Comparing The Effects of Glycyrrhiza glabra Root Extract, A Cyclooxygenase-2 Inhibitor (Celecoxib) and A Gonadotropin-Releasing Hormone Analog (Diphereline) in A Rat Model of Endometriosis.
The purpose of this study was to compare the effects of Glycyrrhiza glabra (Licorice), a cyclooxygenase- 2 inhibitor (Celecoxib) and a gonadotropin-releasing hormone analog (Diphereline®), with a control group on endometrial implants in rats. In this experimental study, endometriosis was induced in rats by auto transplantation and after confirmation, the rats were divided into 4 groups that were treated for 6 weeks with normal saline (0.5 ml/day, orally), licorice extract (3000 mg/kg/day, orally), celecoxib (50 mg/kg, twice a day, orally) or diphereline (3 mg/kg, intramuscularly). At the end of treatments, the mean area, volume, histopathology and hemosiderin-laden macrophage (HLM) counts of the endometrial implants were evaluated and compared among the four groups. The mean area, volume and HLM counts of the implants in the licorice group were significantly lower than those of the control group (P<0.001). The histopathologic grades of endometrial implants were significantly decreased by licorice compared to the control group (P<0.001). There was no significant change in the mentioned parameters in rats treated with celecoxib compared to the control group. Diphereline was the most potent agent for suppressing the growth of endometrial implants in terms of all of the above-mentioned parameters. Licorice decreased the growth and histopathologic grades of auto-transplanted endometrial implants. However, while celcoxib had no significant effect, diphereline showed the highest potency for decreasing the endometrial growth. Licorice may have the potential to be used as an alternative medication for the treatment of endometriosis.


Cross-modal working memory binding and word recognition skills: how specific is the link?
Recent research has suggested that the creation of temporary bound representations of information from different sources within working memory uniquely relates to word recognition abilities in school-age children. However, it is unclear to what extent this link is attributable specifically to the binding ability for cross-modal information. This study examined the performance of Grade 3 (8-9 years old) children on binding tasks requiring either temporary association formation of two visual items (i.e., within-modal binding) or pairs of visually presented abstract shapes and auditorily presented nonwords (i.e., cross-modal binding). Children's word recognition skills were related to performance on the cross-modal binding task but not on the within-modal binding task. Further regression models showed that cross-modal binding memory was a significant predictor of word recognition when memory for its constituent elements, general abilities, and crucially, within-modal binding memory were taken into account. These findings may suggest a specific link between the ability to bind information across modalities within working memory and word recognition skills.


Spreading depression sends microglia on Lévy flights.
Spreading depression (SD) is thought to cause migraine aura, and perhaps migraine, and includes a transient loss of synaptic activity preceded and followed by increased neuronal excitability. Activated microglia influence neuronal activity and play an important role in homeostatic synaptic scaling via release of cytokines. Furthermore, enhanced neuronal function activates microglia to not only secrete cytokines but also to increase the motility of their branches, with somata remaining stationary. While SD also increases the release of cytokines from microglia, the effects on microglial movement from its synaptic activity fluctuations are unknown. Accordingly, we used time-lapse imaging of rat hippocampal slice cultures to probe for microglial movement associated with SD. We observed that in uninjured brain whole microglial cells moved. The movements were well described by the type of Lévy flight known to be associated with an optimal search pattern. Hours after SD, when synaptic activity rose, microglial cell movement was significantly increased. To test how synaptic activity influenced microglial movement, we enhanced neuronal activity with chemical long-term potentiation or LPS and abolished it with TTX. We found that microglial movement was significantly decreased by enhanced neuronal activity and significantly increased by activity blockade. Finally, application of glutamate and ATP to mimic restoration of synaptic activity in the presence of TTX stopped microglial movement that was otherwise seen with TTX. Thus, synaptic activity retains microglial cells in place and an absence of synaptic activity sends them off to influence wider expanses of brain. Perhaps increased microglial movements after SD are a long-lasting, and thus maladaptive, response in which these cells increase neuronal activity via contact or paracrine signaling, which results in increased susceptibility of larger brain areas to SD. If true, then targeting mechanisms that retard activity-dependent microglial Lévy flights may be a novel means to reduce susceptibility to migraine.


[The identity of the community healthcare agent: a phenomenological approach].
The structure of Brazil's National Health System (SUS) is being firmed up through programs adding a new element to its multi-professional healthcare teams: Community Healthcare Agents. This study examines psycho-social factors that are significant for the construction of this identity, from the standpoint of these Community Healthcare Agents, using the hermeneutic phenomenology of Paul Ricoeur as its reference methodology. The subjects of this survey were seven Community Healthcare Agents who were asked during interviews (with informed consent and after approval by the Research Ethics Committee) to: 'Tell me about your experience as Community Healthcare Agent'. The analysis of their replies indicated the following topics: previous experience; capacity-building for the job; bonding; building up expertise; gratifying experience; feelings of power(lessness); communications; daily work routines, personal growth; criticisms of the institution; user-agent experiences; and insertion into the social reality. The overall analysis disclosed the phenomenon through the convergence and divergence of the grouping of these topics, viewed from the standpoint of these Community Healthcare Agents and the psycho-social aspects constructing their identity.


A method for the quantitative determination of glycerophospholipid regioisomers by UPLC-ESI-MS/MS.
Diacyl glycerophospholipids (GPs) belong to the most abundant lipid species in living organisms and consist of a glycerol backbone with fatty acyl groups in sn-1 and sn-2 and a polar head group in the sn-3 position. Regioisomeric mixed diacyl GPs have the same fatty acyl composition but differ in their allocation to sn-1 or sn-2 of the glycerol unit. In-depth analysis of regioisomeric mixed diacyl GP species composed of fatty acyl moieties that are similar in length and degree of saturation typically requires either chemical derivatization or sophisticated analytical instrumentation, since these types of regioisomers are not well resolved under standard ultra-performance liquid chromatography (UPLC) conditions. Here, we introduce a simple and fast method for diacyl GP regioisomer analysis employing UPLC tandem mass spectrometry (MS/MS). This GP regioisomer analysis is based both on minor chromatographic retention time shifts and on major differences in relative abundances of the two fatty acyl anion fragments observed in MS/MS. To monitor these differences with optimal precision, MS/MS spectra are recorded continuously over the UPLC elution profile of the lipid species of interest. Quantification of relative abundances of the regioisomers was performed by algorithms that we have developed for this purpose. The method was applied to commercially available mixed diacyl GP standards and to total lipid extracts of Escherichia coli (E. coli) and bovine liver. To validate our results, we determined regioisomeric ratios of phosphatidylcholine (PC) standards using phospholipase A2-specific release of fatty acids from the sn-2 position of the glycerol backbone. Our results show that most analyzed mixed diacyl GPs of biological origin exhibit significantly higher regioisomeric purity than synthetic lipid standards. In summary, this method can be implemented in routine LC-MS/MS-based lipidomics workflows without the necessity for additional chemical additives, derivatizations, or instrumentation.


Interaction of cardiac troponin C with calmodulin antagonist [corrected] W7 in the presence of three functional regions of cardiac troponin I.
W7 is a well-known calmodulin (CaM) antagonist and has been implicated as an inhibitor of the troponin C-mediated Ca(2+) activation of cardiac muscle contraction. In this study, we use NMR spectroscopy to study binding of W7 to cardiac troponin C (cTnC) free or in complex with cardiac troponin I (cTnI) peptides. Titration of cTnC.3Ca(2+) with W7 shows that residues throughout the sequence, including the N- and C-domains of cTnC and the central linker, are affected. Analysis of the binding stoichiometry and the trajectories of chemical shift changes indicate that W7 binding occurs at multiple sites. To address the issue of whether multiple-site binding is relevant within the troponin complex, W7 is titrated to a cTnC-cTnI complex (cTnC.3Ca(2+).cTnI(34)(-)(71).cTnI(128)(-)(163)). In the presence of the N-terminal (residues approximately 34-71), inhibitory (residues approximately 128-147), and switch (residues approximately 147-163) regions of cTnI, W7 induces chemical shift changes only in the N-domain and not in the C-domain or the central linker of cTnC. The results indicate that in the presence of cTnI, W7 no longer binds to multiple sites of cTnC but instead binds specifically to the N-domain, and the binding (K(D) = 0.5 +/- 0.1 mM) can occur together with the switch region of cTnI. Hence, W7 may play a role in directly modulating the Ca(2+) sensitivity of the regulatory domain of cTnC and the interaction of the switch region of cTnI and cTnC.


Effect of breast-feeding on the development of atopic dermatitis.
Atopy can be defined as the genetically determined risk to develop allergic disease. Avoidance of one specific allergen may decrease the risk for sensitization against this allergen, but it will not affect atopy. Our aim was to investigate if exclusive breast-feeding is associated with atopic dermatitis during the first 5 years of life. Data on 200 children were taken from parental-administered questionnaires from a case control study in Birjand - Iran (recruited 2003) comprised of a case (100 children with atopic dermatitis) and a control (100 normal children) subgroup. Outcomes were physician-diagnosed atopic dermatitis (AD) and itchy rash. Data were analyzed by using SPSS package, Chi square and Exact Fisher tests.Thirty-four of the case and 50 of control group were exclusively breast-fed, whereas 6 of the case and 2 of control group were exclusively cow milk-fed. These differences were statistically significant. (P less than 0.05). Duration of breast-feeding in case and control group was different. These differences were statistically significant (P less than 0.001). Duration of cow's milk formula feeding in case and control group was different, but these differences were not statistically significant. (P=0.6) Positive family history of allergy in case and control group was 63% and 23% respectively and this difference was statistically significant (P less than 0.001). These findings support the hypothesis that exclusive breast-feeding is a protective factor for development of atopic dermatitis if compared with conventional cow's milk formula.


