Handheld vital microscopy for the identification of microcirculatory alterations in cervical intraepithelial neoplasia and cervical cancer.

BACKGROUND: Ninety percent of cervical cancer (CC) diagnoses and deaths occur in low and middle-income countries (LMICs). Especially in these countries, where human and material resources are limited, there is a need for real-time screening methods that enable immediate treatment decisions (i.e., 'see and treat'). OBJECTIVE: To evaluate whether handheld vital microscopy (HVM) enables real-time detection of microvascular alterations associated with cervical intraepithelial neoplasia (CIN) and CC. METHODS: A cross-sectional study was conducted in an oncologic hospital and outpatient clinic, and included ten healthy controls, ten women with CIN, and ten women with CC. The microvasculature was assessed in four quadrants of the uterine cervix using HVM. The primary outcome was the presence of abnormal angioarchitecture (AA). Secondary outcomes included capillary loop density (CD), total vessel density (TVD), functional capillary density (FCD), and the proportion of perfused vessels (PPV). RESULTS: 198 image sequences of the cervical microvasculature were recorded. Compared to healthy controls, significantly more abnormal image sequences were observed in women with high-grade CIN (11 % vs. 44 %, P < 0.001) and women with CC (11 % vs. 69 %, P < 0.001). TVD, FCD, and PPV were lower in women with CIN and CC. CONCLUSIONS: HVM enables easy, real-time, non-invasive assessment of cervical lesions through the detection of microvascular alterations. Thereby, HVM potentially provides an opportunity for point-of-care screening, which may enable immediate treatment decisions (see and treat) and reduce the number of unnecessary surgical interventions.

Embedded macrophages induce intravascular coagulation in 3D blood vessel-on-chip.

Macrophages are innate immune cells that prevent infections and help in wound healing and vascular inflammation. While these cells are natural helper cells, they also contribute to chronic diseases, e.g., by infiltrating the endothelial layer in early atherosclerosis and by promoting vascular inflammation. There is a crosstalk between inflammatory pathways and key players in thrombosis, such as platelets and endothelial cells - a phenomenon known as 'thromboinflammation'. The role of the embedded macrophages in thromboinflammation in the context of vascular disease is incompletely understood. Blood vessels-on-chips, which are microfluidic vascular cell culture models, have been used extensively to study aspects of vascular disease, like permeability, immune cell adhesion and thrombosis. Blood perfusion assays in blood vessel-on-chip models benefit from multiple unique aspects of the models, such as control of microvessel structure and well-defined flow patterns, as well as the ability to perform live imaging. However, due to their simplified nature, blood vessels-on-chip models have not yet been used to capture the complex cellular crosstalk that is important in thromboinflammation. Using induced pluripotent stem cell-derived endothelial cells and polarized THP-1 monocytes, we have developed and systematically set up a 3D blood vessel-on-chip with embedded (lipid-laden) macrophages, which is created using sequential cell seeding in viscous finger patterned collagen hydrogels. We have set up a human whole blood perfusion assay for these 3D blood vessels-on-chip. An increased deposition of fibrin in the blood vessel-on-chip models containing lipid-laden macrophages was observed. We anticipate the future use of this advanced vascular in vitro model in drug development for early atherosclerosis or aspects of other vascular diseases.

Cost-utility analysis of a structured medication review compared to usual care in Parkinson's disease.

