[Overcoming experiences of family members caring for elderly patients with dementia at home].
The purpose of the study was to understand and describe the overcoming experiences of family members caring for elderly patients with dementia at home. Data came from autobiographies on the overcoming experiences of caregiving from 31 participants, who had submitted the autobiographies to a public contest held by the Seoul Metropolitan Center for Dementia in 2012. Data were analyzed using qualitative content analysis. Four overcoming stages emerged from the analysis: confronting stage; challenging stage; integrating stage; and transcendental stage, representing transformation of experiences from frustration and suffering to happiness and new hope in life. The confronting stage illustrates severe negative feelings and exhaustion occurring after the diagnosis of dementia. The challenging stage signifies major driving forces in taking good care of their patients. It includes tender loving memories about the patients as well as family and social supports. The integrating stage shows genuine empathy for the patients' situation and the happiness of 'here and now', while the transcendental stage represents new hope in the future. Health professionals need to support caregivers to find true meaning of caring and happiness in everyday life, while providing specific information on dementia care and relieving various negative feelings.


Comparative supragenomic analyses among the pathogens Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae using a modification of the finite supragenome model.
Staphylococcus aureus is associated with a spectrum of symbiotic relationships with its human host from carriage to sepsis and is frequently associated with nosocomial and community-acquired infections, thus the differential gene content among strains is of interest. We sequenced three clinical strains and combined these data with 13 publically available human isolates and one bovine strain for comparative genomic analyses. All genomes were annotated using RAST, and then their gene similarities and differences were delineated. Gene clustering yielded 3,155 orthologous gene clusters, of which 2,266 were core, 755 were distributed, and 134 were unique. Individual genomes contained between 2,524 and 2,648 genes. Gene-content comparisons among all possible S. aureus strain pairs (n = 136) revealed a mean difference of 296 genes and a maximum difference of 476 genes. We developed a revised version of our finite supragenome model to estimate the size of the S. aureus supragenome (3,221 genes, with 2,245 core genes), and compared it with those of Haemophilus influenzae and Streptococcus pneumoniae. There was excellent agreement between RAST's annotations and our CDS clustering procedure providing for high fidelity metabolomic subsystem analyses to extend our comparative genomic characterization of these strains. Using a multi-species comparative supragenomic analysis enabled by an improved version of our finite supragenome model we provide data and an interpretation explaining the relatively larger core genome of S. aureus compared to other opportunistic nasopharyngeal pathogens. In addition, we provide independent validation for the efficiency and effectiveness of our orthologous gene clustering algorithm.


Functional genomics with a comprehensive library of transposon mutants for the sulfate-reducing bacterium Desulfovibrio alaskensis G20.
The genomes of sulfate-reducing bacteria remain poorly characterized, largely due to a paucity of experimental data and genetic tools. To meet this challenge, we generated an archived library of 15,477 mapped transposon insertion mutants in the sulfate-reducing bacterium Desulfovibrio alaskensis G20. To demonstrate the utility of the individual mutants, we profiled gene expression in mutants of six regulatory genes and used these data, together with 1,313 high-confidence transcription start sites identified by tiling microarrays and transcriptome sequencing (5' RNA-Seq), to update the regulons of Fur and Rex and to confirm the predicted regulons of LysX, PhnF, PerR, and Dde_3000, a histidine kinase. In addition to enabling single mutant investigations, the D. alaskensis G20 transposon mutants also contain DNA bar codes, which enables the pooling and analysis of mutant fitness for thousands of strains simultaneously. Using two pools of mutants that represent insertions in 2,369 unique protein-coding genes, we demonstrate that the hypothetical gene Dde_3007 is required for methionine biosynthesis. Using comparative genomics, we propose that Dde_3007 performs a missing step in methionine biosynthesis by transferring a sulfur group to O-phosphohomoserine to form homocysteine. Additionally, we show that the entire choline utilization cluster is important for fitness in choline sulfate medium, which confirms that a functional microcompartment is required for choline oxidation. Finally, we demonstrate that Dde_3291, a MerR-like transcription factor, is a choline-dependent activator of the choline utilization cluster. Taken together, our data set and genetic resources provide a foundation for systems-level investigation of a poorly studied group of bacteria of environmental and industrial importance. Sulfate-reducing bacteria contribute to global nutrient cycles and are a nuisance for the petroleum industry. Despite their environmental and industrial significance, the genomes of sulfate-reducing bacteria remain poorly characterized. Here, we describe a genetic approach to fill gaps in our knowledge of sulfate-reducing bacteria. We generated a large collection of archived, transposon mutants in Desulfovibrio alaskensis G20 and used the phenotypes of these mutant strains to infer the function of genes involved in gene regulation, methionine biosynthesis, and choline utilization. Our findings and mutant resources will enable systematic investigations into gene function, energy generation, stress response, and metabolism for this important group of bacteria.


Application of active and kinase-deficient kinome collection for identification of kinases regulating hedgehog signaling.
To allow genome-scale identification of genes that regulate cellular signaling, we cloned >90% of all human full-length protein kinase cDNAs and constructed the corresponding kinase activity-deficient mutants. To establish the utility of this resource, we tested the effect of expression of the kinases on three different cellular signaling models. In all screens, many kinases had a modest but significant effect, apparently due to crosstalk between signaling pathways. However, the strongest effects were found with known regulators and novel components, such as MAP3K10 and DYRK2, which we identified in a mammalian Hedgehog (Hh) signaling screen. DYRK2 directly phosphorylated and induced the proteasome-dependent degradation of the key Hh pathway-regulated transcription factor, GLI2. MAP3K10, in turn, affected GLI2 indirectly by modulating the activity of DYRK2 and the known Hh pathway component, GSK3beta. Our results establish kinome expression screening as a highly effective way to identify physiological signaling pathway components and genes involved in pathological signaling crosstalk.


Fatal poisoning of chilhood in the Eastern Black Sea region of Turkey (2009-2013).
Poisoning is a major problem worldwide among children. Nonetheless, the offending agent, the associated morbidity and mortality vary from place to place and show changes over a period of time. The aim of this study was to investigate the medico-legal paediatric autopsies of childhood poisonings in the Eastern Black Sea Region of Turkey. Reports of autopsies performed between 2009 and 2013 in the Morgue Department of the Council of Forensic Medicine. All medico-legal paediatric autopsies in Trabzon (n:1049) were retrospectively examined. The study comprised an investigation into 62 deaths from poisoning in children aged 0-18 years. The parameters of age, sex, toxic substance category and origin were evaluated. Poisoning accounted for 5.9% of the deaths of children aged 0-18 years. Of the 62 cases, 32 (51.6%) were male and 30 (48.4%) were female, giving a female to male ratio of 1/1.1. The primary causes of fatal poisoning in children were carbon monoxide (64.5%, n = 40), followed by drugs (16.1%, n = 10), insecticides (9.7%, n = 6), mushrooms (6.5%, n = 4), and snake venom (3.2%, n = 2). The results of this study implicated carbon monoxide poisoning as a serious risk factor for mortality in our region. Childhood poisoning may be prevented by public education and simple precautions in general.


[Glycogen breakdown in the tissue of human cerebral glial tumors].
The activity of gamma-amylase (acid alpha-glucosidase) and phosphorylase in the tissue of human glial tumours and the brain tissue adjacent to the tumour was studied. A sharp (more than three-fold) increase of the activity of gamma-amylase was found in the tissue of glial tumours. In the adjacent tissues of the brain its activity was also elevated (approximately, two-fold). The activity of phosphorylase is practically lacking in human glial tumours, and is only slightly apparent in the brain tissue neighbouring the tumour. Gamma-amylase may be suggested to play an important role in glycogen metabolism of glial tumours in man.


The impact of different perceptual cues on fear and presence in virtual reality.
The impact of perceptual visual cues on spider phobic reactions has been thoroughly investigated over the last years. Although the fear of being touched by a spider is part of the clinical picture of spider phobia, findings on the impact of tactile fear cues are rare. This study uses virtual reality to selectively apply visual and tactile fear cues. Self-reported fear and the experience of presence in VR were measured in 20 phobic and 20 non-phobic participants. All participants were repeatedly exposed to visual cues, tactile cues, the combination of both and no fear relevant perceptual cues. Participants were exposed in each condition for five times in random order. Results show that tactile fear cues have the power to trigger fear independent of visual cues. Participants experienced highest levels of presence in the combined and the control condition. Presence may not only be seen in association with the emotional impact of specific cues in VR but also appears to depend on the comparability of a virtual environment to a real life situation.


Sol-Gel Derived Tertiary Bioactive Glass-Ceramic Nanorods Prepared via Hydrothermal Process and Their Composites with Poly(Vinylpyrrolidone-Co-Vinylsilane).
Bioactive glass (BG) nanoparticles have wide applications in bone repair due to their bone-bonding and biodegradable nature. In this work, nanometric rod-shaped ternary SiO2-CaO-P2O5 bioactive glass particles were prepared through sol-gel chemistry followed by a base-induced hydrothermal process at 130 °C and 170 °C for various times up to 36 h. This facile, low-temperature and surfactant-free hydrothermal process has shown to be capable of producing uniform nanorods and nanowires. One-dimensional growth of nanorods and the characteristics of siloxane bridging networks were dependent on the hydrothermal temperature and time. Hardened bioactive composites were prepared from BG nanorods and cryo-milled poly(vinylpyrrolidone-co-triethoxyvinylsilane) in the presence of ammonium phosphate as potential bone graft biomaterials. Covalent crosslinking has been observed between the organic and inorganic components within these composites. The ultimate compressive strength and modulus values increased with increasing co-polymer content, reaching 27 MPa and 500 MPa respectively with 30% co-polymer incorporation. The materials degraded in a controlled non-linear manner when incubated in phosphate-buffered saline from 6 h to 14 days. Fibroblast cell attachment and spreading on the composite were not as good as the positive control surfaces and suggested that they may require protein coating in order to promote favorable cell interactions.


