Atomic force microscopy analysis of normal and photoablated porcine corneas.
We showed the capabilities and accuracy of atomic force microscopy (AFM) techniques for imaging and analyzing the corneal epithelium and the photoablated corneal stroma. Eight normal porcine corneas, half of which were ablated using a scanning-spot excimer laser, were examined. All the corneas were imaged in balanced salt solution after fixation in glutaraldehyde. In the normal untreated corneas we observed the epithelial surface showing the typical polygonal cells and presenting numerous microprojections. The superficial epithelial cells were classified in three types as a result of the anterior-surface roughness measurements. AFM images of the photoablated corneal specimens showed undulations and granule-like features on the ablated stromal surface, specific to 193-nm ArF laser irradiation. Nevertheless, the quantitative analysis confirmed the precision of excimer laser surgery in removing sub-micrometric amounts of tissue. AFM showed to be a high-resolved imaging tool for the scanning of both native as well as photoablated corneal specimens. Also, this technique permits precise topographic analysis of the corneal plane, in the nanometric scale, of which smoothness is an important physical characteristic and necessary to achieve an optimal optical quality of the eye.


Spin on adverse effects in abstracts of systematic reviews of orthodontic interventions: a cross-sectional study (part 2).
It is critical that abstracts of systematic reviews transparently report both the beneficial and adverse effects of interventions without misleading the readers. This cross-sectional study assessed whether adverse effects of interventions were reported or considered in abstracts of systematic reviews of orthodontic interventions and whether spin on adverse effects was identified when comparing the abstracts with what was sought and reported in these reviews. This cross-sectional study (part 2 of 2) used the same sample of 98 systematic reviews orthodontic interventions as used in part 1. Eligible reviews were retrieved from the Cochrane Database of Systematic Reviews and the 5 leading orthodontic journals between August 1 2009 and July 31 2021. Prevalence proportions were sought for 3 outcomes as defined in the published protocol. Univariable logistic regression models were built to explore associations between the presence of spin in the abstract and a series of predictors. Odds ratios (OR) 95% confidence intervals (95% CI) were used to quantify the strength of associations and their precision. 76.5% (75/98) of eligible reviews reported or considered (i.e., discussed, weighted etc.) potential adverse effects of orthodontic interventions in the abstract and the proportion of spin on adverse effects was 40.8% (40/98) in the abstract of these reviews. Misleading reporting was the predominant category of spin, i.e., 90% (36/40). Our explorative analyses found that compared to the Cochrane Database of Systematic Reviews all 5 orthodontic journals had similar odds of the presence of spin on adverse effects in abstracts of systematic reviews of orthodontic interventions. The odds of the presence of spin did not change over the sampled years (OR: 1.03, 95% CI: 0.9 to 1.16) and did not depend on the number of authors (OR: 0.93, 95% CI: 0.71 to 1.21), or on the type of orthodontic intervention (OR: 1.1, 95% CI: 0.45 to 2.67), or whether conflicts of interests were reported (OR: 0.74, 95% CI: 0.32 to 1.68). End users of systematic reviews of orthodontic interventions have to be careful when interpreting results on adverse effects in the abstracts of these reviews, because they could be jeopardized by uncertainties such as not being reported and misleading reporting as a result of spin.


HRCT quantitative analysis of airway remodeling and airway trapping in the small airway asthma phenotype and its correlation with pulmonary function.
We aimed to explore whether large airway remodeling and small airway structural changes exist in subjects with small airway asthma phenotype and to evaluate the relationships between quantitative high-resolution computed tomography (qHRCT) parameters and lung function. We enrolled 15 subjects with small airway asthma phenotype and 18 healthy controls. The two groups were matched by age, sex and body square area (BSA) with propensity score matching (PSM). Pulmonary function and qHRCT parameters [wall thickness (WT), wall area (WA), lumen area (LA), wall area percentage (WA%) of the 4th-6th generations in the right upper lobe apical segmental bronchus (RB1), adjusted by BSA, WT/BSA, WA/BSA, and LA/BSA, relative volume change -860 HU to -950 HU (RVC-860 to -950) and the expiration to inspiration ratio of mean lung density (MLDE/I)) were compared between the groups. Correlation analysis was employed to assess the relationship between qHRCT parameters and pulmonary function. The small airway asthma phenotype had significantly higher WA%, RVC-860 to -950 and MLDE/I and lower LA/BSA than the healthy control. Additionally, we found moderate to strong correlations between impulse oscillation (IOS) indices and WA6% and WT6/BSA. No significant correlation was found between bronchial parameters and air trapping parameters (p > 0.05). Combining physiological tests with imaging approaches can lead to better evaluation of small airway disfunction (SAD) in asthmatic patients. Additionally, despite nonexistent airflow obstruction in patients with small airway asthma phenotype, large airway remodeling and small airway structural changes may appear simultaneously in the early stage of disease.


The Effect of Triglyceride Concentration on Attainment of Lipid Targets in Patients with Diabetes.
To evaluate the effects of triglyceride (TG) and glycated hemoglobin (A1C) concentrations in the percentage of patients with diabetes who are within target (WT) for low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C) and apolipoprotein B (ApoB), as defined by the Canadian Lipid Guidelines, in a cohort of outpatients presenting at a 350-bed community hospital. Laboratory samples from 1919 patients, 18 years or older, who had A1C levels of 6.5% or above were used. Fasting lipid profiles were retrieved, and ApoB was measured. We found no significant difference in the percentage of those WT for LDL-C as TG increased from normal to intermediate and high levels. For non-HDL-C, we saw a substantial decrease in the percentage of patients WT as TG levels increased from normal (61%) to intermediate (30.4%) and high levels (14.0%). ApoB showed a similar pattern to non-HDL-C: decreasing from normal (68.8%) to intermediate (40.7%) and high levels (21.0%). No significant difference was seen in the percentage of patients WT for the 3 lipid parameters studied with the increase in A1C levels. As TG increases, we saw discordance in the percentage of patients WT for LDL-C in relation to non-HDL-C and ApoB. Alternative targets to LDL-C should preferentially be used when the TG concentration is elevated.


Highly sensitive polymer-based cantilever-sensors for DNA detection.
We present a technology for the fabrication of cantilever arrays aimed to develop an integrated biosensor microsystem. The fabrication process is based on spin coating of the photosensitive polymer and near-ultraviolet exposure. Arrays of up to 33 microcantilevers are fabricated in the novel polymer material SU-8. The low Young's modulus of the polymer, 40 times lower than that of silicon, enables to improve the sensitivity of the sensor device for target detection. The mechanical properties of SU-8 cantilevers, such as spring constant, resonant frequency and quality factor are characterized as a function of the dimensions and the medium. The devices have been tested for measurement of the adsorption of single stranded DNA and subsequent interstitial adsorption of lateral spacer molecules. We demonstrate that sensitivity is enhanced by a factor of six compared to that of commercial silicon nitride cantilevers.


Interstitial delivery of vascular endothelial growth factor to skin flaps.
To demonstrate the feasibility of using microporous catheters to deliver a growth factor in a skin flap model, and to determine whether removal of excess fluid by ultrafiltration catheters reduces edema. In a controlled study at a research laboratory associated with major teaching hospital, vascular endothelial growth factor was delivered to porcine skin flaps by direct infusion using hollow fiber catheters. Treated flaps received either infusion alone or infusion and ultrafiltration via hollow fibers inserted into the distal portion of the flap. Controls had neither type of catheter placed. The main outcome measure was flap survival and edema. Treated anterior flaps were found to have increased survival (mean [SD] increase, 49.9% [9.4%]) compared with control flaps (44.1% [4.5%]) for group (P = .005) and side (P = .01) but not by interaction (P = .14). Water content was significant by analysis of variance for group, position, and interaction (all P < .001, df = 31) for treated (55.3% [9.7%]) and control (61.9% [8.2%]) groups. This study demonstrated feasibility of using hollow fiber technology to deliver a growth factor to skin flaps. Further study may yield clinical applications for human patients undergoing reconstructive procedures.


Febrile nonhaemolytic transfusion reaction caused by antibodies against human platelet antigen 5a.
Anti-human platelet antigens (HPA) alloantibodies are seldom involved in febrile nonhaemolytic reactions (FNHTRs). We describe a case in which anti-HPA-5a alloantibodies are related to an FNHTR. We studied the specificity of the alloantibodies by flow cytometry, ELISA and MACE. Typing of donors and the patient was performed by sequence-specific polymerase chain reaction. The alloantibodies were found reactive with HPA-5a antigens. The patient was HPA-5b/b, whereas the donor of the platelet apheresis involved in the FNHTR was HPA-5a/a. Despite the low frequency of anti-HPA-5a antibodies, they might be responsible for FNHTR.


miR-124, -128, and -137 Orchestrate Neural Differentiation by Acting on Overlapping Gene Sets Containing a Highly Connected Transcription Factor Network.
The ventricular-subventricular zone harbors neural stem cells (NSCs) that can differentiate into neurons, astrocytes, and oligodendrocytes. This process requires loss of stem cell properties and gain of characteristics associated with differentiated cells. miRNAs function as important drivers of this transition; miR-124, -128, and -137 are among the most relevant ones and have been shown to share commonalities and act as proneurogenic regulators. We conducted biological and genomic analyses to dissect their target repertoire during neurogenesis and tested the hypothesis that they act cooperatively to promote differentiation. To map their target genes, we transfected NSCs with antagomiRs and analyzed differences in their mRNA profile throughout differentiation with respect to controls. This strategy led to the identification of 910 targets for miR-124, 216 for miR-128, and 652 for miR-137. The target sets show extensive overlap. Inspection by gene ontology and network analysis indicated that transcription factors are a major component of these miRNAs target sets. Moreover, several of these transcription factors form a highly interconnected network. Sp1 was determined to be the main node of this network and was further investigated. Our data suggest that miR-124, -128, and -137 act synergistically to regulate Sp1 expression. Sp1 levels are dramatically reduced as cells differentiate and silencing of its expression reduced neuronal production and affected NSC viability and proliferation. In summary, our results show that miRNAs can act cooperatively and synergistically to regulate complex biological processes like neurogenesis and that transcription factors are heavily targeted to branch out their regulatory effect.


