Participatory design of bodysymptoms.org: An interactive web resource to explain multisystem functional somatic symptoms.

OBJECTIVE: There is a lack of trustworthy information about Functional Somatic Symptoms (FSS) on the internet. This means integrative bio-psycho-social explanations of FSS and related health advice are not readily available to the public. To explore and address this problem, we carried out the bodysymptoms project, with the aim to build a website which presents current widely accepted explanations for FSS and shows how different explanations are inter-connected. METHODS: Bodysymptoms was set up as a research-in-action project with a diverse range of international stakeholder-participants, combining approaches from patient and public involvement in healthcare with participatory design. 7 participants with lived experience of multi-system functional symptoms took part in the project and measures of meaningful engagement throughout the project were rated highly. This manuscript describes the methodology by which the website was developed. RESULTS: Through iterative cycles we determined the requirements for an interactive explanatory model and co-created a novel online health interactive resource with integrated actionable health advice. The target end user are young adults with persistent physical symptoms, maintained by functional mechanisms. The overall aim is to empower people at risk of developing functional disorders to seek better health outcomes. The website is intended to be used prior to or alongside engagement with healthcare. CONCLUSION: Bringing lived experience and multi-disciplinary perspectives into dialogue through participatory design can harness the power of research to create immediate shared value. This project has resulted in a usable open access website, bodysymptoms.org, which provides education about FSS for patients, healthcare professionals and members of the public looking to understand FSS.

Demographic and Clinical Presentations of Youth using Enhanced Mental Health Services in Six Indigenous Communities from the ACCESS Open Minds Network.

OBJECTIVE: In many Indigenous communities, youth mental health services are inadequate. Six Indigenous communities participating in the ACCESS Open Minds (AOM) network implemented strategies to transform their youth mental health services. This report documents the demographic and clinical presentations of youth accessing AOM services at these Indigenous sites. METHODS: Four First Nations and two Inuit communities contributed to this study. Youth presenting for mental health services responded to a customized sociodemographic questionnaire and presenting concerns checklist, and scales assessing distress, self-rated health and mental health, and suicidal thoughts and behaviors. RESULTS: Combined data from the First Nations sites indicated that youth across the range of 11-29 years accessed services. More girls/women than boys/men accessed services; 17% identified as LBGTQ+. Most (83%) youth indicated having access to at least one reliable adult and getting along well with the people living with them. Twenty-five percent of youth reported difficulty meeting basic expenses. Kessler (K10) distress scores indicated that half likely had a moderate mental health problem and a fourth had severe problems. Fifty-five percent of youth rated their mental health as fair or poor, while 50% reported suicidal thoughts in the last month. Anxiety, stress, depression and sleep issues were the most common presenting problems. Fifty-one percent of youth either accessed services themselves or were referred by family members. AOM was the first mental health service accessed that year for 68% of youth. CONCLUSIONS: This report is the first to present a demographic and clinical portrait of youth presenting at mental health services in multiple Indigenous settings in Canada. It illustrates the acceptability and feasibility of transforming youth mental health services using core principles tailored to meet communities' unique needs, resources, and cultures, and evaluating these using a common protocol. Data obtained can be valuable in evaluating services and guiding future service design. Trial registration name and number at Clinicaltrials.gov: ACCESS Open Minds/ACCESS Esprits ouverts, ISRCTN23349893.

Ecoimmune reallocation in a native lizard in response to the presence of invasive, venomous fire ants in their shared environment.

Exposure to stressors over prolonged periods can have fitness-relevant consequences, including suppression of immune function. We tested for effects of presence of an invasive species threat on a broad panel of immune functions of a coexisting lizard. Eastern fence lizards (Sceloporus undulatus) have been exposed to invasive fire ants (Solenopsis invicta) for over 80 years. Fire ants sting and envenomate lizards, causing physiological stress, but we do not have a comprehensive understanding of the broad immune consequences of lizard exposure to fire ant presence. We conducted a suite of immune measures on fence lizards caught from areas with long histories of fire ant invasion and lizards from areas not yet invaded by fire ants. The effect of fire ant presence on immunity varied depending on the immune component measured: within fire ant invaded areas, some portions of immunity were suppressed (lymphocytic cell-mediated immunity, complement), some were unaffected (phagocytic respiratory burst, natural antibodies), and some were enhanced (anti-fire ant immunoglobulin M, basophils) compared to within uninvaded areas. Rather than fire ants being broadly immunosuppressing, as generally assumed, the immune response appears to be tailored to this specific stressor: the immune measures that were enhanced are important to the lizards' ability to handle envenomation, whereas those that were unaffected or suppressed are less critical to surviving fire ant encounters. Several immune measures were suppressed in reproductive females when actively producing follicles, which may make them more susceptible to immunosuppressive costs of stressors such as interactions with fire ants.

