Understanding the association between pressure ulcers and sitting in adults what does it mean for me and my carers? Seating guidelines for people, carers and health & social care professionals.

The aim of the publication was to develop a practical guide for people, carers and health and social care professionals on how the research and evidence base on pressure ulcer prevention and management can be applied to those who remain seated for extended periods of time. This publication was developed at the request of the Tissue Viability Society in order to revise the original seating guidelines from 2008 as evidence and subsequent care has moved forward in relation to this area. Since 2008, the costs for the prevention and management of pressure ulcers have increased significantly and there is limited published advice from health and social care organisations on seating and preventing pressure ulcers. These guidelines have been written for: Who live or work in primary, secondary, and tertiary settings.

Meta-analysis: hoarding symptoms associated with poor treatment outcome in obsessive-compulsive disorder.

DSM-5 recognizes hoarding disorder as distinct from obsessive-compulsive disorder (OCD), codifying a new consensus. Hoarding disorder was previously classified as a symptom of OCD and patients received treatments designed for OCD. We conducted a meta-analysis to determine whether OCD patients with hoarding symptoms responded differently to traditional OCD treatments compared with OCD patients without hoarding symptoms. An electronic search was conducted for eligible studies in PubMed. A trial was eligible for inclusion if it (1) was a randomized controlled trial, cohort or case-control study; (2) compared treatment response between OCD patients with and those without hoarding symptoms, or examined response to treatment between OCD symptom dimensions (which typically include hoarding) and (3) examined treatment response to pharmacotherapy, behavioral therapy or their combination. Our primary outcome was differential treatment response between OCD patients with and those without hoarding symptoms, expressed as an odds ratio (OR). Twenty-one studies involving 3039 total participants including 304 with hoarding symptoms were included. Patients with OCD and hoarding symptoms were significantly less likely to respond to traditional OCD treatments than OCD patients without hoarding symptoms (OR=0.50 (95% confidence interval 0.42-0.60), z=-7.5, P<0.0001). This finding was consistent across treatment modalities. OCD patients with hoarding symptoms represent a population in need of further treatment research. OCD patients with hoarding symptoms may benefit more from interventions specifically targeting their hoarding symptoms.

Viral co-infection, autoimmunity, and CSF HIV antibody profiles in HIV central nervous system escape.

Antiretroviral therapy (ART) suppresses plasma and cerebrospinal fluid (CSF) HIV replication. Neurosymptomatic (NS) CSF escape is a rare exception in which CNS HIV replication occurs in the setting of neurologic impairment. The origins of NS escape are not fully understood. We performed a case-control study of asymptomatic (AS) escape and NS escape subjects with HIV-negative subjects as controls in which we investigated differential immunoreactivity to self-antigens in the CSF of NS escape by employing neuroanatomic CSF immunostaining and massively multiplexed self-antigen serology (PhIP-Seq). Additionally, we utilized pan-viral serology (VirScan) to deeply profile the CSF anti-viral antibody response and metagenomic next-generation sequencing (mNGS) for pathogen detection. We detected Epstein-Barr virus (EBV) DNA more frequently in the CSF of NS escape subjects than in AS escape subjects. Based on immunostaining and PhIP-Seq, there was evidence for increased immunoreactivity against self-antigens in NS escape CSF. Finally, VirScan revealed several immunodominant epitopes that map to the HIV envelope and gag proteins in the CSF of AS and NS escape subjects. Whether these additional inflammatory markers are byproducts of an HIV-driven process or whether they independently contribute to the neuropathogenesis of NS escape will require further study.

Peroxisome proliferator-activated receptor alpha (PPARalpha) protects against oleate-induced INS-1E beta cell dysfunction by preserving carbohydrate metabolism.

