Conservation implications of asymmetric introgression and reproductive barriers in a rare primrose species.
Primula is a large genus of flowering herbs well known for their heterostyly. Currently few natural hybrids are known and reproductive barriers in this genus in the wild have received little attention. However, there is instance of hybridization between rare and widely-spread species, and conservation implications of such situation is poorly understood. In the present study, we investigated hybridization patterns and reproductive barriers between a wide spread species, Primula poissonii and a rare species P. anisodora, of which only three populations are currently known. Pollinator-mediated reproductive isolation was strong between parental species but not significant between hybrids and parental species. Hand pollination experiments showed significant reduction of both fruit- and seed-set for heterospecific pollination as compared with conspecific pollination for both parental species. Furthermore, hybrids had higher fruit- and seed-set when pollinated with P. anisodora pollen as opposed to P. poissonii pollen. Microsatellites identified backcrosses to P. anisodora in two of the three populations of P. anisodora, and additionally more individuals of P. anisodora showed introgression from P. poissonii than vice versa. These results provide evidence for potential genetic swamping of the P. anisodora populations, which could pose a serious threat for this locally endemic species.


Magnesium in cardiac arrest (the magic trial).
The prognosis of out of hospital cardiac arrest (OHCA) is dismal. Recent reports indicate that high dose magnesium may improve survival. A prospective randomized double blind placebo controlled trial was conducted at the emergency department (ED) of Royal Perth Hospital, a University teaching hospital. Patients with OHCA of cardiac origin received either 5 g MgSO4 or placebo as first line drug therapy. The remainder of their management was standard advanced cardiac life support (ACLS). Study endpoints were: (1) ECG rhythm 2 min after the trial drug; (2) return of spontaneous circulation; (3) survival to leave the ED; (4) survival to leave intensive care; and (5) survival to hospital discharge. Of 67 patients enrolled, 31 received magnesium and 36 placebo. There were no significant differences between groups for all criteria, except that there were significantly more arrests witnessed after arrival of EMS personnel in the magnesium group (11 or 35% vs 4 or 11%). Return of spontaneous circulation occurred in seven (23%) patients receiving magnesium and eight (22%) placebo. Four patients in each group survived to leave the ED and one from the magnesium group survived to hospital discharge. There were no survivors in the placebo group. In this study, the use of high dose magnesium as first line drug therapy for OHCA was not associated with a significantly improved survival. Early defibrillation remains the single most important treatment for ventricular fibrillation (VF). Further studies are required to evaluate the role of magnesium in cardiac and cerebral resuscitation.


Effects of the community-based health planning and services on anemia and acute malnutrition amongst under-fives in Ghana: A comparative study.
Ghana implemented a community-based health planning and services (CHPS) in 2000 with the aim of bringing health services to the doorsteps of the deprived in the communities. Japan International Cooperation Agency (JICA) supported the implementation of the project with a distinct approach in the Upper West region, employing supportive supervision. To investigate the impact of the JICA CHPS model on anemia and acute malnutrition prevalence amongst children less than five years of age. This is a quasi-experimental study design that compares the upper west region with the two other regions of the North implementing the traditional model of CHPS. We used the Ghana demographic and health survey dataset for 2003 as the baseline and 2014 as the follow-up year and employed the difference-in-difference approach. We find a reduction in the likelihood of anemia and acute malnutrition prevalence among children less than five years by 17 and 8 percentage points respectively. We find the project to be cost-effective, at a cost of $7 per each anemia prevalence averted. The results indicate that the JICA model of CHPS is cost-effective in the reduction of anemia and acute malnutrition prevalence compared to the traditional model. We recommend a nationwide expansion of the JICA model to enhance the reduction of anemia and acute malnutrition in Ghana.


Selectivity of Terahertz Gas-Phase Spectroscopy.
Analytical potential of terahertz (THz) spectroscopy is assessed by comparing selectivity for a set of eight environmentally important gases over THz and infrared (IR) optical frequencies. Selectivity coefficients are determined over selected spectral regions for acetaldehyde, acetonitrile, ethanol, water, methanol, ammonia, propionaldehyde, and propionitrile. These selectivity coefficients quantify the magnitude of the net analyte signal for each test compound relative to the other seven. In addition to the THz spectral range (2-125 cm(-1)), selectivity coefficients are determined for the following IR regions 600-1300, 1300-2000, 2600-3100, 3100-4000, and 4000-6500 cm(-1). Highest selectivity is afforded over the THz frequencies for six of the eight test compounds and THz selectivity coefficients for the other two gases (water and acetonitrile) are acceptable for environmental measurements.


Microtensile Bond Strength Evaluation of Composite Resin to Discolored Dentin After Amalgam Removal.
Background To obtain prolonged clinical success with composite restorations, better bonding of resin to the tooth substrate is crucial. Aim The study was aimed to evaluate the microtensile bond strength (µTBS) of bulk-fill composite resin restorations when bonded to a cavity previously restored with amalgam, comparing with that of freshly prepared dentin. Materials and method Mesio-occlusal cavity preparations were done on 80 extracted human mandibular molars with a buccolingual width of 4 mm and a 1.5 mm axial depth by placing the gingival seat 0.5 mm coronal to the cementoenamel junction (CEJ) and were restored with fine-grain amalgam alloy. After thermocycling, the amalgam restorations were removed. Disto-occlusal cavities with similar dimensions of mesial cavities were prepared, and both the proximal surfaces were filled with bulk-fill composite using either etch-and-rinse or self-etch adhesives. Following thermomechanical cyclic loading, all the teeth were sectioned for µTBS testing. Bond strength data expressed in megapascals (MPa) were subjected to statistical analyses using analysis of variance (ANOVA) and Tukey's multiple post-hoc tests. Results The total-etch adhesive exhibited statistically higher bond strength values to both dentin substrates compared to self-etch adhesives (p<0.05). Failure mode analysis reported more of adhesive failures. Conclusion The µTBS of bulk-fill composite resin restorations bonded to a cavity previously restored with amalgam was significantly lower than that of freshly prepared dentin. Total-etch adhesives bond strength was higher than self-etch adhesives to both the substrates tested.


Memory Retrieval in Mice and Men.
Retrieval, the use of learned information, was until recently mostly terra incognita in the neurobiology of memory, owing to shortage of research methods with the spatiotemporal resolution required to identify and dissect fast reactivation or reconstruction of complex memories in the mammalian brain. The development of novel paradigms, model systems, and new tools in molecular genetics, electrophysiology, optogenetics, in situ microscopy, and functional imaging, have contributed markedly in recent years to our ability to investigate brain mechanisms of retrieval. We review selected developments in the study of explicit retrieval in the rodent and human brain. The picture that emerges is that retrieval involves coordinated fast interplay of sparse and distributed corticohippocampal and neocortical networks that may permit permutational binding of representational elements to yield specific representations. These representations are driven largely by the activity patterns shaped during encoding, but are malleable, subject to the influence of time and interaction of the existing memory with novel information.


Small town development and urban illiteracy: comparative evidence from Leicestershire marriage registers 1754-1890.
"Based on the analysis of Anglican marriage registers for the period 1754 to 1890, the article explores patterns of illiteracy in three small Leicestershire [England] towns with contrasting economic functions. Illiteracy levels were closely related to urban occupational and social structures, which also affected distinct gender differentials. Evidence [of] the effect of literacy on age at marriage and marriage distance suggests that demographic behaviour and spatial interaction were determined more by socio-economic factors than by the possession of literacy skills. Literacy attainment, however, was linked to extended marriage distances when both spouses could sign the register."


Molecular Identification of the Western Drywood Termite (Isoptera: Kalotermitidae) by Loop-Mediated Isothermal Amplification of DNA from Fecal Pellets.
A rapid and technically simple molecular detection method was developed for the western drywood termite, Incisitermes minor (Hagen), which is among the most harmful pests of wooden architectures. The method features DNA extraction from fecal pellets and species-specific loop-mediated isothermal amplification (LAMP) of DNA. As drywood termites have low moisture requirements, they easily infest artificial wooden products, and are likely to spread by human transportation of infested wood and wooden products. Rapid detection and accurate identification are essential tools for termite eradication at new sites of introduction. Our molecular detection method exploits the detectability and accessibility of fecal pellets and the accuracy and rapidity of the LAMP assay. The methodology permits rapid detection and identification of various drywood termites by designing specific primers for each species, and will be applicable to regulatory applications.


Partially coherent flattened Gaussian beam and its paraxial propagation properties.
A simple model called partially coherent flattened Gaussian beam (FGB) is proposed to describe a partially coherent beam with a flat-topped spatial profile. An explicit and analytical formula is derived for the cross-spectral density of a partially coherent FGB propagating through a paraxial ABCD optical system. The propagation factor and propagation properties of a partially coherent FGB in free space are studied in detail and found to be closely related to its coherence and beam order.


Attaching the fluorine atom to organic molecules using BrF3 and other reagents directly derived from F2.
Elemental fluorine is a starting point for nucleophilic fluorinations (e.g., BrF3), radical fluorinations (e.g., F2 under irradiation), and electrophilic fluorinations (e.g., AcOF). All three categories are represented in this Account. Bromine trifluoride, although commercially available, can be readily made from the elements and is a very good source for naked nucleophilic fluoride ions. To minimize radical reactions, an anchor has to be installed in the molecules with which it reacts. Such an anchor is constituted of a soft base such as nitrogen and especially sulfur atoms. This reagent was used for constructing compounds with a CF2, CF3, CHF2, or CF2COOH group in specific sites. F2 itself was used for completing perfluorination of various polyfluoroethers, while the electrophilic acetyl hypofluorite is an excellent tool for introducing a single fluorine atom into organic molecules such as carboxylic acids and nitro compounds.


GenoCore: A simple and fast algorithm for core subset selection from large genotype datasets.
Selecting core subsets from plant genotype datasets is important for enhancing cost-effectiveness and to shorten the time required for analyses of genome-wide association studies (GWAS), and genomics-assisted breeding of crop species, etc. Recently, a large number of genetic markers (>100,000 single nucleotide polymorphisms) have been identified from high-density single nucleotide polymorphism (SNP) arrays and next-generation sequencing (NGS) data. However, there is no software available for picking out the efficient and consistent core subset from such a huge dataset. It is necessary to develop software that can extract genetically important samples in a population with coherence. We here present a new program, GenoCore, which can find quickly and efficiently the core subset representing the entire population. We introduce simple measures of coverage and diversity scores, which reflect genotype errors and genetic variations, and can help to select a sample rapidly and accurately for crop genotype dataset. Comparison of our method to other core collection software using example datasets are performed to validate the performance according to genetic distance, diversity, coverage, required system resources, and the number of selected samples. GenoCore selects the smallest, most consistent, and most representative core collection from all samples, using less memory with more efficient scores, and shows greater genetic coverage compared to the other software tested. GenoCore was written in R language, and can be accessed online with an example dataset and test results at https://github.com/lovemun/Genocore.


