Risk factors for stunting among children: a community based case control study in Nepal.
Stunting, a chronic condition, is an underlying cause of child morbidity and mortality in Nepal. This study intends to identify the factors causing stunting among children that will help to prioritize the strategies at the district level. The objective of the study was to identify the risk factors for stunting among children of age between 6 to 59 months. The study was based on community-based case control design in the mid-west, Surkhet Nepal from August to September 2010. The cases were stunted children and controls were the children without stunting. Data was collected by interviewing those children's mothers and measured length/height of 118 children as cases and 236 children as controls. Logistic regression analysis was performed to identify the best model of factors leading to stunting. Odds ratio and 95% confidence interval were used as a measure of association. Socio-economic risk factors for stunting comprised mothers without earning (OR=3.11, 95% CI 1.26-7.65), food deficit families (OR=4.26, 95% CI 1.73-10.45) and care taker of the children other than mother (OR=3.02, 95% CI 1.19-7.70). Environmental risk factors for stunting consisted of kitchen without ventilation and children exposed to pesticide. Inappropriate exclusive breast feeding (OR=6.90, 95% CI 2.81-16.97), complementary feeding less than four times a day (OR=3.60, 95% CI 1.32-9.95) and dietary diversity below WHO standard (OR=4.06, 95% CI 1.70-9.67) were factors of stunted children. Diarrhea was found significantly associated with stunting (OR=7.46, 95% CI 2.98-18.65). Stunting was found to be as a result of multiple factors such as socio-economic, environmental and inappropriate feeding practices.


Identification of critical amino-acid residues on the erythroid intercellular adhesion molecule-4 (ICAM-4) mediating adhesion to alpha V integrins.
Intercellular adhesion molecule-4 (ICAM-4, syn. LW glycoprotein) interacts with the integrins alpha(L)beta(2), alpha(M)beta(2), A(4)beta(1), the alpha(V) family, and alpha(IIb)beta(3). Systematic mutagenesis of surface-exposed residues conserved between human and murine ICAM-4 defined 12 single amino-acid changes that affect the interaction of ICAM-4 with alpha(V) integrins. Mutation of 10 of these residues, 8 of which are spatially close on the surface of the molecule, led to a reduction in adhesion. Moreover, peptides corresponding to regions of ICAM-4 involved in its interaction with alpha(V) integrins inhibited these interactions. The other 2 mutations increased the extent of interaction of ICAM-4 with alpha(V) integrins. These mutations appear to prevent glycosylation of N160, suggesting that changes in glycosylation may modulate ICAM-4-alpha(V) integrin interactions. The region of ICAM-4 identified as the binding site for alpha(V) integrins is adjacent to the binding sites for alpha(L)beta(2) and alpha(M)beta(2). Selective binding of ICAM-4 to different integrins may be important for a variety of normal red cell functions and also relevant to the pathology of thrombotic disorders and vasoocclusive events in sickle cell disease. Our findings suggest the feasibility of developing selective inhibitors of ICAM-4-integrin adhesion of therapeutic value in these diseases.


Male Spouses of Women Physicians: Communication, Compromise, and Carving Out Time.
As the numbers of female physicians continue to grow, fewer medical marriages are comprised of the traditional dyad of male physician and stay-at-home wife. The "two-career family" is an increasingly frequent state for both male and female physicians' families, and dual-doctor marriages are on the rise. This qualitative study explored the contemporary medical marriage from the perspective of male spouses of female physicians. In 2010, we conducted semi-structured, in-depth interviews with nine spouses of internal medicine resident and faculty physicians. Interviewers queried work-home balance, career choices, and support networks. We used an interpretive, inductive, iterative approach to thematically analyze interview transcripts and develop broad, consensus-derived themes. A conceptual framework based on three major themes emerged: "A time for us? Really?", "Supporting and protecting her, sometimes at my expense,'" and "Hers is a career, mine is a job." This framework described the inflexibility of physicians' time and its impact on spousal time, career development, and choices. Having a set time for synchronizing schedules, frequent verbal support, and shared decision-making were seen as important by the husbands of female, full-time physicians. This exploratory study examined the contemporary medical marriage from the male spouse's perspective and highlights specific strategies for success.


[Assessment of sleep with polysomnography in patients with interstitial lung disease].
In our study we aimed to examine the sleep structure, oxygenation and breathing pattern in interstitial lung disease (ILD) patients. We also aimed to determine whether relevance between the advanced disease and the sleep disorders exists and whether polysomnography is necessary in those patients. A total of 37 patients were examined in the study and whole night standard polysomnography was performed to all. Polysomnography results revealed that, total sleep time, time spent in NREM sleep stage III and IV, and in REM sleep were decreased. The patients had poor sleep efficiency and they spent more time as wake after sleep onset (WASO). Severe oxygen desaturations were detected during sleep and statistically significant positive correlations were found between mean awake O2 saturation and mean and lowest sleep O2 saturations. Clinical, Radiological and Physiological (CRP) scoring system was used to assess the disease stage, whether advanced or not, and statistically significant negative correlations were found between CRP score and awake and sleep O2 saturations. Obstructive sleep apnea syndrome (OSAS) was diagnosed in 24 (64.9%) patients. In those patients it was found that not the apneas but the hypopneas predominate. No difference was found among body mass indices (BMI) between the patients with and without OSAS. As a result it was concluded that a sleep study should be considered as part of the overall assessment in managing patients with ILD, and is especially indicated if there is incipient pulmonary hypertension, cor pulmonale and nocturnal arrhythmia despite normal awake blood gas tensions and symptoms as snoring and excessive day time sleepiness.


Toward the discovery of dual HCMV-VZV inhibitors: Synthesis, structure activity relationship analysis, and cytotoxicity studies of long chained 2-uracil-3-yl-N-(4-phenoxyphenyl)acetamides.
The need for novel therapeutic options to fight herpesvirus infections still persists. Herein we report the design, synthesis and antiviral evaluation of a new family of non-nucleoside antivirals, derived from 1-[ω-(4-bromophenoxy)alkyl]uracil derivatives--previously reported inhibitors of human cytomegalovirus (HCMV). Introduction of the N-(4-phenoxyphenyl)acetamide side chain at N(3) increased their potency and widened activity spectrum. The most active compounds in the series exhibit submicromolar activity against different viral strains of HCMV and varicella zoster virus (VZV) replication in HEL cell cultures. Inactivity against other DNA and RNA viruses, including herpes simplex virus 1/2, points to a novel mechanism of antiviral action.


Serial peripheral blood cytotoxic lymphocyte gene expression measurements for prediction of pancreas transplant rejection.
Acute rejection after pancreas transplantation remains a significant problem and contributes to immunological graft loss. No clinical markers of pancreas rejection have been universally accepted. The purpose of this study was to investigate the use of genetic markers; granzyme B, perforin, and HLA-DRA in the peripheral blood of pancreas transplant recipients. These genes have been identified in renal and islet cell transplant recipients as noninvasive tools to predict acute rejection. Blood samples were collected weekly for up to 1 year posttransplant. Surveillance biopsies of the pancreas were scheduled at weeks 2, 4, 8, and 12 as part of the typical posttransplant protocol for patients with pancreas alone or pancreas after kidney transplantation. Exclusion criteria included a diagnosis of biopsy-proven chronic rejection alone, pancreatitis, or kidney rejection within 2 months after pancreas biopsy. Gene expression levels of granzyme B, perforin, and HLA-DRA were compared in patients with (n = 7) and without biopsy proven acute rejection (n = 7). Recipients with acute rejection showed increased expression of granzyme B, HLA-DRA, as well as perforin genes compared to patients without biopsy-proven rejection. In addition, we observed that elevation of these genes occurred as early as 4 weeks before the traditional biopsy diagnosis, while the recipients with no rejection showed no change in gene expression. Our data indicated that serial measurements of peripheral blood granzyme B, perforin, and HLA-DRA gene expression can be a useful tool to predict pancreas rejection in its earliest stage.


[The Hungarian suicide enigma].
Hungary has had a traditionally high suicide rate in the last century. With a twofold increase between 1960 and 1985, this country had the highest recorded suicide rate in the world. This dramatic increase was due to an extreme high suicide mortality in elderly people. A very strong age effect, especially in women, is a unique phenomenon. Further demographic, epidemiological, psychosocial and biological investigations were carried out in the recent years, and overviewed here briefly. Post-mortem psychiatric assessment of suicide victims, biological research and epidemiological data suggest that undiagnosed and untreated depression is a significant factor in the high suicide mortality.


Selenium levels in related biological samples: human placenta, maternal and umbilical cord blood, hair and nails.
A study on selenium levels has been carried out in human placenta, maternal and umbilical cord blood, hair and nails of a group of 50 mothers and in the hair of the newborns. The determinations were perfomed by electrothermal atomic absorption spectrometry. The selenium concentration obtained for each sample type was as follows: For the human placenta the values obtained were between 0.56 and 1.06 microg/g (mean +/- standard deviation: 0.81 +/- 0.02 microg/g). The levels for the umbilical cord blood were 51.1-104.2 microg/l (76.3 +/- 6.5 microg/l). For the maternal blood the values measured were between 57.3 and 117.9 microg/l (90.0 +/- 15.2 microg/l), and for hair and nails were 0.22-1.5 microg/g (0.60 +/- 0.37 microg/g) and 0.46-1.57 microg/g (0.90 +/- 0.27 microg/g), respectively. For the hair of the newborns the values obtained were between 0.40 and 2.53 microg/g (1.04 +/- 0.48 microg/g). The effect of different variables as age, habitat, nutritional index or gestation age of the mothers on the selenium concentration in the samples was studied. The influence of the habitat is significant with a confidence level of 95% for the selenium concentration in maternal blood and umbilical cord blood samples. The influence of the mothers' age is significant with a confidence level of 95% for the selenium concentration in the umbilical cord blood samples. For the placenta samples, the effect of the nutritional index is significant with a confidence level of 95%. There is a positive correlation between samples of umbilical cord blood and the newborns' hair, between placenta and umbilical cord, and between cord blood and maternal blood.