Lack of a relationship between plasma fibroblast growth factor-23 and phosphate utilization in young chicks.

Fibroblast growth factor 23 (FGF-23) is proposed to be the hormone that controls phosphate (P) homeostasis in chickens. This study was initiated to investigate the effect of feeding young chicks diets that were either adequate (0.45%) or marginal (0.25%) in available P content on plasma FGF-23 levels. The dietary level of available P significantly (P ≤ 0.05) affected bone mineralization and bone length, but was without effect (P > 0.05) on growth rate and circulating FGF-23 concentrations. Substantial individual variation in bone mineralization and plasma FGF-23 levels was observed, and the correlation between these two variables was non-significant (P > 0.05). This suggested that there was no alteration in FGF-23 activity in response to suboptimal dietary P intake. The relationship of these observations to studies on the immunosuppression of FGF-23 activity is subsequentlydiscussed.

Malignant Peripheral Nerve Sheath Tumor of the Infraorbital Nerve.

The objective of this study is to report a large, rare, and ulcerative infiltrated skin lesion. Its diagnosis, therapeutic management, and progress are described. The patient is a 78-year-old white man, who presented with a 12-month ulcerative perforated lesion that had affected and infiltrated the skin, with easy bleeding. He had a history of hypertension, although controlled, was a 40-year smoker, had chronic atrial fibrillation, diabetes, and microangiopathy. During the consultation, the patient also presented with ocular obstruction due to an inability to open the eye. He mentioned having reduced vision. The computed tomography scan showed upper maxilla osteolysis without eye involvement. We underwent a radical resection in which upper maxilla and the anterior orbital margin were included. We used a Becker-type flap that allowed us to rebuild the cheek and to complete a modified neck dissection. Progress was favorable; the patient recovered ocular motility and his vision improved to 20/200. The final biopsy result was "malignant peripheral nerve sheath tumor, malignant schwannoma." Malignant schwannoma of the peripheral nerve is extremely rare. The total resection and reconstruction being completed in one surgery represented a challenge due to the difficulty in obtaining tissues in addition to the necessity of an oncological resection.

Bone sialoprotein keratan sulfate proteoglycan (BSP-KSPG) and FGF-23 are important physiological components of medullary bone.

Medullary bone is a specialized bone found in the marrow cavity of laying birds. It provides a significant contribution to the calcium supply for egg shell formation. Medullary bone is distinguished from cortical bone by the presence of large amounts of a keratan sulfate proteoglycan (KSPG). The aims of the present experiment are to confirm the identity of the core protein of KSPG, identify a marker of medullary bone metabolism, and determine whether changes in keratan sulfate (KS) concentration in blood are associated with the egg-laying cycle. Using two different isolation techniques- one specific for bone and another for blood- we have identified bone sialoprotein (BSP) to be the core protein of this KSPG. We also determined that the amount of keratan sulfate (KS) in laying hen blood fluctuates in synchrony with the egg-laying cycle, and thus can serve as a specific marker for medullary bone metabolism. During the course of this investigation, we also found FGF-23 (phosphatonin) to be expressed in medullary bone, in synchrony with the egg-laying cycle. Western blotting was used to demonstrate the presence of this peptide in both laying hen blood and medullary bone extracts. The importance of FGF-23 (phosphatonin) and parathyroid hormone in normalizing the dramatic changes in plasma calcium and phosphorus during the 24h egg-laying cycle is discussed.

Biological clocks in the duodenum and the diurnal regulation of duodenal and plasma serotonin.

Serotonin in blood plasma is primarily synthesized in the duodenum, as brain derived serotonin does not cross the blood-brain barrier. Because serotonin in the brain and retina is synthesized under the control of a circadian clock, we sought to determine if a circadian clock in the duodenum regulates serotonin synthesis and release in blood. We examined gene expression in the duodenum of chickens at different times of the day and found that the duodenum rhythmically expresses molecular circadian clock genes and genes controlling serotonin biosynthesis, specifically tryptophan hydroxylase, in a light dark cycle (LD). Analysis of the duodenum and blood plasma showed that the amount of serotonin in the duodenum varies across the day and that serotonin profiles in blood plasma are also rhythmic in LD, but were not rhythmic in constant darkness. Because serotonin in the gut affects duodenal nutrient absorption and gut motility, the control of serotonin production in the duodenum by LD cycles could provide an additional mechanism by which the external environment controls nutrient uptake and digestive function. The diurnal regulation of plasma serotonin may also serve as an additional biochemical signal in the blood encoding time and could be used by target tissues to indicate the status of nutrient absorption.

