Gestational Pityriasis Rosea: Suggestions for Approaching Affected Pregnant Women.
Dear Editor, Pityriasis rosea is a common, acute, and self-limiting dermatosis, which is associated with the endogenous systemic reactivation of human herpesvirus (HHV)-6 and/or HHV-7 (1). It predominantly affects individuals of both sexes in their second or third decade of life and is clinically characterized by the occurrence of an initial erythematosquamous plaque followed by the appearance of disseminated similar but smaller lesions one or two weeks later. Several patients develop systemic symptoms such as nausea, anorexia, malaise, headache, fever, arthralgia, and lymphadenopathy that may precede or accompany the eruption; the latter follows the cleavage lines of the trunk creating the configuration of a Christmas tree and spontaneously resolves within 4 to 8 weeks. Mainly based on the nature of the underlying viral reactivation, pityriasis rosea is classified into five different forms (2): 1) Classic and 2) Relapsing (characterized by sporadic and relapsing HHV-6/7 systemic reactivation, respectively), 3) Persistent (persistence of HHV-6/7 viremia), 4) Pediatric (longer activity of HHV-6/7 infection; recent primary infection) and 5) Gestational (HHV-6/7 reactivation and possible intrauterine transmission). Clearly, the inevitable impairment of immune response in pregnancy favors viral reactivation and possibly also the intrauterine transmission of HHV-6/7. Indeed, it is well known and documented that pityriasis rosea more frequently occurs in pregnant women (18%) as compared to the general population (6%) (3). However, the literature concerning the possible effect of pityriasis rosea on the outcome of pregnancy is surprisingly sparse. Only an Italian group, Drago et al (4,5), has systematically investigated the impact of this disorder on pregnant women. They found that 22 out of 61 women (36%) who developed pityriasis rosea during pregnancy had unfavorable outcomes, whereas 8 others miscarried (13%). None of the latter had any risk factors, other than pityriasis rosea, for intrauterine fetal death. All miscarrying women reportedly revealed an aggressive course of widespread eruption and severe constitutional symptoms; all of them had HHV-6 DNA in the plasma, placenta, skin lesions, and fetal tissues, whereas HHV-7 DNA was detected in the plasma and skin lesions in 3 out of 8 (37.5%) miscarrying women. HHV-6 DNA was found only in the plasma of 2 out of 31 women (6.45%) with normal pregnancy, whereas HHV-7 DNA was detected in the plasma of 3 (9.45%) and in the skin lesions of 2 women (6.45%) with normal pregnancy. The total abortion rate in women who developed pityriasis rosea during their pregnancy (13%) does not differ from that observed in the general population. Nevertheless, it is markedly higher in cases affected during the first 15 gestational weeks (57%) (4,5). Surprisingly, this devastating impact of pityriasis rosea on the outcome of pregnancy is almost completely unknown not only to the public but also to many members of the medical community. It is also largely unknown that, particularly during the first 15 gestational weeks, all pregnant women should avoid any contact with patients known to have pityriasis rosea. Since we have received a considerable number of requests for consultation with pregnant women with pityriasis rosea over the last few years, our group has compiled suggestions approaching the affected patients: 1. If an eruption suggestive for pityriasis rosea occurs in a pregnant woman, the following factors should be excluded: a. Exposure to drugs prior to the development of the rash (biologic agents, captopril, clonidine, hydrochlorothiazide, atenolol, lamotrigine, nortriptyline, barbiturates, metronidazole, terbinafine, omeprazole, non-steroidal anti-inflammatory drugs, and isotretinoin), which are capable of inducing a pityriasis rosea-like eruption (6) and b. Disorders included in the differential diagnosis (syphilis and infections due to parvovirus, herpes virus, cytomegalovirus, and Epstein-Barr virus). 2. The clinical diagnosis of pityriasis rosea should be made according to the morphological criteria (peripheral collarette scaling with central clearance on at least two lesions) put forth by Chuh (7). 3. Since specific anti-HHV-6 and -7 IgM antibodies are detected only in a low percentage of infected pregnant women (8), HHV-6 and -7 DNA should be assessed in plasma by nested PCR. Especially during the first 15 gestational weeks, pregnant women with positive PCR results deserve, apart from close monitoring, appropriate information about the existing risks in order to be able to make informed decisions. 4. Reliable and definite data from adequate and controlled human studies on the safety of acyclovir or valacyclovir in pregnant women and their efficacy in pityriasis rosea are lacking. Thus, the decision on whether these antiviral compounds will be administered should be tailored to each individual pregnant woman, subsequent to a meticulous assessment of the potential risks and their balancing against the potential benefits.


Asiatic acid enhances intratumor delivery and the antitumor effect of pegylated liposomal doxorubicin by reducing tumor-stroma collagen.
Tumor-targeted drug delivery systems (Tt-DDSs) are proposed as a promising strategy for cancer care. However, the dense collagen network in tumors stroma significantly reduces the penetration and efficacy of Tt-DDS. In order to investigate the effect of asiatic acid (AA) on antitumor effect of pegylated liposomal doxorubicin (PLD) by attenuating stroma-collagen, colon cancer xenograft mice (SW620 cell line) were treated by PLD, AA, or combined regimes, respectively; the collagen levels were estimated by Sirius red/fast green dual staining and immunohistochemistry (IHC) staining; the intratumor exposure of doxorubicin was visualized by ex vivo fluorescence imaging and quantified by HPLC/MS analysis. In addition, the impact of AA on collagen synthesis of fibroblast cell (HFL-1) and cytotoxic effect of PLD and doxorubicin to cancer cell (SW620) were studied in vitro. In the presence of AA (4 mg/kg), the intratumor collagen level was restricted in vivo (reduced by 22%, from 4.14% ± 0.30% to 3.24% ± 0.25%, P = 0.051) and in vitro. Subsequently, doxorubicin level was increased by ~30%. The antitumor activity of PLD was significantly improved (57.3% inhibition of tumor growth and 44% reduction in tumor weight) by AA combination. Additionally, no significant improvement in cytotoxic effect of PLD or doxorubicin induced by AA was observed. In conclusion, AA is a promising sensitizer for tumor treatment by enhancing intratumor drug exposure via stromal remodeling.


Preschool children's performance in task switching on the dimensional change card sort task: separating the dimensions aids the ability to switch.
Fifty-seven children (53% female) at 3 ages (2 1/2, 3, and 3 1/2 years) were tested on the standard Dimensional Change Card Sort (DCCS) task with integrated stimuli (e.g., a red truck) and on a separated-dimensions version where colorless shapes were presented on a colored background (e.g., a black truck on a red background). Roughly twice as many children successfully switched sorting dimensions when color was a property of the background than when color was a property of the shape itself. Children succeeded 6 months earlier in switching sorting criteria when the dimensions were separated. When evidence of both indecision and accuracy was taken into account, a clear and rich developmental progression emerged. These results support an inhibitory control interpretation of preschoolers' problems on the DCCS task. Diamond theorized that young children can have difficulty integrating features not part of a single object and separating features of a single object so that the object can be categorized first by one attribute and then by another. Preschoolers remain stuck in thinking about objects according to the objects' initially relevant attribute (attentional inertia; Kirkham, Cruess, & Diamond, 2003). To switch perspectives, the old way of thinking about the objects must be inhibited. Separating color and shape reduced the need for such inhibition; a truck was always a truck, and the background was always red.


Does prior recall of past week alcohol use affect screening results for at-risk drinking? Findings from a randomized study.
Underreporting of alcohol consumption is one of the major challenges in survey research including self-reports. The aim of this study was to test whether underreporting can be reduced by prompting respondents to first reflect on their drinking in the past week and then answer quantity-frequency based screening questions on their typical alcohol use. Data come from 2,379 adults (54% female; mean age = 31.8 years, SD = 11.4 years) consecutively recruited at a local registration office in northeastern Germany. Participants responded to an electronic, self-administered questionnaire on different health behaviors. They were randomized to receiving the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) either before or after the assessment of past week timeline follow-back questions. Logistic regression models were calculated predicting positive screening results for at-risk drinking. Potential interaction effects with gender, age and educational background were explored. Results show that the assessment of past week alcohol consumption prior to the assessment of the AUDIT-C reduced the odds of obtaining positive screening results (OR = 0.83; 95% CI = 0.70-0.99). There were no interaction effects with gender, age and educational background. As a secondary finding, participants reported consistently lower alcohol consumption in the alcohol measure that was administered later in the questionnaire. Preceding questions about alcohol consumption in the past week reduced the probability of positive screening results for at-risk drinking. Our findings suggest that prompting people to recall past week alcohol use prior to screening may not be a solution to reduce underreporting.


Fitness Costs of Two Maize Lepidopteran Pests Fed on Bacillus thuringiensis (Bt) Diets Enriched with Vitamins A and C.
Serious malnutrition problems occur in developing countries where people's diets are mainly based on staple crops. To alleviate this, high-production crops are being developed that are better adapted to climate change, enriched in micronutrients and vitamins, or resistant to pests. In some cases, new varieties have been developed with several of the characteristics mentioned above, such as biofortified and pest-resistant crops. The development of biofortified Bacillus thuringiensis (Bt) crops raises the question of whether vitamin enrichment of Bt crops can in any way favor those pests that are not very susceptible to the Bt toxin that feed on these crops, such as Helicoverpa armigera (Hübner) or Mythimna unipuncta (Haworth) (Lepidoptera: Noctuidae). In this study, the response to a Bt diet enriched with vitamins A (β-carotene) and C (ascorbic acid) was somewhat different between the two species. M. unipuncta was less sensitive to the toxin than H. armigera, although the ingestion of the Bt diet resulted in oxidative stress (longer larval development and lower pupal weight) which was not mitigated by the vitamins. However, the two vitamins reduced the mortality of H. armigera larvae fed on a Bt-enriched diet; in addition, ß-carotene reduced the activity of the antioxidant glutathione S-transferase (GST) of both species, suggesting it has an antioxidant role. The results obtained here indicate that biofortified Bt crops will not favor the development of H. armigera very much and will not affect M. unipuncta's development at all, although the effect of the increase in vitamins may be very variable and should be studied for each specific phytophagous.


