Demonstration of in vivo synthesis of pro-opiomelanocortin-, beta-endorphin-, and alpha-melanotropin-like species in the adult rat brain.
An in vivo labeling technique was utilized to demonstrate the in situ biosynthesis of pro-opiomelanocortin (POMC)-, beta-endorphin- and alpha-melanotropin (MSH)-like molecular species in rat brain. Unrestrained adult female rats were bilaterally cannulated in the hypothalamic arcuate nuclear region; [35S]methionine was infused either over a 15-min period with sacrifice 2 hr subsequently, or at a constant rate for 6 hr prior to sacrifice. Sequential immune-affinity chromatography and several chromatographic and electrophoretic techniques were employed to detect and characterize POMC-related material in the hypothalamic arcuate nuclear region, preoptic area, and median eminence. Four molecular species containing both corticotropin (ACTH) and beta-endorphin antigenic determinants within the same molecules were detected in the arcuate nuclear region and preoptic area. Two forms were similar to rat pituitary POMC with respect to apparent molecular weight (35,000 and 31,500) and [35S]methionine-containing tryptic fragments (one methionine each in N-terminal glycopeptide, ACTH, and beta-endorphin sequences of rat POMC). The other two forms (apparent Mr of 21,000 and 19,000) contained only the labeled tryptic fragments characteristic of ACTH and beta-endorphin. The detection of the latter forms suggests that POMC in brain, unlike its post-translational processing in rat pituitary, undergoes primary cleavage between the N-terminal peptide and the ACTH sequence. Peptides physicochemically indistinguishable from authentic beta-endorphin and des-acetyl alpha-MSH were detected in approximately equimolar amounts in all three brain regions. The ratio of POMC-like material to the alpha-MSH- and beta-endorphin-sized peptides was highest in the arcuate nuclear region, suggesting that POMC-like proteins are synthesized in the arcuate nuclear region and are processed into the smaller molecular species during axonal transport.


Health care report cards: implications for vulnerable patient groups and the organizations providing them care.
Standardized public reporting on the quality of health care (report cards) offers an opportunity to empower purchasers and consumers so that they can make choices that can result in better health care for less money. However, not all population subgroups are equally well served by the publication of such data. In particular, vulnerable patient groups such as the poor, the less educated, the chronically sick, and members of ethnic or linguistic minorities may find issues of importance to them largely neglected. In addition, the way that report card data are collected, analyzed, and presented may further marginalize the experiences of these groups who in any case are already underserved by the health system. This observation also has important implications for health care providers who serve primarily large numbers of vulnerable patients. The differential impacts of report card data on vulnerable patient groups (and their providers) need to be addressed by researchers and policy makers if access issues are not to be damaged further by the providers' pursuit of quality and value.


A high-resolution root spatiotemporal map reveals dominant expression patterns.
Transcriptional programs that regulate development are exquisitely controlled in space and time. Elucidating these programs that underlie development is essential to understanding the acquisition of cell and tissue identity. We present microarray expression profiles of a high-resolution set of developmental time points within a single Arabidopsis root and a comprehensive map of nearly all root cell types. These cell type-specific transcriptional signatures often predict previously unknown cellular functions. A computational pipeline identified dominant expression patterns that demonstrate transcriptional similarity between disparate cell types. Dominant expression patterns along the root's longitudinal axis do not strictly correlate with previously defined developmental zones, and in many cases, we observed expression fluctuation along this axis. Both robust co-regulation of gene expression and potential phasing of gene expression were identified between individual roots. Methods that combine these profiles demonstrate transcriptionally rich and complex programs that define Arabidopsis root development in both space and time.


The effect of compliance to a Rigo System Cheneau brace and a specific exercise programme on idiopathic scoliosis curvature: a comparative study: SOSORT 2014 award winner.
There is controversy as to whether conservative management that includes wearing a brace and exercises is effective in stabilising idiopathic scoliosis curves. A brace only prevents progression of the curve and has been shown to have favourable outcomes when patients are compliant. So the aim of this study was to: determine the effect of compliance to the Rigo System Cheneau (RSC) brace and a specific exercise programme on Idiopathic Scoliosis curvature; and to compare the Quality of Life (QoL) and psychological traits of compliant and non compliant subjects. A pre/post test study design was used with a post study comparison between subjects who complied with the management and those who did not. Fifty one subjects, girls aged 12-16 years, Cobb angles 20-50 degrees participated in the study. Subjects were divided into two groups, according to their compliance, at the end of the study. The compliant group wore the brace 20 or more hours a day and exercised three or more times per week. The non-compliant group wore the brace less than 20 hours a day and exercised less than three times per week. Cobb angles, vertebral rotation, scoliometer readings, peak flow, quality of life and personality traits were compared between groups, using the student's two sample t-test and an analysis of covariance. The compliant group, wore the brace 21.5 hours per day and exercised four times a week, and significantly improved in all measures compared to non compliant subjects, who wore the brace 12 hours per day, exercised 1.7 times a week and significantly deteriorated (p < 0.0001). The major Cobb angles in the compliant group improved 10.19°(±5.5) and deteriorated 5.52°(±4.3) in the non compliant group (p < 0.0001). Compliant subjects had a significantly better QoL than the non compliant subjects (p = 0.001). The compliant group were significantly more emotionally mature, stable and realistic than the non compliant group (p = 0.03). Good compliance of the RSC brace and a specific exercise regime resulted in a significant improvement in curvatures, poor compliance resulted in progression/deterioration. A poorer QoL in the non compliant group possibly was caused by personality traits of the group, being more emotionally immature and unstable.


New Method to Prepare N-t-Butoxycarbonyl Derivatives and the Corresponding Sulfur Analogs from di-t-Butyl Dicarbonate or di-t-Butyl Dithiol Dicarbonates and Amino Acids.
Di-t-butyl dicarbonate and one of its dithiol analogs, practical methods of preparation for which are given, react with amino-acid esters to form the N-t-butoxycarbonyl (t-BOC) derivatives and the thiol analogs in good yield under mild conditions. The thiol analogs are stable to acidic conditions, which rapidly remove the t-BOC group itself. t-Butyl trimethylsilyl carbonate forms a (CH(3))(3)Si ether from a N-thiol-t-BOC serine methyl ester. The N-thiol-t-BOC group can be removed from the -NHCOSR (R = t-butyl) by heating with peroxide-acetic acid.Action of the dicarbonates described above has not been attended by racemization in the cases examined. The two dicarbonates may be useful as agents for selective blocking and deblocking of amino or other groups.


Perceptions and experiences of two survivors of stroke who participated in constraint-induced movement therapy home programs.
The purpose of this study was to explore and describe the perceptions and experiences of two survivors of stroke who participated in constraint-induced movement therapy (CIMT) home programs. Data sources were analyzed with a phenomenological approach, and common themes were identified. Themes were translated using the Occupational Adaptation frame of reference as a template. Three themes were generated from the data: (a) motivational factors and expectations represented personal desires to increase functional ability and environmental demands that created a press to participate in CIMT; (b) neurorehabilitation as an ongoing process suggested that rehabilitation should continue as long as functional deficits exist; and (c) perceived changes in function represented perceived changes in efficiency, effectiveness, and satisfaction after CIMT. CIMT was found to help the participants in this study become more satisfied with performance and to increase efficiency and effectiveness of function in daily activities.


A naphthalimide derivative can release COS and form H2S in a light-controlled manner and protect cells against ROS with real-time monitoring ability.
As an important gasotransmitter, hydrogen sulfide having multiple biological roles cannot be easily probed in cells. In this study, a light controllable H2S donor, Nap-Sul-ONB, derived from naphthalimide was developed. Under the irradiation of 365 nm light, a readily controlled stimulus, the donor could release COS to form H2S and exhibit turn on fluorescence to indicate the release of payload and its cellular location. Besides, the ROS scavenging ability and cell protective effect of Nap-Sul-ONB against endogenous and exogenous ROS were studied. The results showed that upon 365 nm light irradiation, Nap-Sul-ONB could reduce the cellular ROS level and increase the survival rate of PMA-treated cells.


PIK3CA mutations are an early genetic alteration associated with FGFR3 mutations in superficial papillary bladder tumors.
Bladder tumors constitute a very heterogeneous disease. Superficial tumors are characterized by a high prevalence of FGFR3 mutations and chromosome 9 alterations. High-grade and muscle-invasive tumors are characterized by Tp53 mutations and aneuploidy. We have analyzed the sequence of exons 9 and 20 of PIK3CA in a panel of bladder tumors covering the whole spectrum of the disease. DNA from formalin-fixed, paraffin-embedded tumor sections was amplified by PCR and products were sequenced. In an unselected panel of tumors representative of the disease, the PIK3CA mutation prevalence was 13% (11 of 87). Mutations occurred mainly at the previously identified hotspots (codons 542, 545, 1007, and 1047). The distribution according to stage was as follows: papillary urothelial neoplasms of uncertain malignant potential (PUNLMP; 11 of 43, 25.6%), T(a) (9 of 57, 16%), T(1) (2 of 10, 20%), and muscle-invasive tumors (0 of 20, 0%; P = 0.019). Mutations were associated with low-grade tumors: grade 1 (6 of 27, 22.2%), grade 2 (3 of 23, 13%), and grade 3 (2 of 37, 5.4%; P = 0.047). Overall, PIK3CA mutations were strongly associated with FGFR3 mutations: 18 of 69 (26%) FGFR3(mut) tumors were PIK3CA(mut), versus 4 of 58 (6.9%) FGFR3(wt) tumors (P = 0.005). Our findings indicate that PIK3CA mutations are a common event that can occur early in bladder carcinogenesis and support the notion that papillary and muscle-invasive tumors arise through different molecular pathways. PIK3CA may constitute a novel diagnostic and prognostic tool, as well as a therapeutic target, in bladder cancer.


Facial first impressions form two clusters representing approach-avoidance.
Existing models of facial first impressions indicate between two and four factors that underpin all social trait judgements. Here, we submitted several large databases of these first impression ratings to unsupervised learning algorithms with the aim of clustering together faces, rather than traits, to examine the ways in which impressions may be grouped together. Experiment 1 revealed two clusters of faces that exist in both a full-dimensional, and two- or three-factor representations, of social impressions, while Experiment 2 indicated that these clusters also emerged in additional datasets. In Experiment 3, using Bayesian modelling approaches, we extracted the impression profile of each cluster and also derived a vector that maximally separated the clusters. The resulting vector related strongly to the valence and approachability components in existing models. In a further test of our model, we showed in Experiment 4 that mere facial appearance, rather than perceptions, is sufficient to separate these clusters, demonstrating probabilistically that facial cues like smiling may drive the perceptual profile that gives rise to the perceptual clusters. Finally, Experiment 5 showed that observer responses to faces in these two clusters mapped closely on to approach-avoidance behaviour, with observers responding rapidly and without instruction to approach faces from one cluster over the other. Taken together, our findings provide compelling evidence, drawing upon both computational and behavioural approaches, that existing models of social impressions are realised practically in terms of basic approach-avoidance mechanisms.