Sunflower Meal Inclusion Rate and the Effect of Exogenous Enzymes on Growth Performance of Broiler Chickens.
The study examined the effect of de-hulled sunflower meal (SFM) inclusion rate and exogenous enzymes (EE) on broilers production performance. A four-feeding phase of pre-starter (1-9 d), grower (10-20 d), finisher (21-28 d) and post-finisher (29-35 d) was used with SFM included as low (BSL) and high (BSH) in all phases. BLS inclusion was 3% throughout phases and BSH inclusion was 7.5%, 10%, 13% and 13.5% for the 4-phases. Each SFM had a negative control (NC) (BSL- and BSH-) and positive (PC) (BSL+ and BSH+) control with additional 80 kcal Apparent Metabolizable Energy. Enzymes: xylanase (X), xylanase + beta-glucanase (XB), xylanase + beta-glucanase + protease (XBP) and xylanase + amylase + protease (XAP) were added to the NC and PC to give 6 treatments. Pen body weight gain (BWG) and feed intake (FI) were determined at 9, 20, 28 and 35 d and feed conversion ratio (FCR) was calculated accordingly. Diets were fed ad libitum to 1920 male Ross 308 broilers. Diet type, enzyme and diet by enzyme interactions were not significantly different amongst treatment diets. During the pre-starter and the grower phase, all studied parameters did not significantly differ from each other. All studied parameters were significantly influenced by enzyme addition and diet-type and enzyme interaction at 35 d except for diet type on FCR. Broilers fed BSH supplemented with XAP recorded the highest BWG (2.69 kg), whereas broiler chickens on BSL and supplemented with XBP recorded the lowest BWG (2.60 kg). SFM can be increased to 13% and 13.5% finisher and post-finisher diets without negatively affecting performance, and X and XAP enzymes can improve BWG of broilers grown to 35 d.


Clinical experience with Org GB94 (mianserin hydrochloride), a new tetracyclic antidepressant.
(1) Org GB94 (Mianserin hydrochloride), a new tetracyclic antidepressant, was administered to 21 patients with depression or with depressive states. (2) Remarkable antidepressive response was obtained with Org GB94 in moderate and mild forms of endogenous, involutional and senile depression. (3) The onset of action of Org GB94 was rapid. (4) Anticholinergic side effects were extremely rare and other untoward effects were mild in nature.


Recombinant human erythropoietin, epoetin beta, in patients with relapsed lymphoma treated with aggressive sequential salvage chemotherapy--results of a randomized trial.
The aim of the study was to investigate the effects of erythropoietin (epoetin beta) on red blood cell (RBC) transfusions, hemoglobin (Hb) levels, and quality of life (QOL) in patients with relapsed lymphoma treated with an aggressive sequential salvage chemotherapy (SSCT) regimen. Sixty patients with early or late relapsed Hodgkin's disease ( n=39) or first relapse of aggressive non-Hodgkin's lymphoma ( n=21) were randomized to receive epoetin beta 10,000 IE subcutaneously three times a week or no epoetin during salvage chemotherapy. Patients in both study arms received two cycles of DHAP (dexamethasone, high-dose cytarabine, cisplatin); patients in partial remission (PR) or complete remission (CR) then received cyclophosphamide, followed by peripheral blood stem cell (PBSC) harvest, methotrexate plus vincristine, and etoposide. The final myeloablative course was BEAM (carmustine, etoposide, cytarabine, and melphalan) followed by autologous stem cell support. The primary endpoint of the study was the number of RBC units needed during SSCT. In addition, Hb levels and QOL were measured. The mean number of RBC units given in the epoetin beta arm was 4.5 compared to 8.3 in the control arm ( P=0.0134). The mean Hb levels during therapy were 10.4 g/dl in the epoetin beta arm and 9.7 g/dl in the control ( P=0.018). From baseline until BEAM therapy QOL (EORTC QLQ C30) and fatigue (MFI) assessment showed little QOL worsening or stable levels in both arms with a steeper increase of fatigue levels in the control group. Patients with relapsed lymphoma undergoing aggressive chemotherapy and stem cell support benefited from epoetin beta therapy, with a decrease of RBC transfusion requirements and lower rise of fatigue levels.


Comparison of force development strategies of spinal manipulation used for thoracic pain.
To date, there is a paucity of comparative analysis of manual therapeutic procedures for the treatment of pain in the same spinal region. This paper examines the cross correlation of force-time histories across three distinct strategies of force production for the same thoracic spine procedure. Secondary analysis includes examination of the characteristics that account for potential differences. A homogeneous sample of 21 male volunteers and three clinicians were selected as a convenience sample. The force-time histories were recorded using a table mounted force plate (AMTI model number OR6-7-2000, London, ON), and cross-correlation analysis was applied by strategy type, for analysis between group data. Secondary parameters included: peak force, preload force, slope of the thrust, instantaneous loading rate and thrust duration, of the total force magnitude. Primary results indicate strong correlations among all strategies but with notably different cross-correlation coefficients (0.894 ≤ r ≤ 0.946) based on individual comparisons. Classical descriptive components of the force-time curves (e.g. preload, peak force, slope) for each strategy group were examined. Significant differences in the raw data were noted on slope and loading rate (adjusted p < 0.01). One strategy of force development was significantly different from the others in four of the five characteristics. The effects of clinician stature were evaluated by normalizing force to body mass. Quantitative biomechanical differences in procedures may be responsible for differences in outcomes based on the method of treatment selected. This data set begins a basis for translational research to assist in identifying populations of thoracic spine pain patients for whom one procedure or other may be more effective.


Removal and inactivation of indicator bacteriophages in fresh waters.
The removal and inactivation of faecal coliform (FC) bacteria, enterococci (ENT), sulphite-reducing clostridia (SRC), somatic coliphages, F-specific RNA bacteriophages and bacteriophages infecting Bacteroides fragilis in fresh waters. Removal was studied in two areas of a river. The results showed different removal of each group of microbes. Faecal coliform bacteria were removed faster than any other, whereas SRC and bacteriophages infecting Bact. fragilis were the most persistent. Inactivation was measured by 'in situ' experiments, which showed significant differences in survival of the different groups of bacterial and bacteriophage indicators. The SRC and bacteriophages were more resistant than faecal coliforms and enterococci, with the exception of F-specific RNA bacteriophages in the summer. Inactivation experiments with pure cultures of bacteriophages confirmed that phage B40-8 of Bact. fragilis was the most resistant. Bacteria and bacteriophages show different resistance to natural inactivation. The use of phages allows information to be obtained in addition to that provided by bacterial indicators. Somatic coliphages and phages infecting Bact. fragilis might supply that indicator function. Confirmation was obtained that bacteriophages provided additional information to that provided by bacterial indicators to monitor the natural inactivation of viruses and/or pathogens.


New development in diagnosis of vascular cognitive impairment.
Despite availability of harmonized criteria for the investigation of patients with presumed "vascular cognitive impairment (VCI)" there exists no clear definition of VCI. The challenge lies in the definition of those vascular components being responsible for the cognitive-behavioural decline of elderly patients. We advocate the use of longitudinal brain MRI studies to establish what type and extent of lesion progression parallels cognitive deterioration in elderly patients who often present with a plethora of diffuse and focal brain abnormalities that may or may not contribute to their cognitive phenotype. So far, a temporal relationship between lesion progression and cognitive decline has been established only for two types of "vascular" abnormalities. The most convincing evidence exists for confluent white matter lesions, less, but clearly supportive data are available for lacunes. All other brain abnormalities including microbleeds, loss of brain volume due to vascular processes or ultrastructural brain changes as seen with new imaging techniques need to be further explored in terms of their pathological correlates, rates of progression and their relationship to cognitive functioning. Such data are the pre-requisite to further develop the currently vague concept of VCI to a clearly defined diagnostic entity.


Wild and cultivated barleys show differences in the expression pattern of a cold-regulated gene family under different light and temperature conditions.
Cold acclimation in plants involves the expression of many genes and gene families. The present study reports the expression analysis of three members of the blt14 gene family in barley. Gene-specific antisense oligonucleotides were used as probes in northern experiments so as to follow independently the expression of individual members of the gene family. Each clone revealed different accumulation kinetics when a spring and a winter cultivar were compared, suggesting that the different regulatory mechanisms leading to mRNA accumulation of an individual member of the blt14 gene family are genotype-dependent. In a collection of Hordeum spontaneum genotypes both qualitative and quantitative polymorphisms were found for the accumulation of blt14-related mRNAs, although no clear relationships were found between blt14 expression and frost resistance. The accumulation of the blt14-related mRNAs was also modulated by light and by the albino mutation a(n). The effects of light on the accumulation of the transcripts corresponding to the blt14 gene family were evaluated by comparing etiolated and green plants. Etiolated plants accumulate the blt14-related mRNAs at a detectable level already at 22 degrees C. When the same plants are exposed to cold in absence of light an increased mRNA accumulation above the level present in green cold-treated plants can be detected. On the contrary, etiolated plants showed a reduced blt14 accumulation when exposed to cold in the presence of light. Cold-induced expression of the blt14 gene family was strongly reduced in plants carrying the albino mutation a(n). This mutant showed a defective molecular response to cold even when probed with a cDNA coding for LEA type protein (paf93). The albino mutant a(n) was not able to harden when exposed to low temperature providing a direct evidence of the relationship between expression of cold-regulated (COR) genes and the development of cold hardening. Failure of cold acclimation in the mutant cannot be merely ascribed to the absence of photosynthetic activity, since etiolated wild-type plants accumulated COR mRNAs and improved frost resistance when exposed to cold.


Tryptophan fluorescence lifetimes in lysozyme.
Tryptophan fluorescence lifetimes at pH 2 and pH 8 have been obtained for lysozyme and for lysozyme derivatives in which tryptophan-62 or tryptophan-108 or both are nonfluorescent. The lifetimes range from about 0.5 ns to 2.8 ns for the various emitting tryptophans. The tryptophan lifetimes appear to increase with exposure of tryptophan to solvent, but intramolecular contacts, probably with cystine residues, can considerably shorten the lifetime. Intertryptophanyl interactions can also affect fluorescence lifetimes. The trytophan-108 lifetime in lysozyme is shorter than in the derivative in which tryptophan-62 is oxidized; this is ascribed to energy transfer from tryptophan-108 to tryptophan-62. From the lifetime results the relative intensities emitted by specific tryptophans can be estimated, and these values also support the existence of intertryptophanyl energy transfer. The emission intensity from tryptophan-62 is greater in the presence of tryptophan-108, and the emission intensity of tryptophan-108 appears to be greater in the absence of tryptophan-62. Conformational effects accompanying chemical modification of tryptophan cannot be completely ruled out, however. The tryptophan-62 lifetime at pH 8 in lysozyme is shorter than in the derivatives, which might indicate a subtle conformational effect. Studies with tri-(N-acetyl-glucosamine)-protein complexes indicate that both the tryptophan lifetimes and the number of emitting tryptophans may be changing upon complexation. The results illustrate the usefulness and the limitations of lifetime measurements in understanding protein fluorescence.