Phenotypic characterization of gamma interferon-induced human monocyte polykaryons.
Multinucleated giant cells of mononuclear phagocyte origin (monocyte or macrophage polykaryons [MPs] ) are seen in numerous different normal and pathologic states. We have previously shown that gamma interferon (IFN-gamma) induces fusion of uninuclear monocytes (UMs) to form MPs. This study was designed to characterize these IFN-gamma-induced MPs. Control and IFN-gamma-treated UMs and MPs did not have peroxidase activity, but they stained intensely for nonspecific esterase and acid phosphatase. The esterase of UMs and MPs was abolished by fluoride, but the acid phosphatase of UMs and MPs was only minimally decreased by tartrate. The phagocytosis of polystyrene spheres and glutaraldehyde-fixed erythrocytes by MPs was moderately depressed as compared with control or treated UMs, whereas the phagocytosis of IgG-coated erythrocytes was markedly depressed. Populations of control monocytes produced less H2O2 in response to 200 nmol/L of phorbol myristate acetate than did IFN-gamma-treated monocytes (37 +/- 7 v 199 +/- 29 nmol/h per milligram of cell protein). However, when examined microscopically, individual MPs had less ability to reduce NBT (18% +/- 5% positive for MP, 91% +/- 3% for treated UMs, and 67% +/- 3% for control UMs). The surface membrane antigens Leu M3, OKM1 (C3bi receptor), DU-HL60-3, DU-HL60-4, TE5, and V1 were not expressed or were expressed poorly in MPs; they were expressed normally in control and treated UMs. However, HLA-DR expression was increased in treated UMs and MPs. The binding of the lectins RCA, Con A, WGA, DBA, UEA, and PNA was equivalent in all cells. Thus, MPs formed by fusion of UMs in vitro after culture with IFN-gamma differ in several features from UMs.


Developmental and tissue-specific regulation of the Q10 class I gene by DNA methylation.
The H-2 class I genes encode cell-surface glycoproteins that play a critical role in the immune presentation of aberrant cells. The Q10 class I gene, however, encodes a secreted glycoprotein that is highly homologous to the membrane-bound molecules. While the H-2 genes are activated in all tissue types, the expression of the Q10 gene is restricted to only the liver. Analysis of DNA from different tissues revealed a unique methylation profile for the Q10 gene in liver. Developmental activation of this gene in newborn mice is also reflected by a coordinated temporal change in DNA methylation. By comparing the methylation profiles between congenic mice, which differed in their levels of expression of the Q10 gene, it is observed that methylation at the 3'-flanking region correlates with expression. Methylations were at both CG and CC sequences. Since treatment of newborns with 5-azacytidine, which led to inhibition of methylation, resulted in the suppression of Q10, we conclude that hypermethylation in the 3'-flanking region is responsible, at least in part if not in full, for the activation of the Q10 gene in the liver.


Effect of acute hypercapnia on PTH-stimulated phosphaturia in dietary Pi-deprived rat.
The effects of respiratory acidosis on renal inorganic phosphate (Pi) handling are controversial. Clearance experiments, therefore, were performed in fasted, chronically parathyroidectomized (PTX), dietary Pi-deprived rats. The objectives were twofold: to study the effects of compensated and uncompensated hypercapnia per se on renal Pi excretion and to examine the interaction between acute hypercapnia, dietary Pi, and parathyroid hormone (PTH) on the renal handling of Pi. Acute hypercapnia increased the plasma Pi (delta 2.82 +/- 0.65 mg/dl, P less than 0.05) without altering the glomerular filtration rate (GFR). The FEPi increased (delta 7.26 +/- 0.48%, P less than 0.001) but the TRPi/GFR also increased. PTH (3 U X kg-1 X h-1) superimposed on hypercapnia resulted in a plasma Pi comparable to hypercapnia alone. The FEPi (7.56 +/- 0.78 vs. 24.43 +/- 2.20%; P less than 0.001) was higher and the TRPi/GFR (117 +/- 4 vs. 80 +/- 2 micrograms/min, P less than 0.01) lower, in the former group. PTH infusion during normocapnia resulted in a lower FEPi (0.20 +/- 0.10 vs. 24.43 +/- 2.20%, P less than 0.001) and a higher TRPi/GFR (106 +/- 2 vs. 80 +/- 2 micrograms/min, P less than 0.01) compared with PTH infusion during hypercapnia. Urinary adenosine 3',5'-cyclic monophosphate (cAMP) excretion was similar between the groups. During hypercapnia, when the extracellular acidemia was neutralized, the phosphaturic action of PTH persisted. These studies offer direct evidence that in chronically PTX, dietary Pi-deprived rats, the phosphaturic action of PTH is restored by hypercapnia per se. This effect appears to be independent of extracellular acidemia, changes in the plasma Pi and calcium, urinary pH and Na and cAMP excretion.


Large scale synchronous mating and the study of macronuclear development in Euplotes crassus.
After conjugation in hypotrichous ciliates, a new macronucleus is produced from a copy of the micronucleus. This transformation involves large-scale reorganization of DNA, with conversion of the chromosomal micronuclear genome into short, gene-sized DNA molecules in the macronucleus. To study directly the changes that occur during this process, we have developed techniques for synchronous mating of large populations of the hypotrichous ciliate Euplotes crassus. Electron microscope studies show that the micronuclear chromosomes are polytenized during the first 20 h of macronuclear development. The polytene chromosomes lack the band-interband organization observed in other hypotrichs and in the Diptera. Polytenization is followed by transectioning of the chromosomes. We isolated DNA at various times of macronuclear development and found that the average molecular weight of the DNA decreases at the time of chromosome transectioning. In addition, we have shown that a small size group of macronuclear DNA molecules (450-550 base pairs) is excised from the chromosomal DNA approximately 10 h later in macronuclear development.


Experimental Models of Brugada syndrome.
Brugada syndrome is an inherited, rare cardiac arrhythmogenic disease, associated with sudden cardiac death. It accounts for up to 20% of sudden deaths in patients without structural cardiac abnormalities. The majority of mutations involve the cardiac sodium channel gene SCN5A and give rise to classical abnormal electrocardiogram with ST segment elevation in the right precordial leads V1 to V3 and a predisposition to ventricular fibrillation. The pathophysiological mechanisms of Brugada syndrome have been investigated using model systems including transgenic mice, canine heart preparations, and expression systems to study different SCN5A mutations. These models have a number of limitations. The recent development of pluripotent stem cell technology creates an opportunity to study cardiomyocytes derived from patients and healthy individuals. To date, only a few studies have been done using Brugada syndrome patient-specific iPS-CM, which have provided novel insights into the mechanisms and pathophysiology of Brugada syndrome. This review provides an evaluation of the strengths and limitations of each of these model systems and summarizes the key mechanisms that have been identified to date.


A systematic literature review exploring the prevalence of post-traumatic stress disorder and the role played by stress and traumatic stress in breast cancer diagnosis and trajectory.
Stress has been extensively studied as a psychosomatic factor associated with breast cancer. This study aims to review the prevalence of post-traumatic stress disorder (PTSD), its associated risk factors, the role of predicting factors for its early diagnosis/prevention, the implications for co-treatment, and the potential links by which stress could impact cancer risk, by closely examining the literature on breast cancer survivors. The authors systematically reviewed studies published from 2002 to 2016 pertaining to PTSD, breast cancer and PTSD, and breast cancer and stress. The prevalence of PTSD varies between 0% and 32.3% mainly as regards the disease phase, the stage of disease, and the instruments adopted to detect prevalence. Higher percentages were observed when the Clinician Administered PTSD Scale was administered. In regard to PTSD-associated risk factors, no consensus has been reached to date; younger age, geographic provenance with higher prevalence in the Middle East, and the presence of previous cancer diagnosis in the family or relational background emerged as the only variables that were unanimously found to be associated with higher PTSD prevalence. Type C personality can be considered a risk factor, together with low social support. In light of the impact of PTSD on cognitive, social, work-related, and physical functioning, co-treatment of cancer and PTSD is warranted and a multidisciplinary perspective including specific training for health care professionals in communication and relational issues with PTSD patients is mandatory. However, even though a significant correlation was found between stressful life events and breast cancer incidence, an unequivocal implication of distress in breast cancer is hard to demonstrate. For the future, overcoming the methodological heterogeneity represents one main focus. Efficacy studies could help when evaluating the effect of co-treating breast cancer and post-traumatic stress symptoms, even if all the criteria for a Diagnostic and Statistical Manual of Mental Disorders diagnosis are not fulfilled.


Connectivity of GABAergic calretinin-immunoreactive neurons in rat primary visual cortex.
In rat visual cortex neurons that are immunoreactive for the calcium-binding protein calretinin (CR+) constitute a distinct family which accounts for 17% of gamma-aminobutyric acid (GABA)-expressing cells. It is not clear, however, (i) whether CR is expressed exclusively in GABAergic neurons and (ii) how CR+ neurons are incorporated into neuronal circuits of rat visual cortex. To address these questions we studied synaptic relationships of CR+ neurons with GABA+ and GABA- elements in the neuropil of rat primary visual cortex (area 17). All CR+ neurons are nonpyramidal cells with smooth or sparsely spiny and often beaded dendrites. Of all CR+ neurons, 56% are located in layers 1 and 2/3. In layer 2/3, most CR+ neurons are bipolar-shaped and have vertically oriented dendrites. Many ascending dendritic branches reach layer 1 where they run parallel to pial surface. CR+ axons are thin, highly branched near the cell body and often send descending collaterals to layers 5 and 6. Double immunofluorescence labeling revealed GABA in 94% of CR+ cell bodies in layer 2/3. Electron microscopic analysis shows that all CR+ axon terminals contain elongated vesicles and form symmetric synapses. Postembedding staining shows that 98% of CR+ terminals are GABA+. GABA-immunoreactivity is also present in somata and thick dendrites of CR+ neurons but many thin dendrites are GABA-. CR+ somata, dendrites and axon terminals are enriched in mitochondria. Somata and thick CR+ dendrites are densely innervated. At least 68% of the targets of CR+ terminals in layer 2/3 are GABA+ and > or = 50% of these are other CR+ neurons. The remainder (32%) of targets of CR+ terminals are thin dendrites of GABA- cells. In contrast, in layers 5 and 6, 60% of CR+ terminals form synapses with GABA- somatic profiles. The preferential interactions of layer 2/3 CR+ neurons with GABAergic neurons, and with CR+ neurons in particular, suggests that these cells play a role in the inhibition of inhibitory neurons of the same layer. Through these interactions CR+ cells may reduce inhibition of pyramidal cells in layers 2/3, 5 and 6 and thus disinhibit a column of neurons.


