Assessing physical activity in people with mental illness: 23-country reliability and validity of the simple physical activity questionnaire (SIMPAQ).

BACKGROUND: Physical inactivity is a key contributor to the global burden of disease and disproportionately impacts the wellbeing of people experiencing mental illness. Increases in physical activity are associated with improvements in symptoms of mental illness and reduction in cardiometabolic risk. Reliable and valid clinical tools that assess physical activity would improve evaluation of intervention studies that aim to increase physical activity and reduce sedentary behaviour in people living with mental illness. METHODS: The five-item Simple Physical Activity Questionnaire (SIMPAQ) was developed by a multidisciplinary, international working group as a clinical tool to assess physical activity and sedentary behaviour in people living with mental illness. Patients with a DSM or ICD mental illness diagnoses were recruited and completed the SIMPAQ on two occasions, one week apart. Participants wore an Actigraph accelerometer and completed brief cognitive and clinical assessments. RESULTS: Evidence of SIMPAQ validity was assessed against accelerometer-derived measures of physical activity. Data were obtained from 1010 participants. The SIMPAQ had good test-retest reliability. Correlations for moderate-vigorous physical activity was comparable to studies conducted in general population samples. Evidence of validity for the sedentary behaviour item was poor. An alternative method to calculate sedentary behaviour had stronger evidence of validity. This alternative method is recommended for use in future studies employing the SIMPAQ. CONCLUSIONS: The SIMPAQ is a brief measure of physical activity and sedentary behaviour that can be reliably and validly administered by health professionals.

Astaxanthin modulates osteopontin and transforming growth factor ß1 expression levels in a rat model of nephrolithiasis: a comparison with citrate administration.

OBJECTIVES: To evaluate the effect of astaxanthin on renal angiotensin-I converting enzyme (ACE) levels, osteopontin (OPN) and transforming growth factor ß1 (TGF-ß1) expressions and the extent of crystal deposition in experimentally induced calcium oxalate kidney stone disease in a male Wistar rat model. To compare the efficacy of astaxanthin treatment with a currently used treatment strategy (citrate administration) for kidney stones. MATERIALS AND METHODS: The expression of OPN was assessed by immunohistochemistry. One step reverse transcriptase polymerase chain reaction followed by densitometry was used to assess renal OPN and TGF-ß1 levels. Renal ACE levels were quantified by an enzyme-linked immunosorbent assay method. Crystal deposition in kidney was analysed by scanning electron microscopic (SEM)-energy-dispersive X-ray (EDX). RESULTS: The renal ACE levels and the expression of OPN and TGF-ß1 were upregulated in the nephrolithiasis-induced rats. Astaxanthin treatment reduced renal ACE levels and the expression OPN and TGF-ß1. SEM-EDX analysis showed that crystal deposition was reduced in the astaxanthin-treated nephrolithiatic group. Astaxanthin treatment was more effective than citrate administration in the regulation of renal ACE levels, OPN and TGF-ß1 expressions. CONCLUSIONS: Astaxanthin administration reduced renal calcium oxalate crystal deposition possibly by modulating the renal renin-angiotensin system (RAS), which reduced the expression of OPN and TGF-ß1 levels. Astaxanthin administration was more effective than citrate treatment in reducing crystal deposition and down-regulating the expression of OPN and TGF-ß1.

Advantages of hyaluronic acid as a component of fibrin sheet for care of acute wound.

Skin injury is followed by accumulation of a fibrin based provisional matrix which normally drives the process of wound repair. Exogenous fibrin with extra cellular matrix (ECM) components can also favor the wound healing process. In a preliminary study we found that lyophilized fibrin sheet (FS) arrest bleeding from rabbit skin wound but it remained dry during the repair period and did not accelerate the healing process better than untreated control. In the current study, hyaluronic acid (HA) was incorporated into FS and the resultant HA-FS promoted water retention and improved wound healing process. Gross-morphology, histopathology and histomorphometry were employed to compare qualitative and quantitative difference of wound healing in treated group against controls. In experimental sites (HA-FS), re-epithelialization was completed by 14 days with neo-vascularization and deposition of wavy bundles of collagen in the treated sites. Rate of healing process was different in treated and untreated wounds and most striking difference was the appearance of appendages, sebaceous gland and hair follicle at some locations in HA-FS treated sites. Therefore, HA with fibrin can create an effective wound care matrix which promotes water retention and wound healing potential.

Decompressive hemicraniectomy in large putaminal hematomas: an Indian experience.

