympathetic activation as is typically expected from fear responses of the fight-flight type. The second phase is characterized by a parasympathetic activation leading to fainting, which is associated with disgust. Subjects with syncope related to BII-phobia have an underlying autonomic dysregulation predisposing them to neurally mediated syncope, even in the absence of any blood or injury stimulus. Many studies report that BII-phobic individuals have a higher level of disgust sensitivity than individuals without any phobia. Secondly, behavioral psychotherapy techniques such as exposure only, applied relaxation, applied tension, and tension only, have demonstrated efficacy with no significant difference between all these techniques. The disgust induction has not improved effectiveness of exposure. CONCLUSION: We have explained the psychophysiology of BII-phobia, the understanding of which is required to study and validate specific techniques, in order to improve the prognosis of this disorder, which is a public health issue.

[Toxoplasma gondii: a potential role in the genesis of psychiatric disorders]. / Toxoplasma gondii : un rôle potentiel dans la genèse de troubles psychiatriques. Une revue systématique de la littérature.

INTRODUCTION: Toxoplasma gondii is the most common protozoan parasite in developed nations. Up to 43% of the French population may be infected, depending on eating habits and exposure to cats, and almost one third of the world human's population may be infected. Two types of infection have been described: a congenital form and an acquired form. Although the medical profession treats these latent cases as asymptomatic and clinically unimportant, results of animal studies and recent studies of personality profiles, behavior, and psychomotor performance have led to reconsider this assumption. PRECLINICAL DATA: Among rats: parasite cysts are more abundant in amygdalar structures than those found in other regions of the brain. Infection does not influence locomotion, anxiety, hippocampal-dependent learning, fear conditioning (or its extinction) and neophobia in rats. Rats' natural predator is the cat, which is also T. gondii's reservoir. Naturally, rats have an aversion to cat urine, but the parasite suppresses this aversion in rats, thus influencing the infection cycle. Tachyzoites may invade different types of nervous cells, such as neurons, astrocytes and microglial cells in the brain, and Purkinje cells in cerebellum. Intracellular tachyzoites manipulate several signs for transduction mechanisms involved in apoptosis, antimicrobial effectors functions, and immune cell maturation. Dopamine levels are 14% higher in mice with chronic infections. These neurochemical changes may be factors contributing to mental and motor abnormalities that accompany or follow toxoplasmosis in rodents and possibly in humans. Moreover, the antipsychotic haloperidol and the mood stabilizer valproic acid most effectively inhibit Toxoplasma growth in vitro with synergistic activity. CLINICAL DATA: The effects of the parasite are not due to the manipulation in an evolutionary sense but merely due to neuropathological or neuroimmunological effects of the parasite's presence. Toxoplasmosis and schizophrenia: epidemiological studies point to a role for toxoplasmosis in schizophrenia's etiology, probably during pregnancy and early life, this association being congruent with studies in animal models indicating that animal exposures of the developing brain to infectious agents or immune modulating agents can be associated with behavioral changes that do not appear until the animal reaches full maturity. Psychiatric patients have increased rates of toxoplasmic antibodies, the differences between cases and controls being greatest in individuals who are assayed near the time of the onset of their symptoms. The increase of dopamine in the brain of infected subjects can represent the missing link between toxoplasmosis and schizophrenia. Toxoplasmosis and Obsessive Compulsive Disorder (OCD): the seropositivity rate for anti-T. gondii IgG antibodies among OCD patients is found to be significantly higher than the rate in healthy volunteers. Infection of basal ganglia may be implicated in the pathogenesis of OCD among Toxoplasma seropositive subjects. Toxoplasmosis and personality: infected men appear to be more dogmatic, less confident, more jealous, more cautious, less impulsive and more orderly than others. Conversely, infected women seem warmest, more conscientious, more insecure, more sanctimonious and more persistent than others. It is possible that differences in the level of testosterone may be responsible for the observed behavioral differences between Toxoplasma-infected and Toxoplasma-free subjects. CONCLUSION: In the future two major avenues for research seem essential. On one hand, prospective studies and research efforts must still be carried out to understand the mechanisms by which the parasite induces these psychiatric disorders. On the other hand, it has not yet been demonstrated that patients with positive toxoplasmic serology may better respond to haloperidol's or valproic acid's antiparasitic activity. These results may appear as a major issue in the drug's prescribing choices and explain variability in response to the treatment of patients with schizophrenia that is not explained by the genetic polymorphism.

Hip arthroplasty practice across the Organisation for Economic Co-operation and Development (OECD) over the last decade.

INTRODUCTION: There are large variations in the number of hip replacements performed between countries, demonstrating large health inequalities; however, there has been limited research on this variation. The aims of this paper were to compare rates of hip replacements using Organisation for Economic Co-operation and Development (OECD) data for the period 2008-2018. The study also compared changes in the number of hip replacements in the total population and in only those aged over 65, and looked for a correlation of health expenditure and gross domestic product (GDP) with rates of hip replacements. METHODS: The OECD collects annual data from all member countries on the numbers of hip replacements, healthcare expenditure and GDP. Data analysis was undertaken using STATA. Descriptive statistics and Pearson's correlation coefficient were performed. RESULTS: The mean number of hip replacements performed in OECD countries in 2018 was 191.5 per 100,000 population per year. The largest number was 310.6 in Germany and the lowest was 8.6 in Mexico. There has been a 21.7% increase in the mean number of hip replacements across OECD countries. There was a moderate and significant Pearson coefficient of 0.468 (p = 0.009) between the number of hip replacements performed per 100,000 population in 2018 and GDP per person, and a strong and significant correlation with health expenditure (R = 0.784, p < 0.001). There was a moderate correlation (R = 0.645, p = 0.003) between the percentage change in the number of hip replacements performed per 100,000 population and the percentage change in healthcare expenditure per person between 2008 and 2018. CONCLUSIONS: There is 36-fold variation in the practice of hip replacements across the OECD and the number of hip replacements has increased by more than 20% over the past decade. The number of hip replacements performed appears to be correlated with health expenditure in each country and may indicate a need that can only be met by increasing health expenditure.