Effects of inulin and oligofructose on the rheological characteristics and probiotic culture survival in low-fat probiotic ice cream.
The effects of supplementation of oligofructose or inulin on the rheological characteristics and survival of Lactobacillus acidophilus La-5 and Bifidobacterium animalis Bb-12 in low-fat ice cream stored at -18 degrees C for 90 d were studied. Addition of oligofructose or inulin to ice cream mix significantly increased apparent viscosity and overrun and developed the melting properties in ice cream during storage (P < 0.05). However, the highest increase in firmness, the lowest change in melting properties, and the longest 1st dripping time were obtained in probiotic ice cream containing inulin (P < 0.05). Some textural properties have also improved especially by the end of storage. Freezing process caused a significant decrease in the viability of Lactobacillus acidophilus La-5 and Bifidobacterium animalis Bb-12 (P < 0.05). Oligofructose significantly improved the viability of L. acidophilus La-5 and B. animalis Bb-12 in ice cream mix (P < 0.05). Although the viable numbers for both bacteria decreased throughout the storage, the minimum level of 10(6) CFU/g was maintained for B. animalis Bb-12 in only ice cream with oligofructose during storage.


Traditional Games as Cultural Heritage: The Case of Canary Islands (Spain) From an Ethnomotor Perspective.
UNESCO in the 2030 agenda for sustainable development establishes respect for the environment and sustainability education as key elements for the challenges of society in the coming years. In the educational context, physical education can have a vital role in sustainability education, through Traditional Sporting Games (TSG). The aim of this research was to study from an ethnomotor perspective the different characteristics of two different groups of TSG (with and without objects) in the Canary Islands, Spain. The corpus of this investigation was made up of 513 TSG, identified by two analysis techniques and collected in a database. The categories corresponding to the variables of the internal logic of the game were the type of motor interaction, related to space, relationships with time (competition), and relationships with objects. The study also examined the variables of external logic or sociocultural conditions such as the protagonists, playing areas, and game moments. The data analysis was carried out using descriptive and inferential statistics: cross-tables, effect sizes, classification trees (CHAID), and the identification of frequency areas. Of the total number of playful activities identified (n = 664), most were physical activities (n = 513/664; 77.26%) (non-physical activities: n = 151/664; 22.74%). These activities were Quasi-games without rules (n = 87) and TSG (n = 426) as well as activities with Objects (n = 299) and without material (n = 214). This research confirms that the TSG in the Canary Islands is a mirror of traditional culture and, from a pedagogical approach, shows great potential for material and social sustainability.


[The oyster mushroom (Pleurotus ostreatus) effectively prevents the development of atherosclerosis in rabbits].
The addition of 10% dried fruiting bodies of the oyster mushroom (Pleurotus ostreatus) to the diet containing 1% of cholesterol reduced serum cholesterol levels by 65% and cholesterol content in the liver, heart, long extensor muscle and aorta of male rabbits (Chinchilla) by 60; 47; 25 and 79%, respectively. Oyster mushroom diet reduced the content of conjugated dienes by 60-70% in the plasma, erythrocytes and liver. However, it did not significantly affect the activities of antioxidant enzymes. Oyster mushroom diet reduced significantly the incidence of atherosclerotic plaques as estimated by sudanophilia (absence of a positive reaction in 3 of 5 animals) as well as plaque size (26% vs. 2% of the area with a positive reaction in control and oyster mushroom-treated animals, respectively). While all animals on control diet showed atherogenic changes in the aorta, oyster mushroom diet prevented the development of these changes in three animals. Fatty streaks and fibromatous plaques were found in the remaining two animals from this group. The oyster mushroom prevented the formation of atheroma plaques (found in three cases from the control diet group) and reduced the incidence of segmental injury of the coronary artery and of focal fibrosis of the myocardium. The oyster mushroom caused lower incidence of foam cells in all types of lesions.


Ministry of Health clinical practice guidelines: Chronic Hepatitis B Infection.
The Ministry of Health (MOH) publishes clinical practice guidelines on Chronic Hepatitis B Infection to provide doctors and patients in Singapore with evidence-based guidance on managing important medical conditions. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Chronic Hepatitis B Infection, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website (http://www.moh.gov.sg/mohcorp/publications.aspx?id=26108). The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.


Estrogen receptor alpha polymorphism and risk of cardiovascular disease, cancer, and hip fracture: cross-sectional, cohort, and case-control studies and a meta-analysis.
We hypothesized that the estrogen receptor alpha (ESR1) IVS1-397T/C polymorphism affects high-density lipoprotein cholesterol response to hormone replacement therapy and risk of cardiovascular disease (CVD), cancer of reproductive organs, and hip fracture. We studied cross-sectionally 9244 individuals from the Danish general population and followed them up for 23 to 25 years. End points were CVD (ischemic heart disease, myocardial infarction, angina pectoris, ischemic cerebrovascular disease, ischemic stroke, other ischemic cerebrovascular disease, venous thromboembolism, deep vein thrombosis, and pulmonary embolism), cancer of reproductive organs (breasts, ovaries, uterus, and prostate), and hip fracture. We also studied patients with ischemic heart disease (n=2495), ischemic cerebrovascular disease (n=856), and breast cancer (n=1256) versus general population controls. The CC, CT, and TT genotypes had general population frequencies of 21%, 50%, and 29%, respectively. Cross-sectionally, genotype did not influence high-density lipoprotein cholesterol response to hormone replacement therapy. In the cohort study, there were no differences in risks of CVD, cancer of reproductive organs, or hip fracture between genotypes. In case-control studies, risk of CVD did not differ between genotypes; however, the odds ratio for breast cancer in women with TT versus CC genotypes was 1.4 (95% CI, 1.1 to 1.7). Meta-analysis in men of 6 previous and the present 2 studies, including 4799 cases and 12,190 controls, showed odds ratios in CC versus CT and TT genotypes for fatal and nonfatal myocardial infarction of 0.81 (95% CI, 0.59 to 1.12) and 1.08 (95% CI, 0.97 to 1.21). ESR1 IVS1-397T/C polymorphism does not influence high-density lipoprotein cholesterol response to hormone replacement therapy or risk of CVD, most cancers of reproductive organs, or hip fracture.


The response of the kidney of the freshwater rainbow trout to true metabolic acidosis.
Infusion of lactic acid into the bloodstream of trout produced a short-lived depression of blood pH and a long-lasting elevation of blood lactate. The lactate injected was distributed in a volume of 198 ml/kg. Renal excretion of lactate anion and total acid increased by approximately equal amounts during the period of high blood lactate levels, but total renal loss over 72 h accounted for only 2% of the lactate load and 6% of the proton load. Comparable differences in the time courses of blood lactate and pH changes occurred when lactacidosis was induced endogenously by normocapnic hypoxia. The immediate response of the kidney was similar to that with lactic acid infusion, but there was a long-lasting (12-72 + h) elevation of urinary acid efflux that was not associated with lactate excretion. Following hypoxia, renal excretion over 72 h accounted for 1% of the estimated lactate load and 12-25% of the proton load. A renal lactate threshold of 4-10 muequiv/ml prevents significant urinary lactate excretion. The response of the trout kidney to true metabolic acidosis is similar to that of the mammalian kidney.


Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection.
Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 104 PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERSMA6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 106 PFU UV-inactivated MERSMA6.1.2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection.IMPORTANCE MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19.


[The Family Health Program in Brazil: analysis of access to basic care].
This article shows a research about the implantation of the Family Helath Program, carried through 12 pioneer cities, related to the access to the basic health services. It was based in the context of social sciences, in the method of the hermeneutics-dialectics. Scripts of interview and focal groups for data collection were used. The study highlights regarding to the primary care accessibility to health sercives, that the PSF has contributed on the reduction of inequalities. However, it faces a sort of social, political, institutional, economic and cultural challenges, that are materialized in the deficiencies of coordination, management, financing, and mainly in medical practical assistance, strongly present in the daily professional practice of the PSF's teams.


Genetic dissection of trehalose biosynthesis in Corynebacterium glutamicum: inactivation of trehalose production leads to impaired growth and an altered cell wall lipid composition.
The analysis of the available Corynebacterium genome sequence data led to the proposal of the presence of all three known pathways for trehalose biosynthesis in bacteria, i.e. trehalose synthesis from UDP-glucose and glucose 6-phosphate (OtsA-OtsB pathway), from malto-oligosaccharides or alpha-1,4-glucans (TreY-TreZ pathway), or from maltose (TreS pathway). Inactivation of only one of the three pathways by chromosomal deletion did not have a severe impact on C. glutamicum growth, while the simultaneous inactivation of the OtsA-OtsB and TreY-TreZ pathway or of all three pathways resulted in the inability of the corresponding mutants to synthesize trehalose and to grow efficiently on various sugar substrates in minimal media. This growth defect was largely reversed by the addition of trehalose to the culture broth. In addition, a possible pathway for glycogen synthesis from ADP-glucose involving glycogen synthase (GlgA) was discovered. C. glutamicum was found to accumulate significant amounts of glycogen when grown under conditions of sugar excess. Insertional inactivation of the chromosomal glgA gene led to the failure of C. glutamicum cells to accumulate glycogen and to the abolition of trehalose production in a DeltaotsAB background, demonstrating that trehalose production via the TreY-TreZ pathway is dependent on a functional glycogen biosynthetic route. The trehalose-non-producing mutant with inactivated OtsA-OtsB and TreY-TreZ pathways displayed an altered cell wall lipid composition when grown in minimal broth in the absence of trehalose. Under these conditions, the mutant lacked both major trehalose-containing glycolipids, i.e. trehalose monocorynomycolate and trehalose dicorynomycolate, in its cell wall lipid fraction. The results suggest that a dramatically altered cell wall lipid bilayer of trehalose-less C. glutamicum mutants may be responsible for the observed growth deficiency of such strains in minimal medium. The results of the genetic and physiological dissection of trehalose biosynthesis in C. glutamicum reported here may be of general relevance for the whole phylogenetic group of mycolic-acid-containing coryneform bacteria.