Does the working environment influence health care professionals' values, meaning in life and religiousness? Palliative care units compared with maternity wards.
Increased altruism, self-transcendence, and quests for meaning in life (MiL) have been found in palliative care (PC) patients and their families who experience the finiteness of life. Similar changes were observed in healthy subjects who were experimentally confronted with their mortality. The study investigated how daily experiences of the transitoriness of life influence PC health care professionals' (HCPs) values, MiL, and religiousness. In a cross-sectional study, the Schwartz Value Survey, the Schedule for Meaning in Life Evaluation, and the Idler Index of Religiosity were used to investigate personal values, MiL, and private religiousness. HCPs working in PC (confronted with death) were compared with a control group of HCPs working at maternity wards (MWs) using multivariate models. Differences were considered to be statistically significant at P < 0.05. Seventy PC- and 70 MW-HCPs took part in the study (response rate 74.0%). No differences between the groups were found in overall MiL satisfaction scores. PC-HCPs were significantly more religious than MW-HCPs; they listed spirituality and nature experience more often as areas in which they experience MiL. Furthermore, hedonism was more important for PC-HCPs, and they had higher scores in openness-to-change values (stimulation and self-direction). MW-HCPs were more likely to list family as a MiL area. They assigned more importance to health and scored higher in conservation values (conformity and security). Duration of professional experience did not influence these results. Basic differences in values, MiL, and religiousness between PC-HCPs and MW-HCPs might have influenced the choice of working environment because no effect of job duration was observed. Longitudinal research is needed to confirm this hypothesis.


Where do graduating pediatric residents seek practice positions?
To profile the characteristics of areas that graduating pediatric residents target in their job searches and to explore whether residents applying to primary care markets with higher pediatrician supplies experience job-search difficulty. A national random sample of 500 graduating categorical pediatric residents was surveyed. The communities that the pediatric residents targeted for jobs were linked to local-area characteristics by using Dartmouth Primary Care Service Areas (PCSAs), which are discrete markets that represent patient travel patterns for primary care services. PCSA population and providers were characterized by using data from the 2000 US Census and American Medical Association/American Osteopathic Association Physician Masterfiles. A total of 308 graduating residents (62%) completed the survey. Of the respondents, 136 (44%) applied for general-practice positions. The characteristics of the PCSAs that residents applied to differed from the PCSAs without an application. Residents' first-choice areas had higher ratios of general pediatricians, had higher median household incomes, and were more likely to be urban areas. Residents applying to higher-supply areas were significantly more likely to report moderate or considerable difficulty in their job searches than were residents applying to lower-supply areas. Residents applying to medium- and higher-supply areas sent out more total applications for positions and received lower starting salaries than did residents applying to lower-supply areas. Residents continue to prefer high-supply areas in their job searches, despite experiencing greater search difficulty in these areas. Current targeted incentives and market forces are unlikely to redress geographic variation in pediatrician supply.


ASSOCIATED FACTORS AND SURGICAL OUTCOMES OF MICROCYSTOID MACULAR EDEMA AND CONE BOUQUET ABNORMALITIES IN EYES WITH EPIRETINAL MEMBRANE.
To investigate the associated features and the surgical outcomes in eyes with microcystoid macular edema (MME) and cone bouquet abnormalities (CBA) undergoing epiretinal membrane peeling. Retrospective study including patients who underwent pars plana vitrectomy for idiopathic epiretinal membrane. Factors associated with MME and CBA at baseline and their regression were identified with logistic regression models. Postoperative visual acuity was evaluated with linear mixed models from baseline to 12 months. Risk factors for new or worsened macular edema were explored with a Cox regression model. One hundred and eighty-seven eyes are included in this study; 30 eyes (16%) had MME and 53 eyes (28%) had CBA preoperatively. Microcystoid macular edema was associated with severe epiretinal membrane stage (odds ratio [95% confidence interval] = 3.6 [1.3-12.7], P = 0.02); CBA was inversely associated with ectopic inner foveal layer thickness (odds ratio [95% confidence interval] = 0.97 [0.97-0.99] for each 1- μ m EIFL increase, P = 0.006). Eyes with MME had worse visual acuity after epiretinal membrane peeling ( P = 0.01) and were at risk of macular edema worsening (hazard ratio [95% confidence interval] = 2.22 [1.01-5.16], P = 0.04). Older age was associated with MME persistence (odds ratio [95% confidence interval] = 2.46 [1.06-6.82] for each 10-year increase, P = 0.04). No significant associations were found for CBA. Although CBA had no prognostic consequences, MME was associated with suboptimal visual recovery and less efficient control of inflammation after surgery. Degeneration of Müller cells may have an alleged role, and further imaging and functional tests are warranted.


Combination of multi-model statistical analysis and quantitative fingerprinting in quality evaluation of Shuang-huang-lian oral liquid.
A model consisting of quantitative fingerprinting integrated with fundamental statistical analysis was established to carry out quality control analysis of Shuang-huang-lian (SHL) oral liquid. The quantitative fingerprinting approach was developed by systematic investigation of the chromatographic condition and optimization of a gradient using a complex sample analysis software system (CSASS). Five pivotal components from three traditional Chinese medicines of SHL oral liquid were determined at dual wavelengths, including phillyrin, baicalin, chlorogenic acid, neochlorogenic acid and cryptochlorogenic acid. Among them, neochlorogenic acid and cryptochlorogenic acid were quantified by quantitative analysis of multi-components with a single marker (QAMS) method. Further, the developed quantitative fingerprinting approach was validated. Good linearity with correlation coefficients (R2) higher than 0.9999 were achieved for phillyrin, baicalin and chlorogenic acid. Recoveries of the three analytes were between 96% and 108%. Relative standard deviation (RSD) values were below 3% regarding the stability and intra-day and inter-day precision. Besides, the feasibility of the QAMS method was verified by an external standard method (ESM) using 18 batches of SHL oral liquid. Fifty-nine batches of SHL oral liquid from nine manufacturers were then analyzed. Effective distinction was realized based on a linear principal component analysis (linear-PCA) model by the combination of the quantitative data and chromatographic fingerprinting. The linear-PCA model based on quantitative chromatographic fingerprinting exhibited great advantage over conventional similarity analysis to distinguish between different samples. The strategy provided a particularly simple and effective approach for quality evaluation of SHL oral liquid from various manufacturers. Graphical abstract.


Microbial metabolite sensor GPR43 controls severity of experimental GVHD.
Microbiome-derived metabolites influence intestinal homeostasis and regulate graft-versus-host disease (GVHD), but the molecular mechanisms remain unknown. Here we show the metabolite sensor G-protein-coupled receptor 43 (GPR43) is important for attenuation of gastrointestinal GVHD in multiple clinically relevant murine models. GPR43 is critical for the protective effects of short-chain fatty acids (SCFAs), butyrate and propionate. Increased severity of GVHD in the absence of GPR43 is not due to baseline differences in the endogenous microbiota of the hosts. We confirm the ability of microbiome-derived metabolites to reduce GVHD by several methods, including co-housing, antibiotic treatment, and administration of exogenous SCFAs. The GVHD protective effect of SCFAs requires GPR43-mediated ERK phosphorylation and activation of the NLRP3 inflammasome in non-hematopoietic target tissues of the host. These data provide insight into mechanisms of microbial metabolite-mediated protection of target tissues from the damage caused allogeneic T cells.


Synthetic pigment analogues of the purple membrane protein.
Nonphysiological analogues of retinal have been shown to form pigments in reactions with the apoprotein of the purple membrane of Halobacterium halobium. Both the all-trans and 13-cis isomers of a retinal analogue, having an elongated chain with an extra double bond, formed pigments. Unlike the native all-trans and 13-cis retinal1-based pigments, the new pigments were not interconvertible with each other and were unstable against hydroxylamine. When incorporated into phospholipid vesicles, they showed no proton pumping activity upon illumination. The ability of the extended-length retinal to form pigments contrasts with its nonreactivity with opsin (apoprotein of rhodopsin), suggesting a less stringent binding site for the purple membrane chromophore. All-trans retinal2 also combined with bleached purple membrane to form a blue pigment absorbing at ca. 590 nm. Like the native purple membrane, the blu membrane showed proton pumping activity upon illumination in phospholipid vesicles.


[Formation of nitrosyl complexes of non-heme iron in the blood of animals in vivo].
Addition of an increased content of iron together with nitrit to the diet results in the formation of nitrozyl complexes of non-hem iron in rats' blood. The same complexes are recorded 9 hours after intraperitoneal injection of water solution of iron nitrozyl complex with cistein. Binding of non-hem iron nitrozyl complexes with RS-groups of blood protein is discussed. Nitrozyl complexes of non-hem iron in regular blood elements in vitro are obtained.


CPNE7 regenerates periodontal ligament via TAU-mediated alignment and cementum attachment protein-mediated attachment.
Once the periodontal ligament (PDL) is damaged, it is difficult to regenerate its characteristic structure. Copine7 (CPNE7) reportedly plays a functional role in supporting periodontal attachment and PDL alignment. Here we demonstrate the regulatory mechanism of CPNE7 coordination with cytoskeleton reorganization and cementum attachment protein (CAP)-mediated attachment in PDL regeneration. The expression and localization of CPNE7, α-TUBULIN, ACTIN, and microtubule associated protein tau (TAU) were investigated in vitro. The effects of recombinant CPNE7 (rCPNE7) and CPNE7-derived peptides (CPNE7-DP) on the regulation of CAP were analysed in vitro, and PDL repair capacity was analysed in vivo. CPNE7 co-localized with F-ACTIN and induced α-TUBULIN expansion to the edge of human PDL cells (hPDLCs). ACTIN and α-TUBULIN protein expressions were not elevated in rCPNE7-treated hPDLCs. rCPNE7 elevated the protein expression of TAU, which co-localized with F-ACTIN and α-TUBULIN. Replantation studies on mice revealed that well-attached and well-aligned PDLs were repaired in the rCPNE7 group. CPNE7-DP directly up-regulate the expression of CAP in vitro and promote PDL regeneration in three-wall defect canine models in vivo. Our findings suggest that CPNE7 helps in PDL repair by supporting PDL alignment through TAU-mediated cytoskeleton reorganization and direct regulation of CAP-mediated PDL attachments of PDLCs.


Testicular neoplasms in children.
Six cases of testicular tumors in children are presented: 3 patients had teratoma, 1 embryonal carcinoma, 1 orchioblastoma, and 1 paratesticular rhabdomyosarcoma. Three of the 6 patients presented with hydroceles. The treatment consisted of orchiectomy alone. All patients were alive and free of disease one and one-half to eight and one-half years after orchiectomy. It is suggested that orchiectomy alone is curative in most children with testicular tumors under the age of two years.