Validation of the six-and-twelve criteria among patients with hepatocellular carcinoma and performance score 1 receiving transarterial chemoembolization.
Transarterial chemoembolization (TACE) is recommended for patients with intermediate hepatocellular carcinoma (HCC) according to treatment guidelines. However, a large number of patients with advanced HCC also receive TACE in clinical practice, especially for those with liver-confined HCC and Eastern Cooperative Oncology Group score (ECOG) 1. In view of previous studies, such patients have different prognoses from advanced HCC patients with macrovascular invasion or extrahepatic spread; therefore, patients with ECOG 1 alone might be classified into the intermediate stage and benefit from TACE treatment, but a study particularly focusing on such patients and exploring the effectiveness of TACE therapy is lacking. To investigate treatment outcomes of TACE in HCC patients with ECOG 1 alone and propose a specific prognostic model. Patients from 24 Chinese tertiary hospitals were selected in this nationwide multicenter observational study from January 2010 to May 2016. Overall survival (OS) was estimated using Kaplan-Meier curves and compared by the log-rank test. Multivariate Cox regression was used to develop the potential prognostic models. The discriminatory ability of the models was compared and validated in various patient subgroups. The individual survival prediction for six-and-twelve (6&12) criteria, defined as the algebraic sum of tumor size (cm) and tumor number, was illustrated by contour plot of 3-year survival probability and nomogram. A total of 792 eligible patients were included. During follow-up, median OS reached 18.9 mo [95% confidence interval (CI): 16.9-21.0]. Three independent multivariate analyses demonstrated that tumor size, tumor number, α-fetoprotein level, albumin-bilirubin grade and total bilirubin were prognostic factors of OS (P < 0.05). The previously proposed 6&12 criteria was comparable or even better than currently proposed with the highest predictive ability. In addition, the 6&12 criteria was correlated with OS in various subgroups of patients. The patients were stratified into three strata with score ≤ 6, > 6 but ≤ 12, and > 12 with different median OS of 39.8 mo (95%CI: 23.9-55.7), 21.1 mo (95%CI: 18.4-23.8) and 9.8 mo (95%CI: 8.3-11.3), respectively (P < 0.001). TACE is effective for advanced HCC patients with ECOG 1 alone, and the 6&12 criteria may help with clinical decision-making.


Inhibition of human polymorphonuclear leukocyte functions by ibuprofen.
We have found that pretreatment of human neutrophils with ibuprofen (0.10-1.0 mg/ml) results in an irreversible, concentration-dependent inhibition of superoxide anion generation and release of lysosomal enzymes (myeloperoxidase, lysozyme) stimulated by the synthetic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP), the complement fragment C5a, and to a lesser extent by serum opsonized zymosan. Inhibition of granule exocytosis and oxygen radical generation at ibuprofen concentrations less than 5 mg/ml was not due to drug cytotoxicity since release of the cytoplasmic enzyme lactate dehydrogenase was not affected by ibuprofen. In contrast to neutrophil responses mediated by C5a or FMLP, ibuprofen did not inhibit either enzyme release or superoxide anion generation by neutrophils stimulated with phorbol myristate acetate. Ibuprofen did not function as an oxygen radical scavenger in a cell-free system in which superoxide anion was generated by the aerobic action of xanthine oxidase on hypoxanthine. Ibuprofen also inhibited in a concentration-dependent fashion both directed migration (chemotaxis) and stimulated random migration (chemokinesis) of neutrophils exposed to either FMLP or C5a. Inhibition of neutrophil adherence to plastic surfaces and bovine pulmonary artery endothelial cells was equally effective when the neutrophils were treated with ibuprofen before stimulation with FMLP or phorbol myristate acetate. The inhibitory effects of ibuprofen pretreatment of neutrophils could not be overcome by addition of prostaglandins E1 or E2 (0.3-300 nM). These results demonstrate that ibuprofen is capable of suppressing many functions thought to be important in neutrophil-mediated acute pulmonary inflammatory processes. Results of these experiments further suggest that ibuprofen may inhibit neutrophil functions by acting on cellular components separate from membrane receptors or by blockade of cyclo-oxygenase products which may be involved in these neutrophil functions.


The prevalence of fibromyalgia and its relation with headache characteristics in episodic migraine.
The objective of this study was to assess the prevalence of fibromyalgia (FM) in patients with episodic migraine and to evaluate the relationship between migraine characteristics and FM. One hundred and eighteen consecutive patients (mean age = 38 years, 75% women) fulfilling the International Classification of Headache Disorders-II criteria for migraine with (n = 22) and without (n = 96) aura from an outpatient headache clinic of a university hospital were evaluated. The diagnosis of FM was made based on the 1990 American College of Rheumatology classification criteria. Participants completed some self-administered questionnaires ascertaining sociodemographics, headache severity, frequency and duration, headache-related disability (Headache Impact Test [HIT-6]) and Migraine Disability Assessment Scale, widespread musculoskeletal pain (visual analog scale), depression (Beck depression inventory), anxiety (Beck anxiety inventory), sleep quality (Pittsburgh Sleep Quality Index), fatigue (Multidimensional Assessment of Fatigue), and quality of life (Short Form-36 Health Survey [SF-36]). In patients with FM, the tender point count and the Fibromyalgia Impact Questionnaire were employed. FM was diagnosed in 37 (31.4%) of the patients. FM comorbidity was equally distributed across patients with and without aura. Severity of migraine headache, HIT-6, and anxiety were especially associated with FM comorbidity. Patients suffering from migraine plus FM reported lower scores on all items of the SF-36. This study indicates that the assessment and management of coexisting FM should be taken into account in the assessment and management of migraine, particularly when headache is severe or patients suffer from widespread musculoskeletal pain.


The effect of fluid resuscitation strategy on monocyte and T-cell surface markers.
Despite initial lifesaving benefits, posttraumatic resuscitation strategies have been associated with immunologic complications leading to systemic inflammatory response syndrome, sepsis, multiple organ failure, and late trauma death. Nevertheless, the direct effect on immunologic surface markers remains inadequately described. We hypothesized that changes in monocyte and T-cell surface markers were associated with initial posttraumatic fluid resuscitation. Data were extracted from the inflammation and host response to injury (Glue Grant) study. Blood samples were drawn from 492 patients on days 0, 1, 4, 7, 14, and 28 and analyzed for 31 monocyte and T-cell surface markers. Resuscitation strategies during the initial 48 h were quantified, including transfusion of packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, and crystalloids. Longitudinal surface marker concentration changes were quantified by the calculation of a within-patient signal intensity change and were associated with resuscitation strategy while controlling confounders. P-values were post hoc corrected using the false detection rate q-value. The monocyte surface marker (CD83) trajectory (as measured by a within-patient signal intensity change) was found to be positively associated with volume of PRBCs transfused (q = 0.002) and negatively associated with the transfused volume of FFP (q = 0.004). T-cell surface marker (CD3) was found to be negatively associated with volume of PRBCs transfused (q = 854 × 10-9) and positively associated with the transfused volume of FFP (q = 0.022). Platelets and crystalloid transfusion volumes were not associated with any surface marker trajectories. PRBC and FFP transfusion was associated with opposing effects on CD3 and CD83 trajectories, which may in part explain some of the protective effects of a high FFP:PRBC ratio in trauma-related resuscitation.


Withdrawal of artificial nutrition and hydration in neonatal intensive care: parents' and healthcare practitioners' views.
Withdrawing Artificial Nutrition and Hydration (WANH) in the neonatal intensive care units (NICUs) has long been controversial. In France, the practice has become a legal option since 2005. But even though, the question remains as to what the stakeholders' experience is, and whether they consider it ethically appropriate. In order to contribute to the debate, we initiated a study in 2009 to evaluate parental and health care professionals (HCP) perspectives, after they experienced WAHN for a newborn. The study included 25 cases from 5 different clinical neonatology departments. We interviewed both the parents and some of the HCP who cared for the baby, at least 6 months after this latter deceased. We proceeded through in-depth individual qualitative interviews. Content was analyzed for themes and patterns that emerged from the data. Some parents expressed that WANH offered an opportunity to the family to spend a few demedicalized days with the baby before she dies, without any tubes and machines, and to be well supported by the HCP during this palliative stage. But others evaluated the practice in retrospect as a terrible ordeal. All said that, at least, the time of waiting for death to ensue should not last too long. After a few days, it becomes unbearable because of the transformation of the baby's appearance and because they, as parents, began to wonder if she was not dying from starvation rather than from her initial disease. An important proportion of HCP also expressed some kind of ethical unease. This was due to the psychological violence involved in the decision for a human being to stop feeding a little one, and also to the difficulty to deal with the fundamental intention behind the decision of WANH: indeed, could it be claim that it does not presuppose the intention of provoking the infant's death? The discussion focuses on the point to know if WANH can be considered as a source of progress from an ethical point of view, particularly in comparison with earlier practices-that in France could involve active euthanasia by lethal injection. We argue that when HCP are merely focused on avoiding that WAHN could be construed as a way of intending to hasten the baby's death, the practice is at risk to be implemented in a way that becomes ethically counterproductive. Focusing on this intention easily distract the clinical teams from what should be their ultimate concern, namely the baby's comfort during the dying process, as well as the support owned to her parents. To conclude, we suggest that the ethical priorities, when WANH is decided, should be the support due to the patient and her family on the one hand, and, on the other hand to implement it in such a way that at least the baby seems to have died of her initial disease and never of starvation. This means that HCP have a duty to control the timing of death, even though this might be incompatible with the worry to avoid the intention of hastening the baby's death.