Endodontic Management of a Mandibular First Molar with Unusual Canal Morphology.
A comprehensive knowledge and understanding of root canal anatomical variations are essential for successful root canal treatment. Mandibular molar teeth show considerable variations in their external and internal radicular morphology that require special attention from dental practitioners to provide the best clinical outcomes to the patients. This report aims to present root canal treatment of a mandibular first molar that has six separate root canals (three root canals in the mesial roots and three in the distal roots [236 M3 D3]). This report points out the importance of proper exploration for identifying additional canals in mandibular molars.


HDL protects against doxorubicin-induced cardiotoxicity in a scavenger receptor class B type 1-, PI3K-, and Akt-dependent manner.
Doxorubicin is a widely used chemotherapeutic with deleterious cardiotoxic side effects. HDL has been shown to protect cardiomyocytes in vitro against doxorubicin-induced apoptosis. Scavenger receptor class B type 1 (SR-B1), a high-affinity HDL receptor, mediates cytoprotective signaling by HDL through Akt. Here, we assessed whether increased HDL levels protect against doxorubicin-induced cardiotoxicity in vivo and in cardiomyocytes in culture and explored the intracellular signaling mechanisms involved, particularly the role of SR-B1. Transgenic mice with increased HDL levels through overexpression of human apolipoprotein A1 (apoA1Tg/Tg) and wild-type mice (apoA1+/+) with normal HDL levels were treated repeatedly with doxorubicin. After treatment, apoA1+/+ mice displayed cardiac dysfunction, as evidenced by reduced left ventricular end-systolic pressure and +dP/d t, and histological analysis revealed cardiomyocyte atrophy and increased cardiomyocyte apoptosis after doxorubicin treatment. In contrast, apoA1Tg/Tg mice were protected against doxorubicin-induced cardiac dysfunction and cardiomyocyte atrophy and apoptosis. When SR-B1 was knocked out, however, overexpression of apoA1 did not protect against doxorubicin-induced cardiotoxicity. Using primary neonatal mouse cardiomyocytes and human immortalized ventricular cardiomyocytes in combination with genetic knockout, inhibitors, or siRNA-mediated knockdown, we demonstrated that SR-B1 is required for HDL-mediated protection of cardiomyocytes against doxorubicin-induced apoptosis in vitro via a pathway involving phosphatidylinositol 3-kinase and Akt1/2. Our findings provide proof of concept that raising apoA1 to supraphysiological levels can dramatically protect against doxorubicin-induced cardiotoxicity via a pathway that is mediated by SR-B1 and involves Akt1/2 activation in cardiomyocytes. NEW & NOTEWORTHY We have identified an important role for the scavenger receptor class B type 1 in facilitating high-density lipoprotein-mediated protection of cardiomyocytes against stress-induced apoptosis and shown that increasing plasma high-density lipoprotein protects against the deleterious side effects of the chemotherapeutic and cardiotoxic drug doxorubicin.


Accumulation of polyphosphate granules in Helicobacter pylori cells under anaerobic conditions.
Helicobacter pylori is known to transform to coccoid forms which might be involved in faecal-oral transmission. When the bacteria enter the intestine, they encounter anaerobiosis that is unfavourable for growth. The effect of anaerobiosis was investigated to determine whether H. pylori is viable under such conditions. H. pylori in the late logarithmic growth phase transformed from spiral to coccoid forms when transferred to and incubated anaerobically in fresh medium. Acridine orange staining indicated that the viability of coccoid forms was significantly reduced, but still measurable even at day 5 or 7 of anaerobic culture. The cells retained low but significant levels of the major sigma factor RpoD at day 5 or 7 of anaerobic culture. The cellular structures of coccoid forms contained polyphosphate granules at day 1 and even at day 7 when incubated anaerobically, whereas only a few granules were observed under micro-aerobic conditions. Poor formation of polyphosphate granules in micro-aerobic cultures correlated particularly well with lower levels of acridine orange staining. These results suggest that acridine orange-positive anaerobic coccoid forms are viable to a certain extent and that polyphosphate may support this viability.


Establishing a prediction model of infection during the intravesical instillation of bladder cancer: a multicenter retrospective study.
Objective: To explore the independent risk factors of infection during the intravesical instillation of bladder cancer and establish a prediction model, which may reduce probability of infection for bladder cancer patients. Material and Methods: 533 patients with newly discovered NMIBC at two hospitals from January 2017 to December 2019 were enrolled in this study. The patients were divided into "infection positive group" and "infection negative group". The clinical data of the two groups were analyzed by logistic regression analyses. Nomogram was generated and ROC curve, calibration curve were structured to assess the accuracy of nomogram. An independent cohort included 174 patients from another hospital validated the nomogram prediction model. Results: Of 533 patients, 185 patients had an infection. Univariate and multivariate logistic regression analyses showed diabetes mellitus, hemiplegia, patients without antibiotics and perfusion frequency (≥2 times/month) were the independent risk factors. AUC of the ROC was 0.858 (0.762-0.904). The nomogram could predict the probability of infection during the intravesical instillation of bladder tumor calibration curve showed good agreement. The external data validation gained good sensitivity and specificity, which indicated that the nomogram had great value of prediction. Conclusions: Individualized prediction of the probability of infection may reduce the incidence of infection by argeted preventive measures.


Ten-year review of a prospective randomized controlled trial of textured versus smooth subglandular silicone gel breast implants.
Although textured silicone breast implants have been shown to reduce the incidence of capsular contracture, there is little evidence if this effect is maintained in the long term. It has been 10 years since the double-blind randomized trial in which 53 patients received either Mentor smooth (26) or textured silicone gel implants (27). Of the 14 patients who were not known to have developed a contracture in the smooth group, 11 were reviewed. Three had bilateral contractures. In the textured group, 18 of the 24 patients not known to have contractures were reviewed. None had developed contractures. At 10 years, the incidence of capsular contracture was 65 percent of patients with smooth implants (an increase of 6 percent on the 3-year results) and 11 percent for the textured implant patients (no change on the 3-year results). A database containing the details of 1100 patients reinforces these results by examining the differences in contracture rates of textured, smooth, and polyurethane-coated implants. The effect of submuscular placement on reducing contracture rates regardless of texturing is discussed, as is the apparent increase in capsular contracture in patients who smoke.


Melatonin attenuates the TLR4-mediated inflammatory response through MyD88- and TRIF-dependent signaling pathways in an in vivo model of ovarian cancer.
Toll-like receptors (TLRs) are effector molecules expressed on the surface of ovarian cancer (OC) cells, but the functions of the TLR2/TLR4 signaling pathways in these cells remain unclear. Melatonin (mel) acts as an anti-inflammatory factor and has been reported to modulate TLRs in some aggressive tumor cell types. Therefore, we investigated OC and the effect of long-term mel therapy on the signaling pathways mediated by TLR2 and TLR4 via myeloid differentiation factor 88 (MyD88) and toll-like receptor-associated activator of interferon (TRIF) in an ethanol-preferring rat model. To induce OC, the left ovary of animals either consuming 10% (v/v) ethanol or not was injected directly under the bursa with a single dose of 100 μg of 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in 10 μL of sesame oil. The right ovaries were used as sham-surgery controls. After developing OC, half of the animals received i.p. injections of mel (200 μg/100 g b.w./day) for 60 days. Although mel therapy was unable to reduce TLR2 levels, it was able to suppress the OC-associated increase in the levels of the following proteins: TLR4, MyD88, nuclear factor kappa B (NFkB p65), inhibitor of NFkB alpha (IkBα), IkB kinase alpha (IKK-α), TNF receptor-associated factor 6 (TRAF6), TRIF, interferon regulatory factor 3 (IRF3), interferon β (IFN-β), tumor necrosis factor alpha (TNF-α), and interleukin (IL)-6. In addition, mel significantly attenuated the expression of IkBα, NFkB p65, TRIF and IRF-3, which are involved in TLR4-mediated signaling in OC during ethanol intake. Collectively, our results suggest that mel attenuates the TLR4-induced MyD88- and TRIF-dependent signaling pathways in ethanol-preferring rats with OC.


[Carcinoma formation in a neovagina following vaginoplasty].
A carcinoma occurs only very rarely in a neovagina. This extremely rare occurrence is a suitable example of an exogenous carcinogenesis. Only 6 cases have so far been reported in literature. The clinical and morphological features are discussed on the basis of the author's own observations on one of his patients.


Combined effects of CO2 and light on the N2-fixing cyanobacterium Trichodesmium IMS101: physiological responses.
Recent studies on the diazotrophic cyanobacterium Trichodesmium erythraeum (IMS101) showed that increasing CO(2) partial pressure (pCO(2)) enhances N(2) fixation and growth. Significant uncertainties remain as to the degree of the sensitivity to pCO(2), its modification by other environmental factors, and underlying processes causing these responses. To address these questions, we examined the responses of Trichodesmium IMS101 grown under a matrix of low and high levels of pCO(2) (150 and 900 microatm) and irradiance (50 and 200 micromol photons m(-2) s(-1)). Growth rates as well as cellular carbon and nitrogen contents increased with increasing pCO(2) and light levels in the cultures. The pCO(2)-dependent stimulation in organic carbon and nitrogen production was highest under low light. High pCO(2) stimulated rates of N(2) fixation and prolonged the duration, while high light affected maximum rates only. Gross photosynthesis increased with light but did not change with pCO(2). HCO(3)(-) was identified as the predominant carbon source taken up in all treatments. Inorganic carbon uptake increased with light, but only gross CO(2) uptake was enhanced under high pCO(2). A comparison between carbon fluxes in vivo and those derived from (13)C fractionation indicates high internal carbon cycling, especially in the low-pCO(2) treatment under high light. Light-dependent oxygen uptake was only detected under low pCO(2) combined with high light or when low-light-acclimated cells were exposed to high light, indicating that the Mehler reaction functions also as a photoprotective mechanism in Trichodesmium. Our data confirm the pronounced pCO(2) effect on N(2) fixation and growth in Trichodesmium and further show a strong modulation of these effects by light intensity. We attribute these responses to changes in the allocation of photosynthetic energy between carbon acquisition and the assimilation of carbon and nitrogen under elevated pCO(2). These findings are supported by a complementary study looking at photosynthetic fluorescence parameters of photosystem II, photosynthetic unit stoichiometry (photosystem I:photosystem II), and pool sizes of key proteins in carbon and nitrogen acquisition.


