ABSTRACT
Nailfold capillary density is lower in patients with pulmonary arterial hypertension (PAH). It is unclear whether this observation signifies a unique systemic manifestation of PAH, or reflects microcirculatory dysfunction secondary to pulmonary hypertension (PH). Capillary density and loop dimensions were measured by nailfold-capillaroscopy (NC) in 30 PAH (23 idiopathic, or iPAH, 7 hereditary, or hPAH), 17 chronic thromboembolic PH (CTEPH) patients and 48 controls. NC-Measurements were repeated after pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) in CTEPH patients. We examined whether NC-measurements were related to markers of disease severity and predictive of time to clinical worsening (TTCW) as tested by univariate linear/logistic regression and cox-regression analysis, respectively. Capillary density was significantly lower in PAH (7.5 ± 1.1, p < 0.001) and in CTEPH (8.4 ± 1.5, p < 0.001) compared to asymptomatic controls (10.3 ± 1.0 capillaries/mm). Capillary density was similar in iPAH and hPAH and unrelated to hemodynamics in either PAH or CTEPH. A lower capillary density was predictive of clinical worsening in PAH (p 0.05). After normalization of pulmonary artery pressures by PEA or BPA, capillary density remained reduced in CTEPH patients. Capillary loop apex, capillary and venous- and arterial limb diameter were increased in patients with PAH and CTEPH compared to controls. Nailfold capillary density is reduced to a similar extent in iPAH, hPAH and CTEPH. Normalization of hemodynamics by PEA or BPA does not lead to a restoration of capillary density in CTEPH. Capillary dimensions were increased in both patients with PAH and CTEPH. Lower capillary density was predictive of clinical worsening in PAH. Our findings indicate that a loss of peripheral capillaries is not specific to PAH and is not related to the hemodynamic disturbance per se, but that shared mechanisms may account for a simultaneous development of a systemic microangiopathy and pulmonary vascular remodeling.
Subject(s)
Capillaries , Hypertension, Pulmonary , Humans , Female , Male , Middle Aged , Capillaries/pathology , Capillaries/physiopathology , Hypertension, Pulmonary/physiopathology , Hypertension, Pulmonary/etiology , Aged , Biomarkers , Pulmonary Embolism/physiopathology , Pulmonary Embolism/complications , Microscopic Angioscopy/methods , Adult , Pulmonary Arterial Hypertension/physiopathology , Pulmonary Arterial Hypertension/surgery , Endarterectomy/methods , Microvascular Density , Chronic Disease , Nails/blood supply , Case-Control StudiesABSTRACT
Background and objectives People with psychotic disorders can experience a lack of active involvement in their decisional process. Clinical decision aids are shared decision-making tools which are currently rarely used in mental healthcare. We examined the effects of Treatment E-Assist (TREAT), a computerized clinical decision aid in psychosis care, on shared decision-making and satisfaction with consultations as assessed by patients. Methods A total of 187 patients with a psychotic disorder participated. They received either treatment as usual in the first phase (TAU1), TREAT in the second phase or treatment as usual in the third phase of the trial (TAU2). The Decisional Conflict Scale was used as primary outcome measure for shared decision-making and patient satisfaction as secondary outcome. Results A linear mixed model analysis found no significant effects between TAU 1 (β = −0.54, SE = 2.01, p = 0.80) and TAU 2 (β = −1.66, SE = 2.63, p = 0.53) compared to TREAT on shared decision-making. High patient rated satisfaction with the consultations was found with no significant differences between TAU 1 (β = 1.48, SE = 1.14, p = 0.20) and TAU 2 (β = 2.26, SE = 1.33, p = 0.09) compared to TREAT. Conclusion We expected TREAT to enhance shared decision-making without decreasing satisfaction with consultations. However, no significant differences on shared decision-making or satisfaction with consultations were found. Our findings suggest that TREAT is safe to implement in psychosis care, but more research is needed to fully understand its effects on the decisional process. (AU)
Subject(s)