"I never thought that it would happen … " Experiences of HIV seroconverters among HIV-discordant partnerships in a prospective HIV prevention study in Kenya.
In spite of access to behavioral and biomedical HIV prevention strategies, HIV transmission occurs. For HIV-serodiscordant couples, prevention programs can be tailored to address individual and couples' needs to preserve their relationship while minimizing HIV risk. Programs for serodiscordant couples may benefit from learning from experiences of couples who transmit HIV. We conducted 20 individual in-depth interviews with 10 initially HIV-serodiscordant couples who transmitted HIV during prospective follow-up at a peri-urban research site in Thika, Kenya. Data were analyzed inductively to identify situations that led to prevention failure and coping mechanisms. Inconsistent condom use driven by low HIV risk perception and alcohol use often preceded seroconversion while persistent blame frequently hindered couples' communication soon after seroconversion. In this emerging era of antiretroviral-based HIV prevention, couples' counseling can capitalize on opportunities to foster a supportive environment to discuss initiation and adherence to time-limited pre-exposure prophylaxis and lifelong antiretroviral therapy, in addition to strategies to reduce alcohol use, diffuse blame, and use condoms.


Role of Neuroimmune Crosstalk in Mediating the Anti-inflammatory and Analgesic Effects of Acupuncture on Inflammatory Pain.
Inflammatory pain is caused by peripheral tissue injury and inflammation. Inflammation leads to peripheral sensitization, which may further cause central sensitization, resulting in chronic pain and progressive functional disability. Neuroimmune crosstalk plays an essential role in the development and maintenance of inflammatory pain. Studies in recent years have shown that acupuncture can exert anti-inflammatory and analgesic effects by regulating peripheral (i.e., involving local acupoints and inflamed regions) and central neuroimmune interactions. At the local acupoints, acupuncture can activate the TRPV1 and TRPV2 channels of mast cells, thereby promoting degranulation and the release of histamine, adenosine, and other immune mediators, which interact with receptors on nerve endings and initiate neuroimmune regulation. At sites of inflammation, acupuncture enables the recruitment of immune cells, causing the release of opioid peptides, while also exerting direct analgesic effects via nerve endings. Furthermore, acupuncture promotes the balance of immune cells and regulates the release of inflammatory factors, thereby reducing the stimulation of nociceptive receptors in peripheral organs. Acupuncture also alleviates peripheral neurogenic inflammation by inhibiting the release of substance P (SP) and calcitonin gene-related peptide from the dorsal root ganglia. At the central nervous system level, acupuncture inhibits the crosstalk between glial cells and neurons by inhibiting the p38 MAPK, ERK, and JNK signaling pathways and regulating the release of inflammatory mediators. It also reduces the excitability of the pain pathway by reducing the release of excitatory neurotransmitters and promoting the release of inhibitory neurotransmitters from neurons and glial cells. In conclusion, the regulation of neuroimmune crosstalk at the peripheral and central levels mediates the anti-inflammatory and analgesic effects of acupuncture on inflammatory pain in an integrated manner. These findings provide novel insights enabling the clinical application of acupuncture in the treatment of inflammatory diseases.


Practical Synthesis of the Bicyclic Darunavir Side Chain: (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-ol from Monopotassium Isocitrate.
A practical synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol-a key intermediate in the synthesis of darunavir-from monopotassium isocitrate is described. The isocitric acid salt, obtained from a high-yielding fermentation fed by sunflower oil, was converted in several steps to a tertiary amide. This amide, along with the compound's ester functionalities, was reduced with lithium aluminum hydride to give, on acidic workup, a transient aminal-triol. This was converted in situ to the title compound, the bicyclic acetal furofuranol side chain of darunavir, a protease inhibitor used in treatment of HIV/AIDS. Key to the success of this process was identifying an optimal amide that allowed for complete reaction and successful product isolation. N-Methyl aniline amide was identified as the most suitable substrate for the reduction and the subsequent cyclization to the desired product. Thus, the side chain is produced in 55% overall yield from monopotassium isocitrate.


Superacidity of closo-dodecaborate-based Brønsted acids: a DFT study.
The structures and intrinsic gas-phase acidities (GA) of some dodecaborane acids, the derivatives of YB12H11H (Y = PF3, NH3, NF3, NMe3), B12H12H2, and B12H12H(-) (HA, H2A, and HA(-), respectively) have been computationally explored with DFT B3LYP method at the 6-311+G** level of theory as new possible directions of creating superstrong Brønsted acids. Depending on the nature and number of the substituents different protonation geometries were investigated. In general, the GA values of the neutral systems varied according to the substituents in the following order: CF3 < F < Cl and in case of anionic acids: CF3 < Cl < F. The dodecatrifluoromethyl derivative of H2A, B12(CF3)12H1H2, emerges as the strongest among the considered acids and is expected to be in the gas phase at least as strong as the undecatrifluoromethyl carborane, CB11(CF3)11H1H. The GA values of the respective monoanionic forms of the considered acids all, but the (CF3)11 derivative, remained higher than the widely used threshold of superacidity. The HA derivatives' (Y = PF3, NF3) GA's were approximately in the same range as the H2A acids'. In the case Y = NH3 or NMe3 the GA values were significantly higher. Also, the pKa values of B12H12H2, CB11H12H, and their perfluorinated derivatives in 1,2-dichloroethane (DCE) were estimated with SMD and cluster-continuum model calculations. The obtained estimates of pKa values of the perfluorinated derivatives are by around 30 units lower than that of trifluoromethylsulfonylimide, making these acids the strongest ever predicted in solution. The derivatives of B12H12H2 are as a rule not significantly weaker acids than the respective derivatives of CB11H12H. This is important for expanding practical applicability of this type of acids and their anions, as they are synthetically much more accessible than the corresponding CB11H12(-) derivatives.


Interaction of the pesticide chlordimeform with adrenergic receptors in mouse brain: an in vitro study.
Chlordimeform (N'(4-chloro-o-tolyl)-N, N-dimethylformamidine; CDM) is a formamidine insecticide acaricide whose major active metabolite is its N-monomethyl analog, desmethylchlordimeform, (DCDM). While their pesticidal action in invertebrates appears to be related to activation of octopamine receptors, their mechanism of action in mammals has not been established. Because of similarities between octopamine and adrenergic receptors and suggestions of CDM and DCDM action on adrenoceptors, the in vitro interactions of CDM and DCDM with adrenoceptors were studied. In mouse brain membrane preparations CDM inhibited the binding of [3H]-clonidine to alpha 2- adrenoceptors and of [3H]-WB4101 to alpha 1-adrenoceptors with IC50 values of 18.2 and 87 microM, respectively. DCDM was a much more potent inhibitor, with IC50 values toward alpha 2-, and alpha 1-adrenoceptors of 44 nM and 1 microM, respectively. Both compounds were only weak inhibitors of the binding of [3H]-dihydroalprenolol to beta-adrenoceptors and of [3H]-quinuclidinyl benzilate to muscarinic receptors and were inactive toward benzodiazepines and gamma aminobutyric acid (GABAA) receptors. Inhibition of [3H]-clonidine binding by both compounds was competitive, as indicated by a decreased receptor affinity without changes in receptor density. Interaction of CDM and DCDM with [3H]-WB4101 binding, on the other hand, was more complex, and not of the competitive type. These results show that CDM and its metabolite DCDM can interact directly in vitro with alpha-adrenergic receptors, suggesting that these receptors could mediate some of the effects of CDM and DCDM in vivo.


Migration of wooden skewer foreign bodies from the gastrointestinal tract in eight dogs.
Wooden skewer foreign bodies were found in eight dogs. Five presented for evaluation of draining sinuses and two for inflammatory disease referrable to the thorax, abdomen or pelvic region. In an additional case, pneumothorax resulted from perforation of the stomach and diaphragm. Ingestion was considered the most likely mode of access of the foreign body in all cases. Although the wooden foreign bodies were seen radiographically in only two dogs, identification of soft tissue or bony changes, or the results of contrast sinography assisted diagnosis. Surgical retrieval led to resolution of signs in all cases.


Vasoreactivity in CADASIL: Comparison to structural MRI and neuropsychology.
Impaired cerebrovascular reactivity precedes histological and clinical evidence of CADASIL in animal models. We aimed to more fully characterise peripheral and cerebral vascular function and reactivity in a cohort of adult CADASIL patients, and explore the associations of these with conventional clinical, imaging and neuropsychological measures. A total of 22 adults with CADASIL gave informed consent to participate in an exploratory study of vascular function in CADASIL. Clinical assessment, comprehensive vascular assessment, MRI and neuropsychological testing were conducted. We measured cerebral vasoreactivity with transcranial Doppler and arterial spin labelling MRI with hypercapnia challenge. Number and volume of lacunes, subcortical hyperintensity volume, microbleeds and normalised brain volume were assessed on MRI. Analysis was exploratory and examined the associations between different markers. Cerebrovascular reactivity measured by ASL correlated with peripheral vasoreactivity measured by flow mediated dilatation. Subjects with ≥5 lacunes were older, with higher carotid intima-media thickness and had impaired cerebral and peripheral vasoreactivity. Subjects with depressive symptoms, disability or delayed processing speed also showed a trend to impaired vasoreactivity. Impaired vasoreactivity and vascular dysfunction may play a significant role in the pathophysiology of CADASIL, and vascular assessments may be useful biomarkers of severity in both longitudinal and clinical trials.


Tailoring Fluorescence-Phosphorescence Emission with a Single Nanocavity.
Realizing the dual emission of fluorescence-phosphorescence in a single system is an extremely important topic in the fields of biological imaging, sensing, and information encryption. However, the phosphorescence process is usually in an inherently "dark state" at room temperature due to the involvement of spin-forbidden transition and the rapid non-radiative decay rate of the triplet state. In this work, we achieved luminescent harvesting of the dark phosphorescence processes by coupling singlet-triplet molecular emitters with a rationally designed plasmonic cavity. The achieved Purcell enhancement effect of over 1000-fold allows for overcoming the triplet forbidden transitions, enabling radiation enhancement with selectable emission wavelengths. Spectral results and theoretical simulations indicate that the fluorescence-phosphorescence peak position can be intelligently tailored in a broad range of wavelengths, from visible to near-infrared. Our study sheds new light on plasmonic tailoring of molecular emission behavior, which is crucial for advancing research on plasmon-tailored fluorescence-phosphorescence spectroscopy in optoelectronics and biomedicine.


