Pathogenic Helicobacter pylori strains translocate DNA and activate TLR9 via the cancer-associated cag type IV secretion system.

Helicobacter pylori (H. pylori) is the strongest identified risk factor for gastric cancer, the third most common cause of cancer-related death worldwide. An H. pylori constituent that augments cancer risk is the strain-specific cag pathogenicity island, which encodes a type IV secretion system (T4SS) that translocates a pro-inflammatory and oncogenic protein, CagA, into epithelial cells. However, the majority of persons colonized with CagA+ H. pylori strains do not develop cancer, suggesting that other microbial effectors also have a role in carcinogenesis. Toll-like receptor 9 (TLR9) is an endosome bound, innate immune receptor that detects and responds to hypo-methylated CpG DNA motifs that are most commonly found in microbial genomes. High-expression tlr9 polymorphisms have been linked to the development of premalignant lesions in the stomach. We now demonstrate that levels of H. pylori-mediated TLR9 activation and expression are directly related to gastric cancer risk in human populations. Mechanistically, we show for the first time that the H. pylori cancer-associated cag T4SS is required for TLR9 activation and that H. pylori DNA is actively translocated by the cag T4SS to engage this host receptor. Activation of TLR9 occurs through a contact-dependent mechanism between pathogen and host, and involves transfer of microbial DNA that is both protected as well as exposed during transport. These results indicate that TLR9 activation via the cag island may modify the risk for malignancy within the context of H. pylori infection and provide an important framework for future studies investigating the microbial-epithelial interface in gastric carcinogenesis.

Age-specific prevalence of intellectual disability in Finland at the beginning of new millennium--multiple register method.

BACKGROUND: In the national study of multiple registers in 2000, the average prevalence of intellectual disability (ID) was 0.70%, with marked differences by age group (range 0.38-0.96%) - what are these differences in detail, and can they be understood? METHOD: This study was based on two national health registers and six social benefit registers. Prevalence of ID was calculated by 1-year age cohorts. RESULTS: The multiple register prevalence of ID increased steadily from 0.20% in the first life year to 0.74% (male: 0.90%, female: 0.58%) at 10 years. For boys, the rate fell to 0.71% at 11 years. For both sexes, a steady increase was noted in the distribution up to 40 years (male: 0.84%, female: 0.73%), followed by a sharper increase to the maximum prevalence (male: 1.19% at 48 years, female: 1.05% at 50 years). At the pension age of 66 years, a sudden drop to 0.49% occurred for men and women. Different registers gave very different age distributions. CONCLUSIONS: By examining the data by 1-year age cohorts, and by understanding the role of each register, it could be deduced that a proportion of cases in younger age groups is lacking, and a remarkable proportion of elderly ID persons is missing from the pooled data. The findings were more difficult to interpret, if the data were grouped into bigger age groups.

Patients with univentricular heart in early childhood: parenting stress and child behaviour.

AIMS: To assess perceptions of child behaviour and parenting stress among the parents of young children with hypoplastic left heart syndrome (HLHS) and other forms of functionally univentricular heart defects (UVH). METHODS: As part of our prospective nation-wide neurodevelopmental follow-up study, the parents of 23 patients with HLHS, 14 with UVH and 46 healthy controls at the mean age of 18 months received the questionnaires Child Behavior Checklist and Parenting Stress Index. RESULTS: The reported level of total parenting stress was significantly higher among the mothers (mean score 241 vs 205, p < 0.001) and fathers (235 vs 202, p = 0.003) of patients with HLHS compared with those of controls. The parents of patients with HLHS reported significantly more total (mean T score 52 vs 45, p = 0.005) and internalizing (51 vs 41, p < 0.001) behaviour problems than the controls, but among the syndrome scales, a significant difference was only found in somatic complaints. The parents of patients with UVH did not report more parenting stress or emotional problems than the controls. CONCLUSION: Hypoplastic left heart syndrome, a severe congenital heart defect, increases parenting stress. The reported emotional maladjustment in affected children might in part be owing to somatic complaints.