PURPOSE: For controlling symptoms in Parkinson's disease (PD) together with treating additional comorbidities, patients often face complex medication regimens, with suboptimal adherence, drug-related problems, and diminished therapy efficacy as a common consequence. A medication review could potentially tackle these issues, among others by optimizing drug treatment. Even if no change in clinical outcomes is observed, this intervention might decrease health care costs by reducing drug-related problems and hospital admissions. This study aimed to gain more insight in the health benefits and costs of a structured medication review (SMR) in PD. METHODS: A cost-utility analysis was performed, based on a multicenter randomized controlled trial with 202 PD patients with polypharmacy. The intervention group received an SMR, whereas the control group received usual care. The intervention effect after 6 months of follow-up was presented as incremental quality-adjusted life years (QALY) using the EQ-5D-5L questionnaire. Costs were based on real-world data. Missing data was imputed using multiple imputation techniques. Bootstrapping was used to estimate the uncertainty in all health and economic outcomes. RESULTS: The QALY gain in the intervention group compared to the control group was - 0.011 (95% CI - 0.043; 0.020). Incremental costs were €433 (95% CI - 873; 1687). When adapting a willingness-to-pay threshold of €20,000/QALY and €80,000/QALY, the probability of SMRs being cost-effective was 18% and 30%, respectively. CONCLUSION: A community pharmacist-led SMR in PD patients in the current setting shows no apparent benefit and is not cost-effective after 6 months, compared to usual care. TRIAL REGISTRATION: Netherlands Trial Register, NL4360. Registered 17 March 2014.

Protocol for a randomized controlled multicenter trial assessing the efficacy of leuprorelin for severe polycystic liver disease: the AGAINST-PLD study.

BACKGROUND: In patients with severe polycystic liver disease (PLD), there is a need for new treatments. Estrogens and possibly other female sex hormones stimulate growth in PLD. In some patients, liver volume decreases after menopause. Female sex hormones could therefore be a target for therapy. The AGAINST-PLD study will examine the efficacy of the GnRH agonist leuprorelin, which blocks the production of estrogen and other sex hormones, to reduce liver growth in PLD. METHODS: The AGAINST-PLD study is an investigator-driven, multicenter, randomized controlled trial. Institutional review board (IRB) approval was received at the University Medical Center of Groningen and will be collected in other sites before opening these sites. Thirty-six female, pre-menopausal patients, with a very large liver volume for age (upper 10% of the PLD population) and ongoing liver growth despite current treatment options will be randomized to direct start of leuprorelin or to 18 months standard of care and delayed start of leuprorelin. Leuprorelin is given as 3.75 mg subcutaneously (s.c.) monthly for the first 3 months followed by 3-monthly depots of 11.25 mg s.c. The trial duration is 36 months. MRI scans to measure liver volume will be performed at screening, 6 months, 18 months, 24 months and 36 months. In addition, blood will be drawn, DEXA-scans will be performed and questionnaires will be collected. This design enables comparison between patients on study treatment and standard of care (first 18 months) and within patients before and during treatment (whole trial). Main outcome is annualized liver growth rate compared between standard of care and study treatment. Secondary outcomes are PLD disease severity, change in liver growth within individuals and (serious) adverse events. The study is designed as a prospective open-label study with blinded endpoint assessment (PROBE). DISCUSSION: In this trial, we combined the expertise of hepatologist, nephrologists and gynecologists to study the effect of leuprorelin on liver growth in PLD. In this way, we hope to stop liver growth, reduce symptoms and reduce the need for liver transplantation in severe PLD. Trial registration Eudra CT number 2020-005949-16, registered at 15 Dec 2020. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-005949-16 .

Lifetime prevalence and determinants of hand eczema in an adolescent population in Germany: 15-year follow-up of the LISA cohort study.