Characterization of a new ion selective electrode for ionized magnesium in whole blood, plasma, serum, and aqueous samples.
Results from a novel ion selective electrode (ISE) for ionized magnesium (Mg2+) correlate well with atomic absorption spectroscopy on aqueous solutions containing from 0.1-3.0 mmol MgCl2/L. Day to day precision (coefficient of variation) of the electrode on protein-based controls is < 4%; aqueous-based controls < 6%. The new ISE is selective for Mg2+ with a selectivity constant for Ca2+ (KMgCa) of 8 x 10(-2). Adding pathophysiologic concentrations of Cd2+, Ca2+, Cu2+, Fe3+, K+, Na+, or Zn2+ to serum and aqueous solutions gave negligible to minimal changes in measured Mg2+. Ligand binding studies in aqueous solution indicate that pathophysiologic concentrations of different anions (e.g. heparin, lactate, bicarbonate, phosphate, acetate and sulfate) bind to Mg2+, effectively reducing its concentration in solution. Likewise, silicon (as either found in Vacuutainer tubes or as chlorosilane) failed to exert any significant effect on measured Mg2+. Addition of Intralipid (up to 500 mg/dL) gave negligible to minimal changes in Mg2+. Mg2+ measurements on whole blood, plasma, and serum for a given human subject's samples are virtually identical, at least within the reference range for Mg2+. Typically, Mg2+ is 71% of TMg, but varies from subject to subject; i.e. Mg2+ cannot be predicted from TMg. Clinical studies revealed that the Mg2+/TMg ratio could be remarkably consistent in sequential samples (e.g., throughout the course of coronary bypass surgery) taken from one patient, but that this ratio could differ dramatically from the ratio in sequential samples taken from another. Mg2+ is held within a narrow range (0.53-0.67 mmol/L) in normal, healthy subjects when compared to TMg (0.70-0.96 mmol/L).


Use of high-frequency repetitive transcranial magnetic stimulation to probe the neural circuitry of food choice in anorexia nervosa: A proof-of-concept study.
Repetitive transcranial magnetic stimulation (rTMS) is used to modulate neural systems and provides the opportunity for experimental tests of hypotheses regarding mechanisms underlying anorexia nervosa (AN). The present pilot study has investigated whether high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) to a region of the right dorsolateral prefrontal cortex (DLPFC) might be associated with change in food selection among adult inpatients with AN. Ten women received one session of sham and one session of HF-rTMS targeting the right DLPFC while completing a computerized Food Choice Task. Compared to sham, HF-rTMS was associated with changes in food ratings and food choice: inpatients reported higher healthiness ratings of low- and high-fat foods and selected a significantly greater proportion of high-fat foods over a neutrally rated reference item while receiving HF-rTMS. Findings suggest that HF-rTMS to the right DLPFC was associated with a reduction of fat avoidance on a food choice task among inpatients with AN and provide additional support for the possibility that this region, and related neural circuits, may underlie restrictive food choice. Research using rTMS to experimentally test neural mechanisms is needed to elucidate the underpinnings of AN and supports the development of novel treatment targets.


Comparisons of health-related and appearance-related smoking risk perceptions and worry on motivation to quit.
This research examined main and interactive associations of perceived risk and worry of health and appearance smoking consequences on motivation to quit and the relative importance of each of these. Hierarchical regressions controlling for other measures found that perceived conditional risk and worry of health consequences were associated with motivation to quit; only conditional risk of appearance consequences was associated with motivation to quit. Relative weights analysis indicated that perceived conditional risk of appearance consequences and worry about health consequences were the most important variables in the model. Consideration of appearance consequences may aid in motivating smokers to try quitting.


Calretinin and CD34 immunoreactivity of the endometrial stroma in normal endometrium and change of the immunoreactivity in dysfunctional uterine bleeding with evidence of 'disordered endometrial stroma'.
We investigated the pattern of reactivity of calretinin and CD34 in normal and pathological endometria. Various endometrial tissues were submitted for calretinin and CD34 immunostaining. Calretinin reactivity was limited to the endometrial stromal cells (ESC) of the superficial zone of the functionalis layer (FL) in the proliferative phase, and was extensive in all stages of the secretory phase. The ESC of the post-menopausal, ectopic, hyperplastic or neoplastic endometria showed negative or focal weak reactivity for calretinin. In dysfunctional uterine bleeding (DUB) with a normal or an abnormal histopathological appearance on routine stain, there were varying degrees of focal to extensive decreases in calretinin reactivity. The foci of negative calretinin reactivity in the FL displayed varying reactivity for CD34 and appeared to be continuous with the basalis layer (BL). Endometrial polyps were often reactive for CD34, but not reactive for calretinin. Immunostaining for calretinin and CD34 is helpful in the diagnosis of endometrial polyp and hyperplasia. In DUB, with or without abnormal histopathological findings, there were alterations of the zonal pattern of calretinin reactivity in the FL. This alteration appears to be an expansion of the stroma of the BL into the FL, resulting in a 'disordered endometrial stroma'.


Cytophotometric DNA measurements of chondrosarcoma: methodologic aspects of measurements in tissue sections from old paraffin-embedded specimens.
The methodologic prerequisites of cytophotometric DNA measurements of normal and tumor cells in tissue sections obtained from paraffin blocks and preserved as archival material were investigated. The optimal time of hydrolysis in 5-N HCl at room temperature was one hour for the different cell types analyzed. Paraffin-embedded tissues, stored for two decades, were still suitable for quantitative cytophotometric DNA determinations of Feulgen-stained nuclei. Different cell types in the Feulgen-stained sections could be identified with accuracy. The 90th percentile of fibroblast (internal control cells) DNA values was used as an upper limit of the diploid DNA content. By determining the number of tumor cells with DNA values exceeding this limit, nondiploid (hyperploid) tumor cell populations could be discriminated from diploid tumor cell populations. Cell population analysis of ploidy level, performed in this way, was found to be accurate in tissue sections of 4 micrometer. The accuracy of this analysis was not improved by increasing the section thickness. Since tissue sections obtained from old paraffin blocks could be used for the determination of hyperploidy, the prognostic significance of this parameter in different tumors can be assessed retrospectively.


A variant on promoter of the cannabinoid receptor 1 gene (CNR1) moderates the effect of valence on working memory.
Cannabinoid receptor 1 gene (CNR1) variants have been related to affective information processing and, in particular, to stress release. Here, we aimed to examine whether the endocannabinoid system via CNR1 signaling modulates affective working memory, the memory system that transiently maintains and manipulates emotionally charged material. We focused on rs2180619 (A > G) polymorphism and examined genotype data collected from 231 healthy females. Analyses showed how a general positivity bias in working memory (i.e., better memory for positive words) emerged as task strings lengthened only in carriers of the major allele (AA/AG). Differently, GG carriers showed better memory for affective items in general (i.e., positive and negative words). These findings are some of the first to directly highlight the role of variant on promoter of the CNR1 gene in affective working memory and to evidence a differentiation among CNR1 genotypes in terms of larger difficulties in disengaging from negative stimuli in GG carriers.


Areca (betel) nut chewing habit among high-school children in the Commonwealth of the Northern Mariana Islands (Micronesia).
To investigate the prevalence of its use by high-school children in Saipan in Micronesia. Usage of the areca nut is indigenous to south Asia and the western and south Pacific. Some serious health effects of areca nut chewing are recognized and the International Agency for Research on Cancer has recently classified regular use of areca nut as being carcinogenic to humans. Information on usage by young people, however, is scarce. Data on consumption of areca nut were obtained by a self-administered questionnaire. Following an oral mucosal examination using WHO criteria any detectable oral mucosal diseases were recorded. Of 309 schoolchildren surveyed (mean age 16.3 +/- 1.5 years), 63.4% claimed regular use, the highest level recorded in any school population survey. Significant oral diseases detected were oral leukoplakia in 13% and oral submucous fibrosis in 8.8% of children. These findings from Saipan suggest that areca nut chewing starts at a young age in Micronesia. As many users develop dependency this raises important concerns regarding its consequences for oral health.


The effect of graphic organizers on subjective and objective comprehension of a health education text.
This study examined the effect of graphic organizers on the comprehension of a health education brochure text and compared subjective with objective comprehension measures. Graphic organizers are graphical depictions of relations among concepts in a text. Participants read a brochure text about asthma with and without these organizers, and subjective and objective text comprehension was measured. It was found that graphic organizers had effects on four levels of objective comprehension as indicated by open comprehension questions. However, on the subjective comprehension measure using Likert-type scales, the groups with and without graphic organizers did not differ from each other. It is concluded that health education texts could benefit from relatively simple techniques to increase comprehension. Furthermore, in developing health education materials, comprehension should be measured objectively.


Differences in cortisol, aldosterone and testosterone responses to ACTH 1-17 administered at two different times of day.
The effects of 100 micrograms, i.m. of the analog ACTH 1-17 administered at 0800 and 1800 on the secretion of cortisol, aldosterone and testosterone have been studied in normal subjects: 8 male and 8 female. The group as a whole and the males had significantly greater absolute and percent increments in plasma cortisol after administration at 1800. In the females, there was only a greater percent increment in cortisol after the evening administration. The heptadecapeptide always significantly stimulated serum aldosterone, with no difference between the two times of administration. In the females, ACTH 1-17 significantly stimulated testosterone, with a more protracted secretion after the evening administration. In the males, there was always a significant testosterone decrease after the administration of the drug, with no difference between morning and evening. In conclusion, 100 micrograms i.m. of the analog ACTH 1-17 stimulates cortisol secretion more when given during the circadian nadir of plasma cortisol, but only in men. ACTH 1-17 increases testosterone in women and decreases it in men, whereas it seems to increase aldosterone secretion in both sexes.


Pichia pastoris secretes recombinant proteins less efficiently than Chinese hamster ovary cells but allows higher space-time yields for less complex proteins.
Chinese hamster ovary (CHO) cells are currently the workhorse of the biopharmaceutical industry. However, yeasts such as Pichia pastoris are about to enter this field. To compare their capability for recombinant protein secretion, P. pastoris strains and CHO cell lines producing human serum albumin (HSA) and the 3D6 single chain Fv-Fc anti-HIV-1 antibody (3D6scFv-Fc) were cultivated in comparable fed batch processes. In P. pastoris, the mean biomass-specific secretion rate (qp ) was 40-fold lower for 3D6scFv-Fc compared to HSA. On the contrary, qp was similar for both proteins in CHO cells. When comparing both organisms, the mean qp of the CHO cell lines was 1011-fold higher for 3D6scFv-Fc and 26-fold higher for HSA. Due to the low qp of the 3D6scFv-Fc producing strain, the space-time yield (STY) was 9.6-fold lower for P. pastoris. In contrast, the STY of the HSA producer was 9.2-fold higher compared to CHO cells because of the shorter process time and higher biomass density. The results indicate that the protein secretion machinery of P. pastoris is much less efficient and the secretion rate strongly depends on the complexity of the recombinant protein. However, process efficiency of the yeast system allows higher STYs for less complex proteins.