Risk factors for mortality in patients with Coronavirus Disease 2019 (COVID-19) in Bolivia: An analysis of the first 107 confirmed cases.
The present study is aimed to assess the risk factors for mortality in the first 107 rRT-PCR confirmed cases of SARS-CoV-2 infections in Bolivia. For this observational, retrospective and cross-sectional study, the epidemiological data records were collected from the Hospitals and the Ministry of Health of Bolivia, obtaining the clinical and epidemiological data of the COVID-19 cases that were laboratory-diagnosed during March 2-29, 2020. Samples were tested by rRT-PCR to SARS-CoV-2 at the Laboratory of the National Center of Tropical Diseases (CENETROP), following the protocol Charite, Berlin, Germany. The odds ratio (OR) with respective 95% confidence interval (95%CI) for mortality as dependent variable was calculated. When we comparatively analyzed survivors and non-survivors in this first group of 107 cases in Bolivia, we found that at bivariate analyses, age (±60 years old), hypertension, chronic heart failure, diabetes, and obesity, as well as the requirement of ICU, were significantly exposure variables associated with death. At the multivariate analysis (logistic regression), two variables remained significantly associated, age, ±60 years-old (OR=9.4, 95%CI 1.8-104.1) and hypertension (OR=3.3, 95%CI 1.3-6.3). As expected, age and comorbidities, particularly hypertension, were independent risk factors for mortality in Bolivia in the first 107 cases group. More further studies are required to better define risk factors and preventive measures related to COVID-19 in this and other Latin American countries.


Spatial cues influence the visual perception of gender.
Spatial localization is a basic process in vision, occurring reliably when people encounter an object or person. Yet the role of spatial-location in the visual perception of people is poorly understood. We explored the extent to which spatial-location distorts the perception of gender. Consistent with evidence that the perception of objects is constrained by their location in visual scenes, enhancing perception for objects in their typical location (e.g., Biederman et al., 1982), we hypothesized that people would see relatively greater femininity in faces that appeared lower in space. On each of many trials, participants briefly viewed a pair of faces that varied in gender-ambiguity. One face appeared higher than the other, and participants identified the 1 that looked more like a woman's face (Study 1) or indicated whether the 2 faces were the same (Study 2). Across 2 experiments, participants perceived greater femininity in faces seen lower (vs. higher) in space. These effects seem to be perceptual-changes to spatial location were sufficient for altering whether 2 faces looked identical or different. Thus, spatial-location modulates visual percepts of gender, providing a biased foundation for downstream processes involved in gender biases, sexual attraction, and sex-roles. (PsycINFO Database Record


Sporulation of the "thermophilic anaerobes".
A reasonable degree of synchrony in the sporulation of Clostridium thermosaccharolyticum 3814 was obtained by using three 10% transfers of 8-hr cultures in a medium containing 0.5% L-arabinose, 0.5% peptone, 0.5% yeast extract, and Gc minerals. Sporulation was stimulated by L-arabinose and L-xylose, but was repressed by glucose, mannose, fructose, and D-pentoses. Sporulating cells were long and thin, whereas repressed cells were shorter and thicker. The optimal pH for sporulation was in the range of pH 5.0 to 5.5. As sporulation continued, the accumulated acetate decreased. Label studies indicated that a significant amount of acetate-2-C(14) was incorporated into the spore lipid. The calcium, phosphorus, and dipicolinic acid (DPA) concentrations on a dry weight basis were 2.55, 2.60, and 7.25%, respectively. The molar ratio of Ca-DPA was 1.47.


Revealing the correlation between charge carrier recombination and extraction in an organic solar cell under varying illumination intensity.
The design and fabrication of better excitonic solar cells are the need of the hour for futuristic energy solutions. This designing needs a better understanding of the charge transport properties of excitonic solar cells. One of the popular methods of understanding the charge transport properties is the analysis of the J-V characteristics of a device through theoretical simulation at varied illumination intensity. Herein, a J-V characteristic of a polymer:fullerene based bulk heterojunction (BHJ) organic solar cells (OSCs) of structure ITO/PEDOT:PSS (∼40 nm)/PTB7:PC71BM (∼100 nm)/Al (∼120 nm) is analyzed using one- and two-diode models at varied illumination intensity in the range of 0.1-2.33 Sun. It was found that the double diode model is better with respect to the single diode model and can explain the J-V characteristics of the OSCs correctly. Further, the recombination mechanism is investigated thoroughly and it was observed that fill factor (FF) is in the range of 62.5%-41.4% for the corresponding values of the recombination-to-extraction ratio (θ) varying from 0.001 to 0.023. These findings are attributed to the change in charge transport mechanism from trap-assisted to bimolecular recombination with the variation of illumination intensity.


[Differential diagnosis of first episode psychosis: importance of optimal approach in psychiatric emergencies].
To review the literature regarding the diagnosis of first episode psychosis in the context of emergency psychiatry. Review of empirical and review articles selected by electronic search in the database PubMed. Specific features of emergency care--single, brief and cross section assessment, and with little information--may jeopardize the diagnostic process. These limitations can be circumvented by application of operational diagnostic criteria, the use of scales and structured interviews and a short period of observation, between 24-72 hours. Diagnoses of bipolar disorder, schizophrenia, psychotic depression and delusional disorder developed in the context of emergency have good stability, but not the diagnoses of brief psychotic disorder, schizophreniform disorder and schizoaffective disorder. First episode psychosis can occur in the course of the use of psychoactive substances, with relatively frequent maintenance of psychotic symptoms even after cessation of the use of the substance. The rational use of subsidiary tests may help the differential diagnosis of psychotic episodes due to general medical conditions. Diagnoses of first psychotic episode can be adequately performed during psychiatric emergencies, if routines are implemented based on scientific evidence.


Metacognitive domain specificity in feeling-of-knowing but not retrospective confidence.
Previous research has converged on the idea that metacognitive evaluations of memory dissociate between semantic and episodic memory tasks, even if the type of metacognitive judgement is held constant. This often observed difference has been the basis of much theoretical reasoning about the types of cues available when making metacognitive judgements of memory and how metacognition is altered in memory pathologies. Here, we sought to revisit the difference between episodic and semantic feeling-of-knowing (FOK) judgements in the light of recent research which has supported a domain general account of metacognition. One hundred participants performed classical episodic and semantic memory tasks with FOK judgements and confidence judgements. Using the meta-d' framework, we applied a hierarchical Bayesian model to estimate metacognitive sensitivity and cross-task covariance. Results revealed a significant correlation in metacognitive efficiency (meta-d'/d') between the episodic memory task and the semantic memory task for confidence judgements; however, no evidence was found for a cross-task correlation for FOK judgements. This supports the view that FOK judgements are based on different cues in semantic and episodic memory, whereas confidence judgements are domain general.


Investigating the dependency of in vitro benchmark concentrations on exposure time in transcriptomics experiments.
There is increasing interest to employ in vitro transcriptomics experiments in toxicological testing, for example to determine a point-of-departure (PoD) for chemical safety assessment. However current practices to derive PoD tend to utilise single exposure time-despite the importance of exposure time on the manifestation of toxicity caused by a chemical. It is important therefore to investigate both concentration and exposure time to determine how these factors affect biological responses, and as a consequence, the derivation of PoDs. In this study, metabolically competent HepaRG cells were exposed to five known toxicants over a range of concentrations and time points for subsequent gene expression analysis, using a targeted RNA expression assay (TempO-Seq). A non-parametric factor-modelling approach was used to model the collective response of all significant genes, which exploited the significant interdependence of differentially expressed gene responses. This in turn allowed to determine an isobenchmark-response (isoBMR) curve for each chemical in a reproducible manner. For 2 of the 5 chemicals tested, the PoD was observed to vary by 0.5-1 log-order within the 48-h timeframe of the experiment. The approach and findings presented here clearly demonstrate the need to take both concentration and exposure time into account when designing in vitro toxicogenomics experiments to determine PoD. Doing so also provides a means to use concentration-time-response modelling as a basis to extrapolate a PoD from shorter to longer exposure durations, and to identify chemicals of concern that can cause cumulative effects over time.


A 4-Year Longitudinal Study of the Sex-Creativity Relationship in Childhood, Adolescence, and Emerging Adulthood: Findings of Mean and Variability Analyses.
The relationship between sex and creativity remains an unresolved research question. The present study aimed to approach this question through the lens of the developmental theory of sex differences in intelligence, which posits a dynamic pattern of sex differences in intellectual abilities from female superiority in childhood and early adolescence to male superiority starting at 16 years of age. A total of 775 participants from three age groups (i.e., children, adolescents, and emerging adults) completed a 4-year longitudinal study comprising four assessments of creative thinking at 1-year intervals. Creative thinking was assessed with the Test for Creative Thinking-Drawing Production. While the results revealed female superiority in childhood and early adolescence, male superiority was not found in adolescence and emerging adulthood. Rather, greater sex similarities and greater male variability were found based on mean and variability analyses, respectively. This study elucidated the link between sex and creativity by (1) taking a developmental perspective, (2) employing a 4-year longitudinal design in three age groups (i.e., children, adolescents, and emerging adults), and (3) analyzing sex differences based on both mean and variability analyses.