BACKGROUND: Hand eczema is a common inflammatory skin disorder in both adolescence and adulthood. OBJECTIVES: We sought to assess the lifetime prevalence of hand eczema and associated exogenous and endogenous risk factors among adolescents in Germany. METHODS: This was a cross-sectional study embedded into a prospective population-based birth cohort in four regions of Germany, which recruited healthy neonates born between November 1997 and January 1999. We included 1736 participants who had completed the 15-year follow-up from birth cohort and 84.6% (1468/1736) had clearly reported whether they have ever had hand eczema. All the data were based on questionnaires and blood tests (immunoglobulin E). Multivariable logistic regression analysis was used to examine endogenous and exogenous factors in relation to the lifetime prevalence of hand eczema among adolescents. RESULTS: One thousand four hundred and sixty-eight adolescents (715 girls, 48.7%) were included in the final analysis. The lifetime prevalence of hand eczema among adolescents at the age of 15 was 10.4% (95% confidence interval [CI]: 8.9%-12.1%), with a significantly higher lifetime prevalence among girls than boys (12.7% vs. 8.2%, P = 0.005). Multivariable logistic regression analysis indicated statistically significant associations between the lifetime prevalence of hand eczema and having ever been diagnosed with atopic dermatitis (aOR = 1.8, 95% CI: 1.1-2.8) or having ever had dry skin (aOR = 1.9, 95% CI: 1.1-3.1), respectively. No statistically significant independent associations were found between asthma, hay fever, allergy-related clinical symptoms, immunoglobulin E positivity and other exogenous factors in relation to hand eczema. CONCLUSION: Our study fills a research gap on the epidemiological burden of hand eczema among adolescents. One out of ten ever suffered from hand eczema until age 15 years indicating that hand eczema constitutes a significant burden in paediatric populations. The role of atopic dermatitis in hand eczema reinforces previous findings. Exogenous risk factors warrant further investigation.

[The life quality of the disabled as a result of diseases of peripheral nervous system].

The article considers results of studying the quality of life of disabled patients because of diseases of peripheral nervous system. The significantly low level of indices of quality of life self-assessment was established on all scales of SF-36 questionnaire that are from 3 to 7 times lower than similar indices in population of Russia. The assessment of quality of life of disabled patients is necessary to determine effectiveness of applied rehabilitation measures and application of obtained results in planning further rehabilitation and habilitation activities.

[The social economic aspects of disability resulted from diseases of peripheral nervous system].

The diseases of peripheral nervous system (PNS diseases) are diagnosed in 48%-72% of workers in various branches of economy. They made up more than half of all occupational diseases and are the main cause of labor ability and of high level of disability able-bodied population. The purpose of the study is to assess social economic importance of disability because of PNS diseases of able-bodied population in the Republic of Bashkortostan. It is established that in 2014-2018 about 107 individuals of able-bodied age for the first time became disabled because of PNS diseases. The average annual level of individuals of able-bodied age with for the first time established disabilities because of PNS diseases made up to 0.1 cases per 10 thousand of population. Among the disabled 69.0 ± 5.4% are males. The disability rate in males (0.142o/ooo) is twice higher than in females (0.063o/ooo). The average age of the disabled is 48.7 ± 5.7 years. In the structure of disability dominate lumbosacral radiculopathy (50.9%), polyneuropathy of upper (15.3%) and lower (13.5%) extremities. In average, the disability develops in 11.3 years prior to age of 60 years and on 3.8-5.5 years earlier than in case of other diseases. The disability because of PNS diseases shortens healthy life expectancy by 16.0% in males and by 17.8% in females. Annual economic losses come to more than 26 million rubles of non-produced production. The disability because of PNS consists significant social economic problem of society and requires increased attention to prevention, early diagnostics, treatment, improvement of quality of medical social expertise, rehabilitation and habilitation.

The sex-shift in single disease and multimorbid asthma and rhinitis during puberty - a study by MeDALL.