Preventing adolescent synaptic pruning in mouse prelimbic cortex via local knockdown of α4βδ GABAA receptors increases anxiety response in adulthood.
Anxiety is increasingly reported, especially in adolescent females. The etiology is largely unknown, which limits effective treatment. Layer 5 prelimbic cortex (L5PL) increases anxiety responses but undergoes adolescent synaptic pruning, raising the question of the impact of pruning on anxiety. Here we show that preventing L5PL pruning increases anxiety in response to an aversive event in adolescent and adult female mice. Spine density of Golgi-stained neurons decreased ~ 63% from puberty (~ PND35, vaginal opening) to post-puberty (PND56, P < 0.0001). Expression of α4βδ GABAA receptors (GABARs) transiently increased tenfold in L5PL at puberty (P < 0.00001), but decreased post-pubertally. Both global and local knockdown of these receptors during puberty prevented pruning, increasing spine density post-pubertally (P < 0.0001), an effect reversed by blocking NMDA receptors (NMDARs). Pubertal expression of the NMDAR-dependent spine protein kalirin7 decreased (50%, P < 0.0001), an effect prevented by α4 knock-out, suggesting that α4βδ-induced reductions in kalirin7 underlie pruning. Increased spine density due to local α4 knockdown at puberty decreased open arm time on the elevated plus maze post-pubertally (62%, P < 0.0001) in response to an aversive stimulus, suggesting that increases in L5PL synapses increase anxiety responses. These findings suggest that prelimbic synaptic pruning is necessary to limit anxiety in adulthood and may suggest novel therapies.


Comparison of peer assessment and faculty assessment in an interprofessional simulation-based team training program.
Challenges related to limited clinical sites and shortage of clinical instructors may reduce the quality of clinical experiences, leading to increased demand for the establishment of simulation-based training programs in the curricula of educational institutions. However, simulation-based training programs in health education place great demands on faculty resources. It is interesting, therefore, to investigate peers contributions in formal assessment, and how this compares to faculty assessment. This paper report the results from the comparison of direct observation by peer observers who had received short rater training, and post-hoc video-based assessment by trained facilitators. An observation form with six learning outcomes was used to rate team performance. Altogether 262 postgraduate nursing students, bachelor of nursing students and medical students participated, organized into 44 interprofessional teams. A total of 84 peers and two facilitators rated team performance. The sum score of all six learning outcomes showed that facilitators were more lenient than peer observers (p = .014). The inter-rater reliability varied considerably when comparing scores from peer observers from the three different professions with those of the facilitators. The results indicate that peer assessment may support, but not replace, faculty assessment.


Azaarenes: 13 Rings in a Row by Cyclopentannulation.
Cyclopentannulation was explored as a strategy to access large, stable azaarenes. Buchwald-Hartwig coupling of previously reported di- and tetrabrominated cyclopentannulated N,N'-dihydrotetraazapentacenes furnished stable azaarenes with up to 13 six-membered rings in a row and a length of 3.1 nm. Their optoelectronic and semi-conducting properties as well as their aromaticity were investigated.


[Cohen syndrome. Description of a new case and study of the central nervous system using nuclear magnetic resonance].
The Cohen syndrome is characterized by dysmorphic face, obesity, narrow hands and feet and mild mental retardation. So far only 42 cases have been described in literature. The Authors describe a patient who presented some cerebral anomalies at the MRI examination. In particular the MRI showed a large sellar cavity compared to the size of the hypophysis.


Combined antitumor effect of Ad-bFGF-siRNA and Ad-Vpr on the growth of xenograft glioma in nude mouse model.
Basic fibroblast growth factor (bFGF) has been demonstrated to correlate with glioma grade and clinical outcome and has established its possible usefulness as a target for glioma therapy. Vpr has been described as an antitumor agent and displays a potent antitumor nature. Here, we try to investigate whether a combined treatment with bFGF-siRNA and Vpr gene would have a enhanced effectiveness on glioma in vitro and in vivo.After treatments with only Ad-bFGF-siRNA, only Ad-Vpr, and a combination of both, we assessed the changes in cell proliferation, cell cycle, and apoptosis in vitro by the methods of MTT, PI and FITC-AnnexinV double staining, respectively. In addition, we also evaluated the combined effect of bFGF-siRNA and Vpr gene therapy on glioma in vivo using xenograft glioma models in nude mice. Combined Ad-bFGF-siRNA and Ad-Vpr treatment was more better successful in inhibiting cell proliferation in comparison with treatments of either Ad-bFGF-siRNA or Ad-Vpr alone. Treatment of Ad-Vpr alone or a treatment of a combination of Ad-bFGF-siRNA and Ad-Vpr induced the G2/M cell cycle arrest and apoptosis; however, combined treatment was more effective than the Ad-Vpr treatment alone. Although each single treatment can slow the growth of xenograft glioma, the combined treatment with Ad-bFGF-siRNA and Ad-Vpr was better than either the Ad-bFGF-siRNA or Ad-Vpr treatment alone. Our results suggest that the combination therapy with bFGF-siRNA and Vpr gene can achieve a enhanced activity of anti-glioma, supporting the idea that the combination of these two antitumor agents could open new perspectives in glioma therapy.


Relationship between red cell distribution width and echocardiographic parameters in patients with diastolic heart failure.
Red cell distribution width (RDW) was found to be a prognostic marker in heart failure patients. The aim of the study was to investigate the relationship between RDW and echocardiographic parameters in diastolic heart failure (DHF). Seventy-one consecutive DHF patients (26 men) and 50 controls (21 men) were included in the study. All of the study population underwent echocardiographic evaluation, and blood samples were obtained. RDW and N-terminal pro-B-type natriuretic peptide (NT-proBNP) values were significantly higher, whereas there was an increasing trend for high-sensitivity C-reactive protein levels in DHF patients than those in controls (p<0.001, p<0.001, and p=0.064, respectively). All of the echocardiographic parameters evaluating diastolic function were more deteriorated in the DHF group. Patients who had an RDW value greater than the cutoff point also had higher NT-proBNP levels, an elevated ratio of mitral peak velocity of early diastolic filling to early diastolic mitral annular velocity, and increased estimated pulmonary capillary wedge pressures by tissue Doppler parameters, but lower creatinine clearance (p<0.05 for all). According to the cutoff values calculated using receiver operating characteristic analysis, RDW>13.6% and NT-proBNP>125pg/mL have high diagnostic accuracy for predicting DHF. RDW values were increased in the DHF population. Our results suggest that the high RDW levels in patients with DHF may be related to increased neurohormonal activity, impaired renal functions, and elevated filling pressure, but not to increased inflammation.


Calcium released by osteoclastic resorption stimulates autocrine/paracrine activities in local osteogenic cells to promote coupled bone formation.
A major cause of osteoporosis is impaired coupled bone formation. Mechanistically, both osteoclast-derived and bone-derived growth factors have been previously implicated. Here, we hypothesize that the release of bone calcium during osteoclastic bone resorption is essential for coupled bone formation. Osteoclastic resorption increases interstitial fluid calcium locally from the normal 1.8 mM up to 5 mM. MC3T3-E1 osteoprogenitor cells, cultured in a 3.6 mM calcium medium, demonstrated that calcium signaling stimulated osteogenic cell proliferation, differentiation, and migration. Calcium channel knockdown studies implicated calcium channels, Cav1.2, store-operated calcium entry (SOCE), and calcium-sensing receptor (CaSR) in regulating bone cell anabolic activities. MC3T3-E1 cells cultured in a 3.6 mM calcium medium expressed increased gene expression of Wnt signaling and growth factors platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and bone morphogenic protein-2 (BMP 2). Our coupling model of bone formation, the receptor activator of nuclear factor-κΒ ligand (RANKL)-treated mouse calvaria, confirmed the role of calcium signaling in coupled bone formation by exhibiting increased gene expression for osterix and osteocalcin. Critically, dual immunocytochemistry showed that RANKL treatment increased osterix-positive cells and increased fluorescence intensity of Cav1.2 and CaSR protein expression per osterix-positive cell. The above data established that calcium released by osteoclasts contributed to the regulation of coupled bone formation. CRISPR/Cas-9 knockout of Cav1.2 in osteoprogenitor cells cultured in basal calcium medium caused a >80% decrease in the expression of downstream osteogenic genes, emphasizing the large magnitude of the effect of calcium signaling. Thus, calcium signaling is a major regulator of coupled bone formation.


Determination of dithiocarbamates and metabolites in plants by liquid chromatography-mass spectrometry.
A quantitative matrix solid-phase dispersion and liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC-APCI-MS) method is outlined for the simultaneous analysis of dithiocarbamates (DTCs) and their degradation products in plants. Compounds analyzed are dazomet, disulfiram, thiram and the metabolites ethylenthiourea and propylenthiourea. The performance of two different sample preparation protocols, the proposed one and other based on solid-phase extraction, as well as, of both atmospheric pressure ionization sources, APCI and electrospray, were compared. The effect of several parameters on the extraction, separation and detection was studied. Dithiocarbamates and metabolites were dispersed with carbograph, eluted with a mixture of dichloromethane-methanol, and then, identified by monitoring the base peak of the spectra corresponding to [M + H]+. The method was validated for avocados, cherries, lemons, nuts, oat, oranges, peaches, rice and tomatoes. Average recoveries varied from 33 to 109%, and relative standard deviation were between 4 and 21% with limits of quantification ranged from 0.25 to 2.5 mg kg(-1), except for thiram and disulfiram, which were not recovered from fruits with high acid content. The procedure was applied to the determination of DTCs and their metabolites in fruits, vegetables and cereals taken from different markets of Valencia, Spain.


Carbon price forecasting based on news text mining considering investor attention.
The carbon market relies on market-oriented financial means to solve the problem of carbon emissions. An effective carbon pricing mechanism can improve market efficiency and better serve the implementation of carbon emission reduction. The limited attention of investors increases the uncertainty of carbon market volatility and is an important exogenous factor affecting the price of carbon assets. This study innovatively mines keywords of investor attention on the carbon market through online news texts and eliminates those that have no causal link to carbon price forecasting in order to reduce noise. The results show that the keyword extraction method based on news text mining is better than that of nontext mining. Meanwhile, a carbon price forecasting model based on a particle-swarm-optimization LSTM model structure is constructed, and the forecasting accuracy is improved. The results show that carbon market investors pay more attention to carbon quota supply and demand, carbon prices, environmental change, and the energy market. The results have important implications for the development of effective carbon market policies and risk management.