AIMS/HYPOTHESIS: Pancreatic beta cells chronically exposed to fatty acids may lose specific functions and even undergo apoptosis. Generally, lipotoxicity is triggered by saturated fatty acids, whereas unsaturated fatty acids induce lipodysfunction, the latter being characterised by elevated basal insulin release and impaired glucose responses. The peroxisome proliferator-activated receptor alpha (PPARalpha) has been proposed to play a protective role in this process, although the cellular mechanisms involved are unclear. METHODS: We modulated PPARalpha production in INS-1E beta cells and investigated key metabolic pathways and genes responsible for metabolism-secretion coupling during a culture period of 3 days in the presence of 0.4 mmol/l oleate. RESULTS: In INS-1E cells, the secretory dysfunction primarily induced by oleate was aggravated by silencing of PPARalpha. Conversely, PPARalpha upregulation preserved glucose-stimulated insulin secretion, essentially by increasing the response at a stimulatory concentration of glucose (15 mmol/l), a protection we also observed in human islets. The protective effect was associated with restored glucose oxidation rate and upregulation of the anaplerotic enzyme pyruvate carboxylase. PPARalpha overproduction increased both beta-oxidation and fatty acid storage in the form of neutral triacylglycerol, revealing overall induction of lipid metabolism. These observations were substantiated by expression levels of associated genes. CONCLUSIONS/INTERPRETATION: PPARalpha protected INS-1E beta cells from oleate-induced dysfunction, promoting both preservation of glucose metabolic pathways and fatty acid turnover.

Reduced endoplasmic reticulum (ER)-to-Golgi protein trafficking contributes to ER stress in lipotoxic mouse beta cells by promoting protein overload.

AIMS/HYPOTHESIS: Saturated fatty acids augment endoplasmic reticulum (ER) stress in pancreatic beta cells and this is implicated in the loss of beta cell mass that accompanies type 2 diabetes. However, the mechanisms underlying the induction of ER stress are unclear. Our aim was to establish whether saturated fatty acids cause defects in ER-to-Golgi protein trafficking, which may thereby contribute to ER stress via protein overload. METHODS: Cells of the mouse insulinoma cell line MIN6 were transfected with temperature-sensitive vesicular stomatitis virus G protein (VSVG) tagged with green fluorescent protein to quantify the rate of ER-to-Golgi protein trafficking. I14 antibody, which detects only correctly folded VSVG, was employed to probe the folding environment of the ER. ER stress markers were monitored by western blotting. RESULTS: Pretreatment with palmitate, but not oleate, significantly reduced the rate of ER-to-Golgi protein trafficking assessed using VSVG. This was not secondary to ER stress, since thapsigargin, which compromises chaperone function by depletion of ER calcium, markedly inhibited VSVG folding and promoted strong ER stress but only slightly reduced protein trafficking. Blockade of ER-to-Golgi protein trafficking with brefeldin A (BFA) was sufficient to trigger ER stress, but neither BFA nor palmitate compromised VSVG folding. CONCLUSIONS/INTERPRETATION: Reductions in ER-to-Golgi protein trafficking potentially contribute to ER stress during lipoapoptosis. In this case ER stress would be triggered by protein overload, rather than a disruption of the protein-folding capacity of the ER.

Menstrual Suppression in Pediatric and Adolescent Patients with Disabilities Ranging from Developmental to Acquired Conditions: A Population Study in an Australian Quaternary Pediatric and Adolescent Gynecology Service from January 2005 to December 2015.