OBJECTIVE: The treatment of large putaminal hematomas is predominantly medical and the role of surgery is debated. Decompressive hemicraniectomy in large hemispheric infarctions has been reported to lower mortality and improve outcomes. Decompressive hemicraniectomy may also have a role in putaminal hematomas. METHODS: In all, 23 patients with putaminal hematoma who underwent decompressive craniectomy in the last 4 years were analyzed. Parameters investigated included clinical presentations, radiologic profile, time interval from ictus to surgery, and Glasgow outcome score at 1 month. RESULTS: There were 13 men and 10 women with ages ranging from 31 to 68 years. All of them presented with neurologic deficits. Seven patients had a Glasgow Coma Scale (GCS) score of 3 to 8, 12 had a GCS score of 9 to 12, and GCS score was above 13 in 4. Seventeen patients had known hypertension. Computed tomography scan was done in all. The hematoma was less than 3 cm in 5 cases, 3 to 5 cm in 11, and larger than 5 cm in 7; and was 30 mL or less in 3, 30 to 60 mL in 13, and more than 60 mL in 7. All patients underwent hemicraniectomy on the side of the lesion and dura was left open. At 3 months, 13 patients had a good outcome and 10 had a poor outcome (including 3 deaths). CONCLUSIONS: Decompressive hemicraniectomy can be a useful alternative surgical procedure in moderate to large putaminal hematomas.

BRCA1 regulation on ß-hCG: a mechanism for tumorigenicity in BRCA1 defective breast cancer.

Human chorionic gonadotropin ß (ß-hCG) has been implicated in breast tumorigenesis. However, the role of this hormone is highly controversial as certain studies suggest it has anti-tumor properties while others have found it to be pro-tumorigenic. To unveil the truth, we have analyzed the expression of ß-hCG in breast cancer. We identified for the first time that ß-hCG expression is linked to BRCA1 status and its overexpression is seen in BRCA1 mutated breast cancer cells, BRCA1 conditional knockout mouse breast cancer tissues and BRCA1 floxed basal cell carcinoma (BCC) tissues. An analysis of three large, transcriptomic data sets from TCGA (The Cancer Genome Atlas) expression profile confirmed the inverse correlation between BRCA1 and ß-hCG in human breast cancer. Using ChIP and luciferase assays, we also demonstrated that the cancer cells with wild-type but not mutant BRCA1 directly repress the expression of ß-hCG by binding to its promoter. Further, ß-hCG promotes migration and invasion predominantly in BRCA1 mutant breast cancer cells. Interestingly, stable overexpression of ß-hCG in BRCA1 mutant but not wild-type breast cancer cells results in the formation of spheres even on monolayer cultures. The cells of these spheres show high expression of both EMT and stem cell markers. Since ß-hCG belongs to a cysteine knot family of proteins like TGFß and TGFß signaling is deregulated in BRCA1 defective tumors, we checked whether ß-hCG can mediate signaling through TGFßRII in BRCA1 mutated cells. We found for the first time that ß-hCG can bind and phosphorylate TGFßRII, irrespective of LHCGR status and induce proliferation in BRCA1 defective cells. Our results confirmed that there exists a transcriptional regulation of BRCA1 on ß-hCG and BRCA1 mutation promotes ß-hCG mediated tumorigenesis through TGFßRII signaling. Thus inhibiting ß-hCG-TGFßRII could prove an effective treatment strategy for BRCA1 mutated tumors.

Biological evaluation of pliable hydroxyapatite-ethylene vinyl acetate co-polymer composites intended for cranioplasty.

Hydroxyapatite (HAP) is undoubtedly a material suitable for repairing the defective bone tissue. However, the brittleness and non-malleability of HAP limit its clinical application as a cranioplastic analogue. To improve these properties, pliable, osteoconductive composites composed of HAP and ethylene vinyl acetate co-polymer (EVA) have been developed. This study reports the biocompatibility evaluation of the newly developed composite material. Composites of two compositions, containing 40 and 50 volume percentage of HAP, were evaluated. In vitro cell culture cytotoxity studies were carried out using L929 cell line. Intracutaneous irritation studies, and intramuscular implantation studies were carried out on rabbits. Cell culture studies showed that the composite was non-cytotoxic to mouse fibroblast cell line. Intracutaneous irritation studies did not show any gross signs of tissue reaction. Histological analysis after six months of implantation in the paravertebral muscles of rabbit showed that all the implants under study were covered with a thin soft tissue capsule. On the basis of these observations, we conclude that the composite materials are biocompatible and hence are a candidate material for implantation in the cranium.

Transforming growth factor-alpha immunoreactivity in a variety of epithelial tissues.