Pesticides in groundwater and drinking water wells: overview of the situation in the Netherlands.
In the Netherlands, many of the fresh groundwater resources are vulnerable to pollution. Owing to high population densities and intensive farming practices, pesticide residues are found in groundwater at many places. Hence a number of drinking water abstraction wells contain pesticides residues, causing considerable costs for purification. The Water Framework Directive (WFD) requires countries to assess the chemical status of groundwater bodies and set up monitoring plans for groundwater quality, including pesticides. 771 groundwater samples were taken from monitoring wells in 2006 and analysed for a broad list of pesticides in order to fulfil these requirements. Pesticide were detected in 27% of samples, while in 11% the WFD limit of 0.1 microg/l was exceeded. In this paper, these and earlier measurements are evaluated further, considering also measurements in drinking water wells, information about the origin of measured pesticides and calculated trends in use and emissions. The measurements in the monitoring wells showed that where pesticides are used, 15-55% (minimal and maximal estimation) of the wells in shallow groundwater (1 to 20 m below soil surface) contain pesticides residues at concentrations above 0.1 microg/l. When the metabolites BAM and AMPA are excluded (as not relevant in human toxicological terms), the estimation range is 7-37%. These patterns observed in shallow groundwater are reflected by the occurrence of pesticides in vulnerable abstraction wells that are used for the production of drinking water. The WFD requires the determination of both status and trends. The design of current monitoring network is evaluated from this perspective. Several recommendations are made for more adequate and efficient monitoring.


Multimodal Image Registration Using a Viscous Fluid Model with the Bhattacharyya Distance.
Image registration is an elementary task in medical image processing and analysis, which can be divided into monomodal and multimodal. Direct 3D multimodal registration in volumetric medical images can provide more insight into the interpretation of subsequent image processing applications than 2D methods. This paper is dedicated to the development of a 3D multimodal image registration algorithm based on a viscous fluid model associated with the Bhattacharyya distance. In our approach, a modified Navier-Stoke's equation is exploited as the foundation of the multimodal image registration framework. The hopscotch method is numerically implemented to solve the velocity field, whose values at the explicit locations are first computed and the values at the implicit positions are solved by transposition. The differential of the Bhattacharyya distance is incorporated into the body force function, which is the main driving force for deformation, to enable multimodal registration. A variety of simulated and real brain MR images were utilized to assess the proposed 3D multimodal image registration system. Preliminary experimental results indicated that our algorithm produced high registration accuracy in various registration scenarios and outperformed other competing methods in many multimodal image registration tasks.Clinical Relevance- This facilitates the disease diagnosis and treatment planning that requires accurate 3D multimodal image registration without massive image data and extensive training regardless of the imaging modality.


Beyond the accolades: a postcolonial critique of the foundations of the Ottawa Charter.
The Ottawa Charter is undeniably of pivotal importance in the history of ideas associated with the establishment of health promotion. There is much to applaud in a charter which responds to the need to take action on the social and economic determinants of health and which seeks to empower communities to be at the centre of this. Such accolades tend to position the Ottawa Charter as 'beyond critique'; a taken-for-granted 'given' in the history of health promotion. In contrast, we argue it is imperative to critically reflect on its 'manufacture' and assess the possibility that certain voices have been privileged, and others marginalized. This paper re-examines the 1986 Ottawa Conference including its background papers from a postcolonial standpoint. We use critical discourse analysis as a tool to identify the enactment of power within the production of the Ottawa health promotion discourse. This exercise draws attention to both the power to ensure the dominant presence of privileged voices at the conference as well as the discursive strategies deployed to 'naturalize' the social order of inequality. Our analysis shows that the discourse informing the development of the Ottawa Charter strongly reflected Western/colonizer centric worldviews, and actively silenced the possibility of countervailing Indigenous and developing country voices. The Ottawa Charter espouses principles of participation, empowerment and social justice. We question then whether the genesis of the Ottawa Charter lives up to its own principles of practice. We conclude that reflexive practice is crucial to health promotion, which ought to include a preparedness for health promotion to more critically acknowledge its own history.


Full dynamic control of dairy wastewater treatment by aerobic granular sludge using electric conductivity and oxygen uptake rate.
The objective of the current study was to determine the applicability of a sensor-based dynamic control strategy for the treatment of real variable dairy wastewater by aerobic granular sludge (AGS) performing enhanced biological phosphorus removal (EBPR). Two parallel sequencing batch reactors (SBRs) were set up that used only an anaerobic feast/aerobic famine microbial selection strategy to successfully obtain sludge granulation. SBR-STA used a fixed cycle length, while the duration of the reaction steps in SBR-DYN was variable. The control strategy was based solely on (derived) signals from low-cost and common sensors. The profile of the electric conductivity during the anaerobic reaction step was related to the microbial release of phosphate (PO4-P) and the associated uptake of dissolved organic carbon (DOC) by polyphosphate-accumulating organisms (PAOs). Control of the aerobic reaction step was based on the oxygen uptake rate (OUR). This resulted in a dynamic reactor operation with significant efficiency gains, such as 32% shorter cycle times and 42% higher sludge loading rates without impairing the effluent quality. These results extend the existing potential of indirect control strategies to full biological nutrient removal processes, which may be of great assistance to the operators and designers of industrial installations.


Human peptidoglycan recognition proteins require zinc to kill both gram-positive and gram-negative bacteria and are synergistic with antibacterial peptides.
Mammals have four peptidoglycan recognition proteins (PGRPs or PGLYRPs), which are secreted innate immunity pattern recognition molecules with effector functions. In this study, we demonstrate that human PGLYRP-1, PGLYRP-3, PGLYRP-4, and PGLYRP-3:4 have Zn(2+)-dependent bactericidal activity against both Gram-positive and Gram-negative bacteria at physiologic Zn(2+) concentrations found in serum, sweat, saliva, and other body fluids. The requirement for Zn(2+) can only be partially replaced by Ca(2+) for killing of Gram-positive bacteria but not for killing of Gram-negative bacteria. The bactericidal activity of PGLYRPs is salt insensitive and requires N-glycosylation of PGLYRPs. The LD(99) of PGLYRPs for Gram-positive and Gram-negative bacteria is 0.3-1.7 muM, and killing of bacteria by PGLYRPs, in contrast to killing by antibacterial peptides, does not involve permeabilization of cytoplasmic membrane. PGLYRPs and antibacterial peptides (phospholipase A(2), alpha- and beta-defensins, and bactericidal permeability-increasing protein), at subbactericidal concentrations, synergistically kill Gram-positive and Gram-negative bacteria. These results demonstrate that PGLYRPs are a novel class of recognition and effector molecules with broad Zn(2+)-dependent bactericidal activity against both Gram-positive and Gram-negative bacteria that are synergistic with antibacterial peptides.


Total hip arthroplasty in the young: special emphasis on post-SCFE patients.
Slipped capital femoral epiphysis (SCFE) is a hip disorder of adolescence, which has the potential for profound implications into adulthood. SCFE patients are at risk of early joint degeneration and subsequent need for arthroplasty. The rate at which arthroplasty is required is not precisely known, but is estimated to be approximately 45% by 50 years after a slip. The femoral neck and shaft displace anteriorly and rotate externally relative to the femoral epiphysis, which remains fixed in the acetabulum. Stabilization of the physis is the goal of acute management. Despite such efforts, accelerated joint degeneration may occur over time. This progression is due to avascular necrosis, chondrolysis, or following years of femoroacetabular impingement. Total hip arthroplasty (THA) and total hip resurfacing (THR) are options for end-stage hip arthritis due to SCFE. THR is technically more challenging, with very limited ability to address deformity-related issues of impingement, decreased hip offset, and trochanteric malposition. THR, as in any metal on metal arthroplasty, may be associated with local metal sensitivity or systemic metal toxicity. Given the limited utility and potential risks, THR is currently not recommended in the majority of cases. THA, although historically demonstrating poor long-term implant performance in the young patient, has become a more reliable option recently. The potential benefits of THA are considerable, even for the young patient with end-stage hip degeneration. Certain cemented and many cementless stem designs show good long-term survival, as do current cementless cups. Advances in bearing surfaces promise to minimize wear and extend implant longevity. Ceramic on ceramic, metal on highly cross-linked polyethylene, and ceramic on highly cross-linked polyethylene bearing couples offer promise.


Plant pathogen recognition as a natural, original and simple model for chemogenomics: a brief overview of cell-based assays to screen for peptides acting as plant defense activators.
As plants lack a circulatory system and adaptive immune system, they have evolved their own defense systems distinct from animals, in which each plant cell is capable of defending itself from pathogens. Plants induce a number of defense responses, which are triggered by a variety of molecules derived from pathogenic microorganisms, referred to as microbe-associated molecular patterns (MAMPs), including peptides, proteins, lipopolysaccharide, beta-glucan, chitin, and ergosterol. The interaction between plants and chemicals in the context of plant defense represents a "natural" and simple model for chemogenomics, at the intersection between chemical and biological diversities. For protection of crop plants from diseases, it has been shown to be effective to stimulate the plant immunity by chemical compounds, the so-called "plant defense activators". Combinatorial chemistry techniques can be applied to the search for novel plant defense activators, but it is essential to establish an efficient and reliable screening system suitable for library screening. For studies of the plant immune system, it is difficult to use isolated proteins as biological targets because the receptors for MAMP recognition are largely unknown and even the receptors identified so far are transmembrane proteins. Therefore, screening for novel peptides acting on MAMP receptors from combinatorial libraries must rely on a solution-phase assay using cells as the biological targets. In this review, we introduce the cell-based lawn format assay for identification of peptides acting as plant defense activators from combinatorial peptide libraries. The requirements and limitations in constructing the screening system using combinatorial libraries in the studies of plant sciences are also discussed.


Wavelet analysis in a canine model of gastric electrical uncoupling.
Abnormal gastric motility function could be related to gastric electrical uncoupling, the lack of electrical, and respectively mechanical, synchronization in different regions of the stomach. Therefore, non-invasive detection of the onset of gastric electrical uncoupling can be important for diagnosing associated gastric motility disorders. The aim of this study is to provide a wavelet-based analysis of electrogastrograms (EGG, the cutaneous recordings of gastric electric activity), to detect gastric electric uncoupling. Eight-channel EGG recordings were acquired from 16 dogs in basal state and after each of two circular gastric myotomies. These myotomies simulated mild and severe gastric electrical uncoupling, while keeping the separated gastric sections electrophysiologically active by preserving their blood supply. After visual inspection, manually selected 10 min EGG segments were submitted to wavelet analysis. Quantitative methodology to choose an optimal wavelet was derived. This 'matching' wavelet was determined using the Pollen parametrization for 6-tap wavelet filters and error minimization criteria. After a wavelet-based compression, the distortion of the approximated EGG signals was computed. Statistical analysis on the distortion values allowed us to significantly (p < 0.05) distinguish basal state from mild and severe gastric electrical uncoupling groups in particular EGG channels.