A lifespan study of classification preference.
Individuals between the ages of 4 and 70 were presented with a revised version of the Conceptual Styles Test. The number of similarity classifications was found to increase from the 4- to the 45- to 50-year-old group and to decrease thereafter; the number of complementary responses was found to decrease and then increase. The 20- to 25-year-old group used more perceptual similarity classifications, whereas the 35- to 40- and 45- to 50-year-old groups used more functional similarity classifications. One purpose of the study was to determine whether, as Kogan has suggested, elderly adults are more creative and free-wheeling in their classification responses than younger individuals. Two measures of creativity were employed; one was based on the experimenter's judgements and one based on the frequency with which the same response was given by other subjects. Neither measure indicated that the elderly individuals were more creative than the other age groups.


Role of some whey components on mass transfer in ultrafiltration.
Ultrafiltration through Carbosep M(4) mineral membrane of protein solutions of decreasing complexity (whey before and after centrifugation or clarification, beta-lactoglobulin) was studied. Mathematical models were used to explain variations in flux with time. Taking into account variations in protein retention and hydraulic resistance of the membrane during ultrafiltration, proteins and lipoproteins were found to be involved not only in the polarization layer (reversible fouling leading to a difference in the osmotic pressure), but also in irreversible fouling by adsorption. Morever, the presence of particles (e.g., inorganic precipitates) in whey explains the build-up of a deposit over and within the membrane which contributes to the decline in flux after 1 h ultrafiltration. The relative importance of these phenomena was quantified.


Delivery route considerations for designing antigen-specific biomaterial strategies to combat autoimmunity.
Disease modifying drugs and biologics used to treat autoimmune diseases, although promising, are non-curative. As the field moves towards development of new approaches to treat autoimmune disease, antigen-specific therapies immunotherapies (ASITs) have emerged. Despite clinical approval of ASITs for allergies, clinical trials using soluble ASITs for autoimmunity have been largely unsuccessful. A major effort to address this shortcoming is the use of biomaterials to harness the features unique to specific delivery routes. This review focuses on biomaterials being developed for delivery route-specific strategies to induce antigen-specific responses in autoimmune diseases such as multiple sclerosis, type 1 diabetes, rheumatoid arthritis, and celiac disease. We first discuss the delivery strategies used in ongoing and completed clinical trials in autoimmune ASITs. Next, we highlight pre-clinical biomaterial approaches from the most recent 3 years in the context of these same delivery route considerations. Lastly, we provide discussion on the gaps remaining in biomaterials development and comment on the need to consider delivery routes in the process of designing biomaterials for ASITs.


Reported completion of the USMLE Step 1 and match outcomes among senior osteopathic students in 2020.
The United States Medical Licensing Examination (USMLE) is not required for osteopathic students to match into postgraduate programs; however, it is unknown if taking the test improves their chances of matching. Our objective was to determine the association between taking the USMLE Step 1 and matching into the applicant's preferred specialty for senior osteopathic students applying to the 10 specialties to which students applied most in 2020. We performed a secondary analysis of the free and publicly available 2020 National Residency Match Program (NRMP) published match report for senior osteopathic students. First, we determined the number of senior osteopathic students that matched into their preferred specialty vs those that did not and stratified them by reported completion of the USMLE Step 1 within each specialty. Next, we calculated odds ratios (ORs) within each specialty for senior osteopathic students matching into their preferred specialty with and without the USMLE Step 1 utilizing the Fisher's exact test. Finally, we repeated the analysis with only senior osteopathic students who had reported USMLE Step 1 scores in ranges including or below the mean for those who matched in their specialty. For senior osteopathic students, reported completion of the USMLE Step 1 was associated with matching for those who applied to Internal Medicine (OR 3.3 [95% confidence interval 2.07 to 5.48]), Emergency Medicine (2.1 [1.35 to 3.17]), Pediatrics (4.4 [1.38 to 18.63]), Psychiatry (2.5 [1.34 to 4.98]), Anesthesiology (3.4 [1.57 to 7.32]), and General Surgery (3.1 [1.56 to 6.14]). After repeating the analysis with only senior osteopathic students who reported low USMLE Step 1 scores, the association remained significant for those who applied to Internal Medicine (2.5 [1.49 to 4.28]), Anesthesiology (2.6 [1.17 to 5.54]), and General Surgery (2.5 [1.24 to 5.04]). In 2020, reported completion of the USMLE Step 1 by senior osteopathic students was associated with matching for those who applied to Internal Medicine, Emergency Medicine, Pediatrics, Psychiatry, Anesthesiology, and General Surgery. In addition, reported completion of the USMLE Step 1 with a low score was associated with matching for those who applied to Internal Medicine, Anesthesiology, and General Surgery.


Biosynthesis of Carotenoids in Plants: Enzymes and Color.
Carotenoids are the most important biocolor isoprenoids responsible for yellow, orange and red colors found in nature. In plants, they are synthesized in plastids of photosynthetic and sink organs and are essential molecules for photosynthesis, photo-oxidative damage protection and phytohormone synthesis. Carotenoids also play important roles in human health and nutrition acting as vitamin A precursors and antioxidants. Biochemical and biophysical approaches in different plants models have provided significant advances in understanding the structural and functional roles of carotenoids in plants as well as the key points of regulation in their biosynthesis. To date, different plant models have been used to characterize the key genes and their regulation, which has increased the knowledge of the carotenoid metabolic pathway in plants. In this chapter a description of each step in the carotenoid synthesis pathway is presented and discussed.


Special Features of Bat Microbiota Differ From Those of Terrestrial Mammals.
Bats (order Chiroptera) are one of the most diverse and widely distributed group of mammals with a close relationship to humans. Over the past few decades, a number of studies have been performed on bat viruses; in contrast, bacterial pathogens carried by bats were largely neglected. As more bacterial pathogens are being identified from bats, the need to study their natural microbiota is becoming urgent. In the current study, fecal samples of four bat species from different locations of China were analyzed for their microbiota composition. Together with the results of others, we concluded that bat microbiota is most commonly dominated by Firmicutes and Proteobacteria; the strict anaerobic phylum Bacteroidetes, which is dominant in other terrestrial mammals, especially humans and mice, is relatively rare in bats. This phenomenon was interpreted as a result of a highly specified gastrointestinal tract in adaptation to the flying lifestyle of bats. Further comparative study implied that bat microbiota resemble those of the order Carnivora. To discover potential bacterial pathogens, a database was generated containing the 16S rRNA gene sequences of known bacterial pathogens. Potential bacterial pathogens belonging to 12 genera were detected such as Salmonella, Shigella, and Yersinia, among which some have been previously reported in bats. This study demonstrated high resolution and repeatability in detecting organisms of rare existence, and the results could be used as guidance for future bacterial pathogen isolation.


Is there a "most chiral tetrahedron"?
A degree of chirality is a function that purports to measure the amount of chirality of an object: it is equal for enantiomers, vanishes only for achiral or degenerate objects and is similarity invariant, dimensionless and normalisable to the interval [0,1]. For a tetrahedron of non-zero three-dimensional volume, achirality is synonymous with the presence of a mirror plane containing one edge and bisecting its opposite, and hence it is easy to design degree-of-chirality functions based on edge length that incorporate all constraints. It is shown that such functions can have largest maxima at widely different points in the tetrahedral shape space, and by incorporation of appropriate factors, the maxima can be pushed to any point in the space. Thus the phrase "most chiral tetrahedron" has no general meaning: any chiral tetrahedron is the most chiral for some legitimate choice of degree of chirality.


L-alanine supplementation in Pompe disease (IOPD): a potential therapeutic implementation for patients on ERT? A case report.
Pompe disease (PD) is a disorder of glycogen metabolism conditioning a progressive and life conditioning myopathy. Enzyme replacement therapy (ERT) is currently the best treatment option for PD, but is not resolutive. While other potential therapeutic approaches have been reported before, these have never been tried as co- treatments. L-alanine oral supplementation (LAOS) has been proven to reduce muscle breakdown: we hereby report the first case of supplementation on a PD patient on ERT. F. is a 9 y.o. infantile onset Pompe Disease (IOPD) girl ERT-treated since age 1 developing a progressive myopathy. We started her on LAOS and performed assessments at baseline, 6 and 9 months. At baseline, F.'s weight, height and BMI were within normal ranges, while body composition showed low fat mass -FM and high resting energy expenditure-REE levels. After LAOS, a progressive FM increase and REE reduction could be observed both at 6 and 9 months. ERT is not curative for PD patients thus additional treatments could be considered to improve outcomes. Our patient showed physical signs of inability to accumulate energy when exclusively on ERT, while FM increase and REE reduction occurred when supplemented with LAOS, likely reflecting anabolic pathways' implementation. This is the first case reporting potential LAOS benefits in PD-on ERT patients. Longitudinal case control studies are yet needed to evaluate possible efficacy of combined LAOS And ERT treatment in PD patients.


Preferable orientation of spherical fullerene inside boron nitride nanotubes.
We provide a systematic analytical method for preferable orientation calculations of spherical fullerenes in single-walled boron nitride nanotubes. Based on the reaction energy calculations, both the minimum entering radii and the energetically favorable radii for encapsulating C(60), C(80) and C(180) molecules in boron nitride nanotubes have been proposed. The van der Waals energy as a function of the various orientations of the encapsulated fullerene molecule is shown by a potential contour map, from which we find that the low-energy state appears in the symmetry axis orientation of the encapsulated fullerene molecules with a different size. We thus propose a new systematic analytical method for optimal orientation predictions of spherical fullerenes in the confinement condition, which is based on the symmetry axis but not the method proposed in previous literature, such as using pentagons, double-bonds, and hexagons to analyze the preferable orientation of confined C(60). Our results show that the C(60) molecule in boron nitride nanotubes exhibits three lowest energy states corresponding to the five-, two- and three-fold axis orientations in three radii intervals, while only two preferable orientations-the five- and three-fold axis orientations have been observed for encapsulated C(80) and C(180) molecules.


