[Glucagonoma - a rare neuroendocrine tumor (NET) that typically originates in the pancreas]. / Nekrolytiskt migrerande erytem och glukagonom.

One of the primary indicators of this condition is a painful and migratory dermatitis. Additionally, early signs often include weight loss and diabetes. Patients with glucagonoma commonly first encounter general practitioners or dermatologists. Unfortunately, due to the nonspecific nature of symptoms such as eczema-like dermatitis, weight loss and diabetes, diagnosis is frequently delayed, often by 2-3 years. Consequently, by the time patients are diagnosed, the tumor has usually grown and metastasized, often spreading to the liver. As a result, surgical intervention is often not possible, and treatment options are usually limited to palliative care. However, with early diagnosis of glucagonoma, treatment can be curative. Therefore, it is crucial for medical professionals who initially meet these patients, including dermatologists, general practitioners, endocrinologists, and others, to be aware of this condition to ensure an early diagnosis. By recognizing the signs and symptoms early, doctors can potentially improve patient outcomes and save lives.

Social Disconnectedness in Individuals with Cardiovascular Disease: Associations with Health Literacy and Treatment Burden.

BACKGROUND: Knowledge is limited on associations between social disconnectedness (i.e. loneliness and social isolation), health literacy and perceived treatment burden in individuals with cardiovascular disease (CVD). However, understanding these associations may be important for clinical practice. METHODS: This study used cross-sectional self-reported data from the 2017 Danish health and morbidity survey entitled 'How are you?', investigating the associations of loneliness and social isolation with low health literacy and high treatment burden in individuals with CVD (n = 2521; mean age = 65.7 years). RESULTS: Logistic regression analysis showed that loneliness and social isolation were associated with low health literacy in terms of difficulties in 'understanding health information' (loneliness: adjusted odds ratio (AOR) = 1.32, 95% confidence intervals (CI) [1.16, 1.50]; social isolation: AOR = 1.47, 95% CI [1.24, 1.73]) and 'engaging with healthcare providers' (loneliness: AOR = 1.53, 95% CI [1.37, 1.70]; social isolation: AOR = 1.21, 95% CI [1.06, 1.40]) and associated with high treatment burden (loneliness: AOR = 1.49, 95% CI [1.35, 1.65]; social isolation: AOR = 1.20, 95% CI [1.06, 1.37]). CONCLUSIONS: Our findings show that loneliness and social isolation coexisted with low health literacy and high treatment burden in individuals with CVD. These findings are critical as socially disconnected individuals experience more health issues. Low health literacy and a high treatment burden may potentially exacerbate these issues.

Reducing loneliness in the community. More Together ('Flere i Fællesskaber')-a complex intervention in Denmark.

The mounting evidence that loneliness is a determinant of poor health and well-being underpins the need for effective interventions and community action. 'More Together' (MoTo) is a large-scale, complex, multi-component and multi-level intervention for community change that addresses loneliness among young people and older adults in Silkeborg Municipality, Denmark. The intervention is inspired by the Collective Impact framework, and it is practice driven and rooted in an extensive cross-sector partnership. This article outlines (i) the organization of the cross-sector partnership, (ii) the structure of the intervention programme, (iii) the key components and activities of the programme and, finally, (iv) the intervention setting and target population. MoTo aims to create new ways to develop, implement and evaluate loneliness interventions. Experiences gained from MoTo hold the potential to transform our understanding of loneliness interventions and may inform and guide future interventions.

Loneliness, social isolation, and healthcare utilization in the general population.

OBJECTIVES: Due to increasing pressure on healthcare resources, knowledge of factors that affect healthcare utilization (HCU) is important. However, the evidence of a longitudinal association between loneliness and social isolation respectively, and HCU is limited. The present prospective cohort study investigated the association of loneliness and social isolation with HCU in the general population over time. METHOD: Data from the 2013 Danish "How are you?" survey (n = 27.501) were combined with individual-level register data with almost complete follow-up over a 6-year follow-up period (2013-2018). Negative binomial regression analyses were performed while adjusting for baseline demographics and preexisting chronic disease. RESULTS: Loneliness measured was significantly associated with more general practice contacts (incident rate ratio [IRR] = 1.03, 95% confidence interval [CI] [1.02, 1.04]), more emergency treatments (IRR = 1.06, [1.03, 1.10]), more emergency admissions (IRR = 1.06, [1.03, 1.10]), and hospital admission days (IRR = 1.05, [1.00, 1.11]) across the 6-year follow-up period. No significant associations were found between social isolation and HCU with one minor exception, in which social isolation was associated with fewer planned outpatient treatments (IRR = 0.97, [0.94, 0.99]). Wald test demonstrated that the association of loneliness with emergency admissions and hospital admissions days was not significantly different from the effects of social isolation on those outcomes. CONCLUSIONS: Our findings suggest that loneliness slightly increased the number of general practice contacts and emergency room treatments. Overall, the effects of loneliness and social isolation on HCU were small. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The longitudinal relation between loneliness and perceived stress: A structural equation modelling analysis of 10,159 individuals.