Analysis of the properties of binding of calcium-channel activators and inhibitors to dihydropyridine receptors in chick heart membranes.
The interaction of 1,4-dihydropyridine derivatives with their receptors on voltage-dependent calcium channels in cardiac membranes was studied to determine if there are basic differences in the binding properties of ligands that cause inhibition or activation of calcium channels. The binding characteristics of 6 pure stereoisomers, (-) and (+)202-791, (-) and (+)Bay k 8644, (-) and (+)PN 200-110, as well as racemic Bay k 8644 and nitrendipine, were compared. Competition studies using the cold ligands and 3 different radiolabelled dihydropyridines, (+)[3H]PN 200-110, (+/-)[3H]nitrendipine, and (+/-)[3H]Bay k 8644, showed that, for each combination tested, the labelled dihydropyridine could be displaced by the cold dihydropyridine. The binding reactions were markedly affected by temperature. The Kd values for most compounds were significantly higher (5-19 times) at 0 degrees than at 37 degrees C. In contrast, the affinity of (+)PN 200-110 was similar at 0 degrees and 37 degrees C, but slightly higher at 25 degrees C. A thermodynamic analysis indicated that the binding of the two pure isomers that are Ca2+-channel activators ("agonists"), (-)Bay k 8644 and (+)202-791, was driven entirely by enthalpy and was associated with an unfavorable decrease in entropy. This was in marked contrast to the binding of the inhibitors ("antagonists"). The binding of (+)PN 200-110 and nitrendipine at low temperatures was driven largely or entirely by entropy. Other antagonist-binding reactions were driven mainly by enthalpy but were associated with favorable increases in entropy. The affinity of the three radiolabelled ligands for the dihydropyridine receptor differed 100 times and appeared to be due to large differences in dissociation rate constants for each of the ligands. The rates of dissociation of (+)[3H]PN 200-110 and (+/-)[3H]nitrendipine, but not of (+/-)[3H]Bay k 8644, were significantly slowed by diltiazem, a calcium-channel inhibitor that binds to another receptor on the calcium channel. The results show that there were marked differences in the binding of the various dihydropyridines and suggest that the energetics of binding of Ca2+-channel activators and inhibitors may be fundamentally different.


FlyView, a Drosophila image database, and other Drosophila databases
FlyView is an image database for Drosophila development and genetics, particularly for gene-expression patterns. Thousands of enhancer-trap lines have now been isolated by different methods, particularly by using a variety of transposons with the resulting flies being kept in a great many laboratories. We are collecting pictures of expression patterns of all lines that are available for use by Drosophila researchers and now offer about 1800 images of about 350 enhancer-trap lines in FlyView. This article also summarizes information on the other main Drosophila resources: FlyBase-the main Drosophila database, Flybrain, an online atlas and database of the Drosophila nervous system, and Interactive Fly, a cyberspace guide to Drosophila genes and their roles in development.Copyright 1997 Academic Press Limited Copyright 1997Academic Press Limited


AMPA silencing is a prerequisite for developmental long-term potentiation in the hippocampal CA1 region.
AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) unsilencing is an often proposed expression mechanism both for developmental long-term potentiation (LTP), involved in circuitry refinement during brain development, and for mature LTP, involved in learning and memory. In the hippocampal CA3-CA1 connection naïve (nonstimulated) synapses are AMPA signaling and AMPA-silent synapses are created from naïve AMPA-signaling (AMPA-labile) synapses by test-pulse synaptic activation (AMPA silencing). To investigate to what extent LTPs at different developmental stages are explained by AMPA unsilencing, the amount of LTP obtained at these different developmental stages was related to the amount of AMPA silencing that preceded the induction of LTP. When examined in the second postnatal week Hebbian induction was found to produce no more stable potentiation than that causing a return to the naïve synaptic strength existing prior to the AMPA silencing. Moreover, in the absence of a preceding AMPA silencing Hebbian induction produced no stable potentiation above the naïve synaptic strength. Thus this early, or developmental, LTP is nothing more than an unsilencing (dedepression) and stabilization of the AMPA signaling that was lost by the prior AMPA silencing. This dedepression and stabilization of AMPA signaling was mimicked by the presence of the protein kinase A activator forskolin. As the relative degree of AMPA silencing decreased with development, LTP manifested itself more and more as a "genuine" potentiation (as opposed to a dedepression) not explained by unsilencing and stabilization of AMPA-labile synapses. This "genuine," or mature, LTP rose from close to nothing of total LTP prior to postnatal day (P)13, to about 70% of total LTP at P16, and to about 90% of total LTP at P30. Developmental LTP, by stabilization of AMPA-labile synapses, thus seems adapted to select synaptic connections to the growing synaptic network. Mature LTP, by instead strengthening existing stable connections between cells, may then create functionally tightly connected cell assemblies within this network.


Combined preoperative irradiation and local hyperthermia delays early healing of experimental colonic anastomoses.
To determine if a combination of preoperative irradiation and local hyperthermia of a colonic segment is detrimental to subsequent early anastomotic healing. A prospective randomized experimental trial. An animal research laboratory. Eighty male Wistar rats were randomly divided into 4 groups. In each animal, a segment of the colon was treated successively by (sham) irradiation and (sham) hyperthermia. After 5 days, a colonic resection was performed and an anastomosis was constructed; the distal limb consisted of (sham) irradiated, (sham) hyperthermia-treated bowel. The rats were killed 3 or 7 days after surgery. Body weight, serum albumin and protein levels, anastomotic bursting pressure, breaking strength, and hydroxyproline content. All animals tolerated (sham) treatment well. Weight was diminished, though not notably, in treated animals vs the control group. After combined preoperative irradiation and hyperthermia, the frequency of local anastomotic complications increased: 4 of 20 animals had a covered perforation when they were killed. In this group, the bursting pressure was lower 3 days after the operation (P = .008). The breaking strength was also lower but not notably. The serum albumin level was significantly lower in this group vs the control group (P = .006); the serum protein level was not decreased. After 7 days, no differences existed between the groups. The hydroxyproline content of the anastomotic tissue was notably higher in rats treated with radiation plus hyperthermia vs control rats (in both the 3- and 7-day groups). The anastomotic hydroxyproline concentration did not differ between the groups. The combination of preoperative irradiation and hyperthermia results in increased local anastomotic complications. Anastomotic strength is at risk in the first days after the anastomotic reconstruction. Preoperative irradiation or hyperthermia alone does not lead to impaired anastomotic healing in the early phase.


Experience of pelvic floor muscle exercises among women in Taiwan: a qualitative study of improvement in urinary incontinence and sexuality.
To gain an in-depth understanding of women's experiences of performing pelvic floor muscle exercises for urinary incontinence and the impact on their sexuality. Urinary incontinence is not a life-threatening disorder; however, it has been shown to have detrimental effects on quality of life in terms of psychological, social and sexual dysfunction. Pelvic floor muscle exercises is the first recommended strategy for managing mild to moderate urinary incontinence as it is noninvasive and cost effective. Pelvic floor muscle exercises reduce incontinence and strengthen the pelvic floor muscles, which positively affects sexual function in women. Currently, the data are scarce for qualitative literature regarding the subjective experiences of Taiwanese women undergoing pelvic floor muscle exercises and the impact on their urinary incontinence and sexuality. Qualitative exploratory study. Semi-structured in depth interviews were undertaken with twelve women who had completed a pelvic floor muscle exercises program in Taiwan. Data were analysed using thematic analysis. Themes were related to Taiwanese women's initial feelings that urinary incontinence was inevitable and the effects on their sexuality. Three core themes were identified: perceptions of inevitability, developing awareness and gaining control and sexual taboo. Through developing awareness and control of their pelvic floor muscles women expressed improvement in urinary incontinence. Sexual enjoyment, body image, self confidence and sexuality were also enhanced. Pelvic floor muscle exercises had a positive effect on urinary incontinence and sexuality. The findings demonstrated that sex is a taboo topic for many Taiwanese women. With the sensitive management of pelvic floor muscle exercises programs this issue can be addressed. This study raises awareness of healthcare professionals by identifying how Taiwanese women perceive pelvic floor muscles. The positive impact of pelvic floor muscle exercises upon both urinary incontinence and sexuality within the Taiwanese context are addressed. Nurses may also, with greater confidence initiate discussion of women's sexual concerns as part of managing urinary incontinence.


Environmental conditions unexpectedly affect the long-term extent of cell death following an hypoxic episode.
Previously we reported delayed cell death, defined by clear-cut cell loss 60 days after a nitrite-induced hypoxic episode. The loss of cells was not apparent two weeks after the treatment, although some changes in cellular appearance were observed at that time. A similar delayed loss of neurons in the hippocampus after hypoxia induced by blood vessel occlusion has also been found. In addition, we reported that the amount of methemoglobinemia induced by the sodium nitrite can be reduced by the stress produced by handling and the injection of saline 2 or 24 h before the nitrite administration. The degree of methemoglobin formed is directly related to cell death in certain areas of the brain, including regions within the hippocampus. Considering the many effects that can be produced by chronic and acute stress of several kinds and the length of time during which these effects manifest themselves, we undertook to determine the histologic effects of the stresses of transport on the neuroanatomic effects of sodium nitrite administration 60 days post administration. Comparisons were made of the effects of two methods of transport from the laboratory in which the animals (male CD-1 mice) were injected with the sodium nitrite or saline (Tufts Medical School) to the laboratory in which the histologic evaluations were made (Binghamton University). The animals began their travel several hours after the injections. One transport method was by commuter airline and the other was by automobile. All animals had the same transport from the supplier to the Boston location (truck). Thus, the stress of experimental interest occurred after the nitrite administration. Upon arrival at Binghamton University, the animals were housed at the University in their own colony room for 60 days before sacrifice. After sacrifice, sections from their brains were subjected to a number of histologic staining procedures, including PTAH, the Bielschowsky silver method, GFAP, and the standard Nissl procedure. Although special attention was paid to hippocampal areas, changes in cells in the habenulae and the linings of ventricular areas were also prominent. Surprisingly, the nitrite treatment before transport to Binghamton offered partial protection against the very substantial and lasting effects of the injections, transport, and handling found in the control animals. Differential effects caused by the two methods of transport were also noted.


Occupational adverse effects and protective factors in bronchoscopy.
The application of bronchoscopy has resolved a series of diagnostic and treatment challenges in pulmonary diseases. However, the occupational adverse effects experienced by healthcare workers in interventional pulmonology should receive increasing attention. Various aspects of adverse effects in bronchoscopy are often neglected, and healthcare workers frequently ignore guidelines for personal protection against factors such as radiation, smoke, pathogenic microbiological aerosols, cryogenic gas, etc. Thus, there is an urgent need to conduct additional research to establish standards for occupational adverse effects and protective measures related to bronchoscopy.


Building Consensus on the Point-of-Care Ultrasound Skills Required for Effective Healthcare Service Delivery at District Hospitals in South Africa: A Delphi Study.
Despite the widespread availability of ultrasound machines in South African district hospitals, there are no guidelines on the competency in point-of-care ultrasound (POCUS) use required by generalist doctors in this setting. This study aimed to define the required POCUS competencies by means of consensus via the Delphi method. An online Delphi process was initiated in June 2022, using the existing American Academy of Family Physicians' ultrasound curriculum (84 skillsets) as the starting questionnaire. Panelists were selected across the country, including two from district hospitals in each province and two from each academic family medicine department in South Africa (N = 36). In each iterative round, the participants were asked to identify which POCUS skillsets were essential, optional (region-specific), or non-essential for South African district hospitals. This process continued until consensus (>70% agreement) was achieved on all of the skillsets. Consensus was achieved on 81 of the 84 skillsets after 5 iterative rounds (96.4%), with 3 skillsets that could not achieve consensus (defined as <5% change over more than 2 consecutive rounds). The final consensus identified 38 essential, 28 optional, and 15 non-essential POCUS skillsets for the South African district hospital context. The list of essential POCUS skillsets provided by this study highlights the predominance of obstetric- and trauma-based skillsets required for generalist healthcare workers in South African district hospitals. The findings will require priority setting and revalidation prior to their implementation across the country.