Somatostatin levels in plasma in nonsmoking and smoking breast-feeding women.
The objective of the study was to record how somatostatin levels in plasma are altered in response to breast-feeding during the lactation period and to relate somatostatin levels to the success of the lactational performance and to smoking habits. Fifty-two women were investigated 4 days post partum and 3-4 months later. Blood samples were collected and the levels of somatostatin-like immunoreactivity (below referred to as SLI) were measured with radioimmunoassay. The periods of exclusive breast-feeding and of mixed feeding were assessed as well as the milk yield. Smoking habits were noted. SLI levels were found to be significantly lower on day 4 after delivery, compared to 3-4 months later. Also the type of response to breast-feeding was different. Thus, a significant fall of SLI was seen during breast-feeding at the maternity unit, but not 3-4 months later. Smoking women breast-fed fully for a significantly shorter time than nonsmokers and had significantly higher SLI levels at onset of breast-feeding day 4 post partum. Whether the high somatostatin levels recorded in connection with breast-feeding in smokers are related to the shorter period of breast-feeding seen in this group remains to be established. In addition, the highest levels of somatostatin were seen the day after the very last breast-feeding and a possible role for somatostatin in the weaning process should be explored.


A yeast purification system for human translation initiation factors eIF2 and eIF2Bε and their use in the diagnosis of CACH/VWM disease.
Recessive inherited mutations in any of five subunits of the general protein synthesis factor eIF2B are responsible for a white mater neurodegenerative disease with a large clinical spectrum. The classical form is called Childhood Ataxia with CNS hypomyelination (CACH) or Vanishing White Matter Leukoencephalopathy (VWM). eIF2B-related disorders affect glial cells, despite the fact that eIF2B is a ubiquitous protein that functions as a guanine-nucleotide exchange factor (GEF) for its partner protein eIF2 in the translation initiation process in all eukaryotic cells. Decreased eIF2B activity measured by a GEF assay in patients' immortalised lymphocytic cells provides a biochemical diagnostic assay but is limited by the availability of eIF2 protein, which is classically purified from a mammalian cell source by column chromatography. Here we describe the generation of a recombinant expression system to produce purified human eIF2 from yeast cells. We demonstrate that human eIF2 can function in yeast cells in place of the equivalent yeast factor. We purify human eIF2 and the C-terminal domain of human eIF2Bε using affinity chromatography from engineered yeast cells and find that both function in a GEF assay: the first demonstration that this human eIF2Bε domain has GEF function. We show that CACH/VWM mutations within this domain reduce its activity. Finally we demonstrate that the recombinant eIF2 functions similarly to eIF2 purified from rat liver in GEF assays with CACH/VWM eIF2B-mutated patient derived lymphocytic cells.


Prevention of TCR-mediated apoptosis by the elevation of cAMP.
The stimulation through TCR-CD3 complexes by immobilized anti-CD3 antibody induced the production of IL-2 and activation-induced cell death (ACD) in the majority of T cell hybridomas. However, some hybridomas produced IL-2 without showing any signs of ACD by the same stimulation, indicating that TCR-CD3-mediated signaling pathways of IL-2 production and of ACD are different. These pathways were discriminated from each other by protein kinase inhibitors and cAMP-elevating reagents such as forskolin. The pathway of IL-2 production but not of ACD was inhibited by protein kinase inhibitors. On the other hand, various cAMP-elevating reagents prevented the T cell hybridomas from TCR-mediated ACD with minimal inhibition of IL-2 production. The elevated cytoplasmic cAMP did not block dexamethasone-induced apoptosis. This indicates that apoptosis is regulated by multiple pathways. Furthermore, the inhibitory effect of cAMP is specific for the TCR-mediated signaling pathway of ACD. Messenger RNA for bcl-2 was detected after treatment with forskolin.


Pneumocystis carinii f. sp. hominis is not infectious for SCID mice.
The infectious power of Pneumocystis carinii f. sp. hominis was explored by inoculating SCID mice intranasally with either P. carinii f. sp. hominis or P. carinii f. sp. muris isolates. Only mice inoculated with mouse parasites developed Pneumocystis pneumonia, as assessed by microscopy and PCR. These results suggest that humans do not contract pneumocystosis from animals.


The acute effects of exercise on prolactin and growth hormone secretion: comparison between sedentary women and women runners with normal and abnormal menstrual cycles.
Acute exercise may stimulate PRL secretion, which, in turn, may contribute to exercise-associated menstrual dysfunction. We compared the response of PRL secretion in sedentary women and women runners with normal and abnormal menstrual cycles. We also studied the GH response to acute exercise, as GH may bind to lactogenic receptors. Five nonrunning women, 5 eumenorrheic running women, four oligomenorrheic running women, and six amenorrheic running women were studied on 2 consecutive days. On day 1, the women cycled on a bicycle ergometer against an increasing workload until total exhaustion. Serum PRL and GH increased several-fold in response to acute exercise in all three groups of running women. On day 2, the women simulated a daily training run by enduring a designed submaximal exercise regimen. In response to submaximal exercise, no group had a significant elevation of PRL or GH. Therefore, a threshold of exercise intensity exists that must be achieved before a significant increase in PRL or GH secretion occurs in women runners; serum PRL and GH in the nonrunning group did not increase significantly even in response to acute maximal exercise. The transient elevations in PRL and GH in women runners probably do not contribute to their menstrual dysfunction unless individual hypersensitivity of the hypothalamic-pituitary-ovarian axis to such intermittent elevations is present.


Multi-compartment microscopic diffusion imaging.
This paper introduces a multi-compartment model for microscopic diffusion anisotropy imaging. The aim is to estimate microscopic features specific to the intra- and extra-neurite compartments in nervous tissue unconfounded by the effects of fibre crossings and orientation dispersion, which are ubiquitous in the brain. The proposed MRI method is based on the Spherical Mean Technique (SMT), which factors out the neurite orientation distribution and thus provides direct estimates of the microscopic tissue structure. This technique can be immediately used in the clinic for the assessment of various neurological conditions, as it requires only a widely available off-the-shelf sequence with two b-shells and high-angular gradient resolution achievable within clinically feasible scan times. To demonstrate the developed method, we use high-quality diffusion data acquired with a bespoke scanner system from the Human Connectome Project. This study establishes the normative values of the new biomarkers for a large cohort of healthy young adults, which may then support clinical diagnostics in patients. Moreover, we show that the microscopic diffusion indices offer direct sensitivity to pathological tissue alterations, exemplified in a preclinical animal model of Tuberous Sclerosis Complex (TSC), a genetic multi-organ disorder which impacts brain microstructure and hence may lead to neurological manifestations such as autism, epilepsy and developmental delay.


Alleviating Neuroinflammation through Photothermal Conjugated Polymer Nanoparticles by Regulating Reactive Oxygen Species and Ca2+ Signaling.
Neuroinflammation is one of the important manifestations of the amyloid β peptide (Aβ) protein-induced neurotoxic signaling pathway in which the aggregation of Aβ causes an increase in reactive oxygen species (ROS) and Ca2+ concentration. Here, near-infrared (NIR) photothermal-responsive conjugated polymer nanoparticles were designed to regulate ROS and Ca2+ signaling to alleviate neuroinflammation. Under 808 nm laser irradiation, the nanoparticles effectively penetrated the blood-brain barrier (BBB) and reduced the aggregation of Aβ and partially disaggregated the aggregates outside the cell, thereby reducing ROS content which downregulated the oxidative stress damage to cells. Meanwhile, the nanoparticles reduced the concentration of Ca2+ by inhibiting the transient receptor potential melastatin-related 2 (TRPM2) ion channel inside the cell. Ultimately, the concentration of inflammatory factor tumor necrosis factor-α was decreased. This study provides an effective strategy to reduce neuroinflammation by simultaneously regulating ROS and Ca2+ signaling.


Use of Daily Interruption of Sedation and Early Mobility in US Hospitals.
Although the Awakening and Breathing Coordination, Delirium assessment, and Early exercise/mobility (ABCDE) bundle may be effective, individual components of ABCDE may not be implemented as intended. We examined the use of daily interruption of sedation (DIS) and early mobility, looking for an association between these bundle elements. Despite the growing use of DIS and early mobility, the two do not seem to be adopted together, with serious implications for the effectiveness of the ABCDE bundle.


Evaluation of Anti-inflammatory and Some Possible Mechanisms of Antinociceptive Effect of Ferula assa foetida Oleo Gum Resin.
Asafetida is well known for its medicinal and therapeutic values in Iranian folk medicine. This study was conducted to investigate the antinociceptive and anti-inflammatory effects of asafetida. In hot plate test, asafetida exhibited a significant antinociceptive effect at all administered doses and the most effective dose was 10 mg/kg. The highest maximum potent effect was observed 15 minutes after asafetida administration. The antinociceptive effect of asafetida was not reversed by administration of any antagonist used in this study but asafetida showed a remarkable antioxidant and also inhibitory action against lipoxygenase activity. Paw weight was significantly reduced only in treated animals with 2.5 mg/kg asafetida. Results clearly indicate that the asafetida could be a potential source of anti-inflammatory and analgesic agent. These effects may be due to its effective constituents such as monoterpenes, flavonoids and phenolic components that have antioxidant properties and inhibit lipoxygenase activity.


Effect of the levonorgestrel intrauterine device on genital HIV-1 RNA shedding among HIV-1-infected women not taking antiretroviral therapy in Nairobi, Kenya.
The effect of the levonorgestrel-releasing intrauterine device (LNG-IUD) on genital HIV-1 RNA shedding and inflammation among 25 HIV-infected women was evaluated. Blood, endocervical, and cervicovaginal lavage samples were collected from HIV-infected women not taking antiretrovirals before LNG-IUD insertion and 1 month, 3 month, and 6 months thereafter. HIV-1 RNA was quantitated by real-time reverse transcriptase-polymerase chain reaction. Inflammatory markers were measured by enzyme immunoassay. Genital HIV-1 RNA shedding and inflammatory markers did not differ between LNG-IUD placement and month 6, with the exception of interleukin 1β that increased (0.42 log10; 95% confidence interval: 0.10 to 0.75). The LNG-IUD did not increase genital HIV-1 RNA shedding after 6 months of use.


Gardening your way to health.
A King's Fund report published in May found overwhelming evidence of the beneficial effects of gardening on physical and mental wellbeing.