Humans , Decision Making, Computer-Assisted , Decision Support Techniques , Psychotic Disorders/diagnosis , Psychotic Disorders/therapy , Decision MakingABSTRACT
In Lesch-Nyhan disease (LND), deficiency of the purine salvage enzyme hypoxanthine guanine phosphoribosyl transferase (HGprt) leads to a characteristic neurobehavioral phenotype dominated by dystonia, cognitive deficits and incapacitating self-injurious behavior. It has been known for decades that LND is associated with dysfunction of midbrain dopamine neurons, without overt structural brain abnormalities. Emerging post mortem and in vitro evidence supports the hypothesis that the dopaminergic dysfunction in LND is of developmental origin, but specific pathogenic mechanisms have not been revealed. In the current study, HGprt deficiency causes specific neurodevelopmental abnormalities in mice during embryogenesis, particularly affecting proliferation and migration of developing midbrain dopamine (mDA) neurons. In mutant embryos at E14.5, proliferation was increased, accompanied by a decrease in cell cycle exit and the distribution and orientation of dividing cells suggested a premature deviation from their migratory route. An abnormally structured radial glia-like scaffold supporting this mDA neuronal migration might lie at the basis of these abnormalities. Consequently, these abnormalities were associated with an increase in area occupied by TH+ cells and an abnormal mDA subpopulation organization at E18.5. Finally, dopaminergic innervation was disorganized in prefrontal and decreased in HGprt deficient primary motor and somatosensory cortices. These data provide direct in vivo evidence for a neurodevelopmental nature of the brain disorder in LND. Future studies should not only focus the specific molecular mechanisms underlying the reported neurodevelopmental abnormalities, but also on optimal timing of therapeutic interventions to rescue the DA neuron defects, which may also be relevant for other neurodevelopmental disorders.
Subject(s)
Lesch-Nyhan Syndrome , Animals , Disease Models, Animal , Dopamine/metabolism , Dopaminergic Neurons/metabolism , Hypoxanthine Phosphoribosyltransferase/genetics , Hypoxanthine Phosphoribosyltransferase/metabolism , Lesch-Nyhan Syndrome/genetics , Lesch-Nyhan Syndrome/metabolism , Mesencephalon/metabolism , MiceSubject(s)
Melanoma , Skin Neoplasms , Fear , Humans , Melanoma/epidemiology , Melanoma/genetics , Prevalence , Risk Factors , Skin Neoplasms/epidemiology , Skin Neoplasms/geneticsABSTRACT
BACKGROUND: Host genetic modifiers of the natural history of chronic hepatitis B (CHB) remain poorly understood. Recently, a genome-wide association study (GWAS)-identified polymorphism in the STAT4 gene that contributes to the risk for hepatocellular carcinoma (HCC) was shown to be associated with the full spectrum of hepatitis B virus (HBV) outcomes in Asian patients. However, the functional mechanisms for this effect are unknown and the role of the variant in modulating HBV disease in Caucasians has not been investigated. AIMS: To determine whether STAT4 genetic variation is associated with liver injury in Caucasian patients with CHB and to investigate potential mechanisms mediating this effect. METHODS: STAT4 rs7574865 was genotyped in 1085 subjects (830 with CHB and 255 healthy controls). STAT4 expression in liver, PBMCs and NK cells, STAT4 phosphorylation and secretion of interferon-gamma (IFN-γ) according to STAT4 genetic variation was examined. RESULTS: STAT4 rs7574865 genotype was independently associated with hepatic inflammation (OR: 1.42, 95% CI: 1.07-2.06, P = 0.02) and advanced fibrosis (OR: 1.83, 95% CI: 1.19-2.83, P = 0.006). The minor allele frequency of rs7574865 was significantly lower than that in healthy controls. rs7574865 GG risk carriers expressed lower levels of STAT4 in liver, PBMCs and in NK cells, while NK cells from patients with the risk genotype had impaired STAT4 phosphorylation following stimulation with IL-12/IL-18 and a reduction in secretion of IFN-γ. CONCLUSION: Genetic susceptibility to HBV persistence, hepatic inflammation and fibrosis in Caucasians associates with STAT4 rs7574865 variant. Downstream effects on NK cell function through STAT4 phosphorylation-dependent IFN-γ production likely contribute to these effects.