Predictors of infant-survival practices among mothers attending paediatric clinics in Ijebu-Ode, Ogun State, Nigeria.
Despite concerted global efforts towards achieving infant-survival, infant mortality lingers as a problem in developing countries. Environmental and personal-level factors are assumed to account for this situation. This study was undertaken to provide better understanding of the dynamics of predictors of infant-survival practices among mothers with infants attending paediatric clinics. A cross-sectional survey design was adopted. Data was collected from 386 nursing mothers selected by convenience sampling. Interviewer-administered questionnaires were used for data collection. The questionnaire consisted of 38-items including demographic information of respondents, health-literacy counsels received during antenatal care, social-support from significant others, and self-efficacy to carry-out infant-survival instructions. Responses were transformed into rating scales for each variable and data analysis was conducted by linear regression analysis with test of hypotheses at 5% level of significance. The mean age of respondents was 29.8 ± 5.8 years. Majority (81.6%) were married. Yorubas (83.90%) were predominant. Participants had mean scores of 10.50 ± 3.83, 10.56 ± 3.70 and 16.61 ± 4.56 respectively computed for levels of health-literacy, social-support, and self-efficacy. The dependent variable measured level of infant-survival practices and respondents scored 16.53 ± 4.71. The study found a significant association among variables. Self-efficacy was the major predictor variable of self-reported infant-survival practices (R = 0.466; R2 = 0.217; P<0.05). We conclude that participants had average levels of health-literacy, social-support, self-efficacy, and infant-survival practices. Healthcare providers should make efforts to empower pregnant women on activities essential for infant-survival. Family members of nursing mothers should as well be knowledgeable about the advantages of supporting them.


Degranulation of polymorphonuclear leucocytes following phagocytosis of microorganisms.
A marked reduction in numbers of cytoplasmic granules in rabbit and human polymorphonuclear leucocytes takes place following ingestion of various microorganisms or of a yeast cell wall preparation. The degranulation occurs within 30 minutes of phagocytosis, and is directly related to the quantity of material engulfed. White cells completely degranulated following phagocytosis of large numbers of microorganisms remain viable for at least 1 hour. The granules of polymorphonuclear leucocytes contain the antimicrobial agent, phagocytin, and various digestive enzymes. These substances thus are released into the cytoplasm or into vacuoles following ingestion of foreign material. The granule system and granule lysis mechanism may well play a central role in the primary function of these specialized cells; namely, that of destroying invading microorganisms.


Observing the Global Ocean with Biogeochemical-Argo.
Biogeochemical-Argo (BGC-Argo) is a network of profiling floats carrying sensors that enable observation of as many as six essential biogeochemical and bio-optical variables: oxygen, nitrate, pH, chlorophyll a, suspended particles, and downwelling irradiance. This sensor network represents today's most promising strategy for collecting temporally and vertically resolved observations of biogeochemical properties throughout the ocean. All data are freely available within 24 hours of transmission. These data fill large gaps in ocean-observing systems and support three ambitions: gaining a better understanding of biogeochemical processes (e.g., the biological carbon pump and air-sea CO2 exchanges) and evaluating ongoing changes resulting from increasing anthropogenic pressure (e.g., acidification and deoxygenation); managing the ocean (e.g., improving the global carbon budget and developing sustainable fisheries); and carrying out exploration for potential discoveries. The BGC-Argo network has already delivered extensive high-quality global data sets that have resulted in unique scientific outcomes from regional to global scales. With the proposed expansion of BGC-Argo in the near future, this network has the potential to become a pivotal observation system that links satellite and ship-based observations in a transformative manner.


Abdominal complications of infectious mononucleosis.
Infectious mononucleosis, a systemic illness caused by the Epstein-Barr virus, is seen frequently by primary care physicians. Mononucleosis affects several organ systems, and, within the abdomen, there can be splenic involvement, hepatitis, mesenteric lymphadenopathy, hyperplasia of gut-associated lymphoid tissue, pancreatitis, and transient malabsorption. Life-threatening abdominal complications require prompt recognition and intervention. Other abdominal complications, though worrisome, are usually short-lived and resolve without sequelae.


Management of patients with liver derangement during the COVID-19 pandemic: an Asia-Pacific position statement.
The COVID-19 pandemic has spread rapidly worldwide. It is common to encounter patients with COVID-19 with abnormal liver function, either in the form of hepatitis, cholestasis, or both. The clinical implications of liver derangement might be variable in different clinical scenarios. With growing evidence of its clinical significance, it would be clinically helpful to provide practice recommendations for various common clinical scenarios of liver derangement during the COVID-19 pandemic. The Asia-Pacific Working Group for Liver Derangement during the COVID-19 Pandemic was formed to systematically review the literature with special focus on the clinical management of patients who have been or who are at risk of developing liver derangement during this pandemic. Clinical scenarios covering the use of pharmacological treatment for COVID-19 in the case of liver derangement, and assessment and management of patients with chronic hepatitis B or hepatitis C, non-alcoholic fatty liver disease, liver cirrhosis, and liver transplantation during the pandemic are discussed.


Reduction of Phosphorylated Tau in Alzheimer's Disease Induced Pluripotent Stem Cell-Derived Neuro-Spheroids by Rho-Associated Coiled-Coil Kinase Inhibitor Fasudil.
Alzheimer's disease (AD) is the most predominant form of dementia. Rho-associated coiled coil kinase (ROCK) inhibitor, fasudil, is one of the candidate drugs against the AD progression. We aimed to investigate possible changes of AD associated markers in three-dimensional neuro-spheroids (3D neuro-spheroids) generated from induced pluripotent stem cells derived from AD patients or healthy control subjects (HC) and to determine the impact of pharmacological intervention with the ROCK inhibitor fasudil. We treated 3D neuro-spheroids with fasudil and tested the possible effect on AD markers by ELISA, transcriptomic and proteomic analyses. Transcriptomic analysis revealed a reduction in the expression of AKT serine/threonine-protein kinase 1 (AKT1) in AD neuro-spheroids, compared to HC. This decrease was reverted in the presence of fasudil. Proteomic analysis showed up- and down-regulation of proteins related to AKT pathway in fasudil-treated neuro-spheroids. We found an evident increase of phosphorylated tau at four different residues (pTau181, 202, 231, and 396) in AD compared to HC-derived neuro-spheroids. This was accompanied by a decrease of secreted clusterin (clu) and an increase of intracellular clu levels in AD patient-derived neuro-spheroids. Increases of phosphorylated tau in AD patient-derived neuro-spheroids were suppressed in the presence of fasudil. Fasudil modulates clu protein levels and enhances AKT1 that results in the suppression of AD associated tau phosphorylation.


Creating biomimetic surfaces through covalent and oriented binding of proteins.
This manuscript describes a novel method for the biofunctionalization of glass surfaces with polyhistidine-tagged proteins. The main innovation of this methodology consists of the covalent binding between the nitrilotriacetic acid (NTA) moiety and the proteins, ensuring not only orientation, but also stability of the recombinant proteins on NTA-covered surfaces. In this work, as C-terminal polyhistidine tagged cadherin extracellular fragments have been used, this methodology guarantees the proper orientation of these proteins, by mimicking their insertion into cell plasma membranes. These biofunctionalized surfaces have been characterized by confocal microscopy, X-ray photoelectron spectroscopy, contact angle, and atomic force microscopy, showing a high density of cadherins on the glass surfaces and the stability of the linkage. The prepared materials exhibited a high tendency to promote cell spreading, demonstrating the functionality of the protein and the high utility of these biomaterials to promote cell adhesion events. Interestingly, differences in the cytoskeleton organization have been observed in cells adhering to surfaces with no cadherins or with nonoriented cadherins, in comparison to surfaces functionalized with well-oriented cadherins. This method, which allows the robust immobilization of polyhistidine tagged proteins due to their covalent binding and with a defined orientation, may also find particular usefulness in the making of protein biochips, for analysis of protein-protein interactions, as well as structural and single-molecule studies.


Assessing health outcomes after extraction of third molars: the postoperative symptom severity (PoSSe) scale.
A postoperative symptom severity (PoSSe) scale was devised from questions commonly used in the clinical assessment of patients who have had third molars extracted, and divided into subscales corresponding to seven main adverse effects that had been identified in a previous study. Ninety-seven patients completed the 15-item questionnaire at one week, and 71 patients at four weeks, after extraction of impacted third molars. After statistical testing, four items were discarded and the final PoSSe scale achieved a high level of internal reliability. Patients' PoSSe scores were highly correlated with scales that measured six distinct health dimensions. The level of social functioning, together with the number of impacted teeth and number of painkillers taken, explained 62% of the variation in PoSSe scores between patients one week postoperatively. The PoSSe was more responsive than the Short Form 36-item Health Survey. In conclusion, we found the PoSSe Scale to be a reliable, valid and responsive measure of the severity of symptoms after extraction of third molars, and of the impact of those symptoms on patients' perceived health.


[Persistence of critical-reading learning in medical residents].
1. To evaluate the persistence of a training course on critical reading of medical articles by medical residents seven months after training. 2. To compare the persistence of training according to type of training (participative vs expositive). We used the same groups of first year medical residents of a previous study. They had received seven months before a 30 hours training in the reading of research articles: Group I (N = 28) had a course of active participation by reading articles previous to meeting discussions; II (n = 17) exposition of research themes by active researchers; III (n = 23) same as II but with non-research trainers. Using an examination questionnaire developed and validated by us to explore critical reading of research papers, the trainees were scored after finishing their training (initial score). Seven months later we retested them using the same test (not all were retested: two were missing in groups I and III and six in Group II). Non parametric statistics were used to compare the groups (Wilcoxon, Kruskal-Wallis, Mann-Whitney). There were no intragroup differences of the retesting versus the initial median in the three groups (I had 17.5 vs 19 initial, II had 7 vs 13, III had 6 vs 3). In the initial testing, Groups I and II scored higher than III, but only Group I was higher than the other groups upon retesting (p < 0.006). An active participatory training to promote critical reading was better than the traditional training techniques still widely used.