STUDY OBJECTIVE: The aim of this study was to review the efficacy of different medical modalities for menstrual suppression in the cohort of patients with disabilities who presented to the Queensland Paediatric and Adolescent Gynaecology (PAG) Service between January 2005 and December 2015. Menstrual suppression in adolescents with disabilities is an important aspect of care to support the patient and their carers in managing the complexities of menstrual hygiene, pain, and other discomfort associated with menses. It is important for general practitioners, pediatricians, and gynecologists to establish the right modality of suppression for each individual adolescent. DESIGN, SETTINGS, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: The study was a retrospective case notes review of 68 adolescents who presented to the Queensland PAG Service, Brisbane, Australia with a request for menstrual suppression. The medical interventions included treatment with either combined oral hormonal contraceptive, oral medroxyprogesterone, depot medroxyprogesterone, or the levonorgestrel intrauterine system (Mirena, Bayer). The primary outcome measure was success of menstrual suppression from commencement of medical intervention to achievement of complete amenorrhea or very light bleeding described as spotting, for each medical modality. Secondary outcomes were length of time from first treatment to first observed menstrual suppression, and the number of outpatient appointments taken to achieve menstrual suppression. RESULTS: Of the 68 adolescents, 59/68 (86.8%) successfully achieved menstrual suppression, with 9/68 (13.2%) having ongoing treatment or loss to follow-up at the time of conclusion of the study; 39/68 (57.4%) were menstrually suppressed with their chosen medical modality after their initial appointment. CONCLUSION: Medical modalities are highly effective in achieving menstrual suppression and no young women at this institution required a hysterectomy. Depot medroxyprogesterone was the most successful modality used to achieve menstrual suppression followed by the levonorgestrel intrauterine system. The combined oral hormonal contraceptive was the least successful medical treatment in achieving menstrual suppression.

Internalizing and externalizing factors on the pathway from adverse experiences in childhood to non-medical prescription opioid use in adulthood.

BACKGROUND: Research demonstrates strong associations between adverse childhood experiences (ACEs) and non-medical prescription opioid use (NMPO), but pathways are not understood, hindering prevention and treatment responses. METHODS: We assessed hypothesized mediators of the association between ACEs and NMPO in a nationally-representative U.S. SAMPLE: National Longitudinal Study of Adolescent to Adult Health data (N = 12,288) yielded an ordinal exposure comprising nine ACEs (neglect; emotional, physical, sexual abuse; parental incarceration and binge drinking; witnessed, threatened with, experienced violence) and a binary lifetime NMPO outcome. Nine potential mediators measured in adolescence and/or adulthood included depression, anxiety, suicidality, delinquency, impulsivity, and risk-taking. We estimated adjusted odds ratios (AOR) and 95% confidence intervals (CI) for sex-stratified associations of: ACEs and mediators; mediators and NMPO; and ACEs and NMPO adjusting for mediators individually and simultaneously. RESULTS: All associations of ACEs and mediators were statistically significant and similar by sex. All mediators had statistically significant associations with NMPO (except one depression measurement for each sex). Delinquency was strongly associated with ACEs and NMPO and was the strongest individual mediator. Every ACE increase was associated with increased NMPO odds of 32% for males and 27% for females. Adjusting for all mediators, odds of NMPO were attenuated partially for males [AOR = 1.18 (95% CI:1.07, 1.31)] and somewhat more for females [AOR = 1.11 (95% CI:1.00, 1.25)]. CONCLUSIONS: Internalizing and externalizing factors partially explained the pathway from ACEs to NMPO. Substance abuse may be more difficult to treat with co-occurring psychopathologies and maladaptive behaviors, highlighting the need to address trauma early in life.

Osmotic demyelination syndrome following rapid correction of hyponatraemia.

We report a case of a young male with adrenal hypoplasia who presented following water intoxication with severe hyponatraemia and seizures. He required a period of intensive care and over the initial 24 h his serum sodium corrected at average of 0.9 mmol x l(-1) h(-1). He subsequently developed osmotic demyelination syndrome. Following supportive treatment he made a full recovery. Severe hyponatraemia carries a risk of cerebral oedema with a significant mortality, yet correcting it too rapidly can result in osmotic demyelination syndrome, again with potentially disastrous consequences. It may be difficult to determine the duration and aetiology of the hyponatraemia and this is necessary to guide treatment. There is no consensus about the optimal rate of correction of hyponatraemia but formulae such as the Adrogue and Madias formula can be used to guide treatment with normal or hypertonic saline. Continuous veno-venous haemofiltration has been used effectively in this setting.