Neuroprotective effect of neuroserpin in rat primary cortical cultures after oxygen and glucose deprivation and tPA.
Besides its role as a thrombolytic agent, tissue plasminogen activator (tPA) triggers harmful effects in the brain parenchyma after stroke, such as inflammation, excitotoxicity and basal lamina degradation. Neuroserpin, a natural inhibitor of tPA, has shown neuroprotective effects in animal models of brain infarct. However, the molecular mechanisms of neuroserpin-mediated neuroprotection after brain ischemia remain to be well characterized. Then, our aim was to investigate such mechanisms in primary mixed cortical cell cultures after oxygen and glucose deprivation (OGD). Primary rat mixed cortical cultures containing both astrocytes and neurons were subjected to OGD for 150min and subsequently treated with either tPA (5μg/mL), neuroserpin (0.125, 0.25, 0.5 or 1μM), and tPA together with neuroserpin at the mentioned doses. Twenty-four hours after treatment, LDH release, caspase-3 activity, MCP-1, MIP-2, active MMP-9, GRO/KC and COX-2 were measured. Statistical differences were analyzed using Student's t-test or one-way ANOVA as appropriate. Treatment with tPA after OGD increased LDH release, active MMP-9, MCP-1 and MIP-2 (all p≤0.05), but not caspase-3, GRO/KC or COX-2 compared to control. Treatment with neuroserpin after OGD decreased LDH release and active MMP-9 (all p≤0.05). It had no effect on caspase-3 activity, or on MCP-1, MIP-2, GRO/KC or COX-2 expression compared to control. Administration of tPA together with neuroserpin decreased LDH release, active MMP-9 and MIP-2 (all p≤0.05) and showed no effect on MCP-1, GRO/KC or COX-2 compared to control. Our results suggest that neuroprotective activity of neuroserpin involves attenuation on tPA-mediated mechanisms of inflammation and BBB disruption after brain ischemia.


Deciphering genome-wide WRKY gene family of Triticum aestivum L. and their functional role in response to Abiotic stress.
WRKY transcription factors (TFs) act in regulating plant growth and development as well as in response to different stress. Some earlier studies done by individual researchers reported different wheat WRKY TFs. Although, the recently released wheat genome has opened an avenue to investigate wheat WRKYs (TaWRKY) TFs. Prime objective of this study to performed genome-wide classifications of TaWRKYs and their functional annotation. The classification of 107 individual identified characterized sequences of TaWRKY (IICS-TaWRKY) and 160 uncharacterized draft sequences of TaWRKY (UDS-TaWRKY), along with their gene structures and motifs analysis was performed. Along with comparative sequence analysis and microarray analysis was performed to mimic out TaWRKYs functions in response to different abiotic stresses, accompanied by in-vitro validation. The comparative phylogenetic analysis and estimation of Ka/Ks ratio with Triticum urartu, illustrate group based clasifications of TaWRKYs and evolutionary divergences. Furthermore, motif-based and protein-DNA interaction analysis of TaWRKYs helps to identify, their putative function in target DNA recognition sites. Subsequently, results of microarray and comparative sequence analysis provides the evidence of TaWRKYs involved in heat and/or drought stress. Further, in-vitro results validates that TaWRKY014, TaWRKY090 are found to participate in response of drought stress, whereas TaWRKY008, TaWRKY122, and WRKY45 are involved in response of heat and drought stress. These findings can be utilized in developing novel heat and drought-tolerant wheat cultivars using marker-assisted breeding and transgenic development.


Superhydrophobic stability of nanotube array surfaces under impact and static forces.
The surfaces of nanotube arrays were coated with poly(methyl methacrylate) (PMMA) using an imprinting method with an anodized alumina membrane as the template. The prepared nanotube array surfaces then either remained untreated or were coated with NH2(CH2)3Si(OCH3)3(PDNS) or CF3(CF2)7CH2CH2Si(OC2H5)3 (PFO). Thus, nanotube arrays with three different surfaces, PDNS, PMMA (without coating), and PFO, were obtained. All three surfaces (PDNS, PMMA, and PFO) exhibited superhydrophobic properties with contact angles (CA) of 155, 166, and 168°, respectively, and their intrinsic water contact angles were 30, 79, and 118°, respectively. The superhydrophobic stabilities of these three surfaces were examined under dynamic impact and static pressures in terms of the transition from the Cassie-Baxter mode to the Wenzel mode. This transition was determined by the maximum pressure (p(max)), which is dependent on the intrinsic contact angle and the nanotube density of the surface. A p(max) greater than 10 kPa, which is sufficiently large to maintain stable superhydrophobicity under extreme weather conditions, such as in heavy rain, was expected from the PFO surface. Interestingly, the PDNS surface, with an intrinsic CA of only 30°, also displayed superhydrophobicity, with a CA of 155°. This property was partially maintained under the dynamic impact and static pressure tests. However, under an extremely high pressure (0.5 MPa), all three surfaces transitioned from the Cassie-Baxter mode to the Wenzel mode. Furthermore, the lost superhydrophobicity could not be recovered by simply relieving the pressure. This result indicates that the best way to maintain superhydrophobicity is to increase the p(max) of the surface to a value higher than the applied external pressure by using low surface energy materials and having high-density binary nano-/microstructures on the surface.


Confirmatory validation analysis of the PROFFIT questionnaire to assess financial toxicity in cancer patients.
The Patient Reported Outcome for Fighting FInancial Toxicity (PROFFIT) questionnaire was developed to measure financial toxicity (FT) and identify its determinants. The aim of the present study was to confirm its validity in a prospective cohort of patients receiving anticancer treatment. From March 2021 to July 2022, 221 patients were enrolled at 10 Italian centres. Selected items of the EORTC-QLQ-C30 questionnaire represented the anchors, specifically, question 28 (Q-28) on financial difficulties, and questions 29-30 measuring global health status/quality of life (HR-QOL). The study had 80% power to detect a 0.20 correlation coefficient (r) between anchors and PROFFIT-score (items 1-7, range 0-100, 100 indicating maximum FT) with bilateral alpha 0.05 and 80% power. Confirmatory factor analysis was conducted. FT determinants (items 8-16) were described. Median age of patients was 65 years, 116 (52.5%) were females, 96 (43.4%) had low education level. Confirmatory factor analysis confirmed goodness of fit of the PROFFIT-score. Significant partial correlation of PROFFIT-score was found with Q-28 (r = 0.51) and HR-QOL (r = -0.23). Mean (SD) PROFFIT-score at baseline was 36.5 (24.9); it was statistically significantly higher for patients living in South Italy, those with lower education level, those who were freelancer/unemployed at diagnosis and those who reported significant economic impact from the COVID-19 pandemic. Mean (SD) scores of determinants ranged from 17.6 (27.1) for item 14 (support from medical staff) to 49.0 (36.3) for item 10 (expenses for medicines or supplements). PROFFIT-score significantly increased with worsening response to determinants. External validation of PROFFIT-score in an independent sample of patients was successful. The instrument is now being used in clinical studies.


Epidemiology and pathogenesis of Neisseria meningitidis.
Neisseria meningitidis, an exclusive pathogen of humans, remains the leading worldwide cause of meningitis and fatal sepsis, usually in otherwise healthy individuals. In recent years, significant advances have improved our understanding of the epidemiology and genetic basis of meningococcal disease and led to progress in the development of the next generation of meningococcal vaccines. This review summarizes current knowledge of the human susceptibility to and the epidemiology and molecular pathogenesis of meningococcal disease.


The genetic background significantly impacts the severity of kidney cystic disease in the Pkd1RC/RC mouse model of autosomal dominant polycystic kidney disease.
Autosomal dominant polycystic kidney disease (ADPKD), primarily due to PKD1 or PKD2 mutations, causes progressive kidney cyst development and kidney failure. There is significant intrafamilial variability likely due to the genetic background and environmental/lifestyle factors; variability that can be modeled in PKD mice. Here, we characterized mice homozygous for the PKD1 hypomorphic allele, p.Arg3277Cys (Pkd1RC/RC), inbred into the BALB/cJ (BC) or the 129S6/SvEvTac (129) strains, plus F1 progeny bred with the previously characterized C57BL/6J (B6) model; F1(BC/B6) or F1(129/B6). By one-month cystic disease in both the BC and 129 Pkd1RC/RC mice was more severe than in B6 and continued with more rapid progression to six to nine months. Thereafter, the expansive disease stage plateaued/declined, coinciding with increased fibrosis and a clear decline in kidney function. Greater severity correlated with more inter-animal and inter-kidney disease variability, especially in the 129-line. Both F1 combinations had intermediate disease severity, more similar to B6 but progressive from one-month of age. Mild biliary dysgenesis, and an early switch from proximal tubule to collecting duct cysts, was seen in all backgrounds. Preclinical testing with a positive control, tolvaptan, employed the F1(129/B6)-Pkd1RC/RC line, which has moderately progressive disease and limited isogenic variability. Magnetic resonance imaging was utilized to randomize animals and provide total kidney volume endpoints; complementing more traditional data. Thus, we show how genetic background can tailor the Pkd1RC/RC model to address different aspects of pathogenesis and disease modification, and describe a possible standardized protocol for preclinical testing.


Double Infection in a Patient with Psoriatic Arthritis Under TNF-alpha Blockers Therapy: A Case Report.
Either direct or indirect tumor necrosis factor (TNF)-alpha blockers are usually used to treat psoriatic arthritis (PA), but their use can increase susceptibility to infectious diseases. We report a rare case of double skin-knee wound and lung non-tubercular infection in a patient with PA under TNF-alpha blockers therapy. About 1 year after the beginning of adalimumab, a 48-year-old smoker suffering of PA was hospitalized for the skin-knee wound. Clinical evaluation and biochemical markers excluded the presence of a systemic disease, and a skin infection sustained by leishmaniasis probably related to adalimumab was diagnosed (Naranjo score: 6). Adalimumab was discontinued and oral treatment with apremilast and topical treatment with meglumine antimoniate was started with a complete remission of skin wound in 2 weeks. About 7 months later when the patient was under apremilast treatment, he presented to our observation for dyspnea, cough and fever. High-Resolution Computer Tomography (HRCT) chest highlighted alveolar involvement with centrilobular small nodules, branching linear and nodular opacities. Microbiological culture of both broncho-alveolar lavage fluid and sputum documented an infection sustained by nontuberculous mycobacteria. Even if apremilast treatment probably-induced lung infection, we can't exclude that it worsened a clinical condition induced by adalimumab. Apremilast was stopped and an empirical antitubercular treatment was started. Patient's breathlessness and cough improved as confirmed also by HRCT chest. This case highlights the importance to consider the possibility to develop leishmaniasis and/or non-tubercular mycobacterial infection in patients treated with TNF-alpha inhibitors.