Methoxyindoles and photoreceptor metabolism: activation of rod shedding.
Using an in vitro eye-cup preparation, we have evaluated a potential relationship between methoxyindole metabolism and photoreceptor disk shedding. Melatonin, 6-chloromelatonin, and 5-methoxytryptophol all activate rod disk shedding in culture. The effect is compound specific since serotonin and N-acetylserotonin are without effect, and it is similar to shedding in vivo because it is evoked by light and is quantitatively comparable to a normal intact animal response. The results suggest the involvement of 5-methoxyindoles in the control of rhythmic photoreceptor metabolism.


Long-term results of implants immediately placed into extraction sockets grafted with β-tricalcium phosphate: a retrospective study.
The aim of this 10 year retrospective study was to evaluate the crestal bone loss around immediate implant placed in tricalcium phosphate (TCP) grafted extraction sockets Data were collected from files of 58 patients (33 females, 25 males, average age 54.78 years) undergoing immediate implant placement into fresh extraction socket with or without the use of TCP (Cerasorb, Curasan AG, Kleinostheim, Germany) grafting. After implant placement, horizontal gaps larger than 1.5 mm between the implant surface and the bony plate were grafted with TCP without the use of a membrane, while smaller gaps were not grafted. Two hundred fifty-four implants were inserted: 79 were placed immediately with the use of β-TCP as grafting material (group A), 175 were placed in healed extraction sites, with 61 implants placed with the use of β-TCP graft material (group B), and 114 implants were placed without any grafting material (group C). Bone loss recordings were performed using periapical radiography. Measurements were performed from the neck of the implant to level of the surrounding bone in the vertical dimension. No implant was lost during the follow-up period. Statistical analysis showed no correlation between implant placement timing (delayed or immediate), the use of bone graft, and extent of bone loss. The use of TCP (Cerasorb) as a grafting material during immediate implant placement allowed no bone loss in 72.1% of the implants, which was very similar to the nongrafted cases for which implants were placed in favorable conditions.


Disease threats to the endangered Iberian lynx (Lynx pardinus).
The Iberian lynx, (Lynx pardinus), is the most endangered felid in the world. To determine whether sympatric carnivores are reservoirs of pathogens posing a disease risk for the lynx, evidence of exposure to 17 viral, bacterial and protozoan agents was investigated in 176 carnivores comprising 26 free-living lynx, 53 domestic cats, 28 dogs, 33 red foxes (Vulpes vulpes), 24 Egyptian mongooses (Herpestes ichneumon), 10 common genets (Genetta genetta) and 2 Eurasian badgers (Meles meles) in the areas inhabited by the last two populations of Iberian lynx, both in Andalusia (South-Western Spain). The results indicated that the lynx had low rates of contact with viral pathogens, with one seropositive finding each for feline leukemia virus, parvovirus and canine adenovirus-1, whereas contact with bacteria and protozoa appeared more frequent. Active infections with parvovirus, Ehrlichia spp., Mycobacterium bovis, Leptospira interrogans and Cytauxzoon spp. were confirmed. In contrast, 53% of the domestic cats were exposed to some infectious agent (prevalence range 4.5-11.4%). Antibodies to canine distemper virus and parvovirus were frequently found in dogs (32% and 42%, respectively) and foxes (30% and 12%). Past or present infections with parvovirus, Ehrlichia spp., Chlamydophila spp., M. bovis, Salmonella enterica, L. interrogans, Toxoplasma gondii, and Neospora caninum were also detected in these and other species surveyed. Questionnaires to owners revealed that 14% of the dogs but none of the cats had been vaccinated, and no cat had been neutered. Based on the apparent absence of acquired immunity of the lynx against infectious agents, the frequent detection of agents among sympatric carnivores, and the reported lack of immunocompetence of the Iberian lynx, a disease outbreak among the local abundant carnivores may pose a serious disease risk for lynx conservation.


GOK: a gene at 11p15 involved in rhabdomyosarcoma and rhabdoid tumor development.
The expression of GOK, a gene recently identified at 11p15.5, was studied in breast cancer, rhabdomyosarcoma, and rhabdoid tumor cell lines. In these neoplasms, deletions at 11p15 and suppression of tumorigenicity induced by a normal human chromosome 11 were previously demonstrated. Whereas breast cancer cell lines express readily detectable levels of GOK mRNA, expression is absent in rhabdomyosarcoma and rhabdoid tumor cell lines. This is in contrast with the high expression of GOK in skeletal muscle, the normal tissue of origin of rhabdomyosarcomas, suggesting that down-regulation of GOK expression could be involved in tumor development. In agreement with this hypothesis, transfection of GOK cDNA into G401 derived from a rhabdoid tumor and RD cells derived from a rhabdomyosarcoma that do not express detectable levels of GOK mRNA, induced cell death. Because GOK expression is not compatible with growth of these tumor cells, these results support the hypothesis that loss of GOK expression plays a role in tumor establishment or progression and suggest that GOK may act as a recessive tumor suppressor gene in rhabdomyosarcomas and rhabdoid tumors. On the contrary, transfection of GOK cDNA into the breast cancer cell line HBL100 produced no detectable effects, indicating that the growth-suppressive effect of GOK in RD and G401 cells was specific. Because rhabdomyosarcomas have been observed in cases of Beckwith-Wiedemann syndrome, a genetic disorder linked to 11p15, a role of GOK in this disease cannot be excluded.


Eating Disorders in Late-life.
Eating disorders are a heterogeneous group of complex psychiatric disorders characterized by abnormal eating behaviours that lead to a high rate of morbidity, or even death, if underestimated and untreated. The main disorders enlisted in the chapter of the Diagnostic and Statistic Manual of Mental Disorders-5 dedicated to "Feeding and Eating Disorders" are: anorexia nervosa, bulimia nervosa and binge eating disorder. Even though these abnormal behaviours are mostly diagnosed during childhood, interesting cases of late-life eating disorders have been reported in literature. In this review, these eating disorders are discussed, with particular attention to the diagnosis and management of those cases occurring in late-life.


A fast replica plating technique for the isolation of post-integration mutants of the Moloney strain of murine leukaemia virus.
Seven temperature-sensitive (ts) mutants of Moloney murine leukaemia virus (Mo-MuLV) were isolated using a rapid, non-selective replica plating technique designed to select for post-integration mutants. Thymus-bone marrow (TB) cells, infected with mutagenized virus, were cloned and incubated at the non-permissive temperature (39 degrees C) for 10 days. The resulting colonies were screened for production of virus by replica plating supernatant from the "master" tray on to a second tray pre-seeded with fu-1 (a cell line derived from L8 myoblasts) indicator cells. The "master" tray was shifted to the permissive temperature (34 degrees C) for 48 h, then re-screened for virus production. Any colony on the "master" tray which produced syncytia-inducing virus at 34 degrees C but not at 39 degrees C was potentially producing a ts mutant. Preliminary characterization by shift-down experiments and scanning electron microscopy of three of the ts mutants isolated by this technique revealed a mutant blocked before budding, one blocked at an early stage in the budding process and one with a defect after release of the virus.


Adenosine echocardiography in the diagnosis of coronary artery disease.
Adenosine is a naturally occurring vasodilator which has been used for the induction of maximal coronary hyperaemia in the cardiac catheterization laboratory and in conjunction with myocardial perfusion scintigraphy. Its use as a stress agent with echocardiography is dependent upon the development of coronary steal. The sensitivity of adenosine stress echocardiography has been reported to be quite variable, depending on the nature of the population studied. However, in individuals without previous myocardial infarction, the test has a poor sensitivity, particularly in patients with single vessel coronary disease. Moreover, although the agent is safe, troublesome side effects are frequent. The combination of lower sensitivity than competing techniques, side effects, and cost do not favour the combination of adenosine stress with echocardiography.


Effect of micro-aeration on the mechanical behaviour of chocolates and implications for oral processing.
Aeration in foods has been widely utilised in the food industry to develop novel foods with enhanced sensorial characteristics. Specifically, aeration at the micron-sized scale has a significant impact on the microstructure where micro-bubbles interact with the other microstructural features in chocolates. This study aims to determine the effect of micro-aeration on the mechanical properties of chocolate products, which are directly correlated with textural attributes such as hardness and crumbliness. Uniaxial compression tests were performed to determine the mechanical properties such as Poisson's ratio, Young's modulus and macroscopic yield strength together with fracture tests to estimate the fracture toughness. In vivo mastication tests were also conducted to investigate the link between the fracture properties and fragmentation during the first two chewing cycles. The uniaxial stress-strain data were used to calibrate a viscoplastic constitutive law. The results showed that micro-aeration significantly affects mechanical properties such as Young's modulus, yield and fracture stresses, as well as fracture toughness. In addition, it enhances the brittle nature of the chocolate, as evidenced by lower fracture stress but also lower fracture toughness leading to higher fragmentation, in agreement with observations in the in vivo mastication tests. As evidenced by the XRT images and the stress-strain measurements micro-aeration hinders the re-arrangement of the microscopic features inside the chocolate during the material's deformation. The work provides a new insight of the role of bubbles on the bulk behaviour of complex multiphase materials, such as chocolates, and defines the mechanical properties which are important input parameters for the development of oral processing simulations.


Recent progress in nano-biotechnology: compartmentalized micro- and nanoparticles via electrohydrodynamic co-jetting.
Compartmentalized particles enable co-presentation of dissimilar sets of properties, thereby offering a broad design space for multifunctional particles. Electrohydrodynamic co-jetting is a simple, yet versatile fabrication technique that can be used to prepare such multicompartmental particles and fibers. Processing conditions are summarized for co-jetting of aqueous and organic polymer solutions as well as nanoparticle suspensions. Because particles can comprise distinct polymers in different compartments, selective surface modification becomes possible. The latter can result in unidirectional interactions with cells or may pave new routes towards targeted drug delivery.