Free radical modulation of insulin release in INS-1 cells exposed to alloxan.

Generation of free radicals is thought to mediate the cytotoxic action of alloxan on the pancreatic beta-cell. In this investigation, the early effects of alloxan on cell function were studied. When INS-1D insulinoma cells were exposed to alloxan (1 mM) for 45 min followed by a 3-hr recovery period, the drug increased basal insulin release while abolishing the effect of glucose in static incubations. This was associated with impaired stimulation of cellular metabolism by glucose and reduced viability, both monitored colorimetrically with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). These alterations were largely counteracted by the antioxidant butylated hydroxyanisol (BHA). Similar changes occurred when glucose was added directly after 5 min of alloxan treatment, whereas KCl-induced secretion was only partially inhibited. In perifusion, alloxan caused transient insulin secretion to 50% of the rates obtained with glucose 30 min later. Under these conditions, epinephrine abolished the stimulation due to both agents. Membrane potential and cytosolic calcium concentrations ([Ca2+]i) were recorded to clarify the action of alloxan. Alloxan-induced insulin release correlated with depolarization of INS-1D cells and a rise in [Ca2+]i. Alloxan did not augment [Ca2+]i in the presence of BHA or the absence of extracellular calcium. Nickel chloride blocked the effect of alloxan on [Ca2+]i, whereas verapamil was ineffective. This suggests that alloxan promotes Ca2+ influx through channels distinct from L-type channels, perhaps through non-selective cation channels. Thus, alloxan causes changes in INS-1D cells prevented by antioxidant treatment, suggesting that free radicals may modulate the ionic permeability leading to functional activation.

Amyloid in prostatic corpora amylacea.

AIM: To determine the presence and nature of amyloid in prostatic corpora amylacea using immunohistological studies. METHODS: Prostatic tissue from 18 transurethral and two open resection specimens was studied. Paraffin wax embedded tissue sections were stained with haematoxylin and eosin and the alkaline Congo red method with and without previous treatment with potassium permanganate. Sections were also stained with antibodies to amyloid A, beta 2 microglobulin, lambda and kappa light chains, prealbumin IgA, G, M, S100 protein, prostatic specific antigen, amyloid P component and CAM 5.2 (control and blocking studies were performed). RESULTS: The prostatic corpora amylacea universally showed the presence of amyloid. In all instances this contained beta 2 microglobulin. CONCLUSION: Prostatic corpora amylacea represents a localised amyloidosis of beta 2 microglobulin origin that is unrelated to chronic renal failure and haemodialysis.

Immunohistological characterisation of amyloid deposits in renal biopsy specimens.

The amyloid deposits in 21 renal biopsy specimens were subjected to a detailed immunohistochemical analysis using a panel of antibodies against recognised constituents of tissue amyloid. This was a retrospective study of material originally submitted during the investigation of various renal abnormalities and studied by a routine protocol including histochemistry, electron microscopy, and immunofluorescence. The presence of an amyloid was confirmed in all 21 cases. Seventeen cases contained P component and either amyloid A (AA) (11 cases) or an immunoglobulin light chain associated amyloid (six cases). Four cases contained amyloid material with unusual immunohistochemical findings; one case had AA and P-component (PC) in the interstitium, one case had lambda light chain and beta-2 microglobulin, one case had kappa light chain and Clq, and one case had lambda light chains only. It was possible, therefore, to identify precisely the amyloid constituents and thereby "type" the amyloid by immunohistochemical means. The availability of the antibodies used and their application using these techniques could simplify the confirmation of clinically suspected amyloidosis.

Systemic amyloidosis of beta 2 microglobulin type.

A patient receiving haemodialysis for 15 years developed systemic amyloidosis of beta 2 microglobulin type. Noticeable deposits of amyloid were present in the myocardium, intervertebral discs, joint cartilages and tendons. Less conspicuous amounts were present in blood vessel walls in the lungs, liver, adrenal glands and brain, and within the stroma of the prostate, testis and kidney, often with foci of calcification.