[Laparoscopy in abdominal emergencies. Indications and limitations].
Laparoscopy, which has been well known as a diagnostic procedure for more than a century, has recently established itself as an important therapeutic procedure in several branches of surgery. In the present study the authors report on 221 patients over a 10-year period (1991-2001), admitted to hospital with a diagnosis of acute abdomen or abdominal trauma. All patients were submitted to emergency laparoscopic surgery; 128 patients (57%) presented acute appendicitis, 40 (18%) acute cholecystitis, 13 (6%) occlusive ileus, 10 (5%) adnexal pathologies, 9 (4%) perforation of abdominal viscera, 3 (1.4%) acute diverticulitis, 3 (1.4%) subdiaphragmatic abscesses, 3 (1.4%) intestinal infarction, 2 (0.8%) other diseases and 10 (5%) abdominal trauma. The operation was completed laparoscopically in 192 cases (87%), while conversion to laparotomy proved necessary in 29 cases (13%). The morbidity of the cases completed laparoscopically was 3%, the mortality 0.5%, and the mean hospital stay 4 days. Advantages of laparoscopy (shorter hospital stay, rapid postoperative recovery and faster return to social activities) emerge from the present study and are confirmed by the literature. The possibility of combining a diagnostic procedure with curative therapy suggests that laparoscopy may have an important role in emergency surgery, demonstrating its efficacy also in acute abdominal syndromes. Nevertheless, emergency laparoscopic surgery is still a technically difficult procedure that needs to be performed by an expert surgical team.


Clearly transparent and air-permeable nanopaper with porous structures consisting of TEMPO-oxidized cellulose nanofibers.
Optically transparent materials that are air permeable have potentially numerous applications, including in wearable devices. From the perspective of sustainable development, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidized cellulose nanofibers with widths of 3-4 nm have attracted considerable attention as starting materials for the preparation of clearly transparent nanofiber paper (denoted as conventional nanopaper). However, conventional nanopaper that is prepared from a water dispersion of TEMPO-oxidized cellulose nanofibers by direct drying exhibits poor air permeability owing to its densely packed layered structure. In this study, we prepared a clearly transparent and air-permeable nanopaper by applying filtration-based solvent exchange from high-surface-tension water to low-surface-tension ethanol and hexane, followed by drying under continuous vacuum filtration. The resulting hexane-exchanged nanopaper had a porous structure with individually dispersed and thin nanofiber networks and interlayer pore spaces. Owing to the tailored porous structures, the hexane-exchanged nanopaper provides similar clear transparency (total light transmittance and haze at 600 nm: 92.9% and 7.22%, respectively) and 106 times higher air permeability (7.8 × 106 mL μm m-2 day-1 kPa-1) compared to the conventional nanopaper. This study will facilitate the development of clearly transparent and air-permeable nanopapers to extend their functional applications.


Determination of total mycophenolic acid and its glucuronide metabolite using liquid chromatography with ultraviolet detection and unbound mycophenolic acid using tandem mass spectrometry.
Two simple, sensitive and reproducible methods for determination of total mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) as well as unbound MPA (fMPA) was developed by the use of HPLC-UV and LC-MS/MS methods, respectively. For the total MPA/MPAG method, the analytes were extracted using Isolute C(2) solid-phase extraction (SPE) cartridges and analyzed at 254 nm over a Zorbax Rx C(8) column (150 mm x 4.6 mm, 5 microm). The mobile phase was a gradient mixture of methanol and water (containing 0.1% (v/v) phosphoric acid). The total run time was 18 min and the extraction recovery was 77% for MPA and 84% for MPAG. The method was precise and accurate with a lower limit of quantification (LLOQ) of 0.5 mg/l for MPA and 5.0 mg/l for MPAG. For the fMPA method, plasma was subjected to ultrafiltration followed by SPE using C(18) cartridges. Analytical column was the same as the HPLC-UV method and the mobile phase was a gradient composition of methanol:0.05% formic acid with a flow rate of 0.6 ml/min for the first 3 min and 0.7 ml for the last 4 min. The chromatographic method separated MPA from its metabolites MPAG and Acyl-MPAG. Mass transitions in negative ionization mode for MPA and the internal standard, indomethacin were m/z: 319-->190.9 and m/z: 356-->312.2, respectively. The assay was linear in the concentration range of 1-1000 microg/l for fMPA with a LLOQ of 1 microg/l and an accuracy of >95%. The two methods reported have an adequate degree of robustness and dynamic concentration range for the measurement of MPA, MPAG and fMPA for therapeutic drug monitoring purposes or pharmacokinetics investigations.


Electrical stimulation to heal dermal wounds.
Numerous human and animal efficacy studies have demonstrated that electrical stimulation of the correct charge, density and total energy causes dramatically improved healing of dermal wounds. The investigations of biological actions (in vitro, animal, and human) demonstrate several effects that go a long way to explaining why electrical stimulation works. To discuss recent research and advances in electrical stimulation of wound healing. Based on the latest scientific understanding of the wound healing process, one would expect a beneficial outcome from a therapy what decreases edema, debrides necrotic tissue, attracts neutrophils and macrophages, stimulates receptor sites for growth factors, stimulates growth of fibroblasts and granulation tissue, increases blood flow, stimulates neurite growth, induces epidermal cell migration, prevents post-ischemic oxygen radical-mediated damage, inhibits bacteria, and reduces numbers of mast cells. Taken together, the efficacy studies and the "mechanism of action" studies provide compelling, scientific evidence that electrical stimulation is safe and effective for promoting the healing of dermal wounds.


Developing clinical placements in times of scarcity.
This article takes the position that the current shortage of clinical placements may be creating problems, but it can also be seen as an opportunity to reconsider the design of students' clinical experiences and the goals to be attained. It begins with a description of paradoxes in professional education. The following sections examine some of the considerations which need to be incorporated in the development of clinical placements and the way they are incorporated into health care courses. The considerations germane to clinical placement development include social participation in clinical settings, communities of learning, and consumer-centred inter-professional collaboration.


Development and evaluation of controlled-release diclofenac microspheres and tabletted microspheres.
Diclofenac wax microspheres were prepared using the congealable dispersephase encapsulation method. Emulsifiers, glyceryl monostearate (GMS) and stearic acid, were added to improve the efficiency of emulsification. Microspheres containing either of the emulsifiers or both showed a high drug content (80-90%) and the particle size distribution was log-normal compared with microspheres without the emulsifiers. Increase in GMS concentration decreased the drug release and, in contrast, stearic acid appeared to channel the drug from the wax matrix. The addition of both emulsifiers at different concentrations modified drug release. Increase in dispersant (PVP) concentration, and decrease in microsphere size accelerated the rate of drug release. Higuchi/Baker Londsdale spherical matrix dissolution kinetics was followed. Disintegrating tableted microspheres were prepared with Avicel and Explotab. With the increase in compression pressure the crushing force and disintegrating time increased, but the thickness decreased, and the dissolution profile did not appear to be affected. Slightly faster release was noticed with tableted microspheres compared with that of uncompressed microspheres. Tablets containing 40 and 60% microsphere loadings had disintegration times of 5.12 +/- 0.63 and 57.73 +/- 3.53 min, respectively. In contrast, tablet formulation containing 80% microsphere load had a significant increase in disintegration time (130.83 +/- 4.26 min). The dissolution from this formulation also showed a lag time of 30 min in contrast with the other two formulations, which showed no lag time. Increased microsphere size from 215 to 630 microns had no effect on tableting properties (such as hardness and thickness); and only very little effect on dissolution. The microspheres appeared deformed but intact irrespective of compression pressures on scanning electron micrographs.


The extent of ribosome queuing in budding yeast.
Ribosome queuing is a fundamental phenomenon suggested to be related to topics such as genome evolution, synthetic biology, gene expression regulation, intracellular biophysics, and more. However, this phenomenon hasn't been quantified yet at a genomic level. Nevertheless, methodologies for studying translation (e.g. ribosome footprints) are usually calibrated to capture only single ribosome protected footprints (mRPFs) and thus limited in their ability to detect ribosome queuing. On the other hand, most of the models in the field assume and analyze a certain level of queuing. Here we present an experimental-computational approach for studying ribosome queuing based on sequencing of RNA footprints extracted from pairs of ribosomes (dRPFs) using a modified ribosome profiling protocol. We combine our approach with traditional ribosome profiling to generate a detailed profile of ribosome traffic. The data are analyzed using computational models of translation dynamics. The approach was implemented on the Saccharomyces cerevisiae transcriptome. Our data shows that ribosome queuing is more frequent than previously thought: the measured ratio of ribosomes within dRPFs to mRPFs is 0.2-0.35, suggesting that at least one to five translating ribosomes is in a traffic jam; these queued ribosomes cannot be captured by traditional methods. We found that specific regions are enriched with queued ribosomes, such as the 5'-end of ORFs, and regions upstream to mRPF peaks, among others. While queuing is related to higher density of ribosomes on the transcript (characteristic of highly translated genes), we report cases where traffic jams are relatively more severe in lowly expressed genes and possibly even selected for. In addition, our analysis demonstrates that higher adaptation of the coding region to the intracellular tRNA levels is associated with lower queuing levels. Our analysis also suggests that the Saccharomyces cerevisiae transcriptome undergoes selection for eliminating traffic jams. Thus, our proposed approach is an essential tool for high resolution analysis of ribosome traffic during mRNA translation and understanding its evolution.


Clinical outcome measures and scoring systems used in prospective studies of port wine stains: A systematic review.
Valid and reliable outcome measures are needed to determine and compare treatment results of port wine stain (PWS) studies. Besides, uniformity in outcome measures is crucial to enable inter-study comparisons and meta-analyses. This study aimed to assess the heterogeneity in reported PWS outcome measures by mapping the (clinical) outcome measures currently used in prospective PWS studies. OVID MEDLINE, OVID Embase, and CENTRAL were searched for prospective PWS studies published from 2005 to May 2020. Interventional studies with a clinical efficacy assessment were included. Two reviewers independently evaluated methodological quality using a modified Downs and Black checklist. In total, 85 studies comprising 3,310 patients were included in which 94 clinician/observer-reported clinical efficacy assessments had been performed using 46 different scoring systems. Eighty-one- studies employed a global assessment of PWS appearance/improvement, of which -82% was expressed as percentage improvement and categorized in 26 different scoring systems. A wide variety of other global and multi-item scoring systems was identified. As a result of outcome heterogeneity and insufficient data reporting, only 44% of studies could be directly compared. A minority of studies included patient-reported or objective outcomes. Thirteen studies of good quality were found. Clinical PWS outcomes are highly heterogeneous, which hampers study comparisons and meta-analyses. Consensus-based development of a core outcome-set would benefit future research and clinical practice, especially considering the lack of high-quality trials.