[Long term evaluation of transanal surgery with automatic suture in Hirschsprung's disease].
Retrospective and descriptive study of patients with diagnosis of Hirschsprung disease (HD) in whom transanal pull-through was performed in our center. All patients with diagnosis of HD in whom transanal surgery was performed between 2006 and 2018 in our center were selected. In all cases laparoscopic biopsy was performed in the previous dilated area. Once intraoperatory biopsy revealed the presence of ganglionic cells, transanal De la Torre surgery was performed, until reaching the localization of the biopsied area. Circular automatic suture was performed in all cases. Surgery was performed in 21 patients (16 boys and 5 girls) with a median age of 12 months (5-62). No patient had enterocolitis. The median resection length was 14.5 cm (3-45) and no intraoperative complications happened. One patient (5%) developed a rectosigmoideal abscess, which was solved with antibiotic. One case (5%) needed another surgery due to umbilical trochar eventration. No patient had enterocolitis after the surgery. One patient (5%) had stenosis, solved by its section and other case (5%) had sleeve compression which was solved by laparoscopic section. After a median follow up of 97 months (12-159), one child (5%) developed encopresis, which is treated with periodic anal irrigations and other patient (5%) has chronic constipation, which require periodic enemas. The rest of the patients have no symptomatology. In conclusion, in our series of cases, transanal pull-through with circular automatic suture was a safe and useful technique. It has a low rate of operative and postoperative complications and provides good prospective results.


Glaucoma following infantile cataract surgery.
To examine incidence, risk factors, and outcomes of glaucoma following infantile cataract extraction. A retrospective chart review of all patients who underwent cataract extraction between January 1, 1993, and December 31, 2006, at the Children's Medical Center in Dallas. Sixty-four eyes met inclusion criteria, of which 11 eyes (17.2%) developed glaucoma during a mean follow-up of 65.1 ± 4.3 months. Age younger than 3 months at cataract diagnosis (odds ratio 4.89, P = .05) or cataract extraction (odds ratio 4.4, P = .047) and the presence of anterior chamber anomalies (odds ratio 8.0, P = .01) were the only risk factors found to have statistical significance for the development of glaucoma. Eight of 11 eyes with glaucoma (72.2%) required at least one surgical intervention. Three of 10 eyes (30%) had a final best-corrected visual acuity below 20/400 and another 4 eyes (40%) demonstrated some degree of amblyopia. Despite modern microsurgical techniques, infantile cataract surgery continues to pose a risk of secondary glaucoma. This was particularly true when cataract was diagnosed and/or extracted in patients younger than 3 months of age. Most eyes that developed glaucoma required surgical management and visual outcomes continue to be poor in this group.


Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms.
Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on celiac disease (CD), an autoimmune enteropathy, and type 1 diabetes (T1D), a hyperglycosaemia caused by a destructive autoimmune process targeting the insulin-producing pancreatic islet cells. Even if environmental factors and genetic susceptibility are clearly involved in the pathogenesis of autoimmunity, for most autoimmune disorders there is no or little knowledge about the causing agent or genetic makeup underlying the disease. In this respect, CD represents a unique autoimmune disorder because a close genetic association with HLA-DQ2 or HLA-DQ8 haplotypes and, more importantly, the environmental trigger (the gliadin fraction of gluten-containing grains wheat, barley, and rye) are known. Conversely, the trigger for autoimmune destruction of pancreatic ss cells in T1D is unclear. Interestingly, recent data suggest that gliadin is also involved in the pathogenesis of T1D. There is growing evidence that increased intestinal permeability plays a pathogenic role in various autoimmune diseases including CD and T1D. Therefore, we hypothesize that besides genetic and environmental factors, loss of intestinal barrier function is necessary to develop autoimmunity. In this review, each of these components will be briefly reviewed.


Non-Hodgkin's lymphoma: a survey from a district general hospital.
We report a retrospective survey of 167 patients with non-Hodgkin's lymphoma (NHL) seen at a district general hospital between 1 August 1971 and 1 August 1983. Details of their clinical presentation, histology, therapy, response rates and survival are presented. The patient population reported is generally older than that seen at specialist centres and has a greater proportion of tumours with low-grade histology. Whereas specialist centres see a pre-selected population of patients, our data may be from a more representative group and this gives a truer incidence of this disease in the general population. The remission rates and overall survival of our patients are comparable to those achieved at specialist centres. We conclude that it is both feasible and desirable for patients with NHL to be assessed and treated in a district general hospital with a radiotherapy department.


Effect of splenectomy on the morphology of haemolymph splenic nodes in Wistar rats.
In 12 Wistar rats the gross and microscopic structure of haemolymph splenic nodes was assessed after splenectomy and the obtained results were compared with those in the control group. It was found that splenectomy leads to generalised morphological changes of the mentioned nodes, including, among other, their blanching, enlargement, filling with a greater number of morphotic elements and decreased count of erythrocytes and products of their disintegration. The splenic nodes demonstrated no regressive changes, typical of uniorgan nodes. The remaining abdominal non-haemolymph nodes in the rats showed no compensatory changes on gross examination after splenectomy.


Identification and classification of bacterial Type III toxin-antitoxin systems encoded in chromosomal and plasmid genomes.
Toxin-antitoxin systems are widespread in bacteria and archaea. They perform diverse functional roles, including the generation of persistence, maintenance of genetic loci and resistance to bacteriophages through abortive infection. Toxin-antitoxin systems have been divided into three types, depending on the nature of the interacting macromolecules. The recently discovered Type III toxin-antitoxin systems encode protein toxins that are inhibited by pseudoknots of antitoxic RNA, encoded by short tandem repeats upstream of the toxin gene. Recent studies have identified the range of Type I and Type II systems within current sequence databases. Here, structure-based homology searches were combined with iterative protein sequence comparisons to obtain a current picture of the prevalence of Type III systems. Three independent Type III families were identified, according to toxin sequence similarity. The three families were found to be far more abundant and widespread than previously known, with examples throughout the Firmicutes, Fusobacteria and Proteobacteria. Functional assays confirmed that representatives from all three families act as toxin-antitoxin loci within Escherichia coli and at least two of the families confer resistance to bacteriophages. This study shows that active Type III toxin-antitoxin systems are far more diverse than previously known, and suggests that more remain to be identified.


NF-kappaB signaling in lymphocytes: a new cast of characters.
Cell-surface antigen receptors on B and T lymphocytes are complex, multisubunit assemblies that must recruit several accessory proteins and activate multiple signaling pathways in order to illicit a proper immune response. One pathway culminates in the activation of specific protein kinase C (PKC) isoforms, which is necessary for the ultimate activation of the NF-kappaB transcription factor. Since NF-kappaB plays a crucial role in the adaptive immune response (e.g. in lymphocyte proliferation and cytokine production), it is important to understand the molecular mechanisms by which NF-kappaB is regulated. Nevertheless, the connection between PKC activation and NF-kappaB has remained a mystery that has now been at least partly solved. Recent findings implicate a new scaffolding protein, Bimp3/CARMA1/CARD11, as a key factor in bridging PKC activation with the downstream activation of Bcl10 and MALT1, which ultimately stimulates NF-kappaB. Since some of these signaling components are lymphocyte specific, therapeutic agents that block this pathway could blunt the inappropriate proliferation of lymphocytes associated with certain inflammatory and neoplastic disorders. Alternatively, agents that specifically augment this pathway, thereby enhancing immune function in immunodeficiency, may be developed.


Seasonal contrasts in the response of coffee ants to agroforestry shade-tree management.
In many tropical landscapes, agroforestry systems are the last forested ecosystems, providing shade, having higher humidity, mitigating potential droughts, and possessing more species than any other crop system. Here, we tested the hypothesis that higher levels of shade and associated humidity in agroforestry enhance coffee ant richness more during the dry than rainy season, comparing ant richness in 22 plots of three coffee agroforestry types in coastal Ecuador: simple-shade agroforests (intensively managed with low tree species diversity), complex-shade agroforests (extensively managed with intermediate tree species diversity) and abandoned coffee agroforests (abandoned for 10-15 yr and resembling secondary forests). Seasonality affected responses of ant richness but not composition to agroforestry management, in that most species were observed in abandoned coffee agroforests in the dry season. In the rainy season, however, most species were found in simple-shade agroforests, and complex agroforestry being intermediate. Foraging coffee ants species composition did not change differently according to agroforestry type and season. Results show that shade appears to be most important in the dry seasons, while a mosaic of different land-use types may provide adequate environmental conditions to ant species, maximizing landscape-wide richness throughout the year.


Natural history of rare diseases using Natural Language Processing of narrative unstructured electronic health records: the example of Dravet syndrome.
The increasing implementation of electronic health records allows the use of advanced text-mining methods for establishing new patient-phenotypes and stratification, and for revealing outcome correlations. In this study we aimed to explore the electronic narrative clinical reports of a cohort of patients with Dravet Syndrome (DS) longitudinally followed at our center, to identify the capacity of this methodology to retrace natural history of DS during the early years. We used a document-based clinical data warehouse employing Natural Language Processing to recognize the phenotype concepts in the narrative medical reports. We included patients with DS who have a medical report produced before the age of two and a follow-up after the age of 3 years ("DS cohort"-56 individuals). We selected two control populations, a "general control cohort" (275 individuals) and a "neurological control cohort" (281 individuals), with similar characteristics in terms of gender, number of reports and age at last report. To find concepts specifically associated with DS, we performed a phenome-wide association study using Cox regression, comparing the reports of the three cohorts. We then performed a qualitative analysis of the surviving concepts based on their median age of first appearance. A total of 76 concepts were prevalent in the reports of children with DS. Concepts appearing during the first 2 years were mostly related with the epilepsy features at the onset of DS (convulsive and prolonged seizures triggered by fever, often requiring in-hospital care). Subsequently, concepts related to new types of seizures and to drug-resistancy appeared. A series of non-seizures related concepts emerged after the age of 2-3 years, referring to the non-seizures comorbidities classically associated to DS. The extraction of clinical terms by narrative reports of children with DS, allows to outline the known natural history of this rare disease in early childhood. This original model of "longitudinal phenotyping" could be applied for other rare and very rare conditions with poor natural history description.