Inhibition of alpha4 integrin and ICAM-1 markedly attenuate macrophage homing to atherosclerotic plaques in ApoE-deficient mice.
Monocytes/macrophages play a central role in many stages of development of atherosclerotic plaques, including the conversion to an unstable morphology with rupture and fissuring. A better understanding of the mechanism of attachment of monocytes to activated endothelial cells would prove useful in developing strategies aimed at blocking this initial step. Here we describe a novel in vivo model that directly demonstrates homing of macrophages to atherosclerotic plaques. Macrophages were loaded with fluorescent microspheres and injected intravenously into 40-week-old apolipoprotein E-deficient mice. After 48 hours, labeled macrophages were observed adhering to all stages of atherosclerotic plaques from the early fatty streak to mature calcified lesion. The mean number of macrophages adherent to atherosclerotic plaques located in the proximal 1 mm of the aortic root was quantitated by counting serial frozen sections and found to be 143 +/- 17 macrophages per aortic root. Pretreatment of the apolipoprotein E-deficient mice with monoclonal antibodies directed against the alpha-subunit of the alpha4beta1 integrin and against intracellular cell adhesion molecule (ICAM-1) reduced macrophage homing by 75% and 65%, respectively, as compared with isotype-matched controls (P<.05). Pretreatment with a monoclonal antibody directed against E-selectin did not significantly reduce macrophage homing. These data demonstrate that alpha4 integrin and ICAM-1 play major roles in the recruitment of macrophages to atherosclerotic plaques, whereas E-selectin does not appear to contribute significantly to macrophage recruitment. This model will be useful for studying the mechanism of macrophage recruitment to atherosclerotic plaques and for evaluating the efficacy of inhibitors to adhesion molecules in preventing macrophage recruitment.


[Rapidly progressive glomerulonephritis associated with hemorrhagic interstitial pneumonia. A report of 4 cases and review of the literature].
Rapidly progressive glomerulonephritis (RPGN) associated with hemorrhagic interstitial pneumonia (HIP) is an uncommon clinical syndrome. Both Goodpasture syndrome and immune complex glomerulonephritis have been recognized as the causes of this critical syndrome. We report 4 cases of RPGN with HIP. The pathological and clinical features and the treatment of RPGN with HIP are discussed.


Epidemiological features of SARS-CoV-2 Omicron infection under new control strategy: a cross-sectional study of the outbreak since December 2022 in Sichuan, China.
A major shift in the "dynamic zero-COVID" policy was announced by China's National Health Commission on December 7, 2022, and the subsequent immediate large-scale outbreak of SARS-CoV-2 infections in the entire country has caused worldwide concern. This observational cross-sectional study aimed to describe the epidemiological characteristics of this outbreak in Sichuan, China. All data were self-reported online by volunteers. We described the epidemic by characterizing the infection, symptoms, clinical duration, severity, spatiotemporal clustering, and dynamic features of the disease. Prevalence ratio (PR), Odds ratios (ORs) and adjusted ORs were calculated to analyze the associations between risk factors and infection and the associations of risk factors with clinical severity using log-binomial and multivariable logistic regression models; 95% confidence intervals (CIs) and Wald test results were reported. The prevalence rates and clinical severity among different subgroups were compared using the Chi-square and trend Chi-square tests. Between January 6 and 12, 2023, 138,073 volunteers were enrolled in this survey, and 102,645 were infected with COVID-19, holding a prevalence rate of 74.34%; the proportion of asymptomatic infections was 1.58%. Log-binomial regression revealed that the risk of infection increased among those living in urban areas. Multivariable logistic regression analysis showed that female sex, chronic diseases, older age and the fewer doses of vaccine received were associated with an increased risk of severe clinical outcomes after infection. We estimated the mean reproduction number during this pandemic was 1.83. The highest time-dependent reproduction number was 4.15; this number decreased below 1 after 11 days from December 7, 2022. Temporal trends revealed a single peak curve with a plateau pattern of incidence during the outbreak, whereas spatiotemporal clustering analysis showed that the onset in 21 cities in the Sichuan province had four-wave peaks. The peak of the first wave of Omicron infection in Sichuan Province had passed and could be considered a snapshot of China under the new control strategy. There were significant increases in the risk of severe clinical outcomes after infection among females, with chronic diseases, and the elderly. The vaccines have been effective in reducing poor clinical outcomes.


Encapsulation and release of a hydrophobic drug from hydroxyapatite coated liposomes.
Hydroxyapatite (HA) coated liposomes (HACL) have been successfully manufactured and filled with a model hydrophobic (lipophilic) drug, indomethacin (IMC). These HACL particles have been characterized in terms of particle size and zeta-potential. The liposomes are formed from 1,2-dimyristoyl-sn-glycero-3-phosphate (DMPA) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Altering their relative proportions caused the zeta-potential to change from -38.8 to -67.0 mV, with a concomitant change in phase transition temperature from 36.4 to 53.3 degrees C. These changes also affect the drug loading efficiency. The release profiles of IMC have been measured. HA coating of the liposome reduces the release rate of IMC over uncoated liposomes. Under the present experimental conditions 70% of the drug is released after approximately 5h from the liposome, but coating with HA changes this time to over 20 h. Perhaps most importantly, it has been observed that for uncoated liposomes, IMC is released at a greater rate at pH=7.4 than at pH=4. However, coating with HA reduced the rate at pH=7.4 compared to pH=4. This behaviour arises because IMC is more soluble under basic conditions, but HA is more soluble under acidic conditions. This behaviour shows that it is now possible to have environmental control over the release of drugs from HA-coated liposomes.


Preclinical corrective gene transfer in xeroderma pigmentosum human skin stem cells.
Xeroderma pigmentosum (XP) is a devastating disease associated with dramatic skin cancer proneness. XP cells are deficient in nucleotide excision repair (NER) of bulky DNA adducts including ultraviolet (UV)-induced mutagenic lesions. Approaches of corrective gene transfer in NER-deficient keratinocyte stem cells hold great hope for the long-term treatment of XP patients. To face this challenge, we developed a retrovirus-based strategy to safely transduce the wild-type XPC gene into clonogenic human primary XP-C keratinocytes. De novo expression of XPC was maintained in both mass population and derived independent candidate stem cells (holoclones) after more than 130 population doublings (PD) in culture upon serial propagation (>10(40) cells). Analyses of retrovirus integration sequences in isolated keratinocyte stem cells suggested the absence of adverse effects such as oncogenic activation or clonal expansion. Furthermore, corrected XP-C keratinocytes exhibited full NER capacity as well as normal features of epidermal differentiation in both organotypic skin cultures and in a preclinical murine model of human skin regeneration in vivo. The achievement of a long-term genetic correction of XP-C epidermal stem cells constitutes the first preclinical model of ex vivo gene therapy for XP-C patients.


CD10 is useful to identify gastrointestinal contamination in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytology from pancreatic ductal adenocarcinoma.
Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytology is an effective tool to diagnose pancreatic ductal adenocarcinoma (PDA). Standard morphological criteria are usually reliable. When contaminating gastrointestinal (GI) epithelial cells are prevalent among neoplastic cells, these can be highlighted by carcinoembryonic antigen (CEA) staining. CD10 is a cell-surface metallopeptidase normally expressed by the GI epithelial apical border, whose expression is decreased or lost in PDA. We included CD10 in a panel, together with CEA, to discriminate the GI contaminant cells from PDA cells on cell blocks. Eight cases of EUS-FNA of PDA, featuring both contaminating GI cells and neoplastic cells, whose corresponding cell blocks were available for immunostaining, were selected. CD10 and CEA were stained on cell blocks by standard methods. CD10 strongly labelled only the GI cells, with a well-defined apical membrane signal; conversely, GI cells did not show CEA staining; benign duodenal cells were faintly labelled in only one case. Malignant cells were positive for CEA and negative for CD10, with the exception of one case with labelled neoplastic cells with weak diffuse cytoplasmic positivity. CD10 apical membrane staining was a feature only seen in benign GI cells. As a loss of CD10 is a consistent feature of PDA, this marker can be useful, together with CEA, to aid the cytopathologist to identify neoplastic cells in a background rich in GI contaminant cells.


Mosquito Bite-Induced Controlled Human Malaria Infection with Plasmodium vivax or P. falciparum Generates Immune Responses to Homologous and Heterologous Preerythrocytic and Erythrocytic Antigens.
Seroepidemiological studies on the prevalence of antibodies to malaria antigens are primarily conducted on individuals from regions of endemicity. It is therefore difficult to accurately correlate the antibody responses to the timing and number of prior malaria infections. This study was undertaken to assess the evolution of antibodies to the dominant surface antigens of Plasmodium vivax and P. falciparum following controlled human malaria infection (CHMI) in malaria-naive individuals. Serum samples from malaria-naive adults, collected before and after CHMI with either P. vivax (n = 18) or P. falciparum (n = 18), were tested for the presence of antibodies to the circumsporozoite protein (CSP) and the 42-kDa fragment of merozoite surface protein 1 (MSP-142) of P. vivax and P. falciparum using an enzyme-linked immunosorbent assay (ELISA). Approximately 1 month following CHMI with either P. vivax or P. falciparum, >60% of subjects seroconverted to homologous CSP and MSP-1. More than 50% of the subjects demonstrated reactivity to heterologous CSP and MSP-142, and a similar proportion of subjects remained seropositive to homologous MSP-142 >5 months after CHMI. Computational analysis provides insight into the presence of cross-reactive responses. The presence of long-lived and heterologous reactivity and its functional significance, if any, need to be taken into account while evaluating malaria exposure in field settings.


Effects of Early Language Deprivation on Brain Connectivity: Language Pathways in Deaf Native and Late First-Language Learners of American Sign Language.
Previous research has identified ventral and dorsal white matter tracts as being crucial for language processing; their maturation correlates with increased language processing capacity. Unknown is whether the growth or maintenance of these language-relevant pathways is shaped by language experience in early life. To investigate the effects of early language deprivation and the sensory-motor modality of language on white matter tracts, we examined the white matter connectivity of language-relevant pathways in congenitally deaf people with or without early access to language. We acquired diffusion tensor imaging (DTI) data from two groups of individuals who experienced language from birth, twelve deaf native signers of American Sign Language, and twelve hearing L2 signers of ASL (native English speakers), and from three, well-studied individual cases who experienced minimal language during childhood. The results indicate that the sensory-motor modality of early language experience does not affect the white matter microstructure between crucial language regions. Both groups with early language experience, deaf and hearing, show leftward laterality in the two language-related tracts. However, all three cases with early language deprivation showed altered white matter microstructure, especially in the left dorsal arcuate fasciculus (AF) pathway.