[Remediation of chromium-polluted soil using municipal solid waste compost].
A study on the feasibiltiy of remediation of Cr-polluted soil using municipal solid waste(MSW) compost was carried out. The result showed that organic matter(O.M.), Eh, pH and < 0.01 mm of clay would influence the bioavailability of chromium in the soil, and O. M. and Eh were the principal influencing factors in the dryfield and inundating soil, up to 73.40% and 55.5% of the contribution rate affecting the bioavailability of chromium, respectively. The osmosis of the soil was improved when compost was applied, but the quantity of movable chromium was reduced because chromium in soil was deoxidized and adsorbed. MSW compost could reduce the absorption of chromium by the tested plant. The yield of the plant grown in the dry soil was increased by 35.9% and the content of Cr in the plant was decreased by 48.9%. The effect was more notable in the inundating soil: 86.3% of the yield increased and 23.8% of the Cr content decreased. However, MSW compost could not increase the risk of other heavy metal pollution.


Characteristics of Legionella pneumophila serogroup 2 strains by colony morphology.
The isolation rate of Legionella pneumophila serogroup 2 from clinical samples is low. In 2007, we encountered the second case known to occur in Japan. As the L. pneumophila serogroup 2 type strain, the Kobe strain isolated in 1988, and the Okinawa strain isolated from the present patient could not be differentiated using the usual biochemical and serological tests, we tried to achieve differentiation by observing colony morphology. In Oxoid BCYEalpha medium, colonies of the Kobe strain developed multiple protuberances on the surface, but these did not develop on the other two strains. In Becton-Dickinson BCYEalpha medium, colonies of the Okinawa strain had several outgrowths from the margin, but the type strain and the Kobe strain did not have any outgrowths. The Okinawa strain isolated from the present case showed intermediate characteristics between the type strain and the Kobe strain in the appearance of colony morphology. It may be useful to conduct an investigation of this rare serogroup.


Design of deterministic light-trapping structures for thin silicon heterojunction solar cells.
We optically designed and investigated two deterministic light-trapping concepts named "Hutong" (wafer thickness dependent, patch-like arrangement of "V" grooves with alternating orientations) and "VOSTBAT" (one directional "V" grooves at the front and saw-tooth like structures at the back) for the application in emerging thin silicon heterojunction (SHJ) solar cells. Calculated photocurrent density (Jph) (by weighting the spectrally resolved absorptance with AM1.5g spectrum and integrating over the wavelength) showed that both the Hutong and VOSTBAT structures exceed the Lambertian reference and achieved Jph of 41.72 mA/cm2 and 41.86 mA/cm2, respectively, on 60 µm thin wafers in the case of directional, normal incidence.


Combining LOPIT with differential ultracentrifugation for high-resolution spatial proteomics.
The study of protein localisation has greatly benefited from high-throughput methods utilising cellular fractionation and proteomic profiling. Hyperplexed Localisation of Organelle Proteins by Isotope Tagging (hyperLOPIT) is a well-established method in this area. It achieves high-resolution separation of organelles and subcellular compartments but is relatively time- and resource-intensive. As a simpler alternative, we here develop Localisation of Organelle Proteins by Isotope Tagging after Differential ultraCentrifugation (LOPIT-DC) and compare this method to the density gradient-based hyperLOPIT approach. We confirm that high-resolution maps can be obtained using differential centrifugation down to the suborganellar and protein complex level. HyperLOPIT and LOPIT-DC yield highly similar results, facilitating the identification of isoform-specific localisations and high-confidence localisation assignment for proteins in suborganellar structures, protein complexes and signalling pathways. By combining both approaches, we present a comprehensive high-resolution dataset of human protein localisations and deliver a flexible set of protocols for subcellular proteomics.


Measurement of the charged-particle multiplicity inside jets from [Formula: see text][Formula: see text] pp collisions with the ATLAS detector.
The number of charged particles inside jets is a widely used discriminant for identifying the quark or gluon nature of the initiating parton and is sensitive to both the perturbative and non-perturbative components of fragmentation. This paper presents a measurement of the average number of charged particles with [Formula: see text] [Formula: see text] inside high-momentum jets in dijet events using 20.3 fb[Formula: see text] of data recorded with the ATLAS detector in pp collisions at [Formula: see text] [Formula: see text] collisions at the LHC. The jets considered have transverse momenta from 50 [Formula: see text] up to and beyond 1.5 [Formula: see text]. The reconstructed charged-particle track multiplicity distribution is unfolded to remove distortions from detector effects and the resulting charged-particle multiplicity is compared to several models. Furthermore, quark and gluon jet fractions are used to extract the average charged-particle multiplicity for quark and gluon jets separately.


Evaluating the induced photon contamination by different breast IOERT shields using Monte Carlo simulation.
Avoiding the underlying healthy tissue over-exposure during breast intraoperative electron radiotherapy (IOERT) is owing to the use of some dedicated radioprotection disks during patient irradiation. The originated contaminant photons from some widely used double-layered shielding disks including PMMA+Cu, PTFE+steel, and Al+Pb configurations during the breast IOERT have been evaluated through a Monte Carlo (MC) simulation approach. Produced electron beam with energies of 6, 8, 10, and 12 MeV by a validated MC model of Liac12 dedicated IOERT accelerator was used for disk irradiations. Each of above-mentioned radioprotection disks was simulated inside a water phantom, so that the upper disk surface was positioned at R90 depth of each considered electron energy. Simulations were performed by MCNPX (version 2.6.0) MC code. Then, the energy spectra of the contaminant photons at different disk surfaces (upper, middle, and lower one) and relevant contaminant dose beneath the studied disks were determined and compared. None of studied shielding disks show significant photon contamination up to 10 MeV electron energy, so that the induced photon dose by the contaminant X-rays was lower than those observed in the disk absence under the same conditions. In return, the induced photon dose at a close distance to the lower disk surface exceeded from calculated values in the disk absence at 12 MeV electron energy. The best performance in contaminant dose reduction at the energy range of 6-10 MeV belonged to the Al+Pb disk, while the PMMA+Cu configuration showed the best performance in this regard at 12 MeV energy. Finally, it can be concluded that all studied shielding disks not only don't produce considerable photon contamination but also absorb the originated X-rays from electron interactions with water at the electron energy range of 6-10 MeV. The only concern is related to 12 MeV energy where the induced photon dose exceeds the dose values in the disk absence. Nevertheless, the administered dose by contaminant photons to underlying healthy tissues remains beneath the tolerance dose level by these organs at the entire range of studied electron energies.


Body mass index of the elderly derived from height and from armspan.
The body mass index (BMI) has been promoted as a useful indicator for chronic energy deficiency, and to a lesser extent to indicate obesity. For the growing sector of elderly in developing countries, such as Indonesia, both issues are taking on public health relevance. The aging process leads to a progressive loss of height, and questions have been raised as to the appropriate value to include in the denominator of the BMI formula, WT(kg)/HT(m2), when applied in this age-group. The armspan has been advanced as a surrogate for height, correcting for the lifelong loss of stature. In a data-set from 69 elderly in Indonesia, 36 women and 33 men, aged 60 to 69 y, we have examined the interrelationships of height and armspan. The correlation coefficient for the regression of the two measures were r = 0.83 and r = 0.81 (p < 0.001), for women and men, respectively. Substituting the armspan term in the denominator to compose a Body Mass using Armspan (BMA) Index, we observe for this population a 32% increase in estimates for Chronic Energy Deficiency (CED) for women and 24% increase in estimates of CED for men. Corresponding estimates for obesity rates declined by 45% and 81% respectively. The senescent changes in stature raise important questions for our capacity to estimate prevalences of body composition disorders in the older population.


Analysis of blood flow velocity and pressure signals using the multipulse method.
This paper shows how the multipulse method from digital signal processing can be used to accurately synthesize signals obtained from blood pressure and blood flow velocity sensors during posture change from sitting to standing. The multipulse method can be used to analyze signals that are composed of pulses of varying amplitudes. One of the advantages of the multipulse method is that it is able to produce an accurate and efficient representation of the signals at high resolution. The signals are represented as a set of input impulses passed through an autoregressive (AR) filter. The parameters that define the AR filter can be used to distinguish different conditions. In addition, the AR coefficients can be transformed to tube radii associated with digital wave guides, as well as pole-zero representation. Analysis of the dynamics of the model parameters have potential to provide better insight and understanding of the underlying physiological control mechanisms. For example, our data indicate that the tube radii may be related to the diameter of the blood vessels.


Improvements in bladder, bowel and sexual outcomes following task-specific locomotor training in human spinal cord injury.
Locomotor training (LT) as a therapeutic intervention following spinal cord injury (SCI) is an effective rehabilitation strategy for improving motor outcomes, but its impact on non-locomotor functions is unknown. Given recent results of our labs' pre-clinical animal SCI LT studies and existing overlap of lumbosacral spinal circuitries controlling pelvic-visceral and locomotor functions, we addressed whether LT can improve bladder, bowel and sexual function in humans at chronic SCI time-points (> two years post-injury). Prospective cohort study; pilot trial with small sample size. Eight SCI research participants who were undergoing 80 daily one-hour sessions of LT on a treadmill using body-weight support, or one-hour of LT and stand training on alternate days, as part of another research study conducted at the Kentucky Spinal Cord Injury Research Center, University of Louisville, were enrolled in this pilot trial. Urodynamic assessments were performed and International Data Set questionnaire forms completed for bladder, bowel and sexual functions at pre-and post-training time points. Four usual care (non-trained; regular at-home routine) research participants were also enrolled in this study and had the same assessments collected twice, at least 3 months apart. Filling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. No significant differences were found for usual care research participants. These results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task-specific stepping and/or loading, can positively benefit the neural circuitries controlling urogenital and bowel functions. ClinicalTrials.gov NCT03036527.


Culture of rabbit meibomian gland using collagen gel.
Rabbit whole meibomian glands were isolated by microsurgical dissection and enzymatic digestion. Both ductal and acinar elements could be separated by subsequent microsurgical manipulation. Epithelial outgrowth could be derived from either the whole gland or the ductal/acinar elements using collagen gel in the serum-containing, growth factor-enriched medium. Two types of outgrowths were observed: a discontinuous spindle-shaped epithelial cell monolayer in which oil-red-O (ORO)-stained meibum containing single cells and cell aggregates were evenly distributed, and a continuous cuboidal epithelial monolayer in which oil-red-O-stained cells formed a gradient with single cells and cell aggregates preferentially distributed in the periphery of the outgrowth. Thus, meibum production and meibomian gland differentiation can be maintained in collagen gel culture and ductal elements may contain progenitor cells for acinar differentiation. This culture system will allow future exploration of the regulatory mechanism of meibomian gland differentiation at the cellular level.