The role of HIV counselling and testing in sexual health behaviour change among undergraduates in Lagos, Nigeria.
In developing countries risky sexual behaviour among young people is on the increase. This study examined the likelihood of HIV counselling and testing (HCT) in reducing risky sexual behaviour among undergraduates in Lagos Metropolis in Nigeria. The main hypothesis tested in the study was the uptake of HCT is likely to reduce risky sexual behaviour among young undergraduates. A multistage sampling procedure was adopted to select a sample of 625 undergraduates in the study setting. A structured questionnaire was administered to respondents to elicit information on previous participation in HCT and sexual behaviour before and after participation. Result indicates that 26.1% of males and 28.9% of females ever participated in HCT. The average number of heterosexual partners kept by the respondents declined among males and females from 3.17 and 2.36, respectively before they participated in HCT to 2.27 and 1.6 after they participated in HCT. The differences in the average number of sexual partners by the respondents before and after they participated in HCT were statistically significant (P=0.000). The proportion of male respondents who engaged in frequent sex also declined from 35.8% (before participating in HCT) to 24.1% (after participating in HCT) and from 25% (before participating in HCT) to 24.7% (after participating in HCT) among females. In conclusion, participation in HCT is likely to reduce the prevalence of risky sexual behaviour among undergraduates in the study setting. Therefore, HCT is an intervention that should be emphasized.


Recent advances in research on carbon nanotube-polymer composites.
Carbon nanotubes (CNTs) demonstrate remarkable electrical, thermal, and mechanical properties, which allow a number of exciting potential applications. In this article, we review the most recent progress in research on the development of CNT-polymer composites, with particular attention to their mechanical and electrical (conductive) properties. Various functionalization and fabrication approaches and their role in the preparation of CNT-polymer composites with improved mechanical and electrical properties are discussed. We tabulate the most recent values of Young's modulus and electrical conductivities for various CNT-polymer composites and compare the effectiveness of different processing techniques. Finally, we give a future outlook for the development of CNT-polymer composites as potential alternative materials for various applications, including flexible electrodes in displays, electronic paper, antistatic coatings, bullet-proof vests, protective clothing, and high-performance composites for aircraft and automotive industries.


[Autoimmunity and glaucoma].
Glaucoma is one of the most common causes of irreversible blindness worldwide. The pathogenesis of the disease is not fully understood. Elevated intraocular pressure is still considered to be one of the most important risk factors, but cannot explain all cases of glaucoma disease. The involvement of autoimmune mechanisms may play an important role in the pathogenesis of glaucoma. Evidence to support this theory has been shown by our group in previous studies: glaucoma patients were found to develop antibody alterations against specific retina and optic nerve proteins. In the experimental autoimmune glaucoma model, we demonstrated that an immunisation with these proteins causes retinal ganglion cell loss in an autoimmune context. In spite of these results, it is still unclear whether the changes in antibody patterns have a causal connection with glaucoma development or are merely an epiphenomena of the disease. However, these changes in the natural autoimmunity offer a new approach to gain deeper insight into glaucoma pathophysiology and to develop a diagnostic approach for early diagnosis.


Breath biomarkers in Non-Carcinogenic diseases.
The analysis of volatile organic compounds (VOCs) from human matrices like breath, perspiration, and urine has received increasing attention from academic and medical researchers worldwide. These biological-borne VOCs molecules have characteristics that can be directly related to physiologic and pathophysiologic metabolic processes. In this work, gathers a total of 292 analytes that have been identified as potential biomarkers for the diagnosis of various non-carcinogenic diseases. Herein we review the advances in VOCs with a focus on breath biomarkers and their potential role as minimally invasive tools to improve diagnosis prognosis and therapeutic monitoring.


Data Management Plans in Horizon 2020: what beneficiaries think and what we can learn from their experience.
Background: Data Management Plans (DMPs) are at the heart of many research funder requirements for data management and open data, including the EU's Framework Programme for Research and Innovation, Horizon 2020. This article provides a summary of the findings of the DMP Use Case study, conducted as part of OpenAIRE Advance. Methods: As part of the study we created a vetted collection of over 800 Horizon 2020 DMPs. Primarily, however, we report the results of qualitative interviews and a quantitative survey on the experience of Horizon 2020 projects with DMPs. Results & Conclusions: We find that a significant number of projects had to develop a DMP for the first time in the context of Horizon 2020, which points to the importance of funder requirements in spreading good data management practices. In total, 82% of survey respondents found DMPs useful or partially useful, beyond them being "just" an European Commission (EC) requirement. DMPs are most prominently developed within a project's Management Work Package. Templates were considered important, with 40% of respondents using the EC/European Research Council template. However, some argue for a more tailor-made approach. The most frequent source for support with DMPs were other project partners, but many beneficiaries did not receive any support at all. A number of survey respondents and interviewees therefore ask for a dedicated contact point at the EC, which could take the form of an EC Data Management Helpdesk, akin to the IP helpdesk. If DMPs are published, they are most often made available on the project website, which, however, is often taken offline after the project ends. There is therefore a need to further raise awareness on the importance of using repositories to ensure preservation and curation of DMPs. The study identifies IP and licensing arrangements for DMPs as promising areas for further research.


Rural and racial disparities in colorectal cancer incidence and mortality in South Carolina, 1996 - 2016.
Colorectal cancer (CRC) is the third leading cause of cancer mortality among men and women in the United States and South Carolina (SC). Since SC has one of the highest proportions of Black (27.9%) and rural residents (33.7%), the purpose of this investigation was to describe the burden of CRC on racial disparities in rural populations. Count data from 2012 to 2016 were obtained from the state central cancer registry using an online data retrieval system. Rural-urban status was determined using Urban Influence Codes (1-2 = urban; 3-12 = rural). Chi-square tests were calculated to examine differences in CRC stage by rurality and race. Annual percent change and annual average percent change (AAPC) were calculated to examine trends in incidence and mortality rates across rural-urban and racial groups between 1996 and 2016. Areas with high mortality-to-incidence ratios tended to be in rural counties. Furthermore, rural residents had higher proportions of distant stage CRC compared to urban residents, and Black populations had higher proportions of distant stage CRC compared to White populations (22.7% vs. 26.3% and 29.3% vs. 23.7%, respectively; P value < 0.05). From 1996 to 2016, Black and White urban-dwelling residents experienced a significant decline in incidence. Urban White, urban Black, and rural White populations experienced significant declines in mortality (AAPC = -2.6% vs -2.4% vs -1.6% vs -0.9%, respectively). Despite improvements in CRC screening in recent decades, focused evidenced-based interventions for lowering incidence and mortality among rural and Black populations in South Carolina are necessary.


Tracing coco de mer's reproductive history: Pollen and nutrient limitations reduce fecundity.
Habitat degradation can reduce or even prevent the reproduction of previously abundant plant species. To develop appropriate management strategies, we need to understand the reasons for reduced recruitment in degraded ecosystems. The dioecious coco de mer palm (Lodoicea maldivica) produces by far the largest seeds of any plant. It is a keystone species in an ancient palm forest that occurs only on two small islands in the Seychelles, yet contemporary rates of seed production are low, especially in fragmented populations. We developed a method to infer the recent reproductive history of female trees from morphological evidence present on their inflorescences. We then applied this method to investigate the effects of habitat disturbance and soil nutrient conditions on flower and fruit production. The 57 female trees in our sample showed a 19.5-fold variation in flower production among individuals over a seven-year period. Only 77.2% of trees bore developing fruits (or had recently shed fruits), with the number per tree ranging from zero to 43. Flower production was positively correlated with concentrations of available soil nitrogen and potassium and did not differ significantly between closed and degraded habitat. Fruiting success was positively correlated with pollen availability, as measured by numbers and distance of neighboring male trees. Fruit set was lower in degraded habitat than in closed forest, while the proportion of abnormal fruits that failed to develop was higher in degraded habitat. Seed size recorded for a large sample of seeds collected by forest wardens varied widely, with fresh weights ranging from 1 to 18 kg. Synthesis: Shortages of both nutrients and pollen appear to limit seed production of Lodoicea in its natural habitat, with these factors affecting different stages of the reproductive process. Flower production varies widely amongst trees, while seed production is especially low in degraded habitat. The size of seeds is also very variable. We discuss the implications of these findings for managing this ecologically and economically important species.


Disposable biosensor test for organophosphate and carbamate insecticides in milk.
A highly sensitive and rapid biosensor test based on disposable screen-printed thick-film electrodes was developed, which is suitable for monitoring organophosphate and carbamate residues in foods of animal origin with increased fat contents such as milk. The wild-type enzyme was combined with three engineered variants of Nippostrongylus brasiliensis acetylcholinesterase (NbAChE), to obtain enhanced sensitivity. The sample pretreatment could be reduced to a minimum. There was no extraction or fat removal necessary. With the biosensor test paraoxon concentrations down to 1 microg/L could be detected in milk. The detection limit for carbaryl was 20 microg/L. Recovery rates for paraoxon and carbaryl in milk samples lay between 89 and 107%. Ten milk samples from local markets were tested both with the biosensor test and with standard chromatographic multiresidue methods. Two milk samples caused AChE inhibition rates of >50%. Accordingly, 4 microg/L tebufenpyrad, 4 microg/L tetraconazole, and 2 microg/L bifenthrin were detected in one of these milk samples. The other milk sample contained 2 microg/L tebufenpyrad.


Mothers' experience of their contact with their stillborn infant: an interpretative phenomenological analysis.
Guidelines surrounding maternal contact with the stillborn infant have been contradictory over the past thirty years. Most studies have reported that seeing and holding the stillborn baby is associated with fewer anxiety and depressive symptoms among mothers of stillborn babies than not doing so. In contrast, others studies suggest that contact with the stillborn infant can lead to poorer maternal mental health outcomes. There is a lack of research focusing on the maternal experience of this contact. The present study aimed to investigate how mothers describe their experience of spending time with their stillborn baby and how they felt retrospectively about the decision they made to see and hold their baby or not. In depth interviews were conducted with twenty-one mothers three months after stillbirth. All mothers had decided to see and the majority to hold their baby. Qualitative analysis of the interview data was performed using Interpretive Phenomenological Analysis. Six superordinate themes were identified: Characteristics of Contact, Physicality; Emotional Experience; Surreal Experience; Finality; and Decision. Having contact with their stillborn infant provided mothers with time to process what had happened, to build memories, and to 'say goodbye', often sharing the experience with partners and other family members. The majority of mothers felt satisfied with their decision to spend time with their stillborn baby. Several mothers talked about their fear of seeing a damaged or dead body. Some mothers experienced strong disbelief and dissociation during the contact. Results indicate that preparation before contact with the baby, professional support during the contact, and professional follow-up are crucial in order to prevent the development of maternal mental health problems. Fears of seeing a damaged or dead body should be sensitively explored and ways of coping discussed. Even in cases where mothers experienced intense distress during the contact with their stillborn baby, they still described that having had this contact was important and that they had taken the right decision. This indicates a need for giving parents an informed choice by engaging in discussions about the possible benefits and risks of seeing their stillborn baby.