The Benefits of Psychosocial Interventions for Mental Health in People Living with HIV: A Systematic Review and Meta-analysis.
In this systematic review and meta-analysis we investigated the effectiveness of different psychosocial treatments for people living with HIV (PLWH) and mental health problems. Additionally, characteristics that may influence the effectiveness of a treatment (e.g., treatment duration) were studied. PubMed, PsycINFO and Embase were searched for randomized controlled trials on psychosocial interventions for PLWH. Depression, anxiety, quality of life, and psychological well-being were investigated as treatment outcome measures. Sixty-two studies were included in the meta-analysis. It was found that psychosocial interventions for PLWH had a small positive effect on mental health (ĝ = 0.19, 95% CI [0.13, 0.25]). Furthermore, there was evidence for publication bias. Six characteristics influenced the effectiveness of a treatment for depression. For example, larger effects were found for studies with psychologists as treatment providers. To conclude, this systematic review and meta-analysis suggests that psychosocial interventions have a beneficial effect for PLWH with mental health problems.


An epi-allele of SMS causes Sanming dominant genic male sterility in rice.
Male sterility is an important trait in rice for hybrid rice (Oryza sativa) breeding. However, the factors involved in dominant male sterility are largely unknown. Here, we identified a gene from Sanming dominant genic male sterile rice, named Sanming dominant male sterility (SMS), and reported that an epi-allele of this locus contributes to male sterility. Segregation analysis attributed dominant male sterility to a single locus, SMS, which we characterized using a male-sterile near isogenic line (NIL) of rice cultivar 93-11. The SMS locus was heterozygous in the male-sterile 93-11 NIL, containing an epi-allele identical to that in 93-11, and an epi-allele identical to that in rice cultivar Nipponbare, which we refer to as SMS9 and SMSN, respectively. SMS9 is silent and hyper-methylated, whereas SMSN is expressed and hypo-methylated in the 93-11 NIL. Overexpressing SMSN led to male sterility. Mutations in SMS rescued the male sterility of the 93-11 NIL. Interestingly, we observed the duplication of SMSN in Nipponbare, but did not observe the duplication of SMS9 in 93-11. Together, these findings suggest that the reduced methylation and enhanced expression of the SMSN epi-allele in the 93-11 NIL is responsible for its role in conferring dominant male sterility.


A transforming growth factor beta 2 (TGF-beta 2)-like immunosuppressive factor in amniotic fluid and localization of TGF-beta 2 mRNA in the pregnant uterus.
This report describes a murine amniotic fluid (MAF) immunosuppressive factor that has properties similar to transforming growth factor beta (TGF-beta). The MAF factor exhibits TGF-beta-like activity in stimulating soft agar colony formation by AKR-2B cells and inhibiting thymidine uptake by Mv1Lu cells. We demonstrate that both the immunosuppressive and TGF-beta-like activities of the MAF factor are completely neutralized by anti-TGF-beta 2-specific antibodies and not by anti-TGF-beta 1-specific antisera. The immunosuppressive factor in MAF is novel in that it appears to be identical or very closely related to TGF-beta 2 and is active in its native state. This active and anti-TGF-beta 2-neutralizable factor chromatographs at approximately 70 kD on Sephadex at neutral pH and appears to be able to complex with alpha-fetoprotein in native amniotic fluid. Chromatography of native MAF under acidic conditions demonstrates a lower molecular mass protein that chromatographs on BioGel in the same position as the mature 25-kD TGF-beta. This protein has the biological properties of TGF-beta and is immunosuppressive. Both of these activities are neutralizable with anti-TGF-beta 2 but not with anti-TGF-beta 1 or other antisera. By Northern analysis, we find high levels of TGF-beta 2 mRNA (with little or no TGF-beta 1) in the pregnant uterus that peak around day 15 of gestation and then fall rapidly by day 19 as birth approaches. The TGF-beta 2-like factor could possibly play a role in maternal immunity, in the retention of the fetal allograft, as well as in regulating fetal and neonatal immunological competence.


Bosea caraganae sp. nov. a new species of slow-growing bacteria isolated from root nodules of the relict species Caragana jubata (Pall.) Poir. originating from Mongolia.
Two Gram-stain-negative strains, RCAM04680T and RCAM04685, were isolated from root nodules of the relict legume Caragana jubata (Pall.) Poir. originating from the south-western shore of Lake Khuvsgul (Mongolia). The 16S rRNA gene (rrs) sequencing data showed that these novel isolates belong to the genus Bosea and are phylogenetically closest to the type strains Bosea lathyri LMG 26379T, Bosea vaviloviae LMG 28367T, Bosea massiliensis LMG 26221T and Bosea lupini LMG 26383T (the rrs-similarity levels were 98.7-98.8 %). The recA gene of strain RCAM04680T showed the highest sequence similarity to the type strain B. lupini LMG 26383T (95.4 %), while its atpD gene was closest to that of B. lathyri LMG 26379T (94.4 %). The ITS, dnaK and gyrB sequences of this isolate were most similar to the B. vaviloviae LMG 28367T (86.8 % for ITS, 90.4 % for the other genes). The most abundant fatty acid was C18 : 1ω7c (40.8 %). The whole genomes of strains RCAM04680T and RCAM04685 were identical (100 % average nucleotide identity). The highest average nucleotide identity value (82.8 %) was found between the genome of strain RCAM04680T and B. vaviloviae LMG 28367T. The common nodABC genes required for legume nodulation were absent in both strains; however, some other symbiotic nol, nod, nif and fix genes were detected. Based on the genetic study, as well as analyses of the whole-cell fatty acid compositions and phenotypic properties, a new species, Boseacaraganae sp. nov. (type strain RCAM04680T (=LMG 31125T), is proposed.


[Efficacy, safety and acceptability of precipitated sulphur petrolatum for topical treatment of scabies at the city of Coro, Falcon State, Venezuela].
In spite of sulphur ointment has been applied during centuries in the treatment of human scabies, nevertheless, its clinical efficacy, as well as safety and acceptability has not been clearly demonstrated. During September 2001-March 2002, attempts have been made to assess the efficacy, safety and acceptability of a mixture of precipitated sulphur 2-8% petrolatum for the treatment of 40 ambulatory consultant patients, of all age groups, including children under 1 year of age, pregnant and lacting women, with suggestive sarcoptic cutaneous lesions from Coro, Falcon State, Venezuela. The diagnosis was made by clinical examination and microscope observation (KOH 10%) of scrapings of cutaneous lesions. The acceptability were quantified using visual analogue scale (VAS) and other two behavioral (BS) scores. Enrolled patients applied ointment 1 daily dose for 6 days, 1 week rest, repeated for 2 days, thoroughly washing off with neutral soap and applying lubricant cream. Differential schedule concentrations were: 2% for children below 2 years and up to 6 years old; 2-5% for scholars, adolescents and pregnant; 5-8% for adults and elderly; being exposition time to the ointment of 3 hours for children under 2 years old, and overnight for reminding age-groups. Efficacy was evaluated 7-30 days post-treatment by clinic observation, quantification and scraping of the sarcoptic lesions. A safety assessment was based on adverse effects reported by patients or observed by the physician. 38 (95%) out of 40 patients were clinical and ectoparasitologically cured 7-30 days after cessation of ointment application, with no relapses or relevant adverse effects, producing a significant (t = 9.26; p < 0.0001) decrease at the end of evaluation period in the median values of number of lesions (28.08-9.18 vs. 0.00). Only 2 (5%) patients developed a mild dermatitis reaction, and subsequently no completed the follow up. It's proven highly therapeutic effectiveness as well as widely availability, low costs with no serious side effects and satisfactory acceptability (X; VAS = 1.14 +/- 1.67; BS: 0.25 +/- 0.38, 0.53 +/- 0.43), allows us to recommend the topical use of the ointment sulfur-petrolatum for the treatment of human scabies, especially in children under 5 years of age, pregnant and lactating women and elderly, in which other drugs are not recommended by its potential toxicity.


Linear Ion Trap Mass Spectrometer (LITMS) Instrument Field and Laboratory Tests as Part of the ARADS Field Campaigns.
The highly compact Linear Ion Trap Mass Spectrometer (LITMS), developed at NASA Goddard Space Flight Center, combines Mars-ambient laser desorption-mass spectrometry (LD-MS) and pyrolysis-gas chromatography-mass spectrometry (GC-MS) through a single, miniaturized linear ion trap mass analyzer. The LITMS instrument is based on the Mars Organic Molecule Analyser (MOMA) investigation developed for the European Space Agency's ExoMars Rover Mission with further enhanced analytical features such as dual polarity ion detection and a dual frequency RF (radio frequency) power supply allowing for an increased mass range. The LITMS brassboard prototype underwent an extensive repackaging effort to produce a highly compact system for terrestrial field testing, allowing for molecular sample analysis in rugged planetary analog environments outside the laboratory. The LITMS instrument was successfully field tested in the Mars analog environment of the Atacama Desert in 2019 as part of the Atacama Rover Astrobiology Drilling Studies (ARADS) project, providing the first in situ planetary analog analysis for a high-fidelity, flight-like ion trap mass spectrometer. LITMS continued to serve as a laboratory tool for continued analysis of natural Atacama samples provided by the subsequent 2019 ARADS final field campaign.


Blood culture gram stain, acridine orange stain and direct sensitivity-based antimicrobial therapy of bloodstream infection in patients with trauma.
The purpose of this study was to ascertain if the simple practice of Gram stain, acridine orange stain and direct sensitivity determination of positive blood culture bottles could be used to guide early and appropriate treatment in trauma patients with clinical suspicion of sepsis. The study also aimed to evaluate the error in interpreting antimicrobial sensitivity by direct method when compared to standard method and find out if specific antibiotic-organism combination had more discrepancies. Findings from consecutive episodes of blood stream infection at an Apex Trauma centre over a 12-month period are summarized. A total of 509 consecutive positive blood cultures were subjected to Gram staining. AO staining was done in BacT/ALERT-positive Gram-stain negative blood cultures. Direct sensitivity was performed from 369 blood culture broths, showing single type of growth in Gram and acridine orange staining. Results of direct sensitivity were compared to conventional sensitivity for errors. No 'very major' discrepancy was found in this study. About 5.2 and 1.8% minor error rates were noted in gram-positive and gram-negative bacteria, respectively, while comparing the two methods. Most of the discrepancies in gram-negative bacteria were noted in beta lactam - beta lactamase inhibitor combinations. Direct sensitivity testing was not reliable for reporting of methicillin and vancomycin resistance in Staphylococci. Gram stain result together with direct sensitivity testing is required for optimizing initial antimicrobial therapy in trauma patients with clinical suspicion of sepsis. Gram staining and AO staining proved particularly helpful in the early detection of candidaemia.