Surgical treatment for early osteoarthritis. Part II: allografts and concurrent procedures.

UNLABELLED: Young patients with early osteoarthritis (OA) represent a challenging population due to a combination of high functional demands and limited treatment options. Conservative measures such as injection and physical therapy can provide short-term pain relief but are only palliative in nature. Joint replacement, a successful procedure in the older population, is controversial in younger patients, who are less satisfied and experience higher failure rates. Therefore, while traditionally not indicated for the treatment of OA, cartilage repair has become a focus of increased interest due to its potential to provide pain relief and alter the progression of degenerative disease, with the hope of delaying or obviating the need for joint replacement. The field of cartilage repair is seeing the rapid development of new technologies that promise greater ease of application, less demanding rehabilitation and better outcomes. Concurrent procedures such as meniscal transplantation and osteotomy, however, remain of crucial importance to provide a normalized biomechanical environment for these new technologies. LEVEL OF EVIDENCE: Systematic review, Level II.

The variability of surgical practice during total knee arthroplasty: results of a national survey amongst Belgian knee surgeons.

PURPOSE: Implant registries have been effective in detecting poorly performing implants and surgical strategies. They learn us however little about many variables that may be equally important to the final result. Today, no standards of care exist for performing total knee arthroplasties (TKA), and little is known about the variability that exists amongst surgeons performing this procedure. METHODS: A questionnaire with 39 aspects regarding standard surgical routine during TKA was sent to all 112 members of the Belgian Knee Society. Surgeons were stratified according to surgical experience and surgical volume. RESULTS: An important number of routines were performed as standard by the majority (>70%) of surgeons. Surgeons however significantly differed in the following aspects of the procedure: radiographic evaluation, use of minimally invasive surgery (MIS), preferred landmark for femoral component rotation, method of closure and activities allowed postoperatively. Both surgical experience and surgical volume had a significant effect, but their influence on strategies was different. Less-experienced surgeons used the posterior condylar line as their reference for femoral component rotation significantly more frequent than more-experienced surgeons and were more aggressive towards postoperative sports activities compared to more-experienced surgeons. High-volume surgeons used significantly more frequent MIS and low-volume surgeons preferred a more extensive postoperative radiographic evaluation. CONCLUSIONS: Data of this study show that an important number of routines are performed similarly by the majority of surgeons, and that minor but significant differences exist between high-volume versus low-volume surgeons, and between experienced versus less-experienced surgeons. LEVEL OF EVIDENCE: Case series, Level IV.

Childhood bullying behaviors at age eight and substance use at age 18 among males. A nationwide prospective study.

Childhood bullying behaviors (bullying and victimization) were studied as risk factors for substance use among Finnish males. The study design was a nationwide prospective general population study, where information was collected in 1989 and 1999. Bullying behaviors and childhood psychopathology at age eight were collected from teachers, parents and boys themselves. At age 18, self-reports of frequent drunkenness (once a week or more often), daily heavy smoking (10 cigarettes or more per day), and illicit drug use during the past six months were obtained from 78% of the boys attending the study at age eight (n=2946). Being frequently victimized at age eight predicted daily heavy smoking, and this was evident even after adjusting for childhood family background, psychopathology at age eight and at age 18, and other forms of substance use. In multivariate analysis, bullying others frequently predicted illicit drug use, while being a victim of bullying associated with a lower occurrence of illicit drug use. Bullying behaviors had no association with frequent drunkenness independent of other factors. Accordingly, being a victim of bullying predisposes in particular to subsequent smoking. Bullying others in childhood can be regarded as an early indicator to illicit drug use later in life. The screening and intervention possibilities in order to recognize the risk group for later health compromising behaviors are emphasized.

Proteome characterization of human articular chondrocytes leads to novel insights in the function of small heat-shock proteins in chondrocyte homeostasis.