[2-Amino-2-thiazoline derivatives--a novel chemotype possessing muscarinomimetic effect].
Derivatives of 2-amino-2-thiazoline exhibit muscarinomimetic properties in model experiments with isolated rat ileum. The activity of compounds strongly depends on the nature of substituents in 5-position of thiazoline ring. The most active spasmogenic compound is 5-iodomethyl-2-amino-2-thiazoline hydroiodide (EC50 = 13 +/- 2 microM). Its effect is very similar to activity of cholinergic agent pilocarpine (EC50 = 14 +/- 4 microM), but "intrinsic activity" parameter a (alpha = 0.87 +/- 0.12) of 5-iodomethyl-2-amino-2-thiazoline was more significant. Ileum contractions induced by this compounds were inhibited by atropine. Derivatives of 2-amino-2-thiazoline (like pilocarpine) were not demonstrated nicotinomimetic properties. These compounds demonstrate very weak anti-AChE activity. For 5-iodomethyl-2-amino-2-thiazoline hydroiodide the IC50 value is 0.39 +/- 0.09 mM.


Imprinting of Microorganisms for Biosensor Applications.
There is a growing need for selective recognition of microorganisms in complex samples due to the rapidly emerging importance of detecting them in various matrices. Most of the conventional methods used to identify microorganisms are time-consuming, laborious and expensive. In recent years, many efforts have been put forth to develop alternative methods for the detection of microorganisms. These methods include use of various components such as silica nanoparticles, microfluidics, liquid crystals, carbon nanotubes which could be integrated with sensor technology in order to detect microorganisms. In many of these publications antibodies were used as recognition elements by means of specific interactions between the target cell and the binding site of the antibody for the purpose of cell recognition and detection. Even though natural antibodies have high selectivity and sensitivity, they have limited stability and tend to denature in conditions outside the physiological range. Among different approaches, biomimetic materials having superior properties have been used in creating artificial systems. Molecular imprinting is a well suited technique serving the purpose to develop highly selective sensing devices. Molecularly imprinted polymers defined as artificial recognition elements are of growing interest for applications in several sectors of life science involving the investigations on detecting molecules of specific interest. These polymers have attractive properties such as high bio-recognition capability, mechanical and chemical stability, easy preparation and low cost which make them superior over natural recognition reagents. This review summarizes the recent advances in the detection and quantification of microorganisms by emphasizing the molecular imprinting technology and its applications in the development of sensor strategies.


Reflections on integrating theories of adult education into a medical school faculty development course.
The purpose of this study was to test a three-day course model for medical school faculty designed to promote self-directed learning, teaching skills, personal awareness and interdisciplinary collegiality. The training program described was conducted three times in our medical school. Fifty-eight faculty from 11 clinical departments have participated in this intensive experience of learning how to teach, based on principles of learner-centered learning and adult education theory. Participants defined their own learning objectives and worked collaboratively in facilitated small groups to develop teaching skills. Reflection groups engaged in discussion on critical incidents of experience as teachers and learners, and promoted awareness regarding personal approaches to teaching. Qualitative and quantitative data showed that the course was effective in: (1) providing an academically and emotionally safe environment for learning; (2) enabling participants to recognize and value learner-centered learning; (3) increasing participant personal awareness, and (4) promoting interdisciplinary collegiality. End-of-course data assessing the following course attributes, using a five-point scale, where 1 was 'not effective' and 5 was 'very effective', showed: (a) exploration of needs: mean 4.20 +/- SD 0.91; (b) interactive sharing of ideas; mean 4.60 +/- SD 0.58; (c) opportunity to receive feedback: mean 4.26 +/- SD 0.80; (d) opportunity to practice new skills; mean 4.11 +/- SD 0.72. In terms of participation in further faculty development, 92% of participants committed themselves to continue the work begun at the course. It was concluded that the faculty development program created a safe, learner-centered environment for participants that promoted both awareness of and commitment to self-directed learning, and facilitated teaching skill development and interdisciplinary collegiality. Our three-day course appears to be highly effective in initiating a long-term faculty development process. Additionally, we conclude that there is a need for longitudinal follow-up to support and expand mastery of these teaching skills.


What do sequential behavioral patterns suggest about the medical decision-making process?: modeling home case management of acute illnesses in a rural Cameroonian village.
It is well recognized that much of the world's medical care is in the hands of laypeople. In pluralistic medical settings, laypeople choose what to do first, second, third, and fourth from a variety of treatment options. In retrospect, laypeople's choices can be represented as an ordered series of health-related behaviors. A systematic of such sequential data provides insights into caregivers' patterns of resort and suggests a tentative theory for how laypeople make medical choices. This study examines sequences of health-related behaviors from a small, Kom-speaking village in Cameroon. Local residents consider seven health actions, including: delaying initial treatment, using various home remedies or pharmaceuticals, going to a government clinic or a Catholic hospital, and consulting a private nurse or a traditional healer. Researchers visited 88 randomly selected compounds on a weekly basis over a 5-month period. Data were collected on the treatments associated with 429 nonchronic episodes. Analysis of the treatment sequences suggests that residents customarily use delay of treatments as a tactic in the decision-making process. Caregivers were more likely to use home-based treatments and to use them earlier in the treatment sequences than they were to seek treatment from outside the compound. When seeking assistance, caregivers often used traditional healers as a conduit to other outside options. Laypeople used a limited number of unique treatment sequences and avoided the repetition of treatment modalities. Caregivers act as if they were following three basic tenets. They minimize uncertainty by identifying illness types that require particular health actions and by delaying action. They minimize the cost of care by first resorting to treatments that are less expensive and easier to administer or by reducing the number of treatments tried. And laypeople maximize treatment variety in the hopes of finding at least one treatment that helps stop the illness.


Effects of phaclofen and the enantiomers of baclofen on cardiovascular responses to intrathecal administration of L- and D-baclofen in the rat.
In a previous study it was found that i.t. administration of L-baclofen decreased arterial pressure and heart rate while D-baclofen differentially increased arterial pressure. The objective of the present study was to determine which of these effects was blocked by prior administration of the GABAB receptor antagonist, phaclofen, and whether the effect of one enantiomer of baclofen could be blocked by prior administration of the other. The decreases in systolic and diastolic arterial pressures and in heart rate produced by i.t. administration of 70 nmol of L-baclofen were unaffected by i.t. administration of 7, 70 or 700 nmol of D-baclofen 10 min prior to administration of L-baclofen, but were blocked by administration of 5 mumol of phaclofen given 3-5 min prior to L-baclofen. On the other hand, the increases in systolic and diastolic arterial pressures induced by i.t. administration of 700 nmol of D-baclofen were blocked by 70 nmol but not by 7 nmol of L-baclofen, as well as by 2.5 mumol of phaclofen; the effect of L-baclofen cannot be attributed to a desensitization of D-baclofen-sensitive receptors as two successive doses of D-baclofen given 7 min apart had quantitatively similar effects. Phaclofen alone increased systolic and diastolic arterial pressures and heart rate. The results are interpreted as indicating that D-baclofen is not an antagonist of L-baclofen in this paradigm; rather, they suggest that L-baclofen reduces the effects of D-baclofen.(ABSTRACT TRUNCATED AT 250 WORDS)


Evolution of Bystander Intention to Perform Resuscitation Since Last Training: Web-Based Survey.
Victims of out-of-hospital cardiac arrest (OHCA) have higher survival rates and more favorable neurological outcomes when basic life support (BLS) maneuvers are initiated quickly after collapse. Although more than half of OHCAs are witnessed, BLS is infrequently provided, thereby worsening the survival and neurological prognoses of OHCA victims. According to the theory of planned behavior, the probability of executing an action is strongly linked to the intention of performing it. This intention is determined by three distinct dimensions: attitude, subjective normative beliefs, and control beliefs. We hypothesized that there could be a decrease in one or more of these dimensions even shortly after the last BLS training session. The aim of this study was to measure the variation of the three dimensions of the intention to perform resuscitation according to the time elapsed since the last first-aid course. Between January and April 2019, the two largest companies delivering first-aid courses in the region of Geneva, Switzerland sent invitation emails on our behalf to people who had followed a first-aid course between January 2014 and December 2018. Participants were asked to answer a set of 17 psychometric questions based on a 4-point Likert scale ("I don't agree," "I partially agree," "I agree," and "I totally agree") designed to assess the three dimensions of the intention to perform resuscitation. The primary outcome was the difference in each of these dimensions between participants who had followed a first-aid course less than 6 months before taking the questionnaire and those who took the questionnaire more than 6 months and up to 5 years after following such a course. Secondary outcomes were the change in each dimension using cutoffs at 1 year and 2 years, and the change regarding each individual question using cutoffs at 6 months, 1 year, and 2 years. Univariate and multivariable linear regression were used for analyses. A total of 204 surveys (76%) were analyzed. After adjustment, control beliefs was the only dimension that was significantly lower in participants who took the questionnaire more than 6 months after their last BLS course (P<.001). Resisting diffusion of responsibility, a key element of subjective normative beliefs, was also less likely in this group (P=.001). By contrast, members of this group were less afraid of disease transmission (P=.03). However, fear of legal action was higher in this group (P=.02). Control beliefs already show a significant decrease 6 months after the last first-aid course. Short interventions should be designed to restore this dimension to its immediate postcourse state. This could enhance the provision of BLS maneuvers in cases of OHCA.