Are femoroacetabular impingement tomographic angles associated with the histological assessment of labral tears? A cadaveric study.
This study sought to investigate the association between tomographic femoroacetabular impingement (FAI) angles and histologically evaluated labral tears. The authors hypothesized that cadavers presenting with cam and pincer morphologies would present a higher prevalence of acetabular labral tears. Twenty fresh cadavers were submitted to computed tomography. Standard FAI angles were measured, including the alpha angle, femoral version, acetabular version, Tonnis angle and center-edge angle. A cam lesion was defined as an alpha angle greater than 50o. A pincer lesion was defined as a center-edge angle greater than 40o, a Tonnis angle less than 0o or acetabular version less than 0o. After dissection, three fragments of each acetabulum, corresponding to the antero-superior, superior and postero-superior acetabular rim, were obtained. These fragments were submitted to routine histological preparation. Each slide was evaluated for possible labral tears. Tears were classified according to their Seldes type. The mean age of the cadavers was 50.2 years (SD: 7.4; 13 males). Sixteen (80%) of the cadavers had a cam lesion, and eight cadavers (40%) had a pincer lesion. Histologically, 16 (80%) of the cadavers had a labral tear in at least one region. According to the Seldes classification, 60.7% and 28.6% of these labral tears were type 1 and type 2, respectively. A mixed type of labral tear (10.7%), which represented a new form of Seldes tear, was described. Cadavers with a labral tear had significantly higher alpha angles than other cadavers (53.29o vs 49.33o, p = 0.01). Pincer lesions were not associated with labral tears. We found no association between pincer or cam lesions and Seldes classification. Cadavers presenting with higher alpha angles had a higher incidence of labral tears. No association was found between FAI and Seldes classification. This study demonstrated a high prevalence of FAI abnormalities associated with histological alterations in a cadaveric sample. Joint damage may be present in the early stages of FAI.


Primary renal synovial sarcoma: molecular and morphologic delineation of an entity previously included among embryonal sarcomas of the kidney.
We report 15 primary renal neoplasms with morphologic, immunohistochemical, and molecular features identical to those of synovial sarcoma. These tumors form a distinct subset of the entity previously designated as embryonal sarcoma of the kidney. Most were diagnosed between the ages of 20 and 50 years. On gross examination, tumors are large, partially necrotic, and usually contain smooth-walled cysts. Microscopically, tumors are characterized by mitotically active, monomorphic plump spindle cells with indistinct cell borders growing in short, intersecting fascicles. Grossly identified cysts are lined by mitotically inactive polygonal eosinophilic cells with apically oriented nuclei ("hobnailed epithelium"). The spindle cells are immunoreactive for vimentin, often immunoreactive for EMA, but typically non-immunoreactive for desmin, actin, S100, or cytokeratins, whereas the cyst epithelium is cytokeratin-positive. These findings are consistent with monophasic, spindled synovial sarcoma encircling dilated native renal collecting ducts. The presence of an SYT-SSX gene fusion resulting from the t(X;18) characteristic of synovial sarcoma was demonstrated by reverse transcriptase polymerase chain reaction in three of three tumors in which adequate RNA could be obtained from paraffin blocks. An additional case demonstrated the characteristic t(X; 18) translocation on cytogenetic analysis, but adequate material to perform molecular studies was not available in this case or the remaining 11 cases. Primary renal synovial sarcoma is a distinctive clinicopathologic entity confirmed by molecular detection of SYT-SSX fusion transcripts.


Flecainide suppresses bidirectional ventricular tachycardia and reverses tachycardia-induced cardiomyopathy in Andersen-Tawil syndrome.
Bidirectional ventricular tachycardia (BVT), although a rare arrhythmia in the general population, is frequently observed in patients with Andersen-Tawil syndrome and long QT interval. However, the pharmacologic treatment of this arrhythmia remains unknown. In the present study, we documented the favorable antiarrhythmic action of flecainide in a young woman with sustained BVT and Andersen-Tawil syndrome. She presented with incessant BVT that could only be terminated with flecainide. During sinus rhythm, a prolonged QT interval was observed. Genetic studies revealed a mutation in the K(+) channel gene KCNJ2. Over a 4-year follow-up period, recurrence of her arrhythmia occurred twice. The first episode was due to noncompliance and resolved with resumption of flecainide therapy. The second recurrence was associated with a tachycardia-induced cardiomyopathy and resolved when the dose of flecainide was increased from 200 to 300 mg daily. This report suggests that flecainide can be effective in controlling BVT associated with Andersen-Tawil syndrome and indicates that the left ventricular dysfunction is secondary to the arrhythmia and not due to an associated phenotypic manifestation of the disorder.


Tyramine as a possible neurotransmitter/neuromodulator at the spermatheca of the African migratory locust, Locusta migratoria.
Tyramine-like immunoreactivity was identified in neurons of the VIIIth abdominal ganglion and in axons projecting to the spermatheca of adult females of Locusta migratoria. Tyramine-like immunoreactive processes were also found throughout all regions of the spermatheca and tyramine-like immunoreactive bipolar or multipolar neurons were present on the spermathecal sac. HPLC coupled with electrochemical detection revealed more tyramine than octopamine present in spermathecal tissue. Electrical stimulation of the ventral ovipositor nerve resulted in a significant increase in calcium-dependent release of tyramine from the spermatheca. Both tyramine and octopamine increase the frequency and basal tonus of spermathecal contractions in a dose-dependent manner, with octopamine having a lower threshold. When tyramine is applied along with a half maximal octopamine dose, there is an additive effect on contractions of the spermatheca with slight synergistic effects at lower doses of tyramine. High concentrations of tyramine (10(-4)M) stimulated increases in cyclic AMP levels of the spermatheca; an effect blocked by phentolamine. Phentolamine has a higher affinity (and thus a lower IC(50) value congruent with 5.6 x 10(-8)M) than yohimbine (IC(50) congruent with 1.1 x 10(-4)M) in reducing tyramine-induced spermathecal contractions. Taken together, these results suggest that tyramine may be a co-transmitter with octopamine at the spermatheca, with both neuroactive chemicals acting on an octopamine receptor.


Genotoxicity of phthalates.
Many of the environmental, occupational and industrial chemicals are able to generate reactive oxygen species (ROS) and cause oxidative stress. ROS may lead to genotoxicity, which is suggested to contribute to the pathophysiology of many human diseases, including inflammatory diseases and cancer. Phthalates are ubiquitous environmental chemicals and are well-known peroxisome proliferators (PPs) and endocrine disruptors. Several in vivo and in vitro studies have been conducted concerning the carcinogenic and mutagenic effects of phthalates. Di(2-ethylhexyl)-phthalate (DEHP) and several other phthalates are shown to be hepatocarcinogenic in rodents. The underlying factor in the hepatocarcinogenesis is suggested to be their ability to generate ROS and cause genotoxicity. Several methods, including chromosomal aberration test, Ames test, micronucleus assay and hypoxanthine guanine phosphoribosyl transferase (HPRT) mutation test and Comet assay, have been used to determine genotoxic properties of phthalates. Comet assay has been an important tool in the measurement of the genotoxic potential of many chemicals, including phthalates. In this review, we will mainly focus on the studies, which were conducted on the DNA damage caused by different phthalate esters and protection studies against the genotoxicity of these chemicals.


Exploring the role of miRNAs in the diagnosis of MODY3
Background/aim: MODY3 associated with HNF1A is the most common form of MODY and is clinically misdiagnosed as type 1 diabetes due to similar clinical symptoms. This study aimed to analyze the role of HNF1A-regulated miRNAs as a biomarker in the diagnosis of MODY3. Materials and methods: MIN6 cells were transfected with the HNF1A cDNA expression vector for overexpression or with siRNA specific to HNF1A to silence its expression. The HNF1A-regulated miRNAs were determined by RNA-Seq of the total RNA extract. Expressions of the candidate miRNAs in blood samples of MODY3, type 1 diabetes, and type 2 diabetes patients and in healthy subjects were compared statistically by Mann-Whitney U tests. Results: This study revealed the presence of 238 known HNF1A-regulated miRNAs in MIN6 cells. miR-129-1-3p, miR-200b-3p, and miR-378a-5p were selected as candidate miRNAs. The expression level of miR-378a-5p significantly decreased in type 2 diabetes and MODY3 patients, while miR-200b-3p expression was significantly decreased only in MODY3 patients. Conclusion: Although further studies with larger numbers of patients are required, this study demonstrated that the expression levels of miR-200b-3p and miR-378a-5p decrease in MODY3 patients and suggests that miR-200b-3p is an especially strong candidate to use clinically for selecting suspected MODY3 patients.


A systematic review of the literature reporting on randomised controlled trials comparing treatments for faecal incontinence in adults.
To perform a review of the literature reporting on randomised controlled trials (RCTs) comparing treatments for faecal incontinence (FI) in adults. A literature search of MEDLINE, Embase, Science Citation Index Expanded and Cochrane was performed in order to identify RCTs reporting on treatments for FI. The review included 60 RCTs reporting on 4838 patients with a mean age ranging from 36.8 to 88 years. From the included RCTs, 32 did not identify a significant difference between the treatments compared. Contradictory results were identified in RCTs comparing percutaneous posterior tibial nerve stimulation and transcutaneous tibial nerve stimulation versus sham stimulation, biofeedback-pelvic floor muscle training (BF-PFMT) versus PFMT, and between bulking agents such as PTQTM versus Durasphere®. In two separate RCTs, combination treatment of amplitude-modulated medium frequency stimulation and electromyography-biofeedback (EMG-BF), was noted to be superior to EMG-BF and low-frequency electrical stimulation alone. Combination of non-surgical treatments such as BF with sphincteroplasty significantly improved continence scores compared to sphincteroplasty alone. Surgical treatments were associated with higher rates of serious adverse events compared to non-surgical interventions. The current evidence has not identified significant differences between treatments for FI, and where differences were identified, the results were contradictory between RCTs.