Physical Activity Among Adolescent Cancer Survivors: The PACCS Study.
Physical activity (PA) may modify risks of late effects after cancer. We aimed to examine levels of PA and sedentary time (ST) in a large, international sample of adolescent childhood cancer survivors in relation to sociodemographic and cancer-related factors and compare levels of PA and ST to reference cohorts. Survivors from any cancer diagnosis who had completed cancer treatment ≥1 year ago, aged 9 to 16 years, were eligible for the multicenter Physical Activity in Childhood Cancer Survivors study. PA and ST were measured by ActiGraph GT3X+ accelerometers. We performed linear regression analyses to assess factors associated with moderate-to-vigorous PA (MVPA) and ST, and compared marginal means of total PA, MVPA, and ST in 432 survivors to sex- and age-stratified references (2-year intervals) using immediate t-tests for aggregated data. Among survivors, 34% fulfilled the World Health Organization's PA recommendation of ≥60 min of daily MVPA on average and their ST was 8.7 hours per day. Being female, older, overweight, a survivor of central nervous system tumor, or having experienced relapse were associated with lower MVPA and/or higher ST. Generally, male survivors spent less time in MVPA compared with references, whereas female survivors had similar levels. Both male and female survivors had higher ST than references in nearly all age groups. The low PA and high ST in this large sample of adolescent childhood cancer survivors is worrisome. Combined, our results call for targeted interventions addressing both PA and ST in follow-up care after childhood cancer.


Completing a scholarly project during residency training. Perspectives of residents who have been successful.
Resident research has potential benefits and scholarly activity is an internal medicine residency training requirement. This study sought to learn about the resources needed and the barriers to performing scholarly work during residency from residents who had been successful. A questionnaire was delivered to 138 internal medicine residents presenting their work at the 2002 American College of Physicians-American Society of Internal Medicine annual session. Residents were asked to comment on why they had participated in a scholarly project, the skills and resources needed to complete the project, as well as the barriers. Comparisons were made between residents who presented a research abstract and those who exhibited a clinical vignette. Seventy-three residents (53%) completed the questionnaire. Thirty-nine residents presented a clinical vignette and 34 displayed a research abstract. Residents participated in research for a variety of reasons, including intellectual curiosity (73%), career development (60%), and to fulfill a mandatory scholarly activity requirement at their residency program (32%). The most common barriers were insufficient time (79%), inadequate research skills (45%), and lack of a research curriculum (44%). Residents who had presented research abstracts devoted more time (median, 200 vs 50 hours; P<.05) to their project than those who exhibited clinical vignettes. Sixty-nine percent of residents thought research should be a residency requirement. The majority of respondents reported that their scholarly project was a worthwhile experience despite considerable barriers. Teaching research skills more explicitly with a focused curriculum and providing adequate protected time may enable residents to be successful.


Contemporary Approaches to Modulating the Nitric Oxide-cGMP Pathway in Cardiovascular Disease.
Endothelial cells lining the vessel wall control important aspects of vascular homeostasis. In particular, the production of endothelium-derived nitric oxide and activation of soluble guanylate cyclase promotes endothelial quiescence and governs vasomotor function and proportional remodeling of blood vessels. Here, we discuss novel approaches to improve endothelial nitric oxide generation and preserve its bioavailability. We also discuss therapeutic opportunities aimed at activation of soluble guanylate cyclase for multiple cardiovascular indications.


Eat dirt and avoid atopy: the hygiene hypothesis revisited.
The explosive rise in the incidence of atopic diseases in the Western developed countries can be explained on the basis of the so-called "hygiene hypothesis". In short, it attributes the rising incidence of atopic dermatitis to reduced exposure to various childhood infections and bacterial endotoxins. Reduced exposure to dirt in the clean environment results in a skewed development of the immune system which results in an abnormal allergic response to various environmental allergens which are otherwise innocuous. This article reviews the historical aspects, epidemiological and immunological basis of the hygiene hypothesis and implications for Indian conditions.


[Effect of a modification of the medium on the structure of bacterial cells based on electron microscopy data].
Electron microscopy was used to study the interactions between microorganisms and the culture medium in the presence of modifying agents. Temperature-dependent changes in the intensity of water-glycerin exchange between the cells and the medium are demonstrated, which is of interest for the optimization of the conditions of using protectors, as well as for the study of the permeability of cell membranes.


[Chemical structure and immunostimulating activity of high molecular weight polysaccharides].
An immunostimulating activity of high molecular polysaccharides, dissimilar in their chemical structure, was studied. Inoculation of mice with bacteria of typhoid fever and Kl. pneumoniae demonstrated that O-polysaccharide from typhoid bacteria--multicomponent, branch-chained, phosphorus-containing polysaccharide--exhibited the highest immunostimulating effect. Mannans and glucans, with linear and branch-chained molecules, involving various types of C-C bonds, had lower stimulating properties, which did not correlate with the level of a molecule branching and the type of C-C bonds. These data were confirmed after evaluation of adjuvant properties of high molecular polysaccharides with sheep erythrocytes and their ability to activate macrophages.


Vasopressor and depressor actions of angiotensin in the anesthetized fowl.
Vasopressor and depressor properties of angiotensins (ANG) were characterized in the anesthetized, adult female chicken Gallus gallus. [Asp1,Val5,Ser9]ANG I and [Asp1,Val5]ANG II (native fowl angiotensins) increased blood pressure, and removal or replacement of the amino acid in position 1 decreased pressor potency. The pressor effect of [Asp1,Val5]ANG II was inhibited nearly completely with [Sar1,Ile8]ANG II (5 micrograms.kg-1.min-1) and partially with [Sar1,Thr8]ANG II, [Ile8]ANG III, and [Ile8]ANG I. Phenoxybenzamine, reserpine, or 6-hydroxydopamine reduced the pressor action to one-third. After administration of these compounds [Asp1,Val5]ANG II caused biphasic responses, a depressor followed by a small pressor response. [Sar1,Ile8]ANG II completely, and meclofenamate partially, blocked the depressor response, whereas propranolol, methysergide, vasopressin antagonists, or atropine did not. These results suggest that in fowl 1) the first (Asp) and eighth (Phe) amino acids are important for receptor binding and action, 2) vasopressor action of angiotensin may be primarily caused by release of catecholamines, and 3) angiotensin may exert depressor action possibly by acting directly on the vascular smooth muscle.


Tissue Expansion Improves the Outcome and Predictability for Alveolar Bone Augmentation: Prospective, Multicenter, Randomized Controlled Trial.
The purpose of this study was to evaluate the effectiveness of the intraoral use of subperiosteally placed self-inflating tissue expanders for subsequent bone augmentation and implant integrity. A prospective, multicenter, randomized controlled trial was performed on patients requiring alveolar bone graft for dental implant insertion. Patients were assigned to three groups: tissue expansion and tunneling graft (TET group), tissue expansion and conventional bone graft (TEG), and control group without tissue expansion. Dimensional changes of soft tissue and radiographic vertical bone gain, retention, and peri-implant marginal bone changes were evaluated and secondary outcomes; clinical complications and thickness changes of expanded overlying tissue were assessed. Among 75 patients screened, a total of 57 patients were included in the final analysis. Most patients showed uneventful soft tissue expansion without any inflammatory sign or symptoms. Ultrasonographic measurements of overlying gingiva revealed no thinning after tissue expansion (p > 0.05). Mean soft vertical and horizontal tissue measurements at the end of its expansion were 5.62 and 6.03 mm, respectively. Significantly higher vertical bone gain was shown in the TEG (5.71 ± 1.99 mm) compared with that in the control patients (4.32 ± 0.97 mm; p < 0.05). Hard tissue retention- measured by bone resorption after 6 months-showed that control group showed higher amount of vertical (2.06 ± 1.00 mm) and horizontal bone resorption (1.69 ± 0.81 mm) compared to that of the TEG group (p < 0.05). The self-inflating tissue expander effectively augmented soft tissue volume and both conventional bone graft and tunneling techniques confirmed their effectiveness in bone augmentation. With greater amount of bone gain and better 6 month hard tissue integrity, the TEG group compared to the control group-without tissue expansion-showed that the combined modality of tissue expander use and guided bone regeneration (GBR) technique may improve the outcome and predictability of hard tissue augmentation.


Biological effects and medical applications of infrared radiation.
Infrared (IR) radiation is electromagnetic radiation with wavelengths between 760nm and 100,000nm. Low-level light therapy (LLLT) or photobiomodulation (PBM) therapy generally employs light at red and near-infrared wavelengths (600-100nm) to modulate biological activity. Many factors, conditions, and parameters influence the therapeutic effects of IR, including fluence, irradiance, treatment timing and repetition, pulsing, and wavelength. Increasing evidence suggests that IR can carry out photostimulation and photobiomodulation effects particularly benefiting neural stimulation, wound healing, and cancer treatment. Nerve cells respond particularly well to IR, which has been proposed for a range of neurostimulation and neuromodulation applications, and recent progress in neural stimulation and regeneration are discussed in this review. The applications of IR therapy have moved on rapidly in recent years. For example, IR therapy has been developed that does not actually require an external power source, such as IR-emitting materials, and garments that can be powered by body heat alone. Another area of interest is the possible involvement of solar IR radiation in photoaging or photorejuvenation as opposites sides of the coin, and whether sunscreens should protect against solar IR? A better understanding of new developments and biological implications of IR could help us to improve therapeutic effectiveness or develop new methods of PBM using IR wavelengths.