BACKGROUND: Cross-sectional studies suggested that allergy prevalence in childhood is higher in boys compared to girls, but it remains unclear whether this inequality changes after puberty. We examined the sex-specific prevalence of asthma and rhinitis as single and as multimorbid diseases before and after puberty onset in longitudinal cohort data. METHODS: In six European population-based birth cohorts of MeDALL, we assessed the outcomes: current rhinitis, current asthma, current allergic multimorbidity (ie, concurrent asthma and rhinitis), puberty status and allergic sensitization by specific serum antibodies (immunoglobulin E) against aero-allergens. With generalized estimating equations, we analysed the effects of sex, age, puberty (yes/no) and possible confounders on the prevalence of asthma and rhinitis, and allergic multimorbidity in each cohort separately and performed individual participant data meta-analysis. FINDINGS: We included data from 19 013 participants from birth to age 14-20 years. Current rhinitis only affected girls less often than boys before and after puberty onset: adjusted odds ratio for females vs males 0.79 (95%-confidence interval 0.73-0.86) and 0.86 (0.79-0.94), respectively (sex-puberty interaction P = .089). Similarly, for current asthma only, females were less often affected than boys both before and after puberty onset: 0.71, 0.63-0.81 and 0.81, 0.64-1.02, respectively (sex-puberty interaction P = .327). The prevalence of allergic multimorbidity showed the strongest sex effect before puberty onset (female-male-OR 0.55, 0.46-0.64) and a considerable shift towards a sex-balanced prevalence after puberty onset (0.89, 0.74-1.04); sex-puberty interaction: P < .001. INTERPRETATION: The male predominance in prevalence before puberty and the "sex-shift" towards females after puberty onset were strongest in multimorbid patients who had asthma and rhinitis concurrently.

Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium.

BACKGROUND: Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity. METHODS: This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores). RESULTS: Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (ß std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged. CONCLUSIONS: Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

Peripartum fetal distress in diabetic women: a retrospective case-cohort study.

BACKGROUND: Major concerns of pregnancies complicated by diabetes mellitus are an increased risk of adverse perinatal outcome. The objective of this study was to analyse the rate of fetal distress during labor in women with type 1, type 2 and gestational diabetes compared to control women. METHODS: A retrospective case-cohort study was conducted at the VU University Medical Center, Amsterdam; a tertiary care hospital. 117 women with type 1 diabetes, 59 women with type 2 diabetes, 303 women with gestational diabetes and 15,260 control women were included, who delivered between March 2004 and February 2014. Linear and logistic regression analyses were used to compare maternal and pregnancy characteristics. Risk of fetal distress and perinatal asphyxia was assessed by multiple regression analyses, adjusted for confounding factors as age, smoking, parity, previous cesarean section, hypertensive disorder, pre-eclampsia, prematurity, induction of labor and macrosomia. Main outcome measure was fetal distress, defined either as clinical indication for instrumental or cesarean delivery; or low umbilical artery pH (UA pH), or admission to neonatal unit (NU). RESULTS: The indication for instrumental or cesarean delivery in women with type 1 and type 2 diabetes mellitus was more frequently based on fetal distress as compared to controls (adjusted OR 2.76 CI 1.74-4.40 and adjusted OR 2.31 CI 1.19-4.51, respectively). In comparison with the control group, infants of women with type 1 diabetes had an increased risk of UA pH < 7.20 (adjusted OR 1.88 CI 1.23-2.87) or UA pH < 7.10 (adjusted OR 3.35 CI 1.79-6.27). Also, infants of women with type 1 diabetes were at increased risk for admission to NU as compared to infants of control women (OR 8.07 CI 4.75-13.70). CONCLUSIONS: Women with type 1 and type 2 diabetes are at increased risk of fetal distress during labor as compared to controls.

Hospitalised cancer patients' perceptions of individualised nursing care in four European countries.

The aim of this study was to describe hospitalised cancer patients' perceptions of individualised care in four European countries and compare these perceptions using the patients' socio-demographic characteristics and the Individualized Care Scale. The patients' socio-demographic characteristics used were: education, age, gender, type of hospital admission, previous hospitalisation and hospital length of stay. The Individualized Care Scale has two parts (1) nurses' support of individuality and (2) patients' receipt of individuality. Data (n = 599) were collected in Cyprus (n = 150), Finland (n = 158), Greece (n = 150) and Sweden (n = 141). Multivariate analysis of variance models were constructed and differences in perceptions of individualised care were analysed using the patients' socio-demographic characteristics as covariates. The level of support for individuality and receipt of individualised care was reported as moderate and good respectively. Generally, the highest assessments were made by the Swedish respondents and the lowest by those in Greece. This study revealed some between-country differences in patients' perceptions of care individualisation. These differences, for example, conceptual, educational, based in clinical practice or in the health organisation, require further research. Enquiry into the individualised care perceptions of health care providers and the families of cancer patients would also be useful.

