Serum matrix metalloproteinase 8 and tissue inhibitor of metalloproteinase 1 : Potential markers for malignant transformation of recurrent respiratory papillomatosis and for prognosis of laryngeal cancer

Background Biomarkers that could predict malignant transformation of recurrent respiratory papillomatosis (RRP) would be useful in patient follow-up. We investigated whether serum matrix metalloproteinase 8 (MMP-8) and tissue inhibitor of metalloproteinase 1 (TIMP-1) could predict malignant transformation of RRP and whether they associate with survival in laryngeal squamous cell carcinoma (LSCC) without preexisting RRP. Methods We analyzed serum MMP-8 (S-MMP-8) and serum TIMP-1 (s-TIMP-1) in 114 patients: 55 were treated for RRP and 59 for LSCC without preexisting RRP. Five patients with RRP developed LSCC during follow-up. Results Elevated S-MMP-8 level in RRP was associated with malignant transformation (P = .01). Compared to patients with RRP, S-MMP-8 in patients with LSCC was significantly higher (P <.001). Increased S-TIMP-1 level in LSCC was associated with poor overall survival (P = .02) and recurrence-free survival (P = .05). Conclusion In RRP, high S-MMP-8 may predict malignant transformation. In LSCC, elevated S-TIMP-1 is connected to poor survival.Peer reviewe

The contribution of psychological distress to socio-economic differences in cause-specific mortality: a population-based follow-up of 28 years

<p>Abstract</p> <p>Background</p> <p>Psychological factors associated with low social status have been proposed as one possible explanation for the socio-economic gradient in health. The aim of this study is to explore whether different indicators of psychological distress contribute to socio-economic differences in cause-specific mortality.</p> <p>Methods</p> <p>The data source is a nationally representative, repeated cross-sectional survey, "Health Behaviour and Health among the Finnish Adult Population" (AVTK). The survey results were linked with socio-economic register data from Statistics Finland (from the years 1979-2002) and mortality follow-up data up to 2006 from the Finnish National Cause of Death Register. The data included 32451 men and 35420 women (response rate 73.5%). Self-reported measures of depression, insomnia and stress were used as indicators of psychological distress. Socio-economic factors included education, employment status and household income. Mortality data consisted of unnatural causes of death (suicide, accidents and violence, and alcohol-related mortality) and coronary heart disease (CHD) mortality. Adjusted hazard ratios were calculated using the Cox regression model.</p> <p>Results</p> <p>In unnatural mortality, psychological distress accounted for some of the employment status (11-31%) and income level (4-16%) differences among both men and women, and for the differences related to the educational level (5-12%) among men; the educational level was associated statistically significantly with unnatural mortality only among men. Psychological distress had minor or no contribution to socio-economic differences in CHD mortality.</p> <p>Conclusions</p> <p>Psychological distress partly accounted for socio-economic disparities in unnatural mortality. Further studies are needed to explore the role and mechanisms of psychological distress associated with socio-economic differences in cause-specific mortality.</p

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease

Identifying Local and Centralized Mental Health ServicesThe Development of a New Categorizing Variable

The challenges of mental health and substance abuse services (MHS) require shifting of the balance of resources from institutional care to community care. In order to track progress, an instrument that can describe these attributes of MHS is needed. We created a coding variable in the European Service Mapping Schedule-Revised (ESMS-R) mapping tool using a modified Delphi panel that classified MHS into centralized, local services with gatekeeping and local services without gatekeeping. For feasibility and validity, we tested the variable on a dataset comprising MHS in Southern Finland, covering a population of 2.3 million people. There were differences in the characteristics of services between our study regions. In our data, 41% were classified as centralized, 37% as local without gatekeeping and 22% as local services with gatekeeping. The proportion of resources allocated to local services varied from 20% to 43%. Reclassifying ESMS-R is an easy way to compare the important local vs. centralized balance of MHS systems globally, where such data exists. Further international studies comparing systems and validating this approach are needed.Peer reviewe