Multisite MRI reproducibility of lateral ventricular volume using the NAIMS cooperative pilot dataset.
The North American Imaging in Multiple Sclerosis (NAIMS) multisite project identified interscanner reproducibility issues with T1-based whole brain volume (WBV). Lateral ventricular volume (LVV) acquired on T2-fluid-attenuated inverse recovery (FLAIR) scans has been proposed as a robust proxy measure. Therefore, we sought to determine the relative magnitude of scanner-induced T2-FLAIR-based LVV and T1-based WBV measurement errors in relation to clinically meaningful changes. This was a post hoc analysis of the NAIMS pilot dataset in which a relapsing-remitting MS patient with no intrastudy clinical or radiological activity was imaged twice on seven different Siemens scanners across the United States. LVV was determined using the automated NeuroSTREAM technique on T2-FLAIR and WBV was determined with SIENAX on high-resolution T1-MPRAGE. Average LVV and WBV were measured, and absolute intrascanner and interscanner coefficients of variation (CoVs) were calculated. The variabilities were compared to previously established annual pathological and clinically meaningful cutoffs of 0.40% for WBV and of 3.51% for LVV. Mean LVV across all seven scan/rescan pairs was 45.87 ± 1.15 ml. Average LVV intrascanner CoV was 1.42% and interscanner CoV was 1.78%, both smaller than the reported annualized clinically meaningful cutoff of 3.51%. In contrast, intra- and interscanner CoVs for WBV (0.99% and 1.15%) were both higher than the established cutoff of 0.40%. Individually, 1/7 intrasite and 2/7 intersite pair-wise LVV comparisons were above the 3.51% cutoff, whereas 4/7 intrasite and 7/7 intersite WBV comparisons were above the 0.40% cutoff. Fully automated LVV segmentation has higher absolute variability than WBV, but much lower relative variability compared to clinically relevant changes, and may therefore be a meaningful proxy outcome measure of neurodegeneration.


Trends in hospital admissions during transition from paediatric to adult services for young people with learning disabilities or autism: Population-based cohort study.
Transition from paediatric to adult health care may disrupt continuity of care, and result in unmet health needs. We describe changes in planned and unplanned hospital admission rates before, during and after transition for young people with learning disability (LD), or autism spectrum disorders (ASD) indicated in hospital records, who are likely to have more complex health needs. We developed two mutually exclusive cohorts of young people with LD, and with ASD without LD, born between 1990 and 2001 in England using national hospital admission data. We determined the annual rate of change in planned and unplanned hospital admission rates before (age 10-15 years), during (16-18 years) and after (19-24 years) transition to adult care using multilevel negative binomial regression models, accounting for area-level deprivation, sex, birth year and presence of comorbidities. The cohorts included 51,291 young people with LD, and 46,270 autistic young people. Admission rates at ages 10-24 years old were higher for young people with LD (54 planned and 25 unplanned admissions per 100 person-years) than for autistic young people (17/100 and 16/100, respectively). For young people with LD, planned admission rates were highest and constant before transition (rate ratio [RR]: 0.99, 95% confidence interval [CI] 0.98-0.99), declined by 14% per year of age during (RR: 0.86, 95% CI: 0.85-0.88), and remained constant after transition (RR: 0.99, 95% CI: 0.99-1.00), mainly due to fewer admissions for non-surgical care, including respite care. Unplanned admission rates increased by 3% per year of age before (RR: 1.03, 95% CI: 1.02-1.03), remained constant during (RR: 1.01, 95% CI: 1.00-1.03) and increased by 3% per year after transition (RR: 1.03, 95% CI: 1.02-1.04). For autistic young people, planned admission rates increased before (RR: 1.06, 95% CI: 1.05-1.06), decreased during (RR: 0.95, 95% CI: 0.93-0.97), and increased after transition (RR: 1.05, 95%: 1.04-1.07). Unplanned admission rates increased most rapidly before (RR: 1.16, 95% CI: 1.15-1.17), remained constant during (RR: 1.01, 95% CI: 0.99-1.03), and increased moderately after transition (RR: 1.03, 95% CI: 1.02-1.04). Decreases in planned admission rates during transition were paralleled by small but consistent increases in unplanned admission rates with age for young people with LD and autistic young people. Decreases in non-surgical planned care during transition could reflect disruptions to continuity of planned/respite care or a shift towards provision of healthcare in primary care and community settings and non-hospital arrangements for respite care. National Institute for Health Research Policy Research Programme.


Down-regulation of HLA-B-associated transcript 3 impairs the tumoricidal effect of natural killer cells through promoting the T cell immunoglobulin and mucin domain-containing-3 signaling in a mouse head and neck squamous cell carcinoma model.
Head and neck squamous cell carcinoma (HNSCC) arises from the malignant mucosal epithelium of the oral cavity, pharynx, and larynx. Natural killer (NK) cells are fundamental immune cells shaping the anti-HNSCC response. Elucidation of the regulatory mechanisms of NK cell activity is crucial for understanding anti-HNSCC immunity. In this study, we characterized the expression and function of HLA-B-associated transcript 3 (Bat3) in NK cells in a mouse HNSCC model. We found that Bat3 expression was down-regulated in HNSCC-infiltrating NK cells. SCC VII, the mouse HNSCC cell line used in this model, induced Bat3 downregulation through direct cell-to-cell contact. By applying lentivirus-mediated silencing of Bat3, we discovered that Bat3 knockdown impaired the tumoricidal effect of NK cells on SCC VII cells and Hepa1-6RAE1, a genetically modified liver cancer cell line. Furthermore, Bat3 knockdown resulted in a significant decrease in perforin, granzyme B, interferon-γ, and tumor necrosis factor-α in NK cells upon co-culture with SCC VII cells. Further investigations revealed that Bat3 knockdown promoted the binding of T cell immunoglobulin and mucin domain-containing-3 (Tim-3) to Fyn and thus activated the Tim-3 signaling. Blockade of Tim-3 with a neutralizing Tim-3 antibody counteracted the effect of Bat3 knockdown on NK cell cytotoxicity. Taken together, our data suggest that HNSCC might down-regulate Bat3 expression to augment Tim-3 signaling and ultimately suppress the tumoricidal activity of NK cells. This study unveils a novel mechanism by which HNSCC evades NK cell killing, and sheds light on designing novel anti-HNSCC immunotherapy targeting Bat3 and Tim-3 signaling.


Urinary tract infections due to Trichosporon spp. in severely ill patients in an intensive care unit.
To evaluate the incidence of urinary tract infections due to Trichosporon spp. in an intensive care unit. This descriptive observational study was conducted in an intensive care unit between 2007 and 2009. All consecutive patients admitted to the intensive care unit with a confirmed diagnosis were evaluated. Twenty patients presented with urinary tract infections due to Trichosporon spp. The prevalence was higher among men (65%) and among individuals > 70 years of age (55%). The mortality rate was 20%. The average intensive care unit stay was 19.8 days. The onset of infection was associated with prior use of antibiotics and was more frequent in the fall and winter. Infection due to Trichosporon spp. was more common in men and among those > 70 years of age and was associated with the use of an indwelling urinary catheter for more than 20 days and with the use of broadspectrum antibiotics for more than 14 days. In addition, patients with urinary infection due to Trichosporon spp. were most often hospitalized in intensive care units in the fall and winter periods.


[A case of posterior communicating artery aneurysm associated with vascular anomaly of circle of Willis].
The patient, 68 year-old, male, was admitted to our clinic with episode of the second attack of subarachnoid hemorrhage in October, 1979. The cerebral angiogram demonstrated an aneurysm arising from the junction of posterior communicating artery and aberrant origin of the anterior choroidal artery. Additionally, bilateral posterior cerebral arteries were filled only through the anterior circulation via the posterior communicating artery. The patient was successfully operated with clipping of the aneurysm through the pterional approach. The aneurysm arising from the posterior communicating artery itself is exceedingly rare. Incidence, symptom and operative approach were discussed with the review of the literature.


Similarities and Dissimilarities in Diet Quality Differences by Acculturation Level between Mexican Americans and Other Hispanic Americans: National Health and Nutrition Examination Survey 2015-2018.
Evidence suggests dietary acculturation can increase obesity and chronic disease risks. However, acculturation effects on diet quality among subgroups of Hispanic Americans is not well studied. Estimating percentages of Hispanic Americans with low, moderate, and high acculturation using 2 proxy measures with different language variables was the first objective. Identifying similarities and dissimilarities in diet quality differences by acculturation level between Mexican Americans and other Hispanic Americans was the second objective. The study sample included 1733 Mexican American and 1191 other Hispanic participants aged ≥16 y from National Health and Nutrition Examination Survey 2015-2018. Proxy measures included in the 2 acculturation scales were nativity/United States residence length, immigration age, language spoken at home (home), and language of dietary recall (recall). Replicate 24-h dietary recalls were conducted, and diet quality was assessed using the 2015 Healthy Eating Index. Analyses included statistical methods for complex survey designs. For Mexican Americans, 8%, 35%, and 58% had low, moderate, and high acculturation on the home scale compared with 8%, 30%, and 62% on the recall scale. For other Hispanics, 17%, 39%, and 43% had low, moderate, and high acculturation on the home scale compared with 18%, 34%, and 48% on the recall scale. Similarities between ethnicities included higher acculturation associated with lower intakes of fruits, vegetables, total protein foods, seafood and plant proteins, and saturated fats and greater intake of sodium. Dissimilarities included higher acculturation associated with more whole grains and added sugars intakes and less refined grains intake (Mexican Americans), and less total dairy and fatty acids intakes (other Hispanic Americans). Higher acculturation is associated with worsening diet quality for fruits, vegetables, and protein foods in all Hispanic Americans. However, associations of higher acculturation with worsening diet quality for grains, added sugars, dairy, and fatty acids were present only in specific subgroups of Hispanic Americans.


Fatty Acids Composition of Stomach Oil of Scopoli's Shearwater (Calonectris diomedea) from Linosa's Colony.
Calonectris diomedea is a Procellariforms seabird having a very representative colony in Linosa Island (Southern Italy). The adult forms of C. diomedea produce a pasty oil from their proventriculus to feed their chicks during the rearing period. In this work, we examined the fatty acids composition of the stomach oil of C. diomedea from Linosa Island by gas chromatography with flame ionization detection (GC-FID). The samples were collected at 20 and 70 days after hatching. Twenty different fatty acids (FAs) were identified. Saturated fatty acids (SFA) were the most abundant in percentage (41.6%) at day 20 followed by polyunsaturated fatty acids (PUFA, 38.7%) and monounsaturated fatty acids (MUFA, 19.7%). MUFAs were the most abundant in samples collected at day 70 (53.8%), followed by SFAs (36.6%) and PUFAs (9.8%). Oleic acid (C18:1ω9) in the samples on day 70 was 4 times higher than that in the samples on day 20. The Principal Component Analysis (PCA) verified a clear separation of the stomach oil samples in two groups, according to the day of sampling. The results obtained confirm the role of FAs analysis of stomach oil to understand the ecology and breeding behaviour of C. diomedea, highlighting a resemblance with signatures recorded in marine organisms of Linosa Island.