[Mutation in the MSH2 gene in Muir-Torre syndrome].
The Muir-Torre syndrome is an autosomal dominant hereditary condition predisposing to cancer. It is characterized by skin tumors associated with adenocarcinoma of the colon or other neoplasias observed in the context of hereditary non-polyposis colorectal cancer (HNPCC). The Muir-Torre syndrome is also characterized by the frequent presence of multiple colonic polyps and the relatively moderate aggressivity of the tumors. We studied a family with Muir-Torre syndrome. We sequenced the exons of the hMSH2 gene in this family and identified heterozygous germinal mutation by G insert at position 2427 (2427insG). This mutation changes the lecture phase producing a premature codon stop. Our study confirms the predominant responsibility of the hMSH2 gene in Tuir-Torre syndrome. This clinical case and data reported in the literature demonstrate the importance of searching for a history of non-polyposis colorectal cancer in patients and relatives and the unstable genome characteristic of these tumors found in sebaceous tumors or keratoacanthomas. Sequencing the hMSH2 gene should be a priority when clinical features, history and laboratory tests suggest Muir-Torre syndrome.


Range-Adaptive Value Representation in Different Stages of Schizophrenia: A Proof of Concept Study.
Amotivation is related to value representation. A comprehensive account of amotivation requires a mechanistic understanding of how the brain exploits external information to represent value. To achieve maximal value discriminability, brain valuation system will dynamically adapt its coding sensitivity to the range of values available in any given condition, so-called range adaptive coding. We administered an experimental task to 30 patients with chronic schizophrenia (C-SCZ), 30 first-episode schizophrenia (FE-SCZ), 34 individuals with high social anhedonia (HSoA), and their paired controls to assess range adaptation ability. C-SCZ patients exhibited over-adaptation and their performances were negatively correlated with avolition symptoms and positive symptoms and positively correlated with blunted-affect symptoms and self-reported consummatory interpersonal pleasure scores, though the results were non-significant. FE-SCZ patients exhibited reduced adaptation, which was significantly and negatively correlated with avolition symptoms and positively correlated with the overall proportion of choosing to exert more effort. Although HSoA participants exhibited comparable range adaptation to controls, their performances were significantly and negatively correlated with the proportion of choosing to exert more effort under the lowest value condition. Our results suggest that different stages of schizophrenia spectrum showed distinct range adaptation patterns. Range adaptation impairments may index a possible underlying mechanism for amotivation symptoms in FE-SCZ and more complicated and pervasive effects on clinical symptoms in C-SCZ.


Low temperature deposition of indium tin oxide films by plasma ion-assisted evaporation.
Coatings of transparent conductive oxides, especially indium tin oxide (ITO), are important in different fields. So far, application of these materials has been limited to substrates with high thermal stability. We describe an improved coating process for ITO based on plasma ion-assisted evaporation at a substrate temperature below 100 degrees C, which is suitable for organic substrates. In characterizing the thin films, we used the classical Drude theory to calculate the resistivity from optical film properties and compared the data with linear four-point measurements. X-ray diffraction spectroscopy was used to determine the structural properties of the thin films.


DNA Damage Induces a Secretory Program in the Quiescent TME that Fosters Adverse Cancer Phenotypes.
Carcinomas develop in complex environments that include a diverse spectrum of cell types that influence tumor cell behavior. These microenvironments represent dynamic systems that contribute to pathologic processes. Damage to DNA is a notable inducer of both transient and permanent alterations in cellular phenotypes. Induction of a DNA damage secretory program is known to promote adverse tumor cell behaviors such as proliferation, invasion, metastasis, and treatment resistance. However, prior studies designed to identify genotoxic stress-induced factors evaluated actively proliferating in vitro cultures of cells such as fibroblasts as experimental models. Conversely, the vast majority of benign cells in a typical tumor microenvironment (TME) are not proliferating but rather exist in quiescent (i.e., G0) or in terminally differentiated states. In this study, the diversity and magnitude of transcriptional responses to genotoxic damage in quiescent prostate fibroblasts were assessed using gene expression profiling. The secretory damage response in quiescent cells was highly concordant with that of actively dividing cells. Quiescent human prostate stroma exposed to genotoxic agents (e.g., mitoxantrone) in vivo resulted in significant upregulation (2.7- to 5.7-fold; P ≤ 0.01) of growth factors and cytokines including IL1β, MMP3, IL6, and IL8. The paracrine effects of damaged quiescent cells consistently increased the proliferation and invasion of prostate cancer cells and promoted cell survival and resistance to apoptosis following exposure to chemotherapy.Implications: Benign quiescent cells in the TME respond to genotoxic stress by inducing a secretory program capable of promoting therapy resistance. Developing approaches to suppress the secretory program may improve treatment responses. Mol Cancer Res; 15(7); 842-51. ©2017 AACR.


A high-intensity functional weight-bearing exercise program for older people dependent in activities of daily living and living in residential care facilities: evaluation of the applicability with focus on cognitive function.
Knowledge concerning the applicability and the effect of high-intensity exercise programs is very limited for older people with severe cognitive and physical impairments. The primary aim of this study was to evaluate the applicability of a high-intensity functional weight-bearing exercise program among older people who are dependent in activities of daily living and living in residential care facilities. A second aim was to analyze whether cognitive function was associated with the applicability of the program. The subjects were 91 older people (mean age=85.3 years, SD=6.1, range=68-100) who were dependent in personal activities of daily living and randomly assigned to participate in an exercise intervention. Their mean score for the Mini-Mental State Examination (MMSE) was 17.5 (SD=5.0, range=10-29). A high-intensity functional weight-bearing exercise program was performed in groups of 3 to 7 participants who were supervised by physical therapists. There were 29 exercise sessions over 13 weeks. Attendance, intensity of lower-limb strength and balance exercises, and occurrence and seriousness of adverse events were the outcome variables in evaluating the applicability of the program. The median attendance rate was 76%. Lower-limb strength exercises with high intensity were performed in a median of 53% of the attended exercise sessions, and balance exercises with high intensity were performed in a median of 73% of the attended exercise sessions. The median rate of sessions with adverse events was 5%. All except 2 adverse events were assessed as minor and temporary, and none led to manifest injury or disease. No significant differences were observed in applicability when comparing participants with dementia and participants without dementia. In addition, there was no significant correlation between applicability and the MMSE score. The results suggest that a high-intensity functional weight-bearing exercise program is applicable for use, regardless of cognitive function, among older people who are dependent in activities of daily living, living in residential care facilities, and have an MMSE score of 10 or higher.


Adenine nucleotide pool and energy charge during growth of a tyrothricin-producing strain of Bacillus brevis.
The adenine nucleotide levels and derived energy charge value of a tyrothricin-producing strain of Bacillus brevis under aerobic conditions were in good agreement with published values for other bacteria. When growing cultures of B. brevis underwent a transition from aerobic to anaerobic conditions, cyclic variations in the level of adenine nucleotides were observed and the energy charge value oxcillated between 0.87 and 0.70. The significance of these changes is considered in relation to antibiotic production as a possible regulatory mechanism in energy metabolism. It is concluded that tyrothricin is not directly involved in the observed changes in energy charge value.


Public health and communication: impasses facing Brazil's National Health System in democratic public opinion formation.
This article discusses the political relations between construction of Brazil's national health system (SUS) and communication. Understanding communication as an underdeveloped field of citizens' rights in Brazil, it proceeds on the hypothesis that the democratic formation of public opinion regarding the SUS is hindered by a media oligopoly in the telecommunication and journalism system. This affects relations between the forces in dispute over construction of the SUS. Drawing on analysis of opinion polls and studies of Brazilian media coverage of the SUS, it argues that communication is a key political determinant in building a social base in support of the SUS and overcoming the impasses identified by the literature. It concludes that the relationship among communication, politics and democracy challenges the SUS to dispute the formation of a public health awareness in the daily lives of Brazilian citizens, as expressed by Giovanni Berlinguer to Brazil's nascent health sector reform movement in the 1970s.


Oligodendroglioma: an analysis of 42 cases.
This paper presents the clinical and pathological data obtained from 42 patients with oligodendroglioma diagnosed over a 20 year period at Addenbrooke's Hospital, Cambridge. In all cases the diagnosis was established unequivocally by histological examination. The principal conclusions of this study were: (1) the outcome was not as favourable as anticipated, nine patients dying within 1 year of diagnosis, and only 10 patients surviving 5 years, (2) age at the time of diagnosis was the single most important prognostic factor, patients under 45 years at diagnosis having a significantly greater survival time than older patients, (3) two other factors had a significantly adverse effect on prognosis, namely the presence of a focal neurological deficit at the time of diagnosis and the presence of nuclear pleomorphism in the tumour when examined histologically, (4) although cells containing glial fibrillary acidic protein were demonstrated in almost every tumour, their number and distribution did not appear to influence the prognosis.


Improving the execution of clinical guidelines and temporal data abstraction high-frequency domains.
The execution of clinical guidelines and protocols (CGPs) is a challenging task in high-frequency domains such as Intensive Care Units. On the one hand, sophisticated temporal data abstraction is required to match the low-level information from monitoring devices and electronic patient records with the high-level concepts in the CGPs. On the other hand, the frequency of the data delivered by monitoring devices mandates a highly efficient implementation of the reasoning engine which handles both data abstraction and execution of the guideline. The language Asbru represents CGPs as a hierarchy of skeletal plans and integrates intelligent temporal data abstraction with plan execution to bridge the gap between measurements and concepts in CGPs. We present our Asbru interpreter, which compiles abstraction rules and plans into a network of abstraction modules by the system. This network performs the content of the plans triggered by the arriving patient data. Our approach evaluated to be efficient enough to handle high-frequency data while coping with complex guidelines and temporal data abstraction.


Drug dreams in outpatients with bipolar disorder and cocaine dependence.
Patients with substance abuse or dependence often have dreams about alcohol or drugs during early recovery. However, the literature on drug dreams in rehabilitating patients with drug-related disorders remains limited. No data are available on drug dreams in people with substance-related disorders and other major mental illness. As part of a large study on the use of lamotrigine in patients with bipolar disorder and cocaine dependence, the frequency and nature of drug dreams, triggers for dreams, and response to the dreams during study participation were assessed in 37 outpatients for as long as 36 weeks. Altogether, 74% of participants experienced at least one drug dream during the study. Furthermore, drug dreams rapidly decreased during study participation. The presence of drug dreams at baseline did not predict mood, cocaine craving, or drug use at exit. No clear risk factors for drug dreams were identified. However, drug dreams were related to survival in the study by a negative U-shaped curve relationship in which those participants with the highest and lowest frequency of drug dreams discontinued from the study the earliest. Content of the dreams frequently included drug use or refusing to use the drug. Dreams of drug use tended to occur during the first few weeks of study participation. Most dreams were associated with triggers for drug use. The findings suggest that drug dreams are common in patients with bipolar disorder and cocaine dependence and are similar in nature to those previously reported in people with pure substance abuse.