The immunohistochemical expression of transforming growth factor-alpha (TGF alpha) has been examined in a range of normal adult epithelial tissues from both man and rat using an anti-hTGF alpha monoclonal antibody (GF10). No differences in distribution were apparent between man and rat. In the continually renewing epithelium of the gastrointestinal tract, no staining was seen within the proliferative compartments, but strong immunoexpression was noted in various differentiated populations. In the testis, the spermatogonia were unstained, but the more luminally orientated germ cells were strongly positive. In the gastrointestinal tract, at least, any mitogenic action of TGF alpha must be mediated through a relatively long paracrine loop. In contrast, the differentiated parenchyma of kidney, salivary gland and liver remained unstained apart from collecting ducts in the kidney, striated ducts in salivary glands and bile ducts in the liver. The association of TGF alpha with tubule formation was reinforced by the very strong staining of newly forming bile ducts in a model of liver oval cell proliferation. Thus, in all the epithelia studied there was a distinct spatial pattern of TGF alpha immunoreactivity.

Long term tissue response to titanium coated with diamond like carbon.

Diamond like carbon (DLC) coatings were deposited on to Ti substrates by plasma enhanced chemical vapor deposition technique. Ti and DLC/Ti samples were implanted in skeletal muscle of rabbits. The samples were explanted after 1, 3, 6 and 12 months and the tissue-cell interaction was studied. Our data indicate both DLC/Ti and bare Ti to be compatible with skeletal muscle.

Squamous cell carcinoma of the feline thymus with widespread apoptosis.

The present report documents a case of squamous cell carcinoma originating from the thymus of a 12-year-old short-haired male cat. The tumour had metastasised to the sternal lymphoid tissue and to the left lung. To the authors' knowledge, thymic carcinoma has not been reported in domestic animals. Furthermore, extensive apoptosis was observed in the tumour mass.

Acute disseminated encephalomyelitis following leptospirosis.

Acute disseminated encephalomyelitis is very rare following leptospirosis. Here we describe a patient who developed the condition after leptospiral infection, which responded to intravenous immunoglobulin only.

Chitosan scaffold co-cultured with keratinocyte and fibroblast heals full thickness skin wounds in rabbit.

This study evaluated the modulatory effect of chitosan sponge co-cultured with keratinocyte and fibroblast on wound healing. Dermal fibroblasts and keratinocyte isolated from rabbit skin were co-cultured on chitosan sponge, to fabricate cell-loaded chitosan tissue engineered construct. Full thickness excision wounds created on the rabbit dorsum were treated with three types of graft materials ­ a noncellular chitosan graft, homologous keratinocyte fibroblast loaded chitosan, and a commercial product. Postgraft skin-wound samples were examined histomorphologically at 7th, 14th, and 28th day after staining with hematoxylin and eosin, picrosirius red and/or immunohistochemistry. Wound healing parameters considered were the extent of re-epithelialization, collagen deposition, and neoangiogenesis. The number of proliferating cells, vimentin positive cells, and alpha smooth muscle actin cells were also quantified. The histology results suggested that the grafts aided wound healing but, the cell-loaded graft induced a differential pattern of healing and had lower scarring tendency. The cell-loaded tissue construct may be useful as a therapeutic graft for treating wounds where there is a total loss of tissue and cells as in burn injury.

Flexible and microporous chitosan hydrogel/nano ZnO composite bandages for wound dressing: in vitro and in vivo evaluation.

Current wound dressings have disadvantages such as less flexibility, poor mechanical strength, lack of porosity, and a tendency for dressings to adhere onto the wound surface; in addition, a majority of the dressings did not possess antibacterial activity. Hydrogel-based wound dressings would be helpful to provide a cooling sensation and a moisture environment, as well as act as a barrier to microbes. To overcome these hassles, we have developed flexible and microporous chitosan hydrogel/nano zinc oxide composite bandages (CZBs) via the incorporation of zinc oxide nanoparticles (nZnO) into chitosan hydrogel. The prepared nanocomposite bandages were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD), and scanning electron microscopy (SEM). In addition, swelling, degradation, blood clotting, antibacterial, cytocompatibility, cell attachment on the material, and cell infiltration into the composite bandages were evaluated. The nanocomposite bandage showed enhanced swelling, blood clotting, and antibacterial activity. Cytocompatibility of the composite bandage has been analyzed in normal human dermal fibroblast cells. Cell attachment and infiltration studies showed that the cells were found attached to the nanocomposite bandages and penetrated into the interior. Furthermore, the in vivo evaluations in Sprague-Dawley rats revealed that these nanocomposite bandages enhanced the wound healing and helped for faster re-epithelialization and collagen deposition. The obtained data strongly encourage the use of these composite bandages for burn wounds, chronic wounds, and diabetic foot ulcers.