AIMS: Prolonged loneliness and severe stress are increasingly recognised as public health concerns and considered risk factors for mental disorders, somatic illnesses and mortality. Loneliness and perceived stress also often co-occur; however, their longitudinal relation remains unclear. To the best of our knowledge, this is the first study aiming to investigate the longitudinal relation between loneliness and perceived stress independently of cross-sectional associations and time effects. METHODS: Designed as a population-based cohort study with repeated measurements, the present study included individuals aged 16-80 years at baseline who participated in the Danish National Health Survey ('How are you?') in 2013 and 2017 (N = 10,159; response rate = 50%). Structural equation modelling was used to examine associations between loneliness and perceived stress in the total sample and across age groups (i.e., 16-29, 30-64 and 65-80 years). RESULTS: The models indicated bidirectional relations between loneliness and perceived stress. The standardized cross-lagged path from loneliness to perceived stress (ß: 0.12, 95% confidence interval (CI) (0.08, 0.16), p < 0.001) and from perceived stress to loneliness (ß: 0.12, 95% CI (0.07, 0.16), p < 0.001) both corresponded to small effect sizes in the total sample. Additionally, the results indicated strong cross-sectional associations, especially among adolescents and young adults (16-29 years), and high temporal stability, especially among the elderly (65-80 years). CONCLUSIONS: Loneliness and perceived stress mutually predict each other over time. The finding of both substantial bidirectional and cross-sectional associations demonstrates an interdependence between loneliness and perceived stress that may be relevant to consider in future interventions.

Loneliness, Social Isolation, and Chronic Disease Outcomes.

BACKGROUND: Research suggests that loneliness and social isolation (SI) are serious public health concerns. However, our knowledge of the associations of loneliness and SI with specific chronic diseases is limited. PURPOSE: The present prospective cohort study investigated (a) the longitudinal associations of loneliness and SI with four chronic diseases (cardiovascular disease [CVD], chronic obstructive pulmonary disease [COPD], diabetes mellitus Type 2 [T2D], and cancer), (b) the synergistic association of loneliness and SI with chronic disease, and (c) baseline psychological and behavioral explanatory factors. METHODS: Self-reported data from the 2013 Danish "How are you?" survey (N = 24,687) were combined with individual-level data from the National Danish Patient Registry on diagnoses in a 5 year follow-up period (2013-2018). RESULTS: Cox proportional hazard regression analyses showed that loneliness and SI were independently associated with CVD (loneliness: adjusted hazard ratio (AHR) = 1.20, 95% confidence interval [CI; 1.03, 1.40]; SI: AHR = 1.23, 95% CI [1.04, 146]) and T2D (loneliness: AHR =1.90, 95% CI [1.42, 2.55]; SI: AHR = 1.59, 95% CI [1.15, 2.21]). No significant associations were found between loneliness or SI and COPD and cancer, respectively. Likewise, loneliness and SI did not demonstrate a synergistic effect on chronic disease. Multiple mediation analysis indicated that loneliness and SI had an indirect effect on CVD and T2D through both baseline psychological and behavioral factors. CONCLUSION: Loneliness and SI were independently associated with a diagnosis of CVD and T2D within a 5 year follow-up period. The associations of loneliness and SI with CVD and T2D were fully explained by baseline psychological and behavioral factors.

Biallelic KRT5 mutations in autosomal recessive epidermolysis bullosa simplex, including a complete human keratin 5 "knock-out".

Epidermolysis bullosa simplex (EBS) is usually inherited as an autosomal dominant disease due to monoallelic gain-of-function mutations in KRT5 or KRT14. Although autosomal recessive forms of EBS have been associated with mutations in at least 10 genes, recessive EBS due to homozygous biallelic KRT5 mutations has not been reported previously; it has been hypothesized that it would result in prenatal lethality. We sought the genetic causes of EB in a cohort of 512 distinct EB families by performing whole exome sequencing (WES) and using an EB-targeting next-generation sequencing (NGS) panel of 21 genes. The pathogenicity and consequences of the mutations were determined by expression profiling and at tissue and ultrastructural levels. Two pathogenic, homozygous missense variants of KRT5 in two patients with generalized EBS and a homozygous null mutation in a patient who died as a neonate from complications of EB were found. The two missense mutations disrupted keratin 5 expression on immunofluorescence microscopy, and the human "knock-out" of KRT5 showed no RNA and protein expression. Collectively, these findings identify biallelic KRT5 mutations with a phenotypic spectrum varying from mild, localized and generalized to perinatal lethal, expanding the genotypic profile of autosomal recessive EBS.