The effect of fasting on enzyme levels in the enlarged and involuting rat pancreas.
1. The effect on pancreatic digestive enzyme levels of fasting and changes from a diet containing trypsin inhibitor (raw soya-bean flour, RSF) to diets free of trypsin inhibitor (heated soya-bean flour, HSF, or commercial rat chow) was studied in rats for up to 7 d. 2. In RSF-fed rats killed without fasting, enzyme levels were low, but after fasting for 24 h before killing there was a marked increase in all enzyme levels. Histological studies showed that pancreatic acinar cells from RSF-fed rats killed without fasting were devoid of zymogen granules, but following a 24 h fast there was a marked accumulation of zymogen granules which extend into the basal cytoplasm. Fasting either produced no change or a fall in enzyme levels in rats fasted after feeding HSF or chow continuously. 3. If animals fed on RSF were changed to HSF and either fed or fasted for 24 h up to the time of killing there was an increase in amylase (EC 188.8.131.52), trypsin (EC 18.104.22.168), lipase (triacylglycerol lipase; EC 126.96.36.199) and protein 1 d after the change, followed by a fall over the next 6 d to levels similar to those seen in rats fed on HSF continuously. 4. Animals changed from RSF to chow showed similar effects as far as trypsin, lipase and protein were concerned, but amylase rose, to reach the level seen in rats fed on chow continuously (about ten times that seen in soya-bean-fed rats), after 2 d. 5. These results suggest that in the rats fed on RSF, pancreatic enzyme synthesis is rapid but secretion is equally rapid and intracellular enzyme levels are low. When these animals are fasted or changed to a diet free of trypsin inhibitor the rate of secretion falls but the high rate of synthesis continues for at least 24 h and enzymes accumulate in the pancreas. In studies of pancreatic enzyme levels in rats fed on trypsin inhibitor the extent of fasting before killing the animal is therefore an important variable. Such animals should probably not be fasted before study.


Ganglion cell and 'dendrite' populations in electric acoustic stimulation ears.
The electric acoustic stimulation (EAS) technique combines electric and acoustic stimulation in the same ear and utilizes both low-frequency acoustic hearing and electric stimulation of preserved neurons. We present data of ganglion cell and dendrite populations in ears from normal individuals and those suffering from adult-onset hereditary progressive hearing loss with various degrees of residual low-frequency hearing. Some of these were potential candidates for EAS surgery. The data may give us information about the neuroanatomic situation in EAS ears. Dendrites and ganglion cells were calculated and audiocytocochleograms constructed. The temporal bones were from the collection at the House Ear Institute in Los Angeles, Calif., USA. Normal human anatomy, based on surgical specimens, is presented. Inner and outer hair cells, supporting cells, ganglion cells and dendrites were preserved in the apical region. In the mid-frequency region, around 1 kHz, the organ of Corti with inner and outer hair cells was often conserved while in the lower basal turn, representing frequencies above 3 kHz, the organ of Corti was atrophic and replaced by thin cells. Despite loss of hair cells and lamina fibers ganglion cells were present even after 28 years of deafness. Conditions with profound sensorineural hearing loss and preserved low-frequency hearing may have several causes and the pathology may vary accordingly. In our patients with progressive adult-onset sensorineural hearing loss (amalgamated into 'presbyacusis'), neurons were conserved even after long duration of deafness. These spiral ganglion cells may be excellent targets for electric stimulation using the EAS technique.


[Involvement of hippocampal NO/PKG signaling pathway in the accumulative analgesic effect of electroacupuncture stimulation of "Zusanli" (ST 36)-"Yanglingquan"(GB 34) in chronic neuropathic pain rats].
To observe the effect of electroacupuncture (EA) at "Zusanli"(ST 36)-"Yanglingquan"(GB 34) on pain behavior and expression of hippocampal neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase(iNOS)and cGMP-dependent protein kinase (PKG) mRNA in rats with chronic neuropathic pain so as to analyze its mechanism underlying analgesia. Forty male Wistar rats were randomly divided into control, CCI model, EA-2 Hz, EA-2 Hz/15 Hz, EA-100 Hz groups, with 8 cases in each group. Chronic neuropathic pain model was established by ligature of the left sciatic nerve under anesthesia (Urethane + Alpha-Chloralose) except rats in the control group. EA(2 Hz, 2 Hz/15 Hz, 100 Hz, 1 mA) was applied to bilateral "Zusanli"(ST 36)-"Yanglingquan"(GB 34) for 30 min, once each day for 2 weeks. The thermal and mechanical paw withdrawal latencies (pain thresholds) of the bilateral limbs were detected before and after EA interventions. The hippocampal tissue of the rat was collected for detecting the expression levels of nNOS, INOS and PKG genes using quantitative real-time-PCR technique. In comparison with the control group, the thermal and mechanical pain thresholds of the model group were decreased obviously (P<0. 05).Compared with the model group, both thermal and mechanical pain thresholds of the EA-2 Hz, EA-2 Hz/15 Hz and EA-100 Hz groups were markedly increased after EA intervention for 3, 7, 10 and 14 days (P<0. 05). Compared with the control group, the expression levels of hippocampal nNOS and PKG mRNA were significantly and moderately up-regulated in the model group (P<0. 05). While in comparison with the model group, the expression levels of hippocampal nNOS and PKG mRNA in the EA-2 Hz, EA-2 Hz/15 Hz and EA-100 Hz groups were markedly down-regulated (P<0. 05). No significant differences were found among the EA-2 Hz, EA-2 Hz/15 Hz and EA-100 Hz groups in the analgesic effect and in down-regulating hippocampal nNOS and PKG mRNA expression (P>0.05). However, the recovery state of the pain reaction of both EA-2 Hz and EA-2 Hz/ 15 Hz groups was relatively better than that of the EA-100 Hz group from day 3 to 10 after EA intervention. EA stimulation of "Zusanli"(ST 36)-"Yanglingquan"(GB 34) at 2 Hz, 2 Hz/15 Hz and 100 Hz can significantly suppress chronic neuropathic pain induced in CCI rats, which may be closely associated with its effects in down-regulating hippocampal nNOS and PKG mRNA expression levels.


Polymorph control of luminescence properties in molecular crystals of a platinum and organoarsenic complex and formation of stable one-dimensional nanochannel.
The mononuclear diiodoplatinum(II) complex (trans-PtI2(cis-DHDAMe)2), where cis-DHDAMe = cis-1,4-dihydro-1,4-dimethyl-2,3,5,6-tetrakis(methoxycarbonyl)-1,4-diarsinine, forms three different crystalline polymorphs that can be either concomitantly or separately obtained on varying the recrystallization conditions. Cubic red crystals (α-phase) and red-orange needles (β-phase) exhibit solid-state red emissions at room temperature. Cubic red crystals of the γ-phase show no solid-state emission at room temperature. All crystalline structures were confirmed by X-ray crystallography. Room-temperature strongly luminescent crystals (α-phase) (λem = 657 nm, Φ = 0.52) have a triclinic P1 (No. 2) structure and no voids in the crystal structure. Red-orange needle-shaped crystals of the β-phase exhibit moderate red luminescence (λem = 695 nm, Φ = 0.09) at room temperature and have a trigonal, R3 (No. 148), structure. In the needlelike crystals of the β-phase, stable hexagonal arrays of nanoporous channels, 5.0 Å in diameter, are formed. Room-temperature nonluminescent crystals (γ-phase) have an orthorhombic, Pbca (No. 61), structure with a void volume that is 4.9% of the total crystal volume. After heating the α-phase crystals at 150 °C for 2 min, a powder XRD pattern different from the original crystal is obtained, and its solid-state emission at room temperature decreased. After heating the β-phase crystals at 150 °C for 2 min, the emission wavelength and the quantum yield of the solid-state emission at room temperature and the powder XRD pattern are the same as those of the α-phase after heating at 150 °C. A crystal-to-crystal transition triggered by the thermal stimulus produces a different stable polymorph of the mononuclear diiodoplatinum(II) complex. The one-dimensional nanoporous crystals encapsulated iodine without distorting the crystal packing.


Necdin and neurotrophin receptors: interactors of relevance for neuronal resistance to oxidant stress.
Necdin is a protein known to interact with the neurotrophin receptors, neurotrophic tyrosine kinase receptor type 1 (TrkA) and 75 kD low-affinity neurotrophin receptor (p75NTR). TrkA and p75NTR play roles in development and disease of the nervous system and chemoresistance of nervous system tumors. Necdin deletion is associated with Prader-Willi syndrome. The present studies demonstrate that the effects of necdin on the susceptibility of neuroblastoma cells to oxidant stress are dependent on the ratio of p75NTR to TrkA in the cell. In low p75NTR:TrkA ratio cells, necdin down-regulation decreases sensitivity to oxidant stress and expression of and signaling through TrkA. In high p75NTR:TrkA cells, necdin down-regulation is without effect. The effects of necdin deletion on the developing nervous system may depend on the relative expression of p75NTR and TrkA in the cells of particular regions of the nervous system.


Synthesis, Physicochemical Characterization, In Vitro 2D/3D Human Cell Culture, and In Vitro Aerosol Dispersion Performance of Advanced Spray Dried and Co-Spray Dried Angiotensin (1-7) Peptide and PNA5 with Trehalose as Microparticles/Nanoparticles for Targeted Respiratory Delivery as Dry Powder Inhalers.
The peptide hormone Angiotensin (1-7), Ang (1-7) or (Asp-Arg-Val-Tyr-Ile-His-Pro), is an essential component of the renin-angiotensin system (RAS) peripherally and is an agonist of the Mas receptor centrally. Activation of this receptor in the CNS stimulates various biological activities that make the Ang (1-7)/MAS axis a novel therapeutic approach for the treatment of many diseases. The related O-linked glycopeptide, Asp-Arg-Val-Tyr-Ile-His-Ser-(O-β-D-Glc)-amide (PNA5), is a biousian revision of the native peptide hormone Ang (1-7) and shows enhanced stability in vivo and greater levels of brain penetration. We have synthesized the native Ang (1-7) peptide and the glycopeptide, PNA5, and have formulated them for targeted respiratory delivery as inhalable dry powders. Solid phase peptide synthesis (SPPS) successfully produced Ang (1-7) and PNA5. Measurements of solubility and lipophilicity of raw Ang (1-7) and raw PNA5 using experimental and computational approaches confirmed that both the peptide and glycopeptide have high-water solubility and are amphipathic. Advanced organic solution spray drying was used to engineer the particles and produce spray-dried powders (SD) of both the peptide and the glycopeptide, as well as co-spray-dried powders (co-SD) with the non-reducing sugar and pharmaceutical excipient, trehalose. The native peptide, glycopeptide, SD, and co-SD powders were comprehensively characterized, and exhibited distinct glass transitions (Tg) consistent with the amorphous glassy state formation with Tgs that are compatible with use in vivo. The homogeneous particles displayed small sizes in the nanometer size range and low residual water content in the solid-state. Excellent aerosol dispersion performance with a human DPI device was demonstrated. In vitro human cell viability assays showed that Ang (1-7) and PNA5 are biocompatible and safe for different human respiratory and brain cells.