Postnatal Migration of Cerebellar Interneurons.
Due to its continuing development after birth, the cerebellum represents a unique model for studying the postnatal orchestration of interneuron migration. The combination of fluorescent labeling and ex/in vivo imaging revealed a cellular highway network within cerebellar cortical layers (the external granular layer, the molecular layer, the Purkinje cell layer, and the internal granular layer). During the first two postnatal weeks, saltatory movements, transient stop phases, cell-cell interaction/contact, and degradation of the extracellular matrix mark out the route of cerebellar interneurons, notably granule cells and basket/stellate cells, to their final location. In addition, cortical-layer specific regulatory factors such as neuropeptides (pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin) or proteins (tissue-type plasminogen activator (tPA), insulin growth factor-1 (IGF-1)) have been shown to inhibit or stimulate the migratory process of interneurons. These factors show further complexity because somatostatin, PACAP, or tPA have opposite or no effect on interneuron migration depending on which layer or cell type they act upon. External factors originating from environmental conditions (light stimuli, pollutants), nutrients or drug of abuse (alcohol) also alter normal cell migration, leading to cerebellar disorders.


Hyperthermia with Chemotherapy for Unresectable Gastric Cancer in a Patient with a Vagus Nerve Stimulator Implant: A Case Report.
BACKGROUND Radiofrequency (RF) hyperthermia is commonly used as an adjunct to established treatment modalities such as chemotherapy and radiotherapy for the management of cancer patients. This case report aims to introduce the use of hyperthermia, in combination with chemotherapy, for the treatment of unresectable gastric cancer in a patient implanted with a vagus nerve stimulator (VNS). CASE REPORT A 55-year-old man with dermatomyositis, laryngeal squamous cell carcinoma in situ and double synchronous gastric cancer was found to have unresectable gastric disease during surgery despite neoadjuvant chemotherapy. Postoperatively, he received chemotherapy with RF hyperthermia. The patient had a VNS implant to treat epileptic seizures. VNS failure due to RF hyperthermia was an area of significant concern, and the procedures were completed with a full preparation to manage epileptic seizures in the event of its anticipated occurrence. Twenty-one thermotherapies were performed over 21 weeks. After 3 courses of S-1 chemotherapy (12 weeks) with RF hyperthermia without any adverse events, the regimen was changed to S-1+ CDDP combination chemotherapy (SP) and RF hyperthermia. The patient continued to receive treatment with a decrease in the size of the primary gastric tumors as well as lymph node metastases, without major adverse events, until he died due to disseminated disease. CONCLUSIONS We report the first case of unresectable gastric cancer with VNS implants in which chemo-hyperthermal therapy was safe and successful. This case report highlights the importance of providing a multidisciplinary treatment with appropriate measures for patients with intractable cancer who have received special treatments for underlying comorbidities.


Multifaceted mitochondrial quality control in brown adipose tissue.
Brown adipose tissue (BAT) controls mammalian core body temperature by non-shivering thermogenesis. BAT is extraordinarily rich in mitochondria, which have the peculiarity of generating heat by uncoupled respiration. Since the mitochondrial activity of BAT is subject to cycles of activation and deactivation in response to environmental temperature changes, an integrated mitochondrial quality control (MQC) system is of fundamental importance to ensure BAT physiology. Here, we provide an overview of the conventional and alternative mechanisms through which thermogenic adipocytes selectively remove damaged parts of mitochondria and how macrophages participate in the MQC system by removing extracellular mitochondrial waste to maintain the thermogenic function of BAT.


Structural specificity of the spermidine requirement of an Escherichia coli auxotroph.
A homologous series of spermidine analogs was synthesized with the general structure NH3+ (CH2)nNH2+(CH2)3NH3+, where spermidine has n = 4. The influence of these compounds on growth and on the syntheses of protein and messenger ribonucleic acid was examined in a spermidine auxotroph of Escherichia coli. All of the homologs tested were taken up by the cells to an intracellular level equivalent to the level of spermidine which gives optimal growth. With increasing chain length of the homologs, there was reduced ability to stimulate growth. The homologs with n = 7 and n = 8 were essentially inactive. A similar specificity was observed when the ability of the homologs to restore the rates of protein and messenger ribonucleic acid chain elongation was compared to that of spermidine. These results suggest that a definite spatial arrangement of the amino groups of spermidine is required for productive interaction at its intracellular site(s) of action.


Uncovering key patterns in self-harm in adolescents: Sequence analysis using the Card Sort Task for Self-harm (CaTS).
Self-harm is a significant clinical issue in adolescence. There is little research on the interplay of key factors in the months, weeks, days and hours leading to self-harm. We developed the Card Sort Task for Self-harm (CaTS) to investigate the pattern of thoughts, feelings, events and behaviours leading to self-harm. Forty-five young people (aged 13-21 years) with recent repeated self-harm completed the CaTS to describe their first ever/most recent self-harm episode. Lag sequential analysis determined significant transitions in factors leading to self-harm (presented in state transition diagrams). A significant sequential structure to the card sequences produced was observed demonstrating similarities and important differences in antecedents to first and most recent self-harm. Life-events were distal in the self-harm pathway and more heterogeneous. Of significant clinical concern was that the wish to die and hopelessness emerged as important antecedents in the most recent episode. First ever self-harm was associated with feeling better afterward, but this disappeared for the most recent episode. Larger sample sizes are necessary to examine longer chains of sequences and differences in genders, age and type of self-harm. The sample was self-selected with 53% having experience of living in care. The CaTs offers a systematic approach to understanding the dynamic interplay of factors that lead to self-harm in young people. It offers a method to target key points for intervention in the self-harm pathway. Crucially the factors most proximal to self-harm (negative emotions, impulsivity and access to means) are modifiable with existing clinical interventions.


Curvature-dependent adhesion of vesicles.
The morphology and motion behavior of a cell are highly influenced by its external biological, chemical, and physical stimuli, and geometric confinement. In this paper, it is revealed that the mean curvature of the substrate significantly influences the adhesion of vesicles. By employing the variational method and investigating the Helfrich free energy, the configuration of axisymmetric vesicles adhered to curved spherical substrates is obtained theoretically. Moreover, numerical simulations based on the finite element method are also carried out to investigate the adhesion of vesicles on curved substrates with complex shapes. It is found that for a fixed area of a vesicle, its total free energy depends mainly on the mean curvature of the adhesion region but is insensitive to the specific shape of the substrate, and the total free energy monotonically decreases with the increase in the mean curvature. In addition, possible biological significances of the curvature-dependent adhesion, such as the shape of the cell and antibiofouling, are discussed. This study may deepen our understanding of the underlying mechanisms of adhesion in cellular activities.


[Eversion carotid endarterectomy].
It is widely accepted and proved the role of carotid endarterectomy in the prevention of cerebrovascular insufficiency. Some mater of controversy lies, presently, apart the role of the endovascular treatment, in the techniques of choice for the endarterectomy, as well as in the method employed for the arteriotomy closure. The authors report their experience with the eversion endarterectomy technique, discussing the results and enhancing the main indications of this alternative method for carotid endarterectomy.


A Case of Pembrolizumab-Induced Myasthenia Gravis.
With the advent of new cancer treatments, immunotherapy has emerged as an increasingly promising strategy. Undoubtedly, it has pushed oncology into a new era and is providing patients with unprecedented results. As with many treatments, however, adverse effects lead to setbacks in progress. Pembrolizumab is an immunomodulating medication that functions by binding to programmed cell death protein 1 (PD-1) receptors of T cells thereby upregulating the immune system to more effectively detect and target cancer. Myasthenia gravis (MG) is a reported side effect of this medication. Our patient is an 87-year-old male with urothelial cell bladder cancer who developed MG following the administration of pembrolizumab and was treated with plasma exchange therapy. We aim to examine the existing literature concerning treatments for MG, with a particular focus on myasthenia gravis induced by pembrolizumab. We will discuss the occurrence rates and results of such instances, along with their implications for the future of these potential therapies.


Glutamate receptor antagonists as fast-acting therapeutic alternatives for the treatment of depression: ketamine and other compounds.
The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bipolar depression. These effects are in direct contrast to the more modest effects seen after weeks of treatment with classic monoaminergic antidepressants. Numerous open-label and case studies similarly validate ketamine's antidepressant properties. These clinical findings have been reverse-translated into preclinical models in an effort to elucidate ketamine's antidepressant mechanism of action, and three important targets have been identified: mammalian target of rapamycin (mTOR), eukaryotic elongation factor 2 (eEF2), and glycogen synthase kinase-3 (GSK-3). Current clinical and preclinical research is focused on (a) prolonging/maintaining ketamine's antidepressant effects, (b) developing more selective NMDA receptor antagonists free of ketamine's adverse effects, and (c) identifying predictor, mediator/moderator, and treatment response biomarkers of ketamine's antidepressant effects.


Changes Experienced by Low-Concentration Lipid Bicelles as a Function of Temperature.
Differential scanning calorimetry (DSC) of dipalmitoyl phosphatidylcholine (DPPC), dihexanoyl phosphatidylcholine, and dipalmitoyl phosphatidylglycerol bicelles reveals two endothermic peaks. Based on analysis of small angle neutron scattering and small angle X-ray scattering data, the two DSC peaks are associated with the melting of DPPC and a change in bicellar morphology─namely, either bicelle-to-spherical vesicle or oblate-to-spherical vesicle. The reversibility of the two structural transformations was examined by DSC and found to be consistent with the corresponding small angle scattering data. However, the peak that is not associated with the melting of DPPC does not correspond to any structural transformation for bicelles containing distearoyl phosphatidylethanolamine conjugated with polyethylene glycol. Based on complementary experimental data, we conclude that membrane flexibility, lipid miscibility, and differential solubility between the long- and short-chain lipids in water are important parameters controlling the reversibility of morphologies experienced by the bicelles.