Early life travelling does not increase risk of atopic outcomes until 15 years: results from GINIplus and LISAplus.

BACKGROUND: Westernized lifestyle has been blamed for allergy epidemics. One of its characteristics is increased distances and frequency of travelling from early life onwards. Early life travelling to places which substantially differ from home environment in terms of climate, vegetation and food could increase the exposure to further unknown allergens and hence promote the development of allergies, but no epidemiological study has investigated this speculation. METHODS: Detailed data on travelling during the first 2 years of life as well as a range of atopic outcomes along with potential confounders up to age 15 years were collected prospectively within two large population-based multicentre German birth cohorts - GINIplus and LISAplus. Farthest travelling destination (within Germany; middle/northern/eastern Europe; southern Europe; outside Europe), total number of trips and their combination were considered as exposures. Six atopic outcomes were used: (1) doctor-diagnosed asthma, (2) doctor-diagnosed allergic rhinitis, (3) nose and eye symptoms, (4) sensitization to food allergens, (5) sensitization to indoor and (6) outdoor inhalant allergens. Longitudinal associations between each exposure and health outcome pair were analysed using generalized estimation equations (GEEs). RESULTS: The results of our longitudinal analyses of 5674 subjects do not support the research hypothesis that travelling abroad to different regions in Europe or beyond Europe and frequency of travelling increase prevalence of doctor-diagnosed asthma and allergic rhinitis, nose and eye symptoms and allergic sensitization up to 15 years of age. Furthermore, there was no indication of age-varying effects. CONCLUSIONS: Early life travelling does not seem to increase risk of atopic outcomes. Nevertheless, as we could not account for the type of visited environment or length of stay, these first findings should be interpreted with caution.

Dual hypothermic oxygenated machine perfusion in liver transplants donated after circulatory death.

BACKGROUND: Experimental studies have suggested that end-ischaemic dual hypothermic oxygenated machine perfusion (DHOPE) may restore hepatocellular energy status and reduce reperfusion injury in donation after circulatory death (DCD) liver grafts. The aim of this prospective case-control study was to assess the safety and feasibility of DHOPE in DCD liver transplantation. METHODS: In consecutive DCD liver transplantations, liver grafts were treated with end-ischaemic DHOPE. Outcome was compared with that in a control group of DCD liver transplantations without DHOPE, matched for donor age, donor warm ischaemia time, and recipient Model for End-stage Liver Disease (MELD) score. All patients were followed for 1 year. RESULTS: Ten transplantations involving liver grafts treated with DHOPE were compared with 20 control procedures. There were no technical problems. All 6-month and 1-year graft and patient survival rates were 100 per cent in the DHOPE group. Six-month graft survival and 1-year graft and patient survival rates in the control group were 80, 67 and 85 per cent respectively. During DHOPE, median (i.q.r.) hepatic adenosine 5'-triphosphate (ATP) content increased 11-fold, from 6 (3-10) to 66 (42-87) µmol per g protein (P = 0·005). All DHOPE-preserved livers showed excellent early function. At 1 week after transplantation peak serum alanine aminotransferase (ALT) and bilirubin levels were twofold lower in the DHOPE group than in the control group (ALT: median 966 versus 1858 units/l respectively, P = 0·006; bilirubin: median 1·0 (i.q.r. 0·7-1·4) versus 2·6 (0·9-5·1) mg/dl, P = 0·044). None of the ten DHOPE-preserved livers required retransplantation for non-anastomotic biliary stricture, compared with five of 20 in the control group (P = 0·140). CONCLUSION: This clinical study of end-ischaemic DHOPE in DCD liver transplantation suggests that the technique restores hepatic ATP, reduces reperfusion injury, and is safe and feasible. RCTs with larger numbers of patients are warranted to assess the efficacy in reducing post-transplant biliary complications.