Improved insulin secretion of cryopreserved human islets by antioxidant treatment.

The viability of islets of Langerhans prior to grafting is believed to influence the clinical outcome of islet transplantation. To determine whether oxidative stress occurs during the isolation-purification procedure as well as during tissue culture and cryopreservation, we have measured the glutathione redox state (GSH/GSSG) of islets. Human islets were purified by standard techniques from organ donors, cultured, and cryopreserved. Glucose-induced insulin release was monitored in parallel during static incubations to assess the function of the islets. Cultured human islets responded by a 2.2-fold increase in insulin release to a glucose challenge. After cryopreservation the hormonal response was lower. Immediately after islet isolation the GSH/GSSG ratio was 25.2 +/- 5.2, and it increased slightly to 32.0 +/- 6.1 after 1-3 days in tissue culture. The GSH/GSSG decreased significantly after cryopreservation to 12.2 +/- 3.4, suggesting that the freezing and thawing procedures imposed oxidative stress on the islets. To explore this hypothesis further, cryopreserved islets were treated with the antioxidant butylated hydroxyanisole (BHA). Islets exposed to BHA showed an improved glucose-induced insulin release and had an increased insulin content. BHA also protected the islets when they were exposed to alloxan, a free radical generating agent. However, after cryopreservation, BHA treatment did not modify the glutathione redox state. Although the BHA effect could not be explained merely by a change in the glutathione redox state, it is not precluded that redox changes of other cell components ameliorate the glucose sensitivity of the beta cells. Further studies will be needed to determine possible ways of improving islet cryopreservation with antioxidant treatments and particularly, to validate the present observations by in vivo experiments in the context of clinical islet transplantation.

The effect of ligation or separation between the intrauterine device horn and adjacent ovary on implantation in the hamster.

The purpose of this study was to determine whether the luteolytic action of an intrauterine device (IUD) is suppressed following interruption of the continuity between the IUD uterine horn and the adjacent ovary. After several estrous cycles, a silk IUD was placed in the cervical end of one uterine horn of adult hamsters. The animals were then mated, and on day 6 of gestation the ovary and oviduct contralateral to the IUD were removed and a ligature was placed between the IUD horn and the adjacent ovary. The hamsters were killed on day 9 or day 13 of gestation. Fetal development in the contralateral horn was suppressed on day 13 but not on day 9. In the second study the animals were treated as in the first study except that the communication between the IUD horn and the adjacent ovary was severed completely. The hamsters were killed on day 9 or day 13. On both days 9 and 13 normal fetal development was observed in the control horn; no implantation sites were present in the IUD side. In the control (non-IUD) animals of each study, normal fetuses were present in both uterine horns. The study demonstrates that luteolysis does not occur if there is complete disruption of the communication between the IUD horn and ovary. The study also demonstrates that, since implantation did not occur in the IUD horn with a normally functioning ipsilateral ovary, the luteolytic action of the device is not the prime factor in suppressing implantation in the hamster.

Effects of synthetic speech output and orthographic feedback on spelling in a student with autism: a preliminary study.

The effects of speech output and orthographic feedback on spelling performance were evaluated in this preliminary study. A nonspeaking student with autism was taught to spell words under three feedback conditions using a voice output communication aid. In the auditoryvisual condition, the participant received speech output and orthographic feedback. In the visual condition, the participant received only the orthographic feedback. In the auditory condition, the student received only speech output. An adapted alternating treatments design was used to evaluate the effects of the three feedback conditions. Although the participant reached criterion and maintained performance in each of the conditions, the provision of speech output alone and in combination with orthographic feedback resulted in more efficient spelling than the provision of orthographic feedback alone. Although replications with other subjects are necessary, findings suggest that speech output contributes to efficient spelling.

Umbilical vessels of spontaneously hypertensive rats.