Automated Identification of Chemical Series: Classifying like a Medicinal Chemist.
We investigate different automated approaches for the classification of chemical series in early drug discovery, with the aim of closely mimicking human chemical series conception. Chemical series, which are commonly defined by hand-drawn scaffolds, organize datasets in drug discovery projects. Often, they form the basis for further project decisions. To trace and evaluate these decisions in historic and ongoing projects, it is important to know or reconstruct chemical series. There is not a unique correct definition of chemical series, and the human definition certainly involves a subjective bias. Hence, we first develop quality metrics for the chemical series definitions, evaluating the size and specificity of chemical series. These metrics are applied to categorize human series definitions and implemented in automated classification approaches. For the automated classification of chemical series, we test different fragmentation and similarity-based clustering algorithms and apply different approaches to infer series definitions from these clusters or sets of fragments. We benchmark the classification results against human-defined series from 30 internal projects. The best results in reproducing the composition of human-defined series are achieved when applying UPGMA (unweighted pair group method with arithmetic mean) clustering to the project dataset and calculating maximum common substructures of the clusters as series definitions. We evaluate this approach in more detail on a public dataset and assess its robustness by 10-fold cross-validation, each time sampling 40% of the dataset. Through these benchmarking and validation experiments, we show that the proposed automated approach is able to accurately and robustly identify human-defined series, which comply with a certain, predefined level of specificity and size. Suggesting a thoroughly tested algorithm for series classification, as well as quality metrics for series and several benchmarking approaches, this work lays the foundation for further analysis of project decisions, and it offers an enhanced understanding of the properties of human-defined chemical series.


Allele-specific activation and expression of the K-ras gene in hybrid mouse lung tumors induced by chemical carcinogens.
A mouse hybrid, (C3H x A/J)F1 or C3A, was developed by crossing male A/J mice (high lung tumor susceptibility) with female C3H mice (low lung tumor susceptibility). The lung tumor responses of the C3A mice to dimethylnitrosamine (DMN) or benzo[a]pyrene (B[a]P) were found to be intermediate between those of the two parental strains. Mutational activation of the K-ras gene was found at a high frequency in both the B[a]P- and DMN-induced C3A lung tumors. To explore the genetic basis of the K-ras gene involvement in mouse lung tumor susceptibility, the parental origin of the K-ras oncogene in the chemically induced C3A lung tumors was determined. K-ras oncogenes were found on the allele inherited from the susceptible A/J parent in 14/16 of DMN-induced tumors and 15/17 of B[a]P-induced tumors from C3A mice. Furthermore, the K-ras mRNA transcribed from the A/J allele was 5-20 times more than C3H K-ras transcripts in 10/10 DMN-induced and 10/10 B[a]P-induced C3A lung tumors. These data suggest that an activated A/J K-ras allele could be more tumorigenic than an activated C3H allele due to the differential expression of the two alleles in lung cells.


Photoluminescent Honeycomb Structures from Polyoxometalates and an Imidazolium-Based Ionic Liquid Bearing a π-Conjugated Moiety and a Branched Aliphatic Chain.
Honeycomb-structured films represent an intriguing class of two-dimensional porous materials. Specifically, polyoxometalate (POM) macroanions can be introduced into these films by complexing with oppositely charged, double-tailed surfactants. Here highly-ordered honeycomb structures are reported that can be constructed by the complexes between POMs and a room temperature ionic liquid (IL1) having an imidazolium moiety in the middle and a naphthyl unit and a branched aliphatic chain at the ends. The complexes can be produced through phase transfer between an aqueous solution of POMs (typically {Mo72 Fe30 }) and a CS2 (or chloroform) solution of IL1. Based on the intrinsic properties of {Mo72 Fe30 } and the functional groups of the IL1, the honeycomb structures show multiple functions with bright photoluminescence and rich electrochemical properties. This work shows that by simply engineering the organic ligands involved in the POM-based inorganic-organic complexes, supramolecular structures with improved properties and wide applications can be obtained.


(Almost) Stationary Isotachophoretic Concentration Boundary in a Nanofluidic Channel Using Charge Inversion.
The present work is an experimental study of a new means to induce a quasi-stationary boundary for concentration or separation in a nanochannel induced by charge inversion. Instead of using pressure-driven counter-flow to keep the front stationary, we exploit charge inversion by a highly charged electrolyte, Ru(bpy)3Cl2, that changes the sign of the zeta potential in part of the channel from negative to positive. Having a non-charge inverting electrolyte (MgCl2) in the other part of the channel and applying an electric field can create a standing front at the interface between them without added dispersion due to an externally applied pressure-driven counterflow. The resulting slow moving front position can be easily imaged optically since Ru(bpy)3Cl2 is fluorescent. A simple analytical model for the velocity field and front axial position that reproduces the experimental location of the front shows that the location can be tuned by changing the concentration of the electrolytes (and thus local zeta potential). Both of these give the charge inversion-mediated boundary significant advantages over current methods of concentration and separation and the method is, therefore, of particular importance to chemical and biochemical analysis systems such as chromatography and separations and for enhancing the stacking performance of field amplified sample injection and isotachophoresis. By choosing a non-charge inverting electrolyte other than MgCl2, either this electrolyte or the Ru(bpy)3Cl2 solution can be made to be the leading or trailing electrolyte.


Slow digestible colored rice flour as wall material for microencapsulation: Its impacts on gut bacterial population and metabolic activities.
Black waxy and red jasmine rice flour (6.5% and 18.7% amylose content, respectively) were modified using pullulanase followed by heat-moisture treatment (Hydrolyzed-HMT) to produce microcapsules that entrapped L. plantarum TISTR 1465. Hydrolyzed-HMT of colored rice flours showed restricted pasting properties, lower breakdown and higher thermal properties than native flour (p<0.05). Hydrolysis treatment was able to promote a low molecular weight starch that easily formed a crystalline structure after HMT. As a consequence, a significant increase in slowly digestible starch was observed (from 23.7% to 37.0% in waxy type and 22.2% to 34.6% non-waxy type). The survival of L. plantarum TISTR 1465 after simulated gastric fluid (90min) and simulated intestinal fluid (120min) of the Hydrolyzed 36h-HMT black waxy rice was higher (8.07±0.13logCFU/g and 7.48±0.12logCFU/g) than gum arabic (6.12±0.11 and 4.72±0.28logCFU/g) and no carrier (3.34±0.23 and 0.43±0.75logCFU/g) respectively. Moreover, these microcapsules also obtained the highest survival (8.67±0.20logCFU/g) after storage for 90days at 4°C. Under scanning electron microscopy, starch granules of the hydrolyzed 36h-HMT were seen as polyhedral shapes in the spherical aggregates that carried the microorganisms and reduced their injury and mortality. Short-chain fatty acids of the hydrolyzed 36h-HMT were much higher than positive control at every fermentation time (p<0.01). The fluorescence in situ hybridization result showed that the prebiotic property of hydrolyzed 36h-HMT black waxy rice can better aid the beneficial probiotic Lactobacillus spp. growth after 24h fermentation than the negative control (from 8.40±0.48 to 7.03±0.21logCFU/g, p<0.05) and commercial prebiotic Orafti®Synergy1 (8.40±0.48 to 7.47±0.08logCFU/g, p<0.01). Microencapsulation of hydrolyzed black waxy rice flour followed by HMT is proposed as a synbiotic ingredient to apply in synbiotic foods.


Cisapride or cimetidine in the treatment of functional dyspepsia. Results of a double-blind, randomized, Swiss multicentre study.
Functional dyspepsia is a major diagnostic and therapeutic challenge for the clinician. Several systems for the identification of 'high-risk' patients and classifications of dyspepsia subtypes and treatment schemes have been proposed in the past with limited experimental evidence to support the claims made. The present trial was designed to compare two different treatment modalities in a group of functional dyspepsia patients selected on the basis of a standardized diagnostic procedure as 'non-risk' for organic disease and to assess the result in the major symptom sub-groups of functional dyspepsia as a means of identifying the potential for improving treatment outcome. The efficacy of the prokinetic drug cisapride (5 mg four times daily) and of the histamine H2-receptor antagonist cimetidine (200 mg four times daily) were evaluated after 1 month of treatment and after a further follow-up of 1 month. Patients were randomized to the trial if they fulfilled the following criteria: 1) 'low-risk' symptoms or negative endoscopy findings, and 2) 2 weeks of single-blind antacid treatment did not provide satisfactory relief. For analysis patients were stratified into dyspepsia subtypes. One hundred and sixty-one patients entered the run-in period, and 137 patients were randomized to the study. At the end of 4 weeks' treatment a small but significant difference in favour of cisapride was found; this difference can mainly be accounted for by the significant difference found in the dysmotility-like subtype (83% improved with cisapride versus 59% with cimetidine). No significant differences could be detected between drugs in the other dyspepsia subtypes at the end of the treatment-or follow-up period. The study confirms the classification into dyspepsia-subtypes as a useful tool in selecting the most appropriate drug therapy.


Metabolic phenotype of B cells from young and elderly HIV individuals.
HIV infection induces inflammaging and chronic immune activation (IA), which are negatively associated with protective humoral immunity. Similar to HIV, aging is also associated with increased inflammaging and IA. The metabolic requirements of B cell responses in HIV infected (HIV+) individuals are not known, although metabolic abnormalities have been reported in these individuals. How these metabolic abnormalities are exacerbated by aging is also not known. B cells were isolated by magnetic sorting from the blood of young and elderly HIV + individuals, as well as from the blood of age-matched healthy controls. We evaluated the composition of the B cell pool by flow cytometry, the expression of RNA for pro-inflammatory and metabolic markers by qPCR and their metabolic status using a Seahorse XFp extracellular flux analyzer. In this study we have evaluated for the first time the metabolic phenotype of B cells from young and elderly HIV + individuals as compared to those obtained from age-matched healthy controls. Results show that the B cell pool of HIV + individuals is enriched in pro-inflammatory B cell subsets, expresses higher levels of RNA for pro-inflammatory markers and is hyper-metabolic, as compared to healthy controls, and more in elderly versus young HIV + individuals, suggesting that this higher metabolic phenotype of B cells is needed to support B cell IA. We have identified the subset of Double Negative (DN) B cells as the subset mainly responsible for this hyper-inflammatory and hyper-metabolic profile. Our results identify a relationship between intrinsic B cell inflammation and metabolism in HIV + individuals and suggest that metabolic pathways in B cells from HIV + individuals may be targeted to reduce inflammaging and IA and improve B cell function and antibody responses.