Metacognitive beliefs mediate the effect of emotional abuse on depressive and psychotic symptoms in severe mental disorders.

BACKGROUND: Early trauma is linked to higher symptom levels in bipolar and psychotic disorders, but the translating mechanisms are not well understood. This study examines whether the relationship between early emotional abuse and depressive symptoms is mediated by metacognitive beliefs about thoughts being uncontrollable/dangerous, and whether this pathway extends to influence positive symptoms. METHOD: Patients (N = 261) with psychotic or bipolar disorders were assessed for early trauma experiences, metacognitive beliefs, and current depression/anxiety and positive symptoms. Mediation path analyses using ordinary least-squares regressions tested if the effect of early emotional abuse on depression/anxiety was mediated by metacognitive beliefs, and if the effect of early emotional abuse on positive symptoms was mediated by metacognitive beliefs and depression/anxiety. RESULTS: Metacognitive beliefs about thoughts being uncontrollable/dangerous significantly mediated the relationship between early emotional abuse and depression/anxiety. Metacognitive beliefs and depression/anxiety significantly mediated the relationship between early emotional abuse and positive symptoms. The models explained a moderate amount of the variance in symptoms (R 2 = 0.21-0.29). CONCLUSION: Our results indicate that early emotional abuse is relevant to depression/anxiety and positive symptoms in bipolar and psychotic disorders, and suggest that metacognitive beliefs could play a role in an affective pathway to psychosis. Metacognitive beliefs could be relevant treatment targets with regards to depression/anxiety and positive symptoms in bipolar and psychotic disorders.

Positive symptoms associate with cortical thinning in the superior temporal gyrus via the ENIGMA Schizophrenia consortium.

OBJECTIVE: Based on the role of the superior temporal gyrus (STG) in auditory processing, language comprehension and self-monitoring, this study aimed to investigate the relationship between STG cortical thickness and positive symptom severity in schizophrenia. METHOD: This prospective meta-analysis includes data from 1987 individuals with schizophrenia collected at seventeen centres around the world that contribute to the ENIGMA Schizophrenia Working Group. STG thickness measures were extracted from T1-weighted brain scans using FreeSurfer. The study performed a meta-analysis of effect sizes across sites generated by a model predicting left or right STG thickness with a positive symptom severity score (harmonized SAPS or PANSS-positive scores), while controlling for age, sex and site. Secondary models investigated relationships between antipsychotic medication, duration of illness, overall illness severity, handedness and STG thickness. RESULTS: Positive symptom severity was negatively related to STG thickness in both hemispheres (left: ßstd = -0.052; P = 0.021; right: ßstd = -0.073; P = 0.001) when statistically controlling for age, sex and site. This effect remained stable in models including duration of illness, antipsychotic medication or handedness. CONCLUSION: Our findings further underline the important role of the STG in hallmark symptoms in schizophrenia. These findings can assist in advancing insight into symptom-relevant pathophysiological mechanisms in schizophrenia.

Compliance with Clostridium difficile treatment guidelines: effect on patient outcomes.

Guidelines for the severity classification and treatment of Clostridium difficile infection (CDI) were published by Infectious Diseases Society of America (IDSA)/Society for Healthcare Epidemiology of America (SHEA) in 2010; however, compliance and efficacy of these guidelines has not been widely investigated. This present study assessed compliance with guidelines and its effect on CDI patient outcomes as compared with before these recommendations. A retrospective study included all adult inpatients with an initial episode of CDI treated in a single academic center from January 2009 to August 2014. Patients after guideline publication were compared with patients treated in 2009-2010. Demographic, clinical, and laboratory data were collected to stratify for disease severity. Outcome measures included compliance with guidelines, mortality, length of stay (LOS), and surgical intervention for CDI. A total of 1021 patients with CDI were included. Based upon the 2010 guidelines, 42 (28·8%) of 146 patients treated in 2009 would have been considered undertreated, and treatment progressively improved over time, as inadequate treatment decreased to 10·0% (15/148 patients) in 2014 (P = 0·0005). Overall, patient outcomes with guideline-adherent treatment decreased CDI attributable mortality twofold (P = 0·006) and CDI-related LOS by 1·9 days (P = 0·0009) when compared with undertreated patients. Compliance with IDSA/SHEA guidelines was associated with a decreased risk of mortality and LOS in hospitalized patients with CDI.