Anti-inflammatory drugs and experimental bronchitis.
Chronic bronchitis (chronic hypersecretion) and chronic bronchiolitis (small airways disease) are two conditions associated with cigarette smoking: both contribute to airflow obstruction in man, the latter associated with progressive deterioration in lung function. Mucous metaplasia and hyperplasia are characteristic histological changes. Experimentally, cigarette smoke given daily for two weeks, induces similar histological changes in the airways of specific pathogen-free rats, providing a suitable animal model for study: an early proliferation of basal cells, accompanied by mucous metaplasia of surface epithelial serous cells is followed by proliferation of newly formed mucous cells. There is also a significant increase in epithelial thickness due to cell hypertrophy without stratification or prior ulceration. Experimentally, secretory cell hyperplasia is inhibited completely or to varying degrees by prophylactic administration (intraperitoneal injection) of either indomethacin, flurbiprofen, dexamethasone, prednisolone, hydrocortisone (each at 2 or 4 mg/kg body weight) or a mucolytic drug, N-acetylcysteine(Nac), given orally as a 1% solution of the drinking water. Nac also inhibits the associated mucus-hypersecretion. It takes between 21 and 84 days, depending on airway level, for the increase in secretory cell number to return to control values (ie recover). Indomethacin and flurbiprofen (4 mg/kg, by ip injection) shorten recovery to between 4 and 9 days in intrapulmonary airways but have no effect on recovery time in the rat trachea. Nac is effective in 6 of 7 airway levels which showed cigarette smoke-induced mucous cell hyperplasia. In conclusion, in the rat, the response to cigarette smoke is one of mucous cell metaplasia and both basal and mucous cell proliferation. Cigarette smoke-induced mucous cell hyperplasia can be inhibited when selected drugs are given concurrently with the cigarette smoke: indomethacin, fluriprofen and Nac are also therapeutic.


Recent insights in primary immunodeficiency diseases: the role of T-lymphocytes and innate immunity.
In recent years, the field of primary immunodeficienciency diseases (PID) has experienced remarkable progress with the identification of a number of new genes associated with specific diseases. Yet the diagnosis of PID remains difficult. In fact, this field requires continuous updating because once a novel molecule related to the immune function is discovered, the corresponding PID will soon be described. Since comprehensive reviews on the classification of PID are available, we concentrate here on reviewing some controversial and new issues, mainly those related to the role of T-cells and innate immunity. We will consider common variable immunodeficiency as an example of a PID where several immune pathways are impaired. We will also discuss the restricted usage of the T-cell receptor repertoire in PID. Innate immunity and Toll-like receptors (TLR) are new major players in this field. We will therefore discuss the association of TLR with the function of Bruton tyrosine kinase (Btk) that is essential in the development of B-cells and in the pathogenesis of X-linked agammaglobulinemia. Finally, we will discuss the role of mast-cells. These cells were once thought to be relevant almost exclusively to the pathogenesis of allergy. Now we know that mast cells are involved in initiating the adaptive response and may contribute to ineffective immune responses.


Adiponectin independently predicts metabolic syndrome in overweight Latino youth.
Adiponectin may be important in the pathogenesis of insulin resistance and the metabolic syndrome in youth. The objective of the study was to determine the unique effect of adiponectin on the metabolic syndrome in overweight Latino youth. Participants included 175 overweight children (aged 11.1 +/- 1.7 yr, body mass index percentile 97.3 +/- 2.9) with a family history of type 2 diabetes. Metabolic syndrome was defined according to a pediatric adaptation of the Adult Treatment Panel III report and included dyslipidemia, abdominal obesity, elevated blood pressure, and prediabetes (impaired fasting glucose or impaired glucose tolerance from a 2-h oral glucose tolerance test). Body composition was estimated via dual-energy x-ray absorptiometry, insulin sensitivity was quantified by the frequently sampled iv glucose tolerance test, visceral fat was measured using magnetic resonance imaging, and adiponectin was determined in fasting serum. In simple linear regression, adiponectin was significantly and inversely related to systolic blood pressure (P < 0.05), waist circumference (P < 0.001), triglycerides (P < 0.001), and 2-h glucose levels (P < 0.05) and positively related to high-density lipoprotein-cholesterol (P < 0.001). In multiple linear regression, adiponectin was significantly related to triglycerides (P < 0.01) and high-density lipoprotein-cholesterol (P < 0.01) independent of age, gender, Tanner stage, body composition, and insulin sensitivity. Analyses of covariance established that adiponectin levels were approximately 25% higher in healthy overweight youth, compared with those with the metabolic syndrome (12.5 +/- 3.5 vs. 9.4 +/- 2.8 microg/ml; P < 0.05). In multiple logistic regression, adiponectin was a significant independent predictor of the metabolic syndrome, even after adjustment for confounders including insulin sensitivity and visceral fat. Hypoadiponectinemia is an independent biomarker of the metabolic syndrome, and thus, adiponectin may play a role in the pathophysiology of the disorder in overweight youth.


Integrated system responses for families impacted by violence: a scoping review protocol.
The impacts of violence have a significant effect on health and well-being, particularly for women and children. Violence within families is widely recognised as a complex problem constituted by constantly interacting and evolving social, economic, health and cultural elements. Calls for integrated services have arisen from growing understanding about the implications of this complexity, which suggest family violence and solutions to it are generated endogenously from the reflexive nonlinear interactions of system agents. Despite these calls for integration, services designed to support families impacted by violence and the systems that design and fund them are often responsive only to one part of the problem and might not pay attention to agent interactions and their adaptive reflexivity. This paper outlines a scoping protocol to explore how integrated approaches to family violence are conceptualised in current literature, with innovative use of a complexity theory lens. Our scoping review protocol follows the framework outlined by Arksey and O'Malley and refined by Levac. It searches 6 databases, 3 journals and 10 websites using keywords to capture the notion of integration and a complex adaptive system, namely the participant (system agents), concept (system agent interaction) and the context (family violence). Selection criteria require the articles to be written in English, have full-text article available, and were published after 2010. Items selected also need to be evidence based showing interaction between system agents. Applying complexity theory, sensitises us to the reflexive patterns of interaction between system elements and routine ways of interacting. The nature of this review means that ethics approval is not required. Findings will be disseminated via academic publications, conferences and discussions with policy decision-makers. The findings will be used to develop a plan for stakeholder consultation to share and validate learnings and inform future research.


Post-stroke hemiplegia rehabilitation: evolution of the concepts.
Stroke rehabilitation has undergone a revolution over the last three decades. Cohort studies have consistently reinforced the importance of post-stroke rehabilitation to stimulate recovery, but the concepts of empirical methods originally proposed by therapists to rehabilitate these patients have not withstood clinical analysis. Functional neuroimaging and animal models have unveiled the mechanisms underlying functional recovery and helped teams understand its limitations and improvement modalities. These neuroscience discoveries constitute the grounds needed to understand the emergence of new technologies: robotics and virtual reality. The objective of this review of the literature was to select key works in this field to better understand current therapeutic possibilities.


The therapeutic and protective effects of bee pollen against prenatal methylmercury induced neurotoxicity in rat pups.
The current study evaluated the protective and therapeutic potency of bee pollen in ameliorating the toxic effects of methylmercury (MeHg), by measuring certain biochemical parameters related to neurotransmission, neuroinflammation, apoptosis, and glutamate excitotoxicity in the male neonate brain. Healthy, pregnant female rats (N = 40) were randomly divided into 5 groups, each comprising10 male neonates, as follows: (i) neonates delivered by control mothers; (ii) neonates delivered by MeHg-treated mothers who received 0.5 mg/kg BW/day MeHg via drinking water from gestational day 7 till postnatal day 7; (iii) neonates delivered by bee pollen treated mothers who received 200-mg/kg BW bee pollen from postnatal day 0 for 4 weeks; (iv) protective group of neonates delivered by MeHg and bee pollen-treated mothers, who continued to receive bee pollen until day 21 at the same dose, and (v) therapeutic group of neonates delivered by MeHg- treated mothers followed by bee pollen treatment, wherein they received 200-mg/kg BW bee pollen from postnatal day 0 for 4 weeks. Selected biochemical parameters in brain homogenates from each group were measured. MeHg-treated groups exhibited various signs of brain toxicity, such as a marked reduction in neurotransmitters (serotonin (5-HT), nor-adrenalin (NA), dopamine (DA)) and gamma aminobutyric acid (GABA) and elevated levels of interferon gamma (IFN-γ), caspase-3, and glutamate (Glu). Bee pollen effectively reduced the neurotoxic effects of MeHg. Minimal changes in all measured parameters were observed in MeHg-treated animals compared to the control group. Therefore, bee pollen may safely improve neurotransmitter defects, inflammation, apoptosis, and glutamate excitotoxicity.


Analysis of prognostic factors and comparison of prognostic index scores in patients with brain metastases after whole-brain radiotherapy.
Brain metastases (BMs) are typically associated with poor patient prognosis. Radiation therapy remains the primary treatment for BMs, and patient's prognosis is affected by many factors. The aim of this study was to identify prognostic factors and to compare prognostic index scores in patients with BMs who received whole-brain radiotherapy (WBRT). A retrospective prognostic study was conducted in 125 patients with BMs who underwent WBRT between Jan 2008 and Jul 2011. The significance of prognostic variables with regard to survival was determined using univariate and multivariate analyses. A prognostic index (PI) was established based on Cox regression analysis and subgrouping values. The recursive partitioning analysis classes (RPA), basic score for brain metastases (BS-BM), Graded Prognostic Assessment index (GPA), and PI were assessed with regard to prognosis. The median survival time was 213 days (7.1 months). In the univariate analysis of the test group, survival was significantly associated with Karnofsky performance status (KPS) score, the number of BMs, the presence of extracranial metastases, primary tumor status and the number of involved extracranial organs. The multivariate analysis showed that the KPS score (P = 0.002, Wald = 9.700), presence of extracranial metastases (P = 0.018, Wald = 5.604) and primary tumor status (P = 0.001, Wald = 10.212) were significantly correlated with overall survival. RPA, BS-BM and GPA were all closely related to prognosis, as determined using a log-rank test. In predicting the 3- and 6-month survival for patients, the PI was superior to the other three modes. The three indexes, RPA, BS-BM and GPA, are valid prognostic index models; however, the PI model was the most powerful.