Subject(s)
Hepatitis B, Chronic/complications , Hepatitis B, Chronic/genetics , Liver Cirrhosis/genetics , Polymorphism, Single Nucleotide , STAT4 Transcription Factor/genetics , White People , Adult , Case-Control Studies , Cells, Cultured , Female , Gene Frequency , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , Hepatitis B, Chronic/ethnology , Humans , Liver Cirrhosis/ethnology , Male , Middle Aged , Risk Factors , White People/genetics , White People/statistics & numerical dataABSTRACT
Attention-deficit/hyperactivity disorder (ADHD) is characterized by symptoms of inattention and/or hyperactivity and impulsivity that lead to dysfunctioning in daily life. One of the affected areas of life that has so far not been studied in ADHD is sexual functioning. The goal of this study was to assess prevalence of sexual dysfunctions and other sexual disorders among adults with ADHD. A total of n = 136 adult patients treated in a Dutch outpatient ADHD clinic filled out two questionnaires to screen for sexual dysfunctions and other sexual disorders. We compared the prevalence of sexual dysfunctions and other sexual disorders in our ADHD patient population to results from two large surveys among the general Dutch population. We found that 39% of the male and 43% of the female ADHD patients had symptoms of a sexual dysfunction, and 17% of the male and 5% of the female ADHD patients had symptoms of any other sexual disorder. Only one male patient had received a diagnosis of a sexual disorder at this clinic prior to study participation. In conclusion, sexual dysfunctions and other sexual disorders are highly prevalent in adults with ADHD. Screening for sexual disorders should be therefore standard procedure during diagnostic assessment.
Subject(s)
Attention Deficit Disorder with Hyperactivity/epidemiology , Sexual Dysfunction, Physiological/epidemiology , Sexual Dysfunctions, Psychological/epidemiology , Adolescent , Adult , Aged , Case-Control Studies , Comorbidity , Female , Humans , Male , Middle Aged , Netherlands/epidemiology , Prevalence , Young AdultABSTRACT
An abundance of noninvasive scores have been associated with fibrosis and hepatocellular carcinoma (HCC) development. We aimed to compare the prognostic ability of these scores in relation to liver histology in chronic hepatitis B (CHB) patients. Liver biopsies from treatment-naïve CHB patients at one tertiary care centre were scored by a single hepato-pathologist. Laboratory values at liver biopsy were used to calculate the PAGE-B, REACH-B, GAG-HCC, CU-HCC and FIB-4 scores. Any clinical event was defined as HCC development, liver failure, transplantation and mortality. HCC and mortality data were obtained from national database registries. Of 557 patients, 40 developed a clinical event within a median follow-up of 10.1 (IQR 5.7-15.9) years. The PAGE-B score predicted any clinical event (C-statistic.86, 95% CI: 0.80-0.92), HCC development (C-statistic .91) and reduced transplant-free survival (C-statistic .83) with good accuracy, also when stratified by ethnicity, antiviral therapy after biopsy or advanced fibrosis. The C-statistics (95% CI) of the REACH-B, GAG-HCC, CU-HCC and FIB-4 scores for any event were .70 (0.59-0.81), .82 (0.75-0.89), .73 (0.63-0.84) and.79 (0.69-0.89), respectively. The PAGE-B event risk assessment improved modestly when combined with the Ishak fibrosis stage (C-statistic .87, 95% CI: 0.82-0.93). The PAGE-B score showed the best performance in assessing the likelihood of developing a clinical event among a diverse CHB population over 15 years of follow-up. Additional liver histological characteristics did not appear to provide a clinically significant improvement.