Umbilical vessels of spontaneously hypertensive rats, control strain Wistar-Kyoto rats and rats treated with alpha-methyldopa were compared using the scanning electron microscope and light microscope. Observations with the scanning electron microscope revealed that the venous endothelial cells were relatively flat, giving the luminal surface of the vein a smooth appearance. The nuclear region of the fusiform arterial endothelial cells was responsible for the bumpy appearance of the luminal surface of the artery. Microvilli were a consistent feature of the endothelium in both umbilical vessels. There was no consistent pattern of distribution or density of microvilli within either vessel, but microvilli were more abundant on the luminal surface of the artery than in the vein. The luminal surface of some endothelial cells of the artery had long straight processes which crossed several cells before terminating. Light microscopic observations revealed that the endothelial cells and cells of the tunica intima and media contained an abundance of glycogen. The same layers stained sparsely for acid glycosaminoglycans. Maternal hypertension and treatment of spontaneously hypertensive rats with the antihypertensive drug, alpha-methyldopa, did not result in significant morphological alterations of either the endothelium or tunica media of the umbilical blood vessels.

Defining the myofibroblast: normal tissues, with special reference to the stromal cells of Wharton's jelly in human umbilical cord.

Cells differing widely in tissue distribution, immunophenotype and ultrastructure have been described as myofibroblasts. The definition of the myofibroblast was analysed as applied to normal tissues, with original observations on Wharton's jelly stromal cells as an example. Stromal cells in Wharton's jelly were studied by conventional histology, immunohistochemistry, and electron microscopy. The normal architecture of the cord was confirmed by light microscopy. Stromal cells and the smooth-muscle cells of the umbilical vessels were positive for vimentin, desmin and alpha-smooth muscle actin, while only the stromal cells were positive for prolyl 4-hydroxylase. Electron microscopy revealed variable but sometimes only moderate amounts of rough endoplasmic reticulum, bundles of smooth-muscle type filaments with focal densities, a large Golgi apparatus with collagen secretion granules, lipid and glycogen. There was no convincing evidence for either lamina or fibronexus junctions. The nature of the stromal cell was discussed in the light of these findings. It was concluded that a myofibroblastic designation was inappropriate and that these cells had phenotypic similarities to vascular smooth muscle cells. The possibility is proposed that most examples of spindle cells cited in the literature as being myofibroblasts and seen in normal tissues not subjected to trauma or showing pathology may be pericytic or smooth-muscle in nature.

[Amyloid in articular cartilage--a new type of amyloid?]. / Amyloid v kloubních chrupavkách--nový typ amyloidu?

Hip and knee joints from 48 randomly selected autopsies have been investigated for amyloid deposits by means of conventional histology and immunohistology. 45 of 48 hip joints (93.75%) and 28 of 32 knee joints (87.5%) contained amyloid deposits. Amyloid has been found in a thin layer along the surface as well as infissures of the cartilage and around chondrocytes with increasing intensity towards the articular surface. Amyloid characteristically showed apple green birefringence in polarized light after staining with alkaline Congo red and pretreatment with potassium permanganate did not change intensity of reaction in most cases. None of the usual constituents of amyloid could be demonstrated by immunohistological methods. P-component (when present) kept the distribution of the amyloid material. It is possible that articular cartilage amyloid represents a new class of amyloid but its identity is to be proved by chemical analysis.

[Beta 2-microglobulin amyloidosis]. / Amyloidóza beta 2-mikroglobulinového typu.

A 35-year-old man who had been treated by hemodialysis for 15 years suffered from systemic amyloidosis. It was identified as a beta 2-microglobulin type according to immunohistochemistry. Extensive amyloid deposits were found in myocardium, cartilages of intervertebral discs and in carpal tunnel ligament. Less conspicuous deposits comprised blood vessels of lungs, liver, suprarenal glands, brain, and stroma of prostate gland, testicles, kidney, often combined with calcified foci.