OBJECTIVE: In recent years, studies have been initiated to disclose the proteome of human chondrocytes and cartilage. Despite these studies, comprehensive information of the chondrocyte proteome remains limited. This study aimed to further explore the proteome expressed by human knee chondrocytes, and to study the functional aspects of heat-shock protein 27 (HSP27), a protein related to the previously described alphaBcrystallin, in chondrocyte biology. METHODS: Chondrocytes isolated from human knee articular cartilage were cultured in a three-dimensional alginate culture system. To simplify the protein mixtures, proteins extracted from chondrocyte cell lysates were fractionated based on hydrophobicity and molecular weight. Proteins were digested and the resulting peptides were separated and identified by an on-line two-dimensional (2-D) nanoliquid chromatography (nanoLC)-system coupled to a quadrupole time-of-flight (Qq-TOF) mass spectrometer. Differential expression analysis of HSP27 was performed by Western Blotting and quantitative polymerase chain reaction (QPCR). The effects of HSP27 on chondrocyte biology were explored by suppression of HSP27 expression induced by RNA interference (RNAi). RESULTS: In this study, we identified proteins with unknown functions together with membrane proteins, transcription factors and other low abundant proteins, which have not yet been described in chondrocytes. Based on previous knowledge on the related protein alphaBcrystallin, we selected HSP27 from the chondrocyte proteome database. Differential expression analysis revealed a decreased expression of HSP27 in Osteoarthritic (OA) chondrocytes. RNAi experiments revealed that HSP27 is involved in interleukin-1beta (IL-1beta) induced IL-6 secretion. CONCLUSION: These findings highlight that small HSPs, especially HSP27, play a prominent role in the maintenance of human articular chondrocyte homeostasis.

The peri-operative use of intra-articular local anesthetics: a review.

Acute and chronic pain are of major concern after orthopedic surgery. The increasing trend toward day case surgery induced the development of different techniques in postoperative pain control. One commonly used strategy in pain management after knee and shoulder joint surgery is the intra-articular (IA) use of local anesthetics (LA). Recent attention has been drawn to the possible toxicity on chondrocytes of local anesthetics. The aim of this manuscript is to evaluate and compare through literature review the existing evidence on the clinical use and possible adverse effects of intra-articular injection of local anesthetics peri-operatively.

Do mental health problems in childhood predict chronic physical conditions among males in early adulthood? Evidence from a community-based prospective study.

BACKGROUND: Previous studies have documented associations between mental and physical health problems in cross-sectional studies, yet little is known about these relationships over time or the specificity of these associations. The aim of the current study was to examine the relationship between mental health problems in childhood at age 8 years and physical disorders in adulthood at ages 18-23 years. METHOD: Multiple logistic regression analyses were used to examine the relationship between childhood mental health problems, reported by child, parent and teacher, and physical disorders diagnosed by a physician in early adulthood. RESULTS: Significant linkages emerged between childhood mental health problems and obesity, atopic eczema, epilepsy and asthma in early adulthood. Specifically, conduct problems in childhood were associated with a significantly increased likelihood of obesity and atopic eczema; emotional problems were associated with an increased likelihood of epilepsy and asthma; and depression symptoms at age 8 were associated with an increased risk of asthma in early adulthood. CONCLUSIONS: Our findings provide the first evidence of an association between mental health problems during childhood and increased risk of specific physical health problems, mainly asthma and obesity, during early adulthood, in a representative sample of males over time. These data suggest that behavioral and emotional problems in childhood may signal vulnerability to chronic physical health problems during early adulthood.

Prevalence of intellectual disability: a comprehensive study based on national registers.