Mutations in SULT2B1 Cause Autosomal-Recessive Congenital Ichthyosis in Humans.

Ichthyoses are a clinically and genetically heterogeneous group of genodermatoses associated with abnormal scaling of the skin over the whole body. Mutations in nine genes are known to cause non-syndromic forms of autosomal-recessive congenital ichthyosis (ARCI). However, not all genetic causes for ARCI have been discovered to date. Using whole-exome sequencing (WES) and multigene panel screening, we identified 6 ARCI-affected individuals from three unrelated families with mutations in Sulfotransferase family 2B member 1 (SULT2B1), showing their causative association with ARCI. Cytosolic sulfotransferases form a large family of enzymes that are involved in the synthesis and metabolism of several steroids in humans. We identified four distinct mutations including missense, nonsense, and splice site mutations. We demonstrated the loss of SULT2B1 expression at RNA and protein levels in keratinocytes from individuals with ARCI by functional analyses. Furthermore, we succeeded in reconstructing the morphologic skin alterations in a 3D organotypic tissue culture model with SULT2B1-deficient keratinocytes and fibroblasts. By thin layer chromatography (TLC) of extracts from these organotypic cultures, we could show the absence of cholesterol sulfate, the metabolite of SULT2B1, and an increased level of cholesterol, indicating a disturbed cholesterol metabolism of the skin upon loss-of-function mutation in SULT2B1. In conclusion, our study reveals an essential role for SULT2B1 in the proper development of healthy human skin. Mutation in SULT2B1 leads to an ARCI phenotype via increased proliferation of human keratinocytes, thickening of epithelial layers, and altered epidermal cholesterol metabolism.

Coupling of Temperament with Mental Illness in Four Age Groups.

Studies of temperament profiles in patients with mental disorders mostly focus on emotionality-related traits, although mental illness symptoms include emotional and nonemotional aspects of behavioral regulation. This study investigates relationships between 12 temperament traits (9 nonemotionality and 3 emotionality related) measured by the Structure of Temperament Questionnaire and four groups of clinical symptoms (depression, anxiety, antisociality, and dominance-mania) measured by the Personality Assessment Inventory. The study further examines age differences in relationships among clinical symptoms and temperament traits. Intake records of 335 outpatients and clients divided into four age groups (18-25, 26-45, 46-65, and 66-85) showed no significant age differences on depression scales; however, the youngest group had significantly higher scores on Anxiety, Antisocial Behavior, Dominance, and Thought Disorders scales. Correlations between Personality Assessment Inventory and Structure of Temperament Questionnaire scales were consistent with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, descriptors showing strong concurrent validity. Several age differences on temperament scales are also reported. Results show the benefits of differentiation between physical, social-verbal, and mental aspects of activities, as well as differentiation between dynamical, orientational, and energetic aspects in studying mental illness and temperament.

Do stress, health behavior, and sleep mediate the association between loneliness and adverse health conditions among older people?

INTRODUCTION: Prior research has established an association between loneliness and a variety of negative health conditions among older people. However, little is known about the mechanisms underlying this association. OBJECTIVE: Building on the Loneliness Model, Hawkley and Cacioppo (2010) identified possible pathways through which loneliness may affect the development of adverse health conditions. The present study was designed to test the pathways proposed by Hawkley and Cacioppo. METHODS: The sample consisted of 8593 elderly ranging from 65 to 102 years of age participating in the 2013 Public Health Survey "How are you?". RESULTS: Findings show that loneliness was significantly associated with cardiovascular disease, diabetes, and migraine. In addition high perceived stress, physical inactivity, daily smoking, and poor sleep mediated the association between loneliness and adverse health conditions. Moreover, findings demonstrate several gender differences in the association between loneliness and various adverse condition and the indirect mechanisms affecting these associations. CONCLUSION: The findings largely support the pathways proposed by Hawkley and Cacioppo.