Diagnosis, management and prevention of Candida auris in hospitals: position statement of the Australasian Society for Infectious Diseases.
Candida auris is an emerging drug-resistant yeast responsible for hospital outbreaks. This statement reviews the evidence regarding diagnosis, treatment and prevention of this organism and provides consensus recommendations for clinicians and microbiologists in Australia and New Zealand. C. auris has been isolated in over 30 countries (including Australia). Bloodstream infections are the most frequently reported infections. Infections have crude mortality of 30-60%. Acquisition is generally healthcare-associated and risks include underlying chronic disease, immunocompromise and presence of indwelling medical devices. C. auris may be misidentified by conventional phenotypic methods. Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry or sequencing of the internal transcribed spacer regions and/or the D1/D2 regions of the 28S ribosomal DNA are therefore required for definitive laboratory identification. Antifungal drug resistance, particularly to fluconazole, is common, with variable resistance to amphotericin B and echinocandins. Echinocandins are currently recommended as first-line therapy for infection in adults and children ≥2 months of age. For neonates and infants <2 months of age, amphotericin B deoxycholate is recommended. Healthcare facilities with C. auris should implement a multimodal control response. Colonised or infected patients should be isolated in single rooms with Standard and Contact Precautions. Close contacts, patients transferred from facilities with endemic C. auris or admitted following stay in overseas healthcare institutions should be pre-emptively isolated and screened for colonisation. Composite swabs of the axilla and groin should be collected. Routine screening of healthcare workers and the environment is not recommended. Detergents and sporicidal disinfectants should be used for environmental decontamination.


Use of precision-fed cecectomized rooster assay and digestible indispensable amino acid scores to characterize plant- and yeast-concentrated proteins for inclusion in canine and feline diets.
Increased consumer interest in high-quality and novel protein sources has driven the demand for the inclusion of protein-rich ingredients in companion animal diets. Novel protein concentrates, with protein contents of at least 50%, have been used to satisfy these consumer demands. However, minimal information is available regarding the macronutrient composition and protein quality of these ingredients that is needed for proper formulation of pet foods. Therefore, the objectives of this study were to determine the macronutrient and amino acid compositions, standardized amino acid digestibility according to the precision-fed rooster assay, and protein quality using digestible indispensable amino acid score (DIAAS like) of pea protein (PP), potato protein (POP), faba bean protein (FBP), soy protein concentrate (SPC), and dried yeast (DY). Precision-fed rooster assays were conducted using cecectomized roosters to calculate standardized amino acid digestibility and true metabolizable energy corrected for nitrogen (TMEn). For all five protein concentrates, all essential amino acids were highly digestible (88.0% to 96.3%, dry matter basis) with differences (P < 0.05) in only lysine, methionine, and tryptophan digestibilities. The TMEn values were highest for POP (4.22 kcal/g) and DY (3.61 kcal/g). The DIAAS-like values for adult dogs indicated that methionine was the first-limiting amino acid in all protein concentrates except POP, where the first-limiting amino acid was tryptophan. Using Association of American Feed Control Officials (AAFCO)-recommended values for adult cats, DIAAS-like values for methionine were lowest (P < 0.05) for FBP at 81.5%, with all other amino acids for all protein concentrates over 100%. The National Research Council (NRC)-recommended allowances for adult cats indicated that DIAAS-like methionine values for PP (92.7%) and FBP (73.8%) were significantly lower (P < 0.05) with these being the first-limiting amino acids, with the remaining amino acids above 100% for the other protein concentrates. The protein quality and high essential amino acid digestibility of these protein concentrates indicate that they would be viable protein sources in canine and feline diets. However, additional complementary protein sources should be included to meet the requirements of all essential amino acids.


Visualization of phagosomal hydrogen peroxide production by a novel fluorescent probe that is localized via SNAP-tag labeling.
Hydrogen peroxide (H2O2), a member of reactive oxygen species (ROS), plays diverse physiological roles including host defense and cellular signal transduction. During ingestion of invading microorganisms, professional phagocytes such as macrophages release H2O2 specifically into the phagosome to direct toxic ROS toward engulfed microbes. Although H2O2 is considered to exert discrete effects in living systems depending on location of its production, accumulation, and consumption, there have been limitations of techniques for probing this oxygen metabolite with high molecular specificity at the subcellular resolution. Here we describe the development of an O(6)-benzylguanine derivative of 5-(4-nitrobenzoyl)carbonylfluorescein (NBzF-BG), a novel H2O2-specific fluorescent probe; NBzF-BG is covalently and selectively conjugated with the SNAP-tag protein, leading to formation of the fluorophore-protein conjugate (SNAP-NBzF). SNAP-NBzF rapidly reacts with H2O2 and thereby shows a 9-fold enhancement in fluorescence. When SNAP-tag is expressed in HEK293T cells and RAW264.7 macrophages as a protein C-terminally fused to the transmembrane domain of platelet-derived growth factor receptor (PDGFR), the tag is presented on the outside of the plasma membrane; conjugation of NBzF-BG with the cell surface SNAP-tag enables detection of H2O2 added exogenously. We also demonstrate molecular imaging of H2O2 that is endogenously produced in phagosomes of macrophages ingesting IgG-coated latex beads. Thus, NBzF-BG, combined with the SNAP-tag technology, should be useful as a tool to measure local production of H2O2 in living cells.


"An on-going individual adjustment": a qualitative study of midwives' experiences counselling pregnant women on physical activity in Sweden.
In Sweden, midwives play prominent supportive role in antenatal care by counselling and promoting healthy lifestyles. This study aimed to explore how Swedish midwives experience the counselling of pregnant women on physical activity, specifically focusing on facilitators and barriers during pregnancy. Also, addressing whether the midwives perceive that their own lifestyle and body shape may influence the content of the counselling they provide. Eight focus group discussions (FGD) were conducted with 41 midwives working in antenatal care clinics in different parts of Sweden between September 2013 and January 2014. Purposive sampling was applied to ensure a variation in age, work experience, and geographical location. The FGD were digitally recorded, transcribed verbatim, and analyzed using manifest and latent content analysis. The main theme--"An on-going individual adjustment" was built on three categories: "Counselling as a challenge"; "Counselling as walking the thin ice" and "Counselling as an opportunity" reflecting the midwives on-going need to adjust their counselling depending on each woman's specific situation. Furthermore, counselling pregnant women on physical activity was experienced as complex and ambiguous, presenting challenges as well as opportunities. When midwives challenged barriers to physical activity, they risked being rejected by the pregnant women. Despite risking rejection, the midwives tried to promote increased physical activity based on their assessment of individual needs of the pregnant woman. Some participants felt that their own lifestyle and body shape might negatively influence the counselling; however, the majority of participants did not agree with this perspective. Counselling on physical activity during pregnancy may be a challenging task for midwives, characterized by on-going adjustments based on a pregnant woman's individual needs. Midwives strive to find individual solutions to encourage physical activity. However, to improve their counselling, midwives may benefit from further training, also organizational and financial barriers need to be addressed. Such efforts might result in improved opportunities to further support pregnant women's motivation for performance of physical activity.


Ligia italica (Isopoda, Oniscidea) as bioindicator of mercury pollution of marine rocky coasts.
In this study, we evaluated the possible role of Ligia italica as a bioindicator for the monitoring of heavy metals pollution in the suppralittoral zone of marine rocky coasts. Between 2004 and 2011 specimens of L. italica were collected along the Eastern Sicilian coasts from sites known for their high pollution levels as they are near to an area where in September 2001 a refinery plant discharged into the sea some waste containing Hg. Other specimens were collected from the Vendicari Natural Reserve located about 30 miles from the polluted sites and used as control area. On a consistent number of animals, the concentration in toto of As, Cd, Cr, Hg, Ni, Pb, V, was determined by Atomic Absorption Spectrometry. On other animals, investigations were carried out in order to check for ultrastructural alterations of the hepatopancreas, that is the main metals storage organ in isopods. Results revealed the presence, in the animals collected in 2004 from the polluted sites, of considerable concentrations of Hg and of lower concentrations of other metals such as As, Pb and V. The Hg bioaccumulation resulted in remarkable ultrastructural alterations of the two cellular types (B and S cells) in the epithelium of the hepatopancreas. Surprisingly, a moderate amount of Hg was also found in specimens collected in 2004 from the Vendicari Natural Reserve, proving that the Hg pollution can also spread many miles away. Animals collected from the polluted sites in the following years showed a progressively decreasing Hg content, reaching very low levels in those from the last sampling. Also, the ultrastructural alterations found in the hepatopancreas of the animals from the last sample were quite irrelevant. In conclusion, Ligia italica can represent a good bioindicator and the ultrastructure of the hepatopancreas could be used as ultrastructural biomarker of heavy metals pollution in the supralittoral zones.