Effect of Acupressure on Early Complications of Menopause in Women Referring to Selected Health Care Centers.
Menopausal period is accompanied by numerous disorders and complications. Nowadays, hormone therapy is the most effective existing method to treat these complications, but many women cannot undergo that due to the known potentiality of risk. So, the present study aimed to investigate the effect of acupressure on early complications of menopause. This is a blind random clinical trial conducted on 70 menopaused women referring to selected health care centers in Tehran who were qualified to enter the study. The subjects were randomly assigned to study (wearing a special acupressure wrist brace, three times a week for 15 min, in both bands on Shenmen and Sanyinjiao acupoints, in addition to receiving conventional menopausal care) and placebo (wearing a special acupressure wrist brace, three times a week for 15 min, but in a counter wise way, in addition to receiving conventional menopausal care) groups. Length of intervention was 4 weeks. Early complications of menopause were evaluated before intervention and 2 and 4 weeks after intervention in both groups. Data were analyzed by descriptive and inferential statistical methods. The findings revealed a significant reduction in the number and severity of hot flashes, the number of night sweats, and state-trait anxiety severity (P < 0.001), but with regard to the severity of night sweats and trait anxiety, there was no significant difference between groups. With regard to the obtained results on the effect of acupressure on reduction of early menopausal complications, acupressure along with conventional menopausal care is suggested as one of the complementary medicine methods to improve the complications of this period.


Reviewing the quality of discourse information measures in aphasia.
Discourse is fundamental to everyday communication, and is an increasing focus of clinical assessment, intervention and research. Aphasia can affect the information a speaker communicates in discourse. Little is known about the psychometrics of the tools for measuring information in discourse, which means it is unclear whether these measures are of sufficient quality to be used as clinical outcome measures or diagnostic tools. To profile the measures used to describe information in aphasic discourse, and to assess the quality of these measures against standard psychometric criteria. A scoping review method was employed. Studies were identified using a systematic search of Scopus, Medline and Embase databases. Standard psychometric criteria were used to evaluate the measures' psychometric properties. The current review summarizes and collates the information measures used to describe aphasic discourse, and evaluates their quality in terms of the psychometric properties of acceptability, reliability and validity. Seventy-six studies described 58 discourse information measures, with a mean of 2.28 measures used per study (SD = 1.29, range = 1-7). Measures were classified as 'functional' measures (n = 33), which focused on discourse macrostructure, and 'functional and structural' measures (n = 25), which focused on micro-linguistic and macro-structural approaches to discourse. There were no reports of the acceptability of data generated by the measures (distribution of scores, missing data). Test-retest reliability was reported for just 8/58 measures with 3/8 > 0.80. Intra-rater reliability was reported for 9/58 measures and in all cases percentage agreement was reported rather than reliability. Per cent agreement was also frequently reported for inter-rater reliability, with only 4/76 studies reporting reliability statistics for 12/58 measures; this was generally high (>.80 for 11/12 measures). The majority of measures related clearly to the discourse production model indicating content validity. A total of 36/58 measures were used to make 41 comparisons between participants with aphasia (PWA) and neurologically healthy participants (NHP), with 31/41 comparisons showing a difference between the groups. Four comparisons were made between discourse genres, with two measures showing a difference between genres, and two measures showing no difference. There is currently insufficient information available to justify the use of discourse information measures as sole diagnostic or outcome measurement tools. Yet the majority of measures are rooted in relevant theory, and there is emerging evidence regarding their psychometric properties. There is significant scope for further psychometric strengthening of discourse information measurement tools.


The Impact of the Risk Factors in the Evolution of the Patients with Left Main Coronary Artery Stenosis Treated with PCI or CABG.
The aim of our study was to identify the cardiovascular risk factors present in patients with left main coronary artery disease (LMCAD), which influenced the progression of these patients in both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). We performed a clinical observational descriptive study in which, during three years, we followed the evolution of 81 patients who were diagnosed with left main coronary artery disease and who were treated either by interventional revascularization by stent implantation, by surgical revascularization by performing an aortic-coronary bypass. In our study the risk factors according to which the evolution of the patients was observed were represented by diabetes, smoking, age and gender. The primary endpoint was mortality from any cause and other clinical endpoints were the reduction of left ventricular ejection fraction, symptomatic ischemic heart disease manifested by angina pectoris, non-procedural myocardial infarction or need for repeated revascularization. In our study diabetes was the risk factor that negatively influenced the evolution of patients with LMCAD treated either by PCI or by CABG for the most part, followed by smoking, male gender and age over 65 years.


Effect of NOS1 regulating ABCG2 expression on proliferation and apoptosis of cervical cancer cells.
The expression of nitric oxide synthase 1 (NOS1) and adenosine triphosphate-binding cassette sub-family G member 2 (ABCG2) in cervical cancer tissues was investigated. The messenger ribonucleic acid (mRNA) levels of NOS1 and ABCG2 in 40 cervical cancer specimens and 20 normal cervical specimens were detected via reverse transcription-polymerase chain reaction, and the correlation between them was analyzed via Pearsons correlation analysis. The protein expression levels were detected via western blotting. Moreover, the regulatory mode between NOS1 and ABCG2 and the effects on proliferation and apoptosis of cervical cancer cells were analyzed using the lentiviral transfection technique. The mRNA levels of NOS1 and ABCG2 in the cervical cancer group were significantly increased compared with those in the normal cervical control group (P<0.05). There was a positive correlation between NOS1 and ABCG2 mRNA expression levels in cervical cancer tissues (r=1.246, P=0.014). HeLa and C-33A cell lines with relatively high expression levels of NOS1 and ABCG2 were selected for the in vitro study. After interference in the NOS1 expression in HeLa and C-33A cells with sh-NOS1, the protein expression of ABCG2 was also decreased. However, the protein expression level of NOS1 remained unchanged after interference in the ABCG2 expression (P<0.05). After interference in the NOS1 expression, the proliferation capacities of HeLa and C-33A cells were significantly decreased, but the apoptosis levels were obviously increased (P<0.05). The mRNA expression of NOS1 and ABCG2 in cervical cancer tissues is significantly increased. NOS1, as an upstream signal regulator of ABCG2, regulates the growth and apoptosis of tumor cells. Both NOS1 and ABCG2 are important proliferation-promoting oncogenes in cervical cancer, which are expected to provide a certain theoretical basis for the treatment of cervical cancer.


Hyperpolarization-activated current Ih in mouse trigeminal sensory neurons in a transgenic mouse model of familial hemiplegic migraine type-1.
Transgenic knock-in (KI) mice that express CaV2.1 channels containing an R192Q gain-of-function mutation in the α1A subunit known to cause familial hemiplegic migraine type-1 in patients, exhibit key disease characteristics and provide a useful tool to investigate pathophysiological mechanisms of pain transduction. Previously, KI trigeminal sensory neurons were shown to exhibit constitutive hyperexcitability due to up-regulation of ATP-gated P2X3 receptors that trigger spike activity at a more negative threshold. This implies that intrinsic neuronal conductances may shape action potential generation in response to ATP, which could act as a mediator of migraine headache. Here we investigated whether the hyperpolarization-activated conductance Ih, mediated by hyperpolarization activated cyclic nucleotide-gated channels (HCN), contributes to sub-threshold behavior and firing in wild-type (WT) and KI trigeminal ganglia (TG) neurons. Whereas most WT and KI trigeminal neurons expressed Ih current, blocked by the specific inhibitor ZD7288, it was smaller in KI neurons despite similar activation and deactivation kinetics. HCN1 and HCN2 were the most abundantly expressed subunits in TG, both in situ and in culture. In KI TG neurons, HCN2 subunits were predominantly present in the cytoplasm, not at the plasma membrane, likely accounting for the smaller Ih of such cells. ZD7288 hyperpolarized the membrane potential, thereby raising the firing threshold, and prolonging the spike trajectory to generate fewer spikes due to P2X3 receptor activation. The low amplitude of Ih in KI TG neurons suggests that down-regulation of Ih current in sub-threshold behavior acts as a compensatory mechanism to limit sensory hyperexcitability, manifested under certain stressful stimuli.


Poly(ADP-ribosyl)ation as a DNA damage-induced post-translational modification regulating poly(ADP-ribose) polymerase-1-topoisomerase I interaction.
Poly(ADP-ribosyl)ation is a post-translational modification that occurs immediately after exposure of cells to DNA damaging agents. In vivo, 90% of ADP-ribose polymers are attached to the automodification domain of poly(ADP-ribose) polymerase-1 (PARP-1), the main enzyme catalyzing this modification reaction. This enzyme forms complexes with transcription initiation, DNA replication, and DNA repair factors. In most known cases, the interactions occur through the automodification domain. However, functional implications of the automodification reaction on these interactions have not yet been elucidated. In the present study, we created fluorescent protein-tagged PARP-1 to study this enzyme in live cells and focused on the interaction between PARP-1 and topoisomerase I (Topo I), one of the enzymes that interacts with PARP-1 in vitro. Here, we demonstrate that PARP-1 co-localizes with Topo I throughout the cell cycle. Results from bioluminescence resonance energy transfer assays suggest that the co-localization is because of a direct protein-protein interaction. In response to DNA damage, PARP-1 de-localization and a reduction in bioluminescence resonance energy transfer signal because of the automodification reaction are observed, suggesting that the automodification reaction results in the disruption of the interaction between PARP-1 and Topo I. Because Topo I activity has been reported to be promoted by PARP-1, we then investigated the effect of the disruption of this interaction on Topo I activity, and we found that this disruption results in the reduction of Topo I activity. These results suggest that a function for the automodification reaction is to regulate the interaction between PARP-1 and Topo I, and consequently, the Topo I activity, in response to DNA damage.