Reversal of diabetes by xenotransplantation of monkey pancreatic islets in rats: an ultrastructural study.
Transplantation of pancreatic islets is considered a potential curative treatment of type 1 diabetes. Electron microscopy plays a major role in the evaluation of pancreatic islets. The aim of this study was to study the reversal of diabetes by xenotransplantation of monkey pancreatic islets into diabetic recipient by functional and structural findings. Islets of Langerhans were isolated from monkeys by collagenase digestion method. Two days after the induction of diabetes in rats with streptozotocin, diabetes was confirmed. Freshly isolated islets were transplanted under the renal capsule of the diabetic rats. The recipients received cyclosporin A (30 mg/kg) every day. Fasting plasma glucose was estimated on days 3, 7, and 14 after transplantation. The presence of glucose and ketone in urine was checked. After 14 days, the grafts were removed and processed for light and electron microscopic study. After the induction of diabetes, the mean fasting plasma glucose was 347.20 mg/dL. On day 3 after transplantation, the mean fasting plasma glucose value was 100 mg/dL. The mean fasting plasma glucose was 94.6 mg/dL on day 7 and 94.8 mg/dL on day 14. Histology of the monkey islet grafts after 14 days showed the survival of pancreatic islets. Ultrastructure of the same grafts showed the presence of alpha, beta, and delta granules similar to those of native pancreatic islets with the other cellular organelles. The diabetic state of rats can be reversed by xenotransplantation of isolated monkey islets. Ultrastructural study confirms the normal synthesis and release of islet hormones. The released insulin from transplanted monkey islets had lowered the plasma glucose level of recipient rats.


Surgery in adults with tethered cord syndrome: outcome study with independent clinical review.
The authors conducted a study to evaluate the risks and short-term benefits of surgical treatment for tethered cord syndrome (TCS) in patients older than 18 years of age. The authors studied a series of 57 consecutive adult patients with TCS of varying origins. Patients were examined by the same neurologist in a standardized fashion before and after surgery, and most were followed for at least 2 years postoperatively. Patient age ranged from 19 to 75 years. The mean age at onset of symptoms and diagnosis was 30 years and 37 years, respectively. Muscle strength improved (15 cases) or showed no change postoperatively (38 cases) in a large majority of patients (93%). In four patients a minor decrease in muscle strength was demonstrated, and there was significant deterioration in two (3.5%). In the two latter patients, a rapid decline in motor function was present preoperatively. Subjective assessment of pain, gait, sensory function, and bladder/bowel function at 4 weeks, 6 months, and 2 years postsurgery revealed improvement in a substantial percentage of patients. No major surgery-related complications occurred. This is the largest series to date in which adult patients with TCS comprise the report. Untethering procedures in these patients were safe and effective, at least in the short term. Patients with rapid loss of motor function, lipomyelomeningocele, or split cord malformation seem to be at a higher risk of postsurgery deterioration. A follow-up period of many more years will be necessary to determine whether aggressive surgery is beneficial in the long term.


The President's Emergency Plan for AIDS Relief: from successes of the emergency response to challenges of sustainable action.
The President's Emergency Plan for AIDS Relief (PEPFAR) has made a major contribution to the reduction of the global HIV/AIDS burden. The program initially focused on rapidly scaling up treatment and prevention services in fifteen low-income countries, then transitioned to an approach that emphasizes sustainability, defined as the capacity to maintain program services after financial, managerial, and technical assistance from the United States and other external donors essentially ceases. Today, PEPFAR continues to expand its HIV prevention, treatment, and care activities while also supporting capacity-building initiatives, coordination efforts, and implementation science. The latter is research focused on improving service delivery, maximizing cost-effectiveness, and achieving public health impact. Recent advances in both scientific knowledge and the provision of prevention, treatment, and care services have bred cautious optimism about greatly reducing the spread of HIV. However, success will require a substantial increase in resources, strengthened health systems, renewed commitment to HIV prevention, and well-financed efforts to develop an effective HIV vaccine.


Isolation and detection of DNA-protein crosslinks in mammalian cells.
DNA-protein crosslinks (DPCs) are toxic DNA lesions wherein a protein is covalently attached to DNA. If not rapidly repaired, DPCs create obstacles that disturb DNA replication, transcription and DNA damage repair, ultimately leading to genome instability. The persistence of DPCs is associated with premature ageing, cancer and neurodegeneration. In mammalian cells, the repair of DPCs mainly relies on the proteolytic activities of SPRTN and the 26S proteasome, complemented by other enzymes including TDP1/2 and the MRN complex, and many of the activities involved are essential, restricting genetic approaches. For many years, the study of DPC repair in mammalian cells was hindered by the lack of standardised assays, most notably assays that reliably quantified the proteins or proteolytic fragments covalently bound to DNA. Recent interest in the field has spurred the development of several biochemical methods for DPC analysis. Here, we critically analyse the latest techniques for DPC isolation and the benefits and drawbacks of each. We aim to assist researchers in selecting the most suitable isolation method for their experimental requirements and questions, and to facilitate the comparison of results across different laboratories using different approaches.


Next-generation sequencing as a tool for breakpoint analysis in rearrangements of the globin gene clusters.
Next-generation sequencing (NGS), now embedded within genomic laboratories, is well suited to the detection of small sequence changes but is less well adapt for detecting structural variants (SV), mainly due to the relatively short sequence reads. Of the available target enrichment methods, bait capture or whole-genome sequencing appears better suited to detecting SV as there is less PCR amplification and is therefore more representative of the genome being sequenced. In 2015, we described the first inversion/deletion causing εγδβ- thalassemia using an NGS approach, with base-pair resolution. Bioinformatic processing of the sequencing data was manual and time-consuming. The methodology relied on detecting the presence or absence of the SV by assessing sequence coverage and then mapping the deletion by capturing and sequencing breakpoint spanning reads (split reads). In the period between developing more automated analytical methods, we identified the first duplication of the entire beta globin cluster. Detecting the presence of the SV is reliable but capturing the breakpoint spanning reads is challenging. Confirmation by Sanger sequencing a breakpoint spanning amplicon has confirmed the NGS results in all cases. We have now streamlined and automated the bioinformatic approach using Exome Depth to assess sequence coverage and Delly to detect split and discordant reads. The combined NGS and bioinformatic strategy has proven to be highly successful and applicable to routine diagnostics.


Molecular speciation controls arsenic and lead bioaccessibility in fugitive dusts from sulfidic mine tailings.
Communities nearby mine wastes in arid and semi-arid regions are potentially exposed to high concentrations of toxic metal(loid)s from fugitive dusts deriving from impoundments. To assess the relation between potentially lofted particles and human health risk, we studied the relationship between pharmacokinetic bioaccessibility and metal(loid) molecular speciation for mine tailings dust particulate matter (PM), with elevated levels of arsenic and lead (up to 59 and 34 mmol kg-1, respectively), by coupling in vitro bioassay (IVBA) with X-ray absorption spectroscopy (XAS). Mine tailing efflorescent salts (PMES) and PM from the surface crust (0-1 cm, PMSC) and near surface (0-25 cm) were isolated to <10 μm and <150 μm effective spherical diameter (PM10 and PM150) and reacted with synthetic gastric and lung fluid for 30 s to 100 h to investigate toxic metal(loid) release kinetics. Bioaccessible (BAc) fractions of arsenic and lead were about 10 and 100 times greater in gastric than in lung fluid simulant, respectively, and 10-100% of the maximum gastric BAc from PM10 and PM150 occurred within 30 s, with parabolic dissolution of fine, highly-reactive particles followed by slower release from less soluble sources. Evaporite salts were almost completely solubilized in gastric-fluid simulants. Arsenate within jarosite and sorbed to ferrihydrite, and lead from anglesite, were identified by XAS as the principal contaminant sources in the near surface tailings. In the synthetic lung fluid, arsenic was released continuously to 100 h, suggesting that residence time in vivo must be considered for risk determination. Analysis of pre- and post-IVBA PM indicated the release of arsenic in lung fluid was principally from arsenic-substituted jarosite, whereas in synthetic gastric fluid arsenic complexed on ferrihydrite surfaces was preferentially released and subsequently repartitioned to jarosite-like coordination at extended exposures. Lead dissolved at 30 s was subsequently repartitioned back to the solid phase as pyromorphite in phosphate rich lung fluid. The bioaccessibility of lead in surface tailings PM was limited due to robust sequestration in plumbojarosite. Kinetic release of toxic elements in both synthetic biofluids indicated that a single IVBA interval may not adequately describe release dynamics.


A Facile Method for Controlled Fabrication of Hybrid Silver Nanoparticle-Poly(-caprolactone) Fibrous Constructs with Antimicrobial Properties.
Infection is one of the major factors affecting wound healing. The use of polymeric fibrous constructs or scaffolds with encapsulated biologically active components has shown great potential in topical wound care as wound dressings to expedite wound healing process; however, there is a limitation in precise control over the release of active components. Therefore, in this study, the authors developed a facile method for controlled fabrication of poly(-caprolactone) (PCL) microfibrous constructs with silver (Ag) nanoparticles as antibacterial agent by single capillary electrospinning. By optimizing spinning parameters, the PCL microfibrous constructs were fabricated. The encapsulation of Ag nanoparticles within the PCL microfibers was confirmed using microstructural analysis. The encapsulation efficacy and release profile of Ag was evaluated in vitro. The diffusion study further revealed the controlled release and optimal bioavailability of Ag during the experimental period. in vitro assessment of antibacterial activity of electrospun hybrid constructs showed a high antibacterial activity and an inhibitory effect on the growth of both staphylococcus aureus and escherichia coli bacteria when compared to PCL and their efficiency of antibacterial activity also varied with respect to the percent of encapsulated Ag nanoparticles. This kind of Ag nanoparticles-loaded PCL microfibrous constructs may be considered for wound care applications.


[Robotics in gynecology. Background, feasibility and applicability].
Robotic surgery is a technology that emerged from the fusion and improvement of laparoscopy, robotics and telepresence. All these three technologies underwent a long experimentation process in which several applications and innovations were tested until the only system approved for use in humans was developed: the Da Vinci system by Intuitive Surgical Inc. Gynecology, being one of the pioneer branches of Medicine involved in the development of laparoscopy, is one of the fields with the greatest possibilities for robotics, which offers great diversity of applications in hysterectomies, myomectomies, endometriosis, and in the fields of urogynecology and, most importantly, oncology. There are no publications in Mexico with a proper description of the clinical experience with gynecologic robotic surgery, though a great amount of clinical experience has been accumulated in institutions that already have such equipment. A serious evaluation of the cost-benefit ratio is required because of the high cost of this technology. Evaluate and analyze the accumulated experience on this technology of foreign institutions in order to assess the benefits, cost and effectiveness of robotic surgery. The key to the optimal use of robotic technology is to diminish costs and speed the learning curve, and this implies the entry of other systems into the market as well as institutions with a high volume of patients and determined to invest in a highly trained and skilled surgical team. In order to recommend its implementation in our country an assessment of the efficiency and advantages of robotic technology considering institutional needs is mandatory.