Subject(s)
Hepatitis B, Chronic/epidemiology , Adult , Biomarkers , Biopsy , Cause of Death , Female , Hepatitis B, Chronic/mortality , Hepatitis B, Chronic/pathology , Humans , Kaplan-Meier Estimate , Liver/pathology , Male , Middle Aged , Netherlands/epidemiology , Outcome Assessment, Health Care , Population Surveillance , Prognosis , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Young AdultABSTRACT
Natural killer (NK) cells have long been thought of as a purely innate immune cell population, but increasing reports have described developmental and functional qualities of NK cells that are commonly associated with cells of the adaptive immune system. Of these features, the ability of NK cells to acquire functional qualities associated with immunological memory and continuous differentiation resulting in the formation of specific NK cell repertoires has recently been highlighted in viral infection settings. By making use of a unique cohort of monitored, at-risk intravenous drug users in this study, we were able to dissect the phenotypic and functional parameters associated with NK cell differentiation and NK cell memory in patients 3 years after acute HCV infection and either the subsequent self-clearance or progression to chronicity. We observed increased expression of cytolytic mediators and markers CD56bright and NKp46+ of NK cells in patients with chronic, but not self-limited HCV infection. Patients with a self-limited infection expressed higher levels of differentiation-associated markers CD57 and KIRs, and lower levels of NKG2A. A more extensively differentiated NK cell phenotype is associated with self-clearance in HCV patients, while the NK cells of chronic patients exhibited more naïve and effector NK cell phenotypic and functional characteristics. The identification of these distinct NK cell repertoires may shed light on the role NK cells play in determining the outcome of acute HCV infections, and the underlying immunological defects that lead to chronicity.
Subject(s)
Cell Differentiation , Hepacivirus/immunology , Hepatitis C/immunology , Hepatitis C/virology , Immunologic Memory , Killer Cells, Natural/cytology , Killer Cells, Natural/immunology , Adult , Biomarkers , CD56 Antigen/metabolism , Cell Differentiation/immunology , Cohort Studies , Cytokines/metabolism , Female , Genotype , Granzymes/metabolism , Hepatitis C/metabolism , Humans , Immunophenotyping , Killer Cells, Natural/metabolism , Lymphocyte Count , Male , Middle Aged , Receptors, Natural Cytotoxicity Triggering/metabolism , TNF-Related Apoptosis-Inducing Ligand/metabolism , Viral Load , Young AdultABSTRACT
BACKGROUND: Routine Outcome Monitoring (ROM) has become part of the treatment process in mental health care. However, studies have indicated that few clinicians in psychiatry use the outcome of ROM in their daily work. The aim of this study was to explore the degree of ROM use in clinical practice as well as the explanatory factors of this use. METHODS: In the Northern Netherlands, a ROM-protocol (ROM-Phamous) for patients with a psychotic disorder has been implemented. To establish the degree of ROM-Phamous use in clinical practice, the ROM results of patients (n=204) were compared to the treatment goals formulated in their treatment plans. To investigate factors that might influence ROM use, clinicians (n=32) were asked to fill out a questionnaire about ROM-Phamous. RESULTS: Care domains that were problematic according to the ROM-Phamous results were mentioned in the treatment plan in 28% of cases on average (range 5-45%). The use of ROM-Phamous in the treatment process varies considerably among clinicians. Most of the clinicians find ROM-Phamous both useful and important for good clinical practice. In contrast, the perceived ease-of-use is low and most clinicians report insufficient time to use ROM-Phamous. CONCLUSIONS: More frequent ROM use should be facilitated in clinicians. This could be achieved by improving the fit with clinical routines and the ease-of-use of ROM systems. It is important for all stakeholders to invest in integrating ROM in clinical practice. Eventually, this might improve the diagnostics and treatment of patients in mental health care.
Subject(s)
Mental Health Services/organization & administration , Outcome Assessment, Health Care , Patient Care Planning/organization & administration , Psychotic Disorders/therapy , Adult , Evidence-Based Medicine , Female , Follow-Up Studies , Humans , Male , Netherlands/epidemiology , Psychiatry/organization & administration , Psychotic Disorders/epidemiology , Surveys and QuestionnairesABSTRACT
We investigated innate immune gene expression in clinical phases of chronic hepatitis B infection, including immune tolerant (IT), immune active (IA), inactive carrier (IC) and hepatitis B e antigen (HBeAg)-negative phases, as well as healthy controls. Expression levels of interferon types I, II and III, their receptor subunits, IRFs, TLRs and other IFN-induced genes in peripheral blood mononuclear cells were compared. Forty HBsAg-positive treatment-naïve subjects without co-infection with HIV, HCV or HDV were enrolled. To complement the viral load, the expression levels of 37 innate immune genes were measured by qPCR. The highest response of the innate immune system was observed in the IT and HBeAg-negative phases, and the IC phase had the lowest response; 31 of the 37 studied genes reached their maximum mRNA expression levels in the IT and HBeAg-negative phases, and the minimum expression levels of 23 genes were found in the IC phase. The highest mRNA expression levels of IFNs, IFN receptor subunits, IRFs and TLRs genes in all clinical phases were IFN-λ2 and 3, IFN-γR2, IRF7 and TLR7, and the lowest levels of mRNA expression were observed for IFN-α, IFN-λR1, IRF8 and TLR2. We conclude that innate immune response genes are expressed differentially among chronic HBV phases, and this difference may help to develop new precise and noninvasive methods to determine the progression of disease in chronic HBV patients.