Corticospinal responses to sustained locomotor exercises: moving beyond single-joint studies of central fatigue.
There is substantial evidence that fatiguing exercise is accompanied by changes within the central nervous system that reduce the force that can be produced by working muscles. Here we review studies that used non-invasive neurophysiological techniques to show that sustained single-joint contractions have the capacity to increase corticospinal responsiveness and reduce motoneuronal responsiveness. We contrast these findings with new evidence from our laboratory regarding corticospinal responsiveness during sustained cycling exercise. There seems to be a similar increase in responsiveness of the intracortical inhibitory interneurons during sustained locomotor and single-joint exercise which might be due to acute exercise responses that are common to fatiguing exercise of any nature, such as local accumulation of fatigue metabolites. In contrast, the pattern of changes in corticospinal responsiveness is fundamentally different between the two modes of exercise which might be due to greater systemic fatigue responses to locomotor exercises.


Theoretical study of the electronic and optical properties of photochromic dithienylethene derivatives connected to small gold clusters.
In the course of developing electronic devices on a molecular scale, dithienylethenes photochromic molecules constitute promising candidates for optoelectronic applications such as memories and switches. There is thus a great interest to understand and control the switching behavior of photochromic compounds deposited on metallic surfaces or nanoparticles. Within the framework of the density functional theory, we studied the effect of small gold clusters (Au3 and Au9) on the electronic structure and absorption spectrum of a model dithienylethene molecule. The molecular orbital interactions between the photochromic molecule and the gold cluster made it possible to rationalize some experimental findings (Dulic, D.; van der Molen, S. J.; Kudernac, T.; Jonkman, H. T.; de Jong, J. J. D.; Bowden, T. N.; van Esch, J.; Feringa, B. L.; van Wees, B. J. Phys. Rev. Lett. 2003, 91, 207402). For the closed-ring isomer, grafting a photochromic molecule on a small gold cluster does not change the characteristics of the electronic transition involved in the ring-opening reaction. On the opposite, the absorption spectrum of the photochromic open-ring isomer is strongly modified by the inclusion of the metallic cluster. In agreement with experimental results, our study thus showed that the cycloreversion reaction which involves the closed-ring isomer should be still possible, whereas the ring-closure reaction which involves the open-ring isomer should be inhibited. Connecting a dithienylethene molecule to a small gold cluster hence provides a qualitative comprehension of the photochromic activities of dithienylethenes connected to a gold surface.


Molecular aspects of implantation failure.
Despite expanding global experience with advanced reproductive technologies, the majority of IVF attempts do not result in a successful pregnancy, foremost as a result of implantation failure. The process of embryo implantation, a remarkably dynamic and precisely controlled molecular and cellular event, appears inefficient in humans and is poorly understood. However, insights gained from clinical implantation failure, early pregnancy loss, and emerging techologies that enable molecular interrogation of endometrial-embryo interactions are unravelling this major limiting step in human reproduction. We review current molecular concepts thought to underlie implantation failure, consider the contribution of embryonic and endometrial factors, and discuss the clinical value of putative markers of impaired endometrial receptivity. Finally we highlight the nature of the dialogue between the maternal endometrium and the implanting embryo and discuss the concept of natural embryo selection. This article is part of a Special Issue entitled: Molecular Genetics of Human Reproductive Failure.


Molecular evidence of recurrent histoplasmosis with 9-year latency in a patient with Addison's disease.
We present a case of fatal histoplasmosis in a patient with Addison's disease and long-term use of corticosteroid. The patient acquired Histoplasma capsulatum in China and initially presented with a laryngeal mass. He developed fulminant pneumonia and respiratory failure 9 years later. Nucleotide sequences of internal transcribed spacer regions of rRNA genes of the H. capsulatum isolate recovered from biopsied lung tissue and of the extracted fungal DNA from the laryngeal lesion were identical, indicating the recurrent nature of infection.


[Anesthesia and Anesthesia-related Technology].
Although there is no remarkable change of anesthetics or anesthesia methods in recent years, several new technologies are used for safety management of cardiac, lung or thoracic surgery. Stroke volume variation (SVV) monitoring indicates SVV, a parameter to optimize fluid infusion and is used to avoid edema or congestive heart damage due to over hydration. SmartPilot View, a pharmacokinetic simulator during anesthesia, represents the measured effective site concentration of anesthetics and contributes the optimization of induction and maintenance of anesthesia. Pressure controlled ventilation-volume guarantee (PCV-VG) is a ventilation mode that can secure preset tidal volume even under PCV to avoid hypoxemia and hypercapnia, even when unexpected airway pressure raised. AutoFlow system supplies tidal volume at the lowest airway pressure and has the function of maintaining tidal volume while keeping low airway pressure according to the change of pulmonary compliance. In 2017, we modified the position of cuff air delivery lumen while maintaining the strength and elasticity of double-lumen tube (DLT) made by a company to avoid deflation failure of bronchial cuff by our team.


NTRK gene alterations were enriched in hepatoid or enteroblastic differentiation type of gastric cancer.
AimsCurrently, the clinicopathological characteristics of gastric cancer (GC) with oncogenic NTRK alterations are not well known. Although NTRK fusion has been identified as prevalent in DNA mismatch repair protein deficient (dMMR) colorectal cancer (CRC), the relationship between NTRK alterations and dMMR protein expression in GC has not been previously explored. Our study comprised 51 cases of EBV(Epstein-barr virus)-associated gastric carcinomas, 94 cases of dMMR GC, 90 cases of gastric adenocarcinoma with hepatoid or enteroblastic differentiation (GAHED) and 256 cases of conventional GC. Furthermore, to investigate the connection between NTRK fusion and dMMR proteins, we collected dMMR tumours of various types, including 21 cases of duodenal adenocarcinomas, 46 endometrioid carcinomas and 82 CRCs. NTRK fusion and amplification were screened in GC and various types of dMMR tumours using fluorescence in situ hybridisation (FISH), while cases positive for FISH translocation underwent next-generation sequencing testing. Our findings revealed the existence of two cases each of NTRK fusions and NTRK amplifications, which were all enriched in case of GAHED. Additionally, following an analysis of several types of cancers, we discovered that NTRK gene alterations were only present in dMMR CRC. Our results indicate that NTRK gene alterations are not enriched in GC with dMMR but are specifically enriched in cases of GAHED.


Regional variation is present in elbow capsules after injury.
Myofibroblast numbers and alpha-smooth muscle actin expression are increased in anterior joint capsules of patients with posttraumatic elbow contractures. The purpose of our study was to determine whether these changes occur regionally or throughout the entire joint capsule. We hypothesized that the alpha-smooth muscle actin mRNA expression and the myofibroblast numbers in posterior joint capsules would be elevated in elbows obtained from patients with posttraumatic joint contractures compared with joint capsules obtained from organ donor elbows without contractures. Semiquantitative reverse transcription-polymerase chain reaction was used to evaluate relative mRNA levels of alpha-smooth muscle actin. Glyceraldehyde-3-phosphate dehydrogenase was used to normalize the levels. Immunohistochemical analysis was used to determine the myofibroblast cell numbers. Higher alpha-smooth muscle actin mRNA levels were observed in elbows of patients with contractures compared with organ donor elbows without contractures. Immunohistochemical studies determined that myofibroblast numbers and the percentage of total cells that were myofibroblasts were elevated (2-2.5-fold) in the joint capsules from patients with posttraumatic joint contractures compared with similar tissue obtained from organ donor elbows without contractures. These results suggest elevated myofibroblast numbers occur throughout the whole joint capsule in posttraumatic elbow contractures, although there is some regional variation.


[Cysts in the cavum tunica vaginalis testis: a case report].
A case of cysts in the cavum tunica vaginalis testis was reported. A 58-year-old man visited our clinic with the chief complaint of urethral bleeding. Urethro-cystogram revealed stricture of bulbous urethra. We palpated several pea-sized painless masses in the left scrotum. On ultrasonogram of the left scrotal contents several cystic lesions were detected at the cranial side of the left testis. At operation, cysts were found in the cavum tunica vaginalis testis, and were resected along with the tunica vaginalis. Fluid of the cysts was serous without sperm. Histopathologically mesothelial cyst was suspected. The incidence of cysts in the cavum tunica vaginalis testis is rare and only 17 cases have been reported in Japan. We reviewed 9 cases of cysts arising from lamina parietalis of tunica vaginalis.


Altered intra- and inter-hemispheric functional dysconnectivity in schizophrenia.
Despite convergent evidence suggesting that schizophrenia is a disorder of brain dysconnectivity, it remains unclear whether intra- or inter-hemispheric deficits or their combination underlie the dysconnection. This study examined the source of the functional dysconnection in schizophrenia. Resting-state fMRI was performed in 66 patients with schizophrenia and 73 matched healthy controls. Functional brain networks were constructed for each participant and further partitioned into intra- and inter-hemispheric connections. We examined how schizophrenia altered the intra-hemispheric topological properties and the inter-hemispheric nodal strength. Although several subcortical and cingulate regions exhibited hemispheric-independent aberrations of regional efficiency, the optimal small-world properties in the hemispheric networks and their lateralization were preserved in patients. A significant deficit in the inter-hemispheric connectivity was revealed in most of the hub regions, leading to an inter-hemispheric hypo-connectivity pattern in patients. These abnormal intra- and inter-hemispheric network organizations were associated with the clinical features of schizophrenia. The patients in the present study received different medications. These findings provide new insights into the nature of dysconnectivity in schizophrenia, highlighting the dissociable processes between the preserved intra-hemispheric network topology and altered inter-hemispheric functional connectivity.