Diurnal variations and sleep deprivation-induced changes in rat hypothalamic GHRH and somatostatin contents.
Previous reports indicate that hypothalamic growth hormone-releasing hormone (GHRH) promotes sleep and is involved in sleep regulation. The aim of our experiments was to determine whether the GHRH and somatostatin contents of the rat hypothalamus have diurnal variations and whether they are altered by sleep deprivation (SD). Hypothalamic samples were collected at 10 time points during the 24-h light-dark cycle. SD started at light onset. Hypothalamic samples were obtained after 4 and 8 h of SD and after 1 and 2 h of recovery following 8 h of SD. The peptides were determined by means of radioimmunoassay. GHRH displayed significant diurnal variations with low levels in the morning (a transient rise occurred at 1 h after light onset), gradual increases in the afternoon (peak at the end of the light period and beginning of the dark period), and decreases at night. SD induced significant GHRH depletion, which persisted during recovery. The afternoon rise was delayed, and the nocturnal decline of somatostatin was more rapid than the changes in GHRH. Although the patterns of the diurnal variations in GHRH and somatostatin were similar, there was no significant correlation between them. SD did not alter somatostatin significantly. Comparisons of the present results with previously reported changes in hypothalamic GHRH mRNA suggest that periods of deep nonrapid eye movement sleep (first portion of the light period and recovery sleep after SD) are associated with intense hypothalamic GHRH release.


Topographic comparative study of magnetic resonance imaging and electroencephalography in 34 children with tuberous sclerosis.
A series of 34 children with confirmed tuberous sclerosis (TS) were studied prospectively by both EEG and magnetic resonance imaging (MRI) at ages ranging from 5 months to 18 years. Size and topography of the cortical tubers were analyzed on axial and coronal views, in T2 sequences, and the large tubers greater than 10 mm were studied. In addition, EEG follow-up data were reviewed retrospectively. Twenty-six patients (76%) had both MRI large cortical tubers and EEG foci, 3 had normal EEG, 2 had normal MRI, and the remaining 3 had only small tubers. The number of large tubers was significantly related to EEG foci. A topographic MRI/EEG correspondence was observed for at least one tuber in 25 of the 26 patients, and correspondence was complete in 10 patients. Large cortical tubers without corresponding EEG foci were observed in 11 patients; these tubers mainly involved the frontal regions and were found before the patients were 2 years old. EEG foci without corresponding tubers were observed in 4 patients. In addition, secondary bilateral synchrony was preferentially observed in patients with frontal lesions and after the age of 2 years. These data confirm that the cortical tubers are epileptogenic and that their expression may be influenced by regional cortical maturation.


Disproportionate Availability Between Emergency and Elective Hand Coverage: A National Trend?
Traumatic hand injuries represent approximately 20% of emergency department visits; yet, access to emergency care remains inadequate. Recent surveys from several states report a wider availability of hand specialists providing elective care than emergency care. The authors aim to examine this phenomenon in the state of New Jersey and whether there is a national trend toward disproportionate availability between emergency and elective hand coverage. A survey was conducted of all New Jersey hospitals, excepting university hospitals, in August 2014. To assess the availability of hand surgery coverage, the following questions were asked: (1) Does your hospital provide elective hand surgery? and (2) Is there a hand specialist/surgeon on call always, sometimes, or never? A total of 58 hospitals were called, with a 67.2% response rate (n = 39). The majority (87.2%) of hospitals offered elective hand surgery, whereas only 64.1% provided immediate 24/7 hand coverage. Only 38.5% of hospitals located in the same county as a level I trauma center provided 24/7 emergency hand care, whereas 76.9% of hospitals in counties without any level I trauma center did (P < .05). Cities with a higher poverty level were less likely to provide emergency coverage than cities with a lower poverty level (47.4% vs 80.0%; P < .05). There is a discrepancy between emergency and elective hand care in New Jersey. Similar findings across the nation suggest a concerning trend of limited access to emergency hand health care. Alternative systems that can appropriately triage and treat patients are warranted.


Risk factors for obesity in childhood survivors of suprasellar brain tumours: a retrospective study.
To characterize postdiagnosis changes in body mass index (BMI) among childhood survivors of suprasellar brain tumours, and to determine the risk factors associated with obesity. We conducted a retrospective analysis of 46 children (16 boys and 30 girls) with median (IQR) age of 7.49 (3.47-11.59) years at tumour diagnosis, and followed up for 3.93 (1.68-7.27) years. Survival analyses were used to identify risks of developing obesity. There were no sex differences in age at tumour diagnosis, duration of follow-up, tumour types, endocrinopathies, treatment modalities or baseline BMI SDS. In the first year after tumour diagnosis, ΔBMI SDS (median; IQR) was greater in girls (1.32; 0.07-2.08) than in boys (0.48; -0.40 to 0.89) (p = 0.01). At diagnosis, 3/46 children (6%) were obese; this increased to 20/46 (43%) by last follow-up (p < 0.001) and was more common in girls (17/30; 57%) than in boys (3/16; 19%). Female gender (hazard ratio 5.0, 95% CI 1.2-21.7; p = 0.04) and greater than average baseline BMI (hazard ratio 4.7, 95% CI 1.1-20.8; p = 0.02) were risk factors for subsequent obesity. Accurate prediction of obesity risk is important and would allow early targeted intervention in high-risk patients.


DNA Origami-Based Letterpress Printing of Gold Nanostructures with Predesigned Morphologies.
Creating customizable metallic nanostructures in a simple and controllable manner has been a long-standing goal in nanoscience. In this study, we use DNA origami as a letterpress printing plate and gold nanoparticles as ink to produce predesigned gold nanostructures. The letterpress plate is reusable, enabling the repetitive production of predesigned gold nanostructures. Furthermore, by modifying the DNA origami letterpress plate on magnetic beads, we can simplify the printing processes. We have successfully printed gold nanoparticle dimers, trimers, straight and quadrilateral tetramers, and other nanostructures. Our approach improves the flexibility and stability of metallic nanostructures, simplifying both their design and their operation. It promises universal applicability in the fabrication of metamaterials, biosensors, and surface plasma nanooptics.


Nutrition and lysosomal activity. The influence of vitamin E deficiency and its duration on the stability of lysosomes in the kidneys of rats.
1. Experiments on rats were made to find whether the increased liability of the kidney-cortex tubules to autolysis post mortem, which is a well-established abnormality in vitamin E deficiency, can be correlated with changes in lysosomal activity. Parallel observations were made on the development of certain other abnormalities characteristic of avitaminosis E. 2. In rats killed after long periods (8-10 months) of subsistence on a standard vitamin E-deficient diet, containing lard, both the rate of kidney autolysis post mortem and the enzyme activity of lysosome preparations from the fresh tissues were much greater than in controls. A greater percentage difference was usually found in the ;free' enzyme fraction than in ;bound' or ;total' activity. 3. In rats killed after graded periods (3-8 months) of deficiency, two abnormalities (decreased resistance of the erythrocytes to haemolysis, and brown discoloration of the uterus) were already evident at a stage (3-4 months) when the liability to rapid kidney autolysis had not begun. At this point the enzymic activity of kidney extracts differed little between deficient animals and controls given alpha-tocopherol. As the duration of deficiency advanced, parallel increases occurred in the rate of kidney autolysis and in lysosomal instability. 4. When cod-liver oil, rich in polyunsaturated fatty acids but freed from vitamin A, was substituted for lard in the diet, the time (1(1/2) months) required for the inducement of both rapid kidney autolysis and decreased lysosomal stability was greatly shortened. The time for the inducement of brown discoloration of the uterus was not shortened and the kidney abnormalities appeared while the uterus was still normal. 5. Confirmation was thus obtained for the view that the various tissues of the rat respond differently to the relationship between the adequacy of the vitamin E status and the intake of polyunsaturated fatty acids. The kidney-cortex tubules, as evidenced by autolysis post mortem and the corresponding decrease in lysosomal stability, may be classed among those tissues that are most sensitive to the effect of high intakes of polyunsaturated acids.


Male prostitution in the twentieth century: pseudohomosexuals, hoodlum homosexuals, and exploited teens.
Male prostitution altered its form dramatically over the course of the twentieth century. While some of these changes relate to economics and general cultural shifts (the Depression of the 1930s, the rise of a counterculture during the 1960s and 70s), some of the most important changes have arisen in response to transformations in the idea of "homosexuality," and the growing influence this idea had within middle-class and then working-class culture. This essay identifies the diverse forms male prostitution has taken since the late-Victorian period, and also examines the way in which male prostitution has been written about by various commentators in different eras.


Effects of a cardiac rehabilitation programme on plasma cardiac biomarkers in patients with chronic heart failure.
Background Cardiac rehabilitation (CR) improves the symptoms, exercise capacity and quality of life of chronic heart failure (CHF) patients. Its effects on new plasma biomarkers of prognostic importance are unknown. The present study aimed at analysing the effects of a structured CR programme on plasma cardiac biomarkers in a large population of patients with CHF and reduced left ventricular ejection fraction (LVEF). Methods We enrolled 107 consecutive CHF patients with LVEF ≤ 45% in an ambulatory CR programme. Peak VO2 and plasma levels of Galectin-3, mid-regional proANP (MR-proADM), soluble suppressor of tumorigenicity 2 (sST2) and mid-regional pro-adrenomedullin (MR-proANP) were assessed at inclusion and at the end of CR. Twenty-four unenrolled patients were managed with standard medical care and evaluated over the same period (no-CR group). Results Galectin-3, sST2, MR-proADM and MR-proANP plasma levels decreased after CR, with respective median reductions of 6.3% for Galectin 3 ( p < 0.001), 7.4% for sST2 ( p = 0.036), 6.4% for MR-proADM ( p = 0.001) and 16% for MR-proANP ( p < 0.001). MR-proADM was negatively correlated with peak VO2 (ρ = -0.529, 95% confidence interval [CI] -0.654 to -0.375, p < 0.001), and so were their relative variations along the course of CR (ρ = -0.357, 95% CI -0.518 to -0.172, p < 0.001). No change occurred in terms of biomarkers in the no-CR group. Conclusions Plasma cardiac biomarkers such as Galectin-3, MR-proADM, sST2 and MR-proANP all decreased after CR in CHF patients, suggesting an overall improvement in the neuro-hormonal profile.