Subject(s)
Gene Expression Profiling , Hepatitis B virus/immunology , Hepatitis B, Chronic/immunology , Immunity, Innate , Immunologic Factors/biosynthesis , Adolescent , Adult , Female , Humans , Immunologic Factors/genetics , Leukocytes, Mononuclear/immunology , Male , Middle Aged , RNA, Messenger/analysis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Young AdultABSTRACT
BACKGROUND/OBJECTIVES: In Guatemala, population-wide vitamin A fortification of table sugar has been operating for two decades. The objective of this study was to estimate the adequacy of vitamin A intakes in pregnant and lactating women from low-income, urban and rural communities. SUBJECTS/METHODS: One or two previous-day dietary recalls were collected in a convenience sample of 234 pregnant and lactating women in the Western Highlands of Guatemala. Estimated daily intakes and main sources of total vitamin A, provitamin A and preformed vitamin A were calculated. Total intakes, adjusted for day-to-day variation, were examined in relation to estimated average requirements (EAR). RESULTS: Median estimated 1-day total vitamin A intake was 1177 µg retinol activity equivalents (RAE) (interquartile range (IQR) 832-1782) in the urban site and 567 µg RAE (IQR 441-737) in the rural site. Women not meeting their status-specific vitamin A requirement were 3.5 times more common in the rural communities (31%) than in the urban confines (9%). In the urban area, 26 women (21%) had preformed vitamin A intakes above 1500 µg on the day of data collection. Preformed vitamin A accounted for a median of 83.9% and 60.9% of the daily total vitamin A intake in the urban and rural sites, respectively. Sugar was the principal source of vitamin A, contributing 512 µg RAE (IQR 343-749) in the urban site and 256 µg RAE (IQR 189-363 µg) in the rural area. CONCLUSIONS: The vitamin A contribution from fortified sugar can be a determinant of reaching adequacy; nevertheless, a significant proportion of pregnant and lactating women do not meet the EAR, especially in the rural setting.
Subject(s)
Dietary Sucrose/analysis , Eating , Food, Fortified/statistics & numerical data , Vitamin A Deficiency/epidemiology , Vitamin A/analysis , Adolescent , Adult , Diet Records , Dietary Sucrose/chemistry , Female , Food, Fortified/analysis , Guatemala/epidemiology , Humans , Lactation , Pregnancy , Rural Population/statistics & numerical data , Urban Population/statistics & numerical data , Vitamin A Deficiency/etiology , Young AdultABSTRACT
In humans, CD16 and CD56 are used to identify functionally distinct natural killer (NK) subsets. Due to ubiquitous CD56 expression, this marker cannot be used to distinguish between NK cell subsets in chimpanzees. Therefore, functional analysis of distinct NK subsets during hepatitis C virus (HCV) infection has never been performed in these animals. In the present study an alternative strategy was used to identify four distinct NK subsets on the basis of the expression of CD16 and CD94. The expression of activating and inhibiting surface receptors showed that these subsets resemble human NK subsets. CD107 expression was used to determine degranulation of the different subsets in naive and HCV-infected chimpanzees. In HCV-infected chimpanzees increased spontaneous cytotoxicity was observed in CD94(high/dim) CD16(pos) and CD94(low) CD16(pos) subsets. By contrast, increased natural cytotoxicity receptor (NCR)- mediated degranulation after NKp30 and NKp44 triggering was demonstrated in the CD94(dim) CD16(neg) subset. Our findings suggest that spontaneous and NCR-mediated cytotoxicity are effector functions of distinct NK subsets in HCV-infected chimpanzees.