Sex, military occupation and rank are associated with risk of anterior cruciate ligament injury in tactical-athletes.

INTRODUCTION: Anterior cruciate ligament (ACL) injury is common within the US military and represents a significant loss to readiness. Since recent changes to operational tempo, there has not been an analysis of ACL injury risk. The aim of this retrospective cohort study was to evaluate military occupation, sex, rank and branch of service on ACL injury risk in the US military from 2006 to 2018. METHODS: The Defense Medical Epidemiology Database was queried for the number of US tactical athletes with International Classification of Diseases diagnosis codes 717.83 (old disruption of ACL), 844.2 (sprain of knee cruciate ligament), M23.61 (other spontaneous disruption of ACL) and S83.51 (sprain of ACL of knee) on their initial encounter. Relative risk and χ2 statistics were calculated to assess sex and military occupation effects on ACL injury. A multivariable negative binomial regression model evaluated changes in ACL injury incidence with respect to sex, branch of service and rank. RESULTS: The study period displayed a significant decrease in the ACL injury rate at 0.18 cases per 1000 person-years or relative decrease of 4.08% each year (p<0.001) after averaging over the main and interactive effects of sex, rank and branch of service. The interaction effect of time with sex indicated a steeper decline in the incidence in men as compared with women. The risk of ACL injury by sex was modified by rank. The incidence among military personnel varied by occupation. CONCLUSION: Despite the decline among tactical athletes over time, rates of ACL injury remain much higher than the general US population. Sex, rank, branch of service and military occupation were found to be risk factors for ACL injury. It is critical for policy makers to understand the salient risk factors for ACL injury to guide proactive measures to prevent injury.

Medical correlates of first-term attrition in US Navy personnel.

INTRODUCTION: First-term attrition (FTA), or failure of a military service member to complete their initial service contract, is a major financial burden and source of lost manpower in the US Navy. The objective of the present study was to examine medical correlates of FTA using healthcare and disability rating data. METHODS: In this retrospective cohort study, all US Navy-enlisted personnel between the years 2003 and 2018 with FTA (n=58 777) and regular discharge (n=203 084) were identified for analysis from accession dates in the Career History Archival Medical and Personnel System. Medical diagnoses from outpatient and inpatient records were abstracted from the Military Health System Data Repository. For a subgroup of the study population discharged with a disability rating (n=12 880), diagnoses were identified from the Integrated Disability Evaluation System. The FTA and regular discharge groups were compared using relative risks (RRs) and 95% CIs, and per cent differences for the disability subgroup analysis. RESULTS: Compared with regular discharges, those with FTA were more likely to have outpatient and inpatient diagnoses for mental health disorders. Personality disorder yielded the strongest association with FTA in both outpatient (RR=10.45, 95% CI 9.79 to 11.16) and inpatient settings (RR=18.97, 95% CI 14.16 to 25.42). Other disorders associated with FTA included schizophrenia, substance-related disorders, poisoning by psychotropic agents and adjustment disorders. In the disability analysis, the FTA group relative to regular discharges had the largest per cent differences for 'arthritis, degenerative (hypertrophic or osteoarthritis)' (10.8% vs 2.5%) and 'tibia and fibula, impairment' (3.0% vs 0.4%). CONCLUSIONS: This study provides evidence that FTA is associated with both mental and physical health conditions. Mental and physical factors related to FTA require further examination, particularly whether pre-enlistment screening or early career intervention could lead to mitigation strategies. Future research should extend this analysis to other services and population subgroups.

Does policy that provides choice in athletic footwear affect musculoskeletal injury risk in US Coast Guard recruits?

INTRODUCTION: Musculoskeletal injuries (MSKIs) are ubiquitous during initial entry military training, with overuse injuries the most common. A common injury mechanism is running, an activity that is integral to US Coast Guard (USCG) training and a requirement for graduation. The purpose of this study was to assess the effects of a policy that allowed for athletic footwear choice on risk of lower quarter MSKI in USCG recruits. METHODS: A retrospective cohort study was performed that included 1230 recruits (1040 men, 190 women) who trained under a policy that allowed self-selection of athletic footwear and 2951 recruits (2329 men, 622 women) who trained under a policy that mandated use of prescribed uniform athletic shoes and served as controls. Demographic data and physical performance were derived from administrative records. Injury data were abstracted from a medical tracking database. Unadjusted risk calculations and multivariable logistic regression assessing the effects of group, age, sex, height, body mass and 2.4 km run times on MSKI were performed. RESULTS: Ankle-foot, leg, knee and lumbopelvic-hip complex injuries were ubiquitous in both groups (experimental: 13.13 per 1000 person-weeks; control: 11.69 per 1000 person-weeks). Group was not a significant factor for any of the injuries assessed in either the unadjusted or adjusted analysis, despite widespread reports of pain (58.6%), perceived injury attribution (15.7%), perceived deleterious effect on performance (25.3%), general dissatisfaction (46.3%) and intended discontinuance of use following graduation (87.7%). CONCLUSION: MSKI continues to be a major source of morbidity in the recruit training population. The policy that allowed USCG recruits to self-select athletic footwear did not decrease or increase the risk of MSKI. While regulations pertaining to footwear choice did not influence injury outcomes, there was general dissatisfaction with the prescribed uniform athletic footwear conveyed by the recruits and widespread reports of discomfort, perceived deleterious effects from wear and intended discontinued use following training completion.