Sensitization to skin-associated microorganisms in adult patients with atopic dermatitis is of importance for disease severity.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Environmental and genetic factors, as well as microbial products from yeasts and bacteria, play a role in triggering the disease. A cohort of 619 adult patients with AD was screened for severity of AD, sensitization to Malassezia sympodialis, Candida albicans, Staphylococcus aureus enterotoxins and Dermatophagoides pteronyssinus. Serum levels of interleukin (IL)-18 were measured. Immunoglobulin E (IgE) sensitization to the combination of both yeast and mite antigens was found to be associated with more severe disease and higher levels of total IgE. AD patients with IgE sensitization to several microbial antigens had more severe disease than those with no IgE sensitization to microbial antigens. Sera from patients with IgE-associated AD showed higher levels of IL-18. Skin-associated microorganisms are exogenous factors triggering IgE-response and severity of AD. These findings are clinically important, and sensitization to these organisms should be assessed and considered in treatment strategies.

Identification of Culex pipiens complex mosquitoes in a hybrid zone of West Nile virus transmission in Fresno County, California.

Culex pipiens sensu lato mosquitoes were collected from 24 gravid traps (mid-June to mid-October, 2005) in Fresno County, CA. Captured gravid females were allowed to oviposit before sibling species identification by Ace.2 PCR and detection of West Nile virus (WNV) RNA by RT-PCR were performed on the mother and her offspring. Of the 442 Cx. pipiens s.l. female mosquitoes collected, 88 were positive for WNV viral RNA (peaked in August) with no significant differences among complex members or habitat. Vertical transmission was detected in 4 out of 20 families originating from WNV-positive mothers, however, in only a small number of offspring from each family. Out of 101 families that had PCR-based maternal and offspring identifications, the offspring from 15 families produced inexplicable amplicon patterns, suggesting ambiguities in the PCR assay identifications. Male genitalia (DV/D ratio) and Ace.2 PCR identifications revealed numerous discrepancies in our ability to accurately determine the identity of Cx. pipiens complex members in the hybrid zone of Fresno County.

A detailed larval salivary gland polytene chromosome photomap for Culex quinquefasciatus (Diptera: Culicidae) from Johannesburg, South Africa.

The suitability of polytene chromosomes for population genetic and in situ DNA physical mapping was investigated in Johannesburg, South Africa, Culex quinquefasciatus Say and Culex pipiens L.. The most defined and consistent polytene spreads were obtained from salivary glands of early fourth instars from Cx. quinquefasciatus. A photomap is provided for a Cx. quinquefasciatus colony originating from Johannesburg. Variations in banding patterns, chromosome aberrations, and paracentric inversions within the colony and comparisons with previous published descriptions are discussed. Chromosomes of sufficient quality were obtained such that a DNA coding for an odorant binding protein could be mapped by colorimetric in situ hybridization.

Effects of lambda-cyhalothrin on mosquito larvae and predatory aquatic insects.

Agricultural insecticides can affect mosquito production in rice fields by controlling mosquitoes, disrupting biological control or contributing to selection of insecticide resistance. The duration of insecticidal activity of the pyrethroid lambda-cyhalothrin was quantified on predatory insects in rice fields and on three kinds of mosquito larva: a pyrethroid-susceptible strain of Culex tarsalis Coquillet, a pyrethroid-resistant strain of Cx pipiens L. (sensu lato) and non-resistant Cx pipiens s.l. Lambda-cyhalothrin killed most caged, susceptible mosquitoes for up to 21 days. It killed fewer resistant Cx pipiens s.l., but suppressed their survival for over a week. Lambda-cyhalothrin suppressed field populations of predatory insects through day 29. Agricultural use of lambda-cyhalothrin can provide incidental mosquito control. However, the pyrethroid persisted in sediment and gradually decreased in activity, which could contribute to selection of pyrethroid-resistant mosquitoes. Because caged mosquitoes showed good survival before predators recovered, disruption of biological control is possible. It is therefore advisable for growers and mosquito control agencies to communicate about pesticide use.

Development of a HPLC/tandem-MS method for the analysis of the larvicides methoprene, hydroprene, and kinoprene at trace levels using Diels-Alder derivatization.

The invasion and subsequent spread of the mosquito-borne West Nile virus in the United States has resulted in increased use of methoprene. With the increased need for sensitive detection and monitoring of methoprene in the environment, an analytical LC/ESI-MS/MS method has been developed for the analysis of methoprene and two analogues, kinoprene and hydroprene, in water. To improve the ionization efficiency of the nonpolar analytes, a derivatization step with the Cookson-type reagent 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) was used. Derivatization improved the limit of detection 100-fold. For tandem MS analyses, limits of detection in environmental water samples (S/N = 3) are about 6 pg/mL for methoprene and 20 pg/mL for kinoprene and hydroprene, resulting in limits of quantification (S/N = 10) of 20 pg/mL for methoprene and 60 pg/mL for hydroprene and kinoprene extracted from 10 mL of water. This method was applied to measure methoprene concentrations in water samples from a treated site.