Differential regulation of adipokines may influence migratory behavior in the white-throated sparrow (Zonotrichia albicollis).

White-throated sparrows increase fat deposits during pre-migratory periods and rely on these fat stores to fuel migration. Adipose tissue produces hormones and signaling factors in a rhythmic fashion and may be controlled by a clock in adipose tissue or driven by a master clock in the brain. The master clock may convey photoperiodic information from the environment to adipose tissue to facilitate pre-migratory fattening, and adipose tissue may, in turn, release adipokines to indicate the extent of fat energy stores. Here, we present evidence that a change in signal from the adipokines adiponectin and visfatin may act to indicate body condition, thereby influencing an individual's decision to commence migratory flight, or to delay until adequate fat stores are acquired. We quantified plasma adiponectin and visfatin levels across the day in captive birds held under constant photoperiod. The circadian profiles of plasma adiponectin in non-migrating birds were approximately inverse the profiles from migrating birds. Adiponectin levels were positively correlated to body fat, and body fat was inversely related to the appearance of nocturnal migratory restlessness. Visfatin levels were constant across the day and did not correlate with fat deposits; however, a reduction in plasma visfatin concentration occurred during the migratory period. The data suggest that a significant change in the biological control of adipokine expression exists between the two migratory conditions and we propose a role for adiponectin, visfatin and adipose clocks in the regulation of migratory behaviors.

The effects of melatonin on the physical properties of bones and egg shells in the laying hen.

Laying hens often experience unbalanced calcium utilization which can cause deficiencies in bone and egg mineralization. Because melatonin has been shown to affect bone mineralization in other animals, we examined whether treating hens with melatonin would affect eggshell thickness and improve skeletal performance, thereby reducing skeletal and egg shell defects. Birds were given a diet containing either low (30 µg/kg), medium (300 µg/kg), or high (3 mg/kg) concentrations of melatonin, or control feed through approximately one laying cycle. We examined the weight, length, and strength of egg, femur, tibia, and keel. Hens treated with a high concentration of melatonin showed significant strengthening in their femur and tibia, as measured by maximum force sustained and breaking force, compared to controls. Egg weights from hens treated with melatonin were significantly greater than those from hens that were not treated with melatonin. Conversely, egg shell mass of hens treated with melatonin was significantly lower than those of hens not treated with melatonin. Our data suggest that melatonin may affect the allocation of calcium to bone at the expense of egg shell mineralization.

Assessing genetic polymorphisms using DNA extracted from cells present in saliva samples.

BACKGROUND: Technical advances following the Human Genome Project revealed that high-quality and -quantity DNA may be obtained from whole saliva samples. However, usability of previously collected samples and the effects of environmental conditions on the samples during collection have not been assessed in detail. In five studies we document the effects of sample volume, handling and storage conditions, type of collection device, and oral sampling location, on quantity, quality, and genetic assessment of DNA extracted from cells present in saliva. METHODS: Saliva samples were collected from ten adults in each study. Saliva volumes from .10-1.0 ml, different saliva collection devices, sampling locations in the mouth, room temperature storage, and multiple freeze-thaw cycles were tested. One representative single nucleotide polymorphism (SNP) in the catechol-0-methyltransferase gene (COMT rs4680) and one representative variable number of tandem repeats (VNTR) in the serotonin transporter gene (5-HTTLPR: serotonin transporter linked polymorphic region) were selected for genetic analyses. RESULTS: The smallest tested whole saliva volume of .10 ml yielded, on average, 1.43 ± .77 µg DNA and gave accurate genotype calls in both genetic analyses. The usage of collection devices reduced the amount of DNA extracted from the saliva filtrates compared to the whole saliva sample, as 54-92% of the DNA was retained on the device. An "adhered cell" extraction enabled recovery of this DNA and provided good quality and quantity DNA. The DNA from both the saliva filtrates and the adhered cell recovery provided accurate genotype calls. The effects of storage at room temperature (up to 5 days), repeated freeze-thaw cycles (up to 6 cycles), and oral sampling location on DNA extraction and on genetic analysis from saliva were negligible. CONCLUSIONS: Whole saliva samples with volumes of at least .10 ml were sufficient to extract good quality and quantity DNA. Using 10 ng of DNA per genotyping reaction, the obtained samples can be used for more than one hundred candidate gene assays. When saliva is collected with an absorbent device, most of the nucleic acid content remains in the device, therefore it is advisable to collect the device separately for later genetic analyses.