Subject(s)
Cell Lineage/immunology , Cytotoxicity, Immunologic , Hepacivirus/immunology , Hepatitis C/immunology , Killer Cells, Natural/immunology , Animals , Ape Diseases , Cell Degranulation/drug effects , Flow Cytometry , Gene Expression Regulation , Hepatitis C/pathology , Hepatitis C/virology , Immunophenotyping , Interleukin-2/pharmacology , Interleukins/pharmacology , Killer Cells, Natural/classification , Killer Cells, Natural/cytology , Killer Cells, Natural/drug effects , Lymphocyte Activation/drug effects , Lysosomal-Associated Membrane Protein 1/genetics , Lysosomal-Associated Membrane Protein 1/immunology , NK Cell Lectin-Like Receptor Subfamily D/genetics , NK Cell Lectin-Like Receptor Subfamily D/immunology , Natural Cytotoxicity Triggering Receptor 2/genetics , Natural Cytotoxicity Triggering Receptor 2/immunology , Natural Cytotoxicity Triggering Receptor 3/genetics , Natural Cytotoxicity Triggering Receptor 3/immunology , Pan troglodytes , Receptors, IgG/genetics , Receptors, IgG/immunologyABSTRACT
Hepatitis B core-related antigen (HBcrAg), a new serum marker, may be useful in monitoring chronic hepatitis B infection. HBcrAg was measured in 175 hepatitis B e antigen-positive patients treated with entecavir (ETV) with or without peginterferon (PEG-IFN) add-on therapy. Decline in HBcrAg was stronger in patients with vs. without combined response (ETV: -3.22 vs. -1.71 log U/mL, p <0.001; PEG-IFN add-on: -3.16 vs. -1.83 IU/mL, p <0.001) and in patients with vs. without hepatitis B surface antigen (HBsAg) response (ETV: -2.60 vs. -1.74 log U/mL, p <0.001; PEG-IFN add-on: -2.38 vs. -2.15 log U/mL, p = 0.31). HBcrAg was associated with combined response (adjusted odds ratio 0.3, 95% confidence interval 0.2-0.5, p <0.001), but was not superior to quantitative HBsAg (qHBsAg).
Subject(s)
Antiviral Agents/therapeutic use , Drug Monitoring/methods , Guanine/analogs & derivatives , Hepatitis B Core Antigens/blood , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B, Chronic/drug therapy , Adult , Female , Guanine/therapeutic use , Humans , Interferon-alpha/therapeutic use , Male , Randomized Controlled Trials as Topic , Young AdultABSTRACT
BACKGROUND: Professional musicians receive little attention in pain medicine despite reports of high prevalence of musculoskeletal complaints. This study aims to investigate the association between work-related postures and musculoskeletal complaints of professional bass players. METHOD: Participants were 141 professional and professional student double bassists and bass guitarists. Data about self-reported functioning, general and mental health status, location and intensity of musculoskeletal complaints and psychosocial distress were collected online with self constructed and existing questionnaires. Logistic regression analyses were performed to analyse associations between work-related postural stress (including type of instrument and accompanying specific exposures) and physical complains, adjusted for potential confounders. RESULTS: Logistic regression analyses revealed no association between complaints and the playing position of the left shoulder area in double bassists (p = 0.30), the right wrist area in the bass guitarists (p = 0.70), the right wrist area for the German versus French bowing style (p = 0.59). CONCLUSION: All three hypotheses were rejected. This study shows that in this sample of professional bass players' long-lasting exposures to postural stress were not associated with musculoskeletal complaints. This challenges a dominant model in pain medicine to focus on ergonomic postures.