[Lamotrigine add-on therapy for childhood-onset refractory epilepsy: comparison of the efficacy between 3 months and 6 months after initiation].
We investigated the effect of lamotrigine (LTG) add-on therapy in 50 patients with childhood-onset refractory epilepsy (25 males and 25 females): 15 with localization-related epilepsy, 33 with generalized epilepsy, and 2 with undetermined epilepsy. Twenty-four patients had experienced a period of West syndrome during their clinical course. Age at the start of LTG therapy ranged from 2 years 6 months to 41 years 2 months: <16 years in 43 and > or = 16 years in 7. Seizure frequency was > or = 1 per day in 36 patients (72%) and > or = 1 per week in 14 (28%). We increased the LTG dosage every two weeks in accordance with usage recommendations. We evaluated efficacy at two points: 3 and 6 months after the start of LTG. At the 6-month point, seizure freedom was achieved in 2 patients (4%), > or = 50% seizure reduction in 14 (28%), 25 to 50% seizure reduction in 20 (40%), no effect in 6 (12%), and aggravation in 4 (8%). Only 4 patients (8%) stopped LTG therapy within 6 months due to LTG-related mild skin rash in 2 and suspicion of seizure aggravation in the other 2. In terms of seizure types, seizure freedom or > or = 50% seizure reduction was achieved in 29% for epileptic spasms, 32% for tonic seizures, and 29% for partial seizures. A comparison between the 3- and 6-month points revealed that the efficacy level was increased or maintained in 77% of the patients and decreased in 23%. In most cases, the highest level of efficacy appeared within 3 months with doses that were smaller than maintenance doses. Observed CNS-related adverse effects included somnolence in 16 patients, irritability in 14, and sleep disturbance in 11. Positive psychotropic effects in daily activities were seen in 28 patients (56%). These effects appeared regardless of the change in seizure frequency with doses that were smaller than maintenance doses.


Na(+)-H+ exchanger and its role in essential hypertension and diabetes mellitus.
The Na(+)-H+ exchanger is a ubiquitous transport system that is involved in the regulation of intracellular pH, cell growth and proliferation, cell volume regulation, and transepithelial absorption of Na+, Cl-, and HCO3-. Altered activity of the Na(+)-H+ exchanger has been implicated as a mechanism contributing to the development of high blood pressure in subgroups of patients with essential hypertension and in various animal models of hypertension. Many of these studies measured Na(+)-Li+ exchange rather than Na(+)-H+ exchange, hypothesizing that Na(+)-Li+ exchange represents a functional mode of the Na(+)-H+ exchanger. However, this is a controversial assumption. Several studies have also shown an association between erythrocyte Na(+)-Li(+)-exchange rate and predisposition to nephropathy in patients with insulin-dependent diabetes mellitus. The recent cDNA cloning of at least one isoform of the Na(+)-H+ exchanger will help clarify the cellular mechanisms of regulation of the exchanger and its possible role in pathophysiological states such as hypertension.


Neural correlates of recall of life events in conversion disorder.
Freud argued that in conversion disorder (CD) the affect attached to stressful memories is "repressed" and "converted" into physical symptoms, although this has never been subject to scientific study to our knowledge. To examine the neural correlates of recall of life events judged to be of causal significance in CD. Case-control study. Academic research setting among 12 patients with motor CD and 13 healthy control subjects. Stressful life events were assessed using the Life Events and Difficulties Schedule and rated by a blinded panel for their likelihood to cause CD based on the threat posed and the extent to which subsequent illness might allow escape from some of their consequences (termed escape). Recall of those events (escape condition) was compared with recall of equally threatening control events from the same epoch (severe condition) in a functional magnetic resonance imaging task. Relative to controls, patients showed significantly increased left dorsolateral prefrontal cortex and decreased left hippocampus activity during the escape vs severe condition, accompanied by increased right supplementary motor area and temporoparietal junction activity. Relative to controls, patients failed to activate the right inferior frontal cortex during both conditions, and connectivity between amygdala and motor areas (supplementary motor area and cerebellum) was enhanced. These data offer support for the notion that the way adverse events are processed cognitively can be associated with physical symptoms in CD. Abnormal emotion (dorsolateral prefrontal cortex and right inferior frontal cortex) and memory control (hippocampus) are associated with alterations in symptom-related motor planning and body schema (supplementary motor area and temporoparietal junction).


Efficiency of Thermally Activated Delayed Fluorescence Sensitized Triplet Upconversion Doubled in Three-Component System.
As in many fields, the most exciting endeavors in photon upconversion research focus on increasing the efficiency (upconversion quantum yield) and performance (anti-Stokes shift) while diminishing the cost of production. In this vein, studies employing metal-free thermally activated delayed fluorescence (TADF) sensitizers have garnered increased interest. Here, for the first time, the strategy of ternary photon upconversion is utilized with the TADF sensitizer 2,4,5,6-tetrakis(carbazol-9-yl)isophthalonitrile (4CzIPN), resulting in a doubling of the upconversion quantum yield in comparison to the binary system employing p-terphenyl as the emitter. In this ternary blend, the sensitizer 4CzIPN is paired with an intermediate acceptor, 1-methylnaphthalene, in addition to the emitter molecule, p-terphenyl, yielding a normalized upconversion quantum yield of 7.6% while maintaining the 0.83 eV anti-Stokes shift. These results illustrate the potential benefits of utilizing this strategy of energy-funneling, previously used only with heavy-metal based sensitizers, to increase the performance of these photon upconversion systems.


Midwives' experiences of caring for women with female genital mutilation: Insights and ways forward for practice in Australia.
Female genital mutilation (FGM) has serious health consequences, including adverse obstetric outcomes and significant physical, sexual and psychosocial complications for girls and women. Migration to Australia of women with FGM from high-prevalence countries requires relevant expertise to provide women and girls with FGM with specialised health care. Midwives, as the primary providers of women during pregnancy and childbirth, are critical to the provision of this high quality care. To provide insight into midwives' views of, and experiences working with, women affected by FGM. A descriptive qualitative study was undertaken using focus group discussions with midwives from four purposively selected antenatal clinics and birthing units in three hospitals in urban New South Wales. The transcripts were analysed thematically. Midwives demonstrated knowledge and recalled skills in caring for women with FGM. However, many lacked confidence in these areas. Participants expressed fear and a lack of experience caring for women with FGM. Midwives described practice issues, including the development of rapport with women, working with interpreters, misunderstandings about the culture of women, inexperience with associated clinical procedures and a lack of knowledge about FGM types and data collection. Midwives require education, training and supportive supervision to improve their skills and confidence when caring for women with FGM. Community outreach through improved antenatal and postnatal home visitation can improve the continuity of care provided to women with FGM.


Feasibility Study of a Small Animal PET Insert Based on a Single LYSO Monolithic Tube.
There are drawbacks with using a Positron Emission Tomography (PET) scanner design employing the traditional arrangement of multiple detectors in an array format. Typically PET systems are constructed with many regular gaps between the detector modules in a ring or box configuration, with additional axial gaps between the rings. Although this has been significantly reduced with the use of the compact high granularity SiPM photodetector technology, such a scanner design leads to a decrease in the number of annihilation photons that are detected causing lower scanner sensitivity. Moreover, the ability to precisely determine the line of response (LOR) along which the positron annihilated is diminished closer to the detector edges because the spatial resolution there is degraded due to edge effects. This happens for both monolithic based designs, caused by the truncation of the scintillation light distribution, but also for detector blocks that use crystal arrays with a number of elements that are larger than the number of photosensors and, therefore, make use of the light sharing principle. In this report we present a design for a small-animal PET scanner based on a single monolithic annulus-like scintillator that can be used as a PET insert in high-field Magnetic Resonance systems. We provide real data showing the performance improvement when edge-less modules are used. We also describe the specific proposed design for a rodent scanner that employs facetted outside faces in a single LYSO tube. In a further step, in order to support and prove the proposed edgeless geometry, simulations of that scanner have been performed and lately reconstructed showing the advantages of the design.


Zebrafish Enhancer TRAP transgenic line database ZETRAP 2.0.
Our first Zebrafish Enhancer TRAP lines database (ZETRAP) generated a few years ago was a web-based system informing the scientific community about the developmental, genetic, and genomic aspects of transgenic zebrafish lines expressing the cytosolic version of EGFP. These transgenic lines were obtained in a primary screen using Tol2 transposon-mediated transgenesis. Following that, several hundreds transgenics were generated by a systematic "rejump" of the transposon from the two distinct genomic sites. This collection was expanded further by generation of transgenics expressing the membrane-tethered version of a novel red protein KillerRed. These KR transgenics are useful not only to complement the cytosolic GFP in compound GFP/KR transgenics for improved bioimaging. They also could be used to affect cells physiology by tissue-specific optogenetic generation of reactive oxygen species. We have compiled the genomic data and expression patterns of these novel ET transgenic lines in an updated online database--the Zebrafish Enhancer TRAP lines database version 2.0 (ZETRAP 2.0). This improved and expanded version contains the sequence of regions flanking the insertion sites, links to genes in zebrafish genome, and confocal images of embryos/larvae of these transgenics.