BACKGROUND: Based on standard social benefit registers, the prevalence of intellectual disability (ID) in Finland is estimated to be 0.6%, while epidemiological surveys yield 1.1%. Combining several registers, our aim was to find a more reliable estimate of the prevalence of ID, especially among children and adolescents. This is important when special or inclusive general services are planned to meet the various needs of people with ID. METHOD: A survey based on eight national health and social benefit registers. RESULTS: Combining different registers yielded a mean ID prevalence of 0.70% (95% CI 0.69-0.70%), with marked differences according to sex and age group (range 0.38-0.96%). Capture-recapture analysis gave higher prevalence estimates (range 0.57-1.08%). CONCLUSIONS: When several health and social benefit registers are surveyed, the estimated prevalence of ID increases, approaching that obtained in epidemiological surveys.

Infertility treatment and marital relationships: a 1-year prospective study among successfully treated ART couples and their controls.

BACKGROUND: Evidence about the effects of infertility and assisted reproduction technique (ART) on marital relationships is discrepant. Here, we examined the impact of ART on marital relationships. The roles of life stressors, infertility and treatment characteristics in predicting marital relations were also evaluated. SUBJECTS: 367 couples with singleton IVF/ICSI pregnancies. CONTROLS: 379 couples with spontaneous singleton pregnancies. Women and men were assessed when the child was 2 months (T2) and 12 months old (T3). They further reported stressful life events at T2 and depression in pregnancy. RESULTS: No between-group differences were found in marital satisfaction and dyadic cohesion. Dyadic consensus deteriorated from T2 to T3 only among control women. Sexual affection was low among control men at T2 and stressful life events decreased it further. Depression during pregnancy predicted deteriorated marital relations only in control couples. Several unsuccessful treatment attempts were associated with good dyadic consensus and cohesion among ART women. Spontaneous abortions and multiple parity predicted poor marital satisfaction in ART women, whereas long duration of infertility and multiple parity predicted poor marital relations in ART men. CONCLUSIONS: Successful ART does not constitute a risk for marital adjustment. The shared stress of infertility may even stabilize marital relationships.

A prospective study on knee proprioception after meniscal allograft transplantation.

The meniscus plays an important role in the proprioceptive ability of the knee joint. The aim of this prospective study was to assess the short-term influence of a meniscus replacement on the proprioception of the knee. Fourteen patients who had undergone a fresh meniscal allograft transplantation between May 2001 and June 2003 were tested pre-operatively and 6 months post-operatively. Disability regarding pain, stiffness and functionality of the affected knee during daily activities was measured by the Western Ontario and McMaster Universities Arthritis (WOMAC) scale. The knee joint position sense was assessed using the Biodex System 3 isokinetic dynamometer. The results of the WOMAC scale showed no significant differences concerning pain, stiffness or knee function between the pre- and post-operative condition of the knee. Assessment of the knee joint position sense at a reference point of 70 degrees of knee flexion revealed a significant improvement of the proprioception of the operated knee at 6 months after surgery compared with the pre-operative condition. The results of this study suggest that although no significant improvement of pain and functionality of the operated knee occurred at this short-term follow-up period, a meniscal allograft transplantation seems to have a significant positive effect on the joint position sense of the previously meniscectomised knee.

Risk factors for psychiatric disturbance in children with intellectual disability.

BACKGROUND: Children with intellectual disability (ID) have a higher risk for psychiatric disturbance than their peers with normal intelligence, but research data on risk factors are insufficient and partially conflicting. METHOD: The subjects comprised 75 children with ID aged 6-13 years. Data were obtained from case files and the following four questionnaires completed by their parents or other carers: Developmental Behaviour Checklist, American Association of Mental Deficiency (AAMD) Adaptive Behavior Scale, a questionnaire on additional disabilities, and a questionnaire on family characteristics and child development. RESULTS: The risk of psychopathology was most significantly increased by moderate ID, limitations in adaptive behaviour, impaired language development, poor socialization, living with one biological parent, and low socio-economic status of the family. CONCLUSIONS: The risk of psychopathology in children with ID is increased by factors related to family characteristics and child development. Identifying these factors will help diagnose and possibly prevent psychiatric disorders in these children.