Subject(s)
Musculoskeletal Pain/epidemiology , Music , Occupational Diseases/epidemiology , Occupational Exposure/adverse effects , Posture , Adult , Ergonomics , Female , Health Status , Humans , Male , Mental Health , Middle Aged , Musculoskeletal Pain/etiology , Prevalence , Shoulder Pain/etiology , Social Behavior , WristABSTRACT
Background. Since 2000, incidence of sexually acquired hepatitis C virus (HCV)-infection has increased among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). To date, few case-control and cohort studies evaluating HCV transmission risk factors were conducted in this population, and most of these studies were initially designed to study HIV-related risk behavior and characteristics. Methods. From 2009 onwards, HIV-infected MSM with acute HCV infection and controls (HIV-monoinfected MSM) were prospectively included in the MOSAIC (MSM Observational Study of Acute Infection with hepatitis C) study at 5 large HIV outpatient clinics in the Netherlands. Written questionnaires were administered, covering sociodemographics, bloodborne risk factors for HCV infection, sexual behavior, and drug use. Clinical data were acquired through linkage with databases from the Dutch HIV Monitoring Foundation. For this study, determinants of HCV acquisition collected at the inclusion visit were analyzed using logistic regression. Results. Two hundred thirteen HIV-infected MSM (82 MSM with acute HCV infection and 131 MSM without) were included with a median age of 45.7 years (interquartile range [IQR], 41.0-52.2). Receptive unprotected anal intercourse (adjusted odds ratio [aOR], 5.01; 95% confidence interval [CI], 1.63-15.4), sharing sex toys (aOR, 3.62; 95% CI, 1.04-12.5), unprotected fisting (aOR, 2.57; 95% CI, 1.02-6.44), injecting drugs (aOR, 15.62; 95% CI, 1.27-192.6), sharing straws when snorting drugs (aOR, 3.40; 95% CI, 1.39-8.32), lower CD4 cell count (aOR, 1.75 per cubic root; 95% CI, 1.19-2.58), and recent diagnosis of ulcerative sexually transmitted infection (aOR, 4.82; 95% CI, 1.60-14.53) had significant effects on HCV acquisition. Conclusions. In this study, both sexual behavior and biological factors appear to independently increase the risk of HCV acquisition among HIV-infected MSM.
ABSTRACT
Evidence is accumulating that the level of text comprehension is dependent on the situatedness and sensory richness of a child's mental representation formed during reading. This study investigated whether these factors involved in text comprehension also serve a functional role in writing a narrative. Direct influences of situatedness and sensory richness as well as indirect influences via the number of sensory and situational words on the creativity (i.e., originality/novelty) of a written narrative were examined in 165 primary school children through path analyses. Results showed that sensory richness and situatedness explained 35 % of the variance in creativity scores. Sensory richness influenced the originality/novelty of children's narrative writing directly, whereas situatedness had an indirect influence, through the number of sensory words, but both pathways influenced the outcomes to a comparable extent. Findings suggest that creative writing requires similar representational processes as reading comprehension, which may contribute to the development of instructional methods to help children in creative writing assignments.
ABSTRACT
Memory B cells play a pivotal role in alloreactivity in kidney transplantation. Follicular T helper (Tfh) cells play an important role in the differentiation of B cells into immunoglobulin-producing plasmablasts [through interleukin (IL)-21]. It is unclear to what extent this T cell subset regulates humoral alloreactivity in kidney transplant patients, therefore we investigated the absolute numbers and function of peripheral Tfh cells (CD4(POS) CXCR5(POS) T cells) in patients before and after transplantation. In addition, we studied their relationship with the presence of donor-specific anti-human leucocyte antigen (HLA) antibodies (DSA), and the presence of Tfh cells in rejection biopsies. After transplantation peripheral Tfh cell numbers remained stable, while their IL-21-producing capacity decreased under immunosuppression. When isolated after transplantation, peripheral Tfh cells still had the capacity to induce B cell differentiation and immunoglobulin production, which could be inhibited by an IL-21-receptor-antagonist. After transplantation the quantity of Tfh cells was the highest in patients with pre-existent DSA. In kidney biopsies taken during rejection, Tfh cells co-localized with B cells and immunoglobulins in follicular-like structures. Our data on Tfh cells in kidney transplantation demonstrate that Tfh cells may mediate humoral alloreactivity, which is also seen in the immunosuppressed milieu.