COVID-19 Awareness Among Dental Professionals in Indonesia.
Background: The COVID-19 pandemic caused by SARS-CoV-2 has claimed thousands of lives worldwide. To enhance knowledge and awareness of COVID-19, considerable online resources have been made available, including aspects related to the dental profession. The study aim was to examine the knowledge, perception, and attitude of dental professionals in Indonesia toward COVID-19. We conducted a survey via a questionnaire created using Google docs and distributed to 632 members of the Indonesian Dental Association in the context of a webinar hosted by the Indonesian Oral Biology Association on first June, 2020. Materials and Methods: The questionnaire consisted of 17 items pertaining to demographic data, knowledge and virus identification, awareness regarding drugs commonly used in dentistry during pandemic and research opportunities. Participants were asked to complete the questionnaire after the webinar by choosing one answer to each question. For the analysis, participants were divided into three groups according to their professional background i.e., employment at national hospital, private hospital, or academic faculty. Data were analyzed using descriptive statistics and expressed as frequencies and percentages. The chi-square test was used to investigate the association between professional activity and the level of knowledge, perceptions, and attitudes about COVID-19. Results: Sixty percent of the participants correctly identified the pathogenesis of the disease. This knowledge was not associated with their professional affiliation (p = 0.95). Sixty-seven percentage had comprehensive knowledge about virus detection methods. This knowledge was not associated with their affiliation either (p = 0.54). Questions regarding drugs of choice, prevention, and the spread of COVID-19 were correctly answered by 89, 96, and 82% of the participants, respectively. Knowledge of these aspects were significantly associated with the professional affiliation (p < 0.05). All respondents were optimistic regarding research opportunities (p < 0.01). Respondents from academics were more interested in joining COVID-19-related research projects with governmental institutions (p < 0.01). Conclusion: Knowledge and awareness of COVID-19 among Indonesian dentists are reasonably good. However, further improvement would be beneficial to manage patients during this pandemic. As the number of COVID-19 cases continue to rise in Indonesia, it is important that dentists keep abreast of the updated knowledge on this moving field. Dentist knowledge on infection control should be strengthened through continuous educational programs.


[Postexposure prevention after occupational exposure to HBV, HCV and HIV].
After occupational exposure to HBV, HCV, and HIV, the patient from whom the potentially infectious material originates (index patient) as well as the exposed person should undergo serological and, if needed, molecular screening. Active and passive immunoprophylaxis after exposure to HBV is an effective tool against infection with hepatitis B virus in unvaccinated persons. The post-exposure prophylaxis (PEP) should be given within 24 h after exposure of an unprotected person to HBV-positive material. Once acute hepatitis B infection is diagnosed, therapy is not recommended for immunocompetent persons. At present, PEP against HCV infection is not available. Monotherapy with interferon-alpha avoids chronification in most patients suffering from acute hepatitis C. After exposure with an increased risk for transmission of HIV (percutaneous needle stick injury, cut), PEP should be recommended and can also be offered for further indications. PEP should be started as early as possible and carried out for 28 days. The recommended PEP consists of two inhibitors of the reverse transcriptase and one inhibitor of the protease.


Immunomodulatory Potential of Cannabidiol in Multiple Sclerosis: a Systematic Review.
Multiple sclerosis (MS) is the most common chronic autoimmune disease of the central nervous system. Efficacy of treatments for MS is associated with risk of adverse effects, and effective and well-tolerated drugs remain a major unmet need. Cannabis (Cannabis sativa L., fam. Cannabaceae) and cannabinoids are popular among MS patients to treat spasticity and pain. Cannabinoids are endowed with remarkable immunomodulating properties, and in particular the non-psychotropic cannabinoid cannabidiol (CBD) is increasingly recognized as anti-inflammatory and immunosuppressive, nevertheless with excellent tolerability even at high doses. In this systematic review, we retrieved and critically evaluated available evidence regarding the immune and disease-modifying effects of CBD in experimental autoimmune encephalomyelitis (EAE) and in MS. Evidence in rodent models of EAE strongly supports CBD as effective, while clinical evidence is still limited and usually negative, due to paucity of studies and possibly to the use of suboptimal dosing regimens. Better characterization of targets acted upon by CBD in MS should be obtained in ex vivo/in vitro studies in human immune cells, and higher doses should be tested in well-designed clinical trials with clinically relevant efficacy endpoints. Graphical Abstract.


Treatment and prevention of malnutrition in Latin America: focus on Chile and Bolivia.
Seven million children under 5 years of age died worldwide in 2011, and one-third had malnutrition. Latin America and Caribbean countries stand out for the notable improvement of their health and nutrition situation, particularly in pregnant women and young children. Nutrition-sensitive interventions such as promoting food security, women's empowerment, social safety nets, clean water, and sanitation, among others, are critical for success. In Bolivia, the program Desnutrición Cero (Malnutrition Zero) was able to reduce mortality from severe malnutrition after 5 years from 25% to less than 5%, based on widespread implementation of the World Health Organization 10-steps protocol for hospitalized care and the application of community management. The Economic Commission for Latin America estimated the cost of malnutrition for Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, Panama, and the Dominican Republic as US $6,658 million. Approximately 1 million children have dropped out of school because of malnutrition, and as a result, malnourished children have 2 years less schooling, which brings social and economic losses not only to those affected but to society at large. National and international nutrition and food programs developed over the past 50 years have been implemented as integral components of broader strategies of primary healthcare and education, oriented toward preventing deaths and improving the quality of life of low-socioeconomic-status groups. Treating hundreds or thousands of affected children will not solve the global public health problem of malnutrition. Access to adequate amounts of quality foods represents a basic human right and is a necessary precondition for health. In turn, good nutrition and health are prerequisites for human, social, and economic development.


Peritectic phase transition of benzene and acetonitrile into a cocrystal relevant to Titan, Saturn's moon.
Benzene and acetonitrile are two of the most commonly used solvents found in almost every chemical laboratory. Titan is one other place in the solar system that has large amounts of these compounds. On Titan, organic molecules are produced in the atmosphere and carried to the surface where they can mineralize. Here, we report the phase diagram of mixtures of acetonitrile and benzene, and provide an account of the structure and composition of the phases. To mimic the environment on Titan more accurately, we tested the stability of the structure under liquid ethane. The results provide new insights into the structure and stability of potential extraterrestrial minerals. In light of Dragonfly, NASA's upcoming mission to Titan, revisiting the fundamental chemistry of the smallest molecules with modern methods and techniques can have significant contributions to this epochal mission and can open new research directions in chemistry.


Micro-respirometry of whole cells and isolated mitochondria.
Oxygen consumption is a key metric of metabolism in aerobic organisms. Current respirometric methods led to seminal discoveries despite limitations such as high sample demand, exchange with atmospheric O2, and cumulative titration protocols leading to limited choice of useable tissue, complex data interpretation, and restricted experimental design. We developed a sensitive and customizable method of measuring O2 consumption rates by a variety of biological samples in microliter volumes without interference from the aerobic environment. We demonstrate that O2 permeability of the photopolymer, VeroClear, is comparable to that of polyetheretherketone (0.125 vs. 0.143 barrer, respectively) providing an efficient barrier to oxygen ingress. Optical transparency of VeroClear, combined with high resolution 3D printing, allows for optode-based oxygen detection in enclosed samples. These properties yield a microrespirometer with over 100× dynamic range for O2 consumption rates. Importantly, the enclosed respirometer configuration and very low oxygen permeability of materials makes it suitable, with resin pre-conditioning, for quantitative assessment of O2 consumption rates at any desired [O2], including hyperbaric, physiological or hypoxic conditions as necessary for each cell type. We characterized two configurations to study soluble enzymes, isolated mitochondria, cells in suspension, and adherent cells cultured on-chip. Improved sensitivity allows for routine quantitative detection of respiration by as few as several hundred cells. Specific activity of cell suspensions in the microrespirometer was in close agreement with that obtained by high-resolution polarographic respirometry. Adherent cell protocols allowed for physiologically relevant assessment of respiration in retinal pigment epithelial cells, ARPE-19, which displayed lower metabolic rates compared with those in suspension. By exchanging medium composition, we demonstrate that cells can be transiently inhibited by cyanide and that 99.6% of basal O2 uptake is recovered upon its removal. This approach is amenable to new experimental designs and precision measurements on limited sample quantities across basic research and applied fields.


Local Degradation of PEDOT:PSS on Silicon Nanostructures Using Scanning Electrochemical Microscopy.
Conducting polymers show attractive characteristics as electrode materials for micro-electrochemical energy storage (MEES). However, there is a lack of characterization techniques to study conjugated/conducting polymer-based nanostructured electrodes. Here, scanning electrochemical microscopy (SECM) is introduced as a new technique for in situ characterization and acceleration of degradation processes of conducting polymers. Electrodes of PEDOT:PSS on flat silicon, silicon nanowires (SiNWs) and silicon nanotrees (SiNTrs) are analyzed by SECM in feedback mode with approach curves and chronoamperometry. The innovative degradation method using SECM reduces the time required to locally degrade polymer samples to a few thousand seconds, which is significantly shorter than the time usually required for such studies. The degradation rate is modeled using Comsol Multiphysics. The model provides an understanding of the phenomena that occur during degradation of the polymer electrode and describes them using a mathematical constant A0 and a time constant τ.


Low-dose oral mini-pulse dexamethasone therapy in progressive unstable vitiligo.
The course of vitiligo is unpredictable. If the disease is spreading rapidly, the progression can be controlled with the use of systemic steroids daily or in pulsed form. The present study was planned to assess the efficacy of low-dose dexamethasone oral mini-pulse therapy in progressive unstable vitiligo. In this retrospective study, the case records of patients with vitiligo during the period from January 2006 to December 2010 were studied. Patients who had progressive unstable disease were included. These patients were administered oral dexamethasone 2.5 mg per day on 2 consecutive days after breakfast in a week. The patients were asked to come for regular follow-up to assess the arrest of disease activity, relapse of disease activity, and adverse effects. A total of 444 patients were analyzed. In 408 (91.8%) patients, arrest of disease activity was achieved at a mean duration of 13.2 ± 3.1 weeks. In addition, some repigmentation of the lesions was seen in all patients after a mean of 16.1 ± 5.9 weeks. During the follow-up, 50 of 408 (12.25%) patients experienced one or two episodes of relapse in disease activity, which were treated with reinstitution of low-dose dexamethasone oral mini-pulse therapy. The mean disease-free survival (DFS) until the first relapse was 55.7 ± 26.7 weeks, and the mean DFS until the second relapse was 43.8 ± 7.2 weeks. Adverse reactions such as weight gain, lethargy, and acneiform eruptions were observed in 41 (9.2%) patients. Low-dose oral mini-pulse dexamethasone therapy is a good option for arresting progressive unstable vitiligo with minimal adverse effects.