Multiple-frequency ultrasonic imaging by transmitting pulsed waves of two frequencies.
The aim of this study was realization of a broadband measurement system that is capable of effectively carrying out a frequency compound method. In the present method, the secondary wave components of difference and sum frequencies are generated along with the higher harmonic components through the nonlinear interaction of two-frequency ultrasound. A multiple-frequency beam is generated together with the initially radiated frequency components. For the structure of a transducer capable of simultaneously radiating two sound waves with different frequencies, a coaxial arrangement of a circular-disc piezoelectric transducer and a ring piezoelectric transducer was designed. The radiating frequencies chosen were 2 and 8 MHz. In addition to the 4-MHz second harmonic sound of the 2-MHz primary sound, sounds of the 6-MHz difference frequency and the 10-MHz sum frequency can be generated. By measuring the acoustic pressure distribution, the formation of a multiple-frequency beam was confirmed. The signal-to-noise ratio in an agar-gel phantom image was increased by 5-6 dB with application of the frequency compound method. The validity of the proposed method was demonstrated through the generation of a human finger image. Further, it was found that the influence of the Doppler effect was small enough that almost all the secondary waves were attributable to the nonlinear propagation of sounds. A multiple-frequency sound beam was realized by radiating a two-frequency sound. The effectiveness of the presented method was demonstrated through actual imaging.


[Evaluation of anthropometric development in patients with enuresis].
An epidemiological study was conducted to assess the anthropometric development in children diagnosed with primary monosymptomatic nocturnal enuresis, depending on the treatment option selected. A longitudinal series of cases including 548 children aged 5-10 years. Anthropometric parameters of children were assessed at diagnosis, and after one and two years of treatment. Children with primary monosymptomatic nocturnal enuresis showed no anthropometric changes when their data were compared to the standard deviation score of height, weight, and body mass index (BMI). Overall, no changes were seen in the above mentioned parameters after two years of treatment for enuresis (except for a weight standard deviation score (SDS) decrease in boys). We only found a decrease in the size and weight in those children undergoing behavioral therapy with or without an alarm, findings that, given the limitations of the study, were not considered significant. The odds ratio for cure after one and two years of treatment was 1.41 (95% CI: 0.85-2.34) and 1.52 (95% CI: 0.86-2.70) for desmopressin (and watchful waiting) as compared to all other options. In this study, children had SDS values of height, weight, and BMI similar to healthy children of the same age and sex before and after treatment for primary monosymptomatic nocturnal enuresis. Desmopressin appeared to increase the probability of cure after one and two years of treatment, however these data should be corroborated in future randomized clinical trials.


Discovery of the novel HLA allele, HLA-A*30:72, in a Chinese platelet donor by sequence-based typing.
HLA-A*30:72 has one nucleotide change from HLA-A*30:01:01:01 where isoleucine (95) is changed to threonine.


Photofuel cell-based self-powered biosensor for HER2 detection by integration of plasmonic-metal/conjugated molecule hybrids and electrochemical sandwich structure.
Human epidermal growth factor receptor 2 (HER2) has been regarded as the considerable biomarker of breast and gastric cancer. Thus, precise detection of HER2 is of significance for the early diagnosis and treatment. Here, a photofuel cell-based self-powered biosensor (PFC-SPB) was constructed for the ultrasensitive HER2 detection, which was composed of a plasmonic gold nanoparticles (Au NPs)/organic semiconductor hybrid photoanode and a cathode with biosensing strategy of electrochemical sandwich structure. The localized surface plasmon resonance effect of Au NPs can obviously enhance the separation efficiency of photo-generated electron/hole pair, which was beneficial to the sensitivity and stability of PFC-SPB. Meanwhile, the cathodic sandwich structure not only was used for the target recognition, but also can guarantee the enrichment of electroactive molecules (molybdophosphate). Consequently, with the open circuit voltage (EOCV) as the output signal, the PFC-SPB can achieve the HER2 detection in the range of 0.1-500 pg mL-1 with a low detection limit of 0.02 pg mL-1. Moreover, the as-proposed bioassay can be applied in cell lysate sample without any pretreatment, providing a promising and powerful tool early clinical diagnosis of cancer.


Molecular cloning of a novel human leukemia-associated gene. Evidence of conservation in animal species.
We have recently described an 18-kilodalton polypeptide (p18) that is present in much greater abundance in acute leukemic blast cells (myeloid and lymphoid) than in resting or proliferating nonleukemic lymphoid cells or chronic lymphoid and myeloid leukemic cells. In this report we describe the cloning of two different sized full-length cDNAs that code for p18. The two cDNAs differ in their 3'-noncoding regions as a result of alternative polyadenylation. Analysis of the complete nucleotide sequence and the corresponding amino acid sequence did not reveal significant homology to any previously described sequences. We show evidence that this gene is highly conserved in several animal species and low stringency hybridization studies suggest that the p18 gene may be a member of a family of partially homologous genes in the human genome.


Transient trimethylaminuria in childhood.
Trimethylaminuria, also called fish-odour syndrome, is an inherited disorder caused by deficient N-oxidation and increased excretion of trimethylamine. This study reports on two unrelated and otherwise healthy children with transient trimethylaminuria, a hitherto unknown abnormality, without N-oxidation deficiency. This demonstrates that a diagnosis of fish-odour syndrome should include the analysis of urinary excretion not only of trimethylamine but also of trimethylamine-N-oxide. Since transient trimethylaminuria may be a common condition and no cause for it can presently be recognized, such patients will require careful follow-up.


Systematics, character evolution, and biogeography of Cistus L. (Cistaceae) based on ITS, trnL-trnF, and matK sequences.
This paper presents the first phylogenetic hypotheses for the 20 species of Cistus based on plastid (trnL-trnF, matK) and nuclear (ITS) DNA sequence data. Phylogenetic relationships reveal that: (1) Halimium and Cistus form a cohesive, natural group; (2) two major lineages of purple-flowered and white-flowered species are defined, except for the purple-flowered C. parviflorus; (3) monophyly of conspecific populations is congruent with the circumscription of species. Topological congruence between nuclear and plastid phylogenies does not support a predominant reticulate system of evolution in Cistus. Reconstruction of character evolution suggests an increment of number of fruit valves in the Cistaceae from 3 to 12 in a unidirectional manner. In contrast, reproductive characters, such as sepal number, petal color, and style length, evolved multiple times in the course of evolution. A single colonization of Cistus into the Canary Islands appears to be responsible for a lineage of four species sharing a most recent common ancestor with five sepals, purple flowers, styles as long as stamens, and five fruit valves. Species diversity in Cistus (14) and Halimium (8), coupled with sister-group relationships and molecular divergence, lead us to suggest the western Mediterranean as a major center of present-day differentiation, but paleobotanical data indicate an earlier formation of the Cistus-Halimium assemblage in different areas.


Prevention of Medical Events During Air Travel: A Narrative Review.
Prior to traveling, and when seeking medical pretravel advice, patients consult their personal physicians. Inflight medical issues are estimated to occur up to 350 times per day worldwide (1/14,000-40,000 passengers). Specific characteristics of the air cabin environment are associated with hypoxia and the expansion of trapped gases into body cavities, which can lead to harm. The most frequent medical events during air travel include abdominal pain; ear, nose, and throat pathologies; psychiatric disorders; and life-threatening events such as acute respiratory failure or cardiac arrest. Physicians need to be aware of the management of these conditions in this unusual setting. Chronic respiratory and cardiovascular diseases are common and are at increased risk of acute exacerbation. Physicians must be trained in these conditions and inform their patients about their prevention.


Thyroxine inner ring monodeiodinating activity in fetal tissues of the rat.
We studied thyroxine (T4) inner ring monodeiodinating activity (5-MA) in various tissues of fetal, maternal, and adult male rats. Tissue homogenates were incubated with 0.26 microM T4 in 0.1 M phosphate buffer (pH 7.4) containing 10 mM EDTA and 400 mM dithiothreitol (final volume 0.7 ml) for 10 min at 37 degrees C; the 3,3',5'-triiodothyronine (rT3) generated was measured by radioimmunoassay of ethanol extracts of incubation mixture and the result was corrected for rT3 degradation during incubation. Compared to maternal tissues, T4 to rT3 5-MA in the 14-day-old fetus was increased about 70 times in skeletal muscle (mean +/- SEM, velocity, 5.4 +/- 0.9 versus 0.08 +/- 0.01, pmol rT3/h/mg protein); approximately 8 times in intestine (0.72 +/- 0.17 versus 0.09 +/- 0.03);and approximately 4 times in cerebral cortex (19 +/- 0.5 versus 4.5 +/- 0.9), while it was similar in skin (3.2 +/- 0.48 versus 2.6 +/- 0.52). Hepatic T4 5-MA approximated 1.1 +/- 0.63 in the 14-day-old fetus; it could not be measured reliably in maternal or 19-day fetal tissue because of extensive (greater than 90%) degradation of rT3 during incubation. Relative to mother, T4 5-MA in 19-day fetal tissues was increased approximately 30-fold intestine, approximately 20-fold in skeletal muscle, and approximately 6-fold in cerebral cortex while it was similar in skin. The T4 5-MA in maternal rat tissues did not differ significantly from corresponding values in adult male rat, except skin, where it was lower in the mother rat (2.6 +/- 0.52 versus 4.6 +/- 0.61, p less than 0.05). In summary, relative to adult tissues T4 5-MA is exceedingly active in several fetal tissues, most notably in skeletal muscle followed by intestine and cerebral cortex.