Clinical outcomes of sinonasal inverted papilloma surgery. A retrospective study of 67 cases.
Endoscopic sinus surgery has become popular for the management of sinonasal inverted papillomas (IP). The purpose of this report is to review our 13 years of experience in managing IPs. Retrospective chart study. Sixty-seven patients with sinonasal IPs were treated in our department from 1991 to 2004. Seventeen were managed using an endonasal non-endoscopic approach, 39 endoscopically, 8 through external techniques, and the remaining 3 using a combined approach. After 1994, as we gained experience using endoscopic sinus surgery, most cases were treated endoscopically. In only 3 cases, where the tumour attachment site was in the lateral / anterior wall of the maxillary sinus and in the lateral wall of the frontal sinus, could the lesions not be accessed by extended endoscopic techniques, and an appropriate combination with external methods was required. The mean follow up period was 91 (range, 36-146) months. The recurrence rate was 59% using an endonasal non-endoscopic approach, 12.5% using an external incision, and 12.8% using endoscopic techniques. Average time to recurrence was 15 months. Our findings suggest that endoscopic sinus surgery for sinonasal IP is a viable approach, with a low rate of recurrence and minor morbidity. Complete tumour resection at the site of attachment, including a surrounding rim of normal mucosa and drilling the underlying bone, is the key to successful treatment when it is combined with the preservation of healthy tissue. Non-endoscopic endonasal surgery is no longer a treatment option because the recurrence rate is too high.


Sex workers working within a legalised industry: their side of the story.
To examine the characteristics and work attitudes of female sex workers working in licensed brothels in Victoria, Australia. This was a cross-sectional study of sex workers working at 38 of the 92 licensed brothels operating in Victoria during 2006. Of the 108 women approached, 97 (90%) completed the questionnaire. Women working in the legal sex industry in Victoria were generally aged between 23 and 35 years (51%), had completed high school (26%) and had worked in the industry for more than 5 years (43%). Half had dependent children and one third were in a relationship. Women's primary motivation for working in the sex industry was financial, whether this was the reason for their starting (56%), or the barrier to their leaving (61%). Although women valued the higher income and flexibility of this work, many were concerned about sexually transmitted infections (STI) (55%), community attitudes towards the industry (47%), their physical safety (38%) and maintaining their anonymity (37%). Over half of the women would like to leave the industry. The majority (95%) supported the monthly STI checks that are part of the Victorian regulations, with only one fifth reporting that the cost of these tests was prohibitive. The findings of this study indicate that women working in licensed Victorian brothels come from a diverse range of backgrounds and circumstances and hold varying attitudes towards working in the sex industry. It is hoped that these findings go some way to redressing the assumptions commonly made about women working in the sex industry and reducing the stigma associated with this occupation.


Standardization and monitoring of laboratory performance and quality assurance by use of the less-sensitive HIV incidence assay: seven years of results.
The Performance Evaluation Program for HIV-1 incidence tests provided quality assurance services to laboratories conducting the serological testing algorithm for recent HIV seroconversion by use of a modified less-sensitive version of the Vironostika HIV-1 MicroElisa System assay. We report on the performance of the assay using proficiency testing and quality control materials tested from 2001 to 2008. Two sets of 5 blinded serum panels using common calibration and quality control materials were tested. The mean, standard deviation, and coefficient of variation were calculated. Results were analyzed for misclassifications: false recent HIV infection errors (long-term infection classified as HIV infection less than 1 year), false long-term infection errors (HIV infection less than 1 year classified as long-term infection), and differences in standardized optical density means and variances over time. The false recent error rate was 1.26% (n = 2219). The false long-term error rate was 0.25% (n = 1618). No significant trends were observed for misclassification rates by year, and no significant trend in the standardized optical density over 7 years was observed. Laboratories using the less-sensitive Vironostika HIV-1 assay produced consistent results by use of a common calibrator and quality control materials.


HPV-associated oral warts.
Human papillomavirus (HPV) is strictly epitheliotropic, infecting stratified squamous cutaneous and mucosal epithelial cells. Oral HPV infection may be subclinical or putatively associated with benign or malignant oral neoplasms. The benign HPV-associated oral lesions, focal epithelial hyperplasia (Heck disease), oral squamous cell papilloma, oral verruca vulgaris (common wart) and oral condyloma acuminatum, are collectively referred to as oral warts. Oral warts are usually asymptomatic, may be persistent or uncommonly, may regress spontaneously. HPV-associated oral warts have a prevalence of 0.5% in the general population, occur in up to 5% of HIV-seropositive subjects, and in up to 23% of HIV-seropositive subjects on highly active antiretroviral therapy. This paper is a clinico-pathological review of HPV-associated oral warts.


Hindbrain effects of PACAP on gastric motor function in the rat.
Pituitary adenylate cyclase-activating polypeptide (PACAP)-like immunoreactive cell bodies and fibers are visualized in hindbrain nuclei that are involved in the regulation of autonomic function, yet little is known about the gastric and cardiovascular effects of this peptide in the dorsal vagal complex, nucleus raphe obscurus, and nucleus ambiguus. Therefore, multiple-barreled micropipettes were used to inject PACAP-38 (1-100 pmol) into each of these nuclei in alpha-chloralose anesthetized rats, while intragastric pressure, pyloric and greater curvature smooth muscle contractile activity, blood pressure, and heart rate were recorded. For comparison, the effect of L-glutamate (15 nmol) microinjected into the same sites on gastric motor activity was also assessed. L-Glutamate microinjected into each nucleus before PACAP-38 significantly increased intragastric pressure, both in terms of the peak increase and the total area of the response. Microinjections of PACAP-38 (10 and 100 pmol) into each of the nuclei significantly increased peak intragastric pressure, but the total area of the response was only significantly increased by the highest dose (100 pmol) in the case of the dorsal vagal complex and nucleus raphe obscurus. No consistent changes in heart rate and mean arterial blood pressure were noted after microinjection of PACAP-38 into each of the three nuclei. Bilateral vagotomy abolished the increase in intragastric pressure in response to microinjection of PACAP-38 into the dorsal vagal complex and nucleus raphe obscurus. We conclude that PACAP-38 in the dorsal vagal complex and nucleus raphe obscurus is involved in vagally mediated gastric motor excitation.


Lesbians' and gay men's narratives about attitudes in nursing.
Many nurses find it difficult to show compassion and sensitivity, and to give gay patients nursing of a quality equal to that given to heterosexual patients. The aim of the present study was to describe the experiences of gay patients and partners concerning attitudes in nursing. The method included qualitative semi-structured interviews with 17 women and 10 men, from different parts of Sweden. Nearly all informants described a sense of insecurity in 'coming out' to nursing staff. Most patients described being met by the nursing staff in a respectful manner, but sometimes they perceived a kind of distancing in the personnel's behaviour. Informants related that nursing staff judged homosexuality as something abnormal. Informants thought that, as partners, they always felt like outsiders, but these were emotions they believed all relatives experienced irrespective of sexual orientation. However, some partners associated negative attitudes of nursing staff with homosexuality. The informants believed that the insecure feelings affected their ability to interact. The majority of informants stated that they found most of the nursing staff kind and caring, but that there were differences and that the goal should be - for all patients and relatives - equality in nursing care.


Fibrocystin/polyductin modulates renal tubular formation by regulating polycystin-2 expression and function.
Autosomal recessive polycystic kidney disease is caused by mutations in PKHD1, which encodes the membrane-associated receptor-like protein fibrocystin/polyductin (FPC). FPC associates with the primary cilia of epithelial cells and co-localizes with the Pkd2 gene product polycystin-2 (PC2), suggesting that these two proteins may function in a common molecular pathway. For investigation of this, a mouse model with a gene-targeted mutation in Pkhd1 that recapitulates phenotypic characteristics of human autosomal recessive polycystic kidney disease was produced. The absence of FPC is associated with aberrant ciliogenesis in the kidneys of Pkhd1-deficient mice. It was found that the COOH-terminus of FPC and the NH2-terminus of PC2 interact and that lack of FPC reduced PC2 expression but not vice versa, suggesting that PC2 may function immediately downstream of FPC in vivo. PC2-channel activities were dysregulated in cultured renal epithelial cells derived from Pkhd1 mutant mice, further supporting that both cystoproteins function in a common pathway. In addition, mice with mutations in both Pkhd1 and Pkd2 had a more severe renal cystic phenotype than mice with single mutations, suggesting that FPC acts as a genetic modifier for disease severity in autosomal dominant polycystic kidney disease that results from Pkd2 mutations. It is concluded that a functional and molecular interaction exists between FPC and PC2 in vivo.


Tuberculosis transmission across the United States-Mexico border.
In this era of increasing drug resistance among infectious diseases such as tuberculosis (TB), the complex population dynamics of border areas must be monitored more extensively. TB remains a major public health threat; its antimicrobial treatment is long; and the only vaccine licensed in the world, live-attenuated Mycobacterium bovis Bacille Calmette-Guérin (BCG), exhibits varying efficacy. In addition to epidemiological surveillance, the underlying determinants contributing to the health and wellbeing of populations are of key importance. Although it received heightened attention in the past, tuberculosis transmission in the United States-Mexico border area demands renewed interest. Lessons learned should be applied to similar areas around the globe.


Long genes linked to autism spectrum disorders harbor broad enhancer-like chromatin domains.
Genetic variants associated with autism spectrum disorders (ASDs) are enriched in genes encoding synaptic proteins and chromatin regulators. Although the role of synaptic proteins in ASDs is widely studied, the mechanism by which chromatin regulators contribute to ASD risk remains poorly understood. Upon profiling and analyzing the transcriptional and epigenomic features of genes expressed in the cortex, we uncovered a unique set of long genes that contain broad enhancer-like chromatin domains (BELDs) spanning across their entire gene bodies. Analyses of these BELD genes show that they are highly transcribed with frequent RNA polymerase II (Pol II) initiation and low Pol II pausing, and they exhibit frequent chromatin-chromatin interactions within their gene bodies. These BELD features are conserved from rodents to humans, are enriched in genes involved in synaptic function, and appear post-natally concomitant with synapse development. Importantly, we find that BELD genes are highly implicated in neurodevelopmental disorders, particularly ASDs, and that their expression is preferentially down-regulated in individuals with idiopathic autism. Finally, we find that the transcription of BELD genes is particularly sensitive to alternations in ASD-associated chromatin regulators. These findings suggest that the epigenomic regulation of BELD genes is important for post-natal cortical development and lend support to a model by which mutations in chromatin regulators causally contribute to ASDs by preferentially impairing BELD gene transcription.