Tumor ovárico virilizante mixto de células de Sertoli-Leydig/granulosa (ginandroblastoma) en adolescente de 15 años / Virilizing mixed Sertoli-Leydig/ granulosa cell (gynandroblastoma) ovarian tumor in a 15-year-old girl

Los tumores de Sertoli-Leydig constituyen menos del 5% de los tumores ováricos. Presentamos el caso de una adolescente de 15 años de edad, con un cuadro de virilización, amenorrea y dolor abdominal, que fue diagnosticada de tumoración anexial izquierda. En el estudio analítico destacaba una elevación aislada de testosterona. Debido a la integridad de la cápsula, ser unilateral y los deseos de fertilidad de la paciente, se practicó una anexectomía izquierda. El estudio histológico reveló un tumor mixto de células de Sertoli-Leydig/células de la granulosa juvenil con componente heterólogo cartilaginoso, que podría ser considerado como ginandroblastoma. El cuadro de virilización mejoró progresivamente

Sertoli-Leydig cell tumors constitute less than 5% of ovarian tumors. We report the case of a 15-year-old girl with virilization, amenorrhea, and abdominal pain, who was diagnosed with a left annexal tumor. Laboratory investigations revealed isolated testosterone elevation. Because the tumor was unilateral, the capsule was intact, and the patient wished to preserve her fertility, left salpingo-oophorectomy was performed. Histopathological examination revealed a mixed Sertoli-Leydig/juvenile granulosa cell tumor with a cartilaginous heterologous component, which could be considered a gynandroblastoma. Symptoms of virilization progressively improved

The Methodist Hospital CCU: a Beacon unit of excellence.

This article features the Coronary Care Unit of The Methodist Hospital of Houston, Texas. This unit was one of the first Beacon Critical Care Units recognized by the American Association of Critical Care Nurses. This article focuses on how to achieve this award. The Coronary Care Unit nursing infrastructure is described, and specific unit examples are included.

Oxytocin is not a valid biomarker when measured in saliva by immunoassay.

The integration of oxytocin (OT) into behavioral science seems to hold considerable promise for advancing our understanding of human health and development but methodological issues restrict the measurement of OT in large studies, in everyday social settings, or when repeated sampling is required. Measuring OT in saliva could overcome many of these limitations. In this paper, we rigorously evaluate the feasibility of doing so. A series of experiments leads to the conclusion that saliva does not contain oxytocin in measurable amounts, and that OT is not a valid salivary biomarker when measured by currently available immunological methods. Levels of immuno-reactive OT in saliva are primarily due to non-specific interference with antibody-antigen binding. We can state with a high degree of certainty that measurement of OT in saliva does not yield meaningful indices of individual differences or intra-individual change.

NELF and DSIF cause promoter proximal pausing on the hsp70 promoter in Drosophila.

NELF and DSIF collaborate to inhibit elongation by RNA polymerase IIa in extracts from human cells. A multifaceted approach was taken to investigate the potential role of these factors in promoter proximal pausing on the hsp70 gene in Drosophila. Immunodepletion of DSIF from a Drosophila nuclear extract reduced the level of polymerase that paused in the promoter proximal region of hsp70. Depletion of one NELF subunit in salivary glands using RNA interference also reduced the level of paused polymerase. In vivo protein-DNA cross-linking showed that NELF and DSIF associate with the promoter region before heat shock. Immunofluorescence analysis of polytene chromosomes corroborated the cross-linking result and showed that NELF, DSIF, and RNA polymerase IIa colocalize at the hsp70 genes, small heat shock genes, and many other chromosomal locations. Finally, following heat shock induction, DSIF and polymerase but not NELF were strongly recruited to chromosomal puffs harboring the hsp70 genes. We propose that NELF and DSIF cause polymerase to pause in the promoter proximal region of hsp70. The transcriptional activator, HSF, might cause NELF to dissociate from the elongation complex. DSIF continues to associate with the elongation complex and could serve a positive role in elongation.