Subject(s)
B-Lymphocytes/immunology , Graft Rejection/immunology , Immunity, Humoral , Immunologic Memory , Kidney Transplantation , T-Lymphocytes, Helper-Inducer/immunology , Adult , Aged , B-Lymphocytes/physiology , Cell Line , Female , Graft Rejection/pathology , Graft Rejection/prevention & control , Humans , Immunosuppression Therapy/methods , Interleukins/immunology , Male , Middle Aged , T-Lymphocytes, Helper-Inducer/pathologyABSTRACT
BACKGROUND: Polymorphisms of the HLA-DP gene are associated with the natural clearance of the hepatitis B virus in Asian patients. AIM: To investigate the association of HLA-DP polymorphisms with response to peginterferon (PEG-IFN) in Caucasian chronic hepatitis B (CHB) patients. METHODS: We studied 262 Caucasian chronic hepatitis B patients infected with HBV genotype A or D, treated with PEG-IFN for 1 year in two randomised controlled trials (HBV 99-01 and PARC study). Response was defined as an HBV DNA <2000 IU/mL at 6 months post-treatment. Variations at HLA-DPA1 and HLA-DPB1 were genotyped. RESULTS: Of the 262 patients, 58% was HBeAg-positive and HBV genotype A and D was observed in 32% and 68%, respectively. At 6 months post-treatment, 57 (22%) patients had achieved an HBV DNA <2000 IU/mL. HLA-DPB1 was independently associated with virological response [adjusted odds ratio (OR) 1.8, 95% confidence interval (CI):1.1-3.0, P = 0.025], and with an undetectable HBV DNA (adjusted OR 2.4 95% CI: 1.2-4.7, P = 0.015) when adjusted for HBeAg status and other known response modifiers. In HBeAg-positive patients, combined HBeAg seroconversion with HBV DNA <2000 IU/mL was increasingly observed with each addition of an HLA-DPB1 G-allele (adjusted OR 2.7, 95% CI: 1.2-5.9, P = 0.012). Furthermore, HLA-DPA1 and HLA-DPB1 haplotype block GG showed comparable results for virological and combined response. CONCLUSION: In this large cohort of Caucasian chronic hepatitis B patients infected with HBV genotypes A or D, polymorphisms of HLA-DP are independently associated with both virological and serological response to PEG-IFN therapy at 6 months post-treatment.
Subject(s)
HLA-DP alpha-Chains/genetics , HLA-DP beta-Chains/genetics , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/genetics , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Adult , DNA, Viral/analysis , Female , Genotype , Haplotypes , Hepatitis B e Antigens , Hepatitis B virus/genetics , Hepatitis B, Chronic/immunology , Humans , Male , Middle Aged , Polymorphism, Genetic , White People/genetics , Young AdultABSTRACT
Attention-deficit/hyperactivity disorder (ADHD) is linked to impaired executive functioning (EF). This is the first study to objectively investigate the effects of a long-acting methylphenidate on neurocognitive test performance of adults with ADHD. Twenty-two adults with ADHD participated in a 6-weeks study examining the effect of osmotic-release oral system methylphenidate (OROS-mph) on continuous performance tests (CPTs; objective measures), and on the self-reported ADHD rating scale (subjective measure) using a randomized, double-blind, placebo-controlled cross-over design. OROS-mph significantly improved reaction time variability (RTV), commission errors (CE) and d-prime (DP) as compared to baseline (Cohen's d>.50), but did not affect hit reaction time (HRT) or omission errors (OE). Compared to placebo, OROS-mph only significantly influenced RTV on one of two CPTs (p<.050). Linear regression analyses showed predictive ability of more beneficial OROS-mph effects in ADHD patients with higher EF severity (RTV: ß=.670, t=2.097, p=.042; omission errors (OE): ß=-.098, t=-4.759, p<.001), and with more severe ADHD symptoms (RTV: F=6.363, p=.019; HRT: F=3.914, p=.061). Side effects rates were substantially but non-significantly greater for OROS-mph compared to placebo (77% vs. 46%, p=.063). OROS-mph effects indicated RTV as the most sensitive parameter for measuring both neuropsychological and behavioral deficits in adults with ADHD. These findings suggest RTV as an endophenotypic parameter for ADHD symptomatology, and propose CPTs as an objective method for monitoring methylphenidate titration.