Diet-induced obesity reduces the production of influenza vaccine-induced antibodies via impaired macrophage function.
Obesity is a metabolic disease characterized by low-level chronic inflammation. Obese individuals are susceptible to infection by viruses, and vaccination against these pathogens is less effective than in nonobese individuals. Here, we sought to explore the immunological environment in a mouse model of obesity induced by a high-fat diet (HFD). HFD treatment increased the body weight and epididymal fat mass. The proportion of activated B cells, T cells, and macrophages was similar between mice in the HFD group and the regular-fat diet (RFD) group. The Th1 cell subpopulation in the HFD group was increased, whereas the proportion of Treg cells was reduced compared with the RFD group. Moreover, T-cell proliferation and cytokine production did not differ between the groups when cells were stimulated with anti-CD3 and anti-CD28 antibodies in vitro. In macrophages, phagocytic activity was higher in mice fed an HFD than in those fed an RFD, but expression levels of CD86 and MHC class II antigens were similar. When macrophages were cultured in vitro, the proportion of CD86-expressing macrophages was lower in those isolated from mice in the HFD group than in those isolated from the RFD group. Furthermore, lipopolysaccharide-induced interleukin 6 (IL-6) and tumor necrosis factor alpha secretions were significantly reduced in macrophages isolated from the HFD group. In addition, influenza vaccine-induced antibodies in the HFD group diminished more rapidly than in the RFD group. These results suggest that poor functionality of macrophages during obesity might contribute to a reduction in vaccine efficacy.


Accumulation of α-Synuclein in Cerebellar Purkinje Cells of Diabetic Rats and Its Potential Relationship with Inflammation and Oxidative Stress Markers.
Objective. The present study was conducted to evaluate the relationship between plasma oxidative stress markers such as malondialdehyde (MDA) and glutathione (GSH), inflammatory marker pentraxin-3 (PTX3), and cerebellar accumulation of α-synuclein in streptozotocin- (STZ-) induced diabetes model in rats. Methods. Twelve rats were included in the study. Diabetes (n = 6) was induced with a single intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). Diabetes was verified after 48 h by measuring blood glucose levels. Six rats served as controls. Following 8 weeks, rats were sacrificed for biochemical and immunohistochemical evaluation. Results. Plasma MDA levels were significantly higher in diabetic rats when compared with the control rats (p < 0.01), while plasma GSH levels were lower in the diabetic group than in the control group (p < 0.01). Also, plasma pentraxin-3 levels were statistically higher in diabetic rats than in the control rats (p < 0.01). The analysis of cerebellar α-synuclein immunohistochemistry showed a significant increase in α-synuclein immunoexpression in the diabetic group compared to the control group (p < 0.01). Conclusion. Due to increased inflammation and oxidative stress in the chronic period of hyperglycemia linked to diabetes, there may be α-synuclein accumulation in the cerebellum and the plasma PTX3 levels may be assessed as an important biomarker of this situation.


Interference of the blood clot on granulation tissue formation after tooth extraction. Histomorphological study in rats.
The interference of a blood clot in the first postoperative hours of dental extraction wounds was studied in rats. Sixty male albino rats were divided into two groups: Group I, immediately after extraction of right maxillary incisor the gingival mucosa was approximated and sutured; Group II, after 6 to 8 minutes postoperatively the blood clot was removed with saline irrigation and absorbent paper cones. The mucosa was then approximated and sutured. Six animals in each group were sacrificed after 12 hours, 1, 4, 7 and 10 days. There was a profound delay in healing in Group II since, although a new blood clot was later formed, it was not organized. The quality and the constitution, maintenance and retraction of the clot are the regulating factors in connective tissue formation during alveolar healing.


Ten year neurocognitive trajectories in first-episode psychosis.
Neurocognitive impairment is commonly reported at onset of psychotic disorders. However, the long-term neurocognitive course remains largely uninvestigated in first episode psychosis (FEP) and the relationship to clinically significant subgroups even more so. We report 10 year longitudinal neurocognitive development in a sample of FEP patients, and explore whether the trajectories of cognitive course are related to presence of relapse to psychosis, especially within the first year, with a focus on the course of verbal memory. Forty-three FEP subjects (51% male, 28 ± 9 years) were followed-up neurocognitively over five assessments spanning 10 years. The test battery was divided into four neurocognitive indices; Executive Function, Verbal Learning, Motor Speed, and Verbal Fluency. The sample was grouped into those relapsing or not within the first, second and fifth year. The four neurocognitive indices showed overall stability over the 10 year period. Significant relapse by index interactions were found for all indices except Executive Function. Follow-up analyses identified a larger significant decrease over time for the encoding measure within Verbal Memory for patients with psychotic relapse in the first year [F (4, 38) = 5.8, p = 0.001, η(2) = 0.40]. Main findings are long-term stability in neurocognitive functioning in FEP patients, with the exception of verbal memory in patients with psychotic relapse or non-remission early in the course of illness. We conclude that worsening of specific parts of cognitive function may be expected for patients with on-going psychosis, but that the majority of patients do not show significant change in cognitive performance during the first 10 years after being diagnosed.


TRIM24 links a non-canonical histone signature to breast cancer.
Recognition of modified histone species by distinct structural domains within 'reader' proteins plays a critical role in the regulation of gene expression. Readers that simultaneously recognize histones with multiple marks allow transduction of complex chromatin modification patterns into specific biological outcomes. Here we report that chromatin regulator tripartite motif-containing 24 (TRIM24) functions in humans as a reader of dual histone marks by means of tandem plant homeodomain (PHD) and bromodomain (Bromo) regions. The three-dimensional structure of the PHD-Bromo region of TRIM24 revealed a single functional unit for combinatorial recognition of unmodified H3K4 (that is, histone H3 unmodified at lysine 4, H3K4me0) and acetylated H3K23 (histone H3 acetylated at lysine 23, H3K23ac) within the same histone tail. TRIM24 binds chromatin and oestrogen receptor to activate oestrogen-dependent genes associated with cellular proliferation and tumour development. Aberrant expression of TRIM24 negatively correlates with survival of breast cancer patients. The PHD-Bromo of TRIM24 provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis.


Epigenome-Wide Analyses Identify Two Novel Associations With Recurrent Stroke in the Vitamin Intervention for Stroke Prevention Clinical Trial.
DNA methylation, a well-characterized epigenetic modification that is influenced by both environment and genetic variation, has previously been implicated in a number of complex diseases, including cardiovascular disease and stroke. The goal of this study was to evaluate epigenome-wide associations with recurrent stroke and the folate one-carbon metabolism-related trait, plasma homocysteine (hcy). Differential methylation analyses were performed on 473,864 autosomal CpG loci, using Illumina HumanMethylation 450K array data in 180 ischemic stroke cases from the Vitamin Intervention for Stroke Prevention (VISP) clinical trial. Linear regression was used to assess associations between number of strokes prior to VISP enrollment and measures of hcy with degree of methylation (β-values), while logistic regression was used to evaluate recurrent stroke status and incident recurrent stroke associations. All regression analyses were stratified by race. Two differentially methylated CpG sites exceeded epigenome-wide significance (p ≤ 1.055 × 10-7) for prior number of strokes (PNS) in European Americans. The top locus, cg22812874, was located in the ankyrin repeat and SOCS box containing 10 gene (ASB10; p = 3.4 × 10-9; β = -0.0308; 95% CI = -0.040, -0.002). Methylation locus cg00340919, located in an intron of the tetratricopeptide repeat domain 37 gene, was also statistically significant (TTC37; p = 8.74 × 10-8; β = -0.0517; 95% CI = -0.069, -0.034). An additional 138 CpG sites met our threshold for suggestive significance (p ≤ 5 × 10-5). We evaluated DNA methylation associated with recurrent stroke and hcy phenotypes across the epigenome. Hypermethylation at two CpG sites located in ASB10 and TTC37 was associated with fewer strokes prior to VISP enrollment. Our findings present a foundation for additional epigenome-wide studies, as well as mechanistic studies into epigenetic marks that influence recurrent stroke risk.


Periosteum responds to dynamic fluid pressure by proliferating in vitro.
Periosteum provides a source of undifferentiated chondrocyte precursor cells for fracture healing that can also be used for cartilage repair. The quantity of cartilage that can be produced, which is a determining factor in fracture healing and cartilage repair, is related to the number of available stem cells in the cambium layer. Cartilage formation during both of these processes is enhanced by motion of the fracture or joint in which periosteum has been transplanted. The effect of dynamic fluid pressure on cell proliferation in periosteal tissue cultures was determined in 452 explants from 60 immature (2-month-old) New Zealand White rabbits. The explants were cultured in agarose suspension for 1-14 days. One group was subjected to cyclic hydrostatic pressure, which is referred to as dynamic fluid pressure, at 13 kPa and a frequency of 0.3 Hz. Control explants were cultured in similar chambers without application of pressure. DNA synthesis ([3H]thymidine uptake) and total DNA were measured. The temporal pattern and distribution of cell proliferation in periosteum were evaluated with autoradiography and immunostaining with proliferating cell nuclear antigen. Dynamic fluid pressure increased proliferation of periosteal cells significantly, as indicated by a significant increase in [3H]thymidine uptake at all time points and a higher amount of total DNA compared with control values. On day 3, when DNA synthesis reached a peak in periosteal explants, [3H]thymidine uptake was 97,000+/-5,700 dpm/microg DNA in the group exposed to dynamic fluid pressure and 46,000+/-6,000 dpm/microg in the controls (p < 0.001). Aphidicolin, which blocks DNA polymerase alpha, inhibited [3H]thymidine uptake in a dose-dependent manner in the group subjected to dynamic fluid pressure as well as in the positive control (treated with 10 ng/ml of transforming growth factor-beta1) and negative control (no added growth factors) groups, confirming that [3H]thymidine measurements represent proliferation and dynamic fluid pressure stimulates DNA synthesis. Total DNA was also significantly higher in the group exposed to dynamic fluid pressure (5,700+/-720 ng/mg wet weight) than in the controls (3,700+/-630) on day 3 (p < 0.01). Autoradiographs with [3H]thymidine revealed that one or two cell cycles of proliferation took place in the fibrous layer prior to proliferation in the cambium layer (where chondrocyte precursors reside). Proliferating cell nuclear antigen immunophotomicrographs confirmed the increased proliferative activity due to dynamic fluid pressure. These findings suggest either a paracrine signaling mechanism between the cells in these two layers of the periosteum or recruitment/migration of proliferating cells from the fibrous to the cambium layer. On the basis of the data presented in this study, we postulate that cells in the fibrous layer respond initially to mechanical stimulation by releasing growth factors that induce undifferentiated cells in the cambium layer to divide and differentiate into chondrocytes. These data indicate that cell proliferation in the early stages of chondrogenesis is stimulated by mechanical factors. These findings are important because they provide a possible explanation for the increase in cartilage repair tissue seen in joints subjected to continuous passive motion. The model of in vitro periosteal chondrogenesis under dynamic fluid pressure is valuable for studying the mechanisms by which mechanical factors might be involved in the formation of cartilage in the early fracture callus and during cartilage repair.