Does Compassion Predict Blood Pressure and Hypertension? The Modifying Role of Familial Risk for Hypertension

Background This study investigated (i) whether compassion is associated with blood pressure or hypertension in adulthood and (ii) whether familial risk for hypertension modifies these associations. Method The participants (N = 1112-1293) came from the prospective Young Finns Study. Parental hypertension was assessed in 1983-2007; participants' blood pressure in 2001, 2007, and 2011; hypertension in 2007 and 2011 (participants were aged 30-49 years in 2007-2011); and compassion in 2001. Results High compassion predicted lower levels of diastolic and systolic blood pressure in adulthood. Additionally, high compassion was related to lower risk for hypertension in adulthood among individuals with no familial risk for hypertension (independently of age, sex, participants' and their parents' socioeconomic factors, and participants' health behaviors). Compassion was not related to hypertension in adulthood among individuals with familial risk for hypertension. Conclusion High compassion predicts lower diastolic and systolic blood pressure in adulthood. Moreover, high compassion may protect against hypertension among individuals without familial risk for hypertension. As our sample consisted of comparatively young participants, our findings provide novel implications for especially early-onset hypertension.Peer reviewe

Mutations in the COL18A1 gen associated with knobloch syndrome and structural brain anomalies : a novel case report and literature review of neuroimaging findings

AbstractCOL18A1 gene mutations have been associated with Knobloch syndrome, which is characterized by ocular and brain abnormalities. Here we report a 4.5 years-old male child with autism and two novel COL18A1 mutations (NM_030582.4: c.1883_1891dup and c.1787C>T). Hypermetropic astigmatism, but not brain migration disorders, was observed. However, an asymmetric pattern of cerebellar perfusion and a smaller arcuate fascicle were found. Low levels of collagen XVIII were also observed in the patient’s serum. Thus, biallelic loss-of-function mutations in COL18A1 may be a new cause of autism without the brain malformations typically reported in patients with Knobloch syndrome.Abstract COL18A1 gene mutations have been associated with Knobloch syndrome, which is characterized by ocular and brain abnormalities. Here we report a 4.5 years-old male child with autism and two novel COL18A1 mutations (NM_030582.4: c.1883_1891dup and c.1787C>T). Hypermetropic astigmatism, but not brain migration disorders, was observed. However, an asymmetric pattern of cerebellar perfusion and a smaller arcuate fascicle were found. Low levels of collagen XVIII were also observed in the patient’s serum. Thus, biallelic loss-of-function mutations in COL18A1 may be a new cause of autism without the brain malformations typically reported in patients with Knobloch syndrome

Genome-wide association analysis on normal hearing function identifies PCDH20 and SLC28A3 as candidates for hearing function and loss

Hearing loss and individual differences in normal hearing both have a substantial genetic basis. Although many new genes contributing to deafness have been identified, very little is known about genes/variants modulating the normal range of hearing ability. To fill this gap, we performed a two-stage meta-analysis on hearing thresholds (tested at 0.25, 0.5, 1, 2, 4, 8 kHz) and on pure-tone averages (low-, medium-and high-frequency thresholds grouped) in several isolated populations from Italy and Central Asia (total N = 2636). Here, we detected two genome-wide significant loci close to PCDH20 and SLC28A3 (top hits: rs78043697, P = 4.71E-10 and rs7032430, P = 2.39E-09, respectively). For both loci, we sought replication in two independent cohorts: B58C from the UK (N = 5892) and FITSA from Finland (N = 270). Both loci were successfully replicated at a nominal level of significance (P <0.05). In order to confirm our quantitative findings, we carried out RT-PCR and reported RNA-Seq data, which showed that both genes are expressed in mouse inner ear, especially in hair cells, further suggesting them as good candidates for modulatory genes in the auditory system. Sequencing data revealed no functional variants in the coding region of PCDH20 or SLC28A3, suggesting that variation in regulatory sequences may affect expression. Overall, these results contribute to a better understanding of the complex mechanisms underlying human hearing function.Peer reviewe

Regional Correlates of Psychiatric Inpatient Treatment

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