The importance and potential of artificial insemination in CANDES (companion animals, non-domestic, endangered species).
Artificial insemination (AI) is the least invasive assisted reproductive technology, and is therefore of great interest to breeders of companion animals, non-domestic, and endangered species (CANDES). This most fundamental artificial breeding technique circumvents physical or behavioral impediments to natural mating and provides the means for genetic exchange between populations without transfer of live animals. In addition, because oocytes grow, mature and are fertilized in vivo and embryos are not subjected to in vitro culture conditions, AI eliminates the epigenetic effects on the female gamete that are inherent in more invasive assisted reproductive technologies. Although the management of CANDES differs significantly from current livestock husbandry practices, the cattle industry is a powerful example of the potential for AI to enhance the genetic health and sustainability of animal populations. Ultimately, successful AI requires sperm of adequate quality and quantity, oocytes that have attained nuclear maturation and cytoplasmic competence, operational gamete transport systems, accurate timing, and proper placement of sperm in the female reproductive tract. Increased understanding of semen collection, evaluation and preservation techniques, estrus synchronization and superovulation, estrus and ovulation detection, and insemination instrumentation is needed for each CANDES before AI success rates will approach those of the livestock industry. Concentrated, collaborative research in these areas must be encouraged among private breeders, universities and zoological institutions to realize the full potential of AI in the management of CANDES.


Percutaneous Coronary Intervention or Surgery for Unprotected Left Main Disease: EXCEL Trial at 5 Years.
Although coronary artery bypass graft (CABG) surgery traditionally has been considered the gold standard for left main revascularization, percutaneous coronary intervention has evolved in the past decades so that it now represents a valid alternative to CABG in a large proportion of cases. The landmark Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial is the largest contemporary randomized comparison assessing the impact of revascularization strategies for left main disease. This review discusses the background, rationale, design, results, and implications of the EXCEL trial.


The COVID-19 hangover: why we need to take harm caused by alcohol seriously as an indirect effect of the pandemic.
In the UK, harm caused by alcohol has worsened since 2020. A recent report from the Institute of Alcohol Studies projecting future rates of major alcohol-related diseases highlights what this means for health and healthcare. The authors argue that this additional burden is not inevitable if effective policies are introduced.


Regional vulnerability of brain white matter in vanishing white matter.
Vanishing white matter (VWM) is a leukodystrophy that primarily manifests in young children. In this disease, the brain white matter is differentially affected in a predictable pattern with telencephalic brain areas being most severely affected, while others remain allegedly completely spared. Using high-resolution mass spectrometry-based proteomics, we investigated the proteome patterns of the white matter in the severely affected frontal lobe and normal appearing pons in VWM and control cases to identify molecular bases underlying regional vulnerability. By comparing VWM patients to controls, we identified disease-specific proteome patterns. We showed substantial changes in both the VWM frontal and pons white matter at the protein level. Side-by-side comparison of brain region-specific proteome patterns further revealed regional differences. We found that different cell types were affected in the VWM frontal white matter than in the pons. Gene ontology and pathway analyses identified involvement of region specific biological processes, of which pathways involved in cellular respiratory metabolism were overarching features. In the VWM frontal white matter, proteins involved in glycolysis/gluconeogenesis and metabolism of various amino acids were decreased compared to controls. By contrast, in the VWM pons white matter, we found a decrease in proteins involved in oxidative phosphorylation. Taken together, our data show that brain regions are affected in parallel in VWM, but to different degrees. We found region-specific involvement of different cell types and discovered that cellular respiratory metabolism is likely to be differentially affected across white matter regions in VWM. These region-specific changes help explain regional vulnerability to pathology in VWM.


Biosynthetic pathway of citrinin in the filamentous fungus monascus ruber as revealed by 13C nuclear magnetic resonance
Carbon isotope distribution of [13C]citrinin from Monascus ruber incubated with [13C]acetate revealed that the biosynthesis of the toxin originated from a tetraketide, instead of a pentaketide as has been shown for Penicillium and Aspergillus species. The production of polyketide red pigments and citrinin by M. ruber may therefore be regulated at the level of the tetraketide branch point.


Heavy metal and phthalate contamination and labeling integrity in a large sample of US commercially available cannabidiol (CBD) products.
The demand and availability of commercially available cannabidiol (CBD) products has grown substantially, which is of particular interest among medically vulnerable people. Because the cannabis plant is recognized as a bioaccumulator, which is highly effective at absorbing and retaining contaminants (e.g., heavy metals) in soil, it is important to characterize the degree of contamination in CBD products and their label accuracy to better estimate potential health benefits and risks associated with consumption. Levels of lead, cadmium, arsenic, mercury, four phthalates, and CBD labeling accuracy were quantified in a selection of commercially available CBD products in the US. Heavy metal concentrations were quantified by inductively coupled plasma-mass spectrometry. Phthalates were quantified by liquid chromatography-tandem mass spectrometry. CBD labeling accuracy was determined by extracting samples into a suitable organic solvent and analyzing using liquid chromatography with diode array detection. Lead was detected in 42 %, cadmium in 8 %, arsenic in 28 %, and mercury in 37 % of 121 edible CBD products. Four edible CBD products exceeded the California Proposition 65 threshold for daily lead consumption of 0.5μg in two servings. The percentage of edible products with detectable phthalate concentrations varied between 13 % and 80 % across the four phthalates, with DEHP being most prevalent. Among all products tested for CBD labeling accuracy (topicals, edibles, N = 516), 40 % contained <90 % of the CBD indicated on the product label, 18 % contained >110 %, and only 42 % of products fell within ±10 % of the CBD claimed on the manufacturer label. Concentrations of heavy metals and phthalates were not associated with CBD potency. Low-level contamination of edible CBD products with heavy metals and phthalates is pervasive. There is substantial discrepancy between the product label claims for CBD potency and the amount measured in both edible and topical products, underscoring the need for tight regulations for CBD product label integrity to protect consumers.


Correction: Heteroleptic iron(II) complexes of chiral 2,6-bis(oxazolin-2-yl)-pyridine (PyBox) and 2,6-bis(thiazolin-2-yl)pyridine ligands - the interplay of two different ligands on the metal ion spin state.
Correction for 'Heteroleptic iron(II) complexes of chiral 2,6-bis(oxazolin-2-yl)-pyridine (PyBox) and 2,6-bis(thiazolin-2-yl)pyridine ligands - the interplay of two different ligands on the metal ion spin state' by Namrah Shahid et al., Dalton Trans., 2022, 51, 4262-4274, DOI: 10.1039/d2dt00393g.


Electro-responsive silk fibroin microneedles for controlled release of insulin.
To date, very limited work has been done on convenient and active control of insulin release. Herein, we report an electro-responsive insulin delivery system based on thiolated silk fibroin. The disulfide cross-linking points in TSF were reduced and broken to form sulfhydryl groups under electrification, which led to the increase of microneedle swelling degree and promoted insulin release. After power failure, the sulfhydryl group is oxidised to form disulfide bond crosslinking point again, resulting in the reduction of microneedle swelling degree and thus the reduction of release rate. The insulin loaded in the electro-responsive insulin delivery system showed good reversible electroresponsive release performance. The addition of graphene reduced the microneedle resistance and increased the drug release rate under current conditions. In vivo studies on type 1 diabetic mice show that electro-responsive insulin delivery system effectively controls the blood glucose before and after feeding by switching on and off the power supply, and this blood glucose control can be maintained within the safe range (100-200 mg/dL) for a long time (11h). Such electrically responsive delivery microneedles show potential for integration with glucose signal monitoring and are expected to build closed-loop insulin delivery systems.


Nanobatteries in redox-based resistive switches require extension of memristor theory.
Redox-based nanoionic resistive memory cells are one of the most promising emerging nanodevices for future information technology with applications for memory, logic and neuromorphic computing. Recently, the serendipitous discovery of the link between redox-based nanoionic-resistive memory cells and memristors and memristive devices has further intensified the research in this field. Here we show on both a theoretical and an experimental level that nanoionic-type memristive elements are inherently controlled by non-equilibrium states resulting in a nanobattery. As a result, the memristor theory must be extended to fit the observed non-zero-crossing I-V characteristics. The initial electromotive force of the nanobattery depends on the chemistry and the transport properties of the materials system but can also be introduced during redox-based nanoionic-resistive memory cell operations. The emf has a strong impact on the dynamic behaviour of nanoscale memories, and thus, its control is one of the key factors for future device development and accurate modelling.


Single-photon emission computed tomography (SPECT) predicted neurological prognosis in heat stroke: A case report.
Heat stroke may cause multi-organ dysfunction and death. Some patients with neurological abnormalities in the acute phase have neurological sequelae, particularly cerebellar ataxia, in the recovery phase. However, there is no method to predict the neurological prognosis, and the usefulness of imaging has not yet been established. We report the case of an 86-year-old woman with dementia brought to our emergency department in a coma and hyperthermia. The patient was diagnosed with heat stroke and promptly treated in the ICU but remained unconscious. The patient gained consciousness on day 19, but difficulty with stillness associated with cerebellar ataxia in her right upper extremity became apparent. On day 1, head magnetic resonance imaging (MRI) showed no obvious abnormality. However, on day 6, high-signal areas, suggestive of edema, were seen in the bilateral cerebellar hemispheres. Single-photon emission computed tomography (SPECT) on day 9 revealed significant hypoperfusion in the right cerebellum. These changes improved at the time of hospital discharge. This was a case of persistent cerebellar ataxia due to heat stroke, in which imaging findings improved over time. In most cases, MRI findings do not match clinical symptoms. However, the low cerebral blood flow in the early SPECT images was consistent with the clinical symptoms. MRI may not be a prognostic indicator; however, SPECT images may be useful for predicting sequelae.


Insulin-like growth factor (IGF)-I, IGF binding protein-3, and prostate cancer: correlation with Gleason score.
Non-androgenic growth factors are involved in the growth regulation of prostate cancer (PCa). This is the first Brazilian study to correlate, in a population of patients operated for PCa, PSA, total testosterone, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) with Gleason score and to compare with a control group with benign prostate hyperplasia (BPH). This retrospective single-center study included 49 men with previously diagnosed PCa and 45 with previously diagnosed BPH. PSA, testosterone, IGF-I, IGFBP-3 were determined in both groups. PSA and IGFBP-3 levels were significantly higher in the PCa group as compared to the BPH group (p < 0.001 and p=0.004, respectively). There was a significant difference when we compared the PSA before surgery (p < 0.001) and at the inclusion in the study (p < 0.001) and IGFBP3 (0.016) among patients with Gleason < 7, ≥7 and BPH. In the PCa group, PSA, testosterone, IGF-I and IGFBP-3 levels were comparable between Gleason < 7 and ≥7. Our data suggest that in localized PCa, the quantification of PSA and, not of IGF-1, may provide independent significant information in the aggressiveness. IGFBP-3 could be a biochemical marker of disease control in PCa patients.