Influence of temperature and concentration of VectoBac on control of the salt-marsh mosquito, Ochlerotatus squamiger, in Monterey County, California.

Laboratory susceptibility bioassays were conducted to determine the efficacy of VectoBac TP (Bacillus thuringiensis var. israelensis [Bti]) at different concentrations and temperatures against the salt-marsh mosquito Ochlerotatus squamiger. Bioassays on late 3rd- and early 4th-stage larvae, read at 72 h and 14 degrees C produced an LD90 of 0.223 mg/liter, whereas more than double this dose was required to produce similar mortality at 6 degrees C. A field trial in the winter of 2001-02 of an aerially applied VectoBac TP formulation in Salinas, CA, corroborated laboratory bioassay observations by producing 97-100% control of Oc. squamiger at 72 h postapplication. Inconsistencies in mortality with field applications of VectoBac TP previously observed by North Salinas Valley Mosquito Abatement personnel were most likely caused by uneven application rates and varying temperatures and water volumes.

Pyrethroid tolerance in Culex pipiens pipiens var molestus from Marin County, California.

In May 2001 a sample of Culex pipiens pipiens variety molestus Forskål from Marin County, California, collected as larvae and reared to adults, was found to show reduced resmethrin and permethrin knock-down responses in bottle bioassays relative to a standard susceptible Cx. pipiens quinquefasciatus Say colony (CQ1). Larval susceptibility tests, using CQ1 as standard susceptible, indicated that the Marin mosquitoes had LC50 resistance ratios of 18.3 for permethrin, 12 for deltamethrin and 3.3 for pyrethrum. A colony of Marin was established and rapidly developed higher levels of resistance in a few generations after exposure to permethrin as larvae. These selected larvae were shown to cross-resist to lambda-cyhalothrin as well as to DDT. However, adult knock-down time in the presence of permethrin, resmethrin and pyrethrum was not increased after increase in tolerance to pyrethroids as larvae. Partial and almost complete reversion to susceptibility as larvae was achieved with S, S, S-tributylphosphorotrithioate and piperonyl butoxide (PBO), respectively, suggesting the presence of carboxylesterase and P450 monooxygenase mediated resistance. Insensitive target site resistance (kdr) was also detected in some Marin mosquitoes by use of an existing PCR-based diagnostic assay designed for Cx. p. pipiens L mosquitoes. Carboxylesterase mediated resistance was supported by use of newly synthesized novel pyrethroid-selective substrates in activity assays. Bottle bioassays gave underestimates of the levels of tolerance to pyrethroids of Marin mosquitoes when compared with mortality rates in field trials using registered pyrethroid adulticides with and without PBO. This study represents the first report of resistance to pyrethroids in a feral population of a mosquito species in the USA.

Role of esterase enzymes in monitoring for resistance of California red scale, Aonidiella aurantii (Homoptera: Diaspididae), to organophosphate and carbamate insecticides.

Eighty-seven populations of California red scale, Aonidiella aurantii (Maskell), from the San Joaquin Valley of California were tested for insecticide resistance by using chlorpyrifos, methidathion, and/or carbaryl in a standard fruit-dip bioassay as well as for general esterase activity by using alpha-naphthyl acetate as a substrate in a colorimetric test. The percentage of individuals that survived a discriminating concentration of methidathion, chlorpyrifos, or carbaryl was significantly correlated with the percentage of individuals showing > 0.4 nmol of esterase activity per minute per microgram of protein in the colorimetric test. Scale survival of the organophosphates showed a higher correlation with esterase activity than survival of carbaryl. These results suggest that the colorimetric test of esterase activity is useful as an indicator of the frequency of organophosphate-resistant and, to a lesser extent, carbamate-resistant individuals in California red scale populations. The results of tests for activity and inhibition of acetylcholinesterase activity suggest that California red scale is using increased amounts of esterase enzymes, including acetylcholinesterase, to sequester organophosphate and carbamate insecticides, rather than modified acetylcholinesterase. Third instars collected from twigs, leaves, and fruit showed similar levels of esterase activity. The colorimetric test of esterase activity is a useful tool to detect organophosphate and carbamate resistance in San Joaquin Valley California red scale because of its speed of testing over a wide range of months, allowing for within-season decision making by citrus growers.