Usurped SLRPs: novel arthritis biomarkers exposed by catabolism of small leucine-rich proteoglycans?
Proteolytic degradation of articular cartilage macromolecules, including the large aggregating cartilage proteoglycan (aggrecan) and small leucine-rich proteoglycans (SLRPs), is a prominent pathophysiological feature of arthritic diseases such as osteoarthritis (OA). Molecular profiling and monitoring of soluble/circulating proteoglycan catabolites that may be released from the cartilage matrix therefore represents an attractive strategy for evaluating OA disease progression and intervention. The recent identification of discrete metalloproteinase-sensitive SLRP cleavage sites, and complementary neoepitope-bearing SLRP catabolites, extends decisive insight into the functional regulation of extracellular matrix integrity, and proffers poignant leads to assist in disclosing and appraising applicable biomarkers of cartilage degeneration during arthritis.


Hearts and Minds: Real-Life Cardiotoxicity With Clozapine in Psychosis.
Schizophrenia has a 1% prevalence in the population; 30% of these patients are treatment refractory. Clozapine is the only drug licensed to treat treatment refractory psychosis, but concerns about potential adverse effects result in only a proportion of eligible patients being treated. Although a well-documented neutropenia risk is mitigated by routine blood testing, cardiac toxicity is a commonly cited reason to discontinue clozapine treatment. However, there is little data on the real-life cardiac outcomes in those receiving clozapine treatment. Retrospective review of electrocardiogram, echocardiogram, and clinical outcomes in 39 inpatients with treatment-refractory schizophrenia, treated with clozapine and other antipsychotic medication, referred for cardiology opinion. Commonest reasons for referral were development of left ventricular (LV) impairment or sinus tachycardia with normal LV function. Patients were reviewed by a range of cardiologists, receiving varied interventions.Median LV ejection fraction in the clozapine group was normal (52%). Serial echocardiograms demonstrated that clozapine-treated patients with LV impairment had no change in LV ejection fraction over a 4-month follow-up. Left ventricular ejection fraction did not differ between patients treated with clozapine and other antipsychotics. However, over an 11-year follow-up period, 48% of patients had discontinued clozapine treatment. This naturalistic study demonstrates that clozapine is not associated with significant cardiac mortality or morbidity. There is a real need for multidisciplinary working between specialist cardiologists and psychiatrists caring for these complex patients to facilitate optimal long-term physical and mental health outcomes.


[Treatment of accidental dural puncture during obstetric epidural analgesia].
To assess the effectiveness of continuous intrathecal analgesia as prophylaxis for postdural puncture headache (PDPH) and for analgesia during labor in 12 patients who suffered accidental dural puncture. A total of 920 patients who received spinal analgesia during labor were enrolled. Group A (no accidental dural puncture) received a single dose of 10 mL of 0.2% ropivacaine, and 5 minutes later continuous epidural infusion of 0.125% ropivacaine and 3 micromg mL(-1) was started at a rate of a 5 mL h(-1); a 5 mL bolus dose was allowed every 20 minutes if needed. In patients who suffered accidental dural puncture (Group B) we inserted an intrathecal catheter to administer an initial dose of 3 mL of 0.2% ropivacaine and the same analgesic mixture at the same dose as was administered in Group A. Patient characteristics, analgesic efficacy, duration of labor and delivery, motor blockade, analgesic volume, and incidence of PDPH were recorded. The Student t test was used for statistical comparisons. No significant differences in duration of labor and delivery, analgesic efficacy, or motor blockade were observed. The incidence of PDPH was 16.6% in Group B and 0.33% in Group A. The patients in Group B required more additional bolus doses: 10 (SD, 2) in Group B and 3 (1.25) in Group A (P<0.01). Continuous intrathecal analgesia after accidental dural puncture was a safe way to provide analgesia during labor and to reduce the expected incidence of PDPH.


Second harmonic scattering from mass characterized 2D graphene oxide sheets.
In this communication, we report the second harmonic scattering from mass characterized 2D graphene oxide sheets dispersed in an aqueous suspension, in the femtosecond regime at 800 nm laser excitation. Charge-detection mass-spectrometry, performing at the single sheet level, allows for an exhaustive molar mass distribution and thus concentration for these 2D nanomaterials samples. The orientation-averaged hyperpolarizability value is (1.36 ± 0.15) × 10-25 esu as determined by the concentration-dependent harmonic scattering signal. In addition, the multi-photon excited fluorescence spectrum is characterized by a broad band in the visible range between 350 and 700 nm centered at about 500 nm.


Acute ethanol alters multiple histone modifications at model gene promoters in the cerebral cortex.
Ethanol (EtOH) exposure alters gene expression in the cerebral cortex (CCx); however, mechanisms of EtOH-induced gene regulation are not well understood. We hypothesized that EtOH regulates gene expression by differentially altering histone modifications at gene promoters that are up- and down-regulated by EtOH. Such epigenetic mechanisms may ultimately contribute to EtOH-induced neuro-adaptations that underlie tolerance, dependence, and EtOH-use disorders. Eight-week-old, male C57BL/6J mice were treated with 3 g/kg EtOH (intraperitoneally) or saline and sacrificed 6 hours after injection; the CCx and hippocampus (HC) were immediately removed and flash frozen. Chromatin immunoprecipitation was used to study the association of model gene promoters with histone modifications. Western blot was used to detect global changes in the histone modifications studied. We also used a polymerase chain reaction (PCR) array to identify changes in expression of chromatin-modifying enzymes. In CCx, acute EtOH decreased expression of Gad1, Hdac2, and Hdac11, which was associated with decreased histone acetylation at the Gad1 and Hdac2 promoters; we also identified increased expression of Mt1, Mt2, Egr1, which was associated with increased H3K4me3 levels at the Mt2 promoter and decreased H3K27me3 levels at the Mt1 promoter. We identified an increase in global levels of H3K4me3 in CCx as well as a global increase in H3K9ac and H3K14ac in HC. The PCR array identified decreased expression of Csrp2 bp, Hdac2, and Hdac11 as well as increased expression of Kat2b in CCx. Acute EtOH induces chromatin remodeling at model up- and down-regulated genes in CCx. Different patterns of histone modifications at these gene promoters indicate that EtOH may be acting through multiple histone-modifying enzymes to alter gene expression; in particular, differential expression of Kat2b, Hdac2, Hdac11, and Csrp2 bp in CCx may mediate EtOH-induced chromatin remodeling. Additional studies are necessary to determine the relationship between EtOH-induced changes in histone-modifying enzymes, specific EtOH-induced histone modifications, and gene expression.


Chromosomal instability in unirradiated hemaopoietic cells induced by macrophages exposed in vivo to ionizing radiation.
The tumorigenic potential of ionizing radiation has conventionally been attributed to DNA damage in irradiated cells induced at the time of exposure. Recently, there have been an increasing number of reports of damage in unirradiated cells that are either neighbors or descendants of irradiated cells, respectively, regarded as bystander effects and genomic instability and collectively termed nontargeted effects. In this study, we show that descendants of normal murine hemaopoietic clonogenic stem cells exposed to bone marrow-conditioned medium derived from gamma-irradiated mice exhibit chromosomal instability unlike the descendants of directly gamma-irradiated cells. The instability is expressed in bone marrow cells of the radiation-induced acute myeloid leukemia (r-AML) susceptible strain (CBA/Ca) but not in mice resistant to r-AML (C57BL/6). Furthermore, crossgenetic experiments show the induction of the instability phenotype requires both the producer and responder cells to be of the susceptible CBA/Ca genotype. Macrophages are the source of the bystander signals, and the signaling mechanism involves tumor necrosis factor-alpha, nitric oxide, and superoxide. The findings show a genotype-dependent chromosomal instability phenotype induced by radiation-induced macrophage-mediated bystander signaling. As the majority of accidental, occupational, and therapeutic exposures to ionizing radiation are partial body exposures, the findings have implications for understanding the consequences of such exposure.


Nonaqueous capillary electrophoretic separation of basic enantiomers using heptakis(2,3-dimethyl-6-sulfato)-beta-cyclodextrin.
The enantiomers of 40 basic analytes, mostly pharmaceuticals, were separated by nonaqueous capillary electrophoresis in acidic methanol background electrolytes using the sodium salt of heptakis(2,3-dimethyl-6-sulfato)-beta-cyclodextrin (HDMS-beta-CD). The effective mobilities, separation selectivities, and peak resolution values were determined as a function of the HDMS-beta-CD concentration in the 0-40 mM range and were found to follow the theoretical predictions of the charged resolving agent migration model (CHARM model). Fast, efficient enantiomer separations were achieved for a large number of both very hydrophobic and hydrophilic weak bases.


A pilot randomised controlled trial of cognitive behavioural therapy for antenatal depression.
Few trials have evaluated the effectiveness of psychological treatment in improving depression by the end of pregnancy. This is the first pilot randomised controlled trial (RCT) of individual cognitive behavioural therapy (CBT) looking at treating depression by the end of pregnancy. Our aim was to assess the feasibility of delivering a CBT intervention modified for antenatal depression during pregnancy. Women in North Bristol, UK between 8-18 weeks pregnant were recruited through routine contact with midwives and randomised to receive up to 12 sessions of individual CBT in addition to usual care or to continue with usual care only. Women were eligible for randomisation if they screened positive on a 3-question depression screen used routinely by midwives and met ICD-10 criteria for depression assessed using the clinical interview schedule - revised version (CIS-R). Two CBT therapists delivered the intervention. Follow-up was at 15 and 33 weeks post-randomisation when assessments of mental health were made using measures which included the CIS-R. Of the 50 women assessed for the trial, 36 met ICD-10 depression criteria and were randomised: 18 to the intervention and 18 to usual care. Thirteen of the 18 (72%) women who were allocated to receive the intervention completed 9 or more sessions of CBT before the end of pregnancy. Follow-up rates at 15 and 33 weeks post-randomisation were higher in the group who received the intervention (89% vs. 72% at 15 weeks and 89% vs. 61% at 33 weeks post-randomisation). At 15 weeks post-randomisation (the end of pregnancy), there were more women in the intervention group (11/16; 68.7%) who recovered (i.e. no longer met ICD-10 criteria for depression), than those receiving only usual care (5/13; 38.5%). This pilot trial shows the feasibility of conducting a large RCT to assess the effectiveness of CBT for treating antenatal depression before the end of pregnancy. The intervention could be delivered during the antenatal period and there was some evidence to suggest that it could be effective. ISRCTN44902048.