Development and validation of the Domestic Violence Questionnaire in married women aged 18-55 years.

BACKGROUND: Intimate partner violence against women is seen in all cultures. It has wide-ranging effects on the physical and psychological health of women. In the local language, available questionnaires are either too exhaustive or inadequate to assess domestic violence comprehensively. OBJECTIVE: To develop a Domestic Violence Questionnaire in Malayalam and validate it for married women aged 18-55 years in the local population. STUDY DESIGN: Descriptive study - Validation of questionnaire. MATERIALS AND METHODS: A 29-item questionnaire, to identify domestic violence over the past 1 year, was developed in the local language, by selecting items from two other questionnaires and based on expert opinion. Item reduction was done after pilot testing. Then, this 25-item questionnaire was administered to 276 married women aged 18-55 years. Reliability and validity were estimated. Factor analysis was done for item reduction. Poor-loading, wrong-loading and cross-loading items were removed from the questionnaire. Taking the subjective perception of the participants regarding themselves experiencing domestic violence as the gold standard, a Receiver Operator Characteristic curve was drawn to decide the cut-off score with optimum sensitivity and specificity. RESULTS: The final questionnaire had 20 items - 13 items for psychological and 7 items for physical violence. Internal consistency reliability was 0.92. At a cut-off score of 5, sensitivity was 89.5% and specificity 87.2%. CONCLUSIONS: The Domestic Violence Questionnaire in Malayalam has adequate psychometric properties to identify intimate partner violence against women in the local population.

Amphotericin B-gum arabic conjugates: synthesis, toxicity, bioavailability, and activities against Leishmania and fungi.

PURPOSE: Gum arabic, a branched polysaccharide consisting of more than 90% arabinogalactan having a molecular weight around 250,000 Da is the oldest and best known of all natural gums. The objective of the present investigation was to examine whether amphotericin B (AmB), the polyene antibiotic when conjugated to periodate oxidized gum arabic still retained its anti-fungal and anti-leishmanial activity and to evaluate its toxicity and bioavailability. METHODS: AmB conjugated to the oxidized polysaccharide through Schiff's linkages in the unreduced (imine) and reduced (amine) forms were characterized for the drug content, hemolytic potential, molecular mass, in vitro release and were examined for anti-fungal activity against Candida albicans and Cryptococcus neoformans and for anti-leishmanial activity against promastigotes of Leishmania donovani in culture. Toxicity and bioavailability were evaluated by intravenous (i.v) injections of the conjugates in mice and rabbits respectively. RESULTS: The conjugates were found to be non-hemolytic and mice withstood a dosage of 20 mg (AmB)/kg body weight of both conjugates. Histological examination of the internal organs of mice showed no lesions in kidney, brain, heart or liver. Estimation of the residual drug in the internal organs 7 days post injection showed that the spleen still retained 8.4 +/- 0.53 microg/g of tissue. AmB was found to be released from both conjugates in vitro although the release from the imine conjugate was much faster than from the amine conjugate. The concentrations inhibiting parasite growth by 50% (IC(50)) values for the imine conjugate against promastigotes of L. donovani LV9 and DD8 strains were 0.37 +/- 0.04 and 1.44 +/- 0.18 microM respectively. The IC(50) values for the amine conjugates were much higher. The minimum inhibitory concentration (MIC) against C. albicans and C. neoformans was in the range of 0.5-0.9 microg/mL for both imino and amino conjugates. The bioavailability of the conjugate in rabbits showed that the imine conjugate maintained a plasma concentration in the range of 20 to 5 microg/mL while for the amine conjugate it was in the range of 17 to 3 microg/mL over 24 h. CONCLUSIONS: The drug conjugates were stable, non-hemolytic and non-toxic to the internal organs of the animal and showed good anti-fungal and anti-leishmanial activity in vitro. In spite of the large molecular weight of the polysaccharide, AmB from the conjugates showed bioavailability after i.v injection. Since the highest concentration of AmB was found in the spleen after a single injection, these conjugates may have potential in anti-leishmanial therapy.

Atrial septal defect in a bonnet macaque (Macaca radiata).

Atrial Septal Defect was detected at autopsy in a subadult bonnet macaque (Macaca radiata). Case history and autopsy findings were described.

The biology and pathology of programmed cell death (apoptosis).

