Losing a loved one to homicide: Prevalence and mental health correlates in a national sample of young adults

The present study examined the prevalence, demographic distribution, and mental health correlates of losing a loved one to homicide. A national sample of 1,753 young adults completed structured telephone interviews measuring violence exposure, mental health diagnoses, and loss of a family member or close friend to a drunk driving accident (vehicular homicide) or murder (criminal homicide). The prevalence of homicide survivorship was 15%. African Americans were more highly represented among criminal homicide survivors. Logistic regression analyses found that homicide survivors were at risk for past year posttraumatic stress disorder (OR = 1.88), major depressive episode (OR = 1.64), and drug abuse/dependence (OR = 1.77). These findings highlight the significant mental health needs of homicide survivors.     

Vitamin D levels in people with multiple sclerosis and community controls in Tasmania,Australia

Abstract Background Adequate 25(OH)D levels are required to prevent adverse effects on bone health. Population-based data on factors associated with 25(OH)D levels of people with MS have been lacking. Objectives To examine the prevalence and determinants of vitamin D insufficiency in a population-based sample of MS cases and controls, and to compare 25(OH)D status between MS cases and controls, taking into account case disability. Methods We conducted a population based case-control study in Tasmania, Australia (latitude 41–43°S) on 136 prevalent cases with MS confirmed by magnetic resonance imaging and 272 community controls, matched on sex and year of birth. Measurements included serum 25(OH)D, sun exposure, skin type, dietary vitamin D intake and disability including EDSS. Results A high prevalence of vitamin D insufficiency was found in MS cases and controls. Among MS cases, increasing disability was strongly associated with lower levels of 25(OH)D and with reduced sun exposure. Cases with higher disability (EDSS > 3) were more likely to have vitamin D insufficiency than controls (OR = 3.07 (1.37, 6.90) for 25(OH)D ≤ 40 nmol/l), but cases with low disability were not (OR = 0.87 (0.41, 1.86)). Conclusion The strong associations between disability, sun exposure and vitamin D status indicate that reduced exposure to the sun, related to higher disability, may contribute to the high prevalence of vitamin D insufficiency found in this population-based MS case sample. Active detection of vitamin D insufficiency among people with MS and intervention to restore vitamin D status to adequate levels should be considered as part of the clinical management of MS.     

Illness perception and health-related quality of life in multiple sclerosis

AIMS - A number of physical and psychological factors have been shown to affect health-related quality of life (HRQoL) in patients with multiple sclerosis (MS). Among these, the role of illness perceptions has not been established as an independent factor. This study, the first of its kind in an Australian population, aimed to use a large sample to determine the relative importance of individual factors to each domain of HRQoL, in particular the role of illness perception. MATERIALS AND METHODS - 580 patients with confirmed MS were assessed cross sectionally in a designated research clinic to determine the relative impact of physical factors (illness severity, duration, age, fatigue and pain) and psychological factors (mood, cognition and illness representations) on each domain of the SF-36. RESULTS - Categorical regression analysis showed that a combination of physical and psychological factors predicted 38-71% of variance in HRQoL. Illness perception was shown to have an independent effect on HRQoL in MS. The Extended Disability Status Scale was a significant determinant in all domains except for mental health. Depression was less prevalent than anxiety, but had a greater effect on function. CONCLUSION - Illness perception is an independent factor contributing to HRQoL in people with MS. Individual domains of HRQoL are associated with different patterns of physical and psychological factors. In the domains of role and social function, activities most highly valued by patients with MS, depression, anxiety, fatigue and illness perceptions are key determinants, all of which have the potential to be improved through specific interventions.     

Use of sentinel lymph node biopsy for melanoma of the head and neck

Sentinel lymph node biopsy (SLN) is a well-accepted procedure for truncal and extremity melanoma (T&E). However, its role in melanoma of the head and neck (H&N) remains controversial. Complex lymphatic and vascular drainage make SLN more challenging in this region. This study was done to evaluate the results of SLN for H&N versus T&E melanoma. Three hundred sixteen patients who underwent SLN for melanoma using a double indicator technique were identified from a prospective database. Records were analyzed retrospectively. Statistical analysis was performed using chi2, t test, or Mann-Whitney U test to evaluate the results, as appropriate. H&N was found in 87 cases (27.5%). The mean age was 63.2 and 53.2 years for H&N and T&E melanoma (P < 0.001), respectively. 99Technetium positivity (89.7% H&N versus 99.6% T&E, P < 0.001) and isosulfan blue positivity (85.1% H&N versus 91.7% T&E, P = 0.08) were more likely in T&E melanoma. There was a significant difference between H&N and T&E melanoma with respect to the incidence of failed SLN, defined as no sentinel nodes identified intraoperatively (8.0% versus 0%, P < 0.001). Both groups had similar rates of positive intraoperative imprint cytologic examination (4.6% H&N versus 6.1% T&E, P > 0.5). There was a trend suggesting a higher mean number of sentinel lymph nodes found (3.1 versus 2.7, P = 0.1) in H&N melanoma. The total number of lymph nodes found in dissection specimens (20.9 versus 21.9, P = 0.45), the total number of positive lymph nodes (3.5 versus 1.6, P = 0.32), the incidence of any recurrence (19.5% versus 12.7%, P = 0.2), and time to recurrence (14.2 versus 20.6 months, P = 0.18) were similar between H&N and T&E melanoma. SLN mapping of H&N lesions is more difficult than at other sites. However, rates of nodal positivity are similar to melanoma of the trunk and extremities. Therefore, despite being more demanding, SLN is useful in diagnosis and treatment of melanomas of the head and neck.     