Modelling difficulties in abstract thinking in psychosis: the importance of socio-developmental background.

INTRODUCTION: Abstract thinking is important in modern understanding of neurocognitive abilities, and a symptom of thought disorder in psychosis. In patients with psychosis, we assessed if socio-developmental background influences abstract thinking, and the association with executive functioning and clinical psychosis symptoms. METHODS: Participants (n = 174) had a diagnosis of psychotic or bipolar disorder, were 17-65 years, intelligence quotient (IQ) > 70, fluent in a Scandinavian language, and their full primary education in Norway. Immigrants (N = 58) were matched (1:2) with participants without a history of migration (N = 116). All participants completed a neurocognitive and clinical assessment. Socio-developmental background was operationalised as human developmental index (HDI) of country of birth, at year of birth. Structural equation modelling was used to assess the model with best fit. RESULTS: The model with best fit, χ2 = 96.591, df = 33, p < .001, confirmed a significant indirect effect of HDI scores on abstract thinking through executive functioning, but not through clinical psychosis symptoms. CONCLUSIONS: This study found that socio-developmental background influences abstract thinking in psychosis by indirect effect through executive functioning. We should take into account socio-developmental background in the interpretation of neurocognitive performance in patients with psychosis, and prioritise cognitive remediation in treatment of immigrant patients.

An insight into the antibiofilm properties of Costa Rican stingless bee honeys.

OBJECTIVE: There is an increasing search for antibiofilm agents that either have specific activity against biofilms or may act in synergy with antimicrobials. Our objective is to examine the the antibiofilm properties of stingless bee honeys. METHOD: Meliponini honeys from Costa Rica were examined along with Medihoney as a reference. All honeys were submitted to a screening composed of minimum inhibitory concentration, inhibition of biofilm formation and biofilm destruction microplate-based assays against a Staphylococcus aureus biofilm forming strain. Dialysis led to the isolation of an antibiofilm fraction in Tetragonisca angustula honeys. The honey antibiofilm fraction was evaluated for protease activity and for any synergistic effect with antibiotics on a Staphylococcus aureus biofilm. The active fraction was then separated through activity guided isolation techniques involving SDS-PAGEs, anion exchange and size exclusion fast protein liquid chromatographies. The fractions obtained and the isolated antibiofilm constituents were tested for amylase and DNase activity. RESULTS: A total of 57 Meliponini honeys from Costa Rica were studied in this research. The honeys studied belonged to the Tetragonisca angustula (n=36) and Melipona beecheii (n=21) species. Costa Rican Tetragonisca angustula honeys can inhibit the planktonic growth, biofilm formation, and are capable of destroying a Staphylococcus aureus biofilm. The antibiofilm effect was observed in the protein fraction of Tetragonisca angustula honeys. The biofilm destruction proteins allowed ampicillin and vancomycin to recover their antimicrobial activity over a Staphylococcus aureus biofilm. The antibiofilm proteins are of bee origin, and their activity was not due to serine, cysteine or metalloproteases. There were 2 proteins causing the antibiofilm action; these were named the Tetragonisca angustula biofilm destruction factors (TABDFs). TABDF-1 is a monomeric protein of approximately 50kDa that is responsible of the amylase activity of Tetragonisca angustula honeys. TABDF-2 is a protein monomer of approximately 75kDa. CONCLUSION: Tetragonisca angustula honeys from Costa Rica are a promising candidate for research and development of novel wound dressings focused on the treatment of acute and chronic Staphylococcus aureus biofilm wound infections.