Ability of Cystatin C to detect changes in glomerular filtration rate after ACE inhibition in patients with uncomplicated type 1 diabetes.
Although it is known that glomerular filtration rate (GFR) declines in response to angiotensin converting enzyme (ACE) inhibition, recent observations using GFR(CYSTATIN C) have shown a paradoxical increase calling into question its validity. In this descriptive study, we aimed to reconcile this observation by simultaneously measuring GFR(CYSTATIN C), GFR(CREATININE), and gold standard GFR(INULIN) responses to ACE inhibition. Adolescents with type 1 diabetes and hyperfiltration (n = 9, GFR(INULIN) ≥ 135 mL/min/1.73 m(2)) or normofiltration (n = 11) were studied during clamped euglycemia at baseline and after 3-week enalapril therapy. In hyperfilterers, the anticipated GFR(INULIN) decline before and after enalapril was observed (174 ± 29 mL/min/1.73 m(2) to 140 ± 26 mL/min/1.73 m(2), P = .01). Although GFR(CYSTATIN C) equations tended to underestimate while GFR(CREATININE) equations tended to overestimate baseline GFR(INULIN) in hyperfilterers, both approaches generally reflected declining GFR(INULIN) responses to enalapril. Normofilterers demonstrated a trend toward rising GFR(INULIN) in response to enalapril (112 ± 16 mL/min/1.73 m(2) to 119 ± 27 mL/min/1.73 m(2), P = .35). Although all estimating equations tended to overestimate baseline GFR(INULIN), they generally reflected the rising trend in GFR(INULIN) in response to enalapril in normofilterers. Although GFR(INULIN) declines in response to enalapril among hyperfilterers, we confirm the previous observation that it demonstrates a trend to rising among normofilterers. These group trends are both reflected by cystatin C- and creatinine-based estimates.


Gastric retention of enteric-coated magnesium chloride tablets.
To describe a patient with gastric retention of enteric-coated magnesium chloride tablets. Potential drug and disease etiologies accounting for failure to empty this dosage form are discussed. Single case report. A seriously ill patient with metastatic small-cell lung cancer accumulated 21 enteric-coated magnesium chloride tablets in his stomach during a four-day administration period. The patient had gastroscopic evidence of mild pylorospasm and suspected gastric motor dysfunction. The latter may have been the result of several factors including concurrent use of oxycodone, vagal dysfunction from chronic alcoholism and cisplatin-based chemotherapy, and possibly a paraneoplastic neuromuscular syndrome involving the gastrointestinal tract. Enteric-coated tablets are indigestible solids, often of considerable size. Strong antral contractions, associated with phase 3 of the interdigestive migrating myoelectric complex, are usually required to carry such dosage forms through a normal pyloric channel and into the duodenum. Seriously ill patients who may have gastric hypomotility or pyloric channel narrowing are probably not good candidates for therapy with large enteric-coated dosage forms.


Association Between Frailty and HIV-Associated Neurodegenerative Disorders Among Older Adults Living with HIV.
The population of aging adults living with human immunodeficiency virus (HIV) is growing worldwide and evidence suggests that frailty occurs prematurely among them. In turn, frailty has been associated with cognitive decline. It is unknown, however, if people with both frailty and HIV infection have a higher risk of cognitive impairment compared with nonfrail HIV-infected persons. Therefore, the main objective of this study was to determine the association between the phenotype of frailty and HIV-associated neurocognitive disorders (HAND) among adults aged 50 years or older living with HIV/AIDS. A cross-sectional study was conducted on 206 adults living with HIV receiving care in a university-affiliated tertiary care hospital in Mexico City. Frailty was defined as per the Fried criteria. The presence of HAND was established according to the Antinori criteria: HIV-associated asymptomatic neurocognitive impairment (ANI), HIV-associated mild neurocognitive disorder (MND), or cognitively nonimpaired. Multinomial logistic regression models were used to test the independent association between frailty and HAND adjusting for potential confounders. Mean age of participants was 60.5 ± 6.3 years and 84.9% were male. Prevalence of HAND and frailty phenotype was 66.0% and 2.9%, respectively. The unadjusted analysis showed that both prefrail and frail statuses were associated with MND but not with ANI. However, after adjustment, the association with MND remained significant only among prefrail participants and no longer for frail persons (risk ratio [RR] = 5.7, 95% confidence intervals [CI] 1.09-29.82; p = .039 and RR = 18.3, 95% CI 0.93-362.6; p = .056, respectively). Prefrailty is associated with symptomatic neurocognitive disorders in older adults living with HIV. The spectrum of the frailty phenotype in this already vulnerable population should serve as an indicator of concomitant cognitive decline.


Flow lines and mixing within drops in microcapillaries.
We present a theoretical and numerical investigation of streamlines and mixing within drops flowing in capillaries. We first study theoretically the limit case of purely viscous flow around a drop of negligible radius, and find that, owing to geometrical constraints, recirculating regions are always present at the front and back of such drops. Using two-dimensional simulations, we visualize streamlines for larger drops, showing that the extent of these recirculating torii increases with drop size and decreases with Reynolds number. We study the mixing within drops as they are subjected to time-dependent shear, thus modeling a sinusoidal channel, and find that while cross-stream mixing is efficient, streamwise mixing is hindered by the front and back recirculating regions.


Effect of vasoactive intestinal polypeptide and somatostatin on secretion of epidermal growth factor and bicarbonate from Brunner's glands.
The effect of VIP and somatostatin on secretion of epidermal growth factor and bicarbonate from Brunner's glands was investigated in the rat. Vasoactive intestinal polypeptide infused in doses of 10 and 100 ng/kg/h significantly increased epidermal growth factor and bicarbonate output, but the concentrations did not change. Somatostatin infused at doses of 1, 10, 100 and 1000 ng/kg/h against a background of VIP 100 ng/kg/h inhibited in dose-dependent fashion the stimulated epidermal growth factor and bicarbonate outputs from rat Brunner's gland pouches. Also basal secretion was inhibited by somatostatin. Infusion of antisomatostatin serum stimulated Brunner's gland secretion. By immunohistochemical studies of rat duodena, it was found that epidermal growth factor, is almost exclusively present in the secretory cells of Brunner's glands. It is concluded that VIP stimulates secretion of epidermal growth factor and bicarbonate from Brunner's glands, an effect which is inhibited by somatostatin. A possible role for somatostatin in the control of Brunner's gland secretion is suggested.


The role of the catecholic and the electrophilic moieties of caffeic acid in Nrf2/Keap1 pathway activation in ovarian carcinoma cell lines.
In recent years, numerous studies have demonstrated the health benefits of polyphenols. A major portion of polyphenols in western diet are derived from coffee, which is one of the most consumed beverages in the world. It has been shown that many polyphenols gain their beneficial properties (e.g. cancer prevention) through the activation of the Nrf2/Keap1 pathway as well as their direct antioxidant activity. However, activation of Nrf2 in cancer cells might lead to resistance towards therapy through induction of phase II enzymes. In the present work we hypothesize that caffeic acid (CA), a coffee polyphenol, might act as an electrophile in addition to its nucleophilic properties and is capable of inducing the Nrf2/EpRE pathway in cancer cells. The results indicate that CA induces Nrf2 translocation into the nucleus and consequently its transcription. It has been demonstrated that generated hydrogen peroxide is involved in the induction process. It has also been found that this process is induced predominantly via the double bond in CA (Michael acceptor). However, surprisingly the presence of both nucleophilic and electrophilic moieties in CA resulted in a synergetic activation of Nrf2 and phase II enzymes. We also found that CA possesses a dual activity, although inducing GSTP1 and GSR, it inhibiting their enzymatic activity. In conclusion, the mechanism of induction of Nrf2 pathway and phase II enzymes by CA has been elucidated. The electrophilic moiety in CA is essential for the oxidation of the Keap1 protein. It should be noted that while the nucleophilic moiety (the catechol/quinone moiety) can provide scavenging ability, it cannot contribute directly to Nrf2 induction. It was found that this process may be induced by H2O2 produced by the catechol group. On the whole, it appears that CA might play a major role in the cancer cells by enhancing their resistance to treatment.


Extrapolation of measures of work for surveyed services to other services.
A national survey of physicians produced detailed data on the work involved in performing 372 different services. This article describes methods developed to extrapolate the study data to a larger universe of services, defined by the Physicians' Current Procedural Terminology, edition 4. Because data measuring work inputs for nonsurveyed services presently are unavailable, we devised an extrapolation method that makes use of available charge data without building their inherent distortions into the extrapolated scale. To neutralize the effect of these distortions, we used small, homogeneous families of services as the basic units for the extrapolations and assumed that charges are reasonable indicators of relative work within such families. To produce extrapolated work values within each family, we multiplied an estimate of work based on survey data for a benchmark procedure by charge-based ratios that represent the relationships between surveyed and nonsurveyed services. These extrapolations can be used in constructing a Resource-Based Relative Value Scale.


Molecular mimicry between a uveitopathogenic site of S-antigen and viral peptides. Induction of experimental autoimmune uveitis in Lewis rats.
S-Antigen (S-Ag) is a well characterized 45,000 m.w. photoreceptor cell protein. When injected into susceptible animal species, including primates, it induces an experimental autoimmune uveitis, a predominantly T cell-mediated autoimmune disease of the retina and uveal tract of the eye, and of the pineal gland. In this study we found an amino acid sequence homology between a uveitopathogenic site of S-Ag, several viral proteins and one additional nonviral protein. An experimental autoimmune uveitis and pinealitis was induced in Lewis rats with these different synthetic peptides, corresponding to the amino sequence of hepatitis B virus DNA polymerase, gag-pol polyprotein of Baboon endogenous virus and gag-pol polyprotein of AKV murine leukemia virus and potato proteinase inhibitor IIa, which contain three or more consecutive amino acids identical to peptide M in S-Ag. Lymph node cells from rats immunized with either peptide M or the different synthetic peptides showed a significant degree of cross-reaction. Mononuclear cells from monkeys (Macaca fascicularis) immunized with peptide M also showed significant proliferation when incubated with either peptide M or synthetic peptides as measured by in vitro lymphocyte mitogenesis assay using [3H]TdR. Based on our findings we conclude that a viral infection may sensitize the mononuclear cells that can cross-react with self proteins by a mechanism termed molecular mimicry. Tissue injury from the resultant autoantigenic event can take place in the absence of the infectious virus that initiated the immune response.


Faculty Motivation for OER Textbook Adoption and Future Use.
Most postsecondary instructors in the United States require students to use textbooks in their courses; however, the cost of commercial materials has increased, and copyright policies impede sharing, editing, and customizations of materials. The current study aimed to examine faculty motivation to adopt Open Educational Resources (OER) and how OER use relates to effective teaching practices. Survey data from 469 professors, instructors, lecturers, and research scientists were analyzed using structural equation modeling, which found that autonomous motivation (engagement with OER textbooks based on enjoyment, value) was the strongest positive predictor of current and future OER textbook use. However, use of OER textbooks was not related to self-reported teaching success. The results of this study contribute to better understanding faculty perceptions of and motivation for OER textbook use, along with informing OER adoption initiatives at postsecondary institutions.