Two factors of the lectin pathway of complement, l-ficolin and mannan-binding lectin, and their associations with prematurity, low birthweight and infections in a large cohort of Polish neonates

Ficolins and one collectin, mannan-binding lectin (MBL), are the only factors known to activate the lectin pathway (LP) of complement. There is considerable circumstantial evidence that MBL insufficiency can increase susceptibility to various infections and influence the course of several non-infectious diseases complicated by infections. Much less information is available concerning l-ficolin. We report the results of a prospective study to investigate any association between either MBL deficiency or l-ficolin deficiency with prematurity, low birthweight or perinatal infections in a large cohort of Polish neonates, representing an ethnically homogenous population (n=1832). Cord blood samples were analysed to determine mbl-2 gene variants, MBL concentrations and MBL-MASP-2 complex activities (MBL-dependent lectin pathway activity) as well as l-ficolin levels. Median concentrations of l-ficolin and MBL were 2500 and 1124 ng/ml, respectively, while median LP activity was 272 mU/ml. After genotyping, 60.6% of babies were mbl-2 A/A, 35.4% were A/O and 4% were O/O genotypes. We found relative l-ficolin deficiency to be associated with prematurity, low birthweight and infections. l-Ficolin concentration correlated with gestational age and with birthweight, independently of gestational age. Preterm deliveries (<38 weeks) occurred more frequently among neonates with low LP activity but not with those having low serum MBL levels. Similarly, no association of serum MBL deficiency with low birthweight was found, but there was a correlation between LP activity and birthweight. Genotypes conferring very low serum MBL concentrations were associated with perinatal infections, and high-MBL-conferring genotypes were associated with prematurity. Our findings suggest that l-ficolin participates in host defence during the perinatal period and constitute the first evidence that relative l-ficolin deficiency may contribute to the adverse consequences of prematurity. Some similar trends were found with facets of MBL deficiency, but the observed relationships were weaker and less consistent.     

Multiple granular cell tumors are an associated feature of LEOPARD syndrome caused by mutation in PTPN11

We report a patient with a clinical and molecular diagnosis of LEOPARD syndrome (LS) associated with multiple granular cell tumors (MGCT). Bidirectional sequencing of exons 7, 12, and 13 of the PTPN11 gene revealed the T468M missense mutation in exon 12. This mutation has been previously reported in patients with LS. To our knowledge, this is the first report of MGCT associated with molecularly characterized LS and provides the first molecular evidence linking granular cell tumors (GCT) to the Ras/mitogen-activated protein (MAP) kinase pathway. We propose that MGCT can be associated with LS. Analysis of GCT from this case tested negatively for loss of heterozygosity (LOH) at the PTPN11 and NF1 loci and did not show deletions of the PTEN gene. The absence of LOH of PTPN11 supports published functional data that T468M is a dominant-negative mutation.     

Multivalent presentation of antihantavirus peptides on nanoparticles enhances infection blockade

Viral entry into susceptible host cells typically results from multivalent interactions between viral surface proteins and host entry receptors. In the case of Sin Nombre virus (SNV), a New World hantavirus that causes hantavirus cardiopulmonary syndrome, infection involves the interaction between viral membrane surface glycoproteins and the human integrin alpha(v)beta(3). Currently, there are no therapeutic agents available which specifically target SNV. To address this problem, we used phage display selection of cyclic nonapeptides to identify peptides that bound SNV and specifically prevented SNV infection in vitro. We synthesized cyclic nonapeptides based on peptide sequences of phage demonstrating the strongest inhibition of infection, and in all cases, the isolated peptides were less effective at blocking infection (9.0% to 27.6% inhibition) than were the same peptides presented by phage (74.0% to 82.6% inhibition). Since peptides presented by the phage were pentavalent, we determined whether the identified peptides would show greater inhibition if presented in a multivalent format. We used carboxyl linkages to conjugate selected cyclic peptides to multivalent nanoparticles and tested infection inhibition. Two of the peptides, CLVRNLAWC and CQATTARNC, showed inhibition that was improved over that of the free format when presented on nanoparticles at a 4:1 nanoparticle-to-virus ratio (9.0% to 32.5% and 27.6% to 37.6%, respectively), with CQATTARNC inhibition surpassing 50% when nanoparticles were used at a 20:1 ratio versus virus. These data illustrate that multivalent inhibitors may disrupt polyvalent protein-protein interactions, such as those utilized for viral infection of host cells, and may represent a useful therapeutic approach.