Transcriptome analysis of hepatopancreas and gills of Palaemon gravieri under salinity stress.
Salinity is an important factor in the aquatic environment, and its fluctuations always result in osmotic stress, which affects the survival, distribution, and physiological activities of crustaceans. Crustaceans counter them through osmoregulation, which consists of many mechanisms. Palaemon gravieri is an important economic species in Palaemonidae, widely distributed in the southern East China Sea and the China Yellow Sea, and has a good adaptability to salinity stress. Currently, there are only a few studies on the effects of salinity on P. graviera. Therefore, it is particularly important to study the molecular responses of P. gravieri to salinity fluctuations. In this study, P. gravieri was treated with salinities of 10, 25, and 40, and the hepatopancreas and gills of shrimp in the different salinity groups were sampled after 24 h. The samples were used for RNA extraction and transcriptome analysis. In total, 80,994 unigenes were obtained, of which 19,114 were annotated. The differences in gene expression between different tissues at the same salinity were more significant. Many metabolism-related genes were downregulated in the gills, such as beta-hexosaminidase subunit alpha (HEXA), 10-formyltetrahydrofolate dehydrogenase (ALDH1L1), and Alcohol dehydrogenase class-3 (ADH5). Scanning transmission electron microscope analysis showed that the expression levels of some stress-(but not salinity stress) related genes changed after stress (mostly upregulated), suggesting the existence of secondary stress. Gene set enrichment analysis (GSEA) focused on the expression of transporters in osmoregulation, and the results showed that they mainly played a role in the gills, but ATP-binding cassette (ABC) transporters were more active in the hepatopancreas. This study showed that the response of P. gravieri to salinity change was different not only between the hepatopancreas and gills, but also between low salinity and higher salinity, and the ion transport-related genes were mainly expressed in the gills. Overall, these results improve our understanding of salt tolerance mechanism in P. gravieri.


How I do it: lateral supra-cerebellar infra-tentorial approach for P2-P3 junction cerebral aneurysms.
P2-P3 junction aneurysms are challenging to treat surgically because of their frequent complex morphology and their location deep in close proximity to the midbrain. The sub-temporal route requires significant retraction of the temporal lobe in addition to potential injury to the vein of Labbe. We describe the technique for treating such aneurysms via a lateral supra-cerebellar infra-tentorial (LSCIT) approach, which eliminates manipulation of the temporal lobe. Cadaveric dissection provided comprehensive understanding of relevant anatomy. Intraoperative video shows clipping of the aneurysm using a LSCIT approach. LSCIT approach allows safe clipping of P2-P3 aneurysms with minimal brain manipulation.


Fetal respiratory distress causing CNS and inner ear hemorrhage.
Fifty-two consecutive temporal bones of infants who died neonatally, or in utero of natural causes, were studied. Complete autopsies were performed. Twenty-eight infants had a variety of pulmonary disorders which resulted in severe respiratory distress prior to their death. Of these, the majority had bleeding intracranially and into the inner ear. There were five major pathways of central nervous system and subarachnoid hemorrhage involvement of the inner ear: 1) the modiolus, 2) cochlear aqueduct, 3) retrograde via the cochlear vein, 4) episodes of spontaneous bleeding into various compartments of the inner ear, and 4) hemorrhage via the otic capsule. The remaining 24 infants died of other natural causes. Two had CNS bleeding with no extension to the inner ear. We propose that there is a syndrome which consists of 1) neonatal respiratory distress, 2) intracranial hemorrhage, and 3) bleeding into the inner ear--an extension of a subarachnoid or subependymal matrix bleeding diathesis.


Receptor-mediated and absorptive endocytosis by male germ cells of different mammalian species.
The routes for adsorptive and receptor-mediated endocytosis were studied in vivo after microinjection of tracers into the lumen of the seminiferous tubules, and in vitro in isolated germ cells of different mammals. Cationic ferritin was located on the plasma membrane, in vesicles, in tubules, in multivesicular bodies and in lysosome-like granules of mouse spermatocytes. In these cells the number of multivesicular bodies varied during spermatogenesis. Spermatids and to a lesser extent residual bodies also performed adsorptive endocytosis. In the rat and monkey (Macaca fascicularis) diferric transferrin was specifically taken up by germ cells via receptor-mediated endocytosis. The labelling was observed subsequently in membrane pits, vesicles, endosome-like bodies and pale multivesicular bodies. A progressive decrease in the frequency of the labelling of the germ cells by transferrin-gold particles was observed from spermatogonia to spermatocytes and to early spermatids, which could indicate that iron is particularly required by germ cells during the mitotic and meiotic processes. Adsorptive and receptor-mediated endocytosis therefore occurs in all classes of germ cells. These endocytic processes are most probably required for germ cell division, differentiation and metabolism.


Quantification of random mutations in the mitochondrial genome.
Mitochondrial DNA (mtDNA) mutations contribute to the pathology of a number of age-related disorders, including Parkinson disease [A. Bender et al., Nat. Genet. 38 (2006) 515,Y. Kraytsberg et al., Nat. Genet. 38 (2006) 518], muscle-wasting [J. Wanagat, Z. Cao, P. Pathare, J.M. Aiken, FASEB J. 15 (2001) 322], and the metastatic potential of cancers [K. Ishikawa et al., Science 320 (2008) 661]. The impact of mitochondrial DNA mutations on a wide variety of human diseases has made it increasingly important to understand the mechanisms that drive mitochondrial mutagenesis. In order to provide new insight into the etiology and natural history of mtDNA mutations, we have developed an assay that can detect mitochondrial mutations in a variety of tissues and experimental settings [M. Vermulst et al., Nat. Genet. 40 (2008) 4, M. Vermulst et al., Nat. Genet. 39 (2007) 540]. This methodology, termed the Random Mutation Capture assay, relies on single-molecule amplification to detect rare mutations among millions of wild-type bases [J.H. Bielas, L.A. Loeb, Nat. Methods 2 (2005) 285], and can be used to analyze mitochondrial mutagenesis to a single base pair level in mammals.


New insights into the effect of ethanol and volatile fatty acids proportions on methanogenic activities and pathways.
During anaerobic digestion, methanogenic activities and pathways can be affected by intermediates. Here, the effects of intermediates acetate, propionate, and ethanol on methanogenesis were investigated. Four anaerobic sequencing batch reactors were acclimated with propionate (ASBR_P), ethanol/propionate (ASBR_EP), acetate/propionate (ASBR_AP), and ethanol/acetate/propionate (ASBR_EAP). Ethanol was the easiest one to be biodegraded, thereby enhancing the maximum methane production rate and shortening the lag phase, while the longest acclimation time and lowest methane production rate were observed in ASBR_P. Different microbial communities and syntrophic patterns existed in four reactors. Desulfovibrio and Geobacter were the dominant ethanol-oxidizing bacteria in ASBR_EP and ASBR_EAP, respectively. Both Desulfovibrio and Geobacter possessed the potential of extracellular electron transfer, which might be the advantage of ethanol dosage for enhancing methanogenesis through direct interspecies electron transfer. Methanosarcina was enriched in ASBR_P and ASBR_AP, while Methanosaeta in ASBR_EP and ASBR_EAP. Genes responsible for acetoclastic methanogenesis were significantly enriched in ASBR_EAP, possibly resulting in the highest methanogenic activity from acetate. Results from this study will advance the optimization of practical anaerobic systems, which can be achieved by regulating the intermediates with different fermenting pathways.


Pathologic, radiologic and PET scan response of gastrointestinal stromal tumors after neoadjuvant treatment with imatinib mesylate.
The aim of this study is to review the radiologic, PET scan and pathologic response and the outcome of patients with advanced GIST treated with neoadjuvant IM followed by surgical resection. We report a case and review 36 patients reported in MEDLINE with advanced GIST treated with neoadjuvant IM followed by surgical resection. Thirty-seven patients with a median age of 56 years (range, 32-76 years) at presentation were treated with neoadjuvant IM. Radiologic response accurately predicted pathological response in 31/36 patients, whereas PET scan was accurate in predicting treatment response in only 6/23 patients. This study demonstrates that the pathologic response of GIST to IM is usually incomplete and does not correlate with the complete response seen on PET scan. This finding suggests that surgical resection will continue to play a vital role in the treatment of patients with advanced disease responding to IM treatment.


Kazachstania hellenica sp. nov., a novel ascomycetous yeast from a Botrytis-affected grape must fermentation.
Four ascomycetous yeast strains (D4W13, D9W2, D9W4 and D9W17T) were isolated from Botrytis-affected fermenting grape juice originating from Attica Province, Greece. Phylogenetic analysis of rRNA gene sequences (18S, 26S and 5.8S-ITS) showed that the four strains represent a distinct species within the genus Kazachstania, closely related to Kazachstania zonata NBRC 100504T and Kazachstania gamospora NBRC 11056T. Electrophoretic karyotyping and physiological analysis support the affiliation of the four strains in a novel species for which the name Kazachstania hellenica sp. nov. is proposed, with D9W17T (=CBS 10706T=NBRC 103637T) as the type strain.


Basal Anti Mullerian hormone levels and endometrial thickness at midcycle can predict the outcome after clomiphene citrate stimulation in anovulatory women with PCOS, a retrospective study.
Recent studies reported that in polycystic ovary syndrome (PCOS) patients, other stimulation agents are superior to the popular first-line regimen, clomiphene citrate (CC) for ovarian stimulation. Nonetheless, CC is still widely used since it is not clear which patients will not respond to it. Furthermore, the prognostic value of endometrium thickness at midcycle is controversial. We aimed to find factors predicting the response to CC and the prognostic value of endometrial thickness at midcycle. We collected data retrospectively from 89 anovulatory PCOS patients who had the first stimulation with 50 mg CC. We analyzed the basal levels of AMH, testosterone, LH, LH:FSH ratio and the endometrial thickness at midcycle by univariate, followed by multivariate regression. The outcome measures were pregnancy, follicle maturation and endometrial thickness at midcycle. Stimulation with 50 mg CC resulted in follicle maturation in 50.6% of the women and in 27.0% pregnancies. In the univariate analysis, greater endometrial thickness, lower LH and AMH levels and a lower LH:FSH ratio were associated with pregnancy (p < 0.05). In the multivariate analysis, only endometrial thickness remained predictive (p = 0.045). The endometrial thickness cutoff level of ≥ 8 mm showed a sensitivity of 87.5% (96% CI 67.6-97.3) and a specificity of 66.7% (95% CI 43.0-85.4) for prediction of pregnancy. In the multivariate analysis AMH levels 5.4 (3.4; 7.0) (ng/mL) predicted pregnancy (β = - 0.194 ± 0.092; p = 0.034) CONCLUSION: We suggest to refrain from CC as first-line regimen in patients with AMH > 7 ng/ml. Under CC treatment, the cutoff value of ≥ 8 mm endometrium thickness at midcycle is associated with a better outcome.