Impact of infertility characteristics and treatment modalities on singleton pregnancies after assisted reproduction.

Obstetric and neonatal outcomes of assisted reproduction and control singletons were evaluated after taking into account treatment characteristics and infertility background. The elective single embryo transfer (eSET) group (n = 45) was compared with the compulsory single embryo transfer (cSET; n = 52), double embryo transfer (DET; n = 227) and control (n = 304) groups. Infertility-related prognostic factors for neonatal outcomes were also analysed. Data were collected with structured questionnaires at gestational week 20 and 8 weeks after delivery. Spontaneous onset of delivery was more typical of the eSET group than of cSET and DET groups (68.9 versus 52.0%, P = 0.02). Mean (+/-SD) gestation at birth (39.3 +/- 1.6 weeks) and mean birth weight (3,470 +/- 505 g) of eSET singletons were comparable with other assisted reproduction groups, but gestational duration was lower than in the eSET group than in the control group (39.9 +/- 1.4; P < 0.05). However, numbers of preterm births and low birth weight infants were similar between groups. History of induced abortion increased risk of preterm birth (OR 4.5 and 95% CI 1.2-17.1) in assisted reproduction singletons. A small though clinically unimportant difference in gestational age at birth and birth weight between assisted reproduction and control singletons was found regardless of the number of embryos transferred.

The impact of successful assisted reproduction treatment on female and male mental health during transition to parenthood: a prospective controlled study.

BACKGROUND: The dynamics of mental health during the transition to parenthood have not been a focus of research. Our prospective longitudinal study was designed to reveal whether there are differences in mental health during the transition to parenthood between parents undergoing treatment with assisted reproduction techniques (ART) and those who conceive spontaneously. STUDY GROUP: 367 couples with a singleton ART pregnancy using their own gametes. CONTROL GROUP: 379 couples with a spontaneous singleton pregnancy. Men and women separately filled in questionnaires including the General Health Questionnaire: at the 18th-20th week of pregnancy, 2 months postpartum and 1 year postpartum (T3). The effect of social and child-related factors on mental health was examined. RESULTS: ART women had fewer depressive symptoms during pregnancy than controls, but at T3 their depressive symptoms were at the same level as seen in controls. Anxiety symptoms increased among control but not among ART women across the transition. ART men reported generally fewer mental health symptoms than their controls. Social and child-related stressors had negative impacts on mental health changes among control couples, whereas no impact was found among ART couples. CONCLUSIONS: Successful ART did not predict mental health problems during the transition to parenthood. Moreover, ART couples' mental health was remarkably resistant to social and child-related stress during the transition to parenthood.

Magnetic resonance imaging of cartilage and cartilage repair.

Magnetic resonance (MR) imaging of articular cartilage has assumed increased importance because of the prevalence of cartilage injury and degeneration, as well as the development of new surgical and pharmacological techniques to treat damaged cartilage. This article will review relevant aspects of the structure and biochemistry of cartilage that are important for understanding MR imaging of cartilage, describe optimal MR pulse sequences for its evaluation, and review the role of experimental quantitative MR techniques. These MR aspects are applied to clinical scenarios, including traumatic chondral injury, osteoarthritis, inflammatory arthritis, and cartilage repair procedures.

Auditory event-related potential indices of increased distractibility in children with major depression.