Effects of larval diets on some biological parameters and morphometric and biochemical analysis of ovaries of Lucilia cuprina (Wiedemann) (Diptera: Calliphoridae).
The effects of three larval diets (beef meat, chicken meat, and beef liver) on development of Lucilia cuprina (Wiedemann) were evaluated. Egg hatching rates were higher on chicken meat and beef meat (99.5%) than on beef liver (96.5%). Pupation success was higher on chicken meat (99.0%) and beef meat (98.0%) than on beef liver (87.1%). Adult emergence rates were higher in flies reared on chicken meat (99.0%) and beef meat (98.5%) than on beef liver (93.5%). Proportions of female flies were somewhat higher in flies reared on chicken meat or beef meat (54-56% female) than on beef liver (52.5%). Flies that were reared on chicken meat and beef meat had shorter egg-adult development times (16.3 days) than flies reared on beef liver (18.5 days), and the generation time of flies reared on chicken meat or beef meat (51-52 days) was several days shorter than flies reared on beef liver (54 days). Flies reared on chicken meat had larger ovaries and more ovarioles per ovary when larvae were reared on chicken than flies reared on beef meat or beef liver. The ovaries of flies reared on chicken meat had significantly higher amounts of protein (21 mg/g body weight) than flies reared on beef liver (12 mg). Analysis of the larval diets showed that beef liver had the lowest amounts of protein and carbohydrate of the three tested diets, whereas the amounts of lipids did not differ among the diets.


MDCT coronary angiography -- postprocessing, reading, and reporting: last but not least.
Significant literature on MDCT coronary angiography (MDCT-CA) has emerged in the last decade concerning patient's selection, technical aspects of different generations of CT equipment, ECG gating, contrast material and beta-blockade administration, acquisition parameters, and radiation dose. However, the literature regarding postprocessing, reading, and reporting is not so extensive. This review highlights the main elements of MDCT-CA data analysis, thereby allowing the radiologist to take full advantage of this technology and enable a structured report to be generated, promoting best practice with high-quality results.


The relationship between localization and the Franssen effect.
The relationship between localization and the Franssen effect was studied for noise and tones in a sound-deadened and in a live room. The noise was wideband and the tones were 250, 500, 1000, 1500, 2500, and 4000 Hz. Listeners were asked to determine the location of the stimuli in a localization task and to discriminate the difference between a pair of stimuli used to generate the Franssen illusion and a steady-state tone in a Franssen-effect discrimination task. Poor performance in the Franssen-effect discrimination task is consistent with the stimulus conditions leading to a strong Franssen illusion. Poor performance in both the Franssen effect and localization tasks was obtained for midfrequency tones (near 1500 Hz) and in the live room. Thus, the Franssen illusion is strongest for a live room and for midfrequency tones consistent with the difficulty listeners have in localizing sounds under these conditions. These results are consistent with those of Hartmann and Rakerd [J. Acoust. Soc. Am. 86, 1366-1373 (1989)] and support their suggestion of a correlation between the Franssen effect and localization in rooms.


Risk of cross transmission with point-of-care ultrasound system: effect of a glass-sealed control panel on microbial contamination.
Contamination of a point-of-care ultrasound system (POCUS) mainly involved electrocardiography accessories and included pathogenic microorganisms. The use of a glass-sealed control panel significantly facilitated its cleaning and reduced its bacterial contamination compared with a standard control panel. Overall hand hygiene compliance during examinations with POCUS was poor.


Infection of a sylvian Galassi II arachnoid cyst after craniotomy for resection of a parasagittal meningioma.
Arachnoid cysts are CSF-containing entities that rarely are symptomatic or warrant neurosurgical intervention. In addition, infection of these lesions is an even rarer event, with only four reports in the literature capturing this. In this report, we present the case of a 79-year-old man presenting with paraparesis, secondary to a right parasagittal meningioma, with an incidental asymptomatic right sylvian arachnoid cyst (Galassi type II). The initially planned surgery was postponed for 3 months, due to COVID-19 restrictions, and he was kept on high dose of steroids. Following tumour resection, the patient developed bilateral subdural empyemas with involvement of the arachnoid cyst, requiring bilateral craniotomies for evacuation of the empyemas and drainage of the arachnoid cyst. Suppuration of central nervous system arachnoid cysts is a very rare complication following cranial surgery with the main working hypotheses including direct inoculation from surrounding inflamed meninges or haematogenous spread secondary to systemic bacteraemia, potentiated by steroid-induced immunosuppression. Even though being a rarity, infection of arachnoid cysts should be considered in immunosuppressed patients in the presence of risk factors such as previous craniotomy.


A Review of Sensing Applications of Molecularly Imprinted Fluorescent Carbon Dots for Food and Biological Sample Analysis.
Molecularly imprinted fluorescent carbon dots (MI-FCDs) find numerous applications in analytical chemistry due to their outstanding photoluminescent properties and having specific pockets for the recognition of target molecules. Despite significant advances, practical applications of MI-FCDs-based fluorescent sensors are still in their initial stages. Therefore, the topical developments in the synthesis, working, and application of MI-FCDs for sensing various target species (e.g., pharmaceuticals, biomolecules, pesticides, food additives, and miscellaneous species) in food and biological media have been highlighted. Moreover, a careful evaluation has been made to select the best methods based on their performance in terms of analytical parameters. To expand the horizons of this field, important challenges and future directions for developing MI-FCDs for practical use are also presented. This review will highlight important aspects of MI-FCDs-based fluorescent sensors for their applicability in food science, material science, environmental science, nanoscience, and biotechnology.


Cumulative interpersonal traumas and social support as risk and resiliency factors in predicting PTSD and depression among inner-city women.
This study represents one of the largest examinations of how child abuse, adult rape, and social support impact inner-city women (N = 777). Using retrospective self-report, the effects of interpersonal trauma were shown to be cumulative such that women who experienced either child abuse or adult rape were 6 times more likely to have probable posttraumatic stress disorder (PTSD), whereas women who experienced both child abuse and rape were 17 times more likely to have probable PTSD. High social support predicted lower PTSD severity for women who experienced both child abuse and adult rape, but not for women who reported one or none of these traumas. Results suggest that social support, when left intact, might buffer the cumulative impact of child and adult interpersonal traumas.


The diagnostic and therapeutic role of endoscopic retrograde cholangiopancreatography in children.
We performed 121 endoscopic retrograde cholangiopancreatographies (ERCPs) in 92 patients (60 girls and 32 boys), aged 4 months to 19 years, as part of diagnostic evaluation for suspected pancreatic or biliary tract disease or as therapeutic intervention. ERCP was successful in 116 attempts. The most common indications were recurrent pancreatitis (35 children), nonresolving acute pancreatitis (20), unexplained elevated amylase or lipase (19), postcholecystectomy syndrome (14), and elevated biliary tract enzymes (12). One hundred and one ERCPs were performed for more than one indication. The most common findings included chronic pancreatitis (26 cases), pancreas divisum (14), dilated pancreatic duct (10), gallstones or sludge (8), and abnormal common bile duct (8). Complications were uncommon and usually minor. ERCP is a safe and helpful procedure in the evaluation of suspected pancreatic and biliary tract disease in children and frequently allows for nonoperative treatment of these disorders.


Lateral parabrachial nucleus and angiotensin II-induced hypertension.
The objective of this study was to determine if ablation of the lateral parabrachial nucleus (LPBN) would prevent angiotensin II-induced hypertension in rats. Thirteen male Sprague-Dawley rats were studied. Bilateral electrolytic lesions in the LPBN were produced in six rats; the remaining seven rats were subjected to sham lesion surgery only. All rats were instrumented with vascular catheters and housed in metabolism cages. Daily measurements during the 16-day protocol included arterial pressure, heart rate, water intake, urine output, and urinary sodium excretion. Periodically throughout the protocol depressor responses to ganglion blockade and to blockade of V1-type vasopressin receptors also were measured. The protocol was divided into three control-period days, 10 days of continuous (24 hr/day) angiotensin II infusion (10 ng/min i.v.), and three recovery-period days. There were no significant differences between the two groups of rats for any variable during the control period. During angiotensin II infusion, sham-lesion rats exhibited a progressive increase in arterial pressure and the depressor response to ganglion blockade and a decrease in urinary sodium excretion. No other variable was significantly changed. In rats with LPBN lesions, arterial pressure was significantly increased only on days 1 and 3 of angiotensin II infusion. No other variable was affected. It was concluded that ablation of the LPBN in rats prevented sustained hypertension during intravenous infusion of angiotensin II by interfering with neurogenic pressor mechanisms normally activated by the peptide.


Mechanism of Zhen Wu Decoction in the Treatment of Heart Failure Based on Network Pharmacology and Molecular Docking.
Heart failure (HF) is a serious manifestation or advanced stage of various cardiovascular diseases, and its mortality and rehospitalization rate are still on the rise in China. Based on the network pharmacology method, 59 components of Zhen Wu decoction (ZWD) and 83 target genes related to HF were obtained. Through the PPI network, four potential therapeutic targets were identified: AKT1, IL6, JUN, and MAPK8. The beneficial components of ZWD might intervene HF through the AGE-RAGE signalling pathway in the diabetes component, fluid shear stress and atherosclerosis, the TNF signalling pathway, TB, and Kaposi sarcoma related herpesvirus infection, according to a KEGG enrichment study. The protein interaction network of candidate targets was constructed by the STRING database, and the protein interaction network was clustered by MEODE software. GO and KEGG enrichment analyses were performed on the core modules obtained by clustering. Finally, AutoDock Vina software was used for molecular docking verification of key targets and active ingredients. The result was that 75 active ingredients and 109 genes were screened as potential active ingredients and potential targets of Shengjie Tongyu decoction for CHF treatment. The main active components were quercetin, luteolin, kaempferol, dehydrated icariin, isorhamnetin, formononetin, and other flavonoids. Il-6, MAPK1, MAPK8, AKT1, VEGFA, and JUN were selected as the core targets. Molecular docking showed that the key components were well connected with the target. GO enrichment analysis showed that Shengjie Tongyu decoction could play a role through multiple biological pathways including angiogenesis, regulation of endothelial cell proliferation, binding of cytokine receptors, negative regulation of apoptotic signalling pathways, regulation of nitric oxide synthase activity, and reactive oxygen metabolism. Key pathways mainly focus on the toll-like receptor signalling pathway, nod-like receptor signalling pathway, MAPK signalling pathway, mTOR signalling pathway, JAK-STAT signalling pathway, VEGF signalling pathway, and other pathways. Through molecular docking technology, it was found that a variety of effective components in ZWD, such as kaempferol. Molecular docking technology has preliminatively verified the network pharmacology and laid a foundation for the follow-up pharmacological research.