Apoptosis is a process by which cells die in a controlled and programmed manner in response to specific stimuli, often following extrinsic and intrinsic signals which ultimately cause the "switching on" of cell death regulatory genes. Condensation of chromatin and cytoplasm, fragmentation of the cell and formation of membrane-bound bodies containing intact organelles (apoptotic bodies), and phagocytosis of these bodies by resident cells are the major structural changes associated with apoptosis. Biochemically, activation of a nonlysosomal endonuclease is a cardinal feature of this mode of cell death. Several genes have been implicated in the execution of apoptosis. A signal transduction mechanism is suspected to regulate the phenomenon. Although apoptosis is widely considered as an adaptive response to physiological or near physiological stimuli, several noxious agents can initiate the reaction and thus it is often a toxicological response.

Cell behavior in the acetylaminofluorene-treated regenerating rat liver. Light and electron microscopic observations.

When hepatocyte regeneration is impaired, facultative stem cells and their descendants, also called oval cells, become activated and produce cell progeny that eventually differentiate. We have observed these cells in the rat liver after partial hepatectomy when the animals have been fed 2-acetylaminofluorene. Oval cells emerge from the portal areas and stain strongly with monoclonal antibodies raised against cytokeratins 8 and 19 and vimentin, the intermediate filament traditionally associated with mesenchymal cells. The majority of oval cells appeared to be part of a bile ductular reaction, manifest by their cytokeratin expression, and the bile duct injection of pigmented gelatin confirmed that these oval cells were essentially tortuous, arborizing duct-like structures (cholangioles) branched from and continuous with preexisting bile ducts. In situ hybridization studies showed that hepatocyte growth factor mRNA-expressing sinusoid lining cells were most numerous in the periportal areas during the period of ductular proliferation. At 1 week after partial hepatectomy, we observed morphological evidence of areas of in situ focal differentiation in the ductular structures, either to a columnar intestinal-type epithelia or to a hepatocyte phenotype, with abundant large mitochondria and membranous cytokeratin 8 immunoreactivity contrasting with the diffuse staining of the ductular cells. By following the fate of oval cells the authors conclude that in this model proliferated bile ductules represent the oval cell compartment capable of producing pluripotential progenitor cells.

The nature of cytotoxic drug-induced cell death in murine intestinal crypts.

The nature of cell death in murine small intestinal crypts caused by potentially lethal doses of four classes of cancer chemotherapeutic agents was studied. The drugs used were cytosine arabinoside, vincristine, adriamycin and nitrogen mustard. The compounds readily induced massive cell death in the proliferating compartment of the crypt. In each case, cell death was apparent within an hour, and the incidence of dead cells peaked during the following 4-8 h. By 24 h, little damage was discernible in the crypt systems. Remarkably, dead cells or dead cell fragments were phagocytosed rapidly (within about 1 h) by neighbouring healthy enterocytes. When examined by light microscopy, transmission electron microscopy and scanning electron microscopy, the dead cells showed the characteristic features of having succumbed to an apoptotic mode of cell death without any trace of cell and organelle oedema characteristic of necrosis. The study suggests that cell death by apoptosis operates even when the cells are exposed to severe pathological perturbation and that the phenomenon is not solely a process which operates in response to either physiological stimuli or to mild physical or chemical trauma.

The resistant hepatocyte model of carcinogenesis in the rat: the apparent independent development of oval cell proliferation and early nodules.

The early cellular changes in the Solt-Farber resistant hepatocyte model of carcinogenesis have been studied to clarify the relationship of oval cell proliferation to the development of early hepatocyte nodules. Cellular proliferation, intermediate filament profiles and the expression of specific cytochrome P450 enzymes were examined. At 24 h after partial hepatectomy (PH) many of the bile ductular cells were in S phase, but over the next few days DNA synthesis progressively decreased in the portal bile ducts and was more common in arborizing ductules (oval cells) radiating from the portal areas. These cells strongly expressed cytokeratins 8 and 19 and vimentin, and from 1 week after PH they frequently underwent differentiation either into hepatocytes, expressing cytochrome P450 enzymes, or into intestinal-type cells. Five days after PH, numerous basophilic foci were discernible, and these expanded rapidly. The ductular cells swirled around the foci, but their antigenic profile clearly indicated that these cells were not involved in the development of these early nodules. In normal hepatocytes, cytokeratin 8 immunoreactivity was distinctly membranous in location, and could only be readily detected in periportal hepatocytes. In the basophilic hepatocyte foci, overexpression of cytokeratin 8 was consistently associated with cells organizing into acini, with expression reminiscent of authentic bile ducts, possibly indicating a structure-function relationship. In conclusion, early foci and nodules in this model are derived from resistant hepatocytes and not ductular oval cells, the latter being a facultative multipotential stem cell compartment.