OBJECTIVE: Children with major depression (MD) exhibit short-term memory and concentration deficits. Using auditory event-related potentials (ERPs), we aimed to determine whether these problems could be caused by a dysfunction in auditory sensory memory, attentional orienting, or both. METHODS: The subjects were 10 treatment-naïve children with MD and 10 controls. Sound sequences, consisting of frequent stimuli (syllable /ka/, P = 0.08), infrequent deviant stimuli (/ta/, P = 0.01 ), and novel sounds ( P = 0.01 ) were played through loudspeakers while the children watched silent videos and ignored the sound stimuli. Auditory sensory memory was studied by eliciting the ERPs mismatch negativity (MMN) and late discriminative negativity (LDN), and the P3a was used as an index of involuntary attention switch. RESULTS: The children with MD had shorter MMN and LDN latencies than the controls. The late component of the P3a (lP3a) was enhanced in amplitude in the patients as compared with that in the controls. CONCLUSIONS: Auditory sensory memory appears to function normally in children with MD. However, the ERP findings indicated enhanced sensory sensitivity and attentional distractibility in these children. This increased distractibility might underlie the concentration difficulties that compromise school performance in children with MD.

The effect of exercise regimens on reflex response time of the vasti muscles in patients with anterior knee pain: a prospective randomized intervention study.

The purpose of this prospective randomized intervention study was to evaluate the effect of two exercise protocols on reflex response time of vastus medialis obliquus (VMO), vastus lateralis (VL), in patients with anterior knee pain. Sixty patients were randomized into a 5-week treatment program, which consisted of only open kinetic chain tonification exercises (group I) (n = 30), or only closed kinetic chain tonification exercises (group II) (n = 30). Assessment of an aspect of neuromotor control was obtained by measuring the reflex response times of VMO and VL at the time of initial clinical examination, at the end of the exercise period (five weeks), and three months after the completion of the exercise period. At these evaluation occasions, the intensity and the number of times that the patients experienced anterior knee pain during daily life was recorded on a Visual Analog Scale (VAS). No alterations in reflex response times of VMO and VL were observed in either group. Changes of anterior knee pain over time were statistically significant in both groups. Only small and not statistically supported differences in anterior knee pain were found between the two groups. These results suggest that the reflex response times of the two vasti muscles can not be altered after a five week open or closed kinetic chain exercise program. In contrast, knee pain decreased significantly in both groups.

Poor sleep and psychiatric symptoms at school: an epidemiological study.

The objective of this study was to evaluate associations between sleep problems and psychiatric symptoms at school. A random sample consisting of 5813 eight- to nine-year-old children was selected from ordinary schools. Both parents' and children's reports of sleep problems were taken into account. The psychiatric symptoms were addressed according to the teachers' reports (the Rutter Scale B). Children with severe sleep problems were more likely to have a psychiatric disturbance according to the Rutter B Scale (OR 2.45, 95% CI 1.85-3.25). Logistic regression models showed that severe sleep problems were highly associated with emotional problems (OR 2.74, 95% CI 1.84-4.13), school attendance problems (OR 2.53, 95% OR 1.45-4.41), behavioural problems (OR 2.44, 95% CI 1.59-3.75) and hyperactivity (OR 2.02, 95% CI 1.30-3.13). Over 95% of severe sleep problems were reported only by the children themselves. In conclusion, children with severe sleep problems have substantially more teacher-reported psychiatric symptoms than those with no or mild sleep complaints. In diagnosing sleep disorders, it is important to include children as informants because relevant information may be overlooked when only parents are questioned.

An enantioselective ketene-imine cycloaddition method for synthesis of substituted ring-fused 2-pyridinones.

Previously, a method for the stereoselective synthesis of beta-lactams, starting from 2H-Delta(2)-thiazolines and Meldrum's acid derivatives, has been reported from our laboratory. We now report a new method for the synthesis of optically active, highly substituted ring-fused 2-pyridinones. This was discovered when 2-alkyl-Delta(2)-thiazolines and Meldrum's acid derivatives were treated with HCl(g) in benzene at 5 --> 78 degrees C. Further refinement of the synthetic protocol revealed that use of 1,2-dichloroethane as solvent at 0 --> 64 degrees C led to the desired 2-pyridinones in good yields and with excellent enantioselectivity. Use of these conditions allowed preparation of 2-pyridinones from several different Delta(2)-thiazolines and Meldrum's acid derivatives and may be a general route to 2-pyridinones.