Combined use of diffusion-weighted MRI and 1H MR spectroscopy to increase accuracy in prostate cancer detection.
The objective of our study was to establish the sensitivity and specificity for prostate cancer detection using a combined 1H MR spectroscopy and diffusion-weighted MRI approach. Forty-two men (mean age +/- SD, 69.3 +/- 4.7 years) with prostate cancer were studied using endorectal T2-weighted imaging, 2D chemical shift imaging (CSI), and isotropic apparent diffusion coefficient (ADC) maps. Regions of interest (ROIs) were drawn around the entire gland, central gland, and peripheral zone tumor, diagnostically defined as low signal intensity on T2-weighted images within a sextant that was biopsy-positive for tumor. Lack of susceptibility artifact on a gradient-echo B0 map through the slice selected for CSI and no high signal intensity on external array T1-weighted images confirmed the absence of significant hemorrhage after biopsy. CSI voxels were classified as nonmalignant or as tumor (ROI included > or = 30% or > or = 70% tumor). Choline-citrate (Cho/Cit) ratios and average ADCs were calculated for every voxel. A plot of Cho/Cit ratios versus ADCs yielded a line of best separation of tumor voxels from nonmalignant voxels. Receiver operating characteristic (ROC) curves were plotted for Cho/Cit ratios alone, ADCs alone, and a combination of the two. The Cho/Cit ratios were significantly higher (p < 0.001) and the ADCs were significantly lower (p < 0.006) in tumor-containing voxels than in non-tumor-containing voxels. When voxels containing 30% or more tumor were considered positive, the area under the ROC curves using combined MR spectroscopy and ADC (0.81) was similar to that of Cho/Cit alone (0.79) and better than ADC alone (0.66). When voxels containing 70% or more tumor were considered positive and cutoffs to achieve a 90%-or-greater sensitivity chosen, a combination of Cho/Cit and ADC achieved a significant improvement in specificity compared with Cho/Cit alone (p < 0.0001) or ADC alone (p < 0.0001). When voxels containing > or = 70% tumor are considered positive, the combined use of MR spectroscopy and diffusion-weighted MRI increases the specificity for prostate cancer detection while retaining the sensitivity compared with MR spectroscopy alone or diffusion-weighted MRI alone.


Photoluminescence of Two-Dimensional MoS2 Nanosheets Produced by Liquid Exfoliation.
Extraordinary properties of two-dimensional materials make them attractive for applications in different fields. One of the prospective niches is optical applications, where such types of materials demonstrate extremely sensitive performance and can be used for labeling. However, the optical properties of liquid-exfoliated 2D materials need to be analyzed. The purpose of this work is to study the absorption and luminescent properties of MoS2 exfoliated in the presence of sodium cholate, which is the most often used surfactant. Ultrasound bath and mixer-assisted exfoliation in water and dimethyl sulfoxide were used. The best quality of MoS2 nanosheets was achieved using shear-assisted liquid-phase exfoliation as a production method and sodium cholate (SC) as a surfactant. The photoluminescent properties of MoS2 nanosheets varied slightly when changing the surfactant concentrations in the range C(SC) = 0.5-2.5 mg/mL. This work is of high practical importance for further enhancement of MoS2 photoluminescent properties via chemical functionalization.


Detecting Proteins Glycosylation by a Homogeneous Reaction System with Zwitterionic Gold Nanoclusters.
Homogeneous gold nanoclusters (Au NCs) have been widely utilized in drug delivery, chemical sensing, bioassays, and biolabeling due to their unique physical and chemical properties. However, little attention has been paid to their application in detecting protein post-translational modifications. Herein, we describe the development of a homogeneous reaction system with water-soluble zwitterionic Au NCs to capture glycopeptides from complex biological samples. The unique characteristics of Au NCs, such as their molecular-like properties, the excellent homogeneity in aqueous solution, the organic solvent responsive precipitation, and the easy preparation in only 4.5 h, contribute to the high efficiency and high throughput for capturing the targeted glycopeptides. Compared with the conventional heterogeneous system with solid-state adsorbents, the number of characterized glycosylation sites was improved by 35%. Finally, an MS detection limit as low as 50 amol was achieved for the standard glycoprotein (IgG), and 1576 glycosylation sites from 713 glycoproteins were identified from only 60 μg of mouse liver protein. Data are available via ProteomeXchange with identifier PXD005635.


The inter-rater and test-retest reliability of the Home Falls and Accidents Screening Tool.
The Home Falls and Accidents Screening Tool was developed to assist health professionals to identify falls risk among community-dwelling older people arising from their home environment. The aim of this study was to evaluate the Home Falls and Accidents Screening Tool by examining its inter-rater and test-retest reliability. Community-dwelling older people, over the age of 65 (n = 31) were recruited from the caseload of nine occupational therapists across three area health services in Sydney and the Hunter region. A total of 31 home visits were conducted by the researcher and an occupational therapist to independently administer the Home Falls and Accidents Screening Tool. Follow-up visits were then conducted within a two-week period by one of the raters to re-administer the Home Falls and Accidents Screening Tool. Reliability was evaluated using percentage agreement, intra-class correlations and kappa coefficients. The intra-class correlation coefficient for the Home Falls and Accidents Screening Tool overall score was 0.82 (95% CI, 0.66-0.91) for inter-rater reliability and 0.77 (95% CI, 0.57-0.88) for test-retest reliability, indicating a good level of reliability for the tool. 'Undefined stair edges' was the only item that demonstrated poor inter-rater reliability (kappa = 0.37). All items except 'loose mats' (kappa = 0.19) reached acceptable or excellent levels of test-retest reliability with kappa scores greater than 0.40. The Home Falls and Accidents Screening Tool demonstrated consistency across raters and across different time periods. Further studies into the reliability of the Home Falls and Accidents Screening Tool would benefit from sampling raters from varying professional backgrounds and older people with higher levels of function.


Latent prostatic cancer in a consecutive autopsy series.
In a consecutive series of autopsies, 223 prostates were removed. Latent prostatic cancer (LPC) was found in 50 cases (22%). All the tumours were adenocarcinomas. The frequency increased with age. No conclusive evidence was found of a relationship between prostatic hyperplasia and LPC. The extent of the tumour seemed to have greater prognostic significance than the degree of differentiation.


An in-depth neurobehavioral characterization shows anxiety-like traits, impaired habituation behavior, and restlessness in male Cryptochrome-deficient mice.
Many psychiatric disorders, for example, anxiety, are accompanied by disturbances of circadian rhythms, including disturbed sleep/wake cycles, changes in locomotor activity, and abnormal endocrine function. Conversely, alternations of circadian rhythms are a risk factor for the development of psychiatric disorders. This assumption is supported by animals with clock gene mutations which often display behaviors that resemble human psychiatric disorders. In this study, we performed an in-depth behavioral analysis with male mice lacking the central clock genes Cryptochrome 1 and 2 (Cry1/2-/- ), which are thus unable to express endogenous circadian rhythms. With wild-type and Cry1/2-/- mice, we performed an extensive behavioral analysis to study their cognitive abilities, social behavior, and their expression of depression-like and anxiety-like behavior. While Cry1/2-/- mice showed only mild abnormalities at cognitive and social behavioral levels, they were consistently more anxious than wildtype mice. Anxiety-like behavior was particularly evident in reduced mobility in new environments, altered ability to habituate, compensatory behavior, and consistent restless behavior across many behavioral tests. In line with their anxiety-like behavioral phenotype, Cry1/2-/- mice have higher c-Fos activity in the amygdala after exposure to an anxiogenic stressor than wild-type mice. In our study, we identified Cry1/2-/- mice as animals that qualify as a translational mouse model for anxiety disorder in humans because of its consistent behavior of restlessness, increased immobility, and dysfunctional habituation in new environments.


Volumetric properties of human islet amyloid polypeptide in liquid water.
The volumetric properties of human islet amyloid polypeptide (hIAPP) in water were studied in a wide temperature range by computer simulations. The intrinsic density rho(p) and the intrinsic thermal expansion coefficient alpha(p) of hIAPP were evaluated by taking into account the difference between the volumetric properties of hydration and bulk water. The density of hydration water rho(h) was found to decrease almost linearly with temperature upon heating and its thermal expansion coefficient was found to be notably higher than that of bulk water. The peptide surface exposed to water is more hydrophobic and its rho(h) is smaller in conformation with a larger number of intrapeptide hydrogen bonds. The two hIAPP peptides studied (with and without disulfide bridge) show negative alpha(p), which is close to zero at 250 K and decreases to approximately -1.5 x 10(-3) K(-1) upon heating to 450 K. The analysis of various structural properties of peptides shows a correlation between the intrinsic peptide volumes and the number of intrapeptide hydrogen bonds. The obtained negative values of alpha(p) can be attributed to the shrinkage of the inner voids of the peptides upon heating.


Calcium antagonists as first-line antihypertensive agents: a placebo-controlled, comparative trial of isradipine and nifedipine.
The new calcium antagonist isradipine was compared with nifedipine retard in a multicenter, double-blind, placebo-controlled, randomized study involving 159 patients with mild hypertension. A 2-week run-in period was followed by a 6-week course of treatment with the possibility of dose doubling after 3 weeks, depending on blood pressure (BP) response (target diastolic BP less than 90 mm Hg). Systolic and diastolic BPs were reduced by isradipine (mean dose of 3.6 mg daily) from 151/101 to 136/89 mm Hg, by nifedipine (mean dose of 50 mg daily) from 155/101 to 144/90 mm Hg, and by placebo from 155/101 to 154/99 mm Hg. Normalization rates were 64% with isradipine, 56% with nifedipine, and 16% with placebo. Adverse events consisted mainly of flushing, headache, edema, and dizziness. Altogether, 8 patients receiving isradipine experienced adverse events in comparison to 21 taking nifedipine and 4 taking placebo. The superior tolerability of isradipine was paralleled by a significant improvement in the subjective well-being of the patients as assessed by the von Zerssen questionnaire (List of Complaints). With nifedipine and placebo, no statistically significant improvement was observed.