Photodynamic therapy: update 2006. Part 1: Photochemistry and photobiology.
Photodynamic therapy (PDT) is a two-step therapeutic technique in which the topical or systemic delivery of photosensitizing drugs is followed by irradiation with visible light. Activated photosensitizers transfer energy to molecular oxygen, generating reactive oxygen species (ROS). The subsequent oxidation of lipids, amino acids and proteins induces cell necrosis and apoptosis. In addition, ROS indirectly stimulate the transcription and release of inflammatory mediators. The photosensitizers are selective, in that they penetrate and accumulate in tumour cells or in the endothelium of newly formed vessels while generally avoiding the surrounding healthy tissue. The mechanisms of penetration through the cell membrane and the pattern of subcellular localization strongly influence the type of cellular effect. The photobiology and photoimmunology of the haematoporphyrin (Hp) derivative and its purified, lyophilized and concentrated form porfimer sodium have been investigated over the past 30 years. However, interest in PDT in dermatology was not raised until the 1990s with the availability of a simple and effective technique, the topical application of aminolaevulinic acid (ALA) and its methyl ester (methyl aminolaevulinate, MAL) followed by irradiation with broadband red light. At the same time, several new 'second-generation' synthetic sensitizers (e.g. benzoporphyrin derivatives, phthalocyanines, chlorins and porphycenes) became available. These compounds are chemically pure, highly efficient, selective and safe, while offering the advantage that the generalized skin photosensitivity they produce lasts for only a short time. They are currently under clinical evaluation but have not yet been approved for clinical use. This paper provides an overview of the chemistry of the photosensitizers, the photobiology and photoimmunology of the photodynamic reaction as well as the photophysical characteristics of the light sources available for PDT.


Self-Knowledge in Personality Disorder: Self-Referentiality as a Stepping Stone for Psychotherapeutic Understanding.
This article provides a philosophical framework to help unpack varieties of self-knowledge in clinical practice. We start from a hermeneutical conception of "the self," according to which the self is not interpreted as some fixed entity, but as embedded in and emerging from our relating to and interacting with our own conditions and activities, others, and the world. The notion of "self-referentiality" is introduced to further unpack how this self-relational activity can become manifest in one's emotions, speech acts, gestures, and actions. Self-referentiality exemplifies what emotions themselves implicitly signify about the person having them. In the remainder of the article, we distinguish among three different ways in which the self-relational activity can become manifest in therapy. Our model is intended to facilitate therapists' understanding of their patients' self-relational activity in therapy, when jointly attending to the self-referential meaning of what their patients feel, say, and do.


OFF-ON-OFF fluorescent response of N,N,N',N'-tetrakis(1-isoquinolylmethyl)-2-hydroxy-1,3-propanediamine (1-isoHTQHPN) toward Zn(2.).
An isoquinoline-based ligand, N,N,N',N'-tetrakis(1-isoquinolylmethyl)-2-hydroxy-1,3-propanediamine (1-isoHTQHPN), exhibits a fluorescence increase at 475 nm upon addition of 1 equiv. of Zn(2+) (IZn/I0 = 12, ϕZn = 0.023). This fluorescence enhancement turns and then decreases sharply after the addition of more than 1 equiv. of Zn(2+) reaching a constant minimum intensity with more than 2 equiv. of Zn(2+). In contrast, the fluorescence intensity at 353 nm continues to increase until the signal saturates at ca. 5 equiv. of Zn(2+). This observation can be explained by the formation of a fluorescent mononuclear complex ([Zn(1-isoHTQHPN)](2+)) followed by a non-fluorescent dinuclear complex ([Zn2(1-isoTQHPN)](3+)) at 475 nm during the titration of 1-isoHTQHPN with Zn(2+). Both the mono- and dinuclear complexes were characterized by UV-vis, fluorescence, (1)H NMR, ESI-MS, X-ray crystallography and TDDFT calculations. The fluorescence enhancement at 475 nm is Zn(2+)-specific; Cd(2+) induces a much smaller emission increase (ICd/I0 = 3.7, ICd/IZn = 31%). The Zn(2+)/Cd(2+) selectivity of the fluorescent response correlates with the difference in excimer-forming ability derived from the Cd-Nisoquinoline and Zn-Nisoquinoline bond distances.


Genome-wide analysis of the homeodomain-leucine zipper family in Lotus japonicus and the overexpression of LjHDZ7 in Arabidopsis for salt tolerance.
The homeodomain-leucine zipper (HD-Zip) family participates in plant growth, development, and stress responses. Here, 40 HD-Zip transcription factors of Lotus japonicus were identified and gave an overview of the phylogeny and gene structures. The expression pattern of these candidate genes was determined in different organs and their response to abiotic stresses, including cold, heat, polyethylene glycol and salinity. The expression of the LjHDZ7 was strongly induced by abiotic stress, especially salt stress. Subsequently, LjHDZ7 gene was overexpressed in Arabidopsis. The transgenic plants grew obviously better than Col-0 plants under salt stress. Furthermore, LjHDZ7 transgenic lines accumulated higher proline contents and showed lower electrolyte leakage and MDA contents than Col-0 plants under salt stress. Antioxidant activities of the LjHDZ7 overexpression lines leaf were significantly higher than those of the Col-0 plants under salt stress. The concentration of Na+ ion in LjHDZ7 overexpression lines was significantly lower than that of Col-0 in leaf and root parts. The concentration of K+ ion in LjHDZ7 overexpression lines was significantly higher than that of Col-0 in the leaf parts. Therefore, these results showed that overexpression of LjHDZ7 increased resistance to salt stress in transgenic Arabidopsis plants, and certain genes of this family can be used as valuable tools for improving abiotic stresses.


The validity of the pretreated, unilaterally MPTP-treated monkeys as a model of Parkinson's disease: a detailed behavioural analysis of the therapeutic and undesired effects of the D2 agonist quinpirole and the D1 agonist SKF 81297.
The goal of this study was to evaluate the validity of the pretreated, unilaterally MPTP-treated monkey as an animal model of Parkinson's disease (PD). For that purpose, a detailed ethogram was developed and assessed in four male rhesus monkeys that had received MPTP (2.5 mg) in the carotid artery contralateral to the dominant limb. Subsequently, the behavioural effects of the dopamine D2 agonist quinpirole and the dopamine D1 agonist SKF 81297 were studied. The ethogram was found to allow a clear-cut and objective separation of drug-induced behaviours into therapeutic and undesired effects in the MPTP-treated monkeys. Saline-treated monkeys predominantly displayed ipsilateral goal-directed fore-limb movements, and distinct types of ipsilaterally directed rotations. Although quinpirole and SKF 81297 increased motor behaviours, such as body displacement, contralateral fore-limb movements and contralateral rotational behaviours, assessment of the new detailed ethogram revealed that this increase was completely due to the activation of abnormal, non-goal-directed behaviours, such as dyskinetic fore-limb movements, pivoting and shuffling. Moreover, the new ethogram made clear that the drug treatments induced not only dyskinesia and dystonia, but also epileptoid behaviour, which was confirmed by EEG analysis. In summary, the detailed behavioural analysis showed that this model does not adequately predict the clinical effects of the D2 agonist. It is concluded that the pretreated, unilaterally MPTP-treated monkey is not a valid model to predict the therapeutic and undesired effects of dopaminergic drugs in humans.


Immunohistochemical detection of BH3-only proteins in ameloblastic tumors.
To evaluate expression of BH3-only proteins in odontogenic tumors, expression of Bid, Bim, Bad, Noxa, and Puma was analyzed in ameloblastic tumors as well as in tooth germs. Nine tooth germs, 37 ameloblastomas, and five malignant ameloblastic tumors were examined immunohistochemically with antibodies against Bid, Bim, Bad, Noxa, and Puma. Immunohistochemical reactivity for Bid, Bim, Bad, Noxa, and Puma was detected in the cytoplasm of cellular components in normal and neoplastic odontogenic tissues. Expression of these BH3-only proteins was evident in odontogenic epithelial cells near the basement membrane in tooth germs and ameloblastic tumors. Acanthomatous ameloblastomas showed no reactivity for Bid, Bim, Bad, Noxa, or Puma in keratinizing cells, whereas granular cells in granular cell ameloblastomas reacted with these BH3-only proteins. Basal and desmoplastic ameloblastomas and ameloblastic carcinomas showed immunoreactivity for the BH3-only proteins in most neoplastic cells. Expression of Bid, Bim, Bad, Noxa, and Puma in tooth germs and ameloblastic tumors suggests that the BH3-only proteins have a role in apoptotic cell death of normal and neoplastic odontogenic epithelium. Distinctive expression patterns of these BH3-only proteins in ameloblastoma variants suggest that the BH3-only proteins might be involved in tumor cell differentiation of ameloblastomas.


Effects of chronic modification of dietary fat and carbohydrate in rats.
1. Rats were fed on diets enriched with starch, sucrose, corn oil or beef tallow for 3 weeks and the activities of various enzymes in the liver were measured. 2. The mitochondrial glycerol phosphate acyltransferase activity was lower in rats fed on the starch diet than on the two high-fat diets. 3. The non-microsomal (presumably peroxisomal) dihydroxyacetone phosphate acyltransferase activity was higher in rats fed on the starch diet and corn-oil diets than in those fed on the sucrose and beef-tallow diets. Urate oxidase activity was higher in rats fed on the starch diet than in the three other groups. There were no significant differences in the activity of acyl-CoA oxidase among the groups. 4. The activity of soluble phosphatidate phosphohydrolase was not significantly different among the dietary groups. There were increases of 3.3--4.3-fold in this activity in the dietary groups 6h after injection of corticotropin. The equivalent increases for the mitochondrial glycerol phosphate acyltransferase were 1.4--1.6 fold. 5. The corticosterone responses to the corticotropin injection were not significantly different between dietary groups. However, the corticosterone response of the rats fed on the two high-fat diets was prolonged when the rats were given an acute load of fructose [Brindley, Cooling, Glenny, Burditt & McKechnie (1981) Biochem. J. 200. 275--283]. 6. Rats fed on the high-fat diets had higher concentrations of circulating cholesterol than those fed on the starch and sucrose diets. Serum triacylglycerol concentrations were lower in the rats fed on the starch diet than in the three other groups. 7. The results are discussed in terms of the relationship between diet, hormonal balance